Textbook of Regional Anesthesia PDF

Textbook of Regional Anesthesia
2003 EDITION
P. PRITHVI RAJ MD
Professor of Anesthesiology
Co-Director of Pain Services
International Pain Institute
Texas Tech University Health Sciences Center School of Medicine
Lubbock, Texas
CHURCHILL LIVINGSTONE
An imprint of Elsevier Science
New York•Edinburgh•London•Melbourne•Tokyo
Volume
CHURCHILL LIVINGSTONE
An imprint of Elsevier Science
The Curtis Center
Independence Square West
Philadelphia, Pennsylvania 19106
NOTICE
Anesthesiology is an ever-changing field. Standard safety precautions must be followed, but as

new research and clinical experience broaden our knowledge, changes in treatment and drug
therapy may become necessary or appropriate. Readers are advised to check the most current
product information provided by the manufacturer of each drug to be administered to verify the
recommended dose, the method and duration of administration, and contraindications. It is the
responsibility of the treating physician, relying on experience and knowledge of the patient, to
determine dosages and the best treatment for each individual patient. Neither the Publisher nor
the editor assumes any liability for any injury and/or damage to persons or property arising from
this publication.
THE PUBLISHER
Library of Congress Cataloging-in-Publication Data

Raj, P. Prithvi.
Textbook of regional anesthesia/P. Prithvi Raj.
p. ; cm.
ISBN 0–443–06569–1
1. Conduction anesthesia. I. Title.
[DNLM: 1. Anesthesia, Conduction—methods. WO 300 R161t 2002]
RD84 .R35 2002
617.9′64—dc21 2001037149
Acquisitions Editor: Allan Ross

Project Manager: Robin E. Davis
Senior Editorial Assistant: Josh Hawkins
TEXTBOOK OF REGIONAL ANESTHESIA ISBN 0–443–06569–1
Copyright © 2002 Elsevier Science (USA). All rights reserved.
No part of this publication may be reproduced or transmitted in any form or by any means,
electronic or mechanical, including photocopy, recording, or any information storage and
retrieval system, without permission in writing from the publisher.
CHURCHILL LIVINGSTONE and the Sail Boat Design are registered trademarks.
Printed in the United States of America.
Last digit is the print number: 9 8 7 6 5 4 3 2 1
II
Contributors
ELI ALON MD
Professor of Anesthesiology,
University of Zurich,
Zurich, Switzerland;
Chairman, Department of Anesthesiology,
Ospedale Civico and Ospedale Italiano,
Lugano, Switzerland
Efficacy Outcome of Regional Anesthesia Techniques in Obstetrics
SUSAN R. ANDERSON MD
Assistant Professor,
Director of Education,
Advanced Pain Centers of Alaska,
Anchorage, Alaska
Drugs Used in Regional Anesthesia: Chemical Neurolytic Agents;
Continuous Regional Analgesia;
Epiduroscopy;
Discography and Intradiscal Electrothermal Annuloplasty;
Vertebroplasty
JOSE DE ANDRÉS MD
Associate Professor of Anesthesia,

Valencia University Medical School;
Director, Pain Management Center,
Department of Anesthesiology and Critical Care,
Valencia University General Hospital,
Valencia, Spain
Aids to Localization of Peripheral Nerves;
Common Techniques for Regional Anesthesia: Subarachnoid and Epidural Anesthesia
DOUGLAS R. BACON MD
Associate Professor of Anesthesiology,

Mayo Medical School;
Senior Associate Consultant,
Mayo Clinic
Rochester Minnesota
Beyond Blocks: The History of the Development of Techniques in Regional Anesthesia
III
RONALD BANISTER MD
Resident,
Department of Anesthesiology,
Texas Tech University Health Sciences Center School of Medicine,
Lubbock, Texas
Aids to Localization of Peripheral Nerves
ALDO BARBATI MD
Staff Anesthesiologist,
Department of Anesthesia and Intensive Care,
Cardarelli Hospital,
Naples, Italy
Equipment and Techniques
SHAUNA BAUGHCUM CPC
Business Manager,
International Pain Institute,
Texas Tech University Health Sciences, Center School of Medicine
Lubbock Texas
Appendix A: Selected Pain Management Billing Codes;
Appendix B: Selected Diagnoses for Pain Management
DIEGO BELTRUTTI MD
Head, Department of Anesthesia and Resuscitation,

Pain Control Center,
Santo Spirito Hospital,
Bra, Italy
Organization of Chronic Pain Services;
Organization of Palliative Care Services
JAY B. BENDER MD
Pain Fellow,
University of Texas
M.D. Anderson Cancer Center,
Houston, Texas
Chronic Pain: Outcomes Using Procedures for Nociceptive Pain
HONORIO T. BENZON MD
Northwestern University Medical School;
Chief Division of Pain Medicine,
Northwestern Memorial Hospital
Chicago, Illinois
Acute Situations: Trauma
IV
HEMMO A. BOSSCHER MD
Assistant Professor of Anesthesiology,

Lubbock, Texas
Epidural Steroids
CHRISTOPHER M. BURKLE MD
Instructor in Anesthesiology,
Senior Associate Consultant in Anesthesiology,
Mayo Clinic,
Rochester, Minnesota
ALLEN W. BURTON MD

Section Chief of Cancer Pain Management,
University of Texas
Houston, Texas
JEFFREY CARRUTH MD
Chief Resident,
Texas Tech University Health Sciences Center,
Lubbock, Texas
Radiographic Imaging in Regional Anesthesia
VINCENT W. S. CHAN MD
Associate Professor of Anesthesia,

University of Toronto;
Director Regional Anesthesia Acute Pain Service,
Department of Anesthesia University Health Network,
Toronto Western Hospital
Toronto, Ontario, Canada
Training Education of a Physician for Regional Anesthesia
MILES DAY MD, DAPBM
Assistant Professor of Pain Management/Anesthesiology,

Texas Tech University Health Sciences Center School of Medicine;
Staff Physician,
University Medical Center,
Lubbock, Texas
V
Nerve Root Neurolysis;
Sphenopalatine Analgesia
FRANCESCO DONATELLI MD
Resident,
School of Specialization in Anesthesiology,
L’Aquila, Italy
Economic Impact of Regional Anesthesia;
Organization of an Acute Pain Service and Pain Management
CLAUDE ECOFFEY MD
Centre Hospitalier Universitaire de Rennes,
Rennes, France
Common Techniques for Regional Anesthesia: Regional Anesthesia in Children
SERDAR ERDINE MD
Professor,
Medical Faculty of Istanbul University;
Chairman,
Department of Algology,
Capa Klinikleri,
Istanbul, Turkey
Trigeminal Ganglion Procedures
P. M. FINCH MD
Perth Pain Management Centre,

South Perth, Western Australia
Sympathetic Neurolysis
BRIAN FLANAGAN MD
Progressive Pain Management

Dallas, Texas
Discography Intradiscal Electrothermal Annuloplasty
KAREN GALLOWAY MD
Instructor,
Division of Pediatric Anesthesiology,
The Johns Hopkins University School of Medicine,
Baltimore, Maryland;
Anesthesiologist,
Shriners Hospital for Children,
Honolulu, Hawaii
Chronic Pediatric Pain
MELVIN G. GITLIN MD
VI
Professor and Interim Chairman,
Tulane School of Medicine;
Director,
Pain Management Care,
Tulane University Hospital and Clinic,
New Orleans, Louisiana
Epidural Steroids
STEWART GRANT MD

Duke University Medical Center
Durham, North Carolina
Common Techniques for Regional Anesthesia: Peripheral Nerve Blocks
ROY GREENGRASS MD
Associate Professor of Anesthesiology;

Co-Director,
Division of Ambulatory Anesthesiology,
Duke University Medical Center,
PAOLO GROSSI
Director,
Department of Regional Anesthesia and Pain Treatment,
Instituto Policlinico,
San Donato Milano,
Milano, Italy
MARC B. HAHN DO
Dean,
Texas College of Osteopathic Medicine,
University of North Texas Health Science Center at Fort Worth
Fort Worth, Texas
Peripheral Nerve Blockade
RICHARD A. HARDART MD
Instructor,
Baltimore, Maryland
Pediatric Pain Management
CRAIG T. HARTRICK MD
VII
Director,
Anesthesia Research,
William Beaumont Hospital,
Royal Oak, Michigan
Regional Anesthesia for Chronic Situations: Nonmalignant Pain;
Trauma
SAMUEL J. HASSENBUSCH MD
Professor of Neurosurgery,
University of Texas,
Houston, Texas
Neuroaugmentative Procedures for Pain
JAMES E. HEAVNER DVM, PhD
Professor of Anesthesiology and Physiology,

Director of Anesthesia Research,
Lubbock, Texas
Pain Mechanisms and Local Anesthetics: Scientific Foundations for Clinical Practice
CHRISTOPHER J. JANKOWSKI MD

Consultant,
Mayo Clinic and Foundation,
Neuraxial Anesthetic Techniques
MOLLY JOHNSTON RN
Texas Wesleyan University,

Fort Worth, Texas
Organization Function of the Nerve Block Facility
ALAN D. KAYE MD, PhD
Professor and Chairman,

Professor of Pharmacology,
Lubbock, Texas
Drugs Used in Regional Anesthesia: Local Anesthetics;
Epidural Steroids
VIII
HENRIK KEHLET MD, PhD
Copenhagen University,
Hvidovre Hospital,
Hvidovre, Denmark
Endocrine-Metabolic Effects
STEVEN KLEIN MD

Division of Ambulatory Regional Anesthesia,
ADRIENNE E. KNIGHT MD

University of Colorado,
Denver, Colorado
Acute Situations: Trauma
MARK KRAFT MD
Private Practice,
Las Vegas, Nevada
Discography and Intradiscal Electrothermal Annuloplasty
ELLIOT S. KRAMES MD
Medical Director,
Pacific Pain Treatment Centers,
San Francisco, California
Untreated Pain and Its Cost to Society: What Are Our Options?;
Intrathecal Therapies for the Treatment of Chronic Pain
DONALD H. LAMBERT MD, PhD
Anesthesiologist,
Anesthesia Associates of Massachusetts;
Boston University Medical Center,
Boston, Massachusetts
Efficacy of Regional versus General Anesthesia
TIM J. LAMER MD

Mayo Medical School,
Rochester, Minnesota;
Consultant,
IX
Mayo Clinic Jacksonville,
Jacksonville, Florida
Cancer Pain
ERIC LANG MD
Pharmaceutical Licensing Group,

Johnson and Johnson,
Titusville, New Jersey
Clinical Research
ALBERT Y. LEUNG MD
Assistant Clinical Professor of Anesthesiology,

University of California, San Diego,
School of Medicine;
Faculty,
Center for Pain and Palliative Medicine,
University of California, San Diego, Medical Center,
La Jolla, California
Regional Anesthesia for Chronic Situations: Malignant Pain
ANDRES LÓPEZ MD
Chairman,
Móstoles Hospital,
Madrid Montepríncipe Hospital,
Madrid, Spain
EDWARD A. R. LORD MD
Pain Fellow,
University of Texas,
M.D. Anderson Cancer Center
Houston, Texas
LELAND LOU MD, MPH, DABPM
Assistant Professor of Pain Management,

Anesthesiology,
Lubbock, Texas
Drugs Used in Regional Anesthesia: Local Anesthetics;
Radiographic Imaging in Regional Anesthesia;
Spinal Decompressive Neuroplasty via the Caudal and Cervical Approaches
X
DAVID C. MACKEY MD

Mayo Medical School,
Rochester, Minnesota;
Consultant,
Mayo Clinic Jacksonville,
Jacksonville, Florida
Cancer Pain
CARLOS B. MANTILLA MD

Senior Associate Consultant,
Mayo Clinic,
Cancer Pain
FRANCO MARINANGELI MD
Researcher,
School of Specialization in Anesthesiology,
L’Aquila, Italy
MICHAEL D. McBETH MD
Clinical Instructor (Voluntary),

University of California, San Diego,
School of Medicine,
La Jolla, California;
Director,
Pain Management Group,
Assistant Chief,
Kaiser Permanente,
San Diego, California
COLIN J. L. McCARTNEY MD
University of Toronto;
Toronto Western Hospital,
Toronto, Ontario, Canada
Training Education of a Physician for Regional Anesthesia
XI
ROBERT S. F. McKAY MD
Associate Professor of Anesthesiology and Obstetrics/Gynecology,

University of Kansas School of Medicine;
Medical Director and Chairman,
Wesley Medical Center,
Wichita, Kansas
Efficacy and Outcome of Regional Anesthesia Techniques in Obstetrics
SEBASTIANO MERCADANTE MD
Director,
Anesthesia and Intensive Care Unit,
Pain Relief and Palliative Care Unit,
La Maddalena Cancer Center,
Palermo, Italy
Equipment and Techniques
GENE MORETTI MD

MAURO S. NICOSCIA MD
Servizio di Anestesia e Rianimazione,

Ospedale S. Carlo,
Genova Voltri, Italy
Organization of Palliative Care Services
KAREN NIELSEN MD

Duke University Medical Center,
DAVID NIV MD
Professor Sackler Faculty of Medicine,

Tel-Aviv University;
Director Center for Pain Medicine,
Tel-Aviv Sourasky Medical Center
Tel-Aviv, Israel
Clinical Research
XII
MARK C. NORRIS MD
Henry Medical Center,
Stockbridge, Georgia
Acute Situations: Obstetrics
MAURICIO ORBEGOZO MD
Comprehensive Pain Care,

Calumet City, Illinois
Facet Block and Denervation
ANTONELLA PALADINI MD
Regional Hospital “S. Salvatore”

L’Aquila, Italy
Organization of an Acute Pain Service Pain Management
LOUIS M. PANLILIO MD
Assistant Professor of Anesthesiology and Critical Care Medicine,

The Johns Hopkins University School of Medicine;
Director of Acute Pain Medicine,
The Johns Hopkins University Hospital,
Baltimore, Maryland
Chronic Pain: Neuropathic Pain: Outcome Studies on the Role of Nerve Blocks
FRANCIS S. PECORARO MD
Medical Director,
Integrated Pain Rehabilitation,
Integrated Pain Management,
Concord, California
Untreated Pain and Its Cost to Society: What Are Our Options?;
Intrathecal Therapies for the Treatment of Chronic Pain
RICARDO S. PLANCARTE MD
Professor of Postgraduate Medical Especiality in Anesthesia,

Intensive Care and Pain Clinic,
Universidad Nacional Autónoma de México;
Chairman,
Pain Clinic and Palliative Care Department,
Instituto Nacional de Cancerologia,
México D.F. México
Monitoring in Regional Anesthesia
XIII
GABOR B. RACZ MD
Grober and Murray Professor,

Director,
Pain Services,
Chairman Emeritus,
Lubbock, Texas
Spinal Decompressive Neuroplasty via the Caudal and Cervical Approaches;
Trigeminal Ganglion Procedures
P. PRITHVI RAJ MD, DABPM
Co-Director of Pain Services,
Lubbock, Texas
Historical Aspects of Regional Anesthesia;
Organization and Function of the Nerve Block Facility;
Aids to Localization of Peripheral Nerves;
Common Techniques for Regional Anesthesia: Conduction Blocks;
Efficacy of Regional versus General Anesthesia;
Endocrine-Metabolic Effects;
Regional Anesthesia Options in Surgical Specialties
SRINIVASA N. RAJA MD
Critical Care Medicine,
Director of Pain Research,
Division of Pain Medicine,
Baltimore, Maryland
NARINDER RAWAL MD
Professor,
University Hospital,
Örebro, Sweden
MIGUEL ANGEL REINA MD

Móstoles Hospital,
Madrid Montepríncipe Hospital,
Madrid, Spain
XIV
FRANCISCO JAVIER MAYER RIVERA MD
Assistant Professor of Postgraduate Medical Course in Pain Clinic,

Universidad Nacional Autónoma de México;
Coordinator of Palliative Care Service Pain Clinic and Palliative Care,
Instituto Nacional de Cancerologia
México D.F. México
Monitoring in Regional Anesthesia
RICARDO RUIZ-LÓPEZ MD
Clinica del Dolor de Barcelona,

Barcelona, Spain
Organization of Chronic Pain Services;
Organization of Palliative Care Services;
Radiofrequency for the Treatment of Chronic Pain
RAJ SABAR MD
Resident Physician,
Lubbock, Texas
Drugs Used in Regional Anesthesia: Local Anesthetics
XAVIER SALA-BLANCH MD
Staff Anesthesiolgist,
Servicio de Anestesiologia y Reanimacion,
Hospital Clinic de Barcelona,
Universidad de Barcelona
Barcelona, Spain
ROBERT P. SANDS JR. MD
Clinical Assistant Professor of Anesthesiology,

State University of New York at Buffalo;
Director,
Resident Education,
Roswell Park Cancer Institute,
Buffalo, New York
PHILLIP S. SIZER JR. MEd, PT, MOMT, PhD(c)

Lubbock, Texas
Facet Block and Denervation
XV
SUSAN STEELE MD

Director,
Medical Director,
Ambulatory Surgery Center,
CARL A. TANDATNICK MD
Attending Physician,
Diagnostic Clinic,
Largo, Florida
PRABHAV TELLA MPH
Research Program Coordinator,

Baltimore, Maryland
ATHINA N. VADALOUCA MD
Assistant Professor of Anesthesia,

Pain Management,
University of Athens;
Aretaeon Hospital
Athens, Greece
Organization of Palliative Care Services;
Drugs Used in Regional Anesthesia: Adjuvant Drugs
GIUSTINO VARRASSI MD
University of L’Aquila Medical School,
L’Aquila, Italy
RAMANI VIJAYAN MD
Professor of Anaesthesiology,
University of Malaya;
Consultant Anaesthesiologist,
University of Malaya Medical Centre,
Kuala Lumpur, Malaysia
The Practice of Regional Anesthesia in Developing Countries
XVI
MARK S. WALLACE MD
Associate Professor of Clinical Anesthesiology,

Fellowship Program Director,
University of California, San Diego, School of Medicine;
Program Director,
University of California, San Diego, Medical Center,
La Jolla, California
MICHAEL A. WEAVER MD

Pennsylvania State University College of Medicine;
Milton S. Hershey Medical Center,
Hershey, Pennsylvania
BRANKO M. WEISS MD
Consultant,
University Hospital,
Zurich, Switzerland
Efficacy and Outcome of Regional Anesthesia Techniques in Obstetrics
JACK L. WILSON MD

Consultant,
Mayo Clinic
Cancer Pain
CYNTHIA A. WONG MD
Northwestern University Medical School;
Chief,
Section of Obstetric Anesthesiology,
Northwestern Memorial Hospital,
Chicago, Illinois
Acute Situations: Obstetrics
GILBERT Y. WONG MD

XVII
Consultant,
Mayo Clinic,
Cancer Pain
CHRISTOPHER L. WU MD

Critical Care Medicine,
Director,
Acute Pain Service,
Director,
Regional Anesthesia,
Baltimore, Maryland
Efficacy of Neuraxial and Peripheral Nerve Blocks in Acute Pain Management
MYRON YASTER MD
Professor of Anesthesiology, Critical Care Medicine, and Pediatrics,

Baltimore, Maryland
Pediatric Pain Management
XVIII
Foreword
Dr. Raj painstakingly has assembled a stellar roster of internationally recognized experts to put
the stamp of credibility and currency on Textbook of Regional Anesthesia . Sweeping changes
have modernized the practice of regional anesthesia since Dr. Raj first published Handbook of
Regional Anesthesia in 1985: unheard-of imaging techniques, safer local anesthetics, cutting-
edge laboratory experiments, innovative clinical studies, streamlined practice methods, and (at
least in the United States) increasingly restrictive regulation of medical practice that rewards
haste, hustle, and false economy over individualized patient care. All these happenings—the
good, the bad, the new, the challenging, and the basics—have been addressed in this fully current
comprehensive text, a work with a sweeping mandate that promises to set the global gold
standard of regional anesthesia for the present and years to come.
Textbook of Regional Anesthesia is a seminally mature work of awesome breadth and depth—
truly the capstone of a lifetime of research, graduate teaching, clinical experience, and
worldwide travel. The contributors, likewise, are established scholars in their own right whose
global representation makes this not just another North American text, but a learning and
teaching resource of international proportions.
Dr. Raj has the uncanny knack of picking rising young talent and for offering them the
opportunity to prove their worth. Some of the old war horses return to contribute the seasoned
traditional expertise that lends structure and backbone to any comprehensive text. But the input
from younger, less-established voices is refreshing; their chapters contribute the new blood that
gives regional anesthesia currency and nurtures its growth, and they pass on the hard-gained
nuggets of clinical science to the next generation of physicians now in training, but soon to be in
independent practice.
Ten section editors groomed the eight discrete sections to include not just the traditional how,
what, when, and why of regional anesthesia but also the newly emerging trends, such as the hard
data from clinical outcome studies and the ongoing shift toward evidence-based medical
practice. The detailed sections on procedural fundamentals and advanced interventional
techniques will prove of particular interest to busy clinicians. The resulting 54 chapters,
contributed by the editors with the assistance of many international collaborators, span the field
of regional anesthesia from past history, through current practice, to future directions to form a
monumentally defining work.
With its handsome modern design and contemporary ambience, Dr. Raj’s Textbook of Regional
Anesthesia once more demonstrates that the art of regional anesthesia—crafted and refined over
the decades by grand masters such as Labat, Bier, Bonica, Macintosh, and so many others—lives
on to flourish and grow. As one of Dr. Raj’s contemporaries and former pupils, I am honored to
recommend this fine textbook to my colleagues, and I am proud yet humbled to have been asked
to introduce this, the crown jewel of his collective works.
RUDOLPH H. DE JONG, MD
Professor (Hon), University of South Carolina,
Columbia, South Carolina
XIX
Preface
Textbook of Regional Anesthesia is a further progression of regional anesthesia books I have

published along with the publisher, Churchill Livingstone. This book presents a fresh look at the
dynamic field of regional anesthesia. The format and content of the textbook are innovative. The
book has new authors and contains new material, new sections, and updated chapters from the
last book I published on this subject, Clinical Practice of Regional Anesthesia .
The idea of writing this book arose because apart from Neural Blockade in Clinical Anesthesia
and Management of Pain , edited by Cousins and Bridenbaugh, there wasn’t another regional
anesthesia textbook available to clinicians. Rapid advances are occurring in regional anesthesia
and pain management. The aim of Textbook of Regional Anesthesia is to provide updated content
in this field to all clinicians.
This book presents a new organizational structure. Even though I have remained as the chief
editor, well-recognized international authorities in regional anesthesia were asked to be section
editors and provide advice on the topics included. Section editors Christopher Wells, Diego
Beltrutti, James E. Heavner, David Niv, Richard L. Rauck, Honorio T. Benzon, Gabor B. Racz,
Carol Warfield, Peter S. Staats, and Serdar Erdine were chosen for their expertise and
international reputations. Great care has been taken to see that all aspects of regional anesthesia
are included in this edition. Advanced regional anesthesia techniques and outcome sections are
the special features of the book.
Many thanks are to be offered for the completion of this book. The publisher comes to mind first.
Everyone at Churchill Livingstone has been very understanding of my needs and, despite
changes in ownership, support from them has remained solid. The section editors are especially
to be thanked for their foresight, perseverance, and expertise in getting this edition completed.
Illustrators and copy and manuscript editors have been working extremely hard for a prolonged
period, when the demands for completing their tasks were numerous and incessant. I am
indebted especially to Susan Raj for her coordinating efforts and to Marla Hall for her assistance
in getting the manuscripts ready. I congratulate the authors for completing their chapters and
maintaining a high quality of scientific content. I hope readers will find this book current and
useful in their practice.
P. PRITHVI RAJ, MD
XX
Section I - Development of Regional Anesthesia Chapter 1 - Historical Aspects of Regional Anesthesia
Section I - Development of Regional Anesthesia

Christopher Wells
1
Chapter 1 - Historical Aspects of Regional Anesthesia
P. PRITHVI RAJ
Regional nerve blocks are based on the concept that pain is conveyed by nerve fibers, which are amenable to
interruption anywhere along their pathway. The idea that pain is conducted in the nervous system originated with the
specific theory of Johannes P. Müller, described in 1826. This was followed by the alternate intensity theory of Erb
[1]
in 1874 (Dallenbach, 1939), an idea that later culminated in the gate theory of pain by Melzack and Wall in 1965. [2] [3]
Regional anesthesia was not available when general anesthesia was first successfully administered in 1846. It had to
wait until 1855, when Rynd described the idea of introducing a solution of morphine hypodermically around a
peripheral nerve. Because he did not have a needle or a syringe, he improvised by introducing a trocar and cannula
[4]
into the region and then allowing the solution to reach the nerves by gravity. Wood, in 1855, was the first person to
perform a subcutaneous injection with a graduated glass syringe and a hollow needle, a device developed initially by
Pravaz for injection of ferric chloride into an aneurysm to produce a coagulation [5] [6]
( Fig. 1-1 ).
Efforts to Produce Analgesia Before the Discovery of Regional Anesthesia
Primitive man, seeing in illness and pain the work of evil spirits that had taken possession of the body, tried to get
rid of such invaders by methods based on effects on the patient’s imagination. Incantations, charms, amulets, special
ceremonies, and faith in the power of medicine men and sorcerers made more or less deep impressions on the
subject. In many cases, these methods probably contributed to the alleviation, or even abolition, of pain. A kind of
local anesthesia was, therefore, able to be established, which was found valuable in connection with surgical
interference, especially in minor operations.
From early times, mankind has very often used analogous methods, although the procedures have changed with our
supposedly—or perhaps actually— increased understanding of nature and of man himself. Thus, religion has played
a role in this connection and still does to some extent, as well as the personal influence of prominent men (e.g.,
laying on of hands by kings and prophets). Physicians and charlatans have both found similar methods useful in
numerous cases, and it has often been difficult to differentiate between the two types of practitioners. The main
difference between them seems to be that the physician, with his better knowledge of the nature of illnesses and
resources to combat them, has a clearer understanding of the limitations of the psychic methods.
A classic example of the influence of psychic factors in alleviating pain is the well-known story of J. Mesmer
(1734–1815) and his pretended use of “animal magnetism,” which was an effort to apply to living matter proof of
the great progress that had just recently been made in those days with regard to electrical and similar phenomena.
Mesmer’s methods were soon severely criticized, and an official commission, with Lavoisier as one of its members,
concluded, “Imagination does everything, magnetism nothing.” There was certainly, however, a kernel of truth in
Mesmer’s work, insofar as the practical results were remarkable. The mystery may have increased the effects.
In 1843, Elliotson, the first holder of a medical professorship at the University College in London and “one of the
eminent Victorians,” described the successful use of “the mesmeric state” to abolish pain in clinical operations ( [7]
Fig. 1-2 ). His results were interesting and indicated a close connection between bodily functions and the mental
state. Unfortunately, he supported Mesmer’s idea of some “fluid” (in modern language, radiation) as the link
between the doctor and the patient. After meeting with strong opposition, he resigned his professorship and
continued to work on the problem, without convincing even his surgical colleagues of the usefulness of
“mesmerism” in reducing or preventing the pain of operations.
Three years later, Esdaile, who had been inspired
2
Figure 1-1 Syringe and needle as used in 1855.[6]
by Elliotson’s work, published a paper on his experience with “mesmerization” in India. He had obtained
[8]
“complete suspension of sensibility to external impressions of a most painful kind.” Among his successful cases
were the amputation of an arm and the removal of an 80-pound tumor. He had a total record of 261 painless
operations (with 5.5% mortality) under mesmerization. After returning to Scotland, however, Esdaile found it
impossible to repeat his excellent results of India, thus demonstrating the varying susceptibility to the treatment as
well as the role played by racial characteristics in this field.
In his comprehensive work on hypnosis, Braid also dwelled on its power to alleviate or prevent pain in surgery. He
[9]
mentioned that he himself had painlessly extracted teeth from six patients, and that, in other cases, patients
experienced only a little pain under the influence of hypnosis. There were others whose experiences accorded with
those of Braid, as described in the following quotation (translated from the original) from a book by the well-known
Swiss psychiatrist Forel:
I have arranged extraction of teeth during hypnosis. I have removed a corn and made deep stabs without the
hypnotized having felt anything. It was sufficient to assure that the pertinent part of the body was dead, insensible.
Surgical operations and even parturitions are possible, though less often, under hypnosis. … If one succeeds in
suggesting a thorough anesthesia, painless surgical operations are always possible, if they are not too protracted. But
the anxiety before the operation, especially if the patient sees the extensive preparations, usually destroys the
suggestibility. There lies the greatest difficulty.[10]
The limitations of the method and the great individual variations mentioned are clearly illustrated in the passage in
the preceding paragraph. On the other hand, psychological considerations in connection with other factors will
always be important. This may be seen in a report by McGlinn, who says:
It was for the reasons of unpleasant reaction from drugs and the fear of complete loss of consciousness when using
spinal anesthesia that led me to look for some method that would obviate these objections and allay the fears of the
conscious patient. Anything which would appeal to the senses sufficiently to keep the minds of the patients occupied
would divert from them the thought of operation. Music best fulfilled the requirements. … Music has been used for
untold ages during operations and childbirth … to divert the mind of the sufferer. … We have been using music for
a year and have been well satisfied with the results and feel that it is a valuable addition to the operating room. [11]
Mention should also be made of acupuncture, which has been used in China since approximately 2700 B.C. and
which was introduced somewhat later in Japan (Fig. 1-3 (Figure Not Available) ). This method consists of inserting
metal needles at certain points of the skin to varying depths. It has been used against numerous diseases (e.g.,
[12] [13]
sciatica, other kinds of neuritis), with the aim of counteracting pain and other symptoms. According to Hume, Hun [14]
T’O, “the most famous surgeon in Chinese medical history,” who was born about A.D. 190, “used few drugs and
needles, and he used cautery in only a few places. If the disease proved resistant to acupuncture and if drugs proved
unavailing, he then first caused the patient to swallow wine containing an anesthetic effervescent powder, which
produced intoxication and complete insensibility.” He could then perform
3
Figure 1-3 (Figure Not Available) Ming Dynasty acupuncture chart showing puncture points along meridians of the body, which apply to treatment for various organs, often quite distant from
the point. This important Chinese medical technique has been in continual use for thousands of years. (From Lyons AS, Petrucelli JR: Medicine: An Illustrated History. New York, Albans, 1978.)
the desired operation. This shows that although acupuncture was also used as a local anesthetic, it was not always
reliable. It has been noted that the method of acupuncture is used today in places where there is a shortage of
modern chemical anesthetics. Acupuncture has gained a certain level of acceptance in Europe, but it seems to have
[15]
been insufficiently studied by modern methods. Its efficacy has been partly explained as a kind of “referred pain,”
but probably there is also some psychological factor contributing to the effect.
NERVE COMPRESSION
Pressure on nerves to produce local anesthesia may well be of ancient origin, especially in limb amputations. If the
pressure is sufficiently strong, the innervated area becomes anesthetized. In such cases today, we speak of
conduction, or regional anesthesia.
Corradi considered it probable that compressions were used by ancient healers to stop bleeding, but whether this
[16]
also led to abolition of pain, as he assumed, is doubtful. However, the famous military surgeon A. Paré (1510–1590)
gave a good description of the use of compression for amputation, mentioning three advantages derived from firm
ligation above the seat of operation. First, because the muscles were simultaneously pushed proximately, the bone
could be better covered after the amputation and recovery was more rapid; second, bleeding was prevented; and,
third, pain was greatly diminished.
In 1784, a young English surgeon, J. Moore, tried to improve the compression method ( Fig. 1-4 ). In experiments [17]
on himself, he found that complete insensibility of the whole leg and loss of power to move it could be obtained in
about half an hour after he had applied compression to the sciatic as well as the crural and obturator nerves. He
constructed a special apparatus that facilitated compression of two opposite areas while still permitting a certain
flow of blood. In this case, complete insensibility extended only to below the knee. The method was tried in
combination with the tourniquet, which had produced insensibility in a patient whose leg was amputated below the
knee by no less a person than J. Hunter. The operation seems to have been successful, but Moore clearly saw the
necessity for further trials. His work, however, demonstrated the relative difficulties in obtaining the desired result,
which could hardly have had a stimulating influence. Furthermore, discussions arose as to whether the anesthesia
after compression was due to ischemia or to direct action on the nerve. Such a discussion was published after a
communication by Le Fort. The introduction by Esmarch, another prominent military surgeon, of his
[18] [19]
“bandage”—a rubber tube that was greatly stretched and then wound four or five times around the limb above the
place of operation—was a revival
Figure 1-4 Apparatus designed by J. Moore for compression of nerves (1784).
of Paré’s method. When cocaine was introduced as a local anesthetic, it seemed desirable to use the Esmarch
bandage in conjunction with it in order to lower the rate of absorption of the cocaine and thus to prolong its effect.
The method of arresting the local blood flow before the injection of a relatively weak solution of cocaine close to the
regional nerves (e.g., those of the fingers and toes), was adopted by several workers, among them M. Oberst at the
surgical clinic in Halle, as described by Pernice. The question again raised was whether the complete stoppage of
[20]
blood flow to the limb itself contributed to the change in sensibility.
Valuable insight has been obtained on compression and other kinds of anesthesia by studies of the order in which
different nerve fibers are affected. As early as 1881, Lüderitz observed that in animal experiments the motor fibers
[21]
4
were less resistant to pressure than the sensitive fibers, and he therefore assumed that some physiologic difference
existed between the fibers. Boeri and di Silvestro studied the corresponding situation in humans with respect to the
sensitive fibers, using the ulnar and sciatic nerves. During pressure, tactile sensations were blocked first, whereas
[22]
thermal stimuli were less influenced and pain impressions were the least affected. The same order was found after
application of the Esmarch bandage. Refrigeration, however, first affected pain and then thermal sensations, and
finally tactile stimuli became inefficient. The order was thus the reverse of that observed under constriction.
REFRIGERATION
Hunter, who as a military surgeon took a great interest in the prevention of pain, performed experiments on animals
and men to study the effect of refrigeration. Here is a typical example of his observations:
I have taken a bucket of cold spring water with me when I made an attempt on a wasp’s nest, and put my hand into it
after having been stung; and while my hand was in the water I felt no pain, but when I took it out again the pain was
greater than when I put it in.
[23]
Furnas mentions that D. J. Larrey (1766–1842), the famous surgeon-in-chief to the Grande Armée, “recounted the
anesthetic effects of exposure to freezing battlefield conditions in his memoirs; the −19°C temperature allowed him
to perform painless amputations on the half-frozen soldier-patients.” The only references given are the four volumes
of Larrey’s great work from the battles (Larrey, 1812). Braun and Killian, in their respective handbooks, reported
[24] [25]
that Larrey, in February 1807, at the battlefield of Prussian-Eylau painlessly amputated numerous wounded soldiers
with good results. The battle itself (1812) was characterized by Larrey as the most terrible that had ever occurred,
and he complained several times about the cold, which once went down to a low of −19°C and became so intense
that the instruments often fell from the hands of the pupils who were to serve him during the operations. He does not
mention, however, that insensibility had occurred in the patients, although this is very probable.
The most obvious effects of a cold environment on sensibility to pain appear more or less locally in peripheral parts
of the body such as the limbs, ears, and nose, where circulation may be impaired at the same time. There is probably
also some influence on the central nervous system, as is apparent from Larrey’s reports. This may indirectly be of
importance, because it may diminish shock symptoms.
The introduction of general anesthesia through inhalation of ether or chloroform was hailed as one of the greatest
advances in the history of medicine. Early experience of death under the influence of the anesthetics, however, gave
renewed urgency to the question of substituting local anesthetic agents for those of general action. In an article from
1848, Simpson, famous for the introduction of chloroform, emphasized that “if we could by any means induce a
[26]
local anesthesia, without the temporary absence of consciousness which is found in the state of general anesthesia,
many would regard it as a still greater improvement in this branch of practice.” He had tried localized effects of
vapors from chloroform, ether, carbon disulfide, and even hydrocyanic acid. Although a reversible local action
could be obtained, especially in lower animals, the results in mammals were less convincing. In the human subject,
the local effect of chloroform vapors was not sufficiently deep to allow the part to be cut or operated on without
pain, and it would probably have been dangerous.
Simpson’s article led Arnott to call attention to the benumbing effect of cold, which he had described before. A
[27]
bladder, taken from a small pig, containing tepid water was placed so as to cover the skin to be rendered insensible;
ice and salt were then gradually “dropped in” to bring the temperature considerably below the freezing point. After
15 to 20 minutes, all sensations generally having disappeared, the operation could begin. Arnott added the following
remark: “Perhaps … so low a degree of cold as I have mentioned is not required to produce the requisite degree of
insensibility, and if pressure is conjoined with cold, so as to squeeze blood from the part, and check the circulation,
the effect would certainly be more rapid, complete and extensive.”
Richardson found that a frozen nerve showed a considerably lessened conductivity of electric current, and the
[28]
same was observed when mechanical pressure was applied. The nerve was thus temporarily disorganized, but if it
was frozen until all the water had been converted to ice, transmission of the current was stopped completely and
permanently. This is, of course, in agreement with the fact that the metabolic processes in the cells are highly
dependent on the temperature. At a few degrees above zero, the metabolism of a warm-blooded animal is only a few
percentage points less than its value at normal body temperature.
5
In conformity with these results are those obtained by Trendelenburg. In 1914, his interest was aroused by a very
[29]
unusual case of an 8-year-old boy suffering from tetanus infection. When the boy was brought to the hospital, he
was seized within a short time by three heavy attacks of convulsions, with fixation of the thoracic cage, increasing
cyanosis, and, in one of the attacks, unconsciousness. Both phrenic nerves were divided, so that artificial respiration
with oxygen could be applied when needed. This, together with careful supervision and the use of chloral hydrate,
made it possible to save the boy’s life, but owing to the operation he did not regain his diaphragmatic respiration.
This case inspired Trendelenburg to investigate whether it would not be possible to break the transmission in motor
fibers in such a way that regeneration could take place after a period of time. He froze nerves in cats and dogs by
sucking ethyl chloride through a tube positioned around the nerves and thus succeeded in breaking the conductivity
of the motor fibers; after several months, regeneration started and became complete after about a year. Further
experiments demonstrated that sensory fibers of mixed nerves (e.g., sciatic nerve) were put out of action at a
[30] [31]
much lower degree of freezing than the motor fibers; hence, graded freezing could be used in cases of gunshot
wound neuritis and for relieving patients from intolerable pain (the work was performed during World War I) and
some other conditions. Perthes confirmed the beneficial effects of this treatment in humans.
[32]
Development of Regional Anesthesia
The idea that drugs might diminish local pain not only by their action on the central nervous system but also by their
direct effect on the nerve endings or on the nerves themselves was put to trial after syringes for injection were made
available in the middle of the 19th century. Thus, ethyl alcohol, in relatively high concentrations (>50%), was used
to treat patients with neuritis. The injection of alcohol into the affected nerve killed it, resulting in alleviation of the
patient’s pain. The method is still recommended today in certain cases. Injections of opium suspensions and, later,
[15]
of solutions of morphium chloride into the vicinity of the nerves were also tried, but results were poor. As was
demonstrated by Macht and his collaborators, the peripheral action of opium alkaloids is—in contrast to the
[33] [34]
central effect—not prominent, and it was also shown that morphine had a lesser effect in this respect than
papaverine and narcotine.
Cocaine
Long before the conquest of Peru by Francesco Pizarro in 1532, the Incas knew that the leaves of the coca bush
could be used to stimulate a general feeling of well-being and prevent hunger. A small quantity of an amorphous
mixture of coca leaves was prepared by Gaedcke, which on somewhat uncertain grounds, he believed to be an
[35]
alkaloid that he called erythroxyline. He thought erythroxyline might be related to caffeine, but he was unable to
prove it. A few years later, Niemann obtained from coca leaves a crystalline alkaloid to which he gave the name
[36] [36A]
cocaine. He found that on degradation the substance gave rise to a weak base, ecgonine, and also to benzoic acid.
After Niemann’s death, the work was continued by Lossen, who also split off methyl alcohol.
[37]
It has been suggested that the Incas knew about the anesthetic properties of coca leaves, which they used to diminish
local pain during certain surgical procedures. Thus, Singer and Underwood stated, “From early times, the natives of
Peru knew about the anesthetic qualities of the coca plant, and they used to chew leaves and allow the saliva to run
over the part of the body which had to be cut.” Killian goes further and says, “It seems that the juice of the leaves
[38] [25]
of the coca plant was dropped into painful wounds in order to decrease pain when trephining the skull.” Some time
earlier, Leake, in a historical review, made the following statement:
[39]
Local anesthesia was established upon a firm basis with the demonstration of the local anesthetic properties of
cocaine. The aboriginal inhabitants of the highland of South America were acquainted with these properties. Roy L.
Moodie has reconstructed an early surgical operation among the Incas, showing a blanket-clad shaman using a
cautery to make a cruciform incision in the scalp of a woman suffering from melancholia. The operator chewed a
cud of coca leaves, the juice from which he could drop upon the wound if the pain became severe.
To this might be added that another picture of trephining in ancient Peru, as imagined by R. A. Thom, depicts the [40]
corresponding situation without the use of the coca leaves, nor is it mentioned in the accompanying text (written by
Bender and checked by the historian E. H. Ackerknecht). No reference to early observations of the actual use of
coca leaves for the purpose mentioned has been given by any of the authors quoted. Nor was Dr. S. H. Wassén of
the Ethnographical Museum of Gothenburg, who kindly consulted the ethnographic literature to ascertain whether
any mention was made of this point, able to find any indication that such was the case. It seems that the whole story
is only the result of imagination rather than definite knowledge.
Even if the aborigines of Peru had applied coca leaves in any form to wounds for the purpose of allaying pain, such
a practice would undoubtedly have been completely forgotten shortly after the conquest of Peru by the Spaniards. It
is, of course, possible that loss of this knowledge could have been a consequence of the intense efforts by the
6
representatives of the Church to eradicate what they considered to be superstitious behavior. As is well known, the
[41]
Church’s disapproval resulted for some time in the prohibition of chewing of coca leaves as a stimulating agent.
Later, it was demonstrated that chewing coca had a considerable stimulating effect on the working capacity of
Indian laborers, and the ban on chewing coca leaves was lifted, but there may not have been any understanding of
the value of the juice in lessening sensibility.
Niemann described that cocaine on the tongue caused a kind of anesthesia, so that it became temporarily insensible
to touch. He tried it on his own eye and observed no effects from it. Eight years later, Moréno y Maiz, who later
became the physician-in-chief of the Peruvian army, wrote a fairly extensive paper on cocaine. Using frogs and
[42]
guinea pigs, he confirmed an increased irritability of the brain manifested by convulsions. Moreover he also
observed in experiments on himself the effects of cocaine on his general feeling of well-being, leading him to
conclude that “these were the most blessed moments of my life.” He also observed a peripheral effect leading to
insensibility after local injection of the alkaloid into the calf muscle. Although he did not closely follow up on this
finding, he understood its possibilities, because he remarked in a footnote, “Could we use it as a local anesthetic? It
is not possible to give an answer after such a small number of experiments; the future will have to decide this.”
Bennett carried out a comparative study of caffeine (and the identical substance, theine), guaranine, theobromine,
[43]
and cocaine and found that they were to all appearances identical in pharmacologic action. In small doses, they
produced cerebral excitement and partial loss of sensibility; in large doses, complete paralysis. Nothing is mentioned
about local effects. With this background, it is perhaps not so remarkable that a British medical commission in 1881
reported on cocaine as merely being a poor substitute for caffeine. [44]
In the same year, a detailed report by von Anrep was published in which he described a number of experiments
[45]
with the new substance on mammals, birds, and even himself. He confirmed earlier findings on the general
stimulating effects on animals. About the studies on himself he said:
Local Action.
(a) On cutaneous nerves, I have injected a weak solution (0.003–0.5 percent) under the skin of my arm, and at
first experienced a feeling of heat; then insensibility to rather strong pinpricks at the place of injection; after about
15 minutes, the skin became quite red; and after about 25 to 30 minutes, all these manifestations disappeared again.
(b) On the nerves of the tongue: Painting the tongue with a somewhat stronger solution (0.005–0.5 percent) acts
anesthetizing on the taste nerves; after 15 minutes, I was unable to differentiate between sugar, salt, and acids.
Pinpricks gave not rise to pain, whereas the other, not painted side of the tongue reacted normally.…
(c) On the pupil: With local use on the pupil in mammals, there always sets in mydriasis. In frogs not
constantly.…
von Anrep concluded his report on the experiments in the following terms:
I have had the intention after the study of the physiological effects of cocaine on animals also to make experiments
on man. Other engagements until now have prevented me from doing so, and the animal experiments do not permit
practical conclusions. In spite of this, I would like to recommend cocaine as a local anesthetic and in melancholiacs.
Thus, von Anrep has pointed very definitely to the possibility of using cocaine for local anesthesia as well as for its
psychological effects. When one remembers that the disappearance of hunger after chewing coca was considered to
be the result of a local anesthetic effect on the mucous membrane of the stomach, it seems very remarkable that von
Anrep’s advice did not lead to anything for several years, especially because some valuable results in the treatment
of pain had been obtained with cocaine even before von Anrep’s paper. Thus, Collin reported on experiments by
[46]
Ch. Fauvel on the anesthetic action of coca on the mucous membrane of the mouth and also by him and others on
the useful application of preparations containing cocaine, especially in cases of granulatomatous pharyngitis and
tonsillar angina. The preparations used were made by A. Mariani, who had erected a plantation of coca bushes close
to Paris and who made the Mariani brand wine as well as paste and lozenges. The wine was Bordeaux and was
thought to be especially valuable. Einhorn mentioned—without any reference to Mariani—that Bordeaux wine
[47]
often causes local anesthesia of short duration on the tongue; he supposed that this was owing to the presence of
esters of aromatic acids, although he did not think their existence had been proved. One is tempted to question the
remark made by Clark when he discussed the history of general anesthesia: “Indeed, an enemy of our profession
might claim that it showed extreme slowness and conservatism in accepting the gift offered by science.” [48]
7
The Birth of Regional Anesthesia
The decisive step in the development of regional anesthesia was taken by C. Koller (1858–1944), a young Viennese
physician who had been working for some time in S. Stricker’s experimental pathology laboratory, and who also
devoted himself to the study of ophthalmology ( Fig. 1-5 ). Both these circumstances were of importance, because
Koller became familiar with experimental methods and also had personal experience with the need for using local
anesthesia when operating on the eyes. He had observed the unsuitability of general narcosis for eye operations,
because not only is the cooperation of the patient greatly desirable in such operations but the sequelae of general
narcosis— vomiting, retching, and general restlessness—are frequently so severe that they could constitute a grave
danger to the operated eye. This was especially true at a time when narcosis was not skillfully administered by
trained experts, as it is now. During Koller’s time, eye operations were performed without the use of any anesthesia
whatsoever.
The information is from Koller’s retrospective survey written many years later. He, therefore, experimented with
[49]
chloral hydrate, bromide, morphine, and other substances, but without success. For a while, he gave up his
experiments.
In the summer of 1884, Sigmund Freud (later to achieve fame as a psychiatrist) was attached to the general hospital
in Vienna as a “Sekundararzt.” He had been treating a colleague who was a morphine addict by substituting cocaine,
and he asked Koller to cooperate in some studies evaluating the effect of cocaine on muscular strength and degree of
fatigue as measured by a dynamometer.
Koller thus became familiar with cocaine and decided to try it on the eye. Some interesting details have been told by
Koller’s daughter, who quotes an untitled paper from 1919 written by her father. Koller noted that the numbing
[50]
effect of cocaine on the tongue suddenly made him realize that he was carrying in his pocket the local anesthetic he
had searched for years earlier. He immediately went to Stricker’s laboratory with the well-known result. This story
is supported by the only witness to the discovery, the assistant of the laboratory, J. Gaertner.[51]
Freud was planning a vacation, and before he left, he asked his friend L. Königstein, an assistant professor of
ophthalmology, to try cocaine in patients with eye diseases. When Freud returned from his vacation, the preliminary
communication by Koller had already been made. Thus, in 1884, Koller’s famous communication about cocaine as a
local anesthetic took place. He was naturally very anxious to report his findings as soon as possible, and because he
was unable to go in person to the German Ophthalmological Society’s meeting in Heidelberg on September 15 and
16, he invited Dr. Brettauer from Trieste to read the communication at the session. This brief classical report is [52]
quoted in full from the translation published in Archives of Ophthalmology:
It is a well-known fact that the alkaloid cocaine, which is obtained from coca leaves (Erythroxylon coca) makes the
mucous membrane of the throat and mouth anesthetic when brought in contact with it, and this led me to investigate
the action of this agent on the eye. I have reached the following conclusions:
After a few drops of cocaine hydrochloride (I used a 2% watery solution of cocaine in my experiments) are applied
to the cornea of a rabbit or a dog, or after the solution is instilled into the conjunctival sac in the usual manner, a
stage of irritation develops which generally lasts from 1/2 to 1 minute, as shown by the contraction of the eyelids,
and the cornea and the conjunctiva of the eyeball become insensitive to contact. All reflexes, which usually develop
on touching the cornea, such as closure of the lid, eversion of the eyeball, and drawing back of the head, are
eliminated. Insensitiveness is complete and lasts 10 minutes. During this time the cornea can be scratched with a
needle, punctured, or cauterized with silver nitrate until it becomes white, or deep incisions can be made without the
animal reacting in any way. Not until the aqueous escapes or the iris is touched is there a sensation of pain. Whether
additional drops of cocaine hydrochloride applied after a corneal section, or cocaine administered by some other
procedure, will also produce anesthesia of the iris has not been investigated on account of the difficulties of
examining sensation in animals. In my experiments with animals, I found that when anesthesia ceases there exists a
moderate and not always well-pronounced dilatation of the pupil.
As these experiments on animals succeeded, I tried the action of cocaine on myself and on a colleague, with the
following results: The immediate effect of the instillation of 1 or 2 drops of a 2% solution of cocaine was a moderate
burning, which lasted for 1/2 minute and was succeeded by a feeling of dryness. The palpebral fissure appeared
wider than that of the untreated eye. If the cornea or the conjunctiva of the eyeball was touched with the head of a
pin 1 or 2 minutes after beginning the experiment, this contact was appreciated only to the slightest degree. When
the sensation and the reflexes were not completely exhausted, this effect could be obtained by the instillation of
additional drops of cocaine hydrochloride. A depression could be produced in the cornea by pressure on the
conjunctiva, or the eyeball could be grasped with the forceps without producing any sensation whatever.
The state of anesthesia lasted 10 minutes. This was followed by a weakened sensitivity, which was lost after several
hours. During the period of anesthesia, the function of the eye was in no way disturbed. After 20 or 30 minutes
8
following the instillation, the pupil began to dilate. The dilatation increased during the course of an hour to a
moderate grade; in the second hour, it gradually disappeared, and after several more hours (up to 12 hours) was
entirely overcome. During this entire period, the pupil reacted promptly to light and to convergence. The weakness
of accommodation disappeared earlier than the difference in the size of the pupil. I have not had any opportunity to
perform experiments on diseased eyes, though I could convince myself that the anesthetic action of cocaine also
took place in animals in which I had produced keratitis by the introduction of a foreign body.
Perhaps it is not too bold to hope that cocaine can be used with success as an anesthetic in the removal of foreign
bodies from the cornea as well as in more extensive operations, or as a narcotic in diseases of the cornea and
conjunctiva. As I performed these experiments only during the past 2 weeks, I shall have to take up in a later
publication the work which has previously been done on this subject. [53]
Mrs. Koller-Becker placed a facsimile of the original German text at the disposal of Dr. Brettauer. This
communication, a model of scientific accuracy, cautious conclusions, and hopeful optimism, was obviously very
well received by the meeting, especially after demonstrations by Brettauer of the remarkable anesthetic effect of a
2% solution of cocaine hydrochloride on the cornea and conjunctiva of one of the patients at the Heidelberg Eye
Clinic.
The detailed publication mentioned by Koller took the form of a lecture before the Viennese Medical Association on
October 17, 1884. He could then report that his results had already been confirmed in various places in Germany,
and he pointed out that “for us Viennese, cocaine has become a favorite topic because of the thorough review and
interesting therapeutic work of my colleague at the general hospital, Dr. Sigmund Freud.”
He could also add several important observations, such as the fact that ischemia occurred in the normal conjunctiva
after cocaine administration. He saw that the widening of the palpebral fissure preceded the actions on the muscles
in the iris and the ciliary body, and, therefore, should be attributed to removal of stimuli, which determine the width
of the fissure by acting on the cornea and the conjunctiva. He also concluded from the late effects on the pupil and
on accommodation that a slow absorption had taken place. He never saw any signs of stimulation after the
administration of cocaine to the eye. [54]
In Vienna, Koller’s findings were confirmed immediately after his lecture by Königstein, and Koller persuaded
Jellinek to try cocaine in the field of laryngology, so that he could publish a report on its useful application in the
[55]
extirpation of polypous and papillomatous growth. Fränkel soon afterwards found that cocaine was well suited for
anesthetizing the genital mucosa, even if it was inflamed. However, this was only the beginning. Before the end of
[56]
the year, numerous “letters from the readers” appeared about the subject in England in Lancet; in other countries as
well, interest was obviously very great.
Perhaps this is best illustrated by the response in the United States. As early as on October 11, 1884, a report about
the Heidelberg meeting, written by H. D. Noyes, a professor of ophthalmology in New York, was published in a
well-known medical journal. He expressed enthusiasm about Koller’s discovery, and a stream of communications
[57]
on the subject soon poured forth. As shown in the careful retrospect by Matas, the first use in the United States of
[58]
cocaine as an anesthetic for the eye had already taken place on October 8, as a consequence of a letter from Noyes
(the case had not yet been published). Knapp, also a professor of ophthalmology in New York and editor of the
Archives of Ophthalmology, published at the end of the year an article starting with the following words:
“No modern remedy has been received with such general enthusiasm, none has been so rapidly popular, and
scarcely any one has shown so extensive a field of useful application as cocaine, the local anesthetic introduced by
Dr. C. Koller of Vienna.” Knapp then gave the translation mentioned earlier, “not only as an acknowledgment of a
[59]
debt of gratitude we all owe to him, but also as an appropriate introduction.” In conclusion, he said that cocaine had
been found useful in ophthalmology, otology, rhinolaryngology, pharyngology, urology, gynecology, and also in
general surgery. It was, of course, to be expected, especially after von Anrep’s experiments, that the subcutaneous
application of cocaine would also be of value. This was definitely shown by Halsted, who in the year 1884 also
successfully established the efficacy of regional anesthesia by blocking the corresponding nerve, as evident from a
letter to the New York Medical Journal by his collaborator. In the autumn of 1885, Halsted, during a visit to
[60]
Vienna, demonstrated how to use cocaine, with the result that A. Wölffler, assistant at Billroth’s clinic, who had at
first declared cocaine to be without value in surgery, now wrote an enthusiastic article about it in a daily paper.
Regional anesthesia with cocaine was also demonstrated in Vienna by Halsted. Because of his unfortunate
[61]
ignorance of the dangers associated with cocaine, Halsted later became an addict as a result of numerous
experiments on himself. In 1885, he published the first part of an article on the use and abuse of cocaine, but the [62]
last part of it never appeared. He had become a victim of his scientific enthusiasm, and only after great difficulties
did he succeed in recovering from the addiction. In 1885, Corning called attention to the considerable prolongation
[63]
9
of the effect of cocaine injections in the arm brought about by the application of a tourniquet shortly after the
injection.
[64]
It is of interest to discuss the criticism of Koller by Jones in his chapter, “The Cocaine Episode.” His opening
remark was: “When publishing the paper he had read in Vienna in October 1884, he quoted Freud’s monograph as
dating from August instead of July, giving thus the impression that his work was simultaneous with Freud’s and not
after it.” This can be countered with the fact that Koller in his article mentions Freud’s review, pointing out that it
and the therapeutic papers had brought cocaine to the notice of Viennese physicians. The careful reader must
understand that he had no intention of giving the impression insinuated by Jones. It was easy for Koller to make
such a slip. Königstein, in his article of October 19, 1884, made the same mistake. Furthermore, Koller stated in the
Heidelberg report that he had performed his experiments “during the past 2 weeks,” thus mainly in September. Jones
continued his criticism with the following statement: “As time went on, Koller presented the discrepancy in still
grosser terms, even asserting that Freud’s monograph appeared a whole year after his own discovery, which was,
therefore, made quite independently of anything that Freud had ever done.” This is completely wrong. The paper
referred to by Jones was presumably the letter written in 1941 to M.D. Seelig, in which Koller says: “The facts are
that Freud did not have anything whatever to do with cocaine anesthesia, nor did he write a single word about
cocaine in 1885 (whereas my work dates from 1884) that had not been done better and more scientifically by Anrep
in 1878.” Obviously, Koller was not concerned with Freud’s “monograph” at all, the indirect influence of which he
[49]
had already mentioned on various earlier occasions, but with the reports of 1885 on Freud’s own somewhat ill-
[49] [52] [53]
fated experimental work. Jones erroneously assumed that Koller must have meant the literary review of
[65] [65A] [65B] [65C]
1884. A psychoanalyst might find it interesting to analyze the several mistakes made by Jones.
Although there can be no doubt about the importance of Koller’s work, it is often stated, even in modern literature, [15]
that Koller started his work at the suggestion of Freud. This is quite erroneous as is evident already from the well-
[66]
established fact that Freud had turned to Königstein, the elder of the two ophthalmologists and the one with better
opportunities for working on patients, and it would have been very remarkable if Freud had asked both to do the
same job. Moreover, we have Freud’s own words that Koller made his discovery on his own initiative and without
any suggestion from Freud. On the other hand, Koller, as we have seen, emphasized that Freud’s work on cocaine
and his review had influenced interest in cocaine in Vienna.
[65]
It is not surprising that Freud personally regretted that he had missed the opportunity of making the great discovery
that fell on Koller. However, it is probably true, as pointed out by Jones, that “it is not altogether likely that Freud,
even with more time at his disposal, would have thought of the surgical application, one foreign to his interests.”
The similarity between the two great discoveries discussed here was also reflected in the unusually rapid acceptance
of new possibilities and in the early observation of danger, which led to new progress on the foundation that had
been laid. However, it also happened that the men who had fought for the new methods were fated personally to
suffer disagreeable hardships. As was common with the pioneers of general anesthesia, Morton died in poverty,
exhausted from his efforts to get the appreciation he had hoped for, Wells committed suicide, and Jackson’s life
ended in an asylum. Only Long had a peaceful life, but he never fought for the new discovery, preferring to keep it
for himself. The fate of Koller was certainly influenced by the work he had performed. The difficulties he
encountered in Vienna, which he refers to as “distress and continuous humiliating enmities,” were added to the fact
[67]
that he did not even get the position of assistant at the eye clinic as he—with good reason one might say—had
hoped. He finally emigrated to the United States, where he at last found a refuge.
DEVELOPMENT OF COCAINE ANESTHESIA
Cocaine came into general use in 1884, not only for application to mucous membranes but also for subcutaneous
injections, and because of its suitability for blocking nerves, it found use in regional anesthesia. New methods for
cocaine administration were soon added to those mentioned. Thus, in 1885, Corning published a paper in which he
described experiments he had conducted on dogs, injecting 1.18 mL of a 2% solution of cocaine hydrochloride into
the space “situated between the spinous processes of two inferior dorsal vertebrae,” with the result that the animal
did not react for several hours, even if a stimulus was applied from a powerful faradic battery or if the hind limbs
were pinched or pricked ( Fig. 1-6 ). One human experiment produced a similar local effect, and the author
[64]
concluded: “Whether the method will ever find an application as a substitute for etherization in genitourinary or
other branches of surgery, further experiments alone can show.” Corning came back to the problem 3 years later. [68]
His main interest was, however, the alleviation of pain in certain nervous diseases, and from the last of the papers
mentioned, it is obvious that he succeeded with this in four cases. The reservations that were entertained about his
first publication—it seemed uncertain whether he had really been in the subarachnoidal space—were removed, and
there can be little doubt that Corning was the first to apply cocaine (and some other substances) to the nerves at their
origin in the spinal cord. However, the pioneer in introducing the method for surgical purposes was Bier, who was [69]
10
of the opinion that this kind of “spinal anesthesia” was in response to an action on the unmyelinated fibers and
perhaps also on the ganglion cells ( Fig. 1-7 ). He carefully described six patients on whom he had operated for
osteomyelitis, resections, and so forth, with success under spinal anesthesia, obtained with 0.005–0.015 g cocaine
injections. However, because several of the patients had suffered from considerable postoperative effects (e.g.,
headache, vomiting), he decided to do some experiments on himself. Because much of Bier’s cerebrospinal fluid
had escaped during administration of the solution, and because part of this had also been lost, the experiment was
continued on his assistant, Dr. Hildebrandt.
The two subjects confirmed that injection of as little as 5 mg of cocaine into the lumbar theca reduced the sensibility
in approximately two thirds of the body to such an extent that major operations without the patient feeling any pain
would have been feasible. It was also found, however, that some very unpleasant after-effects occurred.
The work of Bier stimulated the interest of many surgeons, and soon spinal anesthesia was tried by others as well.
The after-effects were sometimes mild or absent, but the fact that sometimes they were severe, or even fatal, caused
hesitation in its use. Presumably, the effects were due to attack on the medulla oblongata by the cocaine that had
diffused into the liquor as well as the slow normal circulation of the liquor, which after being “secreted” in the
choroid plexus slowly passed via the ventricles into the epidural space and back through the subarachnoid space,
ending in the pacchionian bodies, where it was partly transferred into the blood. This circulation takes several hours
and is greatly influenced by the body position. In sitting or standing positions, the pressure of the cerebrospinal fluid
increases greatly, and the circulation time consequently increases. This may partly explain the fact that in the cases
of Bier and Hildebrandt it took a longer time for the after-effects to appear and disappear than in patients who were
lying in bed. In order to counteract such effects, Pitkin added to the solution of the anesthetic—procaine—a
[70]
mucilaginous substance and ethyl alcohol in such proportions that the specific gravity and viscosity of the
“spinacene” could be held above those in the cerebrospinal fluid. Solutions of high specific gravity were used when
the upper part of the body was elevated and those with low specific gravity when the operation took place with the
pelvis in a high position. Special measures were also taken to prevent excessive decreases in blood pressure.
A different method was indicated for other cases. Sicard, having used the method of Bier, tried a less dangerous
[71]
technique. After trials on dogs, he found it possible to reach the nerve trunks at their exit from the medulla by
injecting into the extradural space (i.e., between the dura and the bone). He injected cocaine in this way into 9
patients suffering from pains of various kinds (lumbar, sciatic, and even tabetic), who obtained relief of varying
duration. Sicard pointed out that it was the surgeon’s prerogative to ascertain whether the method (“sacral
anesthesia”) could be improved sufficiently to evoke analgesia of the lower limbs. Shortly thereafter, Cathelin [72]
reported similar animal experiments. He also claimed that he had tried the method in four patients with inguinal
hernia, but the resulting reduction in sensibility was not sufficient for serious operations. This, he pointed out, was
probably due to the fact that the nerves passing through the extradural space were still surrounded by a cover of
dura. Because complete analgesia had occurred in the dog, the same result would be expected in the human if the
dose were increased or if the solution were diluted.
Several workers tried sacral anesthesia in human subjects without any evident success, until, in 1910, Läwen [73]
solved the problem. He used a 2% solution of procaine-bicarbonate, varying the amount of the injected fluid
according to the desired degree of anesthesia. Gros had demonstrated that the effect of some local anesthetics (e.g.,
cocaine, procaine) is highly dependent on the pH; therefore, the effect would decrease if the acidity rose, a fact[74]
observed by Königstein in 1884. Owing to its greater lipid solubility, the free base probably penetrates much more
easily into the nerve than salts such as hydrochloride. By injecting in this way, he obtained better penetration into
the nerve. Together with von Gaza he proved that procaine applied intradurally in rabbits was considerably more
toxic than when introduced extradurally; therefore, the prospects for useful application of sacral block were greatly
improved. That variations in the amount of fluid injected determine the area affected is illustrated by the fact that
[75]
10 mL provided saddle block, whereas 50 mL caused the anesthesia to reach as far as the nipple. [15]
Other new and modified methods of application of anesthetics are available, such as paravertebral, parasacral,
venous, and arterial injections, but they need not be discussed here.
The heavy toll exacted by cocainization for surgical purposes (grave intoxications and even several deaths) during
the early years of its general use caused great distrust of the new methods, especially when the substance was
injected or applied to certain mucous membranes where it was easily absorbed. However, these unfortunate
occurrences led to important investigations that aimed to reduce the amount of cocaine applied without unduly
decreasing the anesthetic effect. Careful studies in this area were made by Reclus, who was able to show that the
[76]
concentration of the solutions could be considerably lowered ( Fig. 1-8 ). Whereas in the early days cocaine
solutions of 2% to 5% were used in general surgery and on certain mucous membranes even as high as 20%, Reclus
found 1% to 2% to be enough. In fact, he communicated that he had performed about 3200 operations using these
11
dosages, without a single death, and even without disturbing the physical equilibrium of his patients. Some technical
changes were necessary with use of the lower concentrations, such as anesthetizing successive layers as the
operation proceeded and waiting longer for the anesthetic effect to become strong enough. Even concentrations as
low as 0.5% were sometimes sufficient.
The idea of using still more dilute solutions was further developed by Schleich[ ] [ ] with the introduction of
77 77A
“infiltration anesthesia.” He used three solutions, one[ ] for general purposes and two for special occasions.
2
Solution 1 Solution 2 Solution 3

Cocaine hydrochloride 0.2 0.1 0.01
Morphine hydrochloride 0.02 0.02 0.005
Sodium chloride 0.2 0.2 0.2
Distilled water to 100.0 100.0 100.0
Schleich had observed the well-known phenomenon that the injection of water first caused heavy pain followed by
local anesthesia. Because physiologic saline (0.9%) has no pain-inducing action, he tried to find an intermediate
concentration that would cause no pain but that would still produce some swelling in the surrounding cells, with
consequent disturbance in the functional activity of the nerve endings and decreasing sensibility. The effect was
intended to be a summation of the actions of hypotonicity and cocaine; morphine has so small a peripheral effect
that it seems impossible to prove that it has any effect in this instance. Schleich tried the method of infiltrating
tissues with these solutions and found a good level of anesthesia, permitting performance of many operations
without pain. Schleich’s work was at first met with the greatest distrust, but Braun (1897) showed convincingly that
the method had great potential for use, even in fairly large operations. He denied the results obtained with 0.2%
saline, and he preferred eukaine B to cocaine, but there was no doubt that the principle of infiltration with low
concentrations was correct.
DEVELOPMENT OF OTHER LOCAL ANESTHETICS
It was only natural that discoveries in organic chemistry, both analytic and synthetic, should have led to efforts to
find preparations with good anesthetic properties and without the drawbacks of cocaine. Besides its highly acute
toxicity and the risk of addiction (which came to play a greater role as time went by), cocaine is easily decomposed
when the solution is sterilized. It is also expensive.
As emphasized by Willstätter, the vegetable bases, such as cocaine, are often so complex that the imagination of the
chemist is not equal to the task of shaping them without the natural model, “at least in our time.” The constitutional
[78]
formula of cocaine and its synthesis were not completed before 1934, 60 years after the isolation of the alkaloid by
Niemann. For a long time, the ideas about the structure of the base ecgonine were erroneous, but this did not prevent
great progress from being made in the field of new local anesthetics. The points of departure were the discoveries of
the products split from cocaine, namely, benzoic acid and methyl alcohol. As early as 1887, Filehne called [79]
attention to a certain analogy between cocaine and atropine—an ester between tropic acid and the complex organic
base tropine or tropanol. According to Filehne, a weak local anesthetizing effect is exercised by atropine, and this
was increased if mandelic acid was substituted for tropic acid (homatropine). If the still simpler benzoic acid is
introduced into the molecule instead of tropic acid, the compound obtained (benzoyltropine) becomes a strong local
anesthetic. With ecgonine—obtained from Lossen himself—no anesthetic action at all was observed. Benzoyl
derivatives of several alkaloids, such as quinine and morphine, on the other hand, were highly active. Benzoic acid
must, therefore, play a fundamental role in the anesthetic effect of cocaine. Soon after, Poulsson found that the
[80]
local anesthetic effect of cocaine disappeared if the esterifying alcohol group was removed; the general effects then
changed, and the toxicity decreased considerably, especially for mammals. If an ethyl or propyl group was
introduced instead of the methyl group, the usual cocaine activity remained, on the whole, unchanged; therefore,
esterification of the acidic group was of great importance for the anesthetic action. A second methyl group, attached
to a nitrogen atom, can be removed without any loss of activity; indeed, its removal increases cocaine’s activity.
Ehrlich confirmed that mice fed on cakes containing varying amounts of cocaine developed pathologic liver
[81]
changes (substantial enlargement and vacuolization) and that this effect was much influenced by changing special
groups in the molecule. The intermediate compounds leading from ecgonine to cocaine were only about frac120; as
toxic as cocaine itself. Soon after, Ehrlich and Einhorn observed that the esterifying methyl group in cocaine was
[82]
not the only group that could be substituted by other alcoholic radicals; the benzoyl group could also be replaced by
other acidic groups belonging to the aliphatic or the aromatic series, without the loss of anesthetic action. These
12
observations combined with the imperfect knowledge of the structure of ecgonine led to the development of
hundreds of new synthetic anesthetics, many of them less toxic than cocaine relative to their anesthetic action. It is,
of course, impossible to go into the details here, and the reader is referred to the works of Poulsson, Laubender,[80] [83]
Drill, Braun and Läwen, and Killian for more specific information. Only a few typical examples illustrating the
[13] [84] [25]
trend of the evolution are given here.
Einhorn and Heinz found that even relatively simple derivatives of amino esters were anesthetic, but although their
[85]
salts could not be used owing to their acidity and consequent irritating effects, the free amino esters produced
excellent local anesthesia on wounds. Because the preparations were made soluble in water only with difficulty, the
effect lasted for a long time, which was highly desirable for the type of treatment needed. Many of the new
substances, in contrast to cocaine, caused no contraction of the blood vessels, which led to fairly rapid absorption.
Thanks to the important discovery by Braun that the addition of small amounts of adrenaline to these solutions
[86]
could often act as a “chemical tourniquet,” an increase in anesthetic action could be obtained.
As another example, it should be mentioned that Einhorn and Uhlfelder described a new product, p-aminobenzoic
[87]
acid diethylaminoethylester, or Novocaine (procaine), which was carefully tried on humans by Braun, who [88]
produced wheals on the skin of the forearm by injection and could state that the new compound exhibited potent
local anesthetic action with practically no irritation. The general toxicity was relatively lower than that of cocaine,
its solution could be boiled without decomposition, and the effect was potentiated with adrenaline. Numerous
modifications of procaine have since been developed, but it is still a valuable anesthetic in many cases.
When the final steps in the synthesis of cocaine had been taken by Willstätter and his collaborators, the former also
succeeded in synthesizing a number of its numerous optical isomers. These were studied pharmacologically by
[78]
Gottlieb, who found the dextrorotatory cocaine (with cis-transisometry) to be somewhat less toxic than the
[89] [90]
natural product, probably because the “unnatural” isomers are often metabolized more rapidly than those occurring
in nature. At the same time, dextrorotatory cocaine is about twice as active as cocaine on the sciatic nerve of the
frog, which is explained by its greater lipid solubility; it also has the advantage that the solution can stand
sterilization well. In contrast to cocaine, however, it caused no contraction of the blood vessels, but this could be
changed by Brown’s method. Psicaine, as the product was named, seemed to be suitable, at least for use on mucous
membranes. On the whole, however, the intimate knowledge of the structure of cocaine did not yield the harvest one
had hoped for with regard to new and better local anesthetics.
A valuable impetus in the search for new local anesthetics came from an unexpected quarter. In 1935, von Euler and
Erdtman in a study on the structure of the alkaloid gramine, observed that although this substance had no
[91]
anesthetic effect, its isomer, isogramine, or 2-(dimethylaminomethyl)-indole at first tasted bittersweet and then
caused anesthesia on the tongue. This discovery was duly appreciated, and a series of investigations were started,
beginning with Erdtman and Löfgren. Numerous compounds with local anesthetic action were synthesized, but
[92]
often they also caused irritation or had other effects that precluded practical use. Löfgren and associates (Löfgren,
1946 and 1948) continued the work with great energy, and after more than 100 compounds had been investigated,
they found 2-diethylamine-2′,6′-acetoxylidide (lidocaine [Xylocaine]), a preparation which marked a considerable
advance. It had great stability, no irritating action, and good anesthetic effects. These findings were confirmed by
[66] [93]
extensive pharmacologic studies, especially by Goldberg and also by Björn, who evolved an elegant method for
[94] [95]
estimating the effect of local anesthetics in dentistry. In collaboration with Huldt, Björn demonstrated the value of
[96]
lidocaine in dentistry, whereas Gordh and others made corresponding communications from surgical quarters. At
[97]
present, lidocaine is used extensively throughout the world.
Development of the Technique of Regional Anesthesia
In 1908, August Bier devised a very effective method of bringing about complete anesthesia and motor paralysis of
[98]
a limb. He injected a solution of procaine into one of the subcutaneous veins that was exposed between two
constricting bands in a space that had previously been rendered bloodless by an elastic rubber bandage extending
from fingers or toes. The injected solution permeated the entire section of the limb very quickly, producing what
Bier called direct vein anesthesia in 5 to l5 minutes. The anesthesia lasted as long as the upper constricting band was
kept in place. After it was removed, sensation returned in a few minutes.
Interestingly, the first spinal anesthesia occurred 5 years before the first lumbar puncture. The term spinal anesthesia
was introduced by Corning in his famous second paper of 1885. Unfortunately, what he had in mind was neither
spinal nor epidural anesthesia as presently understood. Corning was under the mistaken impression that the
interspinal blood vessels communicated with those of the spinal cord, and his intention was to inject cocaine into the
minute interspinal vessels and have it carried by communicating vessels into the spinal cord. He made no mention of
cerebrospinal fluid, nor of how far he introduced the needle into the spinal space.
13
It fell to Heinrich Quincke to perform the first lumbar puncture. He based his approach on the anatomic principle
that the subarachnoid spaces of the brain and spinal cord were continuous and ended in the adult at the level of S2,
whereas the spinal cord extended only to L2. Thus, a puncture effected in the third or fourth lumbar intervertebral
space would not damage the spinal cord.
Lumbar puncture was invented as a treatment for hydrocephalus. Quincke acknowledged in his communication that
he followed Essex Wynter, who 6 months earlier had described the use of a Southey’s tube and trocar for a similar
purpose. This device was originally designed to drain fluid in cases of dropsy. Wynter introduced the tube between
[99]
the lumbar vertebrae after making a small incision in the skin for the purpose of instituting drainage of the fluid in
two patients with tuberculous meningitis. Quincke prescribed bedrest for the 24 hours after the puncture. It is
noteworthy that he entered the skin 5 mm to 10 mm from the midline. Thus, the paramedian and not the median
approach is the classic one, contrary to what is sometimes taught.
August Bier published his celebrated paper on spinal anesthesia in 1899, under the title “Versuche uber
Cocainisirung des Ruckenmarkes” (“Research on Cocainization of the Spinal Cord”). Bier assumed that intrathecal
injection of cocaine produced anesthesia by a direct action on the spinal cord. He wanted to apply cocaine anesthesia
for major operations and regarded spinal anesthesia as a means of safely producing a maximal area of anesthesia
using a minimal amount of drug. It was his opinion that the anesthesia evoked by small amounts of cocaine injected
into the dural sac resulted from its spread in the cerebrospinal fluid and that it acted not only on the surface of the
spinal cord but especially on the unsheathed nerves that traverse the intramembranous space. The extent of the
anesthesia produced was somewhat unpredictable, so Bier decided to try the experiment on himself. His assistant,
Hildebrandt, performed a lumbar puncture on Bier, but when the time came to attach the syringe to the needle, a
crisis developed; the needle did not fit. A considerable amount of cerebrospinal fluid and most of the cocaine
dripped onto the floor. To salvage the experiment, Hildebrandt volunteered his own body. This time there was a
good fit and complete success.
However, the incident did not end there. Both of them celebrated the success with wine and cigars, but on the next
day Bier had an oppressive headache that lasted for 9 days. Hildebrandt’s “hangover” developed even before the
night ended.
News of Bier’s work spread quickly, and, although he abandoned it himself, his method of subarachnoid spinal
anesthesia was soon brought into prominence by Tuffier. In 1900, in a report of 63 operations, Tuffier
[100]
promulgated the rule, “Never inject the cocaine solution until the cerebrospinal fluid is distinctly recognized.” The [101]
sensation caused by Tuffier’s demonstrations is well conveyed by Hopkins, who wrote, “To be able to converse with
a patient during the performance of a hysterectomy, the patient all the while evincing not the slightest indication of
pain (and even being unable to tell where the knife was being applied) was certainly a marvel, and was well worth
crossing the Atlantic to see.” Rudolph Matas, in his description of spinal anesthesia, used cocaine hydrochloride,
[102] [58]
10 to 20 mg, dissolved in distilled water. The solution instilled was, therefore, clearly hypotonic. Fowler preferred
[103]
to have his patients in the sitting position for the injection and, not surprisingly, was often astonished by the rapidity
and completeness of the anesthesia. Gravity methods were not yet understood.
Aseptic precautions were strictly observed, and Lee mentions that the injection he used consisted of 12 to 20 minims
of a 2% sterilized solution prepared in hermetically sealed tubes by Truax, Green, and Company of Chicago. This [104]
appears to be the earliest published reference to this method of packaging, which represented an important advance,
because previously it was necessary for the surgeon to prepare his own solution from tablets and sterilize it.
In 1912, Gray and Parsons of Birmingham, England, undertook an extensive study of variations in blood pressure
associated with the induction of spinal anesthesia. They concluded that the bulk of the fall in arterial blood
[105]
pressure during high spinal anesthesia is attributable to diminished negative intrathoracic pressure during
inspiration, which is dependent on abdominal and lower thoracic paralysis. They noted that when the negative
pressure in the thorax was increased, the arterial blood pressure also increased.
It was by then quite clear that one of the principal dangers of spinal anesthesia is the lowering of the blood pressure.
Smith and Porter found that the quantity of anesthetic solution was more important for diffusion than its
[106]
concentration; dilute solutions usually spread farther than concentrated ones. The introduction of procaine beneath
the dura in the region in which the splanchnic nerves arise caused as profound a fall in blood pressure as was caused
by complete resection of the cord in the upper thoracic region. This, they thought, proved that the fall in blood
pressure was not due to toxicity of the drug or to paralysis of the bulbar vasomotor center but to paralysis of the
vasomotor fibers that regulate the tone of the blood vessels in the splanchnic area. Because these nerve roots
originate between T2 and T7, Smith and Porter believed that the main clinical objective was to prevent cephalad
diffusion of the drug from reaching this height and paralyzing these nerve roots.
14
The idea of making the injected solution hyperbaric with glucose to obtain control over the intrathecal spread of the
solution originated with Arthur E. Barker. Barker employed stovaine. It was less toxic than cocaine but was
[107] [108]
slightly irritating and was eventually superseded by procaine.
Pitkin, in 1928, and Etherington-Wilson, in 1934, experimented with a glass model of the spinal canal to obtain
control over the rate of ascent of the drug by making the injected solution hypobaric. Control was achieved by
varying the time the model was kept sitting upright after the injection. Pitkin did this by mixing alcohol with the
procaine solutions, a mixture he called spinocaine, but he categorically warned against having the patient in the
sitting position during injection. He controlled the level of blockade by tilting the table and illustrated this with a
figure showing an “altimeter” attachment. [70]
Barker stressed such points of technique as raising the head on pillows. Whenever he injected a heavy fluid
intradurally, he kept the level of analgesia below the transverse nipple line.
Barker advocated puncture in the midline as being easier and allowing more even spread of the injected fluid than
the paramedian approach. He also emphasized that in no case should the analgesic solution be injected unless the
cerebrospinal fluid ran satisfactorily. Above all else, perfect asepsis throughout the entire procedure was absolutely
necessary. Moreover, no trace of germicides should be left on the skin, because they could be conveyed by the
needle into the spinal canal, where their irritating qualities were particularly undesirable.
Barker’s rational approach to the use of a hyperbaric solution for spinal anesthesia was apparently forgotten when
stovaine was replaced by improved drugs and had to be rediscovered after trials of quasi-isobaric solutions of
several new drugs led to unsatisfactory control of levels. The lessons of the past were ignored or forgotten by
surgeons and not yet learned by anesthesiologists. Indeed, at that time, there were few anesthesiologists to learn. In
1920, W. G. Hepburn revived Barker’s technique with stovaine, and Sise, an anesthesiologist at the Lahey
[109] [110]
Clinic, applied it to procaine in 1928 and to tetracaine in 1935.
Tetracaine’s great advantage as a spinal anesthetic was its relatively prolonged duration of action without undue
toxic effects, but this advantage was partially negated by the vagaries of its segmental spread, which resulted from
its being used in approximately isobaric solution. Therefore, Sise mixed the solution with an equal or greater volume
of 10% glucose and injected it while the patient lay in a lateral position on a table that was tilted head down 10
degrees. The patient was then turned to a supine position with a good-sized pillow inserted under the head and
shoulders to flex the cervical spine forward as much as possible; the slope of the table was adjusted during the next
few minutes as dictated by the level of analgesia needed. [110]
A refinement of this technique was the saddle-block method described in detail by Adriani and Roman-Vega. [111]
Anesthesia deliberately confined to the perineal area was obtained by performing a lumbar puncture and injection of
a hyperbaric solution, with the patient sitting on the operating table and remaining so for 35 to 40 seconds after the
injection.
The technique of hypobaric spinal anesthesia was published by W. W. Babcock in 1912. He dissolved 80 mg of
stovaine in 2 mL of 10% alcohol; thus, a solution was obtained with a specific gravity that was less than 1.000, well
below that of the cerebrospinal fluid, which he calculated to be 1.0065. He believed that the anesthesia that resulted
was chiefly a nerve root anesthesia and not the “true spinal cord anesthesia” obtained with standard solutions.
A method for continuous spinal anesthesia was described by W. T. Lemmon in 1940. It was performed with the
[112]
aid of a special mattress, a malleable needle, and special tubing, and was proposed for long operations that required
abdominal relaxation. In 1907, H. P. Dean wrote of having so arranged the exploring needle that it could be left in
situ during the operation and another dose injected without moving the patient more than a slight degree. He
proposed that additional injections be made postoperatively to treat pain or abdominal distention. Lemmon’s [113]
technique was simplified by Tuohy. He performed continuous spinal anesthesia by means of a ureteral catheter
introduced into the subarachnoid space through a needle with a Huber point.
Tuffier’s favorable experience with spinal anesthesia for surgery on the lower limbs and urogenital organs led O.
Kreis of Basel to try it for childbirth. He injected five parturients with 10 mg of cocaine at the L4 to L5 level and
[114]
claimed that this procedure alleviated pain with little impairment of muscular power or uterine motility; however, he
recommended the method particularly for forceps delivery. In the United States, S. Marx quickly followed with
[115]
several reports praising the efficacy of lumbar cocainization. All of this occurred in the year 1900, but the
enthusiasm soon waned.
15
Interest in obstetric regional anesthesia was revived when W. Stoeckel developed sacral anesthesia with procaine.
[116]
The feasibility of injecting a local anesthetic by the caudal route was demonstrated by Fernand Cathelin in 1901. He
found that fluids injected into the extradural space through the sacral hiatus rose to a height proportional to the
amount and speed of injection. His objective was to develop a method that would be less dangerous but just as
effective as subarachnoid lumbar anesthesia. He was successful in reducing the danger, but his efforts to
demonstrate the efficacy of the caudal injection for surgical operations were disappointing.
In 1909, Stoeckel described his experience with caudal anesthesia in the management of labor. He wrote that [116]
various concentrations of procaine and epinephrine produced predictably varying degrees of success after a single
injection. Pain relief averaged 1 to 1½ hours in duration. He warned, however, that the greater the analgesic effect,
the greater the hazard of impairing the forces of labor. These reservations, of course, would not apply to the use of
caudal anesthesia for surgical operations, and Läwen, in 1910, described how he used Stoeckel’s experience and
Cathelin’s ideas to perform a variety of surgical operations in the perineum.
Matas, the eminent American pioneer and historian of regional anesthesia, recorded that Sellheim, injecting close to
the posterior roots of T8 to T12 in addition to the ilioinguinal and iliohypogastric nerves, was able to perform
abdominal operations successfully. Sellheim was, therefore, credited by Matas as being the originator of the
[58]
paravertebral method of anesthesia.
Kappis described posterior approaches to the lower seven cervical nerves for the purposes of cervical and brachial
plexus block. The method of paravertebral block of the thoracic nerves and the first four lumbar nerves was also
described by Kappis and was used in a great many upper abdominal operations. He pointed out that these techniques
could be used to treat acute and chronic pain with procaine, or even with alcohol if motor function could be
disregarded. Kappis was also responsible for the posterior approach to the splanchnic plexus. [117]
In 1922, Läwen found unilateral paravertebral block of selected spinal nerves useful in the differential diagnosis of
intra-abdominal disease. [118]
In 1925, Mandl reported 16 cases of angina pectoris in which he injected procaine, 0.5%, paravertebrally with
excellent results. In the next year, Swetlow attempted to destroy the afferent sensory fibers altogether by
[119] [120]
substituting 85% alcohol for the procaine; for the most part, patients obtained satisfactory relief of pain for several
months.
The pioneer of alcohol injection for the purpose of producing a long-lasting interruption of neural conduction was
Schloesser. Schloesser presented the method as a means of managing convulsive facial tic. His patients attained
paralysis that lasted from days to months, depending on the quantity of alcohol injected. He suggested that the
method would also be useful for supraorbital neuralgia and tic douloureux. [121]
Segmental peridural anesthesia, under the name of metameric anesthesia, was used for the first time in 1921 by
Fidel Pagés, a Spanish military surgeon. Dogliotti, however, popularized segmental peridural spinal anesthesia.
[122] [123]
He emphasized that injecting the anesthetic solution in sufficient quantity (50–60 mL) and under adequate
[124]
pressure made it quite easy to subject the spinal nerves to the action of the injected fluid throughout their length in
the spinal canal and the intervertebral foramina, and even beyond. Dogliotti’s method was easier and, without
question, simpler than paravertebral regional block, because only one puncture was needed. He stressed the sudden
loss of resistance at the moment when the point of the needle, having pierced the ligamentum flavum, entered the
epidural space. The usefulness of this technique was extended further when Curbelo decided to apply the Tuohy
armamentarium for continuous spinal anesthesia to continuous segmental peridural anesthesia. In one case, he left
[125]
the catheter in place for as long as 4 days and administered a total of 10 injections of 15 mL each of 2% procaine
solution, producing a continuous sympathetic lumbar block.
It was but a short step from the diagnostic block to the therapeutic block, and the step was indeed taken by von Gaza
and by Brunn and Mandl in 1924 in the management of visceral pain. Long-term pain relief by neurolytic injection
of alcohol was developed by Swetlow for the interruption of cardiac afferent inflow and subsequently applied to
paravertebral sympathetic block in the treatment of severe intractable pain, particularly the pain of malignant
disease.
Dogliotti, in 1930, took the bold step of injecting absolute alcohol into the subarachnoid space, hoping to produce by
simple chemical means a posterior rhizotomy equivalent to that previously attainable only by surgery. At the
opposite end of the local anesthetic concentration spectrum, Sarnoff and Arrowood exploited the continuous
subarachnoid injection of dilute procaine (0.2%) to obtain a differential block limited to efferent sympathetic fibers
and afferent fibers subserving pain.[126]
16
Conclusion
Local anesthesia by chemical means has come to play a great role in surgery. Today, practically no part of the body
is inaccessible to this form of pain relief. Whether general or local anesthesia is to be used in an individual case
depends on many factors and must be carefully considered by the surgeon. According to Braun and Läwen, the [84]
proportion of operations performed under local anesthesia in Germany increased considerably during the first
decades of the 20th century; in some clinics, 50% of procedures were performed with regional anesthesia. Demands
on anesthetists have increased greatly: They must master several different methods of regional anesthesia as well as
the controls that are regularly performed on the patient’s reactions during the operation. These requirements have
necessitated special training for anesthetists who practice in modern surgical clinics.
Thus, on the foundation laid by Carl Koller, a new and important branch of medical science has developed. This is
an old story about a young man who became fascinated by a great idea and was ready to grasp the opportunity when
it presented itself. But it is also an illustration of the truth of Pasteur’s famous saying that chance favors only one
whose mind has been prepared.
REFERENCES
1. Riese
W, Arrington GE Jr: The history of Johannes Müller’s doctrine of the specific energies of the senses: Original and later versions. Bull
Hist Med 37:179–183, 1963.
2. Dallenbach KM: Pain: History and present status. Am J Psychol 52:331, 1939.
3. Melzack R, Wall PD: Pain mechanisms: A new theory. Science 150:971–975, 1965.
4. Rynd F: Neuralgia—introduction of fluid to the nerve. Dublin Med Press 13:167, 1845.
5. Pravaz CG: Sur un nouveau moyen d’opérer la coagulation du sang dans les artères, applicable à la guérison des aneurismes. CR Acad Sci
(Paris) 36:88, 1853.
6. Wood A: New method of treating neuralgia by the direct application of opiates to the painful points. Edinburgh Med Surg J 82:265, 1855.
7. Elliotson J: Numerous Cases of Surgical Operations without Pain in the Mesmeric State. Washington, DC, University Publications of America,
1843.
8. Esdaile J:Mesmerism in India and Its Application in Surgery and Medicine. London and Edinburgh, Balllière, 1846.
9. Braid J: Neuropnology: Or the Rationale of Nervous Sleep, Considered in Relation with Animal Magnetism. London and Edinburgh, 1843, p
272. (Quoted from a French translation: Delahaye A, Lecrosnier E, Paris, 1883, p 215.)
10. Forel A: Der Hypnotismus oder die Suggestion und die Psychotherapie, 12th ed. F. Enke, Stuttgart, 1923, p 108–109.
11. McGlinn JA: Music in the operating room. Am Obstet Gynecol 20:678–683, 1930.
12. Soulié de Morant G: Précis de la vrai acuponcture chinoise, 2nd ed. Paris, Mercure de France, 1947.
13. Southworth JL, Hingson RA: Pitkin. Conduction Anesthesia. Philadelphia, JB Lippincott, 1946, pp 838–862.
14. Hume EH: A note on narcotics in ancient Greece and in ancient China. Bull N Y Acad Med 10:618–622, 1934.
15. Bonica JJ: The Management of Pain. Philadelphia, Lea & Febiger, 1953.
16. Corradi A: Dell’ anesthesia e degli anesthetici nella Chirurgia del Medico Evo. Mem 1st Lomb Scienz Matem Natur L4:127–175, 1881.
17. Moore J: A Method of Preventing and Diminishing Pain in Several Operations of Surgery. London, Cadell, 1784, p 50.
18. Le Fort L: Anesthésie produite par la compression. Gaz Hop (Paris) 819–820, 1874.
19. von Esmarch F: Ueber künstliche Blutleere bei Operationen. Volkmann’s Samml Klin Vortr Chir 1:373–384, 1873.
20. Pernice L: Ueber Cocainanästhesie. Dtsch Med Wschr 16:287–289, 1898.
21. Lüderitz C: Versuche über die Einwirkung des Druckes auf die motorischen und sensiblen Nerven. Z Klin Med 2:97–120, 1881.
22. Boeri G, di Silvestro R: Sur la mode de se comporter des différentes sensibilités sous l’action de divers gents. Arch Ital Biol 31:460–464, 1989.
23. Hunter J: A treatise on the blood, inflammation, and gun-shot wounds, 1793. In The Works of John Hunter (reprint). London, Longman, 1835,
17
p 265.
24. Braun H: Die örtliche Betäubung, ihre wissenschaftlichen Grundlagen und praktische Anwendung. Leipzig, JA Barth, 1935.
25. Killian H: Lokalanästhesie und Lokalanästhetika. Stuttgart, G. Thieme, 1959.
26. Simpson JY: Local anaesthesia. Lancet II:39–42, 1848.
27. ArnottJ: I. On cold as a means of producing local insensibility. 2. On cold as a means of producing local anaesthesia in surgical operations.
Lancet II:98–99, 287–288, 1848.
28. Richardson BW: On the influence of extreme cold on nervous fibre. Asclepiad 1:33–37, 1885.
29. Trendelenburg W: Ueber Langdauernde Nervenausschaltung mit sicherer Regenerations fähigkeit. Z Ges Exp Med 5:371–374, 1917.
30. Trendelenburg W: Weitere Versuche über langdauernde Nervenausschaltung für chirurgische Zwecke. Z Ges Exp Med 7:251–274, 1919.
31. Waters RM: The evolution of anesthesia. Mayo Clin Proc 17:428–432, 440–445, 1942.
32. Perthes GC: Ueber die Behandlung der Schmerzzustäande bei Schussneuritis mittels der Vereisungsmethode von W. Trendelenburg. Münch
Med Wschr 65:1367–1369, 1918.
33. MachtDI, Herman NB, Levy CS: A quantitative study of the analgesia produced by opium alkaloids, individually and in combination with
each other. J Pharmacol 8:1–37, 1916.
34. Macht
DI, Johnson SL, Bollinger HG: On the peripheral action of the opium alkaloids. Effect on the sensory nerve terminals. J Pharmacol
8:451–463, 1916.
35. Gaedcke F: Uber das Erythroxylin. Arch Pharm (Weinheim) 132:141–150, 1885.
36. Niemann A: Ueber eine neue organische Base in den Cocablättern. Göttingen, Inaug-diss, 1860.
36A. Wöhler F: Ueber eine organische Base in der Coca [preliminary report]. Justus Liebigs Ann Cham 114:213, 1860.
37. Lossen W: Ueber das Cocain. Ann Chem Pharm 133:351–371, 1865.
38. Singer C, Underwood EA: A Short History of Medicine, 2nd ed. Oxford, Clarendon Press, 1962, p 349.
39. Leake CD: The historical development of surgical anesthesia. Sci Monthly 20:304–328, 1925.
40. Bender GA, Thom RA: Great Moments in Medicine. Detroit, Parke-Davis, 1961.
41. Mortimor WG: Peru History of Coca. New York, JH Bvail, 1901.
42. Moréno y Maiz T: Recherches chimiques et physiologiques sur l’Erythroxylum Coca du Pérou. Thèse de Paris, 1868, p 91.
43. Bennett A: An experimental inquiry into the physiological actions of caffeine, theine, guaranine, cocaine, and theobromine. Edinburgh Med J
19:323–341, 1873.
44. Sollmann T: A Manual of Pharmacology, 8th ed. Philadelphia and London, WB Saunders, 1957, p 323.
45. von Anrep B: Ueber die physiologische Wirkung des Cocain. Pflügers Arch ges Physiol 21:38–77, 1880.
46. Collin P: De la Coca et ses véeritables propriétés thérapeutiques. Un Méd Prat Franc 24:239–240, 1877.
47. Einhorn A: Ueber neue Arzneimittel. Fünfte Abhandlung. Justus Liebigs Ann Chem 371:125–131, 1909.
48. Clark AJ: Aspects of the history of anaesthetics. BMJ II:1029–1034, 1938.
49. Koller
C: Historical notes on the beginning of local anesthesia. JAMA 90:1742–1743 1928. [The article was also published twice in German in
the same journal: Wien Med Wschr 78:601–602, 1928; and again, 84:1179–1180, 1934.]
50. Koller-Becker H: Carl Koller and cocaine. Psychoanal Q 32:309–373, 1963.
51. Gaertner J: Die Entdeckung der Localanästesie. Der neue Tag, 1919. [The article was also published in Neue freie Presse under Unterhaltung.
Quoted from Koller-Becker, 1963, p 331.]
52. Koller
C: Vorläufige Mitteilung über lokale Anästhesierung am Auge. Bericht über die 16. Versammlung der ophthalmologischen
Gesellschaft. Heidelberg. Beilageheft zu Klin Mbl Augenh 60–63, 1884.
18
53. Koller C: Preliminary report on local anesthesia of the eye. Arch Ophthalmol 12:473–474, 1934.
54. Koller
C: Nachträgliche Bemerkungen über die ersten Anfänge der Lokalanästhesie. Wien Med Wschr 85–708, 1935. [The article was also
published in English: Koller C: History of cocaine as a local anesthetic. JAMA 117:1284–1287, 1941.]
55. Jellinek E: Das Cocain als Anaestheticum und Analgeticum für den Pharynx und Larynx. Wien Med Wschr 34:1334–1348, 1364–1367, 1884.
56. Fränkel E: Über Cocain als Mittel zur Anästhesierung der Genitalschleimhaut. Wien Med Wschr 34:1535, 1884.
57. Noyes HD: The Ophthalmologic Congress in Heidelberg. Med Rec 26:417–418, 1884.
58. Matas R: Local and regional anesthesia. A retrospect and prospect. Am J Surg 65:189–198, 362–379, 1934.
59. Knapp H: On cocaine and its use in ophthalmic and general surgery. Arch Ophthalmol 13:402–448, 1884.
60. Hall RJ: Letter to the editor. N Y Med J 41:643, 1884.
61. Fulton JF: Harvey Cushing. A Biography [Letter from Halsted to Cushing]. Springfield, Ill, CC Thomas, 1946, pp 142–144.
62. Halsted
WS: Practical comments on the use and abuse of cocaine. Suggested by its invariably successful employment in more than a thousand
minor operations. N Y Med J 42: 294–295, 1885.
63. MacCallum WG: William Stewart Halsted Surgeon. Baltimore, The Johns Hopkins Press, 1930, pp 54–57.
64. Corning JL: On the prolongation of the anaesthetic effects of the hydrochloride of cocaine when subcutaneously injected. N Y Med J 42:317–
319, 1885.
65. Freud S: Ueber Coca. Cbl Ges Ther 2:289–314, 1885.
65A. Freud S: Beitrag zur Kenntnis der Cocawirkung. Wien Med Wschr 35:129–133, 1884.
65B. Freud S: (1885) Ueber die Allgemeinwirkung des Cocains. Med-chir Cbl 20:374–375, 1885.
65C. Freud S: The Cocaine Papers: 1–26, 35–41 and 45–49. Dunquin Press, Vienna and Zürich, 1884. [English translation was published in 1963.]
66. Löfgren
N: Studies in Local Anesthestics. Xylocaine, a New Synthetic Drug. Thesis I. Stockholm, Haeggström, 1948. [Reprinted, Worcester,
Mass, 1958.]
67. Liljestrand G: Briefe von Carl Koller an Erik Nordenson. Arch Gesch Med 49:280–306, 1965.
68. Corning JL: A further contribution on local medication of the spinal cord. Med Rec (N Y) 33:291–293, 1888.
69. Bier A: Versuche über Cocainisieurung des Rückenmarks. Dtsch Z Chir 51, 1899.
70. Pitkin GP: Controllable spinal anesthesia. Am J Surg 5:537–553, 1928.
71. Sicard A: Les injections medicamenteuses extra-durales par Voie sacro-coccygienne CR Soc Biol (Paris) 53:396–398, 1901.
72. Cathelin
F: Une nouvelle voie d’injection rachidienne. Méthode des injections épidurales par le procédé du canal sacré. Applications à
l’homme. CR Soc Biol (Paris) 53:452–453, 1901.
73. Läwen A: Uber Extraduralanästhesie für chirurgische Operationen. Dtsch Z Chir 108:1–43, 1910.
74. Gros O: Ueber die Narkotika und Lokalanästhetika. Arch Exp Path Pharmak 63:80–106, 1910.
75. Läwen A, von Gaza W: Experimentelle Untersuchungen über Extraduralanästhesie. Dtsch Z Chir 111:289–307, 1911.
76. Reclus P: De l’anesthésie locale par la cocaine. Gax Hebd Méd Chir 27:146–148, 1890.
77. Schleich CL: Schmerzlose Operationen. Örtliche Betäubung mit indifferenten Flössigkeiten, 4th ed. Berlin, Springer, 1894.
77A. Schleich CL: Schmerzlose Operationen. Örtliche Betäubung mit indifferenten Flössigkeiten, 5th ed. Berlin, Springer, 1906.
78. Willstätter R: Ueber die Synthese des Psikains. Münch Med Wschr 71:849–850, 1924.
79. Filehne W: Die local-anästhesirende Wirkung von Benzoylderivaten. Berl Klin Wschr 24:107–108, 1887.
80. Poulsson E: Beiträge zur Kenntniss der pharmakologischen Gruppe des Cocains. Arch Exp Path Pharmak 27:301–313, 1890.
81. Ehrlich P: Studien in der Cocainreihe. Dtsch Med Wschr 16:717–179, 1890.
19
82. Ehrlich P, Einhorn A: Ueber die physiologische Wirkung der Verbindungen der Cocainreihe. Ber Dtsch Chem Ges 27: 1870–1873, 1894.
83. Laubender W: Lokalanaesthetica. Heffter’s Handb Exp Pharmakol (Erg-werk) 8:1–78, 1939.
84. Braun H, Läwen A: Die örtliche Betäbung, 8th ed. Leipzig, JA Barth, 1933.
85. Einhorn A, Heinz R: Orthoform. Ein Lokalanaestheticum für Wundschmerz, Brandwunden, Geschwüre, etc. Münch Med Wschr 44:931–934,
1897.
86. Braun H: Ueber die Bedeutung des Adrenalins für die Chirurgie. Münch Med Wschr 50:352–353, 1903.
87. Einhorn A, Uhlfelder E: Ueber den p-Aminobenzoesäure-diäthyl-amino- and Piperidoäthylester. Justus Liebigs Ann Chem 371:131–142,
1909.
88. Braun H: Die Lokalanästhesie, ihre wissenschaftlichen Grundlagen und praktische Anwendung. Leipzig, JA Barth, 1905.
89. Gottlieb R: Pharmakologische Untersuchungen über die Stereoisomerie der Kokaine. Arch Exp Path Pharmak 97:113–146, 1923.
90. Gottlieb R: Ueber die pharmakologische Bedeutung des Psikains als Lokalanästhetikum. Münch Med Wschr 71:850–851, 1924.
91. von Euler H, Erdtman H: Ueber Gramin aus Schwedischen Gerstensippen. Justus Liebigs Ann Chem 520:1–10, 1935.
92. Erdtman
H, Löfgren N: Ueber eine neue Gruppe von lokalanästhetisch wirksamen Verbindungen. á-N-Dialkylaminosäureanilide. Svensk Kem
T 49:163–174, 1937.
93. Löfgren N: Studien über Lokalanästhetica. Ark Kemi Mineral Geol 22:1–30, 1946.
94. Goldberg L: Studies on local anesthetics. Pharmacological properties of homologues and isomers of xylocain (alkyl aminoacyl derivatives).
Acta Physiol Scand 18:1–18, 1949.
95. Björn H: Electrical excitation of teeth and its application to dentistry. Svensk Tandläk-T 39(Suppl 4):1–101, 1946.
96. Björn H, Huldt S: The efficiency of xylocaine as a dental terminal anesthetic, compared to that of procain. Svensk Tandläk-T 40:831–852,
1947.
97. Gordh T: Xylocain—a new local analgesic. Anaesthesia 4:4–9, 21, 1949.
98. Bier A: Ueber einen neuen Weg Localanasthesie an den Gliedmassen zu erzeugen. Arch Klin Chir 86:1007, 1908.
99. WynterWE: Four cases of tuberculosus meningitis in which paracentesis of the theca vertebralis was performed for the relief of fluid pressure.
Lancet 1:981, 1891.
100. Tuffier T: Analgesie chirurgicale par l’injection sous-arachnoidienne lombaire de cocaine. CR Soc Biol (11th series) 1:882, 1899.
101. Tuffier T: Anesthesie medullaire chirurgicale par injection sous-arachnoidienne lombaire de cocaine; technique et resultats. Semaine Med
20:167, 1900.
102. Hopkins GS: Anesthesia by cocainization of the spinal cord. Philadelphia Med J 6:864, 1900.
103. Fowler RG: Cocaine analgesia from subarachnoid injection, with a report of forty-four cases together with a report of a case in which
antipyrin was used. Philadelphia Med J 6: 843, 1900.
104. Lee EW: Subarachnoidean injections of cocaine as a substitute for general anesthesia in operations below the diaphragm, with report of seven
cases. Philadelphia Med J 6:865, 1900.
105. Gray HT, Parsons L: Blood pressure variations associated with lumbar puncture and the induction of spinal anesthesia. Q J Med 5:339, 1912.
106. Smith GS, Porter WT: Spinal anesthesia in the cat. Am J Physiol, 38:108, 1915.
107. Barker AE: Clinical experiences with spinal analgesia in 100 cases and some reflections on the procedure. BMJ 1:665, 1907.
108. De Lapersonne F: Un nouvel anesthesique local, la stovaine. Presse Med 12:233, 1904.
109. Hepburn WG: Stovain spinal analgesia. Am J Surg 34:87, 1920.
110. Sise LF: Spinal anesthesia for upper and lower abdominal operations. N Engl J Med 199:61, 1928.
111. Adriani J, Roman-Vega D: Saddle block anesthesia. Am J Surg 71:12, 1946.
112. Lemmon WT: A method for continuous spinal anesthesia. Ann Surg 111:141, 1940.
20
113. Dean HP: Relative value of inhalation and injection methods of inducing anaesthesia. BMJ 2:869, 1970.
114. Kreis O: Ueber Medullarnarkose bei Gebarenden. Zentralbl Gynakol 24:724, 1900.
115. Marx S: Analgesia in obstetrics produced by medullary injections of cocain. Philadelphia Med J 6:857, 1900.
116. Stoeckel W: Ueber sakrale Anasthesie. Zentralbl Gynaekol 33:1, 1909.
117. Kappis M: Erfahrungen mit Lokalanasthesie bei Bauchoperationen. Verh Dtsch Ges Chir 43:87, 1914.
118. Läwen A: Ueber segmentare Schmerzaufhebung durch paravertebrale Novokaininjektionen zur Differentialdiagnose intra-abdominaler
Erkrankungen. Med Wochenschr 69:1423, 1922.
119. Mandl F: Die Wirkung der paravertebralen Injektion bei “Angina pectoris.” Arch Klin Chir 136:495, 1925.
120. Swetlow GI: Paravertebral alcohol block in cardiac pain. Am Heart J 1:393, 1926.
121. Schloesser: Heilung peripharer Reizzustande sensibler und motorischer Nerven. Klin Monatsbl Augenheilkd 41:244, 1903.
122. Pagés F: Anestesia metamerica. Rev Sanid Milit Argent 11:351–365, 1921.
123. Dogliotti AM: Eine neue Methode der regionaren Anasthesie: “Die peridurale segmentare Anasthesie.” Zentralbl Chir 58:3141, 1931.
124. Dogliotti AM: A new method of block anesthesia. Segmental peridural spinal anesthesia. Am J Surg 20:107, 1933.
125. Curbelo MM: Continuous peridural segmental anesthesia by means of a ureteral catheter. Anesth Analg (Cleve) 28:13, 1949.
126. Sarnoff SJ, Arrowood JG: Differential spinal block. Surgery 620:150, 194.
21
Section I - Chapter 2 -The History of the Development of Techniques in Regional Anesthesia
Chapter 2 - Beyond Blocks: The History of the Development of

Techniques in Regional Anesthesia
CHRISTOPHER M. BURKLE
ROBERT P. SANDS JR.
DOUGLAS R. BACON
Regional anesthesia, the art of rendering a part of the body insensible for an operation, traces its roots to Karl Koller
of Vienna, who, in 1884, demonstrated the use of topical anesthesia on the eye. However, regional anesthesia would
not have progressed much beyond topical application had not many pioneers tried new and different ways of
producing regional insensibility. In many ways, the history of techniques in regional anesthesia mirrors the way in
which scientific knowledge is obtained: It is an intellectual history of ideas. There are instances in which techniques
were developed, discarded, and revived only when “new” local anesthetics or plastic catheters became available,
making the technique viable. Other researchers made an intellectual leap by speculating that if the pain of surgery
could be ablated by regional anesthetic techniques, such techniques might be used in the treatment of patients with
chronic painful conditions. Thus, from surgical anesthetic experience came the first pain clinics. In addition, there
was a need to disseminate this new, exciting information to a professional audience. The development of
professional organizations devoted to regional anesthesia also underwent this cycle of birth, death, and rebirth. This
chapter explores the continuum of regional techniques, from their inception to their current use or abandonment.
Spinal Anesthesia
The history of spinal anesthesia demonstrates the cyclical nature of regional anesthetic techniques. The advent of
spinal anesthesia has roots that reach much deeper into the past than August Bier’s first administration of cocaine
into the subarachnoid space in August 1898. Over 100 years earlier, in 1764, Domenico Cotugno, an Italian
anatomist, published an almost complete description of cerebrospinal fluid (CSF) in his dissertation entitled De
Ischiade Nervosa Commentarius. This information lay dormant, with little clinical utility, until 1872, when
[1]
Heinrich Quincke published Zur Physiologie de Cerebrospinalflussigkeit. In this landmark paper, Quincke
[2]
reported that there had already been a large number of anatomic and experimental examinations performed on the
distribution and movement of CSF, citing that Magendie had given attention to Cotugno’s description. Although [3]
Quincke has been given credit for having performed the first lumbar puncture, he himself assigned the credit to
Essex Wynter who, in 1891, used a Southey tube to perform a lumbar puncture. Although the Southey tube was
originally employed to relieve edema of the legs by subcutaneous drainage, Wynter theorized that, by inserting the
tube into the subarachnoid space, he could relieve the increased intracranial pressure of tuberculous meningitis. [4]
Also in 1891, Quincke reported his first lumbar puncture in Germany. Two years later, von Ziemssen, a German
[5]
physician whose main medical interest was infectious disease, reported on the feasibility of injecting drugs by
means of a lumbar puncture. He subsequently injected a patient with saline and tetanus antitoxin via the
[6]
subarachnoid route. In 1895, Quincke published a paper in the annual report of La SociétéFrançaise de Bienfaisance
Mutuelle, elaborating on his technique of using lumbar puncture to relieve the pressure of hydrocephalus, based on
“the anatomical and experimentally proven fact that the subarachnoid space communicates with the cerebral
ventricles.” Later that same year, George Jacoby published his report on the diagnostic use of the lumbar puncture.
[7]
The technique he described differs little from the procedure that is currently in use. [8]
THE FIRST SPINAL ANESTHETIC?
James Corning ( Fig. 2-1 ), a New York City neurologist, heard in 1885 of the local anesthetic properties of cocaine,
which had been discovered by the Viennese ophthalmologist, Carl Koller, in 1884. Corning began a series of
[9]
experiments to determine whether local medication of the spinal cord was within the range of practical achievement.
He reasoned that cocaine might be the ideal agent to treat neurologic disease if applied in the vicinity of the venae
spinales of the cord. If it were delivered to the spinal region, it could be absorbed and carried to the affected area,
having a much greater effect, like that of strychnine when it was injected in the same way. His first subject was a
dog. Corning injected cocaine below the spinous processes of two of the inferior dorsal vertebrae. After a few
minutes, the dog’s hindquarters became paralyzed. A short while later, he tried the same technique on a young man
with seminal incontinence. The young man received 2 mL of a 3% solution of the hydrochloride of cocaine between
the spinous processes of T11–12. No effect was seen after 8 minutes, so another 2 mL of the same solution were
22
injected into the same space. Approximately 10 minutes after the second injection, the man’s legs began to “feel
sleepy.” After another 15 to 20 minutes, the intensity of the anesthesia had increased, and although “there were
some evidences of the diffusion part of the anesthetic, the impairment of sensibility was principally limited to the
lower extremities, the lumbar regions, the penis, and scrotum.” While standing with eyes closed, the man
experienced some dizziness, but no incoordination or motor impairment was discernible in his gait. He left the office
1 hour or more after the last injection and seemed “none the worse for the experience.” [10]
Corning performed his experiment and published his paper in 1885. The practicability of dural puncture had not yet
been reported, nor would it be made known until Wynter’s and Quincke’s papers appeared in 1891. For that reason,
and because CSF was not recovered in the syringe nor mentioned explicitly in his paper, it is believed that Corning
performed the first epidural rather than the first spinal administration of anesthetic. [11]
In 1899, 13 years after Corning’s report and 8 years after the first authenticated lumbar puncture, the surgeon
Augustus Bier ( Fig. 2-2 ), a professor at the Royal Chirurgical Clinic in Kiel, Germany, used “cocainization of the
spinal cord” to provide pain relief for orthopedic operations on the lower extremities and coccyx. He proposed that
[12]
injected cocaine would spread in the CSF and affect not only the surface of the cord but also the nonmyelinated
nerves in the meninges and ganglia. He described the course of six patients ranging in age from 11 to 34 years, who
received treatment between August 16 and August 27, 1898. The injections were made in the lumbar area, at an
unidentified interspace, with the patients in a lateral recumbent position. He administered a 0.5 mL of a 1% solution
of cocaine to the two teenagers, whereas the adults received either 1 mL of a 1% solution or 2 to 3 mL of a 0.5%
solution. All of these blocks were successful and proved “that when a relatively small amount of cocaine is injected
into the dural sac, large areas of the body can be made insensitive to pain and major operations can be performed in
these areas. On the other hand, so many complaints had arisen in association with this method (back and leg pain,
vomiting, prolonged headache) that they equaled the complaints usually occurring after general anesthesia.” [13]
Because of these complaints, Bier decided to experiment on himself. Dr. Hildebrandt, Bier’s assistant, performed the
lumbar puncture on Bier after infiltrating the skin and deeper tissues. Bier immediately felt a lancinating pain in one
leg; when the syringe did not adapt to the needle, much CSF was lost. Therefore, most of the cocaine did not reach
the subarachnoid space, and loss of sensation did not develop, as manifested by Bier’s perception of small skin cuts
and needle pricks.[14]
Hildebrandt then volunteered to undergo the same experiment, albeit with a much different outcome. “He first
noticed a feeling of warmth and subsequently had no sensual perception to needle pricks to the thigh, tickling of the
soles of the feet, a small incision in the thigh, pushing a large-helved needle down to the femur, strong pinching and
squeezing with dental forceps, application of a burning cigar, pulling out pubic hairs, a strong blow with an iron
hammer against the tibia, vigorous blows with knuckles against the tibia, and strong pressure on a testicle.” Eighteen
minutes after the injection, pain sensation was greatly decreased up to the nipple line. After 45 minutes, the effect
began to wear off.[14]
After describing the successes in patients and many details of the anesthesia, Bier noted that “other agents related to
cocaine might not cause these unpleasant side reactions, or that additions to cocaine might abolish
them.…Therefore, it did not seem justified to me to make further experiments on human beings. Experiments with
animals might lead to significant results. For these, the dog would be adequate, since it vomits easily, meaning that
the important sign of the unpleasant side effects could thus be observed.” In spite of Bier’s reservations,
[13]
cocainization of the spinal cord attracted widespread attention and immediate use at several centers.
AN AMERICAN TWIST
Although Europe was the birthplace of spinal anesthesia, two pioneering surgeons, F. Dudley Tait and Guido E.
Caglieri, administered the first spinal anesthetic in America on October 26, 1899. Tait and Caglieri studied 7
cadavers, 11 patients, and an unknown number of cats, dogs, rabbits, guinea pigs, and horses in their efforts to
further understand how lumbar puncture could benefit patients. Although they never clearly stated their reasoning,
Tait and Caglieri were apparently trying to exploit for some therapeutic gain the lumbar puncture technique
discovered independently by Quincke and Wynter. Examination of CSF was undoubtedly useful in certain
diagnostic conditions, but the utility of fluid withdrawal or drug injections into the subarachnoid space was still not
established. Infectious diseases of the central nervous system, such as syphilis, tuberculosis, tetanus, and gonorrhea
were important causes of morbidity around the beginning of the 20th century. Tait and Caglieri experimented in the
treatment of tertiary syphilis by subarachnoid injections of mercuric salts and iodides which, when given
systemically, were thought to be beneficial in the treatment of syphilis. Their experiments revealed that the
23
intravenous administration of these drugs did not lead to subarachnoid accumulation; however, subarachnoid
administration did lead to the appearance of these drugs in the bloodstream. [15]
In addition to its usefulness in diagnosis, penetration of the subarachnoid space was reported to have a potential
application with administration of spinal anesthesia. The common anesthetic techniques at that time were inhalation
of nitrous oxide, chloroform, or ether, or infiltration with dilute concentrations of cocaine. None of these anesthetics
provided adequate muscle relaxation. Furthermore, the side effects were serious, ranging from vomiting to
prolonged emergence, airway obstruction, and death. Spinal anesthesia presented a technique that permitted the
avoidance of these worrisome problems, particularly in ill patients.
In April 1900, Tait and Caglieri reported on 11 anesthetic cases in which 5 to 15 mg of cocaine were used
intrathecally for procedures below the umbilicus. Two patients reported minor surgical discomfort and three others
were outright failures. Regardless, unlike Bier, Tait and Caglieri unequivocally supported the technique of spinal
anesthesia. One patient who “had collapsed” with both ether and chloroform anesthesia underwent a bone
curettement without complications after intrathecal administration of 10 mg of cocaine. Thus, relative to the
[15]
constraints under which Tait and Caglieri operated, modest success represented a groundbreaking achievement.
Tait and Caglieri described a few postoperative problems that could be attributed to the administration of cocaine to
the subarachnoid space. Some of their practices could have been responsible for this. For example, they
recommended the use of a fine needle and slow injection of the cocaine to prevent rostral spread. They also
recognized early that the extent of diffusion was influenced by several factors, including the amount of drug
injected, the drug’s composition and density, and the pressure under which the drug was injected. The analgesia
provided by this procedure was
thought to be sufficient for all operations of the lower limbs and pelvis, and Tait and Caglieri recommended a trial in
obstetrics, thus beginning the successful use of the spinal technique during labor, which was later reported by
Kreis. They also experimented with the other available derivatives of benzoic acid, eucaine and nirvanin, and
[16]
found that they offered no advantages over cocaine. One final observation of these investigators is relevant to
current practice. When the present day anesthesiologist advises the patient with a postdural puncture headache to
“drink plenty of fluids,” it brings to mind Tait and Caglieri’s simple observation that the flow of CSF through an
indwelling subarachnoid needle was markedly increased by intravenous administration of saline. A contemporary of
Tait and Caglieri, Rudolf Matas of New Orleans ( Fig. 2-3 ), published his report of spinal anesthesia almost
simultaneously. Matas agreed with Tait and Caglieri, citing the advantages of spinal over general anesthesia, but he
was disappointed with the results. In fact, Matas stopped administering spinal anesthesia until pontocaine became
commercially available. Interest in spinal anesthesia waxed and waned over the next decade. In the 1920s,
[17]
mortality from spinal anesthetics was reported to be as high as one in a hundred patients. Lincoln Sise ( Fig. 2-4 ),
working at the Lahey Clinic in Boston, decreased that number to just under one in a thousand. Sise worked hard to
delineate the causes of the profound hypotension that accompanied successful spinal anesthesia. He found that
ephedrine, given subcutaneously, would block the hypotensive effects of the spinal block. [18]
Another problem that plagued spinal anesthesia in the first decades of the 20th century was duration of the block.
Procaine lasted about an hour, often less time than the surgeon needed to complete the operation. In 1935, Sise
experimented with a new local anesthetic, tetracaine, with a duration of action of about 2 hours. However, tetracaine
was unpredictable when injected into the CSF. Blocks would often be too high, leading to respiratory compromise.
Sise theorized that it was the baricity of the solution relative to the CSF that caused the block to float. By mixing his
tetracaine with 10% dextrose, Sise created a dependable hyperbaric solution. With adjustment of the patient’s
position, he could change the height of the block. For example, when the level was too low, placing the patient in
the Trendelenburg position raised the level of the block. [18]
Neurologic complications were another concern for patients and anesthesiologists. In the 1920s, it was estimated
that 50% of patients suffered debilitating headaches after spinal anesthesia. Sise developed an introducer, a short,
large-bore needle that helped facilitate the passage of a smaller needle through the dura and into the subarachnoid
space. It would be another 20 years before Leroy Vandam and Robert Dripps published their study of over 9000
[18]
spinal anesthetic procedures.
They found that 11% of their patients had postdural puncture headache, with a decreasing incidence with age.
Vandam and Dripps correctly identified the risk factors of pregnancy and needle size and concluded that these were
due to a decrease in CSF pressure. They also studied long-term neurologic sequelae in regional anesthesia.
[19]
24
Vandam and Dripps found that outside of postdural puncture headache, neurologic problems were rare. Most of
these problems were apparent preoperatively if the anesthesiologist had done a detailed neurologic history. To avoid
complications, Vandam and Dripps advocated proper selection of patients. [20]
Perhaps the most famous instances of neurologic complication of regional anesthesia occurred in England on
October 13, 1947. That day, two healthy men underwent routine operations: One had a meniscectomy of the knee
and the other a radical repair of a hydrocele. Both men developed permanent spastic paralysis after administration
[21]
of intrathecal anesthesia. Hyperbaric 1:1500 dibucaine was used. At the time, the explanation given was that
[22]
phenol, which had been used to sterilize the local anesthetic ampules for surgery and which had minute cracks in
them, had caused the contamination of the drug. Sir Robert Macintosh supported this theory and testified before the
court to this effect. The case had a devastating effect on use of subarachnoid anesthesia, including far-reaching
[23]
publicity that lingers to this day. Recent scholarship has demonstrated that phenol was unlikely to have been the
causative agent; the more likely suspect was the acidic solution used to clean the sterilizer. The fact that Cecil Roe
was the first patient anesthetized that Monday morning and that he was more severely affected than Albert Woolley,
who was the second case, supports the theory. Finally, pathologic findings support the conclusion that an acidic
solution was introduced into the subarachnoid space. [24]
CONTINUOUS SPINAL ANESTHESIA
Seven years after Bier’s landmark work on the administration of cocaine via lumbar puncture, Henry Percy Dean, a
British surgeon, introduced a modification of the technique called continuous spinal anesthesia. Unfortunately, [25]
many of his colleagues who attempted the procedure encountered difficulties such as needle trauma and breakage.
Therefore, the technique fell into disfavor, as can be evidenced by the lack of citations referring to continuous spinal
anesthesia in the English language medical literature from 1907 to 1939. [26]
In 1940, all of that changed when William T. Lemmon re-introduced the technique of continuous spinal anesthesia
to the anesthesia community with somewhat different results. Lemmon noted that the problems that Dean
encountered earlier in the century were still present and that solutions needed to be devised. To do this, he used
special equipment for his technique. First, he designed an operating room table mattress that permitted the patient to
lie in the supine position without dislodging the needle or tubing. Second, and more importantly, he totally
redesigned the spinal needle. His 17-gauge (G) or 18-G needle was constructed of German silver, which made it
very malleable. Once the needle was in place, it was connected to the tubing, which was routed through the hole in
the mattress to a spot near the patient’s head, where a syringe containing local anesthetic was attached. The tubing
was made of hard rubber to prevent bulging on injection and contained exactly the 2 mL of drug that needed to be
accounted for when calculating the dose of local anesthetic delivered to the patient. The technique was used with
great success on the battlefields during World War II; it was credited, at least in one unit, for decreasing mortality
from abdominal wounds from 46% to 12.5%. [27]
Edward B. Tuohy modified the technique when he placed a catheter through the needle into the subarachnoid space
to avoid the problem of needle dislodgment from the space. Even with Tuohy’s modification, acceptance of the
[28]
technique was slow. And, in 1950, Robert Dripps compared the malleable needle technique of Lemmon and the
catheter technique of Tuohy with the standard single shot technique used by the majority of practitioners. He
compared technical difficulties and absolute failures of all three techniques. Dripps’ results demonstrated that the
single injection technique was associated with fewer technical difficulties and absolute failures than the other two.
“Because of the number of failures, the technical problems, the degree of trauma, and the increased likelihood of
loss of CSF inherent in the methods of continuous spinal anesthesia, it is our belief that such methods should be
used less frequently.” Interestingly, with respect to both technical difficulties and absolute failures, the malleable
[29]
needle was superior to the catheter technique of Tuohy when the two continuous techniques were compared.
Again, the technique of continuous spinal anesthesia fell into a long period of quiescence. Once again, however, it
rose from the ashes! In 1964, Dante Bizzari stated that he feared continuous spinal anesthesia because of the need
for large-bore needles and the dural rents they caused. He advocated the use of 20-G or 21-G needles with smaller
catheters. Bizzari’s ideas needed technology to catch up with them. In 1987, Hurley and Lambert reported their
[30]
work on the use of a microcatheter in continuous spinal anesthesia and the decreased incidence of postdural
puncture headaches. [31]
Small-gauge continuous spinal anesthesia quickly grew in popularity. However, problems soon arose. Rigler and
colleagues reported on patients developing cauda equina syndrome after receiving treatment via a microcatheter.
Maldistribution of local anesthetic was thought to be responsible. Because of the high resistance of the small lumen
25
of the microcatheter, it was widely believed that the local anesthetic did not diffuse in the subarachnoid space. It
appeared that if the initial dose of local anesthetic failed to provide an adequate block, a second dose would often be
given. This resulted in a restricted block, which appeared to be linked to the cauda equina syndrome. [32]
The Food and Drug Administration (FDA) acted on the initial reports of cauda equina syndrome and issued stringent
guidelines regarding microcatheter use. Unfortunately, the incidence of cauda equina syndrome did not decline, and,
in 1992, all microcatheters were withdrawn from use in the United States by the FDA. Thus, at the time this chapter
was written, those practicing the technique of continuous spinal anesthesia had reverted to large-bore catheters until
the FDA should complete studies of a new catheter.
Epidural Anesthesia
Although Corning may have administered the first epidural anesthetic, Jean Athanase Sicard and Fernand Cathelin
in 1901 independently published their account of peridural anesthesia. They approached the epidural space through
the sacral hiatus, giving what now would be described as a caudal anesthetic. Marin Théodore Tuffier attempted a
lumbar epidural block that same year but had difficulty locating the space. Twenty years later, Fidel Pages
[33]
described the intraspinous approach to the epidural space and reported satisfactory anesthesia for intra-abdominal
procedures. In the early 1930s, Archile Mario Dogliotti, building on Jansen’s discovery of negative pressure in the
epidural space, described a practical technique for administering lumbar segmental anesthesia. Using Dogliotti’s [34]
work as a foundation, Gutierrez, in 1932, described the hanging drop technique to identify the epidural space. [35]
A year earlier, Eugene Aburel placed a silk ureteral catheter in the epidural space and used it to block the pain of
women in labor. During World War II in America, Robert Hingson was assigned to care for the pregnant wives of
[36]
United States Coast Guard seamen. Stationed at a U.S. public heath hospital, Hingson wanted to develop a method
whereby he could alleviate the pain of labor in these women. Unaware of Aburel’s work, Hingson took Lemmon’s
malleable needle and placed it sacrally, deep to the peridural ligament. This safe and effective method of producing
painless childbirth became popularly known as continuous caudal anesthesia. In 1949, Manuel Martinez Curbello
[37]
modified a silk catheter for continuous spinal anesthesia and inserted it into the epidural space, thus creating the first
continuous epidural block. By 1962, the first polyvinyl catheter with a closed tip was introduced, making the
[38]
continuous epidural block much easier to perform correctly. [39]
Controversy concerning use of epidural analgesia in labor continued. Opponents of the practice claimed it increased
the number of instrumental deliveries, but proponents claimed that it did not. By the early 1990s, the combination of
dilute local anesthetic and narcotic was demonstrated to be no different from any other form of obstetric pain
relief. Currently, epidural analgesia has been combined with subarachnoid narcotics to ease the pain of labor.
[40]
Combined spinal-epidural anesthesia is one of the leading techniques on obstetric floors at the dawn of the 21st
century. [41]
Brachial Plexus Block
In 1884, less than a year after the discovery of the anesthetic properties of cocaine, William Halsted performed the
first regional blockade of the brachial plexus. His technique involved surgical exposure of the plexus in the neck
with subsequent intraneural blocking of individual nerves. Effectively providing complete anesthesia to the upper
[42]
extremity, the procedure itself was, at times, nearly as extensive as the surgery for which it was being provided.
Unfortunately, an addiction to cocaine, the very drug that Halsted used to block the plexus, befell him, limiting his
ability to popularize his approach. [43] [44]
It was not until 1887, when George Crile exposed the brachial plexus behind the sternocleidomastoid muscle to help
control tetanic spasms in a young boy, that the block was used with some regularity. While he was at the Cleveland
[45]
Clinic, Crile expanded the use of the brachial plexus block to include surgical anesthesia for upper extremity
procedures. His original article of 1902, published in The Journal of the American Medical Association, spoke
[46]
favorably of the block as being superior hemodynamically to general anesthesia for amputations of the shoulder
joint. It is noteworthy that at this time in history, shoulder amputations were dangerous surgeries, with large blood
loss potential and high subsequent mortality. A procedure that could effectively provide anesthesia as well as limit
[47]
inherent surgical risk would be a popular discovery.
Not until 1911 was the first percutaneous approach to the brachial plexus described by Hirschel. His axillary
approach involved injection both below and above the axillary artery, a novel technique still employed with
modifications in today’s practice. His knowledge of the anatomy of the brachial plexus stemmed from his
26
experience in performing axillary dissections during radical mastectomy procedures. Despite the fact that he injected
local anesthetic in a continuum from the entry of the skin up to the posterior section of the axillary artery, Hirschel
never reported complications of intravascular injection. Because he understood the importance of retaining a strong
concentration of anesthetic in the area of the nerves for as long a period as possible, Hirschel employed a
mechanical blockade against dissipation of the anesthetic by use of a rubber ball that was held in place under the
pectoral muscles by elastic bandages. Later, he found that simply increasing the volume of local anesthetic resulted
in the same efficacy.[45]
In the same year that Hirschel popularized his percutaneous approach to blocking the brachial plexus in the axilla,
Kulenkampff in Germany described the first “blind” supraclavicular approach to blocking the brachial plexus.
Interestingly, he perfected his technique by trying the block on himself. Others who tried to duplicate Hirschel’s
technique for blocking the brachial plexus in the axilla were unable to meet the same level of success that he had
described. One explanation was that the axilla technique lacked precision compared with the supraclavicular
approach to the plexus. [45]
Greater precision and perhaps improved success rates for blocking the brachial plexus at the axilla were not far off.
Capelle in Germany in 1917 wrote of a simplified perivascular approach to blocking the plexus. His knowledge of
the anatomy of the brachial plexus in the region of the axilla did not include an understanding of a fascial
compartment; however, he was aware that the nerves serving the upper extremity did pass proximal to the axillary
artery. Reding in 1921 is thought to have been the first to highlight the importance of the neurovascular sheath in the
plexus block at the axilla. His descriptions of the anatomy of the brachial plexus within the axilla include discussion
of a fascial sheath surrounding a bundle of nerves. Reding was also aware that the musculocutaneous nerve was not
contained within the sheath and that blocking this nerve required injection of local anesthetic within the
coracobrachialis muscle. [45]
The techniques of Capelle and Reding were largely ignored, whereas the supraclavicular approach described by
Kulenkampff remained popular. It was not until 1958 that Preston Burnham, an orthopedic surgeon, revived the
neurovascular sheath approach for blocking the brachial plexus. While repairing an axillary laceration in a child,
Burnham noted that the nerves entering the axilla were proximal to the axillary artery. Additionally, a fascial sheath
surrounded both nerves and vasculature. If the sheath were entered with one pass of a needle, multiple nerves could
be bathed with local anesthetic. Modifications to Burnham’s perivascular approach were made over the years to
include increasing the volume of the local anesthetic to be used in order to ensure a more “solid” block. However,
Burnham’s initial work in developing the technique of blocking multiple nerves with fewer injections simplified this
procedure and subsequently established the popularity that this technique enjoys today.
Preemptive Analgesia
George Crile at the Cleveland Clinic came up with the idea that pain could be controlled through the use of regional
anesthesia combined with a light general anesthetic. The approach that Crile took to the brachial plexus, for
example, became known as “Crile’s technique,” and through its use alone, or as an adjunct to light general
anesthesia, he was able to effectively block a patient’s stress response to surgery. He also found that patients did not
need deep ether anesthesia with its attendant pulmonary risks for intra-abdominal surgery. It is these findings that
[48]
helped prompt his belief that there was “anoci-association” between effective anesthesia and hemodynamic changes
that occur with surgical procedures. Indeed, it was Crile’s search for a method of anesthesia and surgery without
shock that led him to combine regional and general anesthesia. [49]
To follow Crile’s technique completely was cumbersome and time-consuming. Patients had to be kept quiet
preoperatively. Intraoperatively, the plexus of innervating nerves was often dissected under local anesthesia. Crile
admonished surgeons to handle tissue carefully and gently. Rough handling caused shock. Gradually, as better
[44]
local anesthetics made other forms of regional anesthesia reliable and—to some extent—as anesthesia became
professionalized, Crile’s technique was abandoned. Especially after the introduction of muscle relaxants by Harold
Griffith in 1941, and as shock became better understood after World War II, there was little need for the elaborate
planning and slow surgery demanded by anoci-association.
However, in 1983, C. J. Woolf published his animal model experimentation, which demonstrated a central
component to post-injury pain hypersensitivity. Investigation confirmed that the central component in the animal
[50]
model was real and could be blocked by regional anesthetic techniques. The ensuing human studies have been less
clear. However, it appears that a block of the affected nerves needs to be present during surgery to blunt the central
27
component. What is clear is that regional anesthetic techniques have been demonstrated to aid patients’ recovery
[51]
from surgery, and regional analgesia is a “new” direction in the evolution of regional anesthetic techniques.
Dissemination of Information
Professional interaction is critical for the exchange of ideas and the dissemination of new techniques. Gaston Labat (
Fig. 2-5 ), who left Paris in 1920 and traveled to
the Mayo Clinic to bring regional anesthetic techniques there, spent 9 months training the surgeons of the clinic in
regional anesthesia. The most notable accomplishment during his time at the Mayo Clinic was the production of
Regional Anesthesia. This was the first American textbook to be devoted to regional anesthesia and was
[52]
immensely popular; the second printing was greater than the first, a rarity in medical publishing. After leaving
Rochester, Minnesota, Labat settled in New York City and was affiliated with New York University and Bellevue
Hospital. He taught regional anesthesia courses and also administered anesthesia.
[53] [54]
In 1923, the American Society of Regional Anesthesia (ASRA) was created in New York City. Originally, the
society was founded to honor Labat, and the group was a mixture of surgeons, neurosurgeons, and physician
anesthetists. Early meetings focused on regional anesthetic techniques, complications, and the matching of blocks
[55]
to surgical procedures. The proceedings of the meeting and papers presented were published until 1932 in Current
[56]
Researches in Anesthesia and Analgesia. In 1933, Paul Wood was elected secretary of the organization ( Fig. 2-6 ).
[57]
He began to mimeograph the minutes and send them to members across the country who could not attend the New
York City meetings. Thus, ASRA became a truly national society, and the papers presented before it had excellent
exposure to their intended audience. [58]
In the early 1930s, ASRA’s meetings took a slightly different direction. Papers, such as James White’s report on the
use of procaine block to predict the therapeutic value of surgical resection in relieving pain and Philip [59]
Woodbridge’s review of therapeutic blocks for chronic pain, began to dominate the program ( Fig. 2-7 ). Thus,
[60]
regional anesthetic techniques were translated into the emerging new field of pain management. Emery Rovenstine (
Fig. 2-8 ) became president of ASRA in 1935 and moved the organization further into pain management. The 1936
clinical demonstrations, held in conjunction with a meeting of ASRA, were three quarters related to pain
management. [35]
Rovenstine was an active participant in the decision by ASRA to cosponsor the American Board of Anesthesiology (
Fig. 2-9 ). As the necessary second national organization required by the American Medical Association, ASRA was
in a unique position to ensure that regional anesthesia was considered a part of the curriculum of every
anesthesiologist. On the first written examination, the entire anatomy section was devoted to questions germane to
[61]
regional anesthesia. There were regional anesthesia questions in the pathology and pharmacology sections as well. [62]
Unfortunately, by 1939, interest in the organization had waned, and by 1941, the society was enfolded into the
American Society of Anesthesiologists.
In 1975, several prominent anesthesiologists, among them Alon Winnie, P. Prithvi Raj, and John Rolwson,
perceived the need to reintroduce regional anesthetic techniques to anesthesiologists. Without knowledge of the
original society, they organized the American Society of Regional Anesthesia. Within 6 months of its organization,
the group held a meeting in Phoenix, Arizona, on the day before the International Anesthesia Research Society
meeting. The society already had 300 members. Its avowed purpose was to educate and disseminate regional
anesthetic techniques. [63]
Within a year of the founding of the society, a journal was published. Regional Anesthesia, now Regional
Anesthesia and Pain Medicine, is an important journal covering a wide range of topics germane to regional
anesthesia. In addition to an independent 3-day meeting, there are many forums available where a member of ASRA
can learn about regional anesthesia. ASRA’s annual meeting was one of the first to have a hands-on workshop
demonstrating how to do blocks under the tutelage of meeting faculty members who had mastered the technique. In
2000, ASRA celebrated its 25th anniversary. Regional anesthesia is alive and well and is entering the 21st century in
a manner that Gaston Labat could never have imagined.
28
Pain Comes of Age
Rovenstine’s interest in regional anesthesia and pain medicine was not simply political. He ran a “block” clinic
where he tried to help patients with chronic pain problems by applying regional anesthetic techniques. Ralph Waters
( Fig. 2-10 ), his mentor and friend, once chided him by saying that he should not spend “…all of his time in
consultation work in regard to diagnostic and therapeutic blocks.” Rovenstine responded that the work in the pain
[64]
clinic was what he found most stimulating professionally, and that the operating room had lost some of its appeal. [65]
The practice of pain medicine and the ability to help patients whose cases were often thought to be hopeless made
his work exciting.
In treating soldiers with pain problems after World War II, John Bonica found the same rewards as Rovenstine. He
saw that regional anesthetics provided relief to his patients, but often the pain would return when the local
anesthetics “wore off,” or the anesthetics were not at all effective. Bonica noted that some patients in this group
needed neurologic evaluation. Often, they also benefited from the intervention of trained mental health
professionals, but coordination of care was a problem. From these observations, the idea of a multidisciplinary pain
clinic arose. [66]
Bonica would be well remembered for the concept of the multidisciplinary pain clinic, but that was his only
accomplishment. In 1953, Bonica published the first edition of his now classic textbook, The Management of Pain. [67]
Within the confines of the text, Bonica clearly lays out which blocks work for which painful conditions. In addition,
Bonica was active politically and became president of the American Society of Anesthesiologists and the World
Federation of Societies of Anesthesiologists. Through his work in organized medicine, he brought pain issues to the
forefront of anesthesiology, including regional anesthetic techniques.
Conclusions
The history of techniques in regional anesthesia is replete with names that are instantly recognized as well as those
that are somewhat more obscure. And although one person often is awarded credit for the discovery or
popularization of a technique, it takes many anesthesiologists to properly apply the method. Al Winnie entitled his
Labat address, “Nothing New Under the Sun,” and promptly demonstrated that the issues that were responsible for
[63]
the formation of the first ASRA were present more than 50 years later when the second was formed. He also traced
the history of various regional anesthetic techniques, demonstrating that the late 20th century “discoverer,” without
knowledge of the history of regional anesthesia, might have only reinvented what a colleague had done at the
beginning of the century.
At the dawn of the 21st century, regional anesthesia and the techniques for accomplishing it are alive and well. From
the operating room to the pain clinic and beyond, regional anesthesia is evolving and will remain an important part
of patient care. Those who are the Biers, the Criles, and the Cornings of today will leave a rich legacy of caring for
patients in ways that we can only begin to imagine.
REFERENCES
1. Cotugno D: De ischiade nervosa commentarius. Neapoli, Apud Fratres Simonios, 1764.
2. Quincke H: Zur Physiologie de Cerebrospinal flussigkeit. Arch Anat Physiol 153–177, 1872.
3. Vandam L: On the origins of intrathecal anesthesia. Reg Anesth Pain Med 23:335–339, 1998.
4. Wynter WE: Four cases of tuberculous meningitis in which paracentesis of the theca vertebralis was performed. Lancet 1:981–982, 1891.
5. Quincke HI: Die Technik der Lumbalpunktion. Verh Dtsch Ges Inn Med 10:321–331, 1891.
6. von Ziemssen HW: Allgemeine behandlung der infektionskrankenheiten. Jena 1894.
7. Quincke H: Ueber hydrocephalus. Verh Kong f Inn Med 10:322–329, 1887.
8. Jacoby GW: Lumbar puncture of the subarachnoid space. N Y Med J 62:813–818, 1895.
9. Koller C: Vorlaufige Mittheilung uber locale Anasthesirung am Auge. Klin Mbl Augenheilk 22:60–63, 1884.
10. Corning JL: Spinal anaesthesia and local medication of the cord. N Y Med J 42:183–185, 1885.
29
11. Marx GF: The first spinal anesthesia. Who deserves the laurels? Reg Anesth 16:429–30, 1994.
12. Goerig M, Agarwal K, Schulte am Esch J: The versatile August Bier (1861–1949), father of spinal anesthesia. J Clin Anesth 12:561–569,
2000.
13. Bier A: Versuche uber Cocainisirung des Ruckenmarkes. Dtsch Ztschr Chir 51:362–369, 1899.
14. Van Zundert A, Goerig M: August Bier 1861–1949. Reg Anesth Pain Med 25:26–33, 2000.
15. Larson MD: Tait and Caglieri. The first spinal anesthetic in America. Anesthesiology 85:913–919, 1996.
16. Kreis H: Uber Medullanarkose bei Gebarenden. Centralblatt fur Gyn July:724–726, 1900.
17. Adriani J: Labat’s Regional Anesthesia: Techniques and Clinical Applications. St. Louis, Warren H. Green, 1985, p 699.
18. Menendez JV, Burns T, Bacon DR: Lincoln Fleetwood Sise: Regional anesthesia’s forgotten man? Reg Anesth Pain Med 24:364–368, 1999.
19. Vandam LD, Dripps RD: Long-term follow-up of patients who received 10,098 spinal anesthetics. JAMA 161:586–591, 1956.
20. Vandam LD, Dripps RD: Exacerbation of pre-existing neurologic disease after spinal anesthesia. N Engl J Med 255:843–849, 1956.
21. Maltby JR, Hutter CDD, Clayton KC: The Woolley and Roe case. Br J Anaesth 84:121–126, 2000.
22. Morgan M: The Woolley and Roe case. Anaesthesia 50:162, 1995.
23. Cope RW: The Woolley and Roe case. Anaesthesia 9:249–270, 1954.
24. Hutter CDD: The Woolley and Roe case. Anaesthesia 45:859–864, 1990.
25. Dean HP: The importance of anesthesia by lumbar injections in operations for acute abdominal disease. BMJ 1:1086–1090, 1906.
26. Tobis G, Sands R, Bacon D: Continuous spinal anesthesia: A continuous history? Reg Anesth Pain Med 24:453–457, 1999.
27. Bacon D, Lema M: Standing on the promises. Sphere 42:20–24, 1989.
28. Tuohy E: The use of continuous spinal anesthesia. JAMA 128:262–263, 1945.
29. Dripps R: A comparison of malleable needle and catheter techniques for continuous spinal anesthesia. N Y State Med J 50:1595–1599, 1950.
30. Bizzari D, Giuffrida JG, Bandoc L, Fierro F: Continuous spinal anesthesia, using a special needle and catheter. Anesth Analg 43:393–399,
1964.
31. Hurley R, Lambert D: Continuous spinal anesthesia with a microcatheter technique. Reg Anesth 12:54–58, 1987.
32. Riger M, Drasner K, Krejcie T, et al: Cauda equina syndrome after continuous spinal anesthesia. Anesth Analg 275–281, 1991.
33. Bromage PR: Epidural Analgesia. Philadelphia, WB Saunders, 1978, pp 1–7.
34. Dogliotti AM: Anesthesia. Chicago, SB Debour, 1939, pp 529–544.
35. Lund PC: Peridural Analgesia and Anesthesia. Springfield, Ill, Charles C Thomas, 1966, pp 3–10.
36. Aburel E: L’anesthésié locale continue (prolongée) en obstétrique. Bull Soc Obstet Gynecol (Paris) 20:35–9, 1931.
37. Hingson RA: The pathway across half a century of development of safe control of obsetric pain in childbirth. Reg Anesth 6:62–66, 1981.
38. Curbello MM: Continuous peridural segmental anesthesia by means of a ureteral catheter. Anesth Analg 28:13–23, 1949.
39. Lee JA: A new catheter for continuous extradural analgesia. Anaesthesia 17:248–250, 1962.
40. Vertommen JD, Vandermeulen E, Van Aken H, et al: The effects of the addition of sufentanil to 0.125% bupivacaine on the quality of
analgesia during labor and on the incidence of instrumental deliveries. Anesthesiology 74:809–814, 1991.
41. Gogarten W, Van Aken H: A century of regional analgesia in obsetrics. Anesth Analg 91:773–775, 2000.
42. Winnie
AP: The early history of regional anesthesia in the United States. In Scott DB, McClure, Wildsmith JAW (eds): Regional Anesthesia
1884–1984. Sodertalje, Sweden, Information Consulting Medical, 1984, pp 35–38.
30
43. Fink BR: History of neural blockade. In Cousins MJ, Bridenbaugh PO (eds): Neural Blockade, 2nd ed. London, JB Lippincott, 1988 pp 3–21.
44. Olch PD: William S. Halstead and local anesthesia: Contributions and complications. Anesthesiology 42:479–486, 1975.
45. Winnie AP: Plexus Anesthesia—Perivascular Techniques of Brachial Plexus Block. Philadelphia, WB Saunders, 1983, p 68.
46. Gwathmey JT: Anesthesia. New York, D. Appleton, 1914, p 490.
47. Bacon DR: Regional anesthesia and chronic pain therapy: A history. In Brown DL (ed): Regional Anesthesia and Analgesia. Philadelphia, WB
Saunders, 1996, pp 10–22.
48. Crile GW: Anoci-association in relation to oeprations on the gall bladder and stomach. JAMA 63:1335–1337, 1914.
49. Crile GW: An experimental and clinical research into cocain and eucain. JAMA 38:491–499, 1902.
50. Woolf CJ: Evidence for a central component of post injury pain hypersensitivity. Nature 308:686–688, 1983.
51. Kissing I: Preemptive analgesia. Anesthesiology 93:1138–43, 2000.
52. Labat G: Regional Anesthesia: Its Technic and Clinical Application. Philadelphia, WB Saunders, 1922.
53. Advertisement for the New York University Bellevue Hospital regional anesthesia course. Curr Res Anesth Analg 4:13, 1925.
54. Bill from Gaston Labat, M.D., to Mrs. P.S. Rosenheim, November 16, 1927. Wood Library-Museum of Anesthesiology Collection, Gaston
Labat Vertical File, Park Ridge, Ill.
55. Brown DL, Winnie AP: Biography of Louis Gaston Labat, M.D. Reg Anesth 17:249–262, 1992.
56. Minutes
of Meeting of the American Society of Regional Anesthesia, 1925–1939. The Collected Papers of Paul Wood, M.D. The Wood
Library-Museum Collection, Park Ridge, Ill.
57. Labat G: Proceedings of the American Society of Regional Anesthesia. Curr Res Anesth Analg 1925–1932, vol 4–11: passim.
58. Bacon DR, Reddy V, Murphy OT: Regional anesthesia and chronic pain management in the 1920s and 30s. Reg Anesth 20:185–192, 1995.
59. White JC: Diagnostic novocaine block of sensory and sympathetic nerves. Am J Surg 9:264–277, 1930.
60. Woodbridge PD: Therapeutic nerve block with procaine and alcohol. Am J Surg 9:278–288, 1930.
61. Bacon DR, Darwish H, Emery A: Rovenstine and regional anesthesia. Reg Anesth 22:273–279, 1997.
62. BaconDR, Lema MJ: To define a speciality: A brief history of the American Board of Anesthesiology’s first written examination. J Clin
Anesth 4:489–497, 1992.
63. Winnie AP: Nothing new under the sun. Reg Anesth 7:95–102, 1982.
64. Letter from Ralph M. Waters, M.D., to Emery Rovenstine, M.D., July 5, 1944. The Collected Papers of Ralph M. Waters, M.D. Steenbock
Library Collection, University of Wisconsin Archive, Madison, Wis.
65. Letter
from Emery A. Rovenstine, M.D., to Ralph M. Waters, M.D., July 8, 1944. The Collected Papers of Ralph M. Waters, M.D. Steenbock
Library Collection, University of Wisconsin Archive, Madison, Wis.
66. Thompson D: Pain relief’s founding father. Time. June 11, 1984.
67. Bonica JJ: The Management of Pain. Philadelphia, Lea & Febiger, 1953.
31
Section II - Chapter 3 - Economic Impact of Regional Anesthesia
Section II - General Considerations for Regional Anesthesia
Diego Beltrutti
32
Chapter 3 - Economic Impact of Regional Anesthesia
GIUSTINO VARRASSI
FRANCO MARINANGELI
FRANCESCO DONATELLI
ANTONELLA PALADINI
One key approach to evaluating medical practice in the future will be based on assessing the effectiveness of the
intervention in relation to the cost of providing it. Attempts to evaluate the effectiveness of medical interventions are
hardly new. Nearly a century ago, E. A. Codman, M.D., at the Massachusetts General Hospital in Boston, urged that
patients should be followed up long enough to determine the success of the treatment. But the efforts today go
beyond developing clinical evidence of effectiveness; cost is also a factor. For example, in determining the cost of
drug therapy, one must consider not just the price of the drug but also the expense involved in its administration,
whether it is given in hospital or to an outpatient, the pharmacist’s time in preparing the prescription, and so on.
The Need for Economic Evaluation
The increased interest in cost derives from the fact that in the economically developed countries health coverage is
becoming more and more expensive, and the resources absorbed by national healthcare, when extracted from the
rest of the economic system, represent a remarkable portion of the gross domestic product.
It was reported that U.S. healthcare expenditures in 1998 totaled $838.5 billion, or 14% of the gross domestic
products, and more than 40 cents of each dollar spent on healthcare is provided by the government. [1]
The factors mostly responsible for this phenomenon are the laws that rule each type of market. These laws are based
on supply and demand. The latter encompasses the increasing attention given to well-being, quality of life, and the
needs of an aging population, and the former expresses the development of more advanced medical technology. On
the one hand, consumers often find it difficult to correlate their needs with the complex nature of the goods offered,
thus delegating decision making to the physician; on the other hand, particularly in industrialized countries,
individuals, regardless of their economic condition, have been conditioned to expect a guaranteed right to
healthcare, with their communities and governments assuming a large portion of the financial burden. Where this
has happened, as in the United States, the citizen has almost always met the costs of illness by means of recourse to
private insurance. The result is that the abiding presence of the third-party payer prevents the high price from
exercising its action of rationing.
Thus, it is the physician and not the consumer who carries out the decision making, often being influenced by
factors other than the needs of the patient. Even more remarkable is the fact that neither the physician nor the patient
bears the direct economic consequences of the choices made, often preventing the correct distribution of the
resources destined for the healthcare system.
Hence, it became increasingly necessary to find means capable of creating a more efficient distribution of the budget
at the disposal of the healthcare system. Beginning in the year 1960, an attempt was made to develop criteria, tools,
and methods that would allow the evaluation, from an economic point of view, of the investments, programs, and
products in the healthcare system. Since then, an increasing number of studies that reveal the economic
consequences of a specific healthcare choice in the different physician-surgical disciplines have been published in
various scientific magazines. For example, studies of ICU use have attempted to identify the types of patients who
can benefit maximally from ICU admission. Patients who are not predicted to benefit from ICU services may be
[2]
excluded from them. This change in practice is intended to save roughly $60 billion per year spent on ICUs in the
United States, a figure that represents approximately 24% of all inpatient hospital costs, 9% of overall healthcare
expenditures, and 1.1% of the gross national product. [3] [4]
33
Economic Analysis Methods Used in Healthcare
Two characteristics are important in economic analysis, each operating from the sectors of activity to which it is
applied.
The first characteristic is constituted by the resources employed (the costs) and by the results obtained (the
consequences). Few of us would be ready to pay a given price for a parcel without knowing its contents. Moreover,
few of us would acquire a package, even knowing and desiring its content, before knowing its cost. In both cases, it
is the correlation between the costs and the results that influences the decision.
Regarding the second characteristic, economic analysis is based upon the available choices. Because one cannot
provide reliable effective outcome, the scarcity of resources makes us choose the options based mostly on explicit
criteria. The economic analyst strives to identify this set of criteria, which may be useful to the physician for making
decisions.
Economic analysis can be defined as comparative analysis, in terms of costs and consequences of the series of
alternative actions generated by each program. Its primary task, even when applied to the sanitary services sector,
consists, therefore, in identifying, measuring, evaluating, and comparing costs and effects of the alternative actions
considered. It is possible to outline the various types of economic analysis. In Table 3-1 , two questions are asked:
“Are two or more alternatives being compared?” and “Are both the costs and the consequences of each alternative
being examined?” The possible answers define a matrix of six boxes, each of which characterizes a situation being
evaluated. In boxes 1A, 1B, and 2, only one program is taken into consideration, with no comparison made between
different alternatives. In 1A, only the consequences are examined; hence, the box identifies the description of the
results obtained, and in 1B, because only the costs are examined, the box is classified as the description of the costs.
In box 2, the costs and results produced are described.
Boxes 3A and 3B classify situations in which there are two or more alternatives to be compared but in which either
the costs or the effects of each alternative are not examined. In 3A, only the consequences of each alternative are
compared (evaluations of theoretical or real effectiveness). In 3B, only the costs of the alternatives are examined
(analysis of the costs). These analyses do not satisfy the requisites necessary for an economic evaluation; for this
reason, it is defined as a partial evaluation. This, however, does not imply that these studies are not important. In
fact, they represent important intermediary stages for the comprehension of the costs and consequences of the
services or of the programs. Certainly, however, they are not sufficient to solve the problem of efficiency; for this
reason, it is necessary to employ the techniques of economic evaluation listed in box 4:
• Cost minimization
• Cost-effectiveness
• Cost-benefit analysis
• Cost of utility
COST MINIMIZATION
The minimization of the costs consists of comparing two or more alternatives that have identical effects in terms of
health but different consumption modalities of the resources necessary to achieve them. It is the simplest method for
evaluating efficiency because it highlights, among different alternatives retained of equal effect, which option has
the lowest consumption of resources without giving particular attention to the measurement of the same effects.
The purpose of this analysis is to answer, for instance, the question, Which therapeutic program for myofascial pain
costs less?” The cost of two or more treatments for which a complete equivalence of the effects was ascertained or
hypothesized are compared with the aim of identifying the most convenient one.
34
TABLE 3-1 -- HAVE COSTS AND CONSEQUENCES FOR EACH INTERVENTION BEEN EVALUATED?
No Yes
Only the consequences Only the costs Costs and consequences
Have two or more 1A 1B 2
N
alternatives been Partial evaluation Partial evaluation Partial evaluation
O
compared? Description of results Description of costs Description costs/results
3A 3B 4
Partial evaluation Partial evaluation Complete evaluation
Y
Evaluation of the efficacy Cost analysis Cost minimization
E
Cost effectiveness
S
Cost benefit analysis
Cost of utility
A comparison of outpatient surgery with inpatient treatment of hernias or hemorrhoids may also be suitable for a
cost minimization analysis. If there is strong evidence to suggest that there are no great differences in clinical
outcomes for these two defined groups of patients, one can concentrate on identifying the lesser cost option.
Much too often, it is assumed that two programs have identical results. If this were really the case, there would be no
difference between the minimization of the costs in boxes 3B and 4 of Table 3-1 . It would be wise, however, to
furnish some proof to ensure that the results of the two alternatives are equivalent or that they present irrelevant
differences.
COST-EFFECTIVENESS
Cost-effectiveness analysis compares two or more alternatives that have identical effects from the qualitative point
of view but different effects from a quantitative point of view and that involve different modalities of resource
consumption necessary to achieve them.
The choice does not fall automatically on the least expensive program, except when the best result is also the least
expensive choice. A comparison based on cost per unit is always done before the choice is made.
For example, there is a range of treatments available for the control of hypertension. These vary in terms of their
outcomes, side effects, and so on, but they may all be measured primarily in terms of the reduction in diastolic blood
pressure (mm Hg) they achieve.
In practice, this analysis measures the cost to reach a determined therapeutic objective, measured in physical units,
such as lowered Visual Analogic Scale (VAS) score, increase in the degrees of excursion of an articulation, or years
of life earned. The lower the cost of a physical unit obtained, the higher the efficacy of a treatment.
COST-BENEFIT ANALYSIS
Cost-benefit analysis evaluates two or more relief alternatives whose effects are not necessarily identical or that lead
to a single common effect. This type of analysis tries to go beyond the considerations of the specific effects,
individualizing a modality of measurement of all the results of the considered program. One of these measures is the
monetary unit that quantifies, in monetary terms, the benefits of the program. It also facilitates cost comparison.
Successively, the costs of a pharmacologic treatment are compared with the economic benefits (savings of resources
for the reduction of morbidity and mortality rates).
The net benefits are calculated from the difference between the total benefits (savings) and the total costs. The
greater the savings and the lower the costs of a treatment, the more beneficial it is. Each alternative is compared with
the alternative of doing nothing, characterized by additional void costs (i.e., by the maintenance of the status quo). It
implicitly allows comparison of each alternative with the choice not to do anything, a choice without costs or
benefits.
Unlike the analysis of minimization of costs and analysis of cost-effectiveness, this technique of analysis does not
subtend any option for a determined objective that could be rejected if the results do not satisfy the preset criteria.
35
COST OF UTILITY
Another measure of the value of a program, preferred by many analysts, but more difficult to obtain, is utility.
Utility refers to the value of one specific level of the state of health and can be measured on the basis of individual
or societal preferences for a set of results produced by the healthcare services.
The analysis of utility is a relatively new technique in the field of evaluation of services, but it is considered very
promising because it even takes into account the quality of life in judging the results of a treatment program. At the
same time, it has a common denominator that makes the costs and results of different programs homogeneous and
comparable. This common denominator, usually expressed in the formula of days of health or years of life earned
and balanced with the relative quality of life, is obtained case per case by multiplying the duration of the result by a
coefficient of relative utility of the state of health reached.
Cost Analysis
Assessment of cost is essential when performing any evaluation of the economic impact of a healthcare intervention
and is similar for all four methods of analysis.
Definition of the cost accounting terms are listed in Table 3-2 . Cost assessment varies according to the perspective
of the person making the assessment. Common perspectives considered in healthcare cost analyses include those of
society as a whole, those of health insurance companies or other payers, those of healthcare providers, and those of
the patient. What is relevant from one perspective may be irrelevant from another. Many healthcare economic
analysts recommend that wide-ranging policy decisions on drug use should be based on cost assessments that take
the widest possible perspective (i.e., society as a whole). Cost considerations from a narrower point of view may
[5] [6]
overlook shifting cost from one segment of society to another (e.g., early discharge shifts recovery costs from
TABLE 3-2 -- DEFINITIONS OF COMMONLY USED COSTS

Term Definition
Costs Sacrifice measured as the price paid for the irreversible use of a resource
Direct costs Cost of the material and labor used for production
Indirect costs Costs related to the consequences of an event on society or on an individual
Average costs Total costs divided by the number of units produced
Fixed costs Costs that remain the same regardless of the number of goods or services produced
Marginal costs Change in costs for producing one additional unit of output
Variable costs Costs that change with the number of services provided
the healthcare system itself to patients, their families, and their primary care physicians). [7]
The total costs associated with a medical intervention consist of direct and indirect costs. The direct costs of a
particular treatment include not only the acquisition cost of the amount of drug administered but also the costs of
drug wastage, equipment for therapy administration (e.g., intravenous sets, syringes), pharmacy dispensing costs,
and the costs of managing any drug-induced side effects. From the patient’s perspective, total costs include
nonmedical, direct, out-of-pocket costs (e.g., transportation to the site of therapy, family lodging, home help care)
along with indirect costs of wages lost by the patient and the family member who is the caregiver. [8]
The term indirect costs is used differently by physicians, accountants, and healthcare economists. Although some
physicians refer to costs of managing side effects and delayed recovery as indirect costs, most healthcare [9]
economists would describe these as associated direct costs. Accountants include all fixed costs in their
[10] [11]
calculation of indirect costs, whereas economists usually refer to indirect costs as the costs related to lost
productivity. [12]
COSTS OF ANESTHESIA
Expenditures controlled by anesthesia providers represent 3% to 5% of the total healthcare costs of the United
States. The cost implications of anesthesia care are complex. Not only are there significant costs associated with
[13]
36
the delivery of anesthesia care (e.g., cost of drugs, equipment, supplies, provider fees), but there can be additional
costs associated with care (e.g., perioperative testing, consultation with other providers, complications).
Macario and coworkers, reporting on a study elucidating the proportion of anesthesia costs relative to the major
[14]
hospital departments involved in surgical care, estimated that intraoperative anesthesia hospital costs constituted
5.6% of the total hospital cost of an inpatient surgical procedure. The true fraction of resources consumed was
probably higher because some costs outside the operating room (e.g., preoperative laboratory testing) were not
allocated to anesthesia but may have been occasioned by decisions related to anesthesia care.
In this study, 49% of total hospital costs were variable and 57% were direct. The largest hospital cost category was
the operating room (33%) followed by the patient ward (31%). The greatest savings occurred if interventions
addressed variable costs (e.g., intravenous supplies).
Even if this study had been performed in a single university hospital using a well-known cost accounting
application, and even if the results were not necessarily transferable to other institutions with other cost categories,
the proportions of hospital departmental costs are likely to be generalized to other hospitals.
It is possible to divide cost components and cost determinants. Cost components include those expenditures that,
added together, result in the dollar cost of anesthesia. These cost components accrue directly to patients and payers
and are observed in patient bills and records. Cost determinants are the factors that influence the cost components of
anesthesia and are difficult to measure directly. Some costs accrue only to society in general and are best studied as
determinants and measured in terms of tradeoff. The major charges for anesthesia are derived from three sources:
provider services, technology, and site or facility. Minor charges are derived from payer source and side effects.
The two major determinants affecting costs of provider services are the supply and availability of providers and their
geographic locations.
Technology includes the methods for achieving adequate anesthesia. The methods differ among the three basic types
of anesthesia: general, regional, and monitored care. The costs of provider services differ insignificantly among
these three types, but there are major differences in the costs of technology. Charges for anesthesia technology have
three determinants: disposable supplies, equipment, and anesthetic drugs and agents. Some technologies do require
skills that may add from $300 to $1000 to the cost of an anesthetic. Complications such as congestive heart failure
or the requirement of an ICU stay are very expensive, but whether new techniques prevent them in a cost-efficient
fashion is uncertain.
The term facility includes the geographic location where anesthesia is performed and all of its associated contextual
and environmental features, such as the following:
• Elective versus emergency treatment, which determines whether the patient can shop for a surgeon and
surgical facility.
• Political and legal policies, which determine where anesthesia practitioners can practice and the
exclusiveness or competitiveness of these practices.
• The organizational structure, which encompasses the policies, procedures, and philosophies of the
surgical facility and that affects the way anesthesia is administered (i.e., how much preoperative laboratory
work is required, to what extent preoperative consultations are encouraged, and who provides postoperative
pain control.
• Patient demographics, which include the physical, social, and financial diversity of the general patient
population. Patient demographics determine, in part, the level of services needed and the amount of cost-
shifting from full-paying patients required for the facility and provider to continue in business.
Time in Regional Anesthesia
The time spent in the healthcare structures, represented by the period spent in the operating room, the ICU, or the
ward, constitutes one of the most important variables to study in an examination of the economic impact of any new
anesthesia procedure. This is because the major economic impact of the healthcare assistance is made not by
materials and equipment but especially by the personnel’s work, which needs to be well organized. In the literature,
no studies exist that have dealt with this question from all points of view.
In the study by Tessler and coworkers, for example, the authors sought to compare the time efficiency of spinal
[15]
versus general anesthesia. The purpose of the study was to determine the frequency of converting failed spinal
37
anesthesia to general anesthesia and the amount perioperative time needed for patients undergoing spinal or general
anesthesia for vaginal hysterectomy. These operations were all elective and required no additional invasive
monitoring. This arrangement allowed a pure comparison of anesthetic induction time (spinal vs. general) and a
comparison of overall perioperative time that may be related to the choice of anesthetic technique. Their results
indicated that spinal anesthesia and general anesthesia were equally time efficient for that type of surgery. The
patients in the spinal anesthesia group remained in the postanesthesia care unit (PACU) an average of 27 minutes
longer per patient than those receiving general anesthesia alone. However, at their institution, complete recovery
from motor block due to spinal anesthesia is a PACU discharge criterion, and this would explain their finding. Other
anesthesiologists do not believe full recovery from motor block after spinal anesthesia is necessary before discharge
from the PACU. [16]
This study, regardless of costs, does not give any information on the different economic impact that the two different
techniques of anesthesia could have. Moreover, the impact (importance, significance) of the 27 minutes spent in the
PACU per patient for those undergoing spinal anesthesia still remains unclear. In the light of other criteria of
dismissal from the PACU, the results could be inverted.
Another study was designed to ascertain whether interscalene block is reliable and efficient for use in same-day
[17]
surgery compared with general anesthesia for shoulder arthroscopy. The authors retrospectively reviewed patients
treated at the University of Connecticut over a 42-month period in the same-day surgery unit. They found that
compared with general anesthesia, regional anesthesia required significantly less total nonsurgical intraoperative
time use (53 ± 12 vs. 62 ± 13 min) and also decreased PACU stay (72 ± 24 vs. 102 ± 40 min). Interscalene block
anesthesia resulted in significantly fewer unplanned admissions requiring therapy for severe pain, sedation, or
nausea/vomiting than general anesthesia (0 vs. 13) and an acceptable failure rate (8.7%).
In this case also, the study did not evaluate the various economic consequences of a different clinical choice but
concluded only that interscalene block should be considered as a viable alternative to general anesthesia for shoulder
arthroscopy in ambulatory surgery patients.
Among the studies that have considered the economic consequences of different therapies is that of Nakamura and
coworkers. This retrospective study evaluated 67 consecutive patients who underwent an arthroscopically assisted,
[18]
autogenous bone-patellar ligament-bone anterior cruciate ligament reconstruction that was supervised by the same
surgeon. General endotracheal anesthesia was used for 36 patients, and a femoral sciatic nerve block was used in 31
patients. Patients who received regional anesthesia required a significantly longer recovery room stay than those
who received general anesthesia. Most of the patients who received general anesthesia had inpatient procedures. In
the general anesthesia group, 31 of 36 patients spent at least one night in the hospital. Three of 31 patients who
received regional anesthesia required hospital admission. There were no differences in anesthesia-related
complications between the groups. The cost saving of performing anterior cruciate ligament reconstruction under
regional anesthesia compared with that of general anesthesia was calculated at $2907 per patient and predominantly
reflected the outpatient approach used in these cases. Moreover, the use of regional anesthesia was not found to
compromise operating room efficiency.
Another study was performed to assess safety, efficacy, and hospital costs related to general anesthesia and
[19]
regional anesthesia for carotid endarterectomy (CEA). The authors found that patients who received general
anesthesia for CEA spent an average of 1.2 days in the PACU and 6.1 days in a regular hospital bed, for an average
cost of $4547. The patients who underwent CEA under regional anesthesia had an average of 0.1 PACU day and 4.1
regular hospital days, for a cost of $2067. Regional anesthesia saved $2480 per patient and $124,000 in this study
group, with no increase in the rate of mortality and morbidity.
In these studies, the different economic consequences that are reflected on the patient and on the society in general
after the administration of the different anesthesiologic techniques remain unknown.
Choice of anesthetic may affect the recovery rate of gastrointestinal function and, thus, duration and cost of
hospitalization after colonic surgery. A universal complication after major intra-abdominal surgery is postoperative
ileus, which prolongs hospital stays and is estimated to have an annual cumulative U.S. healthcare cost of $750
million. Previous studies suggest that multiple factors may affect the rate of postoperative recovery of
[20]
gastrointestinal function after abdominal surgery. For example, recovery of postoperative gastrointestinal function
may be promoted by early oral feeding, by use of low-fat nutrition, by early patient activity, and by
[21] [22] [23] [24]
administration of nonsteroidal anti-inflammatory agents. The use of epidural analgesia, especially with local
[25]
anesthetics, may accelerate the recovery of gastrointestinal function through blockade of inhibitory sympathetic
reflexes.[26] [27]
38
Liu and coworkers performed a prospective, randomized, double-blind study to examine the effects of different
[28]
techniques of anesthesia and analgesia on recovery of gastrointestinal function and subsequent duration and cost of
hospitalization. Fifty-four patients undergoing partial colectomy procedures were randomized into four groups. All
groups received a standardized general anesthetic. Group MB received a preoperative bolus of epidural bupivacaine
and morphine followed by an infusion of morphine and bupivacaine. Group M received a preoperative bolus of
epidural morphine followed by an infusion of morphine. Group B received a preoperative bolus of bupivacaine
followed by an infusion of bupivacaine. Group P received a preoperative bolus of intravenous morphine followed by
intravenous patient-controlled morphine postoperatively.
The authors found that epidural analgesia with bupivacaine and morphine provided the best balance of analgesia and
side effects. At the same time, this combination of pain relief accelerated postoperative recovery of gastrointestinal
function and time to fulfillment of discharge criteria after colon surgery in relatively healthy patients within the
context of a multimodal recovery program. Based on average charges at the institution, the use of epidural morphine
and bupivacaine potentially generated a net savings of $1200 per patient compared with the use of epidural or
patient-controlled analgesia (PCA) morphine.
In contrast, a major study found that patients who received epidural bupivacaine did not experience the improved
[29]
recovery of bowel function experienced by those who were given systemic opioids. However, in this study, epidural
local anesthetic was administered for only 24 hours and then patients were provided with analgesia via parenteral or
epidural opioids during the time in which gastrointestinal function was beginning to recover. Hence, it seems likely
that early discontinuation of epidural local anesthetic administration may account for this negative finding.
In summary, these data support, but do not conclusively prove, that regional anesthesia results in a superior recovery
compared to general anesthesia. However, several questions need to be answered. Although the patient may leave
the hospital or surgical center sooner after receiving regional anesthesia, how does the patient treat pain at home
once the block has worn off? Who, and at which cost, will take care of the patient?
Few studies performed a comparison of differences in time efficiency, costs, charges, and complications among
regional techniques. Riley and coworkers compared spinal and epidural anesthesia for cesarean delivery with
[30]
respect to time spent in the operating room and the PACU, complications, and requirements for additional analgesia.
The authors found that significantly less time elapsed from entry into the operating room until surgical incision with
spinal anesthesia compared with epidural anesthesia. Thus, patients who received spinal anesthesia spent a shorter
total time in the operating room than those who received epidural anesthesia. PACU times were not statistically
different between the groups. Cost analysis revealed that patients would have been charged an average of $260 more
for operating room use and anesthesia professional fees with epidural anesthesia. Charges to patients who had spinal
anesthesia were significantly less than those to patients who had epidural anesthesia; however, patient charges do
not reflect the true costs of medical procedures and are meaningless in managed or capitated systems. Examining
costs is a better way to compare economic advantages among techniques. In this study, the differences in direct costs
between the techniques was relatively small (approximately $20). In contrast, the increased indirect costs associated
with epidural anesthesia may be of greater consequence. The additional time taken to perform the epidural block
occupies not only the anesthesiologist but also the obstetrician, surgical assistant, and nurses. In addition, the
operating room is occupied for a longer period, which may be significant in a busy obstetric service. Patient
discomfort can also be considered as an additional indirect cost of epidural anesthesia.
Complications in Regional Anesthesia
The act of placing an epidural catheter may determine some of the complications with epidural anesthesia. The most
common complication from placement of epidural catheters is accidental dural puncture with resultant postdural
puncture headache (PDPH). Large surveys encompassing 51,000 epidural catheter placements performed during the
past three decades suggest that the incidence of dural puncture is 0.16% to 1.3%. Subsequent development of
[31] [32]
PDPH depends on several factors and ranges from 16% to 86%. [33]
Less frequent complications include paresthesias. The incidence of transient paresthesia varies from 5% to 25%. [34]
Neurologic damage, which may be long-lasting or even permanent, is the most feared complication of regional
anesthesia. There are several causes of such damage, such as trauma (needle, catheter, injection), arteriosclerosis,
hypotension, the accidental injection of toxic substances such as povidone-iodine (Betadine), hypocoagulation, and
bacteremia. The incidence of these complications is likely to be 0.01% to 0.001%. [34]
39
Paraplegia appears to result most commonly from the formation of an epidural hematoma. Puncture of epidural [35]
vessels during placement of epidural catheters occurs in approximately 3% to 12% of cases. The incidence of [36]
symptomatic epidural hematoma associated with epidural analgesia is difficult to estimate, but combined case series
of more than 100,000 epidural anesthetics have been reported without a single epidural hematoma. Currently, the [37]
risk of epidural hematoma formation after administration of epidural analgesia appears to be increased if patients are
receiving anticoagulant agents or have a coagulation disorder. However, several large series have documented
[36] [37] [38]
safe use of epidural analgesia in patients receiving antiplatelet therapy, warfarin sodium, and high or low doses of
[39] [40]
heparin.[41] [42]
Evaluation of the economic consequences of such complications is not simple. The rarity with which they occur
renders their economic weight almost uninfluential for the healthcare structures.
Administration of local epidural anesthetics for surgical anesthesia frequently results in multiple hemodynamic
changes, including decreases in chronotropism, inotropism, dromotropism, systemic vascular resistance, cardiac
output, and myocardial oxygen consumption. The economic consequences of these hemodynamic changes are far
[43]
from being calculated.
Another dangerous complication of epidural administration of opioids is delayed respiratory depression. Although
virtually all opioids commonly used for epidural analgesia have been reported to cause respiratory depression,
[44]
morphine is associated with the highest risk. Nonetheless, the incidence of delayed respiratory depression after
epidural administration is small. In a prospective survey of 1062 patients receiving epidural analgesia, there were
[45]
1131 episodes in which a local anesthetic and opioid mixture was used, and 160 instances in which opioids alone
were used. Local anesthetic was not used without opioids. Twenty-three percent of catheters were removed
prematurely because of catheter-related problems including accidental dislodgment (13%) and skin site
inflammation (5.3%). No epidural abscess or hematoma was identified. In 14% of the total number of episodes,
there was either no demonstrable block or complications occurred that required a change of solution: 30% of this
group were salvaged after intervention by the acute pain service. The incidence of respiratory depression was
0.24%. There was no case of delayed respiratory depression.
For epidural analgesia, fentanyl, because of its greater lipophilic nature, offers a number of advantages over
morphine, including a lower incidence of side effects and reduced risk of delayed-onset respiratory depression. The
relatively short duration of action of epidural fentanyl makes this agent more ideally suited for continuous infusion
or patient-controlled epidural analgesia (PCEA). [46]
Although morphine and fentanyl remain the predominant epidural opioids, sufentanil offers some unique
advantages. Because of its greater lipophilic action and µ-receptor binding capacity, sufentanil has a faster onset of
action and longer duration than epidural fentanyl. Compared with morphine, sufentanil has been associated with a
[47]
lower incidence of side effects, particularly delayed respiratory depression. [47]
Combined case surveys including more than 20,000 patients suggest that the incidence of this complication is less
than 1%. Even in this case, the related economic impact of this complication has not been calculated.
[48]
Outcome and Regional Anesthesia
Perioperative morbidity and mortality rates are mainly influenced by the type and duration of surgery as well as the
patient’s preoperative state of health. Anesthesia, however, may also result in severe perioperative pathophysiologic
changes, which may be either desirable (e.g., analgesia, vasodilatation in vascular surgery) or detrimental (e.g.,
hypothermia, ventilatory depression) and which may differ depending on the anesthetic technique used (e.g., general
anesthesia vs. regional anesthesia).
Epidural anesthesia has been reported to exert beneficial effects in surgical procedures. In a retrospective study of [49]
90 consecutive high-risk thoracic surgical procedures performed using a combined technique of epidural anesthesia
with light general anesthesia, the outcome of this technique has been examined. The mortality rate for the group of
patients was 2.2% due to myocardial infarction occurring on postoperative days 3 and 4. Morbidity developed in
3.3% of the patients, including the 48-hour requirement of mechanical ventilation in one patient and pneumonia in
two other patients. This approach appears to be preferable to use of general anesthesia alone, in which American
Society of Anesthesiologists (ASA) class II patients have a predicted mortality rate of 5.4% for elective high-risk
procedure.
40
On the contrary, in another study comparing general anesthesia combined with epidural anesthesia with general
[50]
anesthesia for major abdominal surgery, results were equivocal. In fact, the authors found only transient quantifiable
differences in recovery characteristics.
Two major periodical reviews of the effects of regional anesthesia on postsurgical morbidity rate and postoperative
[51]
organ dysfunction have been published. The former concluded that regional anesthesia appears to reduce the early
[52]
postoperative mortality rate after acute hip surgery for fracture, but long-term survival is dependent on factors other
than the choice of anesthesia. The large amount of data suggests that regional anesthesia should be used whenever
possible. The latter, a more recent review, confirms what the previous study underlined: Reduced mortality rate
appears to have been demonstrated under an epidural regimen for postoperative analgesia in high-risk patients
undergoing thoracic, abdominal, and vascular procedures.
Several studies have attempted to identify the most appropriate anesthetic technique for patients with hip fracture. A
significantly lower mortality rate for spinal anesthesia compared with general anesthesia was demonstrated by one
group of researchers, but this has not been confirmed.
[53]
In the largest published study on patients undergoing
[54] [55] [56]
anesthesia for hip fracture surgery, 1333 patients were studied prospectively to assess the effects on outcome of
general and spinal anesthesia. It was demonstrated that the excess mortality rate in some groups was correlated with
age and preexisting medical conditions rather than with the type of anesthesia, and there were no significant
differences between the groups in the length of hospital stay.
In another study, the mortality rate after surgical correction of upper femoral fractures was investigated in 578
[57]
patients randomly allocated to receive spinal or general anesthesia. Thirty days after surgery, the mortality rate was
6% after spinal anesthesia and 8% after general anesthesia. Six months to 2 years after surgery the mortality rate was
identical in the two groups. The estimated blood loss was smaller in patients receiving spinal anesthesia. Regardless
of the anesthetic technique, a high short-term mortality rate was related to age, male sex, and trochanteric fracture,
whereas excess long-term mortality rate was related to male sex and high ASA scores. However, the patients in this
study had a much shorter period in hospital than the patients in other studies. At the same time, mortality rate
[58]
during the first year has been reduced from 27% to 19%, suggesting the possibility of a beneficial effect of early
ambulation and discharge.
The perioperative morbidity rate may be modifiable in high-risk patients by the anesthesiologist’s choice of either
regional or general anesthesia. Outcomes between epidural and general anesthesia have been compared, with a study
made of 100 patients scheduled for elective vascular reconstruction of the lower extremities who were randomized
to receive either epidural anesthesia followed by epidural analgesia or general anesthesia followed by intravenous
PCA. Cardiac ischemia, myocardial infarction, unstable angina, and cardiac death were identified by a cardiologist.
[59]
Other major types of morbidity were determined at the time of hospital discharge and at 1 and 6 months after
surgery. The major finding of this study was that the rate of reoperation for graft occlusion was higher in patients
randomized to receive general anesthesia than in those randomized to receive epidural anesthesia, but no statistically
significant differences were found in overall incidence of death, major cardiac disease, or myocardial ischemia.
These findings have been confirmed in the largest prospective randomized trial to date, which was designed to
[60]
evaluate the effects of regional anesthesia techniques (spinal or epidural) versus general anesthesia on perioperative
cardiac morbidity rate and overall mortality rate in patients undergoing peripheral vascular surgery. The authors, in
fact, found that the choice of anesthesia, when correctly delivered, does not significantly influence cardiac morbidity
and overall mortality rates in patients undergoing peripheral vascular surgery, but it decreases the incidence of
peripheral vascular graft thrombosis.
Also, general anesthesia in carotid endarterectomy has not caused an increase in either mortality or morbidity rates. [61]
Nevertheless, patients who underwent carotid endarterectomy under regional anesthesia saved $2480 each.
Therefore, many trials that aimed at comparing the impact of different anesthetic techniques on the incidence of
postoperative complaints have been performed in the past. No significant advantage of either technique has been
identified up to now with respect to postoperative mortality rate or severe morbidity.
This finding may be due to at least three factors;
• Many side effects related to anesthesia—due to close postoperative monitoring—are detected and treated
early in the postoperative phase (e.g., in the recovery room), thereby preventing serious complications.
• Postoperative mortality rate, related exclusively to anesthesia, is probably so low that huge patient
numbers would be required to demonstrate any significant differences between different techniques.
41
• Besides the factor of anesthesia, many other factors (e.g., anesthetists) contribute to the anesthesia-related
morbidity and mortality rates, which are scarcely quantified.
The fact that clear advantages for a single technique have not yet been demonstrated must not, however, result in
anesthetic nihilism. Rather, there may be good reasons in the individual patient (e.g., lack of a recovery room) to
prefer one anesthetic technique or drug over another, in order to lower the individual’s anesthesia-related risk.
Intraoperative blood loss has been attributed to multiple clinical variables, including age, physical status, type of
[62] [63]
surgery, surgeon, and anatomic and physiologic differences between patients. Nearly 12 million red blood cell
[64] [65] [66]
units are transfused to approximately 3.5 million patients annually in the United States. Approximately 20% of all
[67]
homologous blood transfusions have resulted in some adverse effect in the recipient. The unit cost has varied from
[68]
$60 to $150. In another study, the mean cost for all blood components transfused per patient has been evaluated to
[69]
be $397 ± $244. The advantages of regional anesthesia with regard to intraoperative blood loss compared with
[70]
those of general anesthesia have long been debated. Although the literature has not demonstrated less bleeding with
either anesthetic technique, it is commonly believed that epidural or spinal anesthesia results in less intraoperative
bleeding. [56] [57]
More correctly, it seems that positive pressure ventilation increases bleeding during general anesthesia. This was
demonstrated by comparing the mean blood loss in 100 patients receiving either epidural anesthesia, combined
epidural and general anesthesia, or general anesthesia alone. Mean blood loss in the epidural anesthesia group was
[71]
significantly less than that in either the combined epidural and general anesthesia group or the general anesthesia
alone group. Significantly less blood was transfused during surgery in the epidural group compared with the
remaining two groups.
The decrease in blood loss associated with epidural anesthesia with lower transfusion requirements results in
significantly reduced frequency of deep venous thrombosis compared with results after general anesthesia. Venous [72]
thromboembolic disease is still one of the main causes of postoperative morbidity and death. It is also commonly
believed in this case that continuous lumbar epidural anesthesia could exert a beneficial effect in reducing the
incidence of such an event. Possible explanations for these differences include increased circulation in the lower
extremities, less tendency for intravascular clotting to occur, and more efficient fibrinolysis in association with
epidural anesthesia.
The socioeconomic consequences of routine administration of low-molecular-weight heparin (LMWH) as

thromboprophylaxis in patients undergoing total hip arthroplasty has been evaluated on the basis of data from a
number of clinical studies. Despite the higher direct costs associated with LMWH, this regimen was more cost-
[73] [74]
effective in preventing thromboembolic complication than no prophylaxis, dextran 70, or low-dose unfractionated
heparin.[73] [74]
Analgesic Consumption and Regional Anesthesia
The consumption of analgesic drugs in the postoperative period is another important factor in evaluating the
economic impact of an anesthesiologic technique.
Epidural local anesthetics may be superior to systemic opioids in the dose range used and in reducing postoperative
analgesic requirements because they decrease pain perception in patients. The changes in central neuron excitability
induced by a noxious injury stimulus usually outlast the stimulus duration and may persist beyond the expected
tissue healing period. Consequently, it has been suggested that surgery in humans may lead to alterations in response
properties of central neurons, as in sensitization, similar to the ones produced in experimental animals, resulting in
amplification and prolongation of postoperative pain.
To date, relatively few studies have examined the effects of intraoperative neuraxial block with either local
anesthetics or opioids on postoperative analgesic requirements. One of these studies compared postoperative pain
[75]
and analgesic demand in patients who underwent radical prostatectomy and received general anesthesia alone and in
those who underwent prostatectomy and received epidural anesthesia with bupivacaine, either alone or in
combination with general anesthesia. During surgery, patients in the epidural group received a significantly greater
epidural bupivacaine dose compared with the epidural general anesthesia group. On postoperative day 1, PCA
requirements in the three groups were similar. On postoperative day 2, PCA demand in the epidural general
anesthesia group and in the general anesthesia group was significantly greater than in the epidural anesthesia group.
The same differences continued on postoperative days 3 and 4. The results were not statistically analyzed because
only seven patients still received epidural PCA on postoperative day 5.
42
Other studies[ ] [ ] have confirmed these findings, suggesting that analgesic requirements, time of postoperative
76 77
surveillance, and frequency of treatment of postoperative complaints after both lower abdominal surgery and lower
limb surgery can be significantly decreased if surgery is performed with use of subarachnoid anesthesia.
Furthermore, the results were more interesting when general anesthesia was compared with triple nerve block (three
in one) during surgical correction of fractured femur neck. The nerve blocks significantly reduced the quantity of
[78]
opioid administered after the operation; 48% of these patients required no additional analgesia in the first 24 hours.
Conclusions
Anesthesia costs are a small portion of the overall costs associated with a surgical patient’s hospital encounter.
Greater cost savings may come with improving operating room efficiency as well as those processes of care that
reduce length of hospital stay.
Many studies have observed better pain relief with epidural analgesia than with systemic opioids. [79] [80]
Improved
analgesia is particularly evident when local anesthetics and opioids are combined. [80]
Improved analgesia, however, may not be the only mechanism for improved outcome, at least not through a direct
cause-and-effect-relationship. Epidurally administered analgesics may also produce beneficial effects through other
mechanisms such as inhibition of efferent pathways or inhibition of neural reflex arcs. This study indicates that use
of regional anesthesia and analgesia may be associated with reductions in incidence and severity of many
perioperative physiologic perturbations. Perioperative coagulability can be decreased with epidural analgesia, and
this effect may significantly reduce the incidence of venous and arterial thromboses. Similarly significant
improvements in gastrointestinal motility may result in a more rapid functional recovery from surgery.
Despite the obvious need, there are few studies of the costs and economic consequences of alternative anesthetic
strategies. Healthcare and cost containment strategies and policies often are developed and implemented before their
wider effects are assessed and understood.
When designing outcome studies, it is necessary to strike a balance between two opposing goals: first, the scientific
need to investigate effects of a single intervention by keeping all other aspects of care constant; and second, the
clinical reality that postoperative recovery is a multifactorial event and that a solitary intervention is unlikely to alter
the outcome. Although many of these outcomes are relatively subjective and difficult to evaluate, it is necessary to
expand the horizon beyond the intraoperative or even intrahospital period to see whether and to what degree clinical
interventions influence ultimate patient recovery. The changing economic environment means that it is no longer
sufficient for anesthesiologists merely to determine the best method of postoperative analgesia or merely to believe
that patients will do better. In the future, it will be necessary to demonstrate that every kind of anesthetic-analgesic
technique is cost-effective.
REFERENCES
1. Final accounting of 1998 health spending. Bus Health 18:10–11, 2000.
2. Knaus WA, Wagner DP, Lynn J: Short-term mortality predictions for critically ill hospitalized adults: Science and ethics. Science 254:389–394,
1991.
3. Cerra FB: Health care reform: The role of coordinated critical care. Crit Care Med 21:457–464, 1993.
4. National Center for Health Statistics: Health, United States, 1991. Hyattsville, Md, Public Health Service, 1992, pp 266–278.
5. Eisenberg JM: Clinical economics: A guide to the economic analysis of clinical practices. JAMA 262:2879–2886, 1989.
6. Elixhauser
A: Costs: From whose perspective? Conference Proceedings: Cost analysis methodology for clinical practice guidelines. AHCPR
Pub. No. 95-0001, Edited by Grady ML, Weis KL. Rockville, Md, U.S. Dept. Health and Social Services, Public Health Service, Agency for
Health Care Policy and Research, 1995, pp 5–12.
7. Stott NCH: Day surgery generates no increased workload for community based staff: True or false? BMJ 304:825–826, 1992.
8. Robinson R: What does it mean? BMJ 307:670–673, 1993.
9. Wetchler BV: Economic impact of anesthesia decision making: They pay the money, we make the choice. J Clin Anesth 4:20S–24S, 1992.
10. Sanchez
LA, Hirsch JD: Identification of cost consequences as the critical step in a cost-of-illness study: Postoperative nausea and vomiting in
an ambulatory surgery centre example. J Res Pharm Econ 4:41–53, 1992.
43
11. Parker RH: McMillan dictionary of accounting. London, McMillan, 1992.
12. Davidson S, Stickney CP, Weil RL: Accounting: The language of business. Sun Lakes, Ariz, Thomas Horton and Daughters, 1987.
13. Vital and Health Statistics Series 13 (no. 106). National Center for Health Statistics: Hyattsville, MD, September, 1991.
14. MacarioA, Vitez TS, Dunn B, et al: Where are the costs in perioperative care? Analysis of hospital costs and charges for inpatient surgical
care. Anesthesiology 83:1138–1144, 1995.
15. TesslerMJ, Kardash K, Kleiman S, et al: A retrospective comparison of spinal and general anesthesia for vaginal hysterectomy: A time
analysis. Anesth Analg 81:694–696, 1995.
16. Alexander
CM, Teller LE, Gross JB, et al: New discharge criteria decrease recovery room time after subarachnoid block. Anesthesiology
70:640–643, 1989.
17. D’AlessioJG, Rosenblum M, Shea KP, et al: A retrospective comparison of interscalene block and general anesthesia for ambulatory surgery
shoulder arthroscopy. Reg Anesth 20:62–68, 1995.
18. Nakamura SJ, Conte-Hernandez A, Galloway MT: The efficacy of regional anesthesia outpatient anterior cruciate ligament reconstruction.
Arthroscopy 13:699–703, 1997.
19. Godin MS, Bell WH, Schwedler M, et al: Cost effectiveness of regional anesthesia in carotid endarterectomy. Am Surg 55:656–659, 1989.
20. Livingston E, Passaro E: Postoperative ileus. Dig Dis Sci 35:121–132, 1990.
21. BowerR, Talamini M, Sax H, et al: Postoperative enteral versus parenteral nutrition: A randomized controlled trial. Arch Surg 121:1040–
1045, 1986.
22. Moore F, Moore E, Jones T, et al: TEN vs. TPN following major abdominal trauma—reduced septic morbidity. J Trauma 29:916–923, 1989.
23. Pironi
L, Stanghellini V, Miglioli M, et al: Fat induced ileal brake in humans: A dose dependent phenomenon correlated to the plasma levels of
peptide YY. Gastroenterology 105:733–739, 1993.
24.Moiniche S, Bulow S, Hesselfedt P, et al: Convalescence and hospital stay after colonic surgery during balanced analgesia, enforced oral
feeding and mobilization. Eur J Surg 7:628–633, 1995.
25. Grass JA, Sakima NT, Valley M, et al: Assessment of ketorolac as an adjuvant to fentanyl patient controlled epidural analgesia after radical
retropubic prostatectomy. Anesthesiology 78:642–648, 1993.
26. Ahn H, Bronge A, Johansson K, et al: Effect of continuous postoperative epidural analgesia on intestinal motility. Br J Surg 75:1176–1178,
1988.
27. Jayr C, Thomas H, Rey A, et al: Postoperative pulmonary complications. Epidural analgesia using bupivacaine opioids versus parenteral
opioids. Anesthesiology 78:666–676, 1993.
28. Liu SS, Carpenter RL, Mackey DC, et al: Effects of perioperative analgesic technique on rate of recovery after colon surgery. Anesthesiology
83:757–765, 1995.
29. Wallin G, Cassuto J, Hogstrom S, et al: Failure of epidural anesthesia to prevent postoperative ileus. Anesthesiology 65:292–297, 1986.
30. Riley ET, Cohen SE, Macario A, et al: Spinal versus epidural anesthesia for cesarean section: A comparison of time efficiency, costs, charges
and complications. Anesth Analg 80:709–712, 1995.
31. Tanaka K, Watanabe R, Harada T, et al: Extensive application of epidural anesthesia and analgesia in a university hospital: Incidence of
complications related to technique. Reg Anesth 18:34–38, 1993.
32. Stride PC, Cooper GM: Dural taps revisited: A 20 year survey from Birmingham Maternity Hospital. Anesthesia 48:247–255, 1993.
33. Kopacz DS, Neal JM, Pollok JE: The regional anesthesia “learning curve.” What is the minimum number of epidural and spinal blocks to
reach consistency? Reg Anesth 21:182–190, 1996.
34. Kane RF: Neurodeficits following epidural or spinal anesthesia. Anesth Analg 60:150–161, 1981.
35. Schmidt A, Nolte H: Subdural and epidural hematomas following epidural anesthesia: A literature review. Anesthesist 41:276–284, 1992.
36. Schwander D, Bachmann F: Heparin and spinal or epidural anesthesia: A decision analysis. Ann Fr Anesth Reanim 10:284–296, 1991.
37. Sage DJ: Epidurals, spinals and bleeding disorders in pregnancy: A review. Anaesth Intensive Care 18:319–326, 1990.
38. Jorgensen LN: Lumbar analgesia in patients receiving anticoagulant therapy: Pro et contra. Ugeskr Laeger 153:1491–1494, 1991.
39. Horlocker TT, Wedel DJ, Offord KP: Does preoperative antiplatelet therapy increase risk of hemorrhagic complications associated with
regional anesthesia? Anesth Analg 70:631–634, 1990.
44
40. Odoom JA, Sih IL: Epidural analgesia and anticoagulant therapy. Anaesthesia 38:254–259, 1983.
41. Willie JP, Jorgensen LN, Rasmussen LS: Lumbar regional anaesthesia and prophylactic anticoagulant therapy: Is the combination safe?
Anaesthesia 46:623–627, 1991.
42. Bergqvist D, Linblad B, Matzsch T: Low molecular weight heparin for thromboprophylaxis and epidural/spinal anesthesia: Is there a risk?
Acta Anaesthesiol Scand 36:605–609, 1992.
43. Cousins MJ, Bromage PR: Epidural neural blockade, neural blockade in clinical anesthesia and management of pain. Cousins MJ,
Bridenbaugh PO (eds): Neural Blockade. Philadelphia, JB Lippincott, 1988, pp 253–260.
44. Morgan M: The rational use of intrathecal and extradural opioids. Br J Anaesth 63:165–188, 1989.
45. Burstal R, Wegener F, Hayes C, Lantry G: Epidural analgesia: Prospective audit of 1062 patients. Anaesth Intensive Care 26:165–172, 1998.
46. Grass JA: Fentanyl: clinical use as postoperative analgesic— epidural/intrathecal route. J Pain Symptom Manage 7:419–430, 1992.
47. Grass JA: Sufentanil: Clinical use as postoperative analgesic— Epidural/intrathecal route. J Pain Symptom Manage 7:271–286, 1992.
48. Morgan M: Epidural and intrathecal opioids. Anaesth Intensive Care 15:60–67, 1987.
49. Temeck B, Schafer W, Park WJ, et al: Epidural anesthesia in patients undergoing thoracic surgery. Arch Surg 124:415–418, 1989.
50. Handley GH, Silbert BS, Mooney PH, et al: Combined general and epidural anesthesia versus general anesthesia for major abdominal
surgery: Postanesthesia recovery characteristics. Reg Anesth 22:435–441, 1997.
51. Scott NB, Kehlet H: Regional anaesthesia and surgical morbidity. Br J Surg 75:299–304, 1988.
52. Liu S, Carpenter R, Ncal JM: Epidural anaesthesia and analgesia. Their role in postoperative outcome. Anesthesiology 82:1474–1506, 1995.
53. McLaren AD, Stockwell MC, Reid VT: Anaesthetic techniques for surgical correction of fractured neck of femur. Anaesthesia 33:10–14,
1978.
54. Davis FM, Woolner DF, Frampton C, et al: Prospective, multicentre trial of mortality following general or spinal anaesthesia for hip fracture
surgery in the elderly. Br J Anaesth 59:1080–1088, 1987.
55. Moore DP, Quinlan W: Mortality and morbidity associated with hip fractures. Irish J Med Sci 158:40–42, 1989.
56. Sutcliffe AJ: Mortality after spinal and general anaesthesia for surgical fixation of hip fractures. Anaesthesia 49:237–240, 1994.
57. Valentin N, Lomholt B, Jensen JS, et al: Spinal or general anaesthesia for surgery of the fractured hip? Br J Anaesth 58:284–291, 1986.
58. McKenzie PJ, Wishart HY, Dewar KM, et al: Comparison of the effects of spinal anaesthesia and general anaesthesia on postoperative
oxygenation and perioperative mortality. Br J Anaesth 52:49, 1980.
59. Christopherson R, Beattie C, Frank SM, et al: Perioperative morbidity in patients randomized to epidural or general anesthesia for lower
extremity vascular surgery. Anesthesiology 79:422–434, 1993.
60. Bode RH, Lewis KP, Zarich SW: Cardiac outcome after peripheral vascular surgery. Anesthesiology 84:3–13, 1996.
61. Godin MS, Bell WH, Schwedler M, et al: Cost-effectiveness of regional anesthesia in carotid endarterectomy. Am Surg 55:656–659, 1989.
62. Chin SP, Abou Madi MN, Eurin B, et al: Blood loss in total hip replacement: Extradural vs phenoperidine analgesia. Br J Anaesth 54:491–
495, 1982.
63. Moir DD: Blood loss during major vaginal surgery. A statistical study of the influence of general anaesthesia and epidural analgesia. Br J
Anaesth 52:1117–1121, 1968.
64. Thorburn J: Subarachnoid blockade and total hip replacement. Effect of ephedrine on intraoperative blood loss. Br J Anaesth 57:290–293,
1985.
65. Sorenson RM, Pace NL: Anesthetic techniques during surgical repairs of femoral neck fractures. A meta analysis. Anesthesiology 77:1095–
1104, 1992.
66. Valley MA, Bourke DL, Hamill MP, et al: Time course of sympathetic blockade during epidural anesthesia: Laser Doppler flowmetry studies
of regional skin perfusion. Anesth Analg 76:289–294, 1993.
67. Surgenor DM, Wallace EL, Hao SHS, et al: Collection and transfusion of blood in the United States, 1982–1988. N Engl J Med 322:1646–
1651, 1990.
68. Walker RH: Special report: transfusion risks. Am J Clin Pathol 88:374–378, 1987.
69. Kyriopoulos JE, Michail-Merianou V, Gitona M: Blood transfusion economics in Greece. Transfus Clin Biol 2:387–394, 1995.
70. Goodnough LT, Soegiarso RW, Birkmeyer JD, Welch HG: Economic impact of inappropriate blood transfusions in coronary artery bypass
graft surgery. Am J Med 94:509–514, 1993.
45
71. Shir Y, Raja S, Frank S, et al: Intraoperative blood loss during radical retropubic prostatectomy: Epidural versus general anesthesia. Urology
45:993–999, 1995.
72. Modig J, Borg T, Karlstrom G, et al: Thromboembolism after total hip replacement: Role of epidural and general anesthesia. Anesth Analg
62:174–180, 1983.
73. Borris LC, Lassen MR: Thromboprophylaxis with low molecular weight heparin after major orthopaedic surgery is cost effective. Drugs
52(Suppl 7):42–46, 1996.
74. Bergqvist D, Matzsch TShir Y: Cost-effectiveness of the prevention of postoperative thromboembolism. Orthopade 22:140–143, 1993.
75. Raja S, Frank S: The effect of epidural versus general anesthesia on postoperative pain and analgesic requirements in patients undergoing
radical prostatectomy. Anesthesiology 80:49–56, 1994.
76. Wang JJ, Ho ST, Liu HS, et al: The effect of spinal versus general anesthesia on postoperative pain and analgesic requirements in patients
undergoing lower abdominal surgery. Reg Anesth 21:281–286, 1996.
77. Standl T, Eckert S, Schulte J, et al: Postoperative complaints after spinal and thiopentone-isoflurane anaesthesia in patients undergoing
orthopaedic surgery. Acta Anaesthesiol Scand 40:222–226, 1996.
78. Hood G, Gerrish SP: Postoperative analgesia after triple nerve block for fractured neck of femur. Anaesthesia 46:138–140, 1991.
79. Benzon HT, Wong HY, Belavic AM, et al: A randomized double-blind comparison of epidural fentanyl infusion versus patient controlled
analgesia with morphine for postthoracotomy pain. Anesth Analg 76:316–322, 1992.
80. Negre I, Gueneron JP, Jamali SJ, et al: Preoperative analgesia with epidural morphine. Anesth Analg 79:298–302, 1994.
46
Section II - Chapter 4 - Organization of an Acute Pain Service and Pain Management
Chapter 4 - Organization of an Acute Pain Service and Pain

Management
GIUSTINO VARRASSI
FRANCESCO DONATELLI
FRANCO MARINANGELI
ANTONELLA PALADINI
NARINDER RAWAL
In spite of increasing interest in pain and its management, most patients undergoing surgery do not receive adequate
analgesia. Recent surveys show that a large proportion of patients still receive inadequate postsurgical analgesia; this
problem is international in character. Analgesia techniques such as patient-controlled analgesia (PCA), spinal
opioids alone or in combination with local anesthetics, and other regional analgesic techniques provide superior pain
relief compared with intermittent intramuscular (IM) injection of opioids. However, such techniques carry their own
risks and, therefore, require special monitoring. The first line of defense against serious complications is an
organization that provides appropriate education and policies that permit nurses and physicians to safely care for
patients.
National guidelines for management of postoperative pain have been published in several countries; however, the
impact of these guidelines on patient care is unclear. The available data are not encouraging. In the United
Kingdom, 4 to 5 years after publication of professional guidelines, less than half of the hospitals surveyed had
implemented a key recommendation to introduce an acute pain service (APS); the principal obstacles were financial
constraints and newly qualified doctors who were still undereducated about the management of acute pain. Thus, [1]
pain relief remained inadequate. Similar problems have been identified in the United States, in Germany, and in
[2] [3] [4] [5]
17 European nations. One of the many reasons for their limited impact is the complexity of the published
[6]
guidelines.
The APS, using a multidisciplinary team approach, has received widespread acceptance and formal support from
many institutions and organizations such as the United Kingdom Royal Colleges in 1990, the Australian Faculty of
[7]
Anaesthetists in 1991, the U.S. Acute Pain Management Guideline Panel in 1992, the International Association for
[8] [9]
Study of Pain in 1992, and the German Society of Anaesthesiologists and Surgeons in 1997. The key
[10] [5]
recommendations of the United Kingdom Working Party are shown in Table 4-1 . Similar recommendations have
been made by other institutions.
Postoperative Pain Management
Postoperative pain can be partially or completely relieved by either or both of the following methods:
• Systemic administration of analgesics

• Regional analgesia achieved with analgesics or local anesthetics
SYSTEMIC ADMINISTRATION OF ANALGESICS
Nonopioid analgesics are an important class of drugs in the management of postoperative pain. A nonsteroidal anti-
inflammatory drug (NSAID) or acetaminophen as the sole analgesic may be adequate in the treatment of mild
postoperative pain, and for moderate to severe
47
TABLE 4-1 -- UNITED KINGDOM WORKING PARTY KEY RECOMMENDATIONS

1. Need for education and training in changing antiquated staff attitudes and practice, together with adequate resources.
2. Systematic recording of patients’ pain, as with blood pressure/ heart rate.
3. A named member of staff to be responsible for a hospital policy toward postoperative analgesia, subject to continuous audit and appraisal.
4. All major hospitals performing surgery should introduce an acute pain service using a multi-disciplinary team approach with input of medical,
nursing, pharmaceutical and psychological expertise. The anesthetist has a primary role to play.
5. There is a need for powerful, safe analgesics and long-acting nontoxic local anesthetics.
Modified from Royal College of Surgeons of England and the College of Anaesthetists Commission on the Provision of Surgical Services. Report
of the Working Party on Pain after Surgery. London, September 1990.
pain these drugs can produce significant analgesia to reduce opioid requirements by 20% to 40%. [11]
This effect is not surprising, because much of the pain is a result of the liberation of algogenic substances whose
synthesis is impaired by NSAIDs. These drugs act through a mechanism of cyclooxygenase inhibition, a step in the
synthesis of prostaglandins. The decreased concentration of prostaglandins blocks the transduction of the painful
stimulus at the levels of the nociceptor, where the tissue injury is converted into an electrical signal.
The mechanism of action of acetaminophen is still incompletely understood. There are several hypotheses
suggesting a central inhibitory effect on prostaglandin interactions, a central serotoninergic effect, effects on nitric
oxide mechanisms, and possible peripheral anti-inflammatory activity. [12] [13] [14] [15] [16]
The use of NSAIDs or acetaminophen as adjunctive therapy to opioid analgesics can significantly potentiate
analgesia without increasing opioid-related effects because their mechanisms of action are completely different, and
the two types of drugs block transmission of pain at different levels. NSAIDs must be used with caution in patients
with a history of renal insufficiency, peptic ulcer, or hepatic disease. The introduction of NSAIDs formulated for
[17]
parenteral administration (ketorolac) has significantly increased the use of these analgesics in the early perioperative
period. Ketorolac is the most commonly used intravenous (IV) NSAID in the management of postoperative pain. It
has been demonstrated to produce potent analgesia in adults at doses of 7.5 mg to 30 mg every 6 hours. Higher
doses do not provide significantly better analgesia. Older patients and those at risk for NSAID-related
[18]
complications should be treated with the lowest effective doses (7.5 mg to 15 mg every 6 h).
When oral administration is possible, it is preferred because it is less expensive but not less effective than IV
administration. In this case, the most frequently used NSAID is ibuprofen in doses of 1600 to 3200 mg per 24 hours
administered in divided doses every 6 to 8 hours. To enhance the gastrointestinal tolerance of orally administered
NSAIDs, these drugs should be taken with food.
Acetaminophen is usually administrated at doses of 4 to 6 mg per 24 hours in divided doses. It has been associated
with a significant opioid-sparing effect of up to 40%, especially in patients undergoing orthopedic surgery. [19]
In a double-blind study, propacetamol and ketorolac combined with PCA morphine show similar analgesic efficacy
after gynecologic surgery. Morphine consumption and pain scores were comparable in both groups of patients. The
authors concluded that propacetamol is as effective as ketorolac and has an excellent tolerability after gynecologic
surgery. [20]
Contraindications for acetaminophen use are related primarily to hepatotoxicity when used in high doses or in
patients with preexisting liver disease and possible nephrotoxicity.
Opioid analgesic administration remains the most commonly used method of delivery of postoperative analgesia.
The immense popularity and widespread use of these drugs are a result of their ready availability in most countries,
their ease of use, their low cost, and, when properly used, their effective relief of pain. Unfortunately, as previously
mentioned, these drugs are often improperly used. Consequently, many patients do not derive effective pain relief.
The most common errors are routine administration without regard to the intensity of the pain and associated
phenomena, the emotional makeup, the physical status, and the age of the patient. These errors occur because of the
traditional practice of ordering narcotics pro re nata, without first evaluating the efficacy of the initial dose.
Different narcotics in different individuals show a great variability in analgesic efficacy and in side effects.
To eliminate variability in the peak plasma concentration and in the time taken to reach this peak, narcotics should
be given intravenously rather than intramuscularly. In addition to eliminating the variability of absorption, the IV
route has important advantages:
48
• Rapid onset of action

• Early occurrence of the peak effects, which facilitates the titration
• Rapid decline of the blood concentration upon withdrawal of the drug, which limits the occurrence of
undesirable effects
The most important feature of providing optimal analgesia with systemic opioid analgesics involves the titration of
the drug dose to the individual patient’s analgesic requirement. Because individual opioid analgesic dosage needs
can vary widely, titration to individual patient requirements is essential. In the immediate postoperative period,
opioid analgesia may be initially established through the intermittent IV injection of opioid (2 to 5 mg morphine
equivalents) every 10 minutes. In some patients, this initial IV titration may require 15 to 20 mg of morphine
equivalents or more to establish analgesia. After this initial IV titration, analgesia is more easily maintained with
small, intermittent doses of opioid throughout the postoperative period. Although this technique may provide the
best pharmacologic model for titration of opioid dose and analgesic effect, it is labor-intensive, requiring immediate
access and administration of opioid analgesic doses on patient demand.
The best option for systemic narcotic analgesia is use of a system that permits “on demand” PCA. The patient must
be thoroughly informed about the procedure and given instruction in how to use the device. Individual analgesic
consumption remains almost constant throughout the PCA period. Most patients establish and maintain a
pseudosteady state plasma concentration by triggering new doses as the plasma concentration drops to a critical
level of minimum effective analgesic concentration.
The safety of PCA, especially in relation to respiratory depression, has been addressed by a number of investigators.
In two studies, serial blood gas analyses showed normal values in patients using PCA. The quality of analgesia
[21] [22]
with PCA has been consistently reported as superior or equal to that attained with use of IM opioids. Less PCA
opioid use compared with that of IM control groups is frequently observed, and satisfaction of patients and nurses is
high. The principal advantages of PCA to patients are high-quality analgesia, autonomy, elimination of delay in
decisions to medicate for pain, and freedom from painful intramuscular medication. It may take less nurse time to
provide for the analgesic needs of postoperative patients using PCA.
The prescription of PCA involves physician-determined selection of:
• Opioid analgesic
• Dose on demand
• Lockout interval
• A 1-hour (or 4-hour) total dose limit
Morphine, meperidine, and hydromorphone are among the most commonly prescribed opioid analgesics for PCA. In
a patient with an uncomplicated medical history and no previous history of adverse reaction to opioid
administration, there is little evidence to support improved efficacy or reduced side effects of any opioid analgesic
over those of morphine. [23]
Several studies have investigated the appropriate PCA dose. A dose of between 1.0 and 2.0 mg of morphine (or
morphine equivalents) has generally been found to be the most appropriate starting dose for postoperative pain. [24]
The dose should be reassessed with respect to analgesic effect and side effects throughout the first several hours of
PCA therapy, and it should be adjusted to patient-specific analgesic requirements.
The lockout interval is the minimum time interval between delivery of successive dose demands. This should be
determined according to the time needed to reach peak analgesic effect for the opioid dose. For most opioid
analgesics, the peak time is approximately 10 minutes.
The 1-hour (or 4-hour) dose limit is a secondary overriding safety parameter that limits the total dose delivered
within a specified period of time. The use of postoperative systemic opioid analgesia can range from providing pain
relief with only opioid analgesics throughout the entire postoperative period to a combination with other techniques.
Such a multimodal approach includes the use of locoregional analgesia and opioid and nonopioid analgesics. The
concomitant use of other analgesic techniques that allow reduced dosage and administration of opioid analgesics
appears to have significant benefits in terms of reducing postoperative morbidity associated with opioid medication
related side effects. A report of adverse drug events leading to increased hospital morbidity rates and lengths of stay
identified opioid analgesics as among the most common drugs involved in hospital medical-related complications. [25]
49
SPINAL ANALGESIA
Spinal analgesia refers to the use of opioids and analgesic concentrations of local anesthetics to produce pain relief
by either intrathecal or epidural administration. The epidural route has been used much more extensively for
postoperative pain control. Reasons include popularity of the technique along with, or in combination with, light
general anesthesia during surgery; willingness to leave an epidural catheter in place for extended periods to maintain
analgesia; familiarity with postoperative analgesia using epidural local anesthetics; and freedom from the risk of
post-lumbar puncture headache.
Spinal opioid analgesia, or selective analgesia, is produced by modulation of nociceptive transmission at the level of
the spinal dorsal horn in the absence of sensory, motor, or sympathetic neural blockade. Segmental analgesia is
produced by the epidural administration of local anesthetics and opioid analgesics, in that the extent of analgesia
spread is related to the spinal segmental level of administration and the volume and concentration of local anesthetic
or opioid administered.
Spinal anesthesia used for surgery produces positive respiratory, cardiovascular, and neuroendocrine effects;
reduced thromboembolic complications and blood loss; and reduced convalescence. These observations have been
extended to postoperative pain management. Patients receiving postoperative epidural morphine have reported
superior analgesia, earlier ambulation, fewer pulmonary complications, earlier return of bowel function, and earlier
discharge from the hospital than patients receiving IM morphine. In another study, patients were randomized in
[26]
two groups: The first received general anesthesia and IV opioids for postoperative pain management, and the second
group received combined general/epidural anesthesia and epidural opioids for postoperative pain. Mortality rate,
overall complication rate, infection rate, time to extubation, and hospital costs were significantly lower in the
epidural group.[27]
Preservative-free morphine was the first opioid to gain approval by the U.S. Food and Drug Administration (FDA)
for epidural and intrathecal use. Its duration of action is longer than that of other opioid analgesics
as a result of its hydrophilic physiochemical properties.
Although experience with morphine has primarily involved intermittent injection, it has been used with success as a
continuous infusion. Effective doses may range from less than 0.1 to 1.5 mg per hour. Its early use in relatively large
doses was associated with reports of cases of severe and delayed respiratory depression, and this led to exploration
of the use of less hydrophilic opioid analgesics, including meperidine, fentanyl, and sufentanil.
A lipophilic drug such as fentanyl is useful when rapid onset of epidural analgesia is important. Intermittent epidural
boluses of 50 to 75 µg can be used to promptly achieve analgesia in the immediate postoperative period if the initial
epidural morphine dose is not adequate. Used as the sole opioid, a 25- to 100-µg epidural bolus can be followed by a
continuous infusion of 25 to 100 µg per hour with an accurately calibrated pump. As with other opioids, respiratory
depression can occur.
Until it is possible to identify and eliminate the factors that occasionally lead to severe respiratory depression in
patients receiving intraspinal opioids, it must be assumed that all patients offered these techniques are at risk. To
prevent serious injury or death, there is no substitute for a high level of vigilance. A nurse trained to check at
frequent intervals the rate and depth of respiration as well as the general status and level of consciousness may
provide this level of care. Respiratory rate alone is not an adequate indicator of ventilatory status in postoperative
patients receiving epidural opioids. A more global assessment is necessary, particularly during the first 24 hours of
[28]
treatment. This evaluation should include assessment of the level of consciousness, because increasing sedation
(presumably due to central drug effect and CO2 narcosis) has been noted with advanced respiratory depression.
For maximal analgesic effect with minimal drug injection, the epidural catheter should be placed at a spinal cord
level corresponding to the dermatomal distribution of the surgical pain stimulus. With the epidural catheter
advanced 3 cm to 5 cm beyond the needle tip into the epidural space, the corresponding vertebral levels for optimal
epidural catheter placement for various surgical procedures are as follows:
• C7–T2 for upper extremity surgery

• T4–8 for thoracic surgery
• T8–10 for upper abdominal surgery
• T10–12 for lower abdominal and pelvic surgery
50
• L2–4 for lower extremity surgery
As previously stated, the combination of epidurally administered analgesic concentration of local anesthetics and
opioid analgesics can be expected to produce the greatest balance of analgesia as well as the fewest postoperative
side effects after numerous major surgical procedures. Bupivacaine, in analgesic concentrations up to 0.25%, is the
[29]
most commonly used local anesthetic agent. Infusions of bupivacaine concentrated greater than 0.125% via lumbar
epidural catheter are frequently associated with lower extremity motor blockade.
There is considerable interest in combining the potent analgesic effects of drugs delivered into the epidural space
with the pharmacologic and nonpharmacologic advantages of patient participation associated with the PCA concept.
All the commonly used opioid analgesics have been used for patient-controlled epidural analgesia (PCEA) alone or
in combination with bupivacaine. Some favor the use of the more lipophilic opioid analgesics for PCEA because of
the more rapid onset of effect. [30] [31]
Role of the Acute Pain Nurse
As a result of advances in pain management techniques and technology, anesthesiologists are now offering patients
new and highly effective forms of postoperative analgesia. However, it is the responsibility of trained bedside nurses
to deliver these analgesic therapies and to monitor and treat associated adverse effects. Because anesthesiologists
generally have limited understanding of ward policies, an acute pain nurse (APN) can serve as an important link
between anesthesiologists and bedside nurses.
Increasingly, specialist nurses with particular training in pain management are being appointed, frequently as part of
an acute pain team or pain management service. They make an invaluable contribution to patient care, bridging the
gap between doctors and nurses and their areas of knowledge and responsibility. They can help to direct resources,
educate nurses and doctors in pain management techniques, give necessary support to the primary nurse, and help to
initiate and supervise analgesia. Some APNs are nurse anesthetists with special training in pain management ( Table
4–2 ).
THE NURSE’S ROLE IN PATIENT EDUCATION
Nurses are in a unique position to help patients in pain, because they spend more time with patients than any other
health team member does. As new techniques of pain management are developed, nurses must update their
knowledge to provide safe and effective care. Many nurses who are already overwhelmed with new techniques and
equipment may react with skepticism and resistance to changes in the traditional approaches to pain management.
Even if the changes will eventually save nursing time, new techniques or pieces of equipment, such as epidural
anesthesia and
TABLE 4-2 -- ORGANIZATION OF ACUTE PAIN SERVICES AT ÖREBRO MEDICAL CENTER HOSPITAL, ÖREBRO, SWEDEN
Health Care Member “Pain
Representatives” Responsibility
• Acute pain anesthesiologist Responsible for coordinating hospital- wide acute pain services and inservice teaching
• Section anesthesiologist Responsible for pre-, peri- and postoperative care (including postoperative pain) for his/her
surgical section
• “Pain representative” ward surgeon Formally responsible for pain management for his/her surgical ward.
• “Pain representative” day nurse Responsible for implementation of pain management guidelines and monitoring routines on the
ward *
• “Pain representative” night nurse
• Acute pain nurse (nurse anesthetist) • Daily rounds of all surgical wards
• Check visual analogue scale (VAS) recording on charts (every patient VAS≤3)
• “Trouble-shoot” technical problems (PCA, epidural)
• Refer problem patients to section anesthesiologist (link between surgical ward and
anesthesiologist)
• Daily “bedside” teaching of ward nurses
This organization benefits about 20,000 patients a year (VAS≤3) and has been functioning satisfactorily since 1991. Cost per patient is U.S. $2 to
51
TABLE 4-2 -- ORGANIZATION OF ACUTE PAIN SERVICES AT ÖREBRO MEDICAL CENTER HOSPITAL, ÖREBRO, SWEDEN
Health Care Member “Pain
Representatives” Responsibility
$3 (excluding drug and equipment costs).
* Patients are treated on the basis of standard orders and protocols devel oped jointly by chiefs of anesthesiology, surgery, and nursing sections.
Pain representatives meet every 3 months to discuss and implement improvements in surgical ward pain management routines.
PCA, are stressful for the staff nurses until they become familiar with them.
Background knowledge, skills, and experience of nursing staff influence pain management. Many responsibilities
for pain management rest with the nurse who cares directly for the patient; however, many nurses have, in fact, had
little formal education on the subject of pain management.
The nurse on the ward must be informed of the requirements of an analgesic technique and confident about putting
them into practice. This proficiency can be achieved through education and experience in a supportive environment.
Protocols should be constructed in conjunction with nursing colleagues and modified as necessary to allow for local
nursing practices. Nursing education is widely recognized as an important priority in pain management.
Postgraduate training courses on pain management for practicing nurses are increasingly available, and education on
pain management is becoming more prominent in basic nursing training.
Educational devices such as algorithms to guide analgesic administration can lead to substantial improvements in
quality of pain relief. The attitude of the staff toward pain management has an important influence on the
[1]
effectiveness of pain relief. The APS is best served by developing a small range of standard analgesic techniques to
[2]
achieve a common level of understanding, familiarity, and confidence.
Patients are unlikely to be aware of the standard of care they can expect to receive or what they can demand, and
their attitudes toward pain and analgesia are believed to influence strongly the effectiveness of their pain relief.
Inadequate patient education is associated with a low standard of postoperative pain relief. Patient education is [32]
particularly important when drugs are administered by techniques such as PCA.
It is essential that pain be made visible. Pain should be routinely documented in the patient’s notes in a manner
similar to that used to record blood pressure and heart rate. This process should be simple and convenient for
nursing and medical staff. Documentation also provides data for audit and facilitates review and improvement of
care.
AUDIT OF THE ACUTE PAIN SERVICE
An audit should be carried out regularly with regard to the process of pain management, patient experience, and
cost; the service should be modified according to the outcome. It is essential that pain be regularly evaluated to
ensure that it is effectively managed. The minimum standard should be at least an annual determination of the
number of patients whose pain scores were above the predetermined threshold, and the reasons for the elevated
scores should be identified. The audit method should be developed to meet local conditions. The outcome of an
audit should be reviewed regularly, and the service should be modified to rectify any shortfalls identified. Adverse
effects of treatment should also be assessed and documented, and the dose or dose interval should be adjusted
accordingly.
ACUTE PAIN SERVICE IN THE UNITED STATES
Although the concept of the APS was first introduced in Europe, the APS seems to be better established in the
[33]
United States. Most major institutions in the United States have an anesthesiology-based APS. The comprehensive [34]
pain management teams usually consist of staff and resident anesthesiologists, specially trained nurses, pharmacists,
and physiotherapists. Sometimes, biomedical and infusion pump dispensing personnel are included. Secretarial and
billing personnel are also a part of the APS in the United States. Patients under the care of an APS are visited and
assessed regularly by members of the team. Although pain management is often very satisfactory, the economic
costs of such
52
services are high; therefore, the benefits are not available to all surgical patients because of reimbursement
regulations.
Anesthesiologist-based APS organization models usually provide high technology pain management services. This
approach is not surprising because anesthesiologists have special expertise in the field of advanced analgesic
techniques such as epidural anesthesia and PCA. Therefore, most APSs in the United States are essentially PCA and
epidural services. Although the implementation of an anesthesiologist-based APS has had a considerable impact on
pain management on surgical wards, only a small percentage of patients receive the benefits of an APS. A good APS
organization is one that ensures optimal pain management for every patient who undergoes surgery, including
children and those undergoing surgery on an ambulatory basis. Furthermore, the record of the U.S. APS in
implementing hospital-wide quality assurance measures such as frequent recording of pain intensity and recording
of treatment efficacy (visual analogue scale [VAS] before and after treatment) has been generally unimpressive so
far. Additionally, the costs of a U.S. APS are very high. It is not surprising that such costs are being increasingly
questioned by healthcare payers. Downsizing of many APSs is taking place in the United States; further reductions
are predicted by many. The fee-for-service reimbursement system seems to be reversing the gains made by the
introduction of the APS.
A more important issue with U.S. anesthesiologist-based APS is a lack of continuity, because the anesthesiologist
performing the preoperative evaluation (which includes patient information about the proposed postoperative
analgesic technique) and epidural block (operating room anesthesiologist) is not the same physician who provides
pain management postoperatively (APS anesthesiologist).
The role of an anesthesiologist in any APS model is pivotal. However, in my opinion, such a role is professionally
more satisfying as a teacher, supervisor, pain expert, and performer of regional blocks in a APN-based
anesthesiologist-supervised model.
DEVELOPMENT OF AN ACUTE PAIN NURSE SERVICE
It is becoming increasingly clear that simpler and less expensive models must be developed if the aim is to improve
the quality of postoperative analgesia for every patient who undergoes surgery. The organization should also include
patients who undergo outpatient surgery. Furthermore, in countries with state-financed health services and
budgetary restraints, the overstaffed U.S.-style anesthesiology-based comprehensive, multidisciplinary,
postoperative pain control teams appear unrealistic for most institutions.
At Örebro Medical Center Hospital, our pain nurse-based, anesthesiologist-supervised model is based on the concept
that postoperative pain relief can be greatly improved by provision of inservice training for surgical nursing staff,
optimal use of systemic opioids, and the use of regional analgesia techniques and PCA in selected patients. Regular
recording of each patient’s pain intensity by VAS every 3 hours and recording of treatment efficacy on the vital
signs chart form the cornerstone of this model. A VAS higher than 3 is promptly treated. Participation by the
surgeon and ward nurse is crucial in this organization. A specially trained APN makes daily rounds of all surgery
departments. The APN’s duties are described in Table 4–2 . In this organization, the treatment of individual patients
is based on standard orders and protocols developed jointly by the section anesthesiologist, the surgeon, and the
ward nurse. This approach gives nurses the flexibility to administer analgesics when necessary. The section
anesthesiologist has the overall responsibility for preoperative, perioperative, and postoperative anesthesia care of
these patients; this responsibility includes postoperative pain management. The anesthesiologist selects the patients
for special pain therapies, such as PCA and epidural or peripheral nerve blocks, based on departmental policy.
During regular working hours, this anesthesiologist is available for consultation or any emergency; during other
shifts, the anesthesiologist on call has the same function. The “pain representatives” from each surgical ward meet
four times a year under anesthesiologist and APN supervision to discuss improvements in APS. In the organization
described here, the only additional cost is that of the APN. At our hospital, where about 18,000 to 20,000 surgical
procedures are performed each year, our low-cost ($2 to $3 per patient excluding drug and equipment costs)
organization is designed to benefit all these patients. This organization has been functioning satisfactorily since
1991; it can easily be modified for nonsurgical wards. The safety of newer techniques such as PCA, peripheral
[35]
nerve blocks, and epidural analgesia on surgical wards is dependent on nurse and physician education. An
independent audit in 1996 showed that 95% of the surgical patients were satisfied with their postoperative pain
management.
53
Challenges for the Future
The need for multidisciplinary APS teams involving anesthesiologists, surgeons, nurses, and other staff to optimize
postoperative pain management is not in doubt. An APS addresses important issues such as improvement in quality
of analgesia and efficacy and safety of (current and future) analgesic techniques. Any future APS organization will
have to include the following: Regular pain assessment and documentation (“make pain visible”); outpatients and
children; active cooperation with surgeons and ward nurses for development of protocols; and bedside teaching of
ward nurses for provision of safe and cost-effective analgesic techniques such as PCA and epidural and peripheral
nerve blocks. These components are relatively noncontroversial; the challenge is to incorporate them in an APS
model that exploits the full potential of invasive and expensive techniques such as epidermal anesthesia for
aggressive postoperative patient mobilization, which can be expected to improve outcome.
The current system of acute pain management often does not integrate pain management with the overall
perioperative care and postoperative rehabilitation of the patient. The role of cooperation and a team approach
featuring interaction among anesthesiologists, APNs, surgeons, ward nurses, and physiotherapists will become
increasingly important. The role of a good APS in developing cost-effective pain treatment strategies for different
surgical procedures cannot be overemphasized.
A designated staff member should be responsible for implementing pain management policies in each unit. Patients
should be fully informed preoperatively about the range of treatments available and their adverse effects. Patients
undergoing outpatient surgery should have their pain assessed and documented in the same way as inpatients.
Outpatients should be given a contact number so that they can discuss their pain relief needs after discharge and
review written information about the use of analgesics.
Summary
In spite of unprecedented interest in understanding pain mechanisms and pain management, a significant number of
patients continue to experience unacceptable levels of pain after surgery. Surveys show that there has been no
apparent improvement since the first study in 1952. It is increasingly clear that the solution to the problems of
[36]
postoperative pain management will be found not so much in the development of new techniques but in the
development of an organization to exploit existing expertise.
The most obvious members of an acute pain team are anesthesiologists, surgeons, nurses, and physiotherapists.
Protocols encourage consistent standards of safe and effective care and should be used as a framework to
individualize treatment.
The concept of skilled pain therapists collaborating to provide improved postoperative analgesia within the
framework of an organized APS appears to be universally applicable. APS models have been described from the
United States, the United Kingdom, Germany, Switzerland, and Sweden. The U.S. model, which consists of
anesthesiologist-based comprehensive pain management teams, is quite effective but too selective and too
expensive. It is not transferable to Europe. A recent U.K. survey showed that there is a large degree of variation in
what is thought to constitute an APS in the United Kingdom. A nurse-based, anesthesiologist-supervised APS in
[37]
which pain is evaluated in every patient who undergoes surgery has been developed in Sweden. Pain higher than 3
on the 10-grade VAS is promptly treated. Clearly, neither the anesthesiologist nor the APN guarantees good pain
management on wards; the quality of ward nursing is most important. In this low-cost model, the anesthesiologist’s
role is teaching and training ward nurses, supervising the APN, and selecting patients for special pain therapies such
as PCA and epidural and peripheral nerve blocks. All senior anesthesiologists (section chiefs) working in the
operating room are part of this APS.
The means of providing satisfactory analgesia are already present in most hospitals. Careful planning and a
multidisciplinary approach to pain management will ensure that resources are optimally used and that the quality of
pain management is consistently maintained.
REFERENCES
1. Gould TH, Crosby DL, Harmer M, et al: Policy for controlling pain after surgery: Effect of sequential changes in management. BMJ 305:1165–
1166, 1992.
2. Oats
JDL, Snowman SL, Jason DWH: Failure of pain relief after surgery. Attitudes of ward staff and patients to postoperative analgesia.
Anesthesia 49:755–758, 1994.
54
3. Warbled
CA, Kahn CH: Acute pain management. Programs in US hospitals and experiences and attitudes among US adults. Anesthesiology
83:1090–1094, 1995.
4. Tittle M, McMillan SC: Pain and pain-related side effects in an ICU and on a surgical unit: Nurses’ management. Am J Crit Care 3:25–30,
1994.
5. UlfH, Neugebauer E, Maier C: Die Behandlung akuter perioperativer und posttraumatischer Schmerzen. Empfehlungen einer
interdisziplinaeren Expertenkommission. Stuttgart, G. Thieme, 1997.
6. Rawal
N, Allvin R, EuroPain Acute Pain Working Party: Acute pain services in Europe: A 17-nation survey of 105 hospitals. Eur J Anaesth
15:354–363, 1998.
7. Royal
College of Surgeons of England and the College of Anaesthetists Commission on the Provision of Surgical Services: Report of the
Working Party on Pain after Surgery. London, September 1990.
8. National Health and Medical Research Council (Australia): Management of Severe Pain. Canberra, Australia, NHMRC, 1988.
9. U.S.
Department of Health and Human Services: Acute Pain Management. Clinical Practice Guidelines. AHCPR Publications No 92-0032.
Washington, DC, U.S. Department of Health and Human Services, 1992.
10. International
Association for the Study of Pain (IASP): Management of Acute Pain. A Practical Guide. Task Force on Acute Pain. Seattle,
IASP Publications, 1992.
11. Joris J: Efficacy of nonsteroidal anti-inflammatory drugs in postoperative pain. Acta Anaesthesiol Belg 47:115–123, 1996.
12. Piguet V, Desmeules J, Dayer P: Lack of acetaminophen ceiling effect on R-III nociceptive flexion reflex. Eur J Clin Pharmacol 53:321–324,
1998.
13. Pelissier
T, Alloui A, Caussade F: Paracetamol exerts a spinal antinociceptive effect involving an indirect interaction with 5-
hydroxytryptamine-3 receptors: In vivo and in vitro evidence. J Pharmacol Exp Ther 278:8–14, 1996.
14. Raffa RB, Codd EE: Lack of binding of acetaminophen to 5-HT receptor or uptake sites. Life Sci 59:L37–L40, 1996.
15. Bjorkman R: Central antinociceptive effects of non-steroidal antiinflammatory drugs and paracetamol: Experimental studies in the rat. Acta
Anaesthesiol Scand 103(Suppl):1–144, 1995.
16. Honer P, Buritova, J Besson JM: Aspirin and acetaminophen reduced both Fos expression in rat lumbar spinal cord and inflammatory sign
produced by carrageenan inflammation. Pain 63:365–375, 1995.
17. Mather LE: Do the pharmacodynamics of the nonsteroidal antiinflammatory drugs suggest a role in the management of postoperative pain?
Drugs 44(Suppl 5):1–12, 1998.
18. Reuben SS, Connelly NR, Lurie S, et al: Dose-response of ketorolac as an adjunct to patient controlled analgesia morphine in patients after
spinal fusion surgery. Anesth Analg 87:98–102, 1998.
19. Peduto VA, Ballabio M, Stefanini S: Efficacy of propacetamol in the treatment of postoperative pain: Morphine-sparing effect in orthopedic
surgery. Italian Collaborative Group on Propacetamol. Acta Anaesthesiol Scand 42:293–298, 1998.
20. Varrassi G, Marinangeli F, Agro F, et al: A double blind evaluation of propacetamol versus ketorolac in combination with patient controlled
analgesia morphine: Analgesic efficacy and tolerability after gynecologic surgery. Anesth Analg 88:611–616, 1999.
21. White WD, Pearce DJ, Norman J: Postoperative analgesia: A comparison of intravenous on-demand fentanyl with epidural bupivacaine. BMJ
2:166, 1979.
22. Tamsen A, Hartvig P, Fagerlund C: Patient-controlled analgesic therapy: Clinical experience. Acta Anaesthesiol Scand 26(suppl 74):157,
1982.
23. Plummer JL, Owen H, Ilsley AH, et al: Morphine patient-controlled analgesia is superior to meperidine patient-controlled analgesia for
postoperative pain. Anesth Analg 84:794-799, 1997.
24. Owen H, Plummer JL, Armstrong I, et al: Variables of patient-controlled analgesia: 1. Bolus size. Anaesthesia 44:7–10, 1989.
25. Classen DC, Pestotnik SL, Evans RS, et al: Adverse drug events in hospitalized patients: Excess length of stay, extra costs, and attributable
mortality. JAMA 277:301–306, 1997.
26. Rawal N, Sjostrand U, Christofferson E, et al: Comparison of intramuscular and epidural morphine for postoperative analgesia in the grossly
obese: Influence on postoperative ambulation and pulmonary function. Anesth Analg 63:583, 1984.
27. Yeager MP, Glass DD, Neff RK, et al: Epidural anesthesia and analgesia in high risk surgical patients. Anesthesiology 66:729, 1987.
28. Rawal N, Wattwil M: Respiratory depression after epidural morphine—an experimental and clinical study. Anesth Analg 63:8, 1984.
55
83:757–765, 1995.
30. Veercauteren MP, Van Den Bergh L, Kartawiadi SL, et al: Addition of bupivacaine to sufentanil in patient-controlled analgesia after lower
limb surgery in young adults. Reg Anesth Pain Med 23:182–188, 1998.
31. Liu SS, Allen HW, Olsson GL: Patient-controlled epidural analgesia with bupivacaine and fentanyl on hospital wards: Prospective experience
with 1,030 surgical patients. Anesthesiology 88:124–129, 1998.
32. Kuhn S, Cooke K, Collins M, et al: Perceptions of pain relief after surgery. BMJ:300:1687–1690, 1990.
33. Maier C, Kibbel K, Mercker S, Wulf H: Postoperative pain therapy at general nursing stations. An analysis of eight year’s experience at an
anesthesiological acute pain service. Anaesthesist:43:385–397, 1994.
34. Ready LB: How many acute pain services are there in the US and who is managing patient-controlled analgesia? (Letter)
Anesthesiology:82:322, 1995.
35. Rawal N, Berggren L: Organization of acute pain services—a low cost model. Pain:57:117–123, 1994.
36. Papper EM, Brodie BB, Rovenstine EA: Postoperative pain, its use in the comparative evaluation of analgesics. Surgery 32:107–109, 1952.
37. Windsor AM, Glynn CJ, Mason DG: National provision of acute pain services. Anaesthesia:51:228–231, 1996.
56
Section II - Chapter 5 - Organization of Chronic Pain Services
Chapter 5 - Organization of Chronic Pain Services
RICARDO RUIZ-LÓPEZ
DIEGO BELTRUTTI
Since the initial organization of pain centers carried out in the 1960s by J. J. Bonica in the United States, S. Lipton
in the United Kingdom, and a few other specialists in Western countries, the enormous necessity of this type of
health service has become clear, along with the difficulty of its comprehensive organizational approach in order to
be effective for the diagnosis and therapy of this patient population. [1] [2] [3] [4]
The foundation in 1974 of the International Association for the Study of Pain (IASP) strengthened the development
of pain facilities in the United States and around the world. Consequently, in response to the proliferation of pain
centers during the last 2 decades, various medical associations have defined and classified the types of such
facilities.
[5] [6] [7]
According to the scope of the therapeutic approach, pain centers can be classified into three models:
1. Pain centers following the medical model, in which pain is treated as a symptom of a disease to be
diagnosed
2. Pain centers working with the behavioral model, in which pain behavior and associated impaired function
are considered as important as the underlying pathophysiology
3. Pain centers with a predominant focus on the cognitive-behavioral model, in which patients are considered
to develop aberrant convictions in regard to their functional capacities and prognoses [8]
Today, particularly in Europe and Australasia, chronic pain conditions are treated by a combination of intervention
and the behavioral-rehabilitation model, as reports of the efficacy of cognitive-behavioral programs for the treatment
of chronic pain conditions have shown variable outcomes in comparison with the selection criteria of interventional
approaches, which are better defined. [9] [10] [11] [12] [13]
In the United States, all three models have been established during the past three decades, although recent changes
introduced in managed healthcare have modified in many cases the approach of preexisting pain facilities.
This chapter will cover the following topics:
• Pain treatment facilities

• Pain medicine as a new specialty
• Administrative issues
Appendixes with related recommendations can be found at the end of the chapter.
Pain Treatment Facilities
Pain treatment facilities were established to treat chronic, refractory pain related to conventional medical, surgical,
and rehabilitative modalities. Multidisciplinary pain centers were developed to treat specifically a group of patients
mainly suffering from chronic back pain that did not improve with conventional treatment, causing them to remain
disabled. These patients showed, in addition to the existence of chronic pain, behavioral and psychosocial
impairment that required the intervention of a multidisciplinary team approach that would deal with the patient’s
problem simultaneously.
Regardless of the therapeutic approach, the lack of regulation of pain centers and the various clinical structures that
used the term indiscriminately forced the American Society of Anesthesiology (ASA) and the IASP to classify the
different pain facilities according to their professional composition, modalities of treatment, organization, pain
conditions being treated, clinical or basic research, and teaching potential.
Thus, the ASA classifies pain centers into four types : [6]
57
1. Major comprehensive pain centers

2. Comprehensive pain centers
3. Modality-oriented pain clinics
4. Syndrome-oriented pain clinics
Overall, it is important to note that the function and organization of these pain centers rely greatly on the training,
beliefs, expertise, and specialty of the director; the composition of the staff; and the type of institution. [1]
The variation in staff makeup and available therapeutic modalities has caused both physicians and the public to have
misinformation about differences among the pain syndromes and the types of pain centers or clinics.
Another step in the process of defining chronic pain services was reached by the Commission on Accreditation of
Rehabilitation Facilities (CARF) with the establishment of a certification process for pain clinics for one type of
treatment model (i.e., chronic pain management programs). [10] [14]
Because of this lack of definition, the IASP established guidelines and characteristics for four types of pain
[15]
treatment facilities ( Table 5-1 , Appendix 5-1 ).
This classification makes a clear distinction between the multidisciplinary pain centers and clinics (MPC) and those
facilities without multidisciplinary orientation. The only difference between the multidisciplinary pain centers and
multidisciplinary pain clinics is that the former have to develop research and teaching activities. Nevertheless, both
types of centers must provide inpatient and outpatient treatment, and the teams must contain diversified staff
members, including more than one physician specialty and a psychologist or psychiatrist.
TABLE 5-1 -- INTERNATIONAL ASSOCIATION FOR THE STUDY OF PAIN CLASSIFICATION OF PAIN FACILITIES
Modality-oriented clinic
Provides specific type of treatment (e.g., nerve blocks, transcutaneous nerve stimulation, acupuncture, biofeedback)
May have one or more healthcare disciplines
Does not provide an integrated, comprehensive approach
Pain clinic
Focuses on the diagnosis and management of patients with chronic pain or may specialize in specific diagnoses or pain related to a specific
region of the body
Does not provide comprehensive assessment or treatment
Institution offering appropriate consultative and therapeutic services would qualify but never an isolated solo practitioner.
Multidisciplinary pain clinic
Specializes in the multidisciplinary diagnosis and management of patients with chronic pain or may specialize in specific diagnoses or pain
related to a specific region of the body
Staffed by physicians of different specialties and other healthcare providers
Differs from a multidisciplinary pain center only because it does not include research and teaching
Multidisciplinary pain center
Organization of healthcare professionals and basic scientists that includes research, teaching, and patient care in acute and chronic pain
Typically a component of a medical school or a teaching hospital
Clinical programs supervised by an appropriately trained and licensed director
Staffed by a minimum of physician, psychologist, occupational therapist, physical therapist, and registered nurse
Services provide integrated care based on interdisciplinary assessment and management
Offers both inpatient and outpatient programs
Adapted from Loeser JD: Desirable characteristics for pain treatment facilities: Report of the IASP taskforce. In Bond MR, Charlton JE, Woof
CJ (eds): Pain Research and Clinical Management, vol. 4. 1991, pp. 411–415.
58
Pain Medicine: A New Specialty
Scientific inquiry into the anatomy and physiology of pain perception increased, and with the discovery of opiate
receptors in animal and human tissues, the actions of peptides on endogenous opioid receptors, the development of
new therapies for the alleviation of pain, and the classification and description of chronic pain syndromes, some
essential pieces were added that support modern pain therapy. [16] [17] [18]
The emerging specialty of pain medicine has been increasingly recognized over the last 2 decades by medical
organizations, regulatory agencies, and third-party payers. This specialty is formed by a distinct and unique body of
knowledge and a defined clinical application that supports a clinical practice. Moreover, pain medicine has fostered
growth of scholarly knowledge and research and fills a recognized gap in health professional training ( Table 5-2 ).
In its official policy statement, the American Academy of Pain Medicine (AAPM) defines pain medicine as follows:
The specialty of pain medicine is concerned with the prevention, evaluation, diagnosis, treatment,
and rehabilitation of painful disorders. Such disorders may have pain and associated symptoms
arising from a discrete cause, such as postoperative pain or pain associated with a malignancy, or
may be syndromes in which pain constitutes the primary problem, such as neuropathic pains or
headaches. The diagnosis of painful syndromes relies on interpretation of historical data; review
of previous laboratory, imaging, and electro-diagnostic studies; behavioral, social, occupational,
and avocational assessment; interview and examination by the pain specialist; and may require
specialized diagnostic procedures, including central and peripheral neural blockade or monitored
drug infusions. The special needs of the pediatric and geriatric populations are considered when
formulating a comprehensive treatment plan for these patients.
The pain physician serves as a consultant to other physicians, but is often the principal treating
physician and may provide care at various levels, such as direct treatment, prescribing medication,
prescribing rehabilitative services, performing pain-relieving procedures, counseling of patients
and families, (directing a) multidisciplinary team, (coordinating) care with other healthcare
providers, and (providing) consultative services to public and private agencies pursuant to optimal
healthcare delivery to the patient suffering from a painful disorder. The pain physician may work
in a variety of settings and is competent to treat the entire range of painful disorders encountered
in the delivery of quality healthcare.
However, the official establishment of pain medicine as a medical specialty needs a process of accreditation that
could be obtained, as in other specialties, through any of several, well-defined medical boards. Until now, in the
United States only one medical association—the American Board of Pain Medicine
TABLE 5-2 -- PAIN MEDICINE: OPERATIONAL CRITERIA

A distinct and unique body of knowledge as evidenced by texts and journals; clinical applicability sufficient to support a clinical practice
Ability to generate scholarly knowledge and support research
Ability to meet numerical standards for training programs, trainees, and practicing diplomats
De facto recognition as clear subject area by governmental bodies (e.g., NIH, NCI, AHCPR) and nongovernmental organizations (e.g., WHO,
IASP, AAPM, APS, WIP)
Fills a recognized gap in health professional training
Adapted from Carr DB, Aronoff GM: The future of pain management. In Aronoff GM (ed): Evaluation and Treatment of Chronic Pain, 3rd ed.
Baltimore, Williams & Wilkins, 1998.
AAPM, American Academy of Pain Medicine; AHCPR, Agency for Health Care Policy; APS, acute pain service; IASP, International
Association for the Study of Pain; NCI, National Cancer Institute; NIH, National Institutes of Health; WIP, World Institute of Pain, WHO, World
Health Organization.
(ABPM), recognized by the American Medical Association—offers training and accreditation in pain medicine
59
through rigorous procedures. The ABPM has been granted full recognition in California by the American Board of
Medical Specialties.
In Europe, the situation differs because there is no medical association that links the numerous countries through the
territory, and the lack of homogeneous legislation represents a practical barrier for the recognition of any new
medical specialty. Only a few exceptions to this situation exist, such as in Turkey, where there has been official
recognition of treatment of pain as a medical specialty since 1993, with specific resources for training, research,
education, and clinical practice throughout the country.
In the rest of the world, academic regulatory obstacles and paucity of resources limit the process of accreditation and
the recognition of this specialty.
In an effort to strengthen a world initiative in the process of education and training of physicians interested or
involved in pain medicine, the World Institute of Pain (WIP), an international association of pain centers founded in
1994, defines different goals that meet a common interest for pain physicians:
1. Educate and train personnel of member pain centers, including local hands-on training, international
seminars, and exchange of clinicians.
2. Update pain centers with state of the art pain information, including a newsletter, scientific seminars,
interlinked telecommunications, and publication of a journal and books.
3. Develop common protocols for efficacy and outcome studies.
4. Communicate administrative and patient-related matters on a regular basis by way of a newsletter, a
telephone hookup, a world directory of pain centers (region by region), and video conferencing (including
patient consultation).
5. Categorize and credential pain centers by mail correspondence, local information, and the industry’s
medical representatives.
6. Develop an examination process for pain centers to test trainees and provide information about the
examination process.
7. Encourage interested industrial parties to provide information on pain medicine to each region of the world;
bring local pain physicians into contact with industry for education about new techniques and training in
their use; and formulate a fellowship training program.
Despite the fact that pain clinicians are treating chronic pain on a daily basis, education on pain is absent at the
various levels of the medical career, whether at medical schools or at postgraduate levels. Formal education and
training are essential so that fellowship programs can be set up to precede the establishment of full residency
programs in pain medicine. Residency programs should include specific training in the different areas involved in
the field, including surgical training for interventional procedures and education in the important fields related to
management of chronic pain and cancer pain, such as psychology, oncology, and symptomatic relief.
Many issues and questions remain to be answered or resolved by the scientific community. These include but are not
limited to such areas as the epidemiologic figures on chronic pain, whether associated with disability or not; the
existence of pain in degenerative syndromes and in advanced incurable diseases; the predisposing factors for
suffering pain; the neuromatrix of pain transmission and modulation; the role of the autonomic nervous system in
the neurophysiology of pain; the development of more selective drugs for central and peripheral nervous system
action; the role of affectivity and the psychological processes that are involved in the perception of pain and
suffering; the development of more selective and minimally invasive techniques for pain control; the improvement
in understanding the maturation and aging of the nervous system; and the measurement, assessment, and validation
of pain.
Finally, some attention is due to the administrative issues burdening the clinical practice of pain medicine, because
many difficulties have appeared that complement the above-mentioned situations.
Administrative Issues
The increasing public demand on healthcare services is rapidly changing the shape and characteristics of pain
facilities, much as in other medical specialties in which providers of healthcare services are at the crossroads
between pressure exerted by consumers and the managed care rules. [19]
Patients have acquired an enormous amount of information through the media; specifically, the Internet is becoming
the most popular means of information gathering. In addition, the public has a growing skepticism about the
60
traditional sources of medical information. Chronic pain patients are a very vulnerable population with a large
percentage of malpractice victims. Many of them in desperation look for relief by trying pseudoscientific
approaches, typically by self-referral.
In that scenario, demystification of medicine through health education that provides accurate information to patients
and families is a principal goal of the pain physician. The lack of understanding by the patient of the diagnostic
evaluation, treatment modalities, and prognosis contributes to confusion among patients and health providers.
Healthcare systems have finite resources; that is, the innovations in pain management are viewed quite favorably by
insurers and policy makers who see potential cost savings in a patient’s rapid return to normal function after surgery
or in home care rather than hospital care for a patient with a chronic or terminal illness. [20]
Several Western countries, including the United Kingdom, Canada, and Australia, require economic justification for
approval of any new drug, and there is an increasing trend to apply these criteria to clinical trials by means of cost
analyses through diverse perspectives. Extrapolating this concept to the area of pain management, studies should be
developed in terms of cost-benefit analysis of therapies and their cost-effectiveness and cost of use, in which benefit
is defined in terms of quality of life. [21] [22]
However, findings that can be applied to many medical disciplines in regard to managed care seem to be distorted in
the environment of patients with chronic and complex illnesses. These persons often require advanced
comprehensive care services, well beyond what the primary care physician can generally provide. Such patients
often require well-trained subspecialists or referral to complex comprehensive systems of care. The cost of such
services is often far beyond the customary cost, and only by assuming the challenge of normalization and
accreditation of health services can pain medicine survive. [23] [24]
Pain physicians must be aware that there is a need for moving away from treatment algorithms to a strategy based on
levels of care.
REFERENCES
1. Bonica JJ: Evolution of pain programs. In GM Aronoff (ed): Pain Centers: A Revolution in Health Care. New York, Raven Press, 1988, pp 9–
32.
2. Crue BL, Pinsky JJ: Chronic pain syndrome: Four aspects of the problem. In Ng LKY (ed): New Approaches to the Treatment of Chronic Pain:
A Review of Multidisciplinary Pain Clinics and Pain Centers. Rockville, Md: National Institutes of Drug Abuse, 1981, pp 137–168.
3. Seres JL, Newman RI: Results of treatment of chronic low-back pain at the Portland Pain Center. J Neurosurg 45:32–36, 1976.
4. Rosomoff
HL, Rosomoff RS: Comprehensive multidsciplinary pain center approach of the treatment of low back pain. Neurosurg Clin North
Am 2:877–890, 1991.
5. Brena SF: Pain control facilities: Patterns of operation and problems of organization in the USA. Clin Anesth 3:183–195, 1985.
6. Modell J: Directory of Pain Clinics. Oak Ridge, Ill, American Society of Anesthesiologists, 1977.
7. Curron H: International Directory of Pain Centers/Clinics. Oak Ridge, Ill, The American Society of Anesthesiologists, 1979.
8. Long
DM: The Development of the Comprehensive Pain Treatment Program at Johns Hopkins. In Cohen MJM, Campbell JN (eds): Pain
Treatment Centers at a Crossroads: A Practical and Conceptual Reappraisal. Seattle, IASP Press, 1996.
9. Flor H, Fydrich T, Turk DC: Efficacy of multidisciplinary pain treatment centers: A meta-analytic review. Pain 49:221–230, 1992.
10. Aronoff GM, Evans WO, Enders PL: A review of follow-up studies of multidisciplinary pain units. Pain 16:1–11, 1982.
11. Wells JCD, Miles JB: Pain clinics and pain clinic treatment. Br Med Bull 47:762–785, 1991.
12. Turk DC, Rudy TE, Sorkin BA: Neglected topics in chronic pain treatment outcomes studies: Determination of success. Pain 53:3–16, 1993.
13. Sanders SH, Brena SF: Pain management program in the United States: A problem of image and credibility. Focus Pain 1:3, 1993.
14. Commission on Accreditation of Rehabilitation Facilities: Program evaluation in chronic pain management programs. Tucson, CARF, 1987.
15. International Association for the Study of Pain: Desirable characteristics for pain treatment facilities and standards for physician fellowship in
pain management. Seattle, IASP, 1990.
16. Ghia JN: Development and organization of pain centers. In Raj PP (ed): Practical Management of Pain, 2nd ed. St. Louis, Mosby, 1992, pp
61
16–39.
17. Schwartz DP: Appropriate referral to inpatient vs. outpatient pain management programs: A cliniciaňs guide, Pain Dig 1:2–6, 1991.
18. Merskey H, Bogduk N (eds): Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definition of Pain Terms, 2nd ed.
Seattle, IASP Press, 1994.
19. King RB, Moore B: Managed care: Past, present and future. Arch Neurol 53:851–855, 1996.
20. Carr
DB, Aronoff GM: The future of pain management. In Aronoff GM (ed): Evaluation and Treatment of Chronic Pain. Baltimore, William
& Wilkins, 1998.
21. Bootman LJ, Townsend RJ, McGhan WF (eds): Principles of pharmaeconomics, 2nd ed. Cincinnati, Whitney, 1995.
22. Ruiz-López
R: Continuous care of cancer pain patients. In Aronoff GM (ed): Evaluation and Treatment of Chronic Pain, 3rd ed. Baltimore,
Williams & Wilkins, 1998.
23. http://www.jcaho.org/standard/pm_npfrm.html
24. Chapman CR: New JCAHO standards for pain management: Carpe diem! APS Bull 10:2–3, July/Aug 2000.
APPENDIX 1: Desirable Characteristics of Pain Treatment Facilities [15]
DEFINITION OF TERMS
The following terms are defined briefly in this section; a more complete description of the characteristics of each
type of facility appears in subsequent portions of this chapter.
1. Pain Treatment Facility. This generic term is used to describe all forms of pain treatment facilities without
regard to personnel involved or types of patients served. Pain unit is a synonym for pain treatment facility.
2. Multidisciplinary Pain Center. This organization of healthcare professionals and basic scientists includes
research, teaching, and patient care related to acute and chronic pain. This type of center is the largest and
most complex of the pain treatment facilities and ideally would exist as a component of a medical school or
teaching hospital. Clinical programs must be supervised by an appropriately trained and licensed clinical
director. A wide array of healthcare specialists is required, such as physicians, psychologists, nurses,
physical therapists, occupational therapists, vocational counselors, social workers, and other specialized
healthcare providers. The range of disciplines required of healthcare providers is a function of the varieties
of patients seen and the healthcare resources of the community. The members of the treatment team must
communicate with each other on a regular basis, both about specific patients and about overall
development. Healthcare services in a multidisciplinary pain clinic must be integrated and based upon
multidisciplinary assessment and management of the patient. Inpatient and outpatient programs are offered
in such a facility.
3. Multidisciplinary Pain Clinic. This healthcare delivery facility is staffed by physicians of different
specialties and other nonphysician healthcare providers who specialize in the diagnosis and management of
patients with chronic pain. This type of facility differs from a multidisciplinary pain center only because it
does not include research and teaching activities in its regular programs. A multidisciplinary pain clinic
may have diagnostic and treatment facilities to serve outpatients, inpatients, or both groups.
4. Pain Clinic. This clinic is a healthcare delivery facility that focuses on the diagnosis and management of
patients with chronic pain. A pain clinic may specialize in specific diagnoses or in pains related to a
specific region of the body. A pain clinic may be large or small, but it should never be a label for a solo
practitioner. A single physician functioning within a complex healthcare institution that offers appropriate
consultative and therapeutic services could qualify as a pain clinic if chronic pain patients were suitably
assessed and managed. The absence of interdisciplinary assessment and management distinguishes this
type of facility from a multidisciplinary pain center or clinic. Pain clinics can, and should be encouraged to,
carry out research, but it is not a required characteristic of this type of facility.
5. Modality-Oriented Clinic. This healthcare facility offers a specific type of treatment and does not provide
comprehensive assessment or management. Examples include nerve block clinic, transcutaneous nerve
stimulation clinic, acupuncture clinic, and biofeedback clinic. Such a facility may have one or more
healthcare providers with different professional training; because of its limited treatment options and the
lack of an integrated, comprehensive approach, it does not qualify for the term “multidisciplinary.”
DESIRABLE CHARACTERISTICS OF A MULTIDISCIPLINARY PAIN CENTER
62
1. A multidisciplinary pain center (MPC) should have on its staff a variety of healthcare providers capable of
assessing and treating physical, psychosocial, medical, vocational, and social aspects of chronic pain. These
therapists work with occupational therapists, vocational counselors, social workers, and any other type of
healthcare professional who can make a contribution to patient diagnosis or treatment.
2. At least three medical specialties should be represented on the staff of a multidisciplinary pain center. If
one of the physicians is not a psychiatrist, physicians from two specialties and a clinical psychologist are
the minimum required. An MPC must be able to assess and treat both the physical and the psychosocial
aspects of a patient’s complaints. The need for other types of healthcare providers should be determined on
the basis of the population served by the MPC.
3. The healthcare professionals should communicate with each other on a regular basis both about individual
patients and about the programs offered in the pain treatment facility.
4. There should be a director or coordinator of the MPC. He or she need not be a physician, but if not, there
should be a director of medical services who is responsible for monitoring the medical services provided.
5. The MPC should offer diagnostic and therapeutic services that include medication management, referral for
appropriate medical consultation, review of prior medical records and diagnostic tests, physical
examination, psychological assessment and treatment, physical therapy, vocational assessment and
counseling, and other services as appropriate.
6. The MPC should have a designated space for its activities. The MPC should include facilities for inpatient
and outpatient services.
7. The MPC should maintain records on its patients so as to be able to assess individual treatment outcomes
and to evaluate overall program effectiveness.
8. The MPC should have adequate support staff to carry out its activities.
9. Healthcare providers active in an MPC should have appropriate knowledge of both the basic sciences and
clinical practices relevant to chronic pain patients.
10. The MPC should have a medically trained professional available to deal with patient referrals and
emergencies.
11. All healthcare providers in an MPC should be appropriately licensed in the country or state in which they
practice.
12. The MPC should be able to deal with a wide variety of chronic pain patients, including those with pain
resulting from cancer and other diseases.
13. An MPC should establish protocols for patient management and assess their efficacy periodically.
14. An MPC should see an adequate number and variety of patients for its professional staff to maintain their
skills in diagnosis and treatment.
15. Members of an MPC should carry out research on chronic pain. This does not mean that everyone should
be doing both research and patient care. Some function only in one arena, but the institution should have
ongoing research activities.
16. The MPC should be active in educational programs for a wide variety of healthcare providers, including
undergraduate, graduate, and postdoctoral levels.
17. The MPC should be part of or closely affiliated with a major health sciences educational or research
institution.
DESIRABLE CHARACTERISTICS OF A MULTIDISCIPLINARY PAIN CLINIC
The distinction between an MPC and a multidisciplinary pain clinic is that the former has research and teaching
components that need not be present in the latter. Hence, items 15, 16, and 17 in the foregoing list are not required
for a multidisciplinary pain clinic. All other items should be present.
DESIRABLE CHARACTERISTICS OF A PAIN CLINIC
1. A pain clinic should have access to and regular interaction with at least three types of medical specialties or
healthcare providers. If one of the physicians is not a psychiatrist, a clinical psychologist is essential.
2. The healthcare providers should communicate with each other on a regular basis both about individual
patients and about programs offered in the pain treatment facility.
3. There should be a director or coordinator of the pain clinic. If he or she is not a physician, there should be a
director of medical services who is responsible for the monitoring of medical services provided to the
patients.
4. The pain clinic should offer both diagnostic and therapeutic services.
5. The pain clinic should have designated space for its activities.
6. The pain clinic should maintain records on its patients so as to be able to assess individual treatment
outcomes and to evaluate overall program effectiveness.
7. The pain clinic should have adequate support staff to carry out its activities.
63
8. Healthcare providers working in a pain clinic should have appropriate knowledge of both the basic sciences
and clinical practices relevant to pain patients.
9. The pain clinic should have trained healthcare professionals available to deal with patient referrals and
emergencies.
10. All healthcare providers in a pain clinic should be appropriately licensed in the country and state in which
they practice.
APPENDIX 2: Joint Commission on Accreditation of Healthcare Organizations Standards for Pain

Management [21] [22]
The new standards for pain assessment and management of the Joint Commission on Accreditation of Healthcare
Organizations (JCAHO) apply to ambulatory care facilities, healthcare networks, behavioral healthcare facilities,
home care, hospitals, long-term care organizations, long-term care pharmacies, and managed behavioral healthcare
organizations.
These standards recognize pain as a condition that requires specific assessment and management and is finally
recognized inside the main frame of patient rights with consequent organizational responsibilities.
In summary, the standards point out the various aspects of pain care with which the healthcare organizations must
comply:
• Explicit recognition of the right of patients to appropriate assessment and management of pain.
• Screening for the existence of pain and assessment of the nature and intensity of pain in all patients.
• Recording the results of the assessment in a way that facilitates regular reassessment and follow-up.
• Determining and ensuring staff competency in pain assessment and management, and addressing pain
assessment and management in the orientation of all new staff.
• Establishing policies and procedures that support the appropriate prescription or ordering of effective pain
medications.
• Educating patients and their families about effective pain management.
• Addressing patient needs for symptom management in the discharge planning process.
• Maintaining a pain control performance improvement plan.
These new standards have started to be scored for compliance in 2001, and many key professional organizations and
accredited healthcare organizations will discuss their experiences in managing pain in order to finalize the
guidelines.
APPENDIX 3: Standards for Physician Fellowship in Pain Management [23]
1. Definition. A physician fellowship in pain management is a specialized postgraduate program of study in

assessing and managing patients with chronic pain of all types and understanding the sciences basic to the
practice of pain management.
2. Duration. A fellowship in pain management should require a minimum of 1 year of full-time clinical
training. Additional research training may be desirable, depending on the fellow’s career goals, but should
not erode the clinical training period.
3. Prerequisites for Fellowship in Pain Management. To be eligible for a fellowship in pain management, the
candidate must be board-eligible or board-certified in one of the recognized specialties of medicine;
furthermore, the specialty area must involve experience with patient care. The fellow must be a graduate of
an approved school of medicine. The fellow must provide at least three letters of a reference and a
curriculum vitae when applying for a fellowship position. The fellow must be licensed to practice medicine
by the appropriate governmental agencies.
4. Resources. The fellowship must occur within a medical institution capable of providing a suitable
educational environment. At least three recognized patient care specialty areas must be offered at the same
institution. The institution must have a medical library with appropriate resources for this level of training.
The clinical pain treatment program or its parent institution must be accredited by the appropriate
governmental agencies. The pain treatment facility must have suitable space allocated for its clinical and
educational activities. It must have a sufficient volume and variety of patients to provide the fellow or
fellows with adequate educational opportunities. The pain treatment facility must see at least 100 new
patients per year per fellow; there must be at least 500 patient visits per year per fellow. Pain treatment
facilities that specialize in one region of the body or one type of disease are by themselves not adequate as
a training resource.
64
5. Director. There must be a designated director of the pain management fellowship. The director shall be a
physician who participates in the diagnosis and treatment of patients within the pain management facility
offering the fellowship in pain management. The director of the fellowship need not be the administrative
or medical chief of the pain treatment facility, but the fellowship director and administrative and medical
chiefs, if they are not the same, must demonstrate the ability to interact in such a way as to be conducive to
the education of fellows. The director shall be responsible for the design and implementation of the
fellowship; he or she shall be responsible for certifying that a fellow has successfully completed his or her
training period and has mastered the requisite knowledge, skills, and attitudes. The director must be a
member of the International Association for the Study of Pain (IASP) and a national chapter. It is desirable
that the director have extensive experience in the management of patients with the complaint of pain; it is
also desirable that he or she have educational and administrative experience above and beyond the
fellowship in pain management. The director shall be responsible for maintaining an up-to-date file on each
fellow, documenting his or her educational progress and any deficiencies.
6. Faculty. There shall be at least three members of the pain treatment facility staff who are designated as
faculty in addition to the director. Faculty members shall be appropriately certified in a patient care
specialty. If one of the faculty is not a psychiatrist, an additional faculty member must be a licensed clinical
psychologist who has expertise in pain management. Faculty members shall also be members of the IASP
and a national chapter. Faculty members of a fellowship in pain management shall represent at least three
healthcare delivery specialties. Other types of healthcare providers in addition to physicians and
psychologists may also be members of the faculty. Faculty members must spend a major part of their
professional time working within the pain treatment facility.
CLINICAL TRAINING SUBJECTS
Although not every fellow will be fully trained in every area listed here, every fellow should at least have had some
exposure to patients whose care involves all these areas.
I. Medical diagnosis and therapy

A. History and physical examination
B. Measurement of pain
C. Physical therapies
D. Vocational and rehabilitation assessment and management
E. Participation in multidisciplinary assessment and treatment
F. Anesthesiologic procedures (when appropriate for the fellow’s prior training)
G. Surgical procedures (when appropriate for the fellow’s training)
H. Other procedures appropriate to the fellow’s prior specialty training
II. Psychological diagnosis and therapy
A. Use of diagnostic tests
B. Collection of data from interview and standard forms
C. Comprehensive assessment
D. Treatment options
1. Individual, group, and family psychotherapy
2. Cognitive-behavioral therapies
3. Biofeedback and relaxation techniques
4. Hypnotherapy
III. Pharmacotherapy
A. Analgesics
1. Nonopioids
2. Opioids
3. Adjunctive drugs
B. Antidepressants
C. Sedative-hypnotics
D. Benzodiazepines
E. Others
IV. Specific types of painful conditions to be included in the fellow’s educational program
A. Pain associated with cancer, including issues of death and dying, palliative care, and hospice care
B. Postoperative and post-trauma pain
C. Pain associated with nervous system injuries
D. Pain associated with chronic disease
E. Pain of unknown causation
65
F. Pain in children
G. Pain in the elderly
V. Regional pain syndrome to be included in the fellow’s educational program
A. Headache
B. Facial pain syndromes
C. Neck and upper back pain
D. Low-back pain
E. Extremity pain syndromes
F. Pelvic and perineal pain
66
Section II - Chapter 6 - Organization of Palliative Care Services
Chapter 6 - Organization of Palliative Care Services
RICARDO RUIZ-LÓPEZ
DIEGO BELTRUTTI
ATHINA N. VADALOUCA
MAURO S. NICOSCIA
During the past decade, medical ethical considerations regarding the consequences of developments in healthcare
and medical oncology have led to the general assumption in Western societies that promoting the quality of life
(QOL) and alleviating suffering are almost as important as preserving life. [1]
Moreover, the increasing concerns about economic growth and development of healthcare and the perception that
healthcare policies are determined on the basis of cost-benefit analysis, lay a solid groundwork for the
implementation of multidisciplinary and interdisciplinary teams for the management of patients with advanced
diseases, whose QOL is considered the principal goal of medical therapy.
Palliative care units and hospices are found today in every country of the Western world. There are practical
variations in most countries because these services have been modified appropriately to meet specific cultural needs
and models of local healthcare systems.
This chapter covers the definition of QOL, the relief of pain and other symptoms as a major issue in the
management of cancer pain, the structure and functions of the palliative care team, and the integration of levels of
care.
Definition of Quality of Life
The concept of QOL was introduced as one of the goals of medical treatment in the late 1970s as a result of surveys
conducted in the United States. This concept emerges from the development of Western health policies over the
[2] [3] [4]
past 50 years, ranging from restoration of welfare to objectives related to psychosocial needs.
Although there is no universally accepted definition for this concept, QOL could be considered the functional effect
of an illness and its therapy on a patient as perceived by the patient.
The World Health Organization’;s definition of health as being “a state of complete physical, mental, and social
[5]
well-being and not merely the absence of disease” focuses on the issue of the wholeness of life and the importance
of the psychosocial component.
Although some definitions indicate that terms such as happiness and satisfaction are integral elements, others
mention that measures of sociopersonal balance or QOL should include physical, social, and emotional functions,
attitudes toward illness, and personal features of the patient’;s daily life, including family interactions and the cost of
illness. Some definitions of QOL treat it as related to the individual’;s own perception, emphasizing that the
[6]
breadth of the term covers many aspects of life. [7]
When applied to patients with cancer pain, the term should encompass different clinical dimensions, providing a
framework in which physical toxicity (physical impairment, body image, and function) as well as psychological,
social, spiritual, cultural, and philosophical factors interact in a way specifically individualized to the patient and
changing with the evolution of the disease.
Therefore, QOL measures the difference, during a particular period of time, between the individual’;s hopes and
expectations and the individual’;s actual experience. According to Calman, four stages of action are required to
[8] [9] [9]
modify the QOL:
1. The problems and priorities of the individual must be assessed and defined.
2. The patient should be fully involved in formulating the plan of care. This step involves a comprehensive
discussion with patient and family and requires the patient’;s insight into the dynamics of the situation.
67
3. The action plan must be implemented by either the patient or the caring team. This goal may be
accomplished by lessening the patient’;s physical symptoms, altering the patient’;s psychological status, or
reducing expectations but allowing the patient to retain hope.
4. An evaluation must be made of the results of the intervention and the patient’;s situation must be
reassessed.
TABLE 6-1 -- COMMONLY IDENTIFIED DIMENSIONS OF QUALITY OF LIFE

Physical concerns Treatment satisfaction
Functional ability Future orientation
Family well-being Sexuality/intimacy
Emotional well-being Occupational functioning
Spirituality Social functioning
From Cella DF, Tulsky DS: Measuring quality of life today: Methodologi cal aspects. Oncology 4:29–38, 1990.
A comprehensive view of palliative medicine requires that QOL be considered with regard to the specific disease
and the treatment of symptoms. This involves not only patients in advanced stages of the disease but also those in
the early stages, when more aggressive therapies are usually performed.
Calman described QOL in relation to the size of the gap between an individual’;s expectations and the reality of
those expectations: the smaller the gap, the better the QOL. According to this model, a patient’;s QOL can be
[8]
influenced either by a change in the actual condition or by a change in expectations. There are many ways of
conceptualizing QOL, and, during the past years, a number of questionnaires have been developed. Cella and Tulsky
define 10 distinct issues to be measured, although these dimensions need to be categorized and validated in a
hierarchy model ( Table 6-1 ).
The Relief of Pain and Other Symptoms as a Major Issue in Cancer Care
Various surveys show that pain is experienced by 30% to 60% of cancer patients during the active period of the
therapy and by more than 75% of patients with advanced disease. Thus, alleviation of pain is directly linked to
[10]
achievement of QOL, because pain interferes with physical functioning and social interaction and is associated with
psychological distress. [11] [12] [13]
Continuous pain can interfere with the patient’;s ability to eat, sleep, think, and interact with others. Unbearable
[14] [15]
pain, whether “difficult” or “refractory,” is a major risk factor in cancer-related suicide. [16] [17]
The effective alleviation of pain in cancer and other advanced stages of degenerative diseases is acknowledged by
the World Health Organization (WHO) as a major goal of medicine and medical care, requiring knowledge of [18]
ethical principles and specific training in pain medicine.
The right to alleviation of avoidable pain is derived from the universal concepts of maximal respect for human
beings and is attached to the concept of human ethics. Thus, the relief of pain in cancer and other progressive
diseases in advanced stages is a collaborative task among the different agents involved in patient care. This
interaction includes government agencies, medical and nursing schools, hospitals, healthcare organizations,
physicians, nurses, and other health professionals.
The selection of potentially harmful therapies that may occasionally prolong life, such as radical radiotherapy or
systemic chemotherapy in patients with advanced incurable disease, may cause harm to most patients, and ethical
issues may not be properly addressed. In such cases, treatment protocols must be planned, comprehensible patient-
family information packages must be provided, and clearly worded consent procedures must be offered. Emphasis
on QOL criteria is considered essential. [19] [20] [21] [22] [23] [24] [25] [26]
Leaders in both palliative care and other aspects of cancer are reluctant to encourage integration of their respective
areas. Oncologists and palliative medicine physicians may think that collaboration or clinical integration could
[27]
distort therapeutic objectives and lead to dilution of resources. This confusion can provoke an unfair situation that
affects both patients and families, being a source of misinformation and establishing an unavoidable barrier to
appropriate care.
68
The relief of pain and palliation of symptoms has been traditionally considered as a medical treatment for the last
days of life, when symptoms are much more prominent and more difficult to control. The WHO, in its definition of
palliative care, states: “Palliative care … affirms life and regards dying as a normal process, … neither hastens nor
postpones death, … provides relief from pain and other distressing symptoms, … integrates the psychological and
the spiritual aspects of care, … offers a support system to help patients live as actively as possible until death, …
offers a support system to help the family cope during the patient’;s illness and in their own bereavement.” This
expanded definition of palliative care relates to the previous WHO definition which affirms, “The goal of palliative
care is achievement of the best quality of life for patients and their families. Many aspects of palliative care are also
applicable earlier in the course of the illness in conjunction with the anticancer treatment.” [18]
Structure and Functions of the Pain and Palliative Care Team
Specialized care of persons with cancer and other irreversible diseases has undergone major changes during the past
three decades ( Table 6-2 ). Although the concept of medical effectiveness can be greatly modified by both
physicians’; attitudes and environmental concerns, the organizational issues and the philosophy of a modern pain
and palliative care team are not dissimilar
TABLE 6-2 -- SCHEMATIC ORGANIZATION AMONG PAIN AND PALLIATIVE CARE SERVICES; LEVELS OF CARE AND PATIENTS
From Ruiz-López R: Continuous care of cancer pain patients. In Aronoff GM (ed): Evaluation and Treatment of Chronic Pain. 3rd ed. Baltimore, Williams &
Wilkins, 1998.
to those postulated by J. J. Bonica in his early work, when he stated, “Complex pain problems can be treated more
effectively by a multidisciplinary/interdisciplinary team, each member of which contributes with his or her
specialized knowledge and skills to the common goal of making a correct diagnosis and developing the most
effective therapeutic strategy.” [28]
The development of the hospice movement over the past 50 years has provided interdisciplinary care to patients and
families at home, establishing inpatient units for palliative care in local hospitals or in specialized institutions. [29] [30] [31]
In either type of setting, the multidisciplinary/interdisciplinary team plays a major role in providing medical
[32]
treatment and psychosocial support as well as attending to the spiritual needs of patients and their families. [33] [34] [35]
THE MULTIDISCIPLINARY TEAM
Multidisciplinary care of cancer pain patients must be active and continuous. Their physical, psychological, social,
and spiritual needs should be considered, because the multiple issues that these patients and their families encounter
usually exceed the expertise of a single practitioner or caregiver.
In this type of team, members with diverse training interact as a group of individuals, with the common purpose of
working together and sharing the main goal of improving the QOL of the patient. Team members have particular
expertise and training and make individual decisions within their area of responsibility. Teamwork does not mean
69
joining healthcare workers together in one room; nor is it the same as collaboration. Information must be the key
issue for interaction of members and must be shared by the vehicle of the clinical record. [36]
Structure of a Multidisciplinary Team
The structure of the multidisciplinary team varies with the development of the program of care, its objectives and
goals, the availability of resources, and the type of setting, be it in home, hospice, or hospital. The patient and family
should be considered as members of the team.
PHYSICIAN
The most important challenge—and the first to be considered—is the relief of pain and other symptoms. Thus, the
physician plays a central role on the team. The physician must be competent in general medicine, know the
principles and practice of care, and understand malignant disease and any other disease represented in the patient
population, such as acquired immunodeficiency syndrome or degenerative neurologic diseases. Ideally, the
physician should have specific training in palliative medicine and skills in pain management, including surgical and
anesthesiologic procedures. This assertion suggests that a team must be comprised of physicians from a wide variety
of specialized backgrounds, such as anesthesiology, neurosurgery, oncology, psychiatry, internal medicine, and
family medicine among others.
Physicians may play various roles, which include managing pain and symptoms for an individual patient, being
responsible for medical assessment and coordination, training and supporting the multidisciplinary team, and
ensuring coordination of care of the individual patient. Other physicians may act only as consultants, being
coordinated by the attending physician of the patient.
PSYCHOLOGIST
The role of the psychologist is to perform a first evaluation of the status of patient and family, focusing on personal
problems of illness, disability, and impending death. The psychologist must deal with the patient’;s and relatives’;
emotional needs. The psychologist should cover the patient’;s and family’s understanding of diagnosis, prognosis,
and expectations, the strengths and resources available to the family, the problems precipitated by the terminal
illness, past losses and the way they were handled, particular cultural factors, and expectations and plans for the
future.
The psychologist should help the team when there is dysfunction within the family and participate in the patient’s
symptom control by teaching and assessing relaxation techniques, imagery, distraction techniques, and strategies for
coping.
NURSE
The nurse is the team member who is most likely to visit the patient and family at home or in the inpatient
institution. The nurse’s role begins with examination of the details of physical care: bathing, control of odor,
pressure areas, mouth care, bladder care, bowel care, diet, and fluids. The nurse also provides any information
needed to maintain good hygiene. The nurse’s other responsibilities include organizing the patient’s environment to
minimize loss of control, observing what brings comfort and relief, reporting the patient’s response to medical
treatments or secondary effects, and instructing the patient and family about the medication plan.
SOCIAL WORKER
The social worker’s goals are to assist the patient to develop skills in dealing with the social problems of illness,
disability, and impending death; to link the patient with the community; and to establish practical aid for peer
support.
CHAPLAIN
A sympathetic chaplain who is a skilled listener is a key team member. Sometimes, the patient has feelings of guilt
about past events, a sense of meaninglessness, and a perception that life is unjust. Faith may be questioned. The role
of the chaplain is to listen, facilitate past recollection, deal with regrets, offer spiritual counseling, and help to make
the patient ready for what lies ahead.
70
For a patient with an established tradition of religious rituals and sacraments, the chaplain’s role on the team can be
very meaningful. Therefore, pastoral counseling should be made available, and pastoral care members should
become familiar with information about community resources that provide spiritual care and support.
PHYSICAL THERAPIST
Rather than attempting to improve the patient’s function, the goal of the palliative care physiotherapist is to help
plan activity oriented to maximizing the patient’s diminishing resources. This can be accomplished by active or
passive range of motion exercises that the bedridden patient can perform to prevent contractures and improve
circulation, massage to relax aching muscles, treatment of lymphedema, instruction in transfers or positioning, and
the use of physical therapy for the alleviation of pain.
OCCUPATIONAL THERAPIST
The occupational therapist’s role is to maintain autonomous functions such as control of self-care needs, including
such activities as grooming, feeding, dressing, and moving about. The occupational therapist also assesses functions
with which the patient needs assistance and those that the patient can still perform autonomously. The therapist
should provide adaptive equipment or functional splints, and treatments should be changed in accordance with the
patient’s status. In the inpatient setting, the focus of the occupational therapist on leisure can help to restore a sense
of normal living through the introduction of corrective measures to help the patient adapt residual capacities to
maintain the activities of daily life.
VOLUNTEER
The volunteer’s roles vary according to the patient’s setting, although the focus is on improving the QOL, to provide
a supportive presence that may facilitate communication, and to assist with the normal activities of daily living.
Volunteers should be carefully selected and specifically trained by the pain and palliative care team.
Cancer Pain and Palliative Care: The Continuum Hospital-Hospice Model
One of the most challenging tasks in care of patients with cancer pain is to ensure the delivery of specialized
services throughout the different settings where the patient will be managed during the course of the disease. Most
patients need specialized care in two or more settings because there is an increasing movement in industrialized
countries to enable persons with advanced disease to live until death at their maximal potential, letting patients end
their lives in the setting most appropriate to them and their families. Therefore, a major objective of care in cancer
pain management is, whenever possible, to help patients to reach the limit of their physical and mental capacities
with the highest level of autonomy in their own environments.
The provision of continuity of care with such terms is conditioned by the availability of resources and, mainly, by an
effective communication within the team, including the patient and family.
The place of death and quality of care are among the most important concerns for the patient and family. Until the
19th century, people died where they had spent their lives or where they wished. During the 20th century, because of
different conceptual assumptions, in Western societies, the place of dying has changed from the home to the
hospital, which, in many cases, is not the preference of the patient.
In 1965, in the United Kingdom, 63% of deaths occurred in the hospital compared with 73% in 1987. In the United
States, in 1957, 70% of deaths occurred in the hospital. In Italy, 72% of the deaths occurred in the hospital in 1986
as opposed to 67% in 1990. In Israel, 29% of terminal patients currently die in hospital, 41% at home, and 31% at
institutions for chronic diseases. The availability of home care services in Western Australia has allowed 70% of
patients to die at home.
If the patients are asked where they would like to spend the last days of their lives, the majority answer that they
want to be at home.
HOSPITAL
Since the 19th century, technology and industry have developed enormously, and life expectancy has doubled. In the
20th century, the hospital setting became a place designed to recover health and manage treatable diseases. Healing
71
and prolongation of life have been assumed to be the hospital’s main objectives. There seems to be no time or space
for patients who do not get well. On the other hand, society seems to be trying to eliminate death from its style of
life, and dying persons are sent to the hospital to keep them far from the center of the family.
Today, the hospital setting has to be considered as one important step for the multidisciplinary team in some
circumstances. The hospital is the place where specific palliative therapies can be administered (e.g., radiation
therapy, transfusions) and where difficult-to-control symptoms such as pain can be managed. In some cases, an
admittance to the hospital is needed to perform a surgical procedure, such as nerve block, for the alleviation of pain.
A patient with delirium sometimes requires hospital admission so that a quick and correct diagnosis of the cause of
the delirium can be made and so that treatment can be provided if it is feasible. Severe dyspnea stemming from
pleural effusion or other causes can require thoracocentesis in hospital. Difficult ulcers (paraneoplasic vasculitic
syndromes), ischemic complications, or other miscellaneous conditions can be more effectively controlled in a
hospital setting. In any case, the hospital stay should not be prolonged.
Other causes of hospital admission can arise from the family situation, such as poor coping or extreme anxiety as
well as distressing symptoms such as severe dyspnea, neoplasic ulcers, or agony. The patient who lives alone and
has no means to acquire a caregiver sometimes requires hospital or hospice admission. Finally, the patient may
make the decision to stay in the hospital.
The best way to achieve good results, without the disadvantages of a hospital setting for a terminally ill cancer
patient, is to create a palliative care unit (PCU) in a local hospital. Some hospitals have a PCU, which avoids many
of the problems of the traditional hospital model. To resolve problems that appear during the disease, the team
members must be trained in the treatment and control of the advanced disease and in the integral care of the patient
and family. Communication skills are vital; loss of communication usually means that the patient becomes merely a
care receiver instead of an active participant in the decision making. The team must have time to dedicate to the
patient and family. The patient has to become familiar with the PCU team. The environment must be adequate to
allow some degree of independence, and privacy must be maintained. Usually, the hospital is a hostile place for the
patient who ignores hospital regulations. Also, privacy during family conferences is important, and a special room
for this purpose is desirable to avoid discussions in the corridor. The PCU must have special equipment but not
sophisticated technology. The concept of “nothing more can be done” must be abandoned, and inadequate
therapeutic attempts or prolongation of agony should be avoided.
HOSPICE
The first hospice where modern medicine was applied to terminal patients in a rational and scientific manner was St.
Christopher’s Hospice in London ( Table 6-3 ). The human component was not forgotten, and pain management was
fundamental. It was the beginning of palliative care as we know it today, and from this beginning the hospice
movement expanded throughout the world. [35] [36]
The main purpose of the hospice is to take care of the human being who is ill with no possibility of healing. Its
principal objective is to treat patients as whole
TABLE 6-3 -- LIST OF ELEMENTS BROUGHT TOGETHER AT ST. CHRISTOPHER’s HOSPICE

Beds integrated in local community
Development and monitoring of symptoms control
Family support
Bereavement service
Home care
Research and evaluation
Education and training
From Saunders C, Bains M: Living with Dying: The Management of Terminal Disease. Oxford, England, Oxford University Press, 1983.
persons, enabling them and their families to participate in decision making. The major principles of the hospice
setting are symptom control; rehabilitation; attention to psychological and spiritual needs; allowing patients and
families together to choose where patients will live during the final phase of their diseases and where they will die;
72
maintaining good communication among team members, including patients and their families; and giving support
during agony, providing accessibility to staff, and allotting enough time to comfort patients.
Palliative care teams have developed skills that have enabled previously hospital-bound patients to return home,
with use of techniques such as spinal analgesic delivery systems, pump-delivered subcutaneous medications, and
continuous care of regular symptom management by doctors and nurses at the patients’ homes.
Data on 3362 patients cared for by St. Christopher’;s Hospice between 1972 and 1977 showed that only 1% reported
continuous pain, although more than three quarters of the patients had arrived at the hospice with pain. Cicely [31]
Saunders recognized that the achievement of such results, however, can provoke “staff pain,” resulting from
prolonged exposure to the suffering of patients and families who are facing death. Although she acknowledged and
described the need for formal staff support, she argued that, “The resilience of those who continue to work in this
field is won by a full understanding of what is happening and not by a retreat behind a technique.” [32]
HOME
The home setting offers several advantages for the patient. It helps patients to maintain their social and family roles,
to use their time as they wish, and to develop personally satisfying eating and sleeping habits.
Changing habits in the final days of life can lead to suffering and stress. Furthermore, patients at home can preserve
privacy, can go on with occupational activities, and are in a familiar environment. Family members feel more
satisfied because they can actively participate in giving care and in showing respect for the patient’;s wishes.
Home care as a part of continuous care of the cancer patient benefits the health system by decreasing the number of
hospital admissions, shortening hospital length of stay, and providing quality of care according to modern ethical
principles.
For a patient to be kept in the home, some conditions must be fulfilled ( Table 6-4 ): round-the-clock specialized
care by the palliative care team must be available; the patient and relatives must be instructed on all issues related to
the illness and its complications; information about home remedies for the appropriate management of pain and
other symptoms must be provided; appropriate technical support for medical equipment must be given; and there
must be written information about the use of medication.
The patient and family must be assured that admittance to an institution is available if the clinical situation cannot be
controlled at home.
A bereavement program that provides care of the family after the patient’;s death is crucial. If a family has specific
difficulties immediately after the patient’;s death, referral to community peer support groups or specialized
counseling must be given.
Conclusions
The importance of palliative medicine is expected to increase in upcoming years. For full coverage of the
population, a rational approach is needed that stresses public health rather than institutionalized involvement.
Gaining support for public health involvement should be a priority for the individuals, organizations, and countries
in the worldwide network involved in implementing existing knowledge in palliative care. [37]
The implementation of the WHO recommendations in regard to palliative care could have a major impact on the
QOL of cancer patients. However, strong political motivation and leadership are required to ensure a full
involvement of healthcare systems without extreme expense (Appendix 6–1).
Palliative care in Western societies is considered to be a human right when curative interventions are no longer
indicated. For a large number of less developed
73
TABLE 6-4 -- HOME CARE IN CANCER PAIN MANAGEMENT: CRITICAL ISSUES

24-hour specialized care available
Patient and relatives taught about the disease
Information about home remedies
Appropriate technical support
Written information on the use of medication
countries, palliation should be made available now, even before maturation of the country’;s economy can provide
technical services. An important effort has to be made to encourage legislation that will at least make essential
drugs—including opioids—available to the global population. Education of physicians and health workers in
developing countries must be improved so that these countries can implement their own palliative care teams and
training centers.
REFERENCES
1. Aristotle: Ethics. Harmondsworth, England, Penguin Books, 1976.
2. Aaronson NK, Beckmann J (eds): The Quality of Life of Cancer Patients. New York, Raven Press, 1987.
3. Andrews FM, Withey SB: Social Indicators of Well-Being. New York, Plenum Press, 1976.
4. Campbell A, Converse PE, Rodgers WL: The Quality of American Life. New York, Sage, 1976.
5. World Health Organization Constitution. Geneva, WHO.
6. Spitzer WO, Dobson AJ, Hall J, et al: Measuring the quality of life of cancer patients: A concise QL-index for use by physicians. J Chronic Dis
34:585–597, 1981.
7. Krupinsky J: Health and the quality of life. Soc Sci Med 14a:203–211, 1980.
8. Calman KC: Definitions and dimensions of quality of life. In Aaronson NK, Beckman J (eds): The Quality of Life of Cancer Patients. New
York, Raven Press, 1987, pp 1–9.
9. Calman KC: The quality of life in cancer patients—an hypothesis. J Med Ethics 10:124–127, 1984.
10. Bonica
JJ, Ventafridda V, Twycross RG: Cancer pain. In Bonica JJ (ed): The Management of Pain, 2nd ed. Philadelphia, Lea & Febiger, 400–
460, 1990.
11. Bond MR, Pearson IB: Psychosocial aspects of pain in women with advanced cancer of the cervix. J Psychosom Res 13:13–21, 1969.
12. Daut RL, Cleeland CS: The prevalence and severity of pain in cancer. Cancer 50:1913–1918, 1982.
13. Fishman B: The treatment of suffering in patients with cancer pain: Cognitive behavioral approaches. Adv Pain Res Ther 16:301–316, 1990.
14. Feuz A, Rapin CH: An observational study of the role of pain control and food adaptation of elderly patients with terminal cancer. J Am Diet
Assoc 94:767–770, 1994.
15. Massie MJ, Holland JC: The cancer patient with pain: Psychiatric complications and their management. Med Clin North Am 71:243–258,
1987.
16. Breitbart W: Suicide in the cancer patient. Oncology 1:49–54, 1987.
17. Cleeland CS: The impact of pain on the patient with cancer. Cancer 54:2635–2641, 1984.
18. World Health Organization: Cancer pain relief and palliative care. Technical Report Series 804. Geneva, WHO, 1990.
19. Questionsand Answers About Pain Control: A Guide for People with Cancer and Their Families. Washington D.C., American Cancer Society
and the National Cancer Institute, 1992.
20. Ferrell BR, Rhiner M, Ferrell BA: Development and implementation of a pain education program. Cancer 72(Suppl 11):3426–3432, 1993.
21. The
Wisconsin Cancer Pain Initiative: Cancer Pain CAN Be Relieved: A Guide for Patients and Families. Madison, Wis, The Wisconsin
Cancer Pain Initiative, 1989.
22. The Wisconsin Cancer Pain Initiative: Jeff Asks About Cancer Pain: A Booklet for Teens About Cancer Pain. Madison, Wis, The Wisconsin
74
Cancer Pain Initiative, 1990.
23. Dolore da Cancro e Cure Palliative: Collana Rapporti Tecnici 804. Organizzazione Mondiale de la Sanità. Ginevra, 1990.
24. Manual of Care for Terminally Ill Cancer Patients: Tokyo, Ministry of Health and Japan Medical Association, 1989.
25. FacingForward: A Guide for Cancer Survivors. Rockville, Md, U.S. Department of Health and Human Services, Public Health Service,
National Institutes of Health, National Cancer Institute, 1990.
26. Teamwork: The Cancer Patient’;s Guide to Talking with Your Doctor. Silver Spring, Md., National Coalition for Cancer Survivorship, 1991.
27. Scott J: Canadian Brief on Palliative Care. Presented to Cancer 2000 on behalf of the Canadian Palliative Care Association, Silver Spring, Md.,
1990.
28. Bonica,JJ: General clinical considerations (including organization and function of a pain clinic). In Bonica JJ, Procacci P, Pagni CA, et al
(eds): Recent Advances on Pain: Pathophysiology and Clinical Aspects. Charles C. Thomas, Springfield, Ill, 1974, pp 274–298.
29. Saunders C: Care of patients suffering of terminal illness at St. Joseph’;s Hospice, Hackney, London. Nurs Mirror February 14:vii–x, 1964.
30. Saunders C: The challenge of terminal care. In Symington T, Cater R (eds): The Scientific Foundations of Oncology. London, Heineman,
1964.
31. Saunders C: The philosophy of terminal care. In Saunders C (ed): The Management of Terminal Disease. London, Edward Arnold, 1979.
32. Saunders C: Current views on pain relief and terminal care. In Swerdlow M (ed): The Therapy of Pain. Philadelphia, J.B. Lippincott, 1981.
33. Ventafridda V: Continuing care: A major issue in cancer pain management. Pain 36:137–143, 1989.
34. Parkes CM, Parkes J: Hospice versus hospital care: Reevaluation after ten years as seen by surviving spouses. Postgrad Med J 60:120–124,
1984.
35. Saunders C, Baines M: Living with Dying: The Management of Terminal Disease. Oxford University Press. Oxford, England, 1983.
36. SaundersCMS: Terminal care. In Weatherall DJ, Ledingham JGG, Warrell DA (eds): Oxford Textbook of Medicine. Oxford, England, Oxford
University Press, 1983, p 288(1–28.13).
37. Stjernswärd J: Palliative Medicine—a global perspective. In Doyle D, DWC Hanks DWC, Macdonald N (eds): Oxford Textbook of Palliative
Medicine. Oxford, England, Oxford Medical Publications, 1994.
Suggested Reading
Brody BA (ed): Suicide and Euthanasia: History and Contemporary Themes. Dordrecht, The Netherlands, Kluwer,
1989.
Cassell EJ: The Nature of Suffering and the Goals of Medicine. New York, Oxford University Press, 1991.
Foucault M: The Birth of the Clinic: An Archaeology of Medical Perception. New York, Vintage Books, 1975.
Numbers RL, Amudsen DW: Caring and Curing: Health and Medicine in the Western Religious Traditions. New
York, Macmillan, 1986.
APPENDIX 1: WHO Palliative Care Recommendations
A WHO expert committee on the relief of cancer pain and palliative care has made the following recommendations
to countries for achieving effective palliative care:
1. Governments should establish national policies and programs for palliative care.
2. Governments of member states should ensure that palliative care programs are incorporated into their
existing healthcare systems; separate systems of care are neither necessary nor desirable.
3. Governments should ensure that healthcare workers (physicians, nurses, pharmacists, or other categories
appropriate to local needs) are adequately trained in palliative care.
4. Governments should review their national health policies to ensure that equitable support is provided for
programs of palliative care in the home.
5. In the light of the financial, emotional, physical, and social burdens carried by family members who are
willing to care for cancer patients in the home, governments should consider establishing formal systems of
recompense for the principal family caregivers.
75
6. Governments should recognize the singular importance of home care for patients with advanced cancer and
should ensure that hospitals are able to offer appropriate backup and support for home care.
7. Governments should ensure the availability of both nonopioid and opioid analgesics, particularly morphine
for oral administration. Further, they should make realistic determinations of their opioid requirements and
ensure that annual estimates submitted to the INCB reflect actual needs.
8. Governments should ensure that their drug legislation makes full provision for the following:
• Regular review, with the aim of permitting importation, manufacture, prescribing, stocking, dispensing,
and administration of opioids for medical reasons
• Legally empowering physician, nurses, pharmacists, and, where necessary, other categories of healthcare
workers to prescribe, stock, dispense, and administer opioids
• Review of the controls governing opioid use, with a view to simplification, so that drugs are available in
the necessary quantities for legitimate use
9. With pressure for the legalization of euthanasia likely to increase, governments should make strenuous
efforts to keep fully informed of all developments in the fields of cancer pain relief, palliative care, and
management of terminal cancer.
76
Section II - Chapter 7 - The Practice of Regional Anesthesia in Developing Countries
Chapter 7 - The Practice of Regional Anesthesia in Developing

Countries
RAMANI VIJAYAN
About three quarters of the countries of the world fall into the category of “developing countries,” and four fifths of
the world’s population lives in them. How does one categorize these countries? What is the politically correct
definition of a developing country? The concept of the Third World emerged after World War II as a category to
identify political neutrality in the context of the Cold War, with the distinction originally based on ideologic
commitment rather than conditions of economic development. However, the term quickly became associated with
[1]
economic status and degree of richness or poverty. Hence, the industrial market economy of Western Europe, North
America, Australia, New Zealand, Israel, and Japan made up the First World. The centrally planned economies of
Eastern Europe made up the Second World. Finally, the remaining countries of the world, such as those in Africa,
Asia, the Middle East, the Pacific, Latin America, and the Caribbean, made up the nonaligned Third World. [2]
In the last two decades, the term developing countries has been used largely to identify those countries that have not
yet reached the sophisticated status of industrialized nations such as those of Western Europe and North America. It
also denotes that these countries, in particular the low-income countries, have not achieved an advanced level of
infrastructure development with regard to the provision of clean water, electricity, housing, healthcare, and
education for the large majority of their population. Typically, they have been plagued by poverty, high rates of
population growth, low growth rates of gross domestic product (GDP) and industrialization, high dependence on
agriculture, high rate of unemployment, and uneven income distribution. There is, of course, a very wide range in
[3]
the GDP and per capita income in developing countries. The Overseas Development Administration of the United
Nations divides them into two lists. Part I covers countries such as Bangladesh and Ethiopia that are characterized as
low income (per capita gross national product [GNP] less than U.S. $675 in 1992); low- to middle-income countries
such as Papua New Guinea and Armenia; and upper- to middle-income countries that are relatively rich such as
Greece, Malaysia, and Argentina. Part II covers countries in transition, such as the countries of Central and Eastern
Europe.
Any discussion of the practice of regional anesthesia in developing countries must also take into account the vast
differences in healthcare budgets in developing countries. The main differences between anesthesia in the
prosperous, developed countries and the less affluent developing countries are related to manpower, training,
facilities, equipment, drug availability, and cost of drugs. This difference can be seen even in different parts of the
[4] [5]
same developing country. In some middle-income countries, more favorable national statistics disguise wide
disparities between the conditions of the rural/urban poor and the more affluent urban dwellers who are better
educated and have better access to health services that closely resemble those of industrialized countries. [4] [6]
Anesthesia cannot be separated from the framework of the healthcare system in any given country. It is also linked
to the percentage of the population that lives in rural areas, and the degree of rural development. It is not uncommon
in many rural areas for a pregnant mother to be transported to a health center 100 to 150 km away, crossing a river
or two without bridges. However, the cities and towns in that same country may have excellent facilities typical of
large, thriving communities. When rural facilities and other amenities are scarce, doctors generally congregate in
urban areas, and anesthetic services tend to be provided primarily by trained nurses or other paramedical staff, who
may or may not be taught regional anesthetic techniques. [6]
There are more than 200 developing countries in which the overall population had surpassed 4 billion by the end of
the 20th century. It is estimated to pass 5 billion by 2010. There is marked cultural, economic, and political
[7]
diversity among these countries, and it is difficult to generalize or attempt to categorize the practice of regional
anesthesia without running the risk of being either too superficial or too pedantic. This chapter is a review of some
of the salient and interesting work that has been undertaken in developing countries and published in indexed
journals. It also includes the results of a survey that was conducted in Asian countries in 1999 as well as comments
and personal communications garnered from it.
Regional anesthesia, particularly spinal and nerve blocks, have been practiced for many years in developing
countries. International anesthetic literature, however, does not quite reflect this practice. The reasons for this could
be multifactorial. Papers are often published in local journals, which may not be indexed, and often in languages
other than English. Research and writing require time, sufficient staff, and facilities, all or some of which may not
77
be easily available in many parts of the developing world. The acute shortage of anesthesiologists and the heavy
workload are also not usually conducive to undertaking much research work. Since 1990, however, many of the
countries of East Asia and Latin America have seen phenomenal economic growth. In tandem with this growth,
there have been vast improvements in healthcare allocation and increased sophistication in healthcare delivery
systems. The recent increase in the number of publications from these countries could reflect their growing
affluence. Regional anesthesia covers a large number of different techniques. It ranges from simple procedures such
as local infiltration with local anesthetic agents practiced by surgeons to those that are more complex, such as the
combined-spinal epidural technique.
Regional Anesthesia Administered by Surgeons
Surgeons all over the world use local infiltration anesthesia for minor and intermediate surgery. In many parts of the
developing world, about 30% to 40% of all surgery is performed under local or local-regional anesthesia. The [8] [9]
majority of dental extractions and ophthalmic surgeries are performed under regional anesthesia. Surgeons routinely
use retrobulbar or peribulbar blocks for cataract extraction, which may or may not be supplemented by sedation. [10]
Peribulbar injection, which avoids the serious complications of retrobulbar injection, is widely used for intraocular
surgery and lens implantation. All commonly available local anesthetic drugs, such as lignocaine, bupivacaine, and
[11]
the newer drug, ropivacaine, have been used with or without the addition of hyaluronidase for ophthalmic surgery.
[13] [14]
[12]
Groin surgery accounts for nearly 15% of all general surgery procedures in developing countries and forms a
considerable proportion of the surgical workload. Local-regional anesthesia administered by surgeons is used
[15]
extensively for inguinal hernia repair. When anesthetic services were not available, Nicholls from the Seychelles
[16]
continued to perform inguinal herniorrhaphy using regional anesthesia only. He found the technique was well
tolerated by patients and economical, and he continued using it even after anesthesia became available. Other reports
have also shown that there is widespread use of regional anesthesia for inguinal hernia repair. Soukup and
[17] [18] [19]
Vomacka successfully used local infiltration anesthesia supplemented by sedation in 203 patients undergoing
[20]
percutaneous nephrolithotomy in Czechoslovakia.
Limiting explosive population growth is a national priority in many developing countries, and female sterilization is
one of the more popular methods of family planning. Minilaparotomy to perform tubal ligation under local
anesthesia has been found to be a safe, simple, low-cost, and widely applicable technique suitable for even rural
areas. It has been used extensively in many developing countries, such as Thailand, India, and the Philippines. Apelo
and coworkers from the Philippines reported using local anesthesia in a majority of 2488 women undergoing tubal
[21]
ligation. Local anesthesia was supplemented with sedation initially in the first 650 women but was omitted in later
patients because it was not needed. Of 1546 patients undergoing voluntary sterilization in Nigeria, local anesthesia
was used in 996 patients (64.4%). Occasionally, entire teams of healthcare personnel set up mobile hospitals in
[22]
remote areas to cater to certain specific needs of the rural population. Reichart and coworkers were able to
[23]
successfully perform outpatient laparoscopic tubal ligation on women under local anesthesia in a remote part of
Nicaragua.
The administration of local anesthetic drugs into the subarachnoid space is technically easy because most doctors are
familiar with lumbar puncture. Spinal anesthesia is therefore the regional anesthetic technique that is most often
used by nonspecialists. In many countries, surgeons, medical officers, and nurse anesthetists administer spinal
anesthesia because of the general shortage of trained anesthetists. More than 20 years ago (1977), Ajao and
Adeloye from Nigeria reported their series of 95 patients in whom major abdominal surgery was accomplished
[24]
with minimum complications under spinal anesthesia administered by surgeons. They suggested at that time that all
surgeons working in “peripheral” hospitals should learn to give spinal anesthesia and deal with its side effects!
Inadequate specialist anesthesia service continues up to the present with surgeons providing spinal and epidural
anesthesia for surgery in several parts of the developing world. [25] [26] [27]
Spinal Anesthesia
For several decades, spinal anesthesia has enjoyed great popularity in developing countries. In 1966, El-Shirbiny
and coworkers from Cairo University reported a large series of 20,000 patients who had surgery under spinal
[28]
anesthesia with mepivacaine (carbocaine). The list included all types of general surgical (upper and lower
abdominal), gynecologic, urologic, and orthopedic procedures. High spinal blocks were performed using 2 mL (80
mg) of mepivacaine with the patient placed in a 10-degree to 15-degree Trendelenburg position. Vasopressors were
required only for midlevel and high spinal blocks. A 1976 report from Hungary cites the use of spinal anesthesia
with bupivacaine in 240 patients who required surgery after trauma. There were no serious complications, even
though one third of the patients were elderly and a quarter were in poor general condition. Kosumian from Russia
[29]
78
(1985) reported successful use of spinal anesthesia in 2402 patients in a central regional hospital. Gueguen from
[30] [31]
Senegal reported that 86% of all surgery is performed under spinal anesthesia in his hospital because it has been
found to be a simple and inexpensive technique.
SPINAL ANESTHESIA AND HYPOTENSION (NONOBSTETRIC)
Hypotension is a well-recognized problem associated with spinal anesthesia, and a couple of studies have addressed
this issue. Kafle and colleagues from Nepal investigated the efficacy of oral ephedrine in reducing the incidence of
[32]
hypotension. Two hundred patients undergoing lower abdominal surgery were randomized to receive either oral
ephedrine (30 mg) or placebo half an hour before spinal anesthesia with 3.2 to 3.6 mL of 0.5% heavy bupivacaine.
Both groups had a volume preload with 10 mL/kg of crystalloid solution. The total dose of intraoperative
intravenous (IV) ephedrine supplement was significantly less (P < 0.01) and the number of patients requiring the
supplement was significantly less in the group given oral ephedrine (P < 0.01). None of the patients in the treated
group exhibited any signs of excitation. Prophylactic oral ephedrine appears to be a simple method of curtailing
hypotensive episodes in patients undergoing spinal anesthesia who are classified by the American Society of
Anesthesiologists (ASA) at levels I and II.
Baraka and coworkers from Lebanon compared the influence of prehydration with either hypertonic saline (3%
[33]
NaCl solution, 7 mL/kg) or normal saline (7 mL/kg) on hemodynamic changes and serum sodium concentration in
33 patients undergoing transurethral resection of the prostate under spinal anesthesia. The incidence of hypotension
was less with hypertonic saline, but the difference was not significant. The central venous pressure was significantly
elevated before spinal anesthesia in the hypertonic group, but there was no difference in the serum sodium levels
between the two groups. Although hypertonic saline can be used to prevent the dilutional hyponatremia associated
with surgery for transurethral resection of the prostate, caution should be exercised in the presence of left ventricular
dysfunction.
VOLUME AND BARICITY OF LOCAL ANESTHETIC DRUGS
There appears to be considerable debate about the optimal volume and baricity of local anesthetic solutions that are
needed to provide spinal anesthesia. Several studies have been published to determine the most effective volume and
type of local anesthetic drugs that can ensure adequate spinal anesthesia for various types of surgery. Table 7-1
shows a summary of studies that have investigated the extent of sensory and motor blocks with different volumes
and types of local anesthetic agents.
Attygalle and Rodrigo used the sitting position to administer hyperbaric cinchocaine (2 mL), diluted to either 6 or
[34]
8 mL, to two groups of patients who were taller than 150 cm. A significantly higher level of sensory block was
noted with the 8 mL volume (P < 0.001), but there was no correlation with the height of the patient. In a subgroup of
patients shorter than 150 cm who were given 6 mL of diluted cinchocaine, there was a significant correlation
between the patient’s height and the upper level of sensory block achieved. The study showed that the height of a
patient should be taken into consideration for short patients when deciding the volume of anesthetic solution in
spinal anesthesia. Tay and coworkers investigated three different volumes of dilute bupivacaine 0.125%
[34] [35]
(obtained by diluting 0.5% bupivacaine with normal saline) in 30 patients undergoing postpartum tubal ligation. The
bupivacaine was administered with the patients in a lateral position. A sensory level up to T10 was reliably obtained
with 8 and 10 mL for the duration of the surgery, but not with 6 mL. The incidence of high sensory blockade was
higher with 10 mL. The optimal volume of bupivacaine 0.125% was found to be 8 mL, and this volume could be
recommended as a test dose for epidural analgesia for labor.
Amponsah studied the effect of different volumes of lignocaine 2% for spinal anesthesia in 70 patients undergoing
[36]
lower abdominal and lower limb surgery. The volumes used were 3.0, 3.5, and 4 mL. The levels of sensory blockade
were adequate for the intended surgery, and there was no significant difference in the mean levels of analgesia and
duration of sensory and motor blockade among the three groups. In another study using plain lignocaine 2%,
Imbelloni and Carneiro from Brazil investigated the effect of posture on the extent of sensory blockade. One
[37]
hundred patients were divided into two groups to receive a fixed dose
79
TABLE 7-1 -- SPINAL ANESTHESIA: THE EFFECT OF DIFFERENT VOLUMES AND CONCENTRATION OF LOCAL ANESTHETIC
DRUGS ON THE EXTENT OF BLOCK
Local Anesthetic Type of Surgery Number
Researchers/Country Investigated of Patients Investigation Result
[34]
Attygalle & Rodrigo, Cinchocaine hyperbaric 2 Lower abdominal surgery Effect of varying volumes Significantly higher
1985/Sri Lanka mL No. = 83 Correlation with height sensory block with 8 mL
Diluted with CSF Significant correlation
3 groups: up to 8 mL, 6 between height and
mL, 6 mL (<150 cm, ht) sensory levels in patients
<150 cm
Tay et al.,[35] Bupivacaine 0.125% Postpartum tubal ligation Optimum volume for Optimum volume = 8 mL
1992/Singapore 3 groups—6, 8, 10 mL No. = 30 surgery
Amponsah,[36] 1993/ Lignocaine 2% Lower abdominal/ lower Effect of different volumes No significant difference
Nigeria 3 groups—3.0, 3.5, 4.0 mL limb on extent of block
No. = 70
Cherng et al.,[38] Bupivacaine 0.5% Urologic and orthopedic Effect of CSF dilution on No significant difference
1998/Taipei Diluted with CSF surgery extent or block
3 groups—none, 1 mL, 2 No. = 60
mL
Imbelloni et al.,[37] 1998 Lignocaine 2% General and orthopedic Effect of posture at Significantly greater spread
Brazil 2 groups—sitting, lateral No. = 100 induction with sitting position
of 4 mL of lignocaine 2% either in the sitting or lateral position. The spread of sensory block and analgesia was
significantly greater for those in the sitting posture than for those in the lateral position. Lignocaine 2% was found to
be effective for spinal anesthesia in both studies, indicating that it is a useful alternative to lignocaine 5%, which has
come under suspicion for neurotoxicity.
In another prospective study, Cherng and coworkers from Taipei studied the effect of diluting bupivacaine plain
[38]
0.5% with cerebrospinal fluid in 60 patients undergoing urologic and orthopedic surgery. Patients were divided into
three groups and received either 3 mL of bupivacaine 0.5% or the same volume diluted with 1 or 2 mL of
cerebrospinal fluid in the lateral decubitus position. There was no significant difference among the three groups with
regard to onset time, maximum cephalic spread, duration, and two-segment regression of the sensory block. The
only difference was the time to reach maximal motor block, which was significantly shorter in the undiluted group
but had no clinical relevance.
Outpatient surgery has become increasingly popular owing to lower costs and more efficient use of hospital beds.
Spinal anesthesia is not usually considered an appropriate technique for day surgery because the residual motor
block associated with it precludes early ambulation and discharge. Postdural puncture headache (PDPH) may be
another reason. Liew and his colleagues from Singapore studied the efficacy of lignocaine 0.5% in day case
[39]
surgery. Thirty women undergoing minor gynecologic procedures were allocated to two groups and received 5 mL
of lignocaine 0.5% (total dose of 25 mg) with either a 26-gauge (G) Atraucan (pencil point) or 29-G Spinocan
(cutting bevel) needle. A sensory block up to T10 was obtained in 93% of patients. The mean time for the onset and
duration of sensory block was 8 minutes and 32 minutes, respectively. Motor power returned within 1 hour, and all
patients were discharged on the same day. There was no incidence of postoperative headache. Lignocaine 0.5%
provided reliable analgesia with fairly rapid onset and early return of motor power and was found to be suitable for
minor gynecologic outpatient surgery.
The distribution of a hypobaric solution in the spinal canal depends on posture. Patient position can be used to
restrict the spread of local anesthetic solution and provide selective sensory block. Maroof and colleagues from [40]
Riyadh studied the effect of hypobaric bupivacaine 0.1% for anorectal surgery. Twenty adult male patients were
positioned prone in a jackknife position, with an operating table break angulation of 30 degrees and head down tilt
of 20 degrees. Dural puncture was performed with the patient in this position, and 5 mL of bupivacaine 0.1% were
injected into the subarachnoid space at the L3 to L4 interspace. Surgery was performed without changing the
patient’s position. All patients enjoyed excellent operative analgesia. The onset of sensory block took a mean of 5.3
minutes, with the highest sensory level at T10. There was no motor block, cardiovascular stability was well
maintained throughout surgery, and the time to first postoperative analgesia was a mean of 339 minutes.
SPINAL ANESTHESIA AND SEDATION
Benzodiazepines are commonly used for sedation and anxiolysis during regional anesthesia. Ketamine is widely
used in many developing countries, either as a sole anesthetic agent or to provide additional analgesia for procedures
done under local anesthesia. Tripathi and Saxena (India) compared the effects of a combination of diazepam and
[41]
80
ketamine with diazepam and placebo in providing comfort to patients undergoing spinal anesthesia. One hundred
patients were randomly divided into two groups. The first group was given diazepam 0.1 mg/kg bolus followed by a
bolus of ketamine 0.5 mg/kg and an infusion of 0.5 mg/kg/hour of ketamine. The second group was given the same
dose of diazepam followed by a placebo. The addition of ketamine significantly improved the quality of anesthesia
and the patients’ acceptance of the technique, without any increase in side effects.
Akinyemi and coworkers conducted a survey among 200 Nigerian patients in the postoperative period to determine
[42]
whether patients preferred general or regional anesthesia. There was an equal distribution between men and women,
and all the patients were interviewed between 2 and 7 days after surgery. Most of the patients (59.5%) preferred
general anesthesia because they were afraid to be awake during surgery, although many of them were not really
given a choice. Fear of being awake and feeling pain appears to be a universal feeling and is not really related to any
degree of sophistication in a population. Assurance of intraoperative sedation in addition to adequate preoperative
explanation should also allay patient anxiety, reduce apprehension, and possibly improve the rate of acceptance of
regional anesthesia among patients.
Benzodiazepines, however, should be used with caution in elderly patients, because sedation during regional
anesthesia can lead to episodes of life-threatening hypoxemia.
In a prospective, double-blind, randomized study, Munoz and colleagues from Chile investigated the effect of
[43]
benzodiazepines in 80 elderly patients having surgery under spinal anesthesia. Patients were divided into four
groups, with one serving as a control and the others given 1 mg flunitrazepam, 1 mg lorazepam, and 7.5 mg
midazolam, respectively. Patients who were alert and had a sensory block below T7 had a significantly lower
incidence of hypoxemic episodes than patients who were drowsy and had an anesthetic level above T7. Episodes of
hypoxemia did not correlate with any other factors, such as age, weight, ASA physical status, or position of the
patient. All episodes of desaturation were easily corrected by supplemental oxygen. Oral premedication with
benzodiazepines should be used with caution in elderly patients. Monitoring during surgery should include pulse
oximetry, and supplemental oxygen should be provided for all patients, especially if they are sedated.
In an interesting study, Vale and coworkers (Brazil) investigated circadian variations in the cephalic spread of a
[44]
fixed dose of lignocaine and bupivacaine in 55 patients undergoing spinal anesthesia. Patients who were given a
spinal anesthetic in the morning had a longer latency and a significantly lower level of sensory block compared with
patients who had the spinal anesthetic in the afternoon. The afternoon group also required more pharmacologic
support for hypotension. There was no obvious explanation for these results. Further studies need to be done to
decide whether circadian variation has any significant implications in clinical practice.
COMPLICATIONS OF SPINAL ANESTHESIA
Haleem and colleagues from India studied audiometric changes after spinal anesthesia using different sizes of
[45]
needles. One hundred and twenty-five patients were randomly divided into five groups to receive spinal anesthesia
with five different sizes of spinal needle: 20-G, 22-G, 23-G, 24-G, and 25-G. All patients had baseline audiometric
values recorded at 250 Hz to 500 Hz before surgery. Patients who received spinal anesthesia with 20-G and 22-G
needles had a significant decrease (12% and 8%) in audiometric values on the first postoperative day (P < 0.001).
These alterations returned to normal values by the fifth postoperative day. A significant alteration (8% decrease)
was also noted in the group with 23-G needle (P < 0.05). There was no significant decrease in audiometric values
after spinal anesthesia with the smaller 24-G and 25-G needles. Besides reducing the incidence of PDPH, small-
gauge needles can also minimize audiometric alterations associated with spinal anesthesia.
In a similar study from Turkey, Oncel and coworkers used pure tone audiometry to investigate vestibulocochlear
[46]
dysfunction after central neural blockade. Forty-five patients (age range 23 to 84 years) undergoing urologic surgery
were divided into three groups and received either epidural anesthesia or spinal anesthesia with a 22-G or 25-G
spinal needle. Pure tone audiometry was performed before surgery and repeated on the third and fourth
postoperative days. No statistically significant hearing loss was noted in the epidural group, but the hearing loss in
the 25-G group was significantly less than in the 22-G group (P < 0.01). None of the patients suffered from either
headache or cranial nerve lesions. Audiometry was found to be a more sensitive indicator of cerebrospinal fluid
leakage than headache. Elderly patients often have preexisting hearing impairment, and the use of the 22-G needle
for spinal anesthesia may temporarily make it worse. Every effort should, therefore, be made to use smaller needles,
even in this group.
PDPH continues to be reported with an incidence between 2.8% and 13.9% in different series, indicating the
extensive use of spinal anesthesia for surgery. Epidural blood patches have been considered as the treatment of
[47] [48] [49]
choice for the headache after dural puncture. Pedrosa and coworkers from Brazil successfully treated 60 patients
[50]
81
suffering from PDPH, aged 18 to 42 years, with epidural blood patches, using 10 mL of autologous blood. All
patients could be discharged within 24 hours of receiving the patch. An alternative method for treating headache
after spinal anesthesia was described by Tsenov from Bulgaria. The author used acupuncture to treat PDPH in 35
[51]
women after spinal anesthesia for cesarean section. Thirty out of 35 (85%) of the patients needed only one
treatment, and it was effective in all after three treatments.
Epidural Anesthesia
The incidence of PDPH after spinal anesthesia led to the popularity of epidural anesthesia. Long-acting local
anesthetic drugs, epidural catheters, and the ability to extend anesthesia for prolonged surgery have resulted in a
widespread use of epidural anesthesia for surgery. Epidural and spinal anesthesia are less
[52] [53] [54] [55] [56] [57] [58] [59] [60] [61]
expensive than general anesthesia. This could be an added incentive for their widespread use in developing countries
(see survey discussed later in this chapter).
Xie and Liu conducted a survey of the practice of epidural anesthesia in China. Questionnaires were sent to 237
[59]
hospitals over six geographic areas, including some military hospitals. The response rate was 38% (90 hospitals).
There were 1,304,214 documented epidural blocks in these hospitals. The percentage of blocks performed at
different levels of the spine is shown in Table 7-2 . This survey revealed that epidural anesthesia was used
extensively in China for various types of surgery, ranging from the neck to the lower extremities. The success rate
was 98%, and the incidence of accidental dural puncture was 0.32%. The incidence of total spinal anesthesia as a
complication was reported to be only 0.013%, and about half of these cases required intubation and ventilation.
In a retrospective study, Liu and coworkers reviewed patients undergoing surgery for primary hyperparathyroidism
[61]
TABLE 7-2 -- SURVEY OF THE USE OF EPIDURAL ANALGESIA IN CHINA

Type of Epidural Anesthesia Percentage
Lumbar epidural 38.8
Lower thoracic 32.0
Middle thoracic 23.0
Upper thoracic 4.6
Cervical 1.6
Accidental dural puncture 0.32
Incidence of total spinal anesthesia 0.013
Incidence of respiratory depression 0.54
Modified from Xie R and Liu YP: Survey of the use of epidural analgesia in China. Chin Med J (Engl) 104(6):510–515, 1991.
in Beijing from 1980 to 1989. They noted that nearly two thirds of the operations were performed under continuous
cervical epidural anesthesia, with satisfactory results in 90% of them. General anesthesia was reserved for
complicated cases and patients who had undergone cervical spine surgery. In another 10-year retrospective study,
Guo reviewed 763 patients who had received continuous cervical epidural block for surgery. The technique
[60]
provided satisfactory analgesia at low cost with no air pollution in the operating theatre. They found, however, that
the conduct of cervical epidural anesthesia required a high degree of skill, both in insertion of the catheter and in
intraoperative management.
Surgery of the anal canal for fistulas and fissures in ano is quite common. Maintenance of anal sphincter tone during
surgery is important, as it helps the surgeon delineate the extent of surgery that is required without risk to the
sphincter. A spinal anesthetic provides excellent analgesia but is not suitable owing to complete loss of sphincter
tone. Although it is possible to maintain tone with a light general anesthetic, laryngospasm can be a problem.
Kausalya and Jacob from India investigated the efficacy of low-dose epidural anesthesia in surgery of the anal
[62]
canal and compared it with the efficacy of general anesthesia. Fifty adult patients were randomized to receive either
lumbar epidural bupivacaine 0.375% (12 to 16 mL) or a general anesthetic without the use of neuromuscular
blocking drugs. More patients in the epidural group had normal sphincter tone (80%) as assessed by the surgeon.
The incidence of intra- and postoperative complications was significantly higher in the general anesthesia group, and
the epidural group spent a significantly shorter period in the recovery room because they were less drowsy. Low-
dose epidural anesthesia was found to be an excellent analgesic with minimal motor block for anal surgery. Patients
in the epidural group were given diazepam for intraoperative anxiolysis.
82
Orthopedic surgery of the lower limbs is eminently suitable for central neuraxial blockade, and both total hip and
total knee replacements are commonly done under epidural anesthesia. The ability to provide epidural analgesia in
the postoperative period has encouraged the trend toward bilateral total knee arthroplasty (TKA) at the same time.
Lu and coworkers from Beijing studied the results of one-stage bilateral TKA under epidural anesthesia in patients
[63]
with rheumatoid arthritis. Over a 5-year period, from 1987 to 1992, bilateral simultaneous TKA was performed on
45 patients who were followed over a mean period of 63 months. Improved function and pain relief were noted in all
patients. Revision was needed in five knees owing to aseptic loosening, and the late infection rate was only 5.6%.
Bilateral TKA under epidural anesthesia was found to facilitate early rehabilitation in addition to reducing blood
loss and shortening the period of hospitalization.
The position of the patient during epidural administration of local anesthetic drugs was found to make a significant
difference in two studies. Strnad and coworkers (Czech Republic) investigated the effect of posture (10-degree
[64] [65] [64]
Trendelenburg position) in patients undergoing upper abdominal surgery under epidural anesthesia. Epidural
anesthesia was established in 60 patients, with a mean age of 71 years, with bupivacaine 0.5% administered at the
upper lumbar level. Patients were positioned in a Trendelenburg position with a 10-degree head-down tilt and
maintained in that position until the sensory level reached T3. Half the patients were then straightened to the
horizontal position, and the other half were kept in the same head-down position for surgery. There was no
significant difference in the ephedrine requirements between the two groups. The head-down group required
significantly less intraoperative sedation and showed fewer cardiovascular variations with visceral traction than the
other group. This study showed that posture could be used to enhance the quality of the block.
Epidural anesthesia for cesarean section can be less satisfactory than spinal anesthesia. One of the reasons cited is
that local anesthetic solutions may not reach the sacral segments, resulting in an inadequate block. Chan and
coworkers from Malaysia investigated the effect of maintaining a 10-degree head-up tilt position when establishing
[65]
epidural anesthesia for elective cesarean section. One hundred patients were randomized to receive epidural
bupivacaine 0.5% with 50 µg of fentanyl in either the horizontal or 10-degree head-up position. The patients were
maintained in that position until epidural anesthesia was established up to T6, with additional doses of bupivacaine
0.5%, if necessary. The incidence of intraoperative pain and discomfort was significantly less in the head-up group
(P < 0.05). There was no difference on the effect of blood pressure or motor block.
Regional Anesthesia and Obstetric Practice
Spinal anesthesia is perhaps the commonest anesthetic technique for cesarean section in most developing countries.
[67] [68] [69] [70] [71] [72] [73]
[66]
SPINAL ANESTHESIA AND HYPOTENSION
Hypotension is the commonest problem following spinal anesthesia for cesarean section. It results from a decrease
in arteriolar and venous tone secondary to sympathetic block, with a resulting reduction in systemic vascular
resistance and venous return. The prevention of aortocaval compression by left uterine displacement and the
prophylactic administration of IV crystalloid solutions have been widely advocated for years and are considered
mandatory. These measures may not be adequate and ephedrine is often required to treat hypotension. Table 7-3 is a
summary of several studies that have addressed this problem in different ways. Mathru and coworkers used 5% [74]
albumin in Ringer’s lactate with 5% dextrose solution at 15 mL/kg as a preload and compared it with the same
volume of solution without albumin in 87 patients undergoing
TABLE 7-3 -- TECHNIQUES TO REDUCE THE INCIDENCE OF HYPOTENSION AFTER SPINAL ANESTHESIA FOR ELECTIVE
CESAREAN SECTION
No. Patients/Local
Researcher/Country Investigation Anesthetic Results
[74]
Mathru et al., India 5% albumin in D5RL No. = 87 S—better neonatal outcome with albumin, P<
vs. D5RL 0.02
Bhagwanjee et al.,[77] 1990/S. Africa * Legs wrapped after No. = 24 S—incidence of hypotension less with leg
spinal vs. control Bupivacaine 0.5%, wrapping, P < 0.0033
1.5 mL, sitting
Rout et al.,[78] 1993/S. Africa * Legs wrapped vs. leg No. = 97 S—leg wrapped vs. control, P< 0.004
elevation vs. control Bupivacaine 0.5%, S—leg wrapped vs. leg elevation
1.5 mL NS—leg elevation vs. control
Chan et al.,[75] 1997/Hong Kong * Ephedrine infusion No. = 46 S—incidence of hypotension, less with
vs. volume preload Bupivacaine 0.5% ephedrine P < 0.04
S—umbilical pH higher with ephedrine, P<
83
TABLE 7-3 -- TECHNIQUES TO REDUCE THE INCIDENCE OF HYPOTENSION AFTER SPINAL ANESTHESIA FOR ELECTIVE
CESAREAN SECTION
No. Patients/Local
Researcher/Country Investigation Anesthetic Results
0.02
[76] *
Webb & Shipton, 1998/S. Africa Prophylactic IM No. = 24 NS—ephedrine supplement and SBP soon after
ephedrine 37.5 mg vs. Bupivacaine 0.5% spinal anesthesia, Apgar scores
placebo hyperbaric, 2.5 S—lower incidence of delayed hypotension
mL/sitting
S = significant; NS = not significant; No. = number of patients; SBP = systolic blood pressure; intravenous ephedrine supplement, Apgar scores
in all patients.
*Umbilical arteriovenous pH also recorded.
cesarean section under spinal anesthesia. The incidence of hypotension in the albumin group was significantly less
than in the crystalloid group and could be attributed to the longer intravascular half-life of the colloid. Neonatal
outcome was also significantly better in the albumin group (P < 0.01).
The place of prophylactic ephedrine was reevaluated in two studies. Chan and coworkers compared the efficacy
[75] [76] [75]
of prophylactic IV ephedrine infusion (0.25 mg/kg) with fluid preloading using Ringer’s lactate solution (20 mL/kg)
in preventing maternal hypotension during spinal anesthesia in 46 women undergoing cesarean section. The
incidence of severe hypotension was significantly less in the group given ephedrine (P = 0.04), and the mean
umbilical venous pH was also significantly higher in the ephedrine group (P = 0.02). Doppler ultrasound scans
showed no difference between pre- and postspinal uterine blood flow. In a double-blind randomized controlled study
of 40 patients, Webb and Shipton gave either 37.5 mg of ephedrine or placebo, intramuscularly, before spinal
[76]
anesthesia for cesarean section. All patients were also given a volume preload of 500 mL of Ringer’s lactate over 15
to 20 minutes. The group given intramuscular (IM) ephedrine was found to have a significant reduction in the
incidence of delayed hypotension (>30 minutes) compared with the control group. Umbilical vein pH was within the
normal range in both groups, and IM ephedrine was not associated with any reactive hypertension. They suggested
that IM ephedrine may provide more sustained cardiovascular support than IV ephedrine, and this action may be an
advantage in the postoperative period.
Two studies investigated leg wrapping with Esmarch bandages in an effort to reduce the incidence of hypotension. [77]
Bhagwanjee and coworkers randomly allocated 24 women to either have their legs wrapped immediately after
[78] [77]
the induction of spinal anesthesia or to serve as control subjects. Both groups were given a prophylactic volume
preload with 20 mL/kg of crystalloid solution. Leg-wrapped patients had a significantly lower incidence of
hypotension (P < 0.0033) than control subjects. They also required significantly less ephedrine, and no patient
experienced hypotension when the legs were unwrapped after surgery. In a follow-up study in the same institution,
97 women undergoing elective cesarean section under spinal anesthesia were allocated randomly to have their legs
elevated to 30 degrees on pillows, legs elevated and wrapped with elasticized Esmarch bandages, or neither of the
two (control) after induction of the block. All patients received intravenous crystalloid solution before the block.
Leg wrapping significantly reduced the incidence of postspinal hypotension (18%) compared with the control group
(53%) (P < 0.004). Leg elevation alone did not significantly reduce the incidence of hypotension (39%). Both [78]
studies showed that wrapping the legs can provide a simple means of reducing the accompanying hypotension and is
a technique that should be used more widely.
PETHIDINE AS A LOCAL ANESTHETIC AGENT
Pethidine is the only opioid that is known to have local anesthetic properties in addition to analgesia. Kafle [79]
investigated the efficacy and safety of intrathecal pethidine as the sole anesthetic for cesarean section and compared
it with lignocaine. Fifty full-term women who were scheduled for elective sections were randomly assigned to
receive either preservative-free 5% pethidine, 1 mg/kg, or 5% hyperbaric lignocaine, 1.2 to 1.4 mL for spinal
anesthesia. The sensory and motor block was adequate for surgery in all but two patients who required sedation at
skin incision. The incidence of hypotension was significantly higher in the lignocaine group (P< 0.05). Pruritus and
drowsiness were significantly higher in the patients given pethidine, but their occurrence was not clinically
significant. All patients could be aroused easily, and there were no problems with the neonates. Postoperative
analgesic requirements were significantly less in the pethidine group, with the average duration of pain relief being 6
hours compared with 1 hour in patients given lignocaine (P< 0.01). Pethidine was shown to be an effective
alternative to lignocaine, with a significantly longer duration of postoperative analgesia and less hypotension.
ANALGESIA IN LABOR
84
Regional anesthesia (mainly epidural analgesia) with its selective central sensory blockade is an established
technique for the relief of pain in labor. The conduct of safe epidural analgesia for labor requires anesthetists who
are trained in this technique, skilled midwives, and facilities to monitor patients and staff to deal with any untoward
effects. The provision of an obstetric epidural service in developing countries is often limited to the large teaching
hospitals in urban centers. Shortage of personnel and facilities for monitoring often make it difficult for a majority
of hospitals to offer such a service routinely.
[80] [81]
A nationwide survey conducted by Takacs and colleagues from Hungary in 1993 sums up the situation that is found
in most developing countries. In their survey, information was available for 104,137 deliveries from 98 obstetric
[80]
units. They found that 81% (71,744 patients) who had had vaginal deliveries did not have any type of pain relief. Of
the others who had some form of analgesia, 8.3% were given systemic opioids, and 5% had inhalational (nitrous
oxide/oxygen) analgesia. Only 5.2% received epidural analgesia. Sixty-two of the 98 units surveyed did not
routinely offer epidural analgesia to their patients. Regional anesthesia (spinal/epidural) was used in only 37% of all
cesarean sections. The authors concluded that pain relief in labor was given a low priority in Hungary. The main
reasons cited were shortage of anesthetic staff and the traditional attitudes of obstetricians.
A 1-week survey of analgesic services in the labor ward of a large hospital in South Africa in 1993 reported a
similar situation. Of 249 patients who had normal vaginal deliveries, 113 (45%) received no analgesia whatsoever.
[81]
Intramuscular pethidine was the commonest form of analgesia and was used in 97 patients (39%). Only 36 patients
(14%) received epidural analgesia, and the remaining patients (4%) received Entonox. About 76% of mothers who
had an obstetric indication for epidural analgesia were not given it because of lack of medical staff. Periodic
[81]
surveys such as these are necessary to create awareness among obstetricians, anesthetists, and administrators about
the need to improve analgesic services in labor wards. It may not be possible to improve the staffing situation
quickly, but it serves to focus on these important issues when planning future personnel needs for the healthcare in
the country.
Single-shot intrathecal opioids can provide analgesia in labor, but the onset is slower than that for local anesthetic
drugs. The duration of pain relief with a single dose of opioid is also variable, and, thus, it may not be able to
provide adequate analgesia for the entire duration of labor. Wu and coworkers, from Taiwan, retrospectively
[82]
studied 55 primiparas who were given a combination of morphine 0.5 mg and 2.5 mg of 0.1% bupivacaine for the
relief of pain in the active first stage of labor. They compared these patients with 88 similar patients who did not
receive any analgesia for their labor. The mean onset of analgesia was 2.6 plus or minus 0.5 minutes and the
duration was between 4 and 12 hours. Ninety-three percent of the women did not request any additional analgesia.
The duration of first and second stages was significantly longer, and the frequency of instrument-assisted vaginal
deliveries was higher than in the control group. There was, however, no difference in the rate of cesarean section
and Apgar scores in the neonates. Most of the side effects, such as pruritus and nausea, were mild and alleviated by
naloxone. A combination of a single dose of morphine and bupivacaine appears to be an effective and safe
alternative when epidural analgesia is not available.
Peripheral Neural Blockade
Regional anesthesia is suitable for surgery of arms and legs. It has been extensively used for microsurgery on both
upper and lower limbs in Shanghai, People’s Republic of China. Fang reviewed the anesthetic technique used in
[83]
1185 microsurgical procedures carried out in Number 6 Municipal Hospital, Shanghai, over an 18-year period from
1968 to 1985. The review included 500 reimplantations of amputated fingers and toes, 271 free transfers of toes, 96
free transfers of fibulas, 63 free transfers of muscle, 34 reconstruction of hands, and 88 ear-nose-throat procedures.
Brachial plexus block was used in 33.8% (401 patients), cervical epidural block in 19.6% (232 patients), and general
anesthesia in 16.3% (193 patients) of surgical procedures. A combined lumbar and cervical epidural block was used
in 12.6% (149 patients), brachial plexus with lumbar epidural block in 10.4% (123 patients), lumbar epidural block
alone in 5.4%, and acupuncture in 1.9% of patients. Neural blockade provided excellent operating conditions for
prolonged surgery and was used to reduce or avoid vasospasm and facilitate vascular anastomosis.
BRACHIAL PLEXUS BLOCK
In a series of 126 patients undergoing hand surgery, Koh and Lim from Singapore used interscalene brachial
[84]
plexus blockade. They used a Contiplex plexus cannula (B. Braun) and a nerve stimulator to establish the block with
40 mL (20 mL of bupivacaine 0.5% and 20 mL of 1.5% lignocaine with adrenaline) of local anesthetic solution. The
analgesia was extended into the postoperative period with a continuous infusion of bupivacaine 0.25% via a
disposable infusion device for a mean period of 3 days. Most of the patients (93.7%) obtained excellent pain relief
and were able to participate in active physiotherapy. Catheter complications, which occurred in 18 patients (14.3%),
were minor, such as dislodgment and pain at the site of insertion. Early physiotherapy was vital for a successful
85
outcome, and a low-dose continuous block of the brachial plexus was able to provide excellent analgesia without the
side effects of systemic opioids.
The level of block achieved by an interscalene brachial plexus block is usually inadequate for shoulder and proximal
upper extremity surgery. Ho and Wong described a technique called “Ho’s method” to block C3 and C4 nerve
[85]
roots separately and to combine these blocks with an interscalene block. In their series of 65 patients, 62 were
operated on satisfactorily by this technique for shoulder surgery. This can be a useful alternative to general
anesthesia when one wants to avoid manipulating the airway. Regional anesthetic techniques are also preferable to
general anesthesia in patients with renal failure. Yeboah and coworkers from Ghana reviewed 92 patients with
[86]
renal failure who required vascular access for hemodialysis. One hundred and seven arteriovenous shunts (98 in the
arm, 7 around the ankle, 1 in the groin) were created under local or regional anesthesia. Ultrasonography was found
to be a useful aid in accurately placing a catheter into a neurovascular sheath. It was used as an imaging aid to
enhance the success of brachial plexus blockade by the axillary and infraclavicular approaches. [87] [88]
INTRAPLEURAL BLOCKS
Intrapleural blocks have been advocated as an alternative to thoracic epidural analgesia for pain relief after thoracic
surgery. Mehta and coworkers from New Delhi compared the efficacy of thoracic epidural analgesia and
[89]
intrapleural analgesia after minimally invasive direct coronary artery bypass surgery with regard to quality of
analgesia and complications in 50 patients undergoing elective surgery. The thoracic epidural was inserted (T4-5)
before induction of general anesthesia, whereas the intrapleural catheters were inserted under direct vision by the
surgeon at T6-7 intercostal space. Bupivacaine 0.25% was administered via the catheters for analgesia. The pain
scores in the intrapleural group were significantly lower, with no difference in the hemodynamic or respiratory
parameters or postoperative requirements for supplementary analgesia between the groups. Three patients in the
epidural group had catheter migration, and four patients complained of severe back pain. The investigators
concluded that intrapleural catheters were easy to insert, had fewer complications, and were a safe alternative to
thoracic epidural analgesia, provided they were positioned carefully and the chest tube clamped at administration of
the local anesthetic.
LOWER LIMB PERIPHERAL NERVE BLOCKS
Spinal or epidural anesthesia is usually chosen when regional anesthesia is being considered for lower limb surgery.
An alternative to central neural blockade is the combined femoral and sciatic nerve block. The sciatic nerve block
component is technically more difficult, and, therefore, it is not widely used. In a study of 40 patients undergoing
unilateral total knee replacement, Lau and coworkers (Taiwan) compared spinal anesthesia with combined femoral
[90]
(3-in-1) and sciatic nerve block. The two techniques were comparable for surgery, intraoperative blood loss, and
time to first postoperative analgesia. Ten of the 20 patients in the spinal group developed postoperative urinary
retention, whereas none had this complaint in the femoral/sciatic group. Urinary retention and subsequent bladder
catheterization can be a potential source of infection in patients with an implant. Combined femoral/sciatic nerve
block was shown to be a good alternative to central neuraxial blockade. It can be used in patients with abnormal
spine pathology or previous back surgery. As an extension of the technique, continuous femoral nerve sheath
infusion with dilute local anesthetic solution can provide postoperative analgesia.
INTRAVENOUS REGIONAL ANESTHESIA
Intravenous regional anesthesia (IVRA) is a technique that is simple to perform and readily lends itself to minor and
outpatient surgery, particularly of the upper limb. It is useful in the emergency department for the reduction of
fractures. The volume of local anesthetic solution necessary for adequate analgesia can be a cause of some concern
when there is an inadvertent leak of the applied tourniquet. Several modifications to the classical IVRA technique
have been reported to increase the safety margin in the event of a leak. Acalovschi and Cristea from Romania
[91]
investigated meperidine as the sole anesthetic agent for IVRA in 45 volunteers (medical students in ASA I physical
status). They were divided into three groups of 15 each and were given either 40 mL of meperidine 0.25%,
lignocaine 0.5%, or 0.9% saline. The time to complete motor block and onset of sensory block at six sites on the
forearm and hand was documented. The recovery characteristics after cuff deflation were also noted along with the
incidence of any side effects. The onset of sensory and motor block was significantly faster in the meperidine group
compared with normal saline (P< 0.001) but significantly slower than the lignocaine group (P< 0.001). The sensory
and motor characteristics in the meperidine group indicated that meperidine had local anesthetic properties but was
definitely inferior to lignocaine. The high incidence of nausea and dizziness along with pain on injection with
meperidine also made it unsuitable as a sole agent for IVRA. They suggested that it should perhaps be reserved for
patients who are allergic to local anesthetic drugs.
86
In another modification, Abdulla and Fadhil (Iraq) investigated the effect of adding fentanyl and pancuronium to a
[92]
small dose of lignocaine for IVRA. In a randomized, double-blind study, 80 patients undergoing surgery of the
forearm and hand were assigned to four groups. Each group received one of the following four solutions: 100 mg of
lignocaine in 40 mL of saline alone, lignocaine combined with 0.05 mg of fentanyl or with 0.5 mg of pancuronium,
or lignocaine combined with both. All three drugs were also administered to 20 volunteers and the cuff released
immediately to evaluate the safety of the solutions studied. Analgesia was most profound in the group containing all
three drugs (100%). The number of patients who had successful analgesia in each of the other groups was less than
27%. Volunteers complained only of minor and transient side effects such as dizziness. The authors suggested that
the dose of lignocaine required for IVRA can be significantly reduced with the addition of low-dose fentanyl and
pancuronium, without any serious side effects.
OTHER PERIPHERAL NERVE BLOCKS
Ahuja and coworkers studied the effect of infraorbital nerve blocks for postoperative pain relief. Twenty infants
[93]
were randomized to receive bilateral infraorbital nerve blocks or sham blocks following cleft lip repair under general
anesthesia. Excellent postoperative pain relief was seen in all 10 infants who received the block. It was found to be a
simple and effective technique that can be administered by the surgeon to provide postoperative analgesia in
children. One report from Djibouti describes a local-regional anesthesia technique for outpatient cleft lip repair that
uses block of the superior maxillary nerve, because nearly 50% of patients who need the repair are adults. Blocks [94]
of the inferior alveolar, auriculotemporal, lingual, buccal, and superficial cervical plexus have also been used to
successfully drain and treat submandibular abscesses. [95]
Transphenoidal surgical excision of the pituitary gland often elicits severe cardiovascular responses despite an
adequate depth of anesthesia. Chadha and coworkers from India investigated the effect of bilateral maxillary nerve
[96]
block in suppressing these responses. Thirty-nine patients undergoing transphenoidal excision of the pituitary gland
were randomly assigned to two groups. Group 1 patients did not receive nerve blocks and served as controls, and
Group 2 received 5 to 10 mL of bupivacaine 0.5% and lignocaine 2% (1:1) after induction of general anesthesia.
The local anesthetic was injected into the pterygopalatine fossa via the zygomatic approach on each side to block the
maxillary and sphenopalatine ganglion. The cardiovascular responses to surgery were monitored and recorded in
both groups. The control group in the study was stopped at only seven patients for ethical reasons, because all the
patients assigned to this group developed sudden and sometimes uncontrollable hypertension during manipulation of
the nasal speculum. In the rest of the 32 patients, the block significantly reduced the hypertensive response to nasal
infiltration with adrenaline solution, nasal dissection, and application of the speculum. All patients in the control
group required additional halothane and sodium nitroprusside to control blood pressure. Bilateral maxillary and
sphenopalatine ganglion blocks were shown to be useful adjuncts to transphenoidal surgery.
Regional Anesthesia in Children
Caudal epidural anesthesia and analgesia in children has been popular for many years. It has been extensively used
along with general anesthesia for lower abdominal and lower limb surgery in most developing countries. In [97] [98] [99] [100]
a retrospective study to evaluate regional anesthetic techniques in developing countries, Aguemon and coworkers [101]
from Benin reported using spinal and caudal anesthesia in 1875 children undergoing lower abdominal and lower
limb surgery. There were 1145 children, between 14 days and 17 years of age, who had caudal anesthesia with a
mixture of 1% lignocaine and 0.25% bupivacaine with 1:200,000 adrenaline, whereas 730 neonates and infants
younger than 3 years of age had spinal anesthesia with isobaric bupivacaine 0.5%. The failure rate was less than 1%,
and all the children had stable cardiovascular and respiratory parameters during surgery.
Sadraoui and coworkers from Morocco reported their experience of spinal anesthesia in infants for lower
[102]
abdominal surgery. Hyperbaric 5% lignocaine, 3 mg/kg, was administered at L4-5 in 18 infants, with a mean age of
15 months and a mean weight of 10 kg, to induce spinal anesthesia. Motor block was obtained 2 minutes after the
injection, and the duration of the sensory block was 40 plus or minus 9.7 minutes (mean ± SD). Blood pressure and
heart rate throughout surgery showed only minor variation, and the anesthesia was satisfactory in 16 of 18 cases.
Spinal anesthesia has been suggested as the anesthetic technique of choice for surgery in ex-preterm infants, because
postoperative apnea is associated with general anesthesia. It should be considered as a reasonable option for infants
requiring elective lower abdominal and lower limb surgery lasting less than 45 minutes.
Epidural anesthetic techniques in children have recently gained popularity. There has also been an increasing
appreciation that children should benefit from the excellent pain relief obtained with continuous epidural analgesia
in the postoperative period. The drawbacks to the use of lumbar epidural anesthesia in the past have probably been
the uncertainty of the skin-epidural distance in a child, the fear of accidental dural puncture, and the difficulty in
[103]
obtaining small needles and catheters. Bosenberg from South Africa measured the skin-epidural distance in
[104]
87
children who received lumbar epidural analgesia and correlated it with the weight of the child. The skin-epidural
distance was measured at the L3–4 interspace in 274 children who had lumbar epidural anesthesia. Their pages
ranged from 2 days to 16 years and their weight was between 2 and 43 kg. All lumbar epidurals were performed
under general anesthesia with 19-G Tuohy needles, using a midline approach. A good correlation between weight
and skin-epidural distance (1.00 mm per kg body weight) was found between the ages of 6 months and 10 years of
age, whereas this correlation was not true outside this age range. All the children had an epidural catheter inserted
and had a successful block, with no incidence of either dural puncture or bloody tap. This useful guide should help
popularize the practice of lumbar epidural anesthesia in children.
Central neural blockade is an excellent method of providing analgesia, even in neonates and infants. Although
caudal epidural anesthesia can be readily used for lower abdominal surgery, adequate analgesia for upper abdominal
and thoracic surgery via the caudal route requires large volumes of local anesthetic agents with potential toxicity and
morbidity. Direct lumbar or thoracic epidural administration is an option. However, these procedures can be
technically difficult in a neonate or infant. Bosenberg and colleagues from Durban investigated an alternative
[105]
route of threading catheters up to the thoracic level via the caudal route. They initially investigated the feasibility of
threading the catheters in 14 human cadavers (premature to 11 years) and animals (piglets). Epidural catheters could
be threaded up to the required level in all infant cadavers younger than 9 months of age and in all animals. They
subsequently studied 20 neonates and older infants who were to undergo biliary surgery. Under general anesthesia,
epidural catheters were threaded up via the sacral hiatus to the thoracic level and their position confirmed by
radiographic contrast medium injection. Bupivacaine 0.5%, 0.5 mL/kg, was administered to provide epidural
analgesia in these infants. Analgesia was considered excellent in all cases, and there were no untoward incidents of
hypotension, bradycardia, or arrhythmias. The authors demonstrated a technically simple alternative method of
providing lumbar and thoracic epidural analgesia in small infants.
Peripheral nerve blocks are not commonly attempted in children, because eliciting paresthesia to locate nerves can
be painful. Eliciting paresthesia is not necessary when a peripheral nerve stimulator is used as an aid to locate and
block nerves under general anesthesia. Bosenberg reported the successful use of a peripheral nerve stimulator to
[106]
block femoral and sciatic nerves in 411 children undergoing lower limb surgery over an 8-year period from 1986 to
1994. The mean age was 4.25 (SD 3.8) years and mean weight was 16.8 (SD 9.4) kg, with 120 children younger
than 1 year of age. The blocks were performed using unsheathed or noninsulated needles, which were easily
available and not as expensive as the sheathed needles. The current required to stimulate the more superficial
femoral nerve was 0.5 to 1 mA, and the deeper sciatic nerve required 1.2 to 2 mA. The overall success rate was 98%
with excellent postoperative analgesia. Junior staff under supervision performed nearly 50% of the blocks. The
simplicity of the techniques and the excellent surgical outcomes obtained indicate that peripheral nerve blockade in
children should be used more widely.
Regional Anesthesia for Postoperative Pain Relief
In the last decade, acute pain services (APSs) have been established in many parts of the world for more effective
management of postoperative pain. Many hospitals in developing countries, particularly in Asia, have
[107] [108]
enthusiastically followed this trend by establishing APSs. Most of these are anesthesiology-based services
[109] [110] [111]
that provide specialized techniques, including patient-controlled analgesia (PCA) and epidural analgesia. Epidural
analgesia is either by epidural opioid administration or by continuous infusion of a mixture of low-dose local
anesthetic solution and opioids.
Tsui and coworkers from Hong Kong compared the efficacy of epidural infusion of bupivacaine and fentanyl with
[112]
IV PCA morphine in patients undergoing gynecologic surgery. One hundred and twenty patients undergoing
[112]
gynecologic surgery under general anesthesia were randomized to receive either an epidural infusion of bupivacaine
0.0625% and fentanyl 3.3 µg/mL (10 mL/hour) or IV PCA morphine (PCA bolus of 1 mg and a lockout interval of 5
minutes). Patients were monitored for the degree of pain relief and the incidence of side effects. The epidural group
had a significantly lower score on the verbal rating scale (VRS) for pain both at rest and on cough in the first 40
hours after surgery. There was no incidence of hypotension or respiratory depression in both groups and no
difference in the incidence of nausea. All patients were nursed in the general wards, with continuous pulse oximetry
(SpO2 ) in addition to routine ward monitoring, indicating that the nurses on the general wards are capable of
managing sophisticated postoperative analgesic techniques.
In an audit of their APS, Tsui and coworkers reviewed the adverse effects and safety of postoperative pain
[110]
management in 2509 consecutive patients at a tertiary referral teaching hospital over a 32-month period. All the
patients were managed on the general wards using the APS standard monitoring protocols. Of these patients, 590
(23.5%) received a continuous infusion of either epidural bupivacaine/fentanyl or epidural morphine. Hypotension
due to the analgesic technique was noted in only four patients, and this was promptly detected in the wards and
88
managed with no untoward effects. They demonstrated that patients receiving bupivacaine/fentanyl infusions can be
safely nursed in general wards provided monitoring protocols are in place and ward staff undergo training with
regard to the use of sophisticated techniques.
Ketamine, an N-methyl-D-aspartate (NMDA) antagonist has been investigated to determine its role in reducing central
sensitization of nociceptors and reducing postoperative pain. Chia and coworkers from Taipei studied the
[113] [114] [113]
effect of adding a small dose of ketamine (0.4 mg/mL) to the epidural infusion in patients receiving multimodal
patient-controlled epidural analgesia (PCEA) after major abdominal surgery. Ninety-one patients were divided into
two groups to receive PCEA with bupivacaine 0.08%, morphine 0.02 mg/mL, epinephrine 4 µg/mL with or without
the addition of ketamine. The group given ketamine had significantly better pain relief, particularly during coughing,
and used less analgesic solution than the other group, demonstrating that low-dose epidural ketamine can provide an
additive analgesic effect when added to a multimodal analgesic regime.
In a randomized, placebo-controlled study, Abdel-Ghaffar and colleagues from Saudi Arabia also investigated the
[114]
effect of low-dose epidural ketamine on postoperative analgesic consumption. Sixty-one patients undergoing total
abdominal hysterectomy were assigned to three groups to receive either 30 mg of epidural ketamine before
induction or 20 minutes after skin incision or epidural normal saline. In the postoperative period, all patients
received PCEA with low-dose bupivacaine 0.1% and fentanyl 1 µg/mL after a bolus dose of bupivacaine and
fentanyl given at first request for analgesia. The time to request of first analgesic dose was significantly less in the
control group (P< 0.05) compared with the other two groups. The total amount of analgesia consumed by the control
group was also significantly greater (P< 0.01). There was no difference in the analgesic requirements whether the
ketamine was given before or after skin incision.
Ngan Kee and coworkers from Hong Kong compared a portable disposable device with a standard electronic
[115]
PCEA pump in two groups of patients using PCEA after cesarean section. The disposable device was found to be
just as effective as the more expensive device and allowed the patient greater mobility. The preceding studies on
postoperative pain indicate that many institutions in developing countries are currently trying to improve pain
management using regional analgesic strategies.
Combined use of general and caudal epidural anesthesia is also widely used in children as can be seen by the several
studies that have compared caudal bupivacaine plain with bupivacaine/pethidine or buprenorphine or [116] [117]
bupivacaine/morphine or bupivacaine/midazolam. Kumar and Jacob, in a randomized controlled study of 50

[118] [116]
children, found that although the addition of pethidine provided a significantly longer period of postoperative
analgesia, there was a high incidence of vomiting and urinary retention, which would preclude the routine addition
of pethidine to bupivacaine. Girotra and coworkers compared caudal buprenorphine 4 µg/kg with caudal
[117]
bupivacaine 0.25% in 40 children undergoing genitourinary surgery. Both groups had excellent analgesia in the
immediate postoperative period, but the buprenorphine group had analgesia for 20 to 24 hours. Gulec and
colleagues from Turkey compared the effect of caudal bupivacaine with bupivacaine/morphine and
[118]
bupivacaine/midazolam mixtures in 60 children undergoing inguinal or urogenital surgery. The

bupivacaine/midazolam mixture resulted in a significantly longer duration of analgesia when compared with
bupivacaine plain (P < 0.001) or bupivacaine/morphine (P < 0.01), but was associated with more sedation.
Regional Anesthesia for Battlefield Surgery
Field hospitals play an important role in managing military and civilian casualties, which result from ethnic
conflicts, political strife, and warfare in many developing countries. Surgery is often performed under less than ideal
conditions, on patients who need urgent procedures to prevent loss of life or limb. Anesthesia for these patients can
be challenging owing to difficult circumstances such as shortage of personnel, inadequate equipment, and lack of
drugs. Lenz and coworkers documented their experience of working in Red Cross missions in surgical field
[119]
hospitals on the Thai-Cambodian border, in Lebanon, at the Afghan-Pakistan border, and in Indonesia. Between the
years 1979 and 1984, a total of 3665 civilian emergency patients received anesthesia; 17.5% of the patients were
operated on under local anesthesia, and another 17% received regional anesthesia, in most cases spinal anesthesia.
The remaining patients were managed under general anesthesia, either with halothane or ketamine. Despite the
primitive working conditions, there were no anesthesia-related deaths.
Basic Research
Several studies have concentrated on research that was not directly concerned with the effects of various drugs or
techniques in patients. Bahk and coworkers from Korea conducted a study to identify a method of predicting
[120]
epidural depth in adults using a patient’s readily available physical measurements. Computed tomography was used
to accurately measure the epidural depth at L3–4 in 51 Korean male volunteers between the ages of 20 and 25 years.
89
The skin-epidural, skin-supraspinous, and supraspinous-epidural distances were measured and correlated with
height, weight, shoe size, body mass index (BMI), neck circumference, waist circumference, and the ratios of
weight/height, waist/neck, waist/height, and weight/neck of these volunteers. The value of the supraspinous-epidural
distance was found to be independent of any physical measurement. A significant correlation was found between the
skin-supraspinous distance and physical measurements that were related to obesity. The waist circumference/neck
circumference ratio and BMI resulted in a higher predictive value of epidural depth than the traditional weight or
weight/height ratio.
Enhanced neutrophil activity constitutes an important early defense strategy against bacterial infection during and
after surgery. Erskine and colleagues from Cape Town compared neutrophil biocidal activity during general and
[121]
spinal anesthesia in patients undergoing hip arthroplasty. Twenty-five patients were randomized into three groups to
receive either general anesthesia with halothane or isoflurane or spinal anesthesia. Assays were performed on
neutrophils extracted from blood drawn 1 hour after start of surgery. Neutrophils from patients under spinal
anesthesia exhibited significantly greater bactericidal activity when incubated with Staphylococcus aureus than
those taken from the general anesthesia group. They suggested the possibility that either general anesthesia per se or
the stress response of surgery could be responsible for inhibition of normal neutrophil activity generated by surgery.
Regional blockade, which blunts the stress response, could contribute to a reduction in perioperative sepsis, but
further research in this area is indicated.
The precise mechanism of action of local anesthetic solutions injected into the interpleural space remains
conjectural. McKenzie and Mathe from Harare studied the distribution of India ink, which was injected into the
[122]
interpleural space in six cadavers. Following injection of 20 mL of the dye, autopsy revealed that the spread of the
ink was uniformly wide, with a tendency to pool in the paravertebral gutter. Histologic slides of transverse sections
showed normal bone, skeletal muscle, and nerve tissue with black pigment on the pleural surface and in the
subpleural space. They suggest that local anesthetic solutions probably diffuse through the parietal pleural
membrane, perhaps by bulk flow, into the subpleural space and access intercostal nerves.
Severe bronchospasm has been reported during epidural and spinal anesthesia. This has been attributed to the
sympathetic blockade associated with central neural blockade. Yuan and coworkers from Taipei investigated the
[123]
effects of high thoracic epidural anesthesia on peripheral airway reactivity in an animal model. Peripheral airway
resistance was recorded under steady state conditions in seven mongrel dogs under thiopentone anesthesia. The
animals were then challenged with acetylcholine 8 µg/kg, and histamine, 3 µg/kg, consecutively before and after
establishing thoracic epidural anesthesia with bupivacaine. Thoracic epidural anesthesia did not alter the baseline
peripheral airway resistance and did not affect peak airway resistance induced with acetylcholine and histamine.
They noted, however, that the recovery time of airway resistance was significantly prolonged with epidural
anesthesia, and this was inversely related to the change in cardiac output. They suggested that decrease in cardiac
output might be an important factor in the recovery of airways from any stimulus that produces bronchoconstriction.
Patients with diabetes mellitus often require surgery of the lower limbs because of complications such as nonhealing
ulcers and ischemic gangrene. Regional anesthesia is often the anesthetic of choice. Long-term diabetic patients
have incipient multiorgan dysfunction that may alter the way in which they metabolize local anesthetic drugs.
Peeyush and coworkers from India studied the pharmacokinetic profile of lignocaine administered by the epidural
[124]
route in eight well-controlled patients with type 2 diabetes mellitus and compared it with a similar group of patients
without diabetes. Epidural lignocaine 8 mg/kg was administered by the lumbar route, and plasma drug concentration
in serial blood samples was measured by the HPLC technique. The plasma level of lignocaine was lower in diabetic
patients, although the peak level was obtained at 20 minutes in both groups. The clearance of the drug was
significantly higher (39.9 mL/kg/min vs. 16.7 mL/kg/min) and was associated with a decreased elimination half-life.
This suggested that the rate of absorption of the drug was not altered but that hepatic metabolism was increased in
diabetic patients compared with nondiabetic patients. This may have implications when setting infusion rates for
long-term infusion of lignocaine in patients with diabetes mellitus.
Regional Anesthesia for Chronic Pain Management
Patients with reflex sympathetic dystrophy (RSD) are generally resistant to a variety of conventional pain
management regimens and often suffer from severe pain, allodynia, hyperesthesia, swelling, and loss of function of
the extremity involved. Lin and coworkers from Taipei report two cases in which they used a combination of
[125]
epidural ketamine, morphine, and bupivacaine. Two patients failed to obtain satisfactory pain relief from
nonsteroidal anti-inflammatory drugs, steroids, anticonvulsants, antidepressants, epidural lignocaine
sympathectomy, and rehabilitation. Both suffered from severe pain in their right leg due to RSD. Ketamine 7.5 mg,
morphine 0.75 mg, and 6 mL of bupivacaine 0.1% were injected three times a day via a lumbar epidural catheter for
a period of 1 week. Rehabilitation was initiated with the onset of some pain relief. Several courses of treatment over
90
3 and 6 months achieved satisfactory pain relief in both patients. At the end of 6 months, both patients were able to
manage slight weight bearing in walking with the help of a crutch.
Acupuncture and Analgesia
Acupuncture analgesia is not really classified as a regional anesthetic technique. In some countries, however,
acupuncture analgesia is practiced as a substitute or to enhance the effect of local anesthesia in certain surgical
procedures. Chen and Chen from Shanghai reviewed the records of 1622 patients undergoing appendectomy
[126] [127]
under acupuncture analgesia from 1970 to 1982. The success rate for acupuncture was noted to be 96.6%, and it was
possible to achieve this result by following a set of strict guidelines for its use. These guidelines included stringent
selection of cases, acupuncture point selection based on symptoms and maintenance of needling sensation, relatively
fixed group of surgeons and assistants, improvement of operative technique, and a reasonable use of adjuvant drugs.
No mention was made of the extent of adjuvant drugs used.
Sun and coworkers from Inner Mongolia compared acupuncture analgesia with epidural anesthesia in 80 patients
[128]
who required appendectomy. Patients were randomly assigned to receive either lumbar epidural anesthesia with
local anesthesia or acupuncture using Zusanli points (ST-36) as the main stimulating points and Hegu points (LI-4)
as auxiliaries. The patients who had been given acupuncture had less hypotension and fewer cardiac arrhythmias and
required less IV infusion than those in the epidural group. They also required less analgesia and antibiotics in the
postoperative period.
The mechanism of action of acupuncture analgesia is not known, although it has been extensively practiced in China
for many years. For success with this technique, patient and surgeon must cooperate fully. Acupuncture imposes
considerable limitations on the surgeon and requires careful surgical technique. It may have only a limited role in
contemporary anesthetic practice. [126]
Survey of the Practice of Regional Anesthesia in Asian Countries
A survey was undertaken to assess the role of regional anesthetic techniques in current anesthetic practice in Asian
countries and to identify any factors that may influence their use. The survey included anesthetic departments of
various hospitals in the East and South Asian region. They were chosen from the mailing list of members of the Asia
Oceanic Society of Regional Anesthesia, from addresses of authors in recent publications, and from personal contact
with anesthetic colleagues in the region. Questionnaires were mailed or sent by e-mail (when available) in the
beginning of November 1998. Japan was excluded, as it is not considered a developing country.
The questionnaire included items that sought to identify the type of institution, different regional anesthetic
techniques used in these institutions, the percentage of patients who were operated on under regional anesthesia
alone, obstetric anesthetic practice, and the comparative costs of regional and general anesthesia. Other questions
were on the use of epidural analgesia in the postoperative period, availability of acute pain services, the type of local
anesthetic drugs available, and the type of spinal needles used. Four questions focused on postgraduate training in
anesthesia for doctors and the training of nurse anesthetists. Checkoff options were provided for each item to
facilitate response. In addition, they were invited to make general comments on the practice of regional anesthesia in
their countries. The project was discontinued in the middle of January 1999.
RESULTS
Questionnaires were posted to 61 institutions. Twenty-six were returned by the second week of January 1999, giving
a response rate of 42.6%. One letter sent to Iraq was returned with the word “service suspended” (presumably, the
postal service). Eighteen university teaching hospitals, six state general hospitals, one provincial hospital, and one
urban private hospital responded from India, China, Malaysia, Sri Lanka, Myanmar, Taiwan, Korea, Thailand,
Papua New Guinea, Hong Kong, Singapore, and Bangladesh. There was no response from the Philippines,
Indonesia, Pakistan, Nepal, Iran, and Saudi Arabia. The annual number of surgeries performed annually was a mean
of 16,300 (range, 5000 to 47,000). The number of specialist staff in these institutions ranged from one (Papua New
Guinea) to 54 (Thailand), with a mean of 16 specialists. The number of trainee anesthetists ranged from none (urban
private center) to 65 (Sri Lanka), with a mean of 22 trainees.
Figure 7-1 shows the percentage of surgical procedures performed under regional anesthesia alone in the different
institutions surveyed. In the majority of hospitals, it was between 20% and 30%. Central Women’s Hospital from
Yangon, Myanmar, had the highest rate (>80%). Both hospitals that responded from the People’s Republic of China
(Shanghai and Beijing) reported a rate between 59% and 60%, and the lowest rate (<10%) was from Hong Kong.
91
In 21 of 26 (80.7%) hospitals, spinal and epidural anesthesia constituted 80% of all regional anesthetic practice, with
peripheral nerve blockade (PNB) making up the other 20%. Only 4 of 26 reported that PNB was used in 40% of
their practice (Boroka, Papua New Guinea; Galle, Sri Lanka; Shanghai, China; and Vellore, India). Only three
institutions (11.5%) reported using peripheral nerve stimulators regularly ( Table 7-4 ). PNBs appear to be
underutilized.
Figures 7-2 A and 7-2B show the extent to which the various regional anesthetic techniques are used in the
institutions surveyed. Central neuraxial blockade (spinal and epidural anesthesia) was used in all hospitals, and most
hospitals routinely used catheters for epidural anesthesia. Fifty percent of the hospitals were also familiar with
combined spinal epidural anesthesia, whereas only 4 of 26 (15.3%) used continuous spinal anesthesia. Lower limb
blocks were also less frequently used than upper limb blocks, which may be expected, because spinal and epidural
anesthesia is commonly used for lower limb surgery. IV regional anesthesia had a surprisingly low rate of usage
(50%) for such a simple technique. It may be due to the lack of availability of prilocaine in many countries.
Interpleural block was also used infrequently (26.9%). Other blocks performed occasionally were ankle block,
paravertebral block, and block of the dorsal nerve of the penis.
Regional anesthesia, either spinal (18 of 26) or epidural (3 of 26) was used for cesarean section in the majority of
hospitals. Twelve of the institutions responded that spinal anesthesia had been used for many years (range, 10 to 45
years), whereas the remaining hospitals reported that the use of regional anesthesia was a recent trend (1 to 5 years).
Three hospitals reported using general anesthesia routinely, and two hospitals did not have an obstetric unit. The
commonest gauge of spinal needle in use was 25-G, with some hospitals also using 27-G needles. The cutting bevel
Quincke needle continues to be popular, although the pencil point and Sprotte needles were also available in 50%
and 23% of those surveyed. Only seven institutions routinely offered epidural analgesia for labor pain (see Table 7-4
). The common reasons cited for not offering an epidural analgesia service was shortage of staff, inadequate
monitoring facilities in the labor ward, and preference of the obstetrician (23.0%).
The majority of hospitals combined regional anesthesia and general anesthesia for major abdominal, major
orthopedic, thoracic, and pediatric surgery (see Table 7-4 ). Postoperative epidural analgesia was available in 23 of
26 (88.0%) of the hospitals surveyed; 60% of them nursed these patients on the general wards, and the rest sent them
to high-dependency units. Table 7-4 also shows that an APS was available in 61.5% of the hospitals surveyed.
Spinal opioids were routinely used for postoperative pain relief in 15 of 26 (57.7%) institutions.
Lignocaine and bupivacaine were reported to be freely available in all countries, but three countries reported the
availability of the newer local anesthetic drug, ropivacaine. Prilocaine was available in three countries. Hyperbaric
bupivacaine 0.5% was the most frequently used local anesthetic agent for spinal anesthesia in all institutions.
Bupivacaine 0.5% plain and lignocaine 5% heavy was also routinely used in 23% and 31% of hospitals,
respectively. All but one hospital reported that the cost of regional anesthesia was definitely less (range, 30%–70%)
than the cost of general anesthesia for a similar procedure. Most of the difference
TABLE 7-4 -- SURVEY OF THE PRACTICE OF REGIONAL ANESTHESIA IN 26 HOSPITALS

Selected Questionnaire Items Yes No Occasionally
Do you combine general anesthesia with regional anesthesia? 22 3 1
Do you use peripheral nerve stimulators? 3 11 12
Are catheters used routinely for epidural anesthesia? 26 - -
If yes, are they used for postoperative pain relief? 22 3 1
If yes, do you use them in general wards? 14 8 -
Do you use spinal opioids for postoperative pain relief? * 15 5 -
Does your hospital have an acute pain service? 16 10 -
†
If regional anesthesia is used for cesarean section, is this a recent trend? 9 12
Is epidural analgesia offered for labor routinely? 7 8 9
*Six hospitals did not respond to this question.

†Not a recent trend. Regional anesthesia has been used for the last 10 to 45 years.
92
Figure 7-2 Percentage of hospitals using the different techniques of regional anesthesia. A, Central neuraxial block. B, Peripheral nerve blocks.
CSE, combined spinal-epidural analgesia; Cont, continuous; Epi-cath, epidural catheter; Epi-SS, epidural—single shot.
lay in the cost of expensive general anesthetic agents. In China, the cost of 5 mL of bupivacaine 0.75% was noted as
less than $1.00 (U.S. currency), whereas the cost of 100 mL of isoflurane was $110 (U.S. currency). Similarly, in
Malaysia, the cost of 4 mL of heavy bupivacaine 0.5% was $2.50 (U.S. currency), and isoflurane (100-mL bottle)
costs $100 (U.S. currency).
All institutions reported that postgraduate diplomas and degrees in anesthesia were available in their countries and
that training in regional anesthesia was considered important. Nurses were trained to administer anesthesia in
Thailand, Korea, Taiwan, and Papua New Guinea. In Malaysia, medical assistants (a category similar to that of male
nurse) were trained to provide anesthesia only in East Malaysia, to serve the remote rural hospitals of Sabah and
Sarawak. In the last 2 years, they have been taught to provide spinal anesthesia. In West Malaysia, doctors provided
anesthesia even in the small district hospitals. Nurses in Taiwan and Papua New Guinea were also taught regional
anesthetic techniques such as spinal and epidural anesthesia. Once accredited, these nurses and medical assistants
serve rural hospitals and work under the supervision of the surgeon.
DISCUSSION
The limitation of this survey is that it reflects only the practice of regional anesthesia in the institutions that
responded. The sample size was small, mainly because of the difficulty in obtaining the names and addresses of
hospitals in different countries. There is no Asian directory or list of hospitals available that one could choose from.
The Asia Oceanic Society of Regional Anesthesia mailing list was chosen because it was the most up-to-date list
available, but many of the members had to be ruled out because they were from Australia and Japan. Internet search
for Web sites yielded a few addresses. Another limitation was that of time. Two months was rather short, and it was
not possible to send a round of reminders to those who did not respond. The lack of response from the Philippine
Islands and Indonesia was disappointing because both of them together have a population of 260 million people.
Nevertheless, the 40% response rate was reasonable given the short period of time. There was at least one response
from 12 of the 19 countries that were sent questionnaires. The comments made by some of the senior staff of these
institutions were the most interesting part of the survey.
Regional anesthesia alone was used in 20% to 29% of surgical procedures in the majority of hospitals. It was
interesting to note that there was a marked difference between anesthetic practice in Shanghai/Beijing in Mainland
China and Hong Kong. This difference could reflect the difference in the facilities available in the two regions,
which have been two regions in the same country only since July 1997. Regional anesthesia was usually combined
with general anesthesia except for obstetrics in Hong Kong, and this practice could be attributed to a greater degree
of affluence in Hong Kong than exists in Shanghai or Beijing. With regard to the type of regional anesthetic
techniques practiced, central neuraxial blockade was a major component of the practice of regional anesthesia in
most hospitals. PNBs appear to be underutilized, particularly lower limb blocks. This practice could be due to lower
success rates with blocks, which again is probably due to not using peripheral nerve stimulators routinely. Peripheral
nerve stimulators may not be available in the hospitals that did not use them. Underutilization of PNB has been
reported in a recently published survey of the use of PNB in anesthetic practice in the United States. [129]
Professor Zheng Liping from Beijing wrote as follows:
Prior to 1980, about 80% of all surgery was performed under regional anesthesia, which included continuous
epidural anesthesia, spinal, and plexus blockade. With increase in anesthetic staff and better facilities available since
the 1980s, general anesthesia has become popular. Continuous epidural anesthesia is the most widely used
technique. Thyroid, breast, and, often, upper limb surgery is performed under continuous cervical epidural
anesthesia. The combined spinal and epidural anesthesia technique has recently increased the use of spinal
anesthesia. However, the cost of the needles prevents more widespread use.
In the larger metropolitan hospitals of China, the ratio of general to regional anesthesia is now 1:1; however, in
district hospitals, regional anesthesia is widely practiced. The reasons for its popularity are (1) anesthetists generally
feel it is safer and prefer it; (2) regional anesthesia is a lot cheaper than general anesthesia; (3) facilities for general
anesthesia are limited or not available; hence, there is no choice but to use regional anesthesia.
Professor Zheng also quoted a recent survey of 413 hospitals in China where 50% of the hospitals were large urban
hospitals and the remainder were regional hospitals. The best facilities for anesthesia were concentrated in large
hospitals associated with universities, whereas regional hospitals were poorly equipped, with some not having even
a simple general anesthetic machine (unpublished data).
93
Dr. N. Rodrigo from Sri Lanka wrote:
We are all for regional anesthesia! The most popular is spinal for cesarean section. It has been used in Sri Lanka for
many years and its popularity did not wane even when it disappeared from the United Kigdom after the Woolley and
Roe case. The pencil point and 25-G needles, now available, have cut down the incidence of headache considerably.
In the large teaching hospitals, epidural analgesia is routinely offered to primiparas in labor; whereas, spinal
morphine or fentanyl is offered to multiparas. Obstetricians prefer general anesthesia due to the slightly longer time
taken to establish regional anesthesia! Plexus blocks are less popular because of a higher failure rate and delay in
onset. With regards to cost, a spinal needle and bupivacaine costs Rs.500; whereas, the cost of general anesthesia for
3 hours is approximately Rs. 3000.
Dr. Chia (Taiwan) commented that the reimbursement for general anesthesia is higher than that for regional
anesthesia from the health insurance scheme; hence, a majority of surgical procedures were performed under general
anesthesia. Major thoracic and abdominal surgery was performed under combined general and regional anesthesia,
and postoperative epidural analgesia was offered routinely in their hospital. However, health insurance did not cover
postoperative analgesia and patients had to pay for this service. There was a shortage of anesthesiologists in rural
Taiwan; therefore, nurses or surgeons conducted most of the anesthesia in those areas, with a resulting increase in
morbidity rate.
Professor T. T. Khing from Myanmar noted:
If a survey of the whole of Myanmar were done, then regional anesthetic techniques will constitute 80% of
anesthesia for all surgical procedures. Lignocaine is the commonest local anesthetic used both for spinal and
epidural anesthesia. General anesthesia in rural areas consists of ether supplemented by oxygen via oxygen
concentrators.
Centers in India sent the following comments:
Regional anesthetic techniques such as spinal and epidurals are widely used. Spinal anesthesia is a common
technique even in remote areas of the country and local anesthetic drugs are freely available. Regional anesthesia is
definitely less expensive than general anesthesia. A large number of local anesthetic blocks are used by ophthalmic
and ENT surgeons.
From Papua New Guinea comes:
Bupivacaine has been used for regional anesthesia only in the last 2 years.
Siriraj Hospital, Bangkok, Thailand noted:
The information in this questionnaire does not truly reflect the practice of regional anesthesia in the whole of
Thailand, as Siriraj Hospital is the largest training hospital in Thailand. The problem of shortage of anesthetists in
rural areas persists. Nurse anesthetists provide anesthetic services in these areas, and they are not taught regional
anesthetic techniques. Spinal anesthesia is occasionally performed by surgeons and the patients monitored by nurse
anesthetists.
Summary
Regional anesthesia is practiced in most developing countries. The extent of practice varies enormously between
countries and depends largely on the economic situation and the type of healthcare system in place in individual
countries. In countries where there is a larger pool of physician anesthetists, regional anesthesia is more extensively
practiced than in countries that are less developed and depend largely on nurse anesthetists.
Professor Paul Fenton from Malawi commented:
The general trend all over Africa is for general anesthesia. Nurse anesthetists provide anesthesia in a large number
of hospitals. With regard to regional block there is only one block and that is spinal. Nerve blocks, Bier blocks, and
epidurals are used only occasionally (personal communication).
94
Spinal and epidural anesthesia are the most commonly used of all the regional anesthetic techniques. Regional
anesthesia is also extensively used for cesarean sections in keeping with worldwide trends. Caudal epidural
anesthesia is also widely used, along with general anesthesia in children, to provide intra- and postoperative
analgesia. With increased understanding of the stress response to surgery and the need to provide better
postoperative analgesia, there appears to be an increasing trend toward combining regional anesthesia with general
anesthesia for major surgery. The increasing popularity of regional anesthesia in developing countries of Asia,
Eastern Europe, and South America could also be due to the role of the European, Asian and Oceanic, and Latin
American societies of regional anesthesia.
The cost of providing regional anesthesia is less, sometimes substantially less, than the cost of an equivalent general
anesthetic. The last two decades have seen a rapid escalation of healthcare costs all over the world, and developing
countries have not been spared. The current economic crisis engulfing Asia and many other developing countries
has brought about a greater awareness of providing more cost-effective methods of management, and this could lead
to a greater use of regional anesthesia.
95
Section II - Chapter 8 - Training and Education of a Physician for Regional Anesthesia
Chapter 8 - Training and Education of a Physician for Regional

Anesthesia
COLIN J. L. McCARTNEY
VINCENT W. S. CHAN
To achieve consistently successful outcomes with regional anesthesia, practitioners must have adequate knowledge
and experience. Increasing pressure on both trainers and trainees, combined with the complexity of modern general
anesthetic agents, has caused anesthetic trainees to become less familiar and thus less confident in the practice of
many regional anesthetic techniques. Often, it is easier to give a general anesthetic, especially when faced with a
tight operating room schedule, or a surgeon or patient who does not appreciate the benefits of regional anesthesia.
As a result, a lack of familiarity with regional anesthetic techniques among trainers can lead to a consequent
decrease in exposure for trainees.
However, regional anesthesia offers many advantages over general anesthesia, including reduction in postoperative
pain, nausea, and sedation. The results of a large meta-analysis published in 2000 showed that regional anesthesia
[1]
was superior to general anesthesia, with a decrease in morbidity and mortality rates. The reasons for teaching
[2]
residents to use regional anesthesia are, therefore, becoming clearer to anesthesiologists. In addition, because
regional anesthesia is an important option for so many surgical procedures, there is a responsibility for training
centers to ensure that all trainees are familiar with the most common regional anesthesia techniques by the time they
have completed their training.
This chapter examines the teaching of regional anesthesia techniques to both physicians in training and those who
have completed their training. The parameters that are currently regarded as acceptable for adequate training are
presented as well as the best time frame to provide this training. Finally, current assessment methods for regional
anesthesia skills are discussed.
Why Teach Anesthesiologists Regional Anesthesia?
Regional anesthesia is an important part of the anesthesiologist’s armamentarium. It provides an alternative to

general anesthesia and is customarily performed in “difficult” surgical patients whose severe or unstable disease
processes make general anesthesia undesirable. These patients include those in whom airway manipulation could
precipitate bronchospasm, those for whom general anesthesia might compromise an unstable cervical spine, or those
in whom disturbance of respiratory function could result in decompensation. Regional anesthesia may be beneficial
if the patient’s sympathetic response to tracheal intubation may aggravate myocardial ischemia or if general
anesthesia is likely to cause cognitive dysfunction. Regional anesthesia is particularly indicated for patients
undergoing peripheral limb surgery, because it provides effective intraoperative anesthesia and postoperative pain
control.
However, regional anesthesia should not be reserved for only the most challenging anesthetic cases. Regional
anesthesia also offers some unique perioperative advantages over general anesthesia. Administration of local
anesthetics or other analgesic adjuncts into the subarachnoid or epidural space during and after surgery can attenuate
surgical stress response and therefore lessen the degree of perioperative catabolism and hypermetabolism commonly
seen when general anesthesia is performed alone. Regional anesthesia also provides effective pain control after
surgery, especially when a continuous catheter technique is combined with a constant analgesic infusion. Reduction
of postoperative pain at rest and with movement can further reduce postoperative morbidity and hasten
convalescence, which is especially beneficial for patients after thoracic surgery. Increased use of regional analgesic
techniques significantly reduces dependence on systemic opioids, thus lowering the incidence of opioid-related side
effects such as nausea, vomiting, and sedation in outpatients and of postoperative paralytic ileus in patients who
have had bowel surgery.
Studies in the literature support the application of regional anesthesia in high-risk surgical patients, particularly with
respect to modifying cardiac and respiratory morbidity rates. Some studies confirm the beneficial effects of
[3] [4]
regional anesthesia in patients undergoing major vascular surgery, showing a reduction in the incidence of graft
occlusion and myocardial ischemia. Several meta-analyses confirm a reduction of pulmonary morbidity rates for
[5]
patients after thoracotomy and major abdominal surgery when thoracic epidural analgesia is applied. Data [6]
concerning patients undergoing bowel surgery also advocate the use of thoracic epidural analgesia with local
96
anesthetic, with or without opioid, to speed up recovery from paralytic ileus. The beneficial effects of regional
[7] [8]
anesthesia on blood loss and thromboembolic complications are well documented. [2]
There are, therefore, many clinical advantages associated with use of regional anesthesia. The success of regional
anesthesia is heavily dependent on the technical skill of the anesthesiologist; hence, educating anesthesiologists in
regional anesthesia remains a vital part of any anesthesia training program.
Methods for Teaching Regional Anesthesia
The ability to perform any regional technique adequately is based on the anesthesiologist’s sound knowledge of
anatomy combined with sufficient clinical experience to achieve consistently good results. Traditionally, the
theoretical knowledge required to perform any regional anesthetic technique has been found in textbooks such as
this. Other methods for teaching include lectures and tutorials, video demonstrations, and workshops with hands-on
experience. In addition, more recently, a number of CD-ROMs that provide instruction in regional anesthesia have
become available. However, the technology has to date fallen short of the ability to provide simulation of blocks in a
virtual reality environment.
Other modern media have made available many resources for learning. In particular, there are many excellent
resources on the Internet. The best of these resources, along with summaries of the information presented, are listed
in Table 8–1 . These resources provide instruction, often with video accompaniment and anatomic drawings, as well
as tests of knowledge with the opportunity to complete on-line continuing medical education exercises.
When Is the Ideal Time to Learn Regional Anesthesia Techniques?
It seems logical that the best time to begin learning about regional anesthesia is as early in training as possible. The
principles of good knowledge of anatomy and block technique that ensure success apply to many regional anesthesia
techniques. If these principles are learned early, trainees become confident of their technical ability. This confidence
facilitates learning new anesthesia techniques later in their medical careers. In most training programs, obstetric and
orthopedic experience tends to occur earlier, and these are the areas in which the majority of clinical experience with
regional anesthesia takes place. Later in the training program, more emphasis is placed on the major subspecialties,
which potentially offer fewer opportunities for experience in regional anesthesia. Thus, for trainees who have no
specialized interest in regional anesthesia, optimal training would reasonably include an early overall experience of
regional techniques, followed by regular updates as the trainees progress through the program. For those who would
like to pursue regional anesthesia as a subspecialty, it would seem logical that they should complete a fellowship
year after training.
What Constitutes Adequate Training in Regional Anesthesia?
What constitutes adequate training in regional anesthesia has not been defined. In the past, regional anesthesia
TABLE 8-1 -- REGIONAL ANESTHESIA RESOURCES ON THE INTERNET

Site URL Features
American Society of Regional Anesthesia www.asra.com Details of meetings and review courses, CME
for members
Pain.com (regional anesthesia section) www.pain.com/regional/default.cfm Instructional videos, library, CME, RA forum
Virtual Anaesthesia Textbook www.virtual-anaesthesia-textbook.com/vat/ Anatomy demonstrations and video of nerve
anatomy.html stimulation
Global Textbook of Anesthesiology www.gasnet.org/gta/#regional Cervical block for carotid endarterectomy,
techniques of orbital RA
St. Luke’s Roosevelt Hospital Center, NY www.nysora.com/ RA techniques as practiced at St. Luke’s
Hospital Center, NY
Cleveland Clinic Manual of Orthopedic www.anes.ccf.org:8080/pilot/ortho/ Manual of orthopedic anesthesia for residents
Anesthesia orthintr.htm
Illustrated notes in regional anesthesia www.depts.washington.edu/anesth/regional/ Brachial plexus, femoral, sciatic and stellate
welcome.html blocks with images
CME, continuing medical education; RA, regional anesthesia.
was taught in many institutions in a haphazard manner, and trainees were often left to pursue experience in regional
anesthesia on their own. A common complaint among many anesthetists after completion of training is their lack of
97
experience in performing regional techniques. However, the benefits of good training in regional anesthesia are
evident. Trainees who complete their programs with confidence in their regional anesthesia skills are often more
willing to continue regional anesthesia practice afterward. [9]
What constitutes a core knowledge of regional anesthesia by completion of training is a controversial topic, but it
would seem reasonable to expect a competent practicing anesthesiologist to be able, if necessary, to perform
regional anesthesia on any part of the body below the neck level. Thus, it would seem essential that all anesthetists
should be competent to perform thoracic or lumbar epidural and spinal anesthesia as well as at least one regional
method of anesthetizing the upper limb, such as axillary brachial plexus block.
Journal articles have shown that in North America a large variation exists in trainees’ performance of regional
anesthesia techniques ( Fig. 8–1 ). The majority of their experience is derived from performing central neuraxial
[10]
blocks, particularly for obstetric cases, and they have less experience with peripheral nerve block techniques.
Peripheral nerve blocks provide excellent anesthesia and postoperative analgesia for upper and lower limb surgery.
Many anesthetists are unfamiliar with the practice of peripheral nerve blocks, especially of lower limb blocks. [11]
Lower limb regional anesthesia may become increasingly important for lower limb surgery owing to the increased
use of potent antithrombolytic drugs and the potential complications from those drugs that may stem from use of
central neuraxial techniques.
It has been estimated that residents in the United States may finish training having performed no more than 3 spinal,
27 epidural, and 7 peripheral nerve blocks. Moreover, instruction in administering nerve blocks may occur several
years before the training period is complete. This level of experience does not constitute adequate training in
regional anesthesia.
Assessing Adequate Training in Regional Anesthesia
Attempts have been made in the past few years to determine what constitutes adequate training in several
anesthesia-related practical procedures, including regional anesthesia techniques. Most investigators have
concentrated on quantitative methods.
QUANTITATIVE ASSESSMENT METHODS
Several investigators have made efforts to determine the number of blocks that have to be performed to achieve a
consistent level of success. Kopacz and coworkers examined epidural and spinal anesthesia and found that to
[12]
consistently achieve more than an 80% success rate, 60 attempts and 41 to 45 attempts, respectively, were required.
In a similar study, Konrad and coworkers found results similar to those of Kopacz and coworkers for epidural and
[13]
spinal anesthesia and noted that 60 attempts were required to learn axillary brachial plexus block using a nerve
stimulator technique ( Fig. 8–2 ). Other investigators in other areas of anesthesia practice and medicine have found
similar results for learning new technical skills as diverse as upper and lower gastrointestinal endoscopy and
managing cardiac anesthesia patients. All reports noted that about 20 attempts were required to achieve a marked
[14] [15]
improvement. However, this number was followed by a plateau or a decrease in success that was
98
Figure 8-1 Disparities in the amount of regional anesthesia used in training programs in the United States.(From Kopacz DJ, Bridenbaugh LD:
Are anesthesia residency programs failing regional anesthesia? The past, present, and future. Reg Anesth 18:84–87, 1993.)
Figure 8-2 Illustration of typical learning curve for a regional anesthesia procedure using quantitative teaching methods (axillary brachial plexus
block).(From Konrad C, Schupfer G, Wietlisbach M, et al: Learning manual skills in anesthesiology: Is there a recommended number of cases
for anesthetic procedures? Anesth Analg 86:635–639, 1998.)
only reversed after 45 to 60 attempts, when the expected level of skill was eventually acquired. For most teaching [11]
programs, providing trainees with this level of experience would require restructuring of departmental staff to
successfully increase trainee exposure. Training based on quantitative assessment methods alone would probably
mean that during the short period of time that any trainee spends in the anesthesia apprenticeship (between 4 and 7
years, depending on the training scheme), it would be necessary to concentrate on a number of essential core
regional anesthesia techniques, with the goal of achieving a satisfactory level of experience in these techniques
before completion of training. The volume of experience required to achieve necessary skills (as assessed by
quantitative methods) is not available in many training programs. This has led to an appraisal of qualitative methods
of training and assessment.
QUALITATIVE ASSESSMENT METHODS
Qualitative training and assessment have been developed in the last few years, primarily in surgical training
programs that have had less clinical material available for training. In common with regional anesthesia, the surgical
99
specialties must also certify competency in technical tasks, and most techniques are performed too infrequently for
the trainee to complete the minimum number of procedures required for competency. Surgeons have used informal
subjective assessment for both formative and summated assessment. However, to improve the validity and
[16]
reliability of their trainee evaluations, they have begun to examine other objective methods of assessing technical
skills. The decrease in availability of clinical material is partly due to increasing patient expectations regarding the
[17]
skill of those who perform their surgical procedures and to the decrease in the number of surgical procedures
performed. Qualitative training and assessment methods have allowed improvement in training using smaller
amounts of clinical material.
In regional anesthesia, qualitative training and assessment may allow a broader range of regional anesthesia skills to
be acquired. It is obvious from this discussion that adequate experience with some techniques is difficult to achieve
within a training scheme. Qualitative learning and assessment may, therefore, be more effective for these
procedures. An example of a qualitative assessment tool is the Objective Structured Assessment of Technical Skills
(OSATS). OSATS uses both an operation-specific checklist and a global assessment rating scale to determine the
technical competence of surgical trainees at different stages of training. This type of global rating scale and checklist
is easily applied to regional anesthesia procedures ( Table 8–2 ).
In the surgical setting, the definition of objective parameters of acceptable performance has greatly improved the
assessment of technical skills, and these measures ensure that trainees are being evaluated based on their ability to
perform a task rather than on the relationship that exists between the candidate and the preceptor. The checklist
[18]
turns the examiner into an observer of a skill rather than an interpreter of a performance and, therefore, greatly
reduces subjectivity. Global assessment rating scales ensure that thoroughness demonstrated by conforming to a
checklist is not interpreted as competence. Conversely, structured global rating scales give the experienced
[18]
clinician the opportunity to evaluate the candidate’s performance, regardless of whether or not the checklist criteria
were met.
Using qualitative methods of assessment of regional anesthesia skills may improve training across the core
techniques that are necessary for certification as a specialist in anesthesia without having to increase the number of
blocks performed. To overcome the lack of clinical teaching material available in training programs,
TABLE 8-2 -- GLOBAL RATING SCALE OF OPERATIVE PERFORMANCE AS APPLIED TO REGIONAL

*
ANESTHESIA PROCEDURES
Please circle the number corresponding to the candidate’s performance in each category, irrespective of
training level.
Scale
Performance 1 2 3 4 5
Respect for Frequently used Careful handling of tissue Consistently handled
tissue unnecessary force on but occasionally caused tissues appropriately with
tissue or caused damage inadvertent damage minimal damage
Time and Many unnecessary moves Efficient time/motion but Clear economy of
motion some unnecessary moves movement and maximum
efficiency
Instrument Repeatedly makes Competent use of Fluid moves with
handling tentative or awkward instruments but instruments and no
moves with instruments by occasionally appeared stiff awkwardness
inappropriate use of or awkward
instruments
Knowledge of Frequently asked for Knew names of most Obviously familiar with
instruments wrong instruments or used instruments and used the instruments and their
inappropriate instrument appropriate instrument names
Flow of Frequently stopped Demonstrated some Obviously planned course
procedure procedure and seemed forward planning with of procedure with
unsure of next move reasonable progression of effortless flow from one
procedure move to the next
Use of Consistently placed Appropriate use of Strategically used
assistants assistants poorly or failed assistants most of the time assistants to the best
100
TABLE 8-2 -- GLOBAL RATING SCALE OF OPERATIVE PERFORMANCE AS APPLIED TO REGIONAL

*
ANESTHESIA PROCEDURES
Please circle the number corresponding to the candidate’s performance in each category, irrespective of
training level.
Scale
Performance 1 2 3 4 5
to use assistants advantage at all times
Knowledge of Deficient knowledge Knew all important steps Demonstrated familiarity
procedure of operation with all aspects of
operation
Overall Very poor Competent Clearly superior
performance
Overall rating: PASS FAIL
Modified from Martin JA, Regehr G, Reznick R, et al: Objective structured assessment of technical skill (OSATS)
for surgical residents. Br J Surg 84(2):273, 1997.
*An example of a global rating scale that may be applied to qualitative assessment of regional anesthesia procedures. The table is modified from
the original source to be more applicable to regional anesthesia.
it may be necessary to provide teaching and evaluation of regional anesthesia skills using qualitative rather than
quantitative methods.
Continuing Medical Education
Keeping a formal logbook of continuing medical activities is now essential in many parts of the world and, in some
areas, is required for continuation of certification. It is vital that practitioners of any anesthesia subspecialty maintain
their knowledge, training, and skills in that area. The maintenance of skills requires regular practice of a technique
combined with regular updates of theoretical knowledge. Meetings such as those organized by the American Society
of Regional Anesthesia and other regional anesthesia societies offer resources for maintaining knowledge and skills
as well as an update on recent developments. In addition, societies such as these provide a forum for practitioners to
meet others with similar interests, which is a further aid to maintaining skills.
The great beauty of learning a regional technique as opposed to a surgical technique is that if a regional technique
fails, the patient can usually be aided by measures that may be as simple as infiltration of a local anesthetic or as
extreme as administering propofol and using a laryngeal mask airway! It could, therefore, be argued that a skilled
regional anesthetist should be capable, with minimal experience, of practicing a new technique on a patient.
However, this decision depends to a large degree on the potential adverse effects of a technique. It would seem
reasonable, given that all usual precautions are taken, for an anesthetist without much previous experience in
performing the technique to attempt a relatively benign procedure such as axillary brachial plexus block or femoral
nerve block. However, for a block with potentially serious morbidity, such as neurolytic celiac plexus block,
performing the technique with no supervision and minimal previous experience would be unwise to say the least.
Many workshops have been developed with the aim of teaching interventional pain techniques to clinicians with
minimal experience. The role of short courses such as these is probably to provide an introduction to the use of these
techniques and not to serve as complete training. [19]
Barriers to the Performance of Regional Anesthesia and Potential Solutions
There are many reasons that practicing anesthesiologists may choose not to perform regional anesthetic techniques
with which they are unfamiliar. These reasons include tight operating room schedules with surgeons who may not be
very appreciative of the advantages of regional anesthesia. Owing to the increasing proportion of patients who have
outpatient surgery, anesthesiologists have less time to discuss the performance of blocks with patients. Patients who
are given preoperative education regarding regional anesthesia are more likely to accept a regional anesthetic
technique. Lack of sufficient experience during training makes many anesthesiologists uncomfortable about
performing regional anesthesia, but they are especially reluctant under less than optimal circumstances.
101
At our institution, some of these problems have been overcome by use of a separate room for placement of regional
anesthetic blocks. Many surgeons at our institution have become accustomed to regional anesthesia and realize the
benefits it provides both for the patients’ well-being and for their own operating room schedules. These surgeons
become advocates for regional techniques when they discuss possible anesthetic options with patients in the office.
The separate block room provides an area where anesthesiologists can teach regional anesthetic techniques with less
time pressure than normally exists in the operating room. This block room is staffed by a recovery nurse who is
experienced in providing assistance for administration of regional anesthesia.
Successful regional anesthesia outcomes require careful technique and time for the block to develop. Our surgical
and other operating room colleagues have become aware of the reduction in recovery time at the end of an operative
procedure. Regional anesthesia, when performed well, has been demonstrated not to delay operating room
procedures. Patients who have had a good regional anesthesia experience become advocates for regional anesthesia
by informing their families and friends of its benefits.
Conclusion
Regional anesthesia is an important anesthetic option for any patient undergoing surgery, and, therefore, all
anesthetists should have adequate skills in this area. To date, many anesthesia training programs fail to adequately
provide adequate education in regional anesthesia by the time training is completed. Recognition of the importance
of the subject, combined with improved methods of teaching and assessing regional anesthesia skills, should help to
alleviate some of these problems.
REFERENCES
1. Cousins MI: Acute and postoperative pain. In Melzack R, Wall PD (eds): Textbook of Pain, 3rd ed. Edinburgh, Churchill Livingstone, 1994.
2. Rodgers A, Walker N, Schug S, et al: Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: Results from
overview of randomised trials. BMJ 321:1493, 2000.
3. Leon-Casasola OA, Lema MJ, Karabella D, et al: Postoperative myocardial ischemia: Epidural versus intravenous patient-controlled analgesia.
A pilot project. Reg Anesth 20:105–112, 1995.
4. Yeager MP, Glass DD, Neff RK, et al: Epidural anesthesia and analgesia in high-risk surgical patients. Anesthesiology 66:729–736, 1987.
5. Tuman KJ, McCarthy RJ, March RJ, et al: Effects of epidural anesthesia and analgesia on coagulation and outcome after major vascular
surgery. Anesth Analg 73:696–704. 1991.
6. Ballantyne
JC, Carr DB, deFerranti S, et al: The comparative effects of postoperative analgesic therapies on pulmonary outcome: Cumulative
meta-analyses of randomized, controlled trials. Anesth Analg 86:598–612, 1998.
83:757–765, 1995.
8. Steinbrook RA: Epidural anesthesia and gastrointestinal motility. Anesth Analg 86:837–844, 1998.
9. Buffington CW, Ready LB, Horton WG: Training and practice factors influence the use of regional anesthesia: Implications for resident
education. Reg Anesth 11:2–6, 1986.
10. Kopacz DJ, Bridenbaugh LD: Are anesthesia residency programs failing regional anesthesia? The past, present, and future. Reg Anesth 18:84–
87, 1993.
11. Hadzic
A, Vloka JD, Kuroda MM, et al: The practice of peripheral nerve blocks in the United States: A national survey. Reg Anesth Pain Med
23:241–246, 1998.
12. KopaczDJ, Neal JM, Pollock JE: The regional anesthesia “learning curve.” What is the minimum number of epidural and spinal blocks to
reach consistency? Reg Anesth 21:182–190, 1996.
13. Konrad C, Schupfer G, Wietlisbach M, et al: Learning manual skills in anesthesiology: Is there a recommended number of cases for anesthetic
procedures? Anesth Analg 86:635–639, 1998.
14. Cass OW, Freeman ML, Peine CJ, et al: Objective evaluation of endoscopy skills during training. Ann Intern Med 118:40–44, 1993.
15. Schertz
RD, Baskin WN, Frakes JT: Flexible fiberoptic sigmoidoscopy training for primary care physicians: Results of a 5-year experience.
Gastrointest Endosc 35:316–320, 1989.
16. Winckel CP, Reznick RK, Cohen R, et al: Reliability and construct validity of a structured technical skills assessment form. Am J Surg
167:423–427, 1994.
102
17. Martin
JA, Regehr G, Reznick R, et al: Objective structured assessment of technical skill (OSATS) for surgical residents. Br J Surg 84:273–
278, 1997.
18. Regehr
G, MacRae H, Reznick RK, et al: Comparing the psychometric properties of checklists and global rating scales for assessing
performance on an OSCE-format examination. Acad Med 73:993–997, 1998.
19. Palmer PP: Implantable Pain Therapies—what training is required? Anesth Analg 88:1203–1204, 1999.
103
Section III - Chapter 9 - Pain Mechanisms and Local Anesthetics: Scientific Foundations for Clinical Practice
Section III - Basic and Clinical Researches in Regional Anesthesia
James E. Heavner
David Niv
104
Chapter 9 - Pain Mechanisms and Local Anesthetics: Scientific

Foundations for Clinical Practice
JAMES E. HEAVNER
Block of voltage-gated sodium channels by local anesthetics injected near peripheral nerves produces sensory and/or
motor block. Binding of opioids to opioid receptors, especially µ receptors, produces analgesia. Inhibition of the
enzyme cyclooxygenase (e.g., by aspirin) prevents sensitization of nociceptors. This and other information
fundamental to the management of acute and chronic pain is a result of clinical and basic research that has
progressively built on prior knowledge. In this chapter, I discuss some of the important scientific advances that
provide a rational basis for contemporary approaches to pain management using local anesthetics and other
treatment modalities.
Cornerstones of the scientific knowledge base for pain management include (1) detailed information about the gross
and microscopic anatomy of the body; (2) basic principles of normal physiology, especially with respect to sensory
perception, and the physiology of altered sensory states; and (3) basic pharmacodynamic and pharmacokinetic
principles.
In 1965, Melzack and Wall presented the gate control theory that brought together much of the existing knowledge
about pain (Fig. 9-1 (Figure Not Available) ). The focus of the theory was on how sensory information is processed
[1]
by the spinal cord. However, synthesis of the theory depended on information about how sensory information is
generated, how it gets to the spinal cord, and how it is projected from the cord to higher centers in the central
nervous system, and how signals from higher centers influence sensory information processing at the spinal level.
An essential part of the theory was knowledge of the fact that under normal circumstances all nociceptive
information travels more slowly to the spinal cord than the majority of non-nociceptive information. According to
the theory, the faster arriving non-nociceptive signals activate local inhibitory processes that “close the gate,”
preventing nociceptive signals from reaching the second-order neurons in the spinal cord (central transmission cells
located in the spinal cord dorsal horn). Both nociceptive and non-nociceptive input reaches the transmission neuron
(T-neuron). The T-neuron transmits to higher central nervous system (CNS) centers information in a coded signal
represented by the pattern of the
Figure 9-1 (Figure Not Available) Schematic design of the gate control theory of pain mechanisms: L, large-diameter fibers; S, small-diameter
fibers. The fibers project to the substantia gelatinosa (SG) and first central transmission (T) cells. The inhibitory effect exerted by SG on the
afferent fiber terminals is increased by activity in L fibers and decreased by activity in S fibers. A line running from the large-fiber system to the
central control mechanisms represents the central control trigger; these mechanisms in turn project back to the gate control system. The T cells
project to the entry cells of the action system. +, Excitation; −, inhibition. (Reprinted with permission from Melzack R, Wall PD: Pain
mechanisms: A new theory. Science 150:971–978, 1965. Copyright 1965 American Association for the Advancement of Science.)
TABLE 9-1 -- CLASSIFICATION OF PERIPHERAL NERVES ACCORDING TO FIBER SIZE AND PHYSIOLOGIC PROPERTIES
Conduction
Fiber Velocity
Class Subclass Myelin Diameter µ (M/S) Location Function
A alpha + 6–22 30–120 Afferent to and efferent from Motor, proprioception
muscles and joints
beta + 6–22 30–120 Afferent to and efferent from Motor, proprioception
muscles and joints
gamma + 3–6 15–35 Efferent to muscle spindles Muscle tone
delta + 1–4 5–25 Afferent sensory nerves Pain, temperature, touch
B + <3 3–15 Preganglionic sympathetic Various autonomic functions
C sC − 0.3–1.3 0.7–1.3 Postganglionic sympathetic Various autonomic functions
d gamma − 0.4–1.2 0.1–2.0 Afferent sensory nerves Various autonomic functions;
C pain, temperature, touch
From Berde CB, Strichartz GR: Local anesthetics. In Miller RD (ed): Anesthesia, 5th ed. Philadelphia, Churchill Livingstone, 2000, pp 491–521.
105
T-neurons’ electrical discharge. Descending projections from higher CNS centers reach the spinal cord and
influence the output of T-neurons.
Although not accepted as “gospel truth” by all neuroscientists, the Melzack and Wall gate control theory
nevertheless tied together information and ideas that existed at the time. It was a major stimulus for new research
and provided a conceptual framework for explaining clinical observations.
The Peripheral Nervous System: Receptors and Axons
With respect to sensory signal generation and transmission to the spinal cord, there was, in 1965, a substantial
knowledge base regarding peripheral sensory nerve endings, namely, sensory receptors (not to be confused with
drug receptors) and peripheral axons. Researchers had found evidence to support the fact that the peripheral nervous
system is highly specific with respect to the type of stimulus (adequate) required to activate different types of
sensory receptors, which have distinct morphology. Receptors at the peripheral end of axons were thought
[2]
(correctly) to impart specifically to peripheral axons. Peripheral nerve axons were known to exist in various sizes
(0.3 µ to 22 µ), be surrounded by myelin, and conduct action potentials at various speeds (0.1 m/sec–120 m/sec) (
Table 9-1 ). Nerve axons were classified as myelinated and unmyelinated. Nerve axons are myelinated if individual
axons are surrounded by Schwann cells interrupted at nodes (nodes of Ranvier, which are axonal areas free of
myelin at fixed intervals) and unmyelinated if several axons are surrounded by a Schwann cell forming a Remak
bundle ( Fig. 9-2 ). Action potentials pass thorough myelinated axons by saltatory conduction (i.e., by leaping from
node to node) ( Fig. 9-3 ). This mode of transmission is faster than continuous spread along the axonal membrane.
Within the myelinated axon series, action potential propagation speed is proportional to the size of the axon (i.e., the
larger the axon, the faster the propagation speed).
Action potentials spread along the membrane of unmyelinated axons at a considerably slower speed (0.1–2.0 m/sec)
than through myelinated axons (3.0–120 m/sec). Nociceptors, which are sensory nerve endings activated by noxious
stimuli (thermal, chemical, or mechanical), are the endings of small myelinated (A delta) and unmyelinated (C)
fibers—the two groups of slowest conducting axons (speed of signal conduction in B fibers, preganglionic
autonomic axons, is about the same as in A delta fibers) ( Table 9-2 ).
Fast Pain and Slow Pain
Easy to conceptualize from the foregoing is nociceptive information traveling to the spinal cord at two different
TABLE 9-2 -- THE PROPERTIES OF TWO WIDELY DISTRIBUTED TYPES OF NOCICEPTIVE UNIT FROM THE SKIN
High Threshold Mechano-

receptor (HTM) Polymodal Nociceptor (PMN)
Axon caliber A delta C
Response to strong pressure + +
Response to heat 0 +
Response to irritant chemicals 0 +
Receptive field multiple points one small zone *
Key: + responds well; 0 no response.
*In primates, some PMN units have larger fields.
106
Figure 9-2 Transverse sections of a peripheral nerve (A) showing the outermost epineurium, the inner perineurium that collects nerve axons in
fascicles, and the endoneurium that surrounds each myelinated fiber. Each myelinated axon (B) is encased in the multiple membranous wrappings
of myelin formed by one Schwann cell, each of which stretches longitudinally over approximately 100 times the diameter of the axon. The
narrow span of axon. The narrow span of axon between these myelinated segments, the node of Ranvier, contains the ion channels that support
action potentials. Nonmyelinated fibers (C) are enclosed in bundles of 5 to 10 axons by a chain of Schwann cells that tightly embrace each axon
with but one layer of membrane. (From Berde CB, Strichartz GR: Local anesthetics. In Miller RD (ed): Anesthesia, 5th ed. Philadelphia,
Churchill Livingstone, 2000, pp 491–521.)
speeds, depending on whether the pathway is via A delta fibers or C fibers, that is, “fast” and “slow” pain. Indeed,
multimodal noxious stimulation elicits in humans a sensation of two types of pain arriving at conscious centers at
different speeds. [2]
Figure 9-3 Saltatory propagation. Comparing impulse propagation in nonmyelinated (upper) and myelinated (lower) axons. In nonmyelinated
axons, the impulse moves forward by sequential depolarization of short adjoining membrane segments. On the other hand, depolarization in
myelinated axons is discontinuous; the impulse leaps forward from node to node. Note how much farther ahead the impulse is in the myelinated
axon after four depolarization sequences.(From de Jong RH: Local Anesthetics. St. Louis, Mosby, 1994.)
Peripheral Sensory Receptors and Axons as Targets for Analgesic Drugs and Procedures
An obvious conclusion is that if noxious information is prevented from reaching the central nervous system, no pain
will be felt. The effect is permanent or temporary depending on the nature of the technique used to block the transfer
of information. Destruction of the peripheral sensory neural elements or transsection of peripheral axons
permanently stops information transfer unless regeneration and subsequent recovery of function occur.
Through trial and error, it was discovered early in human history that a number of physical approaches could be
used to render an extremity insensitive. These approaches include cooling the extremity, rendering it ischemic, or
[3]
putting pressure on peripheral nerves. If the ischemia or pressure is not prolonged, and if the cooling is not extreme,
sensation recovers upon removal of the physical assault. Studies have demonstrated that cold, pressure, and ischemia
interfere with peripheral (and central) nervous system function.
107
Another important discovery made early in human history is that ingestion of parts of some plants produces
analgesia (e.g., bark of willow trees [Salix alba] and juice of the poppy plant [Papaver somniferum]). Chewing the
leaves of the coca plant (Erythroxylum coca) produces numbness of the tongue. It is now known that the active
ingredient of willow bark is salicin, which is converted to salic acid when ingested,
Figure 9-4 Local anesthetic interaction at binding site. Scheme of local anesthetic binding to channel protein binding site. Local anesthetic cation
reachs the binding site via the channel’s internal mouth (“local cation”) or via the lipophilic transmembrane route (“local base”). Hydrophilic
access is optimal when channel proteins are in the open state. Hydrophobic uncharged local anesthetic base (e.g., benzocaine) accesses the
channel site via the lipid membrane, independent of channel state. Captured local anesthetic narrows the channel pore, freezes channel protein
realignment, and/or repels like-charged Na+ . Although the dominant mechanism may vary with spatial configuration, the net result is Na+
impermeability and membrane inexcitability. (From de Jong RH: Anesthetics. St. Louis, Mosby, 1994.)
and that salic acid inhibits cyclooxygenase, thereby preventing the production of prostaglandins. One action of [4]
prostaglandins is sensitization of nociceptors. Hence, willow bark, as well as the pharmacologic agent,
acetylsalicylic acid (aspirin) that is a derivative of the active principle in willow bark, blocks pain associated with
sensory receptor inflammation. It is known that receptors for the active ingredient of poppy juice (i.e., morphine),
are present on peripheral neural structures. However, convincing evidence is lacking that binding of morphine to
these structures plays a significant role in the analgesic action of morphine. The local anesthetic, cocaine, is the
active ingredient of the coca plant. Scientific investigation has revealed that local anesthetics act by interfering with
function of voltage-gated sodium channels ( Fig. 9-4 ).
[5]
PHARMACOLOGY
Two important pharmacologic topics are subtly introduced above. These are (1) the concept of a drug
receptor and (2) the concept of isolation of pure principle. In 1905, Langley introduced the concept that
most drugs, hormones, and neurotransmitters produce their biological effects by interacting with receptor
substances in cells. Drug-receptor theory was evoked to explain, among other things, the extraordinary
[6]
potency and specificity with which some drugs mimic a biological response. The existence of receptors is
now firmly established. Receptors, including the morphine receptor, have been isolated and cloned. A
major effort is ongoing to expand our understanding of how binding of a drug to a receptor produces an
effect. Studies have demonstrated the existence of G proteins that couple some receptors (G protein-
coupled receptors) to intracellular structures to produce inhibitory or excitatory responses ( Fig. 9-5 ).
Sertürner pioneered the isolation of pure principle concept. In 1906, he isolated the pure substance in
[7]
poppy juice (opium), which he named morphine after Morpheus, the Greek god of dreams. This
108
established the standard for isolating active substances from impure sources (i.e., morphine from opium).
Some obvious fallouts from this approach are chemical identification of active substance, which does the
following:
1. Opens the possibility for mass production of pure active substance using a controlled
manufacturing process to extract the substance or to synthesize it. (In so doing, quality and
quantity of dose can be assured.)
2. Provides a basis for predicting the structure of the receptor to which the substance binds.
3. Provides the opportunity to explore structure–activity relationships to develop antagonists and/or
pharmacologically more desirable agonists that bind to the same receptor as does the parent
compound.
There is considerable interest in analgesic drugs that act on peripheral nociceptors. The obvious advantage
of such drugs, if they are selective for sites on the nociceptors either for pharmacodynamic or
pharmacokinetic reasons, is absence of such a response as central nervous system side effects. Despite the
existence of numerous drug receptors on nociceptors or on structures that influence nociceptors ( Fig. 9-6
), only drugs that act by inhibiting cyclooxygenase (nonsteroidal anti-inflammatory drugs [NSAIDs]) have
consistent, convincing, clinically useful action. Not to be overlooked is the role of α2 -adrenergic agonists
and antagonists acting at the peripheral receptor level as a diagnostic test and/or treatment for
sympathetically maintained pain (Fig. 9-7 (Figure Not Available) ).
The action of local anesthetics on peripheral nerve axons as a means of preventing nociception is well
known and well described. Key points with respect to local anesthetics include the fact that they produce
reversible block of action potential propagation in nerve axons by blocking voltage-gated, tetrodotoxin-
sensitive, sodium channels. The scientific foundations that support this range from the observations that
electricity flows through peripheral nerves and that nerve axons are polarized to observations with respect
to electric potential changes that occur across axonal membranes and accompanying electrical currents to
results of contemporary molecular biology studies that have revealed the nature of ion channels in axonal
membranes. [5]
In step with—and complementary to—progress in understanding the physiology of nerve conduction was
the accumulation of knowledge about the pharmacology of local anesthetics. Critical events in the
development of modern local anesthetics include the observation that cocaine numbs the tongue; the
isolation, purification, and elucidation of the structure of cocaine; and the discovery of the chemical
structure—the backbone—of molecules, which is essential for an understanding of local anesthetic activity
( Fig. 9-8 ). Although local anesthetics exhibit properties that indicate they act via a drug-receptor
interaction mechanism (i.e., they exhibit a strong structure-activity relationship and are relatively potent),
the concept of a local anesthetic receptor is relatively new. Other means of stopping transmission of
nociceptive information through peripheral axons include destructive lesioning using heat, cold, or a
scalpel, or chemical agents such as alcohol and phenol. [8]
109
Figure 9-5 G proteins couple membrane receptors to intracellular structures, resulting in stimulatory or inhibitory actions.(From Ross EM:
Pharmacodynamics. In Hardman JG, Limbird LE (eds): Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 9th ed. New York,
McGraw-Hill, 1996, pp 29–41.)
110
Figure 9-6 Structures, molecules, and receptors that influence nociceptor activation.(From Levin JD, Fields HL, Basbaum AI: Peptides and the
primary afferent nociceptor. J Neurosci 13:2273–2286, 1993; Copyright © 1993 by the Society for Neuroscience; Reprinted by permission of the
Society for Neuroscience.)
Figure 9-7 (Figure Not Available) The varying contributions of sympathetic independent pain (SIP) and sympathetically maintained pain (SMP)
to the total magnitude of the pain. The diagonal line represents a continuum from total SMP through varying proportions of SMP and SIP to total
SIP. Most of Patient A’s pain is SIP, whereas Patient B’s pain is predominately SMP.(From Heavner JE: Newer concepts of pain mechanisms
and therapeutic implications. Curr Rev Pain 1:377–382, 1997.)
Figure 9-8 Basic molecular structure of local anesthetics.
Figure 9-9 Contribution of tetrodotoxin-sensitive (TTX-s) and tetrodotoxin-resistant (TTX-r) Na+ channels to the excitability of nociceptive
nerve endings and action potential propagation. TTX-s channels are necessary for transduction in many A delta fibers, whereas C-fiber responses
are either wholly or partly dependent on TTX-r channels. Summary of the distribution of functionally important TTX-s and TTX-r Na+ channels
in a hypothetical primary afferent, with probable dependence on fiber diameter shown in parentheses. (Adapted from Baker MD, Wood JN:
Involvement of Na+ channels in pain pathways. Trends Pharmacol Sci 22:27–31, 2001, with permission from Elsevier Science.)
The Dorsal Root Ganglia and Primary Afferent Nerve Terminals
Cell bodies for primary somatosensory afferent axons reside in the dorsal root ganglia. These structures are not
included as elements involved in gate control theory. Only recently have dorsal root ganglia cells drawn the
111
attention of investigators interested in pain. In recent history, changes in ion channels (i.e., tetrodotoxin-insensitive
sodium channels) and in dorsal root ganglion cells and sprouting of sympathetic postganglionic fibers in the ganglia
associated with nerve injury have been demonstrated ( Fig. 9-9 ). [9] [10]
NEUROPATHIC VERSUS NOCICEPTIVE PAIN
One offshoot of the introduction of the gate control theory was awareness that most of the experimental data
drawn upon to support the hypothesis were based on observations of normal animals. There was major
concern that the observations might have little, if any, relevance to chronic painful conditions that exist in
humans. This concern provided a stimulus for the production of animal models of chronic pain. One of the
more prominent methods for producing such models involved damaging nerves by placing a ligature around
a nerve bundle. This technique established the use of the terms neuropathic pain to denote pain induced by
[11]
nerve injury and nociceptive pain to denote pain initiated by nociceptor stimulation. Likewise, investigations
using animal models in conjunction with studies and observations involving human patients laid the
foundation for a proposal that pain can be categorized as a normal sensation, as a symptom, or as a disease [12]
(Fig. 9-10 (Figure Not Available) ). As a sensation, pain is perceived by normal processes structurally and
functionally unaltered by prior insult or injury. As a disease, pain is thought to be a product of structural
and/or functional alteration due to prior insult or injury. Alterations such as these are said to be a reflection
of plasticity within the nervous system ( Fig. 9-11 ).
The major focus of Melzack and Wall’s gate control theory was on how sensory information is processed
after reaching the spinal cord dorsal horn. Electrical signals arrive at nerve terminals (presynaptic terminals)
in the dorsal horn and stimulate the release of neurotransmitters. We know now that complex and numerous
processes control invasion of presynaptic terminals by propagated action potentials arriving initially from
primary afferent axons and subsequently release neurotransmitter substance from the terminals. For example,
processes from other spinal or supraspinal neurons make synaptic contact with the presynaptic terminals (
Fig. 9-12 ). Another important feature of presynaptic terminals is that transmitters which are released from
the terminals as well as the kind of neurotransmitter receptors vary. Many of the transmitters are peptides (
Table 9-3 ).
Presynaptic terminals may be hyperpolarized or depolarized when structures synapsing on them are
activated, producing inhibition or facilitation of neurotransmitter release. Presynaptic control mechanisms
were important physiologic mechanisms embodied in Melzack and Wall’s gate control theory. The DREZ
(dorsal horn entry zone) procedure involves transsection of primary afferent axons as they enter the spinal
cord. More specifically, the goal of the DREZ procedure is to selectively interrupt small nociceptive nerve
fibers. The surgical approach is based on the anatomic observation that small axons enter the spinal cord
lateral to the point where large axons enter.
Figure 9-10 (Figure Not Available) The three phases of pain. Different pain states ranging from normal (top) to abnormal (bottom) are produced by the conditions
indicated.(From Heavner JE: Newer concepts of pain mechanisms and therapeutic implications. Curr Rev Pain 1:377–382, 1997.)
112
Figure 9-11 Schematic diagram of a proposed mechanism of persistent nociception. CGRP, calcitonin gene-related peptide; NMDA, N-methyl-D-
aspartate; SP, substance P. (From Johnson BW: Pain mechanisms: Anatomy, physiology, and neurochemistry. In Raj PP (ed): Practical
Management of Pain, 3rd ed. St. Louis, Mosby, 2000.)
Figure 9-12 Hypothetical synaptic cholinergic circuits in the dorsal horn. Three distinct types of primary sensory fibers (C, A delta and A beta)
terminate in central varicosities of synaptic glomeruli, types I (C1 ), IIa (CIIa ), and IIb (CIIIb ), respectively. Each central glomerular varicosity is
presynaptic at an asymmetrical contact to dendrites of a projection neuron (b), or to an excitatory neuron (c), contacting a projection neuron (a)
and a choline acetyltransferase-immunoreactive (ChAT+) interneuron situated in lamina III. The axons of the ChAT+ cells are presynaptic both
to the central elements of glomeruli (C1 , CIIa , CIIIb ) and to the dendrites of cells linked to the ascending sensory pathway, forming a triadic
arrangement. For simplicity, only one ChAT+ neuron is shown, and only one of the primary sensory fibers (C fiber) is represented terminating in
nonglomerular varicosities (although the latter are known to represent the main form of termination of primary sensory fibers). (From Johnson
BW: Pain mechanisms: Anatomy; physiology, and neurochemistry. In Raj PP (ed): Practical Management of Pain; 3rd ed. St. Louis, Mosby,
2000.)
Spinal Cord Gray Matter and Ascending Neural Pathways
In 1952, Bror Rexed observed that cells in the spinal cord gray matter are layered similar to cells in the cerebral
[13]
cortex. He described the organization in terms of lamina, which are now named Rexed lamina (Fig. 9-13 (Figure
Not Available) ). Rexed proposed that the organization of the spinal gray matter had functional significance.
Subsequent studies showed this to be true. Structure–function observations provided information that Melzack and
Wall used to formulate the gate control
TABLE 9-3 -- PUTATIVE NEUROTRANSMITTERS IN SMALL PRIMARY AFFERENTS

Small Dorsal Capsaicin Neuronal
Transmitter Hyperesthesia Root Ganglion Depletion Release Excitation Algesic Behavior *
Peptides
Substance P + + Yes Yes + ++
Calcitonin gene-related peptide + + Yes Yes + +
Somatostatin + + Yes Yes/no + 0
Bombesin + + Yes Yes + +
Galanin + + Yes ? ? ?
Vasoactive intestinal peptide + + Yes ? 0 −
Cholecystokinin +/? + Yes ? 0 0
Excitatory amino acids
Glutamate + 0 Yes +++ +++ +++
Aspartate ? ? Yes +++ +++ +++
113
TABLE 9-3 -- PUTATIVE NEUROTRANSMITTERS IN SMALL PRIMARY AFFERENTS

Small Dorsal Capsaicin Neuronal
Transmitter Hyperesthesia Root Ganglion Depletion Release Excitation Algesic Behavior *
From Yaksh TL: Anatomy of the pain-processing system. In Waldman SD (ed): Interventional Pain Management, 2nd ed. Philadelphia, WB
* Algesic behavior observed after spinal administration; hyperesthesia observed after spinal administration
Figure 9-13 (Figure Not Available) Schematic drawing of the lamination of the spinal cord gray matter of the fifth lumbar segment in the adult
cat.(From Rexed B: The cytoarchitectonic organization of the spinal cord in the cat. J Comp Neurol 96:415–494, 1952; Copyright © John Wiley
& Sons, Inc. Reprinted by permission of Wiley-Liss, Inc., a subsidiary of John Wiley & Sons, Inc.)
theory. Two spinal cord dorsal horn neurons from two different Rexed lamina were featured in the theory. One was
a substantia gelatinosa neuron (in lamina II) and the other was a central transmission neuron (in lamina IV or V).
Substantia gelatinosa neurons were theorized to exert influence both on presynaptic terminals and central
transmission neurons. Cells classified as central transmission neurons were known to receive both nociceptive as
well as non-nociceptive input.
HISTORY
Two different theories of how sensation is processed by the nervous system existed in 1965. The specificity th [1]
hat different types of sensory information were generated in unique structures and transmitted in highly specific
ecific brain centers (i.e., pain is a specific modality like vision or hearing). The other theory proposed that senso
was contained within the pattern of action potentials generated by neurons (pattern theory) and was not depend
al elements carried the signal. The two theories were held to be mutually exclusive. However, the gate control th
he pattern and specificity theories. Specificity was imparted to primary afferent structures and pattern was impar
r neurons. Subsequent studies by Christensen and Perl showed that cells in the spinal cord dorsal horn margina
[14]
eption in that specificity appeared to persist in these second-order neurons. They responded only to noxious or t
Considerable interest developed in using drugs to target dorsal horn neurons to produce analgesia. Key
support for this approach was the demonstration of specific neurotransmitter (and drug) receptors in the
spinal cord dorsal horn ( Table 9-4 ).
As previously mentioned, an important concept solidified by animal models of chronic pain was that the
nervous system is plastic (i.e., it can be induced to undergo functional and structural alterations). More [15]
specifically, responses of dorsal horn neurons to noxious stimuli and the number and location of transmitter
receptors change when these neurons are exposed repeatedly to noxious input. The wide dynamic range
neuron (WDR), located in Rexed laminae IV and V, which exhibits “wind-up” is an example of this
phenomenon. WDR neurons respond to both non-nociceptive as well as nociceptive input. Duration of
[16]
discharge of WDR neurons increases with repetitive stimulation of C fibers (wind-up). The term central
sensitization was used to explain this behavior of WDR neurons, and neuroscientists pushed on to investigate
the mechanism of central sensitization.
The concepts of convergence of non-nociceptive and nociceptive information onto the same dorsal horn
neuron and central sensitization have been used to propose a basis for allodynia, the production of pain
perception by a normally nonpainful stimulus. If the central transmission neuron is sensitized, it may
generate a nociceptive code when it receives non-nociceptive information. It has been argued that
presynaptic as well as post-synaptic changes could result in miscoding of sensory information (Fig. 9-14 [12]
(Figure Not Available) ). For example, repeated noxious stimulation may induce a phenotypic switch in
presynaptic terminals, causing non-nociceptive terminals to release a neurotransmitter normally released by
nociceptive presynaptic terminals. At the post-synaptic level, phenotypic change may occur (e.g., in the
number and/or location of receptors for nociceptive neurotransmitters) (Fig. 9-15 (Figure Not Available) ).
By 1965, the injection of local anesthetics into the epidural or subarachnoid space to produce regional
anesthesia was well established. In 1976, Yaksh and Rudy reported results of studies demonstrating that
[17]
subarachnoid opioid administration produced analgesia in rats. This opened the possibility of using
epidurally or intrathecally administered opioids for pain control in humans. There were several reports of
114
success with this approach in 1979. [18] [19] [20]
Existing knowledge that provided a rationale for testing for a spinal action of opioids included discovery of
opioid receptors, endorphins (any endogenous substance that exhibits pharmacologic properties of morphine)
and the presence of opioid receptors in the spinal cord dorsal horn. Specific opioid receptors were identified
from 1971 to 1973. Identification of the receptors was done by using exogenous substance (e.g., drugs) as
[21]
ligands, but the realization that the receptors probably were not provided purely for the convenience of the
pharmaceutical industry led to a search for endogenous opioid receptor ligands. This search resulted in the
discovery of endorphins, which are peptides with opioid-like pharmacologic action. Opioid peptides [22] [23]
called enkephalins were shown to have a close association with pain pathways (e.g., in the substantia
gelatinosa of the spinal cord dorsal horn). In 1992, an important milestone in opioid receptor pharmacology
[24]
was reached when the first receptor (the δ receptor) was cloned; shortly thereafter, all three of the opioid
receptor subtypes were cloned. [25]
Figure 9-14 (Figure Not Available) Diagrams illustrating the proposed model for the mechanisms of touch-evoked pain. (A) Normal skin. (B)
Skin after an injury. Two types of afferent fibers are illustrated: large caliber, connected to low threshold mechanoreceptors, and fine fibers,
connected to nociceptors (and showing an axon reflex arrangement). In normal skin, stimulation of A beta afferents evokes primary afferent
depolarization (PAD) in C fibers and pain inhibition. In hyperalgesic skin, the interneurons are sensitized (shaded neurons) by the nociceptive
barrage and A beta stimulation evokes antidromic dorsal root reflexes (DRRs) (and flare) and orthodromic activation of the C fiber terminals (and
allodynia). LT, Low threshold cells; N, nociceptive cells (either normal skin or wide dynamic range). (From Heavner JE: Newer concepts of pain
mechanisms and therapeutic implications. Curr Rev Pain 1:377–382, 1997.)
Figure 9-15 (Figure Not Available) The three forms of neural plasticity that increase gain in the somatosensory
system to produce pain hypersensitivity are illustrated, highlighting changes they produce and their effects on pain
transmission. (Reprinted with permission from Woolf CJ, Salter MW: Neuronal plasticity: Increasing the gain in
pain. Science 228:1765–1772, 2000. Copyright 2000 American Association for the Advancement of Science.)
TABLE 9-4 -- SPINAL RECEPTORS THAT ALTER ACTIVITY EVOKED BY ACUTE HIGH-THRESHOLD INPUT
Receptor Origin of System C Fiber Binding * Inhibits Spinal sP Release † (−) C Fiber Evoked WDR Activity ‡ Spinal Therapeutic Ratio §
Opioid
Mu Intrinsic Yes Yes Yes High
Delta Intrinsic Yes Yes Yes High
Kappa Intrinsic ?? No Yes Low
Adrenergic
Alpha2 Bulbospinal Yes Yes Yes High
Neuropeptide Y Bulbospinal Yes Yes ? High
Serotonin
5HT1 Bulbospinal Yes Yes(?) Yes Medium
5HT3 No No Medium
GABA
A Intrinsic Yes No Yes/no Low
B Intrinsic Yes No Yes Low
Adenosine
A1 ? No No Yes Low
Cholinergic
Muscarinic Intrinsic Yes No(??) Yes Medium
GABA, Gamma-aminobutyric acid.
From Yaksh TL: Anatomy of the pain-processing system. In Waldman SD (ed): Interventional Pain Management, 2nd ed. Philadelphia, WB Saunders, 2001, pp 11–20.
*Indicates presence of capsaicin-sensitive terminals.

†Inhibits release of substance P from spinal cord in vitro or in vivo
‡Blockade of C fiber evoked activity in wide dynamic range neurons
§Ability of agent, when given spinally, to produce analgesia without producing motor dysfunction in the rat
115
MOLECULAR BIOLOGY
Watson and Crick’s discovery of the DNA α helix ( Fig. 9-16 ) in 1953 initiated the modern era of
[26]
molecular biology and provided the framework for understanding how genetic information is transmitted
from generation to generation. Because every nucleated cell in an organism contains identical DNA (the
genotype), an area of focus for molecular biologists is what controls the expression of information
contained in DNA to impart specific properties to cells (i.e., phenotypic expression). A phenotypic switch
in the transmitter released by large myelinated axons is uniquely activated by light touch; thus, terminals
of the axon-released substance P (instead of glutamate) may be a mechanism whereby a non-noxious
signal is converted to a noxious signal.
Spinal Cord Projection Pathways
In the 19th and early 20th centuries, there was considerable investigation of communication among spinal cord
neurons (i.e., propiospinal phenomena). Perhaps most noteworthy was the interest in Lissauer’s tract as a means of
distributing noxious sensory information to multiple spinal segments. As the 21st century begins, interest in the
[2]
cognitive aspects of pain perception directs attention to the question of how nociceptive information is conveyed
from the spinal cord to supraspinal areas of the CNS. A number of pathways are known to carry nociceptive
information cranially from the spinal cord ( Table 9-5 ). The spinothalamic tract that lies in the anterolateral
[27]
quadrant of the spinal cord white matter is recognized as a significant pathway for relaying nociceptive information
rostrally. Results of experiments indicate that spinothalamic axons may send collaterals to multiple brain areas ( Fig.
9-17 ).
A new ascending pathway, the dorsal column post-synaptic tract, has been described relatively recently. This
pathway plays a role in visceral nociception. According to Hirshberg and colleagues, surgical interruption of the
pathway relieves chronic visceral pain. [28]
Descending Pathways
Although descending controls were a prominent feature of the gate control theory, Melzack and Wall were not
specific about which descending pathway might be involved. Sherrington reported in 1906 that a tonic inhibition of
cutaneous reflexes exists in decerebrate animals, thereby establishing a presence of descending
TABLE 9-5 -- DISTRIBUTION IN THE SPINAL CORD GRAY MATTER LAMINA OF NEURONS GIVING RISE TO ASCENDING
NOCICEPTIVE PATHWAYS
Spinal Tract Laminae
Spinothalamic All; most concentrated in LI and LV
Spinoreticular LVII, a few in the posterior horn
Spinomesencephalic Anterior and posterior horns
Postsynaptic dorsal column LIII, LIV, LVII, LX
From Heavner JE, Willis WD: Pain pathways: Anatomy and physiology. In Raj PP (ed): Practical Management of Pain, 3rd ed. Philadelphia,
WB Saunders, 2001, pp 1–10.
116
Figure 9-16 DNA α helix This figure is purely diagrammatic. The two ribbons symbolize the two phosphate-sugar chains, and the horizontal rods
symbolize the pairs of bases holding the chains together. The vertical line marks the fiber axis. (From Watson JD, Crick FHC: Genetical
implications of the structure of deoxyribonucleic acid. Nature 171:737–738, 1953, with permission. Copyright © 1953 Macmillan Magazines
Limited.)
inhibitory controls over spinal cord function. Subsequent studies using neuroanatomic and neurophysiologic
[29]
approaches established the existence of powerful and relatively specific brainstem control of spinal pain
transmission neurons. Wall demonstrated a tonic brainstem inhibition of dorsal horn neurons including, but not
limited to, lamina V neurons, that responded maximally to noxious stimuli. The technique used in these studies
[30]
was reversible block of communication between spinal and supraspinal structures, which was effected by cooling
the spinal cord cephalad to where recordings from the dorsal horn neurons were made. It is now known that
descending controls may be either inhibitive or facilitative. The nucleus raphe magnus forms the major brainstem
[31]
outflow of this control system by a pathway in the dorsolateral funiculus of the spinal cord. These descending axons
terminate primarily in laminae I, II, and V, in proximity to neurons known to receive input from small-diameter,
high-threshold primary afferents. [32]
Important observations that contributed to an understanding of supraspinally descending influences on nociception

control included (1) that mid-brain periaqueductal gray (PAG) and the adjacent hypothalamic periventricular area
are critical sites for morphine-produced antinociception ; (2) that PAG stimulation produces analgesia in rats
[33]
; [34] [35]
and (3) that opioid peptides exist. [22]
The Neural Matrix
Neuroscientists have failed to identify a “pain center” in the brain. Thus, a “neural matrix” concept evolved
117
Figure 9-17 Transmission along the nociceptive pathway with illustration of mechanisms for neuropathic pain, processing nociceptive information at the “first” synapse, and functional mapping
of pain at the level of the cortex. (From Heavner JE, Willis WD: Pain pathways: Anatomy and physiology. In Raj PP (ed): Practical Management of Pain, 3rd ed. St. Louis, Mosby, 2000.)
to explain why (1) multiple supraspinal structures are activated when nociceptive information reaches the brain and
(2) why complex behaviors and cognitive experiences (e.g., sensory discrimination, motivation, affect) are
associated with nociceptive activation of brain structures ( Fig. 9-18 ). [36]
Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) are contemporary brain
imaging techniques that provide scientists with ways to examine how the brain processes nociceptive information.
Brain imaging studies have provided evidence supporting the notion that instead of a common structure or neuronal
master switch, there is a distributed parallel network, or matrix, of cortical and subcortical structures subserved with
afferent input via distinct anatomic pathways for the generation of pain. [37] [38] [39]
The majority of brain imaging studies related to pain have been done with PET and use the two-state subtraction
technique (i.e., subtracting brain images in a painful state from images collected in a controlled state). [40]
By 1997, studies using PET had demonstrated that significant increases in regional cerebral blood flow (rCBF) in
response to phasic pain occurred in the brainstem, thalamus, lentiform nucleus (putamen and striatum), and inferior
parietotemporal-prefrontal (Brodmann’s area [BA] 9/10 and 44/46), insular and anterior cingulate (BA 24)
cortices. [41]
Derbyshire and colleagues summarized the findings of 14 PET studies of regional blood flow in a number of
[42]
cortical and subcortical regions in response to an experimental noxious stimulus, or during clinical pain. The central
region most commonly activated was the anterior cingulate cortex (ACC) (in all 12 studies in which it was
analyzed). Two of the 12 studies reported decreased blood flow in area 24 of the ACC and increased flow in area 25
of the ACC. The insula and thalamus were the second most common areas where increased blood flow was found,
but results from different experiments were less consistent than for the ACC. Structures other than the ACC,
thalamus, and insula were far less consistently activated.
Derbyshire and colleagues concluded that what emerged from analysis of the PET data is that there is a matrix of
[42]
structures, including anterior cingulate,
118
Figure 9-18 The body-self neuromatrix, which comprises a widely distributed neural network including somatosensory, limbic, and
thalamocortical components, is schematically depicted as a circle containing smaller parallel networks that contribute to the sensory-
discriminative (S), affective-motivational (A), and evaluative-cognitive (E) dimensions of pain experience. The synaptic architecture of the
neuromatrix is determined by genetic and sensory influences. The “neurosignature” output of the neuromatrix—patterns of nerve impulses of
varying temporal and spatial dimensions—that is produced by neural programs genetically built into the neuromatrix determines the particular
qualities and other properties of the experience and behavior of pain. Multiple inputs that act on the neuromatrix programs and contribute to the
output signature include (1) sensory input from somatic receptors (phasic cutaneous, visceral, and tonic somatic); (2) visual and other sensory
input that influences the cognitive interpretation of the situation; (3) phasic and tonic-cognitive and emotional input from other areas of the brain;
(4) intrinsic neural inhibitory modulation inherent in all brain functions; and (5) the activity of the body’s stress-regulation systems, including
cytokines and the endocrine, automonic, immune, and opioid systems. (From Melzack RD: Toward a new concept of pain for the new
millennium. In Waldman SD (ed): Practical Management of Pain, 3rd ed. St. Louis, Mosby, 2000.)
prefrontal, insula, inferior parietal and somatosensory cortices, thalamus, and lentiform nucleus, which are variably
activated during pain experiences. Technical or biological factors were cited as possible causes of variability.
Technical sources of variability included differences in the type, duration, and location of stimuli used in studies.
The biological basis for variability was attributed to the “multidimensional” nature of pain experience, resulting in a
“biopsychosocial” model of pain.
Analysis of data from PET studies revealed that, in general, the central response to experimental tonic and phasic
pain is similar ( Table 9-6 ). Although responses to experimental pain produce variable responses in S1 or S2, none
[41]
of the clinical studies reported S1 or S2 activity.
In a study using fMRI, Ploghaus and associates demonstrated that areas of the brain activated by anticipation of
[43]
pain included sites within the medial frontal lobe, insular cortex, and cerebellum distinct from, but close to,
locations mediating pain experience itself. According to these investigators, the responses to pain were dissociated
from responses to the anticipation of pain on the basis of differences in neuroanatomic localization and the time
course of the fMRI signal change. Another study demonstrated that activity in the more posterior regions of the
middle third of the brain seemed to be better correlated with perceived pain than with the applied thermal stimulus. [40]
Tölle and colleagues concluded from a PET study that the gating functions reflected by the pain threshold appeared
[39]
to be related to the anterior cingulate cortex, frontal inferior cortex, and thalamus. The coding of pain intensity was
related to the periventricular gray as well as the posterior cingulate cortex, and the encoding of pain unpleasantness
was related to the posterior sector of the anterior cingulate cortex.
119
LOCAL ANESTHETICS
Local anesthetics are a class of drugs that are widely used in the diagnosis and/or treatment of acute
as well as chronic pain. Not surprising is that evolution of our knowledge about local anesthetics
paralleled evolution of our knowledge about pain and nociception. Earlier in this chapter, the use of
local anesthetics to block nociceptive pain was highlighted. They are also administered intravenously
or orally as a diagnostic test for neuropathic pain or for treatment of neuropathic pain. [44]
Identification of the chemical backbone required for local anesthetic activity led to the synthesis and
testing of series of homologous chemicals to discover new local anesthetics that have clinical
advantage over existing local anesthetics in clinical use. Clinically used local anesthetics belong to
either the aminoester-linked or aminoamide-linked family of compounds ( Fig. 9-19 ). Consequences
of changes in chemical structure include alteration of speed of onset, duration of action, potency, and
toxicity ( Fig. 9-20 ). For a number of reasons, the aminoester-linked molecules fell out of favor in
the search for new local anesthetics ( Fig. 9-21 ). Two of the reasons are (1) these compounds may
produce allergic reactions, and (2) they are relatively unstable in solution.
According to Liljestrand, the identification of benzoic acid and methyl alcohol as molecules
[3]
released from cocaine and the fact that atropine has a weak local anesthetic effect provided a
foundation for the synthesis of compounds that might replace cocaine. If benzoic acid was
introduced into the atropine molecule, the compound formed, benzoyltropine, became a strong local
anesthetic. After it was discovered that (among other things) benzoyl derivatives of quinine and
morphine were highly active local anesthetics, it was concluded that benzoic acid must play a
fundamental role in the anesthetic effect of cocaine. Several synthetic compounds were subsequently
introduced but were both toxic and irritating. Einhorn finally succeeded in synthesizing procaine
[5]
after experimenting with well over 100 compounds. [5]
The foundation for the development of amide local anesthetics was based on studies of the alkaloid,
gramine. It was observed that isogramine (2-dimethylaminomethyl)-indole at first tasted butter-
[3]
sweet and then caused anesthesia of the tongue. After synthesis and evaluation of a large number of
compounds, Löfgren and colleagues in 1943 found that lidocaine (2-diethylamine-2′, 6′-
acetoxylidide) is a nonirritating substance with good local anesthetic action. [3]
Between 1943 and 1971, a number of amino-amide local anesthetics were synthesized with the goal
of finding a substance less toxic than lidocaine to replace it and of finding a long-lasting local
anesthetic. Four compounds produced by this effort were introduced into clinical practice—
prilocaine, mepivacaine, etidocaine and bupivacaine. Of these compounds, bupivacaine emerged as a
long-lasting local anesthetic with highly desirable properties. Both bupivacaine and etidocaine are
long-lasting agents, but the two differ in their sensory and motor-blocking characteristics. Unlike
etidocaine, bupivacaine provides good separation of motor and sensory anesthesia.
Concern in the 1980s about the systemic toxicity of long-acting local anesthetics led to the next
wave of searching for new long acting agents. The search was based on the observations that some
local anesthetic molecules exhibit optical isomerism (chirality) and that for some local anesthetics’
(e.g., bupivacaine) potency and toxicity differ between the R and S isomers. Ropivacaine and
levobupivacaine, which are pure S isomers, were brought to the marketplace.
In modern times, interest in local anesthetics that are really long acting (e.g., 24 hours or more), has
stimulated investigation of sustained-release formulations. A number of different approaches have
been tried, but encapsulation of local anesthetics has generated the greatest interest. One approach
[5]
is to create liposomes that trap drug and water within their cavities, allowing slow, continuous drug
release. None of these formulations have been commercialized.
Overwhelming evidence is that local anesthetics block the conduction of action potentials in
peripheral nerves by preventing a rush of Na+ into axons. The fact is that a physiochemical
interaction with the lipoproteins that form the basic structure of axons probably contributes to the
blocking action. What is most promising for development of new local anesthetic drugs is
capitalization on progress in identification and characterization of a local anesthetic receptor in
120
sodium channels ( Fig. 9-22 ). Targeting receptors offer the possibility of increasing selectivity,
potency, and control over receptor occupancy.
One puzzle of great interest with respect to local anesthetic action concerns the nature of the
mechanism of differential block. Clinicians recognize differential block as block of pain perception
with sparing of motor function. The clinical manifestations of differential block vary, depending on
the local anesthetic used to produce the block. For many years, this was ascribed to the fact that
[45]
smaller axons are more sensitive to local anesthetics than larger ones, but this “size principle” has [46]
been challenged. Berde and Strichartz cite a number of different factors that might contribute to
[47] [45]
differential block, including anatomic and relative selectivity of different local anesthetics for
sodium and potassium channels.
TABLE 9-6 -- RESULTS OF PREVIOUS STUDIES USING PET AND EXPERIMENTAL TONIC PAIN, CLINICAL TONIC PAIN, AND EXPERIMENTAL PHASIC PAIN (SUMMARY
IS SHOWN AT THE BOTTOM)
Regions
Study Methods Tha Ins LN 9/10 44/46 ACC 39/40 S1 S2
Experimental tonic pain
Rainville et al, 1997 8 controls, tonic heat B↑a C↑ − − − B↑ − C↑ C↑
Aziz et al, 1997 8 controls, esophageal stimulation − R↑ − − B↑ B↑ − L↑ −
Silverman et al, 1997 6 controls, visceral pain − − − − − L↑ − − −
Adler et al, 1997 9 controls, tonic heat I↑ ? ? − I↑ I↑ − − −
Craig et al, 1996 11 controls, tonic heat C↑ C↑ C↑a − − C↑ − C↑ C↑
Casey et al, 1996 9 controls, cold pressor B↑a B↑ C↑ I↑ I↑ B↑ − C↑ NA
Hsieh et al, 1995a 4 controls, ethanol injection − C↑ C↑ B↑ I↑ B↑ L↑ C↑ −
Clinical tonic pain
Hsieh et al, 1996 7 patients, cluster headache − B↑ B↑ B↓ R↑ R↑ L↓ − −
Weiller et al, 1995 9 patients, migraine − − − − − B↑ B↑ − −
Hsieh et al, 1995b 8 patients, mononeuropathy pain C↓ B↑ − B↑ − R↑ B↑ − −
Rosen et al, 1994 12 patients, angina pain B↑ − − B↑ B↑ B↑ L↓ − −
Di Piero et al, 1991 5 patients, cancer pain C↓ NA NA − − NA NA − −
Experimental phasic pain
Derbyshire et al, 1997 12 controls, laser heat B↑ C↑ B↑ B↑ B↑ B↑ B↑ C↑ −
Vogt et al, 1996 7 controls, phasic heat pain B↑ B↑ − C↑ − C↑ B↓ − −
Derbyshire et al, 1997 6 controls, phasic heat pain − C↑ C↑ I↑ − C↑ I↑ − −
Coghill et al, 1994 9 controls, phasic heat pain C↑ C↑ I↑ − − C↑ − C↑ C↑
Casey et al, 1994 18 controls, phasic heat pain B↑ C↑ − − − C↑ − C↑ C↑a
Talbot et al, 1991 8 controls, phasic heat pain C↑ − − − − C↑ − C↑ C↑
Jones et al, 1991 6 controls, phasic heat pain C↑ − C↑ − − C↑ − − −
The numbers under “Reported Regions” refer to Brodmann’s areas. Tha, Thalamus; Ins, insula; LN, lentiform nucleus; ACC, anterior cingulate cortex; S1, primary somatosensory cortex; S2,
secondary somatosensory cortex; C, contralateral; B, bilateral; I, ipsilateral; R, right; L, left; NA not assessed; ↑ indicates increased rCBF; ↓ indicates decreased rCBF; ? indicates uncertainty
regarding the activation; a indicates personal communication from the author.
From Heavner JE: Newer concepts in pain mechanisms. Curr Rev Pain 3:453–457, 1999.
121
Figure 9-19 Procaine (synthesized in 1904) and lidocaine (synthesized in 1943) are the prototype local anesthetics in the aminoester and
aminoamide series, respectively, of local anesthetics.
Figure 9-20 The aminoamide-linked local anesthetics mepivacaine, ropivacaine, and bupivacaine vary only by substitution at R on the basic
molecule shown above. As the number of carbon atoms increases at R, potency, lipid solubility, and protein binding increase.
Figure 9-21 Chronology of the introduction of different anesthetics into clinical practice. Chloroprocaine (1955) is the last aminoester-linked
local anesthetic introduced that is still in clinical use. (Courtesy, David A. Scott, Melbourne, Australia, 2000.)
122
Local Anesthetic Toxicity
Side effects of local anesthetics do occur, and the effects may or may not be related to block of sodium channels.
Toxic reactions to local anesthetics are easily categorized ( Table 9-7 ), are well characterized, and generally are not
fatal if recognized early and appropriately treated. The most frequent dramatic reactions observed clinically are
acute reactions involving the direct effects of local anesthetics on the cardiovascular system and/or the CNS. In
recent years, there has been considerable
TABLE 9-7 -- CATEGORIES OF LOCAL ANESTHETIC TOXIC

REACTIONS
Systemic
Cardiac/vascular
Central nervous system
Methemoglobinemia
Localized or Systemic
Allergic reactions
Localized
Tissue toxicity
123
Figure 9-22 Location and chemical structure of sodium channels in peripheral axons. A, Axon drawing is included for orientation. B, Schematic
drawings of lipid bilayer. C, Working hypothesis for a channel. The channel is drawn as a transmembrane macromolecule with a hole through the
center. The external surface of the molecule is glycosylated. The functional regions, selectivity filter, gate, and voltage sensor are deduced from
voltage clamp experiments and are beginning to be charted by structural studies. D, Highly schematic presentation of channel viewed as if
looking across a membrane. The Roman numerals indicate the four repeating α subunits of the channel protein. S1–6 represents the six α-helical
transmembrane segments in each of the four repeating amino acid chains that form a pore. P indicates the pore formed by the four subunits. E,
Linear presentation of the four repeating α subunits of an Na+ channel. Note that segment 4 contains + symbols. This segment corresponds to the
voltage sensor shown in A. P shows phosphorylation sites. The loop between 5 and 6 forms the pore lining. P, Phosphate. (From Heavner JE:
Neurophysiology. In Brown DL (ed): Regional Anesthesia and Analgesia. Philadelphia, WB Saunders, 1996, pp 84–91. By permission of Mayo
Foundation for Medical Education and Research.)
interest in local anesthetic cardiotoxicity, both alone and relative to their CNS toxicity ( Fig. 9-23 ). This interest
stems from cardiotoxicity induced by bupivacaine and resulting in death. Circumstances related to deaths from this
[48]
cause suggest that bupivacaine affects the heart somewhat differently from other local anesthetics. Current thought
is that differences in cardiotoxicity exhibited by different local anesthetics are a reflection of differences in the rate
of association and dissociation between local anesthetic molecules and cardiac sodium channel structures. [5]
Acute toxicity is usually associated with accidental intravascular injection of local anesthetics. There are numerous
strategies for avoiding intoxication via this mechanism, including incremental dosing, aspiration before injection,
and use of test doses or substances. Studies show that premedication with certain drugs (e.g., diazepam) increases
the local anesthetic seizure threshold. Benzodiazepines have value in aborting seizures, as do ultra–short-acting
barbiturates (e.g., thiopental) and propofol. Cardiac rhythm disturbances and cardiovascular collapse generally
[49] [50]
are treated symptomatically (e.g., volume expansion, cardiac stimulants, cardioversion, oxygen, sodium
bicarbonate).
124
CENTRAL NERVOUS SYSTEM TOXICITY
CNS symptoms of local anesthetic toxicity usually occur before cardiovascular changes. In humans, the first signs of
CNS toxicity include drowsiness progressing to numbness of lips, slurring of speech, agitation, tinnitus, diplopia,
fine tremors, and grand mal seizures; large doses produce generalized CNS depression (an isoelectric
electroencephalogram [EEG]). Ironically, there is no evidence that epileptics have a heightened susceptibility to the
CNS toxicity of these drugs. In fact, local anesthetics have anticonvulsant action and have been used effectively to
stop generalized tonic-clonic seizures. Similarly, local anesthetics have been administered intravenously to
[51]
produce general anesthesia. Conclusive evidence about how local anesthetics
Figure 9-23 Dose of lidocaine, bupivacaine, and etidocaine that produces convulsive activity (CD) and cardiovascular collapse (CC) in sheep.
The CC/CD ratio is obviously higher for lidocaine than for the other two agents. (From Berde CB, Strichartz GR: Local anesthetics. In Miller RD
(ed): Anesthesia, 5th ed. Philadelphia, Churchill Livingstone, 2000, pp 491–521.)
produce their effects on the CNS is lacking. Data from human and animal studies indicate that local anesthetic-
induced seizures originate in the limbic brain. At the neuronal level, local anesthetics appear to produce CNS
[52]
symptoms via an effect on sodium conductance, possibly via the same mechanism by which they produce
conduction block in axons of the peripheral nervous system. Evidence indicates that some of the cardiotoxic effects
of local anesthetics, bupivacaine in particular, may actually result from effects of these drugs on the brain. [53]
CARDIOVASCULAR TOXICITY
Local anesthetics can produce profound cardiovascular changes directly by cardiac and peripheral vascular action
and indirectly by conduction blockade of autonomic fibers. The primary site of action is the myocardium, where
decreases in electric excitability, conduction rate, and force of contraction occur. Notable are the cardiac rhythm
[54]
disturbances associated with local anesthetic cardiotoxicity. High concentrations of local anesthetics dilate blood
vessels, but low concentrations may cause vasoconstriction. Inhibition of sodium conductance increase appears to
play a major role in the cardiac effects of local anesthetics and probably in the vascular effects as well. However,
there is evidence that potassium channel block may also contribute to the cardiotoxicity of local anesthetics. [55]
The direct cardiac depressant effects of local anesthetics have been investigated rather intensively during the last
several years. This research was stimulated by the previously mentioned cardiac arrests produced by bupivacaine.
Common practice is to compare the effects of bupivacaine and lidocaine. Both drugs can produce a similar pattern
of cardiovascular toxicity. However, the profound depression of the cardiac conducting tissue produced by
bupivacaine is difficult to treat, whereas prompt treatment of lidocaine depression usually produces an uneventful
125
recovery. Animal studies show that resuscitation is usually successful if prompt treatment is instituted after
[48]
bupivacaine overdose. [56]
Studies indicate that a host of physiologic changes may affect the cardiotoxicity of local anesthetics (e.g.,
progesterone [pregnancy], hyponatremia, and diabetes mellitus). Even at the height of CNS symptoms,
[57] [58] [59]
cardiovascular changes may be minimal, with some increase in pulse rate and a corresponding rise in blood
pressure.
METHEMOGLOBINEMIA
Most discussions regarding the propensity for local anesthetics to produce methemoglobinemia focus on prilocaine,
the only clinically used local anesthetic that is a secondary amine. However, reports implicate prilocaine,
benzocaine, lidocaine, and procaine as causative agents. Methemoglobinemia is formed when ferrous iron (Fe++ ) in
[60]
hemoglobin is oxidized to the ferric (Fe+++ ) form.
TISSUE TOXICITY
Tissue toxicity includes irritation and lysis of cells. Muscles and nerves are of primary concern, with skeletal muscle
appearing to be the most sensitive. High concentrations of local anesthetics clearly are cytotoxic. This toxic property
of local anesthetics became an area of focus when there were reports of several incidences of prolonged sensory and
motor deficits after the accidental intrathecal administration of chloroprocaine. Studies triggered by these reports
[61]
revealed that a number of factors other than local anesthetics could contribute to—or be the primary cause of—
tissue destruction (e.g., solution pH, preservatives). The potent long-lasting anesthetics with high lipid solubility
appear to be more likely than other local anesthetics to cause tissue damage. Electron microscopy studies indicate
that local anesthetics affect the perineurium, Schwann cells, and axons. [62]
ALLERGIC REACTIONS
Allergic reactions to local anesthetics may occur. Reputedly, allergic reactions are more likely to occur with ester-
linked local anesthetics than with amide-linked ones. Methylparaben, a preservative sometimes added to local
anesthetic solutions, may cause allergic-type reactions. Cutaneous and respiratory reactions are the most common
indicators of anaphylaxis.
There is little information about whether or not toxic responses to local anesthetics are age dependent. Preliminary
data from animals suggest that infants may be more resistant than adults to the acute CNS and cardiovascular system
toxic effects of local anesthetics. This is so despite evidence that plasma clearance of local anesthetics may be
slower in infants than in adults. General anesthesia with halothane blocks tonic-clonic seizures but enhances the
acute cardiovascular toxicity of bupivacaine in 2-day-old pigs. [63]
Conclusion
It can be argued that the major focus of this chapter is on nociception and not on pain. Clearly, there is an enormous
and rapidly growing information base about normal and altered biology that produces nociceptive information. How
nociceptive information—or non-nociceptive information for that matter—is transformed into a perceptual
experience of pain and suffering still is understood only in vague terms. The chapter is by no means an exhaustive
review of all aspects of pain; it is intended to provide a review of many ideas that provide the foundation for pain
management.
REFERENCES
1. Melzack R, Wall PD: Pain mechanisms: A new theory. Science 150:971–978, 1965.
2. Willis WD: The Pain System: The Neural Basis of Nociceptive Transmission in the Mammalian Nervous System. Basel, Karger, 1985.
3. Liljestrand G: The historical development of local anesthesia. In Lechat P (ed): Local Anesthetics, vol 1. Oxford, Pergamon Press, 1971, pp 1–
37.
4. Insel
PA: Analgesia-antipyretic and antiinflammatory agents and drugs employed in the treatment of gout. In Hardman JG, Limbird LE (eds):
Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 9th ed. New York, McGraw-Hill, 1996, pp 617–657.
5. de Jong RH: Local Anesthetics. St Louis, Mosby, 1994.
126
6. Cooper JR, Bloom FE, Roth RH: The Biochemical Basis of Neuropharmacology, 7th ed. New York, Oxford University Press, 1986.
7. Reisine T, Pasternak G: Opioid analgesics and antagonists. In Hardman JG, Limbird LE (eds): Goodman & Gilman’s The Pharmacological
Basis of Therapeutics, 9th ed. New York, McGraw-Hill, 1996, pp 521–555.
8. Heavner JE: Neurolytic agents. In Raj PP (ed): Pain Management: A Comprehensive Review. St. Louis, Mosby–Year Book, 1996, pp 285–287.
9. LeeBH, Yoon YW, Chung KS, Chung JM: Comparison of sympathetic sprouting in sensory ganglia in three animal models of neuropathic
pain. Exp Brain Res 120:432–438, 1998.
10. Tanaka
M, Cummins TR, Ishikawa K, et al: SNS Na+ channel expression increases in dorsal root ganglion neurons in the carrageenan
inflammatory pain model. Neuroreport 9:967–972, 1998.
11. Bennet GJ, Xie YK: A peripheral neuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33:87–107, 1988.
12. Cervero F, Laird JMA: One pain or many pains? A new look at pain mechanisms. News Physiol Sci 6:268–273, 1991.
13. Rexed B: The cytoarchitectonic organization of the spinal cord in the cat. J Comp Neurol 96:415–494, 1952.
14. Christensen GN, Perl ER: Spinal neurons specifically excited by noxious or thermal stimuli: Marginal zone of the dorsal horn. J Neurophysiol
33:293–307, 1970.
15. Woolf CJ, Salter MW: Neuronal plasticity: Increasing the gain in pain. Science 228:1765–1772, 2000.
16. Herrero
JF, Laird JMA, Lopez-Garcia JA: Wind-up of spinal cord neurons and pain sensation: Much ado about something? Prog Neurobiol
61:169–203, 2000.
17. Yaksh TL, Rudy TA: Analgesia mediated by a direct spinal action of narcotics. Science 192:1357–1358, 1976.
18. Wang JK, Nauss LA, Thomas JE: Pain relief by intrathecally applied morphine in man. Anesthesiology 50:149–150, 1979.
19. Cousins MJ, Mather LE, Glynn CJ, et al: Selective spinal analgesic. Lancet 2:1141–1142, 1979.
20. Behar M, Olshwang D, Magora F, Davidson JT: Epidural morphine in treatment of pain. Lancet 1:527–528, 1979.
21. Goldstein A: Opiate receptors. Life Sci 14:615–623, 1974.
22. Hughes J, Smith TW, Klosterlitz HW, et al: Identification of two related pentapeptides from the brain with potent opiate agonist activity.
Nature 258:577–579, 1975.
23. Goldstein A: Opioid peptides (endorphins) in pituitary and brain. Science 193:1081–1086, 1976.
24. Frederickson
RCA: Enkephalin pentapeptides—a review of current evidence for a physiological role in vertebrate neurotransmission. Life Sci
21:23–41, 1977.
25. Uhl GR, Childers S, Pasternak G: An opiate receptor gene family reunion. Trends Neurosci 17:89–93, 1994.
26. Watson JD, Crick FHC: Genetical implications of the structure of deoxyribonucleic acid. Nature 171:737–738, 1953.
27. Heavner JE, Willis WD: Pain pathways: Anatomy and physiology. In Raj PP (ed): Practical Management of Pain, 3rd ed. St. Louis, Mosby,
2000.
28. Hirshberg RM, Al-Chaer ED, Lawand NB, et al: Is there a pathway in the posterior funiculus that signals visceral pain? Pain 67:291–305,
1996.
29. Sherrington C: The Integrative Action of the Nervous System. New Haven, CT, Yale University Press, 1906.
30. Wall PD: The laminar organization of dorsal horn and effects of descending impulses. J Physiol 188:403–423, 1967.
31. Ren
K, Zhuo M, Willis WD: Multiplicity and plasticity of descending modulation of nociception: Implications for persistent pain. Prog Pain
Res Manage 16:387–400, 2000.
32. Fields HL, Basbaum AI: Brainstem control of spinal pain-transmission neurons. Ann Rev Physiol 40:217–248, 1967.
33. Tsow K, Jang CS: Studies on the site of analgesic action of morphine by intracerebral microinjections. Sci Sincia 13:1099–1109, 1964.
34. Reynolds DV: Surgery in the rat during electrical analgesia induced by focal brain stimulation. Science 164:444–445, 1969.
35. Mayer DJ, Wolfle TL, Akil H, et al: Analgesia from electrical stimulation in the brainstem of the rat. Science 174:1351–1354, 1971.
127
36. Melzack RD: Toward a new concept of pain for the new millennium. In Waldman SD (ed): Interventional Pain Management. Philadelphia,
37. Melzack R, Casey KL: Sensory, motivational, and central control determinants of pain. In Kenshalo DR (ed): The Skin Senses. Springfield,
Ill, Charles C. Thomas, 1968, pp 423–439.
38. Jones AKP, Derbyshire SWG: Cerebral mechanisms operating in the presence and absence of inflammatory pain. Ann Rheum Dis 55:411–
420, 1996.
39. Tölle RT, Kaufmann T, Siessmeir T, et al: Region-specific encoding of sensory and affective components of pain in the human brain: A
positron emission tomography correlation analysis. Ann Neurol 45:40–47, 1999.
40. Apkarian AV, Darbar A, Krauss BR, et al: Differentiating cortical areas related to pain perception from stimulus identification: Temporal
analysis of fMRI activity. J Neurophysiol 81:2956–2963, 1999.
41. Derbyshire SWG, Jones AKP: Cerebral responses to a continual tonic pain stimulus measured using positron emission tomography. Pain
76:127–135, 1998.
42. Derbyshire SWG, Jones AKP, Gyulai F, et al: Pain processing during three levels of noxious stimulation produces differential patterns of
central activity. Pain 73:431–445, 1997.
43. Ploghaus A, Tracey I, Gati JS, et al: Dissociating pain from its anticipation in the human brain. Science 284:1979–1981, 1999.
44. O’Gorman DA, Raja SN: Infusion tests and therapies in the management of chronic pain. In Raj PP (ed): Practical Management of Pain, 3rd
ed. St Louis, Mosby, 2000, pp 723–731.
45. Berde CB, Strichartz GR: Local anesthetics. In Miller RD (ed): Anesthesia, 5th ed. Philadelphia, Churchill Livingstone, 2000, pp 491–521.
46. Gisson AJ, Covino BG, Gregus J: Differential sensitivities of mammalian nerve fibers to local anesthetic agents. Anesthesiology 53:467–474,
1980.
47. Fink BR, Cairns A: Lack of size-related differential sensitivity to equilibrium conduction block among mammalian myelinated axons exposed
to lidocaine. Anesth Analg 66:948–953, 1987.
48. Albright GA: Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology 51:285–287, 1979.
49. Heavner JE, Arthur J, Zou J, et al: Comparison of propofol with thiopentone for treatment of bupivacaine-induced seizures in rats. Br J
Anaesth 71:715–719, 1993.
50. de Jong RH, Heavner JE: Diazepam prevents local anesthetic seizures. Anesthesiology 34:523–531, 1971.
51. Browne T: Paraldehyde, chloromethiazole and lidocaine for treatment of status epilepticus. Adv Neurol 34:509–517, 1983.
52. Wagman JH, de Jong RH, Prince DA: Effects of lidocaine on the central nervous system. Anesthesiology 28:155–172, 1967.
53. Heavner JE: Cardiac dysrhythmias induced by infusing local anesthetics into the lateral cerebral ventricle of cats. Anesth Analg 65:133–138,
1986.
54. Atlee JL, Bosnjak ZJ: Mechanisms for cardiac dysrhythmias during anesthesia. Anesthesiology 72:347–374, 1990.
55. Courtney KR, Kendig JJ: Bupivacaine is an effective potassium channel blocker in heart. Biochem Biophys Acta 939:163–166, 1988.
56. Kasten GW, Martin ST: Bupivacaine cardiovascular toxicity: Comparison of treatment with bretylium and lidocaine. Anesth Analg 64:911–
916, 1985.
57. Moller RA, Datta S, Fox J, et al: Progesterone-induced increase in cardiac sensitivity to bupivacaine. Anesthesiology 69:A675, 1988.
58. Imai M, Chang KSK, Tang RD, et al: Enhanced myocardial depression from bupivacaine in diabetic rats. Anesthesiology 69:A872, 1988.
59. Betrix L, Timaur Q, Freysz M, et al: Effects of hypo- and hypernatremia on the depression of ventricular condition and arrhythmias.
Anesthesiology 69:A875, 1988.
60. Anderson ST, Hajduczek J, Barker SJ: Benzocaine-induced methemoglobinemia in an adult: Accuracy of pulse oximetry with
methemoglobinemia. Anesth Analg 67:1099–1101, 1998.
61. Covino BG: Toxicity and systemic effects of local anesthetic agents. In Strichartz GR (ed): Handbook of Experimental Pharmacology, vol 81.
Berlin, Springer-Verlag, 1987, pp 187–212.
62. Powell HC, Kalichman MW, Garrett RS, Myers RR: Selective vulnerability of unmyelinated fiber Schwann cells in nerves exposed to local
anesthetics. Lab Invest 59:271–280, 1988.
63. Badgwell JM, Heavner JE, Kytta J: Bupivacaine toxicity in young pigs is age-dependent and is affected by volatile anesthetics.
Anesthesiology 73:297–303, 1990.
64. Ross EM: Pharmacodynamics. In Hardman JG, Limbird LE (eds): Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 9th ed.
New York, McGraw-Hill, 1996, pp 29–41.
65. Levine JD, Fields HL, Basbaum AI: Peptides and the primary afferent nociceptor. J. Neurosci 13:2273–2286, 1993.
128
66. Heavner JE: Newer concepts of pain mechanisms and therapeutic implications. Curr Rev Pain 1:377–382, 1997.
67. Baker MD, Wood JN: Involvement of Na+ channels in pain pathways. Trends Pharmacol Sci 22:27–31, 2001.
68. Johnson BW: Pain mechanisms: Anatomy, physiology, and neurochemistry. In Raj PP (ed): Practical Management of Pain, 3rd ed. St. Louis,
Mosby, 2000.
69. Heavner JE: Neurophysiology. In Brown DL (ed): Regional Anesthesia and Analgesia. Philadelphia, WB Saunders, 1996, pp 84–91.
70. Yaksh TL: Anatomy of the pain-processing system. In Waldman SD (ed): Interventional Pain Management, 2nd ed. Philadelphia, WB
71. Heavner JE: Newer concepts in pain mechanisms. Curr Rev Pain 3:453–457, 1999. 125
129
Section III - Chapter 10 - Clinical Research
Chapter 10 - Clinical Research
Eric Lang
David Niv
Introduction and Historical Perspective
It is the purpose of this chapter to review some of the clinical research in regional anesthesia as it relates to current
developments in surgery and pain management. These advances in clinical research are related to the use of drugs,
administration techniques, and equipment. Many of these developments are far from recent, and it is important to
place them in historical perspective to understand the development of regional anesthesia.
The origins of regional anesthesia may date back thousands of years. The Incas believed that the coca leaf was a gift
from Manco Capac, son of the sun god, who gave it to them as a token of esteem and sympathy for their anguish.
Initially used for religious and political purposes, the leaves were used more abusively after the destruction of the
Incan civilization in the 16th century by Francisco Pizarro and his conquistadors. The lower classes and slaves were
paid with coca leaves, which increased their productivity and provided low-cost, high-output labor. Coca leaves
bound into a ball (cocada) with guano and cornstarch were chewed with lime or alkaline ash to release the active
alkaloid. Anthropologic documentation of that era indicates that trephination was successful, and cocaine-drenched
saliva could be dripped from the physician’s mouth onto the wound, thereby providing local anesthesia and pain
relief.
Cocaine began to receive attention in Europe and America during the mid-19th century. Around 1860, the alkaloid
was isolated in crystalline form. Twenty years later, von Anrep wrote an extensive review on the physiologic and
pharmacologic properties of cocaine, clearly citing the locally numbing effect on the tongue and dilatation of the
pupil, the former leading him to suggest that someday cocaine might become of medical importance. In Vienna,
[1]
Freud began to study the properties of the drug when he was given samples for trial by the Merck Company. In
1884, Freud wrote a report (Uber Coca) about the properties of cocaine. At this time, Karl Koller was an intern in
the Department of Ophthalmology at the Ailgemeinen Krankenhaus in Vienna. Because he was familiar with the
limitations of general anesthesia for ophthalmic surgery, Koller was interested in anesthetizing the cornea and
conjunctiva for ophthalmologic operations and had already tried morphine and chloral bromide. Koller and Joseph
Gartner successfully demonstrated the utility of cocaine for this purpose. A practical demonstration and
[2]
communication of this finding were presented at the Ophthalmological Congress in Heidelberg in September 1884.
James Leonard Corning, a neurologist, deserves acknowledgment for his analytic approach to local anesthesia in
humans based on laboratory experimentation. After a trial in a dog, he injected “hydrochloride of cocaine into the
[3]
space situated between the spinous processes of the 11th and 12th dorsal vertebrae.” After the second injection,
“anesthesia began to appear in the lower extremities, and a sound could be passed through the urethra without pain.”
Corning was unsure if this method could ever be used as a substitute for ether during genitourinary procedures or in
other branches of surgery. This trial was actually performed before the first report of a lumbar puncture. It is ironic
[4]
that Corning was not, in fact, trying to perform anesthesia. He was attempting to medicate the spinal cord with
cocaine as a possible treatment for what was hinted at as masturbation. Under the mistaken notion that a direct
connection existed between the epidural capillaries and those of the spinal cord, he probably performed what is now
known as an epidural injection. The dose of cocaine injected was far in excess of what is now recognized as a lethal
dose, and it is fortuitous that the patient survived. This report was published as a series of two, one experiment with
a dog and one with a human. It is fascinating to observe how the rigors and requirements of clinical research have
changed over the last 120 years. In 1886, Corning published a textbook on local anesthesia, the first book ever
dedicated to the field.
Because of toxicologic problems with chloroform and a high anesthetic mortality, local anesthesia became
fashionable with surgeons in France and Germany, and, to a lesser extent, in the United States. After some efforts at
self-experimentation that resulted in the first-known reported lumbar puncture headache, August Bier began to
administer spinal anesthesia in 1898. Epinephrine was isolated from the capsule of the suprarenal gland in 1897
[5] [6]
and was later crystallized by Takamine. Because of the toxicity and addiction resulting from use of cocaine, a
number of esters were synthesized, including procaine (Novocain) and stovaine (later discarded because of toxicity),
in 1904. Other compounds that were later formulated include cinchocaine (Nupercaine, dibucaine) in 1925,
130
amethocaine (Pontocaine, tetracaine) in 1928, lignocaine (lidocaine) in 1943, mepivacaine in 1956, prilocaine in
1959, bupivacaine in 1957, and etidocaine in 1971.
Most of the currently used techniques of regional anesthesia were devised during the first two decades of the 20th
century. These included caudal epidural analgesia (Sicard, France, 1901), which was later used for obstetric pain
(Läwen, Germany, 1910); lumbar epidural anesthesia (Pagés, Spain, 1921); paravertebral somatic block (Sellheim,
1906); celiac plexus block (Braun, 1906); stellate ganglion, or cervicothoracic sympathetic, block (Labat, 1930);
brachial plexus block (Hirschel, 1911), with an axillary injection followed by the report of a supraclavicular
technique (Kulenkampff, 1911); and intravenous regional analgesia (first described by Bier, 1908).
The use of nerve blockade for the treatment of pain is also not recent. Schloesser performed a trigeminal block with
alcohol in 1903. In 1924, Royle performed a surgical sympathectomy for pain relating to spastic paralysis followed
by Swetlow, who reported a neurolytic sympathetic block with alcohol as treatment for angina pectoris and
abdominal pain in 1926.
Medications Used for Regional Anesthesia
The use of regional anesthesia requires administration of sufficient local anesthetic to be effective but not so much
that toxicity develops. This necessitates thorough familiarization with the pharmacokinetics and pharmacodynamics
of local anesthetics in the body as well as the general structure of the local anesthetic molecule and the properties of
each of its subunits.
The typical local anesthetic molecule is weakly basic, containing an amine residue that contributes water solubility
in its quaternary form and that is separated from a lipophilic domain by an intermediate alkyl chain ( Fig. 10-1 ).
The intermediate chain connecting the lipophilic head and the hydrophilic tail contains either an ester or an amide
linkage, thus subdividing the clinically useful local anesthetics into two main groups: the aminoesters, which are
metabolized by plasma cholinesterase; and the aminoamides, which are metabolized in the liver. The lipophilic
portion of the molecule is usually an aromatic residue, contributed
Figure 10-1 The structure of an unspecified generic local anesthetic molecule.
by a derivative of benzoic acid in the case of the aminoester anesthetics, or by a derivative of aniline in the case of
the aminoamides. The archetypal local anesthetic, cocaine, led to the development of procaine. After World War I,
procaine in turn was used as the basis for developing alternative aminoesters. Two of these that are still in use by
anesthesiologists today are 2-chloroprocaine and tetracaine ( Fig. 10-2 ).
In the early 1930s, dibucaine was introduced by replacing the ester linkage with a carbamoyl group. This agent is
rather toxic. By reversing the carbamoyl link, the labile ester linkage was again replaced, this time by the
aminoamide local anesthetics. Lidocaine was the first of these anesthetics and was followed by mepivacaine,
prilocaine, bupivacaine, and, more recently, etidocaine and ropivacaine (see Fig. 10-2 ).
The local anesthetic molecule is poorly soluble in water, but, because of its basic nature, it combines readily with
acids to form water-soluble salts. Local anesthetics are usually prepared as their salt form, most often as
hydrochlorides. In aqueous solution, the hydrochloride salt ionizes to yield a positively charged quaternary amine
and a chloride anion. The charged quaternary amine exists in solution in equilibrium with its uncharged, free-base,
131
tertiary amine. The degree of ionization is important, because it is the uncharged, free-base form that is most lipid-
soluble and thus most able to cross the axon membrane, which affects the speed of onset of an anesthetic agent.
[10] [11]
[7] [8] [9]
Physicochemical and Clinical Considerations
The physicochemical characteristics of local anesthetics determine their clinical characteristics, including potency,
speed of onset, duration of anesthetic action, and differential sensory or motor blockade. The basic properties of a
local anesthetic can be manipulated through alterations in its molecular structure. [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24]
Increasing the degree of alkyl substitution on the aromatic ring or on the tertiary amine increases lipid solubility and
produces greater local anesthetic potency. Lengthening the intermediate chain increases anesthetic potency but also
increases toxicity. Molecular
Figure 10-2 The chemical structure and various physiochemical properties of various local anesthetic molecules. pKa is measured at 25°C.
Partition coefficient is: Total drug/mL octanol:Total drug/mL buffer at pH 7.4 and 25°C. (Data from Strichartz GR, Sanchez V, Arthur GR, et al:
Fundamental properties of local anesthetics. Anesth Anal 71:158–170, 1990; Strichhartz G: Molecular mechanisms of nerve block by local
anesthetics. Anesthesiology 45:421–441, 1976; McClure JH: Ropivacaine. Br J Anaesth 76:300–307, 1996.)
132
changes that contribute to increased protein binding lead to prolongation of the duration of local anesthetic action.
Local anesthetics belonging to the ethyl esters group are more easily metabolized and generally produce less
systemic toxicity. Finally, when local anesthetic molecules contain asymmetrical carbon atoms and thus can be
resolved into optical isomers, an enantiomeric preparation of the local anesthetic may have a different therapeutic to
toxic ratio compared with the racemic mixture. [25] [26] [27] [28]
Anesthetic Potency
Hydrophobicity is a primary causal factor of local anesthetic potency, because the anesthetic molecule must cross
the nerve membrane to bind to the sodium channel. Procaine and chloroprocaine are examples of local
[29] [30] [31]
anesthetics with low lipid solubility, having partition coefficients of less than 10 (see Fig. 10-2 ). These drugs must
be administered in concentrations of 2% to 3% to be effective in humans. Tetracaine, bupivacaine, and etidocaine
are more lipid-soluble, with partition coefficients from 30 to 140 and are efficacious at lower concentrations of
0.25% to 0.5%.
Mepivacaine and prilocaine have solubility partition coefficients of 21 to 25 and are effective at concentrations of
1% to 2% in vitro. Clinically, however, the correlation is not as clear-cut as it is in an isolated nerve.
Etidocaine is more potent than bupivacaine in an isolated nerve, whereas, clinically, etidocaine is actually less active
than bupivacaine. The difference between in vitro and in vivo results is probably due to factors such as
[32]
vasodilatation or tissue redistribution properties of the local anesthetics. Lidocaine causes a greater degree of
vasodilatation than prilocaine, leading to a more rapid vascular uptake. Therefore, fewer lidocaine molecules remain
for neural blockade. In vitro studies have demonstrated that lidocaine is more potent than mepivacaine on isolated
[33]
nerve preparations. In contrast, clinical trials demonstrate that little clinical difference exists in anesthetic potency
[34]
between the two agents. This, again, is probably due to lidocaine causing more vasodilatation than mepivacaine.
[35]
The clinical measurement of local anesthetic potency and toxicity is worthy of comment. Several recent clinical
trials have compared the relative potencies of bupivacaine and ropivacaine in view of claims that ropivacaine may
be a safer drug. To compare the potencies of these agents, the term minimum local analgesic concentration
[36] [37] [38] [39]
(MLAC) has been defined as the median effective local analgesic concentration in a 20-mL volume for epidural
analgesia in the first stage of labor. This measurement is similar to the measurement of minimal alveolar
concentration (MAC) with volatile anesthetics, using the up-down method of Dixon. This design is much more
[40] [41]
efficient at estimating the effective dose in 50% of a population (ED50 ) than traditional dose-response designs,
because it focuses on all of the sampling doses in the immediate vicinity of the ED50 . After placement of a lumbar
epidural catheter, 20 mL of the test solution is administered (in these studies, either of ropivacaine or bupivacaine).
The concentration of local anesthetic is determined by the response of the previous patient in that group to a higher
or lower concentration with use of up-down sequential allocation. Analgesic efficacy can be assessed using a visual
analogue pain scale with a fixed point defining effective treatment (e.g., ≥10 mm, on a scale of 100 mm, within 30
min). An effective result leads to a 0.01% weight/volume decrement for the next patient. An ineffective result leads
to a 0.01% weight/volume increment (Fig. 10-3 (Figure Not Available) ). Claims of reduced toxicity and motor
block must be considered with attention to differences in analgesic potency. The ED50 measured in an up-down study
design does not provide information regarding the slope or shape of the dose-response curve or the effective dose in
95% of a population (ED95 ). Furthermore, potency should be evaluated over an entire dose-response curve. It is
certainly likely that one anesthetic agent could be more potent than another at a certain spot on a dose-response
curve, whereas potency could be different at another concentration because the curves are not parallel. This could
explain why ropivacaine was 40% less potent than bupivacaine at ED50 concentrations as reported by Polley and
colleagues and D’Angelo and
Figure 10-3 (Figure Not Available) Graph depicting the calculation of the minimum local analgesic concentration (MLAC) of bupivacaine as
determined by the technique of up-down sequential allocation. The minimal local analgesic concentration is 0.067% weight/volume. Error bars
represent 95% confidence intervals. The testing interval was 0.01% weight/volume. See text for further details.(Adapted from Polley LS, Columb
MO, Naughton NN, et al: Relative analgesic potencies of ropivacaine and bupivacaine for epidural anesthesia in labor: Implications for
therapeutic indexes. Anesthesiology 90:944–950, 1999.)
James but was equipotent at higher doses. Another confounding factor that has not been controlled in these
[38] [39]
studies is parity. Pain intensity varies with parity, and recent studies utilizing the up-down method to evaluate the
[42]
ED50 of bupivacaine and ropivacaine have not controlled for this variable. In the future development of local
[39]
anesthetic agents, investigators should evaluate different potencies over an entire dose-response curve to ensure
substantiation of claims of reduced toxicity.
133
Onset of Action
The degree of ionization of a local anesthetic molecule directly influences the speed of anesthetic onset. The pKa [35] [43]
of a chemical compound is the pH at which ionized and nonionized forms are present in equal amounts. The
nonionized (uncharged) form of the local anesthetic is responsible for diffusion across the nerve membranes. At a [44]
pH of 7.4, mepivacaine, lidocaine, prilocaine, and etidocaine (pKa of around 8) are approximately 65% in the
ionized form and 35% in the nonionized base form. Tetracaine has a pKa of 8.6, and only 5% is present in the
nonionized form at a physiologic tissue pH of 7.4. A relationship between the onset of action of a local anesthetic
and pKa has been demonstrated in clinical trials. Compounds such as lidocaine, prilocaine, etidocaine, and
mepivacaine, which are less ionized at body pH (lower pKa), possess a relatively rapid onset of action, whereas
procaine or tetracaine have a slower onset of action, higher pKa’s, and greater ionization.
An exception is chloroprocaine, which has a high pKa (about 9.1) and a rapid onset of action. Chloroprocaine is
clinically used in high concentrations and large doses. This more rapid onset of action may be related to the larger
number of molecules of this agent that are administered to achieve effective anesthesia. In one study, 1.5% lidocaine
produced a more rapid onset of epidural anesthesia than 1.5% chloroprocaine; however, 3% chloroprocaine resulted
in a more rapid onset than 2% lidocaine. A similar phenomenon can be noted with bupivacaine. A 0.25%
[45]
concentration of bupivacaine has a slow onset; however, increasing the concentration to 0.75% results in a
substantially more rapid anesthetic effect. [46]
In an attempt to enhance the onset time of local anesthetics, sodium bicarbonate has been added to local anesthetic
solutions. The addition of 1 mEq of sodium bicarbonate to each 10 mL of 1.5% lidocaine solution increases the pH
[47]
to 7.15. The increase in the pH of the local anesthetic solution leads to an increase in the proportion of nonionized
local anesthetic and thus enhances the rate of diffusion across the nerve sheath and nerve membrane. This
phenomenon has been demonstrated with mepivacaine, bupivacaine, and lidocaine used for brachial plexus and
epidural blockade. It has also been described for peribulbar anesthesia. However, other investigators have not
[47] [48] [49] [50]
found alkalization to be efficacious in improving the onset of brachial plexus blockade. [51] [52] [53]
The addition of carbon dioxide to a local anesthetic solution in an isolated nerve preparation results in a faster onset
of action. In contrast, controversy exists regarding carbonated solutions of local anesthetics. Some
[54] [55] [56] [57] [58] [59]
researchers have reported a more rapid onset of action for lidocaine carbonate compared with lidocaine
hydrochloride for epidural blockade, whereas others have not. Similar clinical divergences are reported for
[60] [61]
bupivacaine hydrochloride and bupivacaine carbonate. [49] [62]
Duration of Action
The degree that a local anesthetic binds to protein influences the duration of anesthetic action. Procaine, with a low
degree of protein binding (less than 6%), has a relatively brief duration of action. Bupivacaine and etidocaine, with
approximately 95% protein binding, possess a longer duration of action. Prilocaine, mepivacaine, and lidocaine,
with protein binding that varies from 55% to 75%, have an intermediate duration. In clinical studies, a brachial
plexus block lasts 30 to 60 minutes with procaine and may last 10 hours with bupivacaine or etidocaine. Duration [34]
of anesthetic action is also related to vasodilation. All local anesthetics have a biphasic effect on the blood vessels,
with the exception of cocaine. At low concentrations, these agents are vasoconstrictors, whereas at higher
[33] [63]
concentrations they cause vasodilatation. Lidocaine is a more potent vasodilator than either mepivacaine or
[63] [64]
prilocaine. Accordingly, lidocaine produces a shorter duration of local anesthesia than either of these drugs;
however, little difference is noted in isolated nerve preparations. [34] [35] [65]
Differential Sensory and Motor Blockade
Differential inhibition of sensory and motor activity is another important characteristic of some local anesthetics.
Bupivacaine is commonly used epidurally for obstetric analgesia and postoperative pain management because it can
provide acceptable analgesia with only mild muscle weakness, particularly in concentrations of 0.125% or less. In
contrast, etidocaine does not possess this differentiating property. Some studies report that ropivacaine provides
greater sensory selectivity than bupivacaine, but other studies do not report this finding. Levobupivacaine, [66] [67] [68] [69] [70]
the S- isomer of bupivacaine, has been approved for use as a local anesthetic in the United States (1999).
Levobupivacaine may possess a safer cardiovascular and central nervous system profile than the commercially
available racemate. It appears to have a clinical profile similar to that of bupivacaine, although it may be a safer drug
in the event of overdose and intravascular injection. Studies comparing the dose response curves of
[71] [72]
134
levobupivacaine and the racemate have yet to be published. As mentioned previously, studies of this nature are
needed to substantiate claims of decreased toxicity.
Addition of Vasoconstrictors
The initial use of cocaine as a local anesthetic was limited because of toxicity and rapid resorption. In 1885, Corning
described the use of an Esmarch bandage as a method of prolonging the local anesthetic effects of cocaine for
surgical and other purposes. Braun coined the term “chemical tourniquet” and substituted epinephrine; therefore,
[73]
the need for an elastic tourniquet was eliminated in 1903. Today, vasoconstrictors are among the most common
[74]
additives to local anesthetic solutions. The duration of a local anesthetic is proportional to the duration of time that
the local anesthetic remains in contact with a nerve; therefore, a vasoconstrictor can prolong the duration by
decreasing vascular resorption.
Epinephrine is the most commonly used vasoconstrictor in combination with local anesthetics; however, compounds
such as norepinephrine and phenylephrine have been used. One study compared equipotent concentrations of
epinephrine and phenylephrine and found that tetracaine spinal anesthesia was prolonged by a similar amount. [75]
Epinephrine has been demonstrated to prolong the duration of both infiltration anesthesia and peripheral nerve
blocks with many agents such as lidocaine. Epinephrine also prolongs the duration of bupivacaine local
[65] [76]
anesthesia ; however, the effect on epidural bupivacaine is more questionable. Sinclair and Scott noted that the
[77] [78]
duration of motor blockade by epidural bupivacaine was not extended with epinephrine; however, sensory blockade
was prolonged. Other studies have found contrasting results. In obstetric patients, the depth and duration of epidural
bupivacaine analgesia were improved with epinephrine 1:300,000. Baranowski and colleagues assessed the effect
[79] [80]
of injecting epidural epinephrine before epidural bupivacaine (priming). No clinical advantage was found with
priming, although epinephrine did prolong the epidural block. However, this was only significant for the duration of
block at T6 and duration of motor block at Bromage level 1.
The Neuraxial Administration of Medications for Regional Anesthesia and Pain

Management
SPINAL AND EPIDURAL OPIOIDS
Pert and colleagues reported on the presence of opioid receptors in high density in the dorsal horn of the spinal cord
in 1973 and thus provided the impetus for the use of spinal opioids reported by Sabbe and Yaksh. The
[81] [82] [83]
intrathecal administration of opioids markedly prolongs the analgesic effect compared with systemic administration.
In patients undergoing cardiac surgery, analgesia of about 36 hours’ duration was reported by lumbar intrathecal
injection of 2 to 4 mg of morphine. In patients having total hip replacement, lower doses gave 24 to 48 hours of
[84]
analgesia. In contrast, other investigators have noted that intrathecal opioids provide prolonged analgesia but of a
[85] [86]
lesser duration. Jacobson and colleagues compared the analgesic effects of intrathecal methadone and intrathecal
morphine in patients scheduled for orthopedic surgery. The time to the onset of discomfort severe enough to
[87]
require supplemental morphine was longer after intrathecal morphine than after methadone; however, it was shorter
than the previously mentioned studies (15 h with morphine 0.5 mg; 6.25 hr, 6.5 hr, and 6 hr with methadone 5 mg,
10 mg, and 20 mg, respectively). The same researchers compared the analgesic effect of intrathecal morphine with
that of intrathecal methadone in patients scheduled to undergo major orthopedic or urologic surgery. Here again, [87]
the time to onset of discomfort severe enough to require supplemental morphine was longer after intrathecal
morphine than after methadone (24 and 29 hr with 0.5 and 1 mg of morphine; 6.5 hr with methadone). It is difficult
to reconcile and compare these contrasting findings. The doses of opioid administered and the methods used differ.
The advantage of epidural administration is the potentially decreased morbidity, notably in regard to postdural
puncture headache (PDPH) and infection. However, systemic absorption adds further pharmacokinetic and
pharmacodynamic considerations. Only 10% to 20% of an epidural dose of morphine (low lipid solubility) crosses
the dura into the cerebrospinal fluid; therefore, this route requires higher doses. In some pain contexts, epidural
opioids alone have not provided adequate analgesia. Experimental studies have demonstrated synergism between
[88] [89]
local anesthetics and opioids in animal models. Clinical observations and studies have validated these findings in
[90] [91]
humans. [92] [93] [94] [95] [96] [97]
Some studies have questioned whether the analgesic efficacy of epidural fentanyl is secondary to systemic
absorption and recirculation to the central nervous system through the blood-brain barrier, or whether it is mediated
by a direct spinal mechanism. If the former premise is accurate, there may be no advantage to the epidural route. For
example, no clinical advantage was seen with epidural fentanyl compared with an intravenous injection of the
135
equivalent dose after orthopedic surgery or after cesarean section. Intravenous alfentanil (0.36 mg/hr), combined
[98] [99]
with epidural bupivacaine 0.125%, was as effective as epidural alfentanil (0.36 mg/hr) after abdominal surgery. [100]
Guinard and colleagues compared the need for epidural or intravenous fentanyl in patients undergoing
[101]
thoracoabdominal esophagectomies. No advantage to epidural fentanyl was noted, and the stress hormone response
to surgery was not statistically different with the two treatments.
In contrast, epidural fentanyl was reported to provide superior analgesia compared with that of intravenous fentanyl
after thoracotomy, and a difference in the magnitude of the hormonal response to surgery was reported. Epidural [102]
fentanyl was found to be superior for labor pain and after cesarean section.
[103] [104]
Baxter and coworkers reported an interesting interpretation of these data. In a double-blinded study, patients
[105]
received either epidural or intravenous fentanyl for postoperative analgesia after having been given a standard
general anesthetic. Visual analogue pain scores were lower in the epidural group at 2 hours postoperatively only,
and there was no difference in the amount of supplementary morphine self-administration. The authors concluded
that a mainly spinal analgesic effect probably occurred in the first few hours after surgery because fentanyl was not
detectable in the plasma of patients in the epidural group until 2 hours after the bolus injection; its concentration was
less at that time than after intravenous injection. Thereafter, there was no difference in the plasma concentration
profiles between the two groups. This study demonstrates the need for systemic controls in epidural studies. The
vascular uptake of an epidurally administered lipid-soluble opioid results in analgesia that is similar in duration and
magnitude to that of a systemically administered dose of the same compound.
It is difficult to draw concrete conclusions from these conflicting data. Many trials are small and probably
insufficiently powered to detect small differences. It is apparent, however, that lipid-soluble opioids alone (without
local anesthetic additives) are poor selections for epidural anesthesia. Low spinal potency and significant systemic
analgesic effect make it difficult to ascertain whether there is any spinal action. The clinical observation of good
epidural analgesia after the combined administration of lipid-soluble opioids and local anesthetics may be due to the
synergism between an epidural anesthetic and a systemic opioid effect.
ALPHA(2)-ADRENERGIC AGONISTS
Epidural or intrathecal clonidine produces analgesia without either the motor and proprioceptive block associated
with local anesthetics or the nausea, pruritus, and potential respiratory depression of opioids; however, the
hemodynamic side effects of clonidine include hypotension and a decrease in heart rate. Clonidine is approved for
intraspinal administration in the treatment of patients with neuropathic cancer pain. This compound is synergistic
with spinal opioids and intrathecally administered local anesthetics.
[106] [107] [108] [109]
Clonidine produces [110] [111] [112] [113]
analgesia by mimicking activation of the descending noradrenergic pathways and inhibiting the release of substance
P. Autoradiographic studies have shown that clonidine binds in the superficial layers of the dorsal horn, which is a
site of major importance for transmission and modulation of pain impulses. Alpha(2)-adrenergic receptors are
[114] [115]
located centrally and peripherally and are both presynaptic and postsynaptic.
A plethora of clinical studies have been performed to evaluate the synergism between clonidine, opioids, and local
anesthetics. Some studies have suggested an analgesic effect after systemic clonidine administration. Eisenach and
associates investigated the analgesic effects of intrathecal and intravenous clonidine by means of acute noxious
[116]
stimulation after the intradermal administration of capsaicin in volunteers. The capsaicin injection produced pain,
followed by hyperalgesia and allodynia. The intrathecal—but not the intravenous—injection of 150 µg of clonidine
reduced capsaicin-induced pain and hyperalgesia in response to heat stimulation. The authors concluded that this
supported the efficacy of intraspinal administration of clonidine for the treatment of acute pain and of pain states
associated with hyperalgesia, inasmuch as this experimental model represented clinical pain states. Gentili and
colleagues evaluated the use of intra-articular morphine and clonidine alone and in combination after knee
[117]
arthroscopy. The authors were unable to demonstrate an advantage with the combination; however, both drugs
administered singly provided analgesia. In contrast, Joshi and coworkers found an advantage to the morphine and
[118]
clonidine combination after arthroscopic procedures.
Other investigators have evaluated clonidine as a component of regional anesthesia in different models. No benefit
was found with clonidine as a component of a peribulbar block or in combination with bupivacaine for wound
[119]
infiltration after inguinal hernia repair. In contrast, clonidine has proved beneficial as a component of a brachial
[120]
plexus block. The addition of clonidine as an adjunct to intravenous regional anesthesia is controversial.
[121]
Kleinschmidt and colleagues report no advantage, whereas other investigators report a decrease in tourniquet pain
[122]
with the addition of clonidine. [123]
136
Armand and associates attempted to perform a meta-analysis of published literature on the efficacy of epidural
clonidine for the treatment of postoperative pain. The investigators concluded that between 1985 and 1997, all but
[115]
16 of the published studies suffered from serious design flaws such as lack of controls, lack of randomization, or
inadequate statistical analysis. The data from these studies were difficult to interpret because of the tremendous
differences in variables, particularly in the dose of clonidine, the level of epidural injection, the time of
administration, type of anesthesia, the type of surgery, and the reference and rescue drugs. These differences
precluded any meta-analysis of this data.
In conclusion, clonidine appears to offer benefit in combination with spinal and epidural local anesthetic solutions
and opioids; however, the hemodynamic and sedative side effects may be bothersome. Evidence exists for the use of
this compound in other types of regional anesthesia, but further trials are needed. Dexmedetomidine is another
alpha(2)-adrenergic agonist that has been used in humans mainly as an intravenous or intramuscular injection.
Intrathecal administration has been evaluated in animal models. Although the compound appears to have analgesic
[124]
properties, its value as a component of regional anesthesia and pain management remains to be determined.
Similarly, Tizanidine, an alpha(2)-adrenergic agonist that is used mainly as a potent, central-acting myotonolytic
agent, has not been evaluated as a component of regional anesthesia, although it may be beneficial in certain pain
states.
[125] [126] [127]
CHOLINOMIMETICS AND CHOLINESTERASE INHIBITORS
Spinal acetylcholine release has been demonstrated with acute pain in animal models and may also occur in humans
in response to pain. These studies, along with the observation that acetylcholine was released from the
[128] [129] [130] [131]
dorsal horn in response to alpha(2)-adrenergic analgesia led to the evaluation of cholinergic receptors as a
mechanism of endogenous analgesia. Laboratory studies have affirmed a role for the muscarinic receptor subtype as
the analgesic mediator.
Intrathecally administered neostigmine has been evaluated as a stand-alone agent in humans but is poorly tolerated
because of a poor efficacy/side-effect ratio. Side effects included nausea, vomiting, and transient lower
[132] [133] [134]
extremity weakness.
In contrast, subanalgesic doses of neostigmine are clinically more useful. Intrathecal neostigmine was demonstrated
to have an opioid-sparing effect when combined with different opioids. It also enhances epidural local [133] [135] [136] [137]
anesthetic analgesia. The side-effect profile improves when doses are less than 100 µg.
[138]
Intrathecally and [132] [133]
epidurally administered neostigmine has been demonstrated to enhance the analgesic effect of clonidine; however,
the combination may increase the incidence of adverse side effects. The addition of intra-articular neostigmine
[139] [140]
after arthroscopy was reported to enhance analgesia ; however, its efficacy for enhancing analgesia during brachial
[141]
plexus blockade is controversial. Future novel cholinomimetic agents may be more efficacious in enhancing
[142] [143]
analgesia while achieving more favorable efficacy/side-effect ratios.
N-METHYL-D-ASPARTATE RECEPTOR ANTAGONISTS
It is commonly accepted that the N-methyl-D-aspartate (NMDA) receptor has a causative role in the generation and
maintenance of central (spinal) states of hypersensitivity. NMDA receptor antagonists do not have the potential of
totally eradicating pain; rather, they have the potential of preventing or blocking hyperalgesic states induced by
tissue damage, inflammation, nerve damage, and ischemia. Several agents have been investigated, including
dizocilpine (MK801), dextromethorphan, phencyclidine, and ketamine. [144] [145] [146] [147] [148] [149] [150] [151] [152] [153]
In postoperative clinical studies, ketamine is usually administered as an adjunctive intravenous medication, although
it has been coadministered for epidural analgesia. Choe and colleagues found a greater duration of analgesia and [154]
reduction in supplemental postoperative analgesic requirements when ketamine (60 mg) was added to morphine (2
mg) given epidurally before induction of anesthesia. In contrast, when ketamine is administered postoperatively as a
single agent, it is not particularly efficacious. Walker and Cousins have demonstrated that subcutaneous infusions
[155]
of ketamine permit tapering of chronically administered intrathecal morphine in patients who have developed opioid
tolerance. Thus, ketamine prevents rebound hyperalgesia when morphine is switched to a local anesthetic as an
intrathecal infusate. The other NMDA antagonist in common clinical use is the antitussive, dextromethorphan;
however, dextromethorphan is not formulated for intrathecal use.
Unfortunately, the utility of most NMDA receptor antagonists appears to be limited by side effects. For example, [156]
3-(2-carboxypiperazin-4)propyl-1-phosphonic acid (CPP), an NMDA receptor antagonist, was administered
137
intrathecally to a patient with severe neuropathic pain. The agent reduced the tendency of mechanical stimulation
[157]
to produce a progressive increase of pain but did not affect the resting pain level. The patient, however, developed
marked anxiety and hyperacusis. In conclusion, blocking NMDA receptors appears, in principle, to be an attractive
option; however, experience so far has been disappointing because of major unwanted side effects.
CALCIUM-CHANNEL BLOCKERS
Changes in the calcium ion concentration surrounding neurons are an important determinant in the functioning of
the nervous system. Several distinct types of calcium channels in sensory neurons have been reported. [158]
Intrathecally delivered N-type calcium channels are antagonized by SNX239, SNX159, and ziconotide (formerly,
SNX111), whereas diltiazem, verapamil, and nimodipine block intrathecal L-type calcium channels. Non-N-, non-L-
type calcium channels are antagonized by SNX230, and P-type calcium channels are blocked by omega-agatoxin
IVA.
Opioids and calcium transport are closely related in the central nervous system. Morphine inhibits calcium ion
influx through the receptor-operated calcium channel in neuronal cells. The L-type calcium-channel blockers
[159]
verapamil and diltiazem potentiate the antinociceptive effects of systemically or supraspinally administered
morphine and other opiate receptor agonists. Additionally, calcium antagonizes the analgesic effects of
[159] [160] [161]
endogenous and exogenous opioids. This has led researchers to evaluate calciumchannel blockers for human
[162] [163]
analgesic therapy.
In the mid-1980s, peptide “conotoxins” were isolated from the venom of fish-hunting cone snails that capture their
prey by paralyzing them. A synthetic analogue of these conopeptides, ziconotide, selectively blocks N-type, voltage-
sensitive calcium channels and is currently being evaluated by the United States Food and Drug Administration
(FDA) for approval in treatment of pain in humans. Phase III trials have been completed and ziconotide was
efficacious for extended periods of time in treating morphine-resistant chronic pain due to malignancy or
neuropathy. The FDA has issued an approval letter for this compound. Unfortunately, the efficacy of the
[164] [165] [166]
compound may be limited by side effects, which include nausea, orthostatic hypotension, lightheadedness,
headache, constipation, and confusion.
Conclusion
It is interesting to examine the research process that is demonstrated in the developments reviewed in this chapter.
Increasing knowledge of basic molecular mechanisms that cause pain leads to the evaluation of medications for
antinociception. These studies are first performed in animal models and later in small human trials that may lead to
larger, controlled, blinded human trials. The rigors required to progress from animal models to human studies are
much greater today than those of the not so distant past. This is exemplified by James Leonard Corning who was
willing to attempt a human experiment after a single trial in a dog. Fortunately for today’s patients, clinical
researchers are held to a higher standard of accountability. Nevertheless, the goal, alleviation of human pain and
suffering, remains the same.
Techniques of Regional Anesthesia
In medical school and residency, the practice of regional anesthesia, when taught, is often viewed simply as a form
of applied anatomy. This is, in fact, an oversimplification. Unique and original research has led to the modern
practice of regional anesthesia. As mentioned previously, the first use of regional anesthesia may have occurred
during the Incan practice of trephination, when cocaine-drenched saliva was dripped from the mouth onto the
wound, thus alleviating the patient’s pain and discomfort. This section briefly summarizes some of the research that
has given rise to the current state of the art.
CENTRAL NEURAL BLOCKADE
The first description of the administration of a central neural axis blockade is attributed to James Leonard Corning in
1885. Nearly another decade passed before Heinrich Irenaeus Quincke described a technique for safely performing
[3]
lumbar punctures. It was only in 1899 that August Bier published the technique of lumbar puncture for the
[4]
administration of spinal anesthesia with cocaine. The use of spinal anesthesia did not become popular until the
[5]
introduction of neurologically safer local anesthetics. The first of these compounds was procaine, synthesized by
Einhorn in 1904. By 1907, the administration of spinal anesthesia was further improved by the use of hyperbaric
138
spinal anesthesia with the addition of glucose and of hypobaric spinal anesthesia that initially used alcohol. The [167]
popularity of the technique was further enhanced with the introduction of other, longer acting local anesthetics,
including cinchocaine, amethocaine, and, later, lidocaine. Continuous spinal anesthesia was described by Lemmon
and Tuohy in the 1940s. [168] [169]
Caudal anesthesia was first described in 1901, and later used to alleviate obstetric pain by Läwen in 1910. Caudal
anesthesia became the preferred route for administration of obstetric and postoperative pain relief, although lumbar
epidural anesthesia was described as early as 1921. Tuohy’s spinal needle was reengineered for epidural use in
1949 and led to the development of continuous catheter techniques for both caudal and lumbar epidural
[170]
administration. Over time, it became apparent that the lumbar epidural route of administration was preferable to
[171]
the caudal route because of its lesser anatomic difficulty, lower local anesthetic dose requirements, and more
segmental nature compared with the relatively “nonselective” caudal approach. By the 1960s, epidural neural
blockade had become the most common form of obstetric pain management throughout North America and parts of
Europe.
It would be beyond the scope of this chapter to review how clinical research has changed the techniques and practice
of epidural and spinal anesthesia. Two examples are reviewed to indicate the research that has led to the current
status of regional anesthesia today.
The Anatomy of the Epidural Space
The epidural space extends from the sacral hiatus to the foramen magnum. Its posterior boundary is the ligamentum
flavum (“yellow ligament”), which is actually made of two separate ligamenta flava—the right and the left—that
fuse in the midline. The right and left portions of these ligaments have been reported by some authors to be fully
joined in the midline, whereas others have found a midsagittal gap
[172]
( Fig. 10-4 ). The phenomenon of the
[173] [174]
unilateral epidural blockade occasionally occurs after epidural anesthesia and is a relatively frequent clinical
observation.
It is interesting to note how modern technical advances have fostered the theoretical understanding of this clinical
observation. Many different techniques have been used in the study of the anatomy of the epidural region, but they
all have limitations and are subject to artifact. Cadaver dissection is subject to distortion because of postmortem
autolysis and preservation with agents that alter tissue properties. Furthermore, the loss of cerebrospinal fluid
pressure at death and possible increase in venous pressure result in changes in the relative volumes occupied by the
dural
Figure 10-4 A drawing of the structures contained in the epidural space. See text for details.
sac and venous plexuses within the spinal canal. Investigations over the past few years have used superior
techniques to attempt to circumvent these problems.
139
Hogan reported the anatomic findings from cryomicrotome sections of 38 cadaver lumbar spines. The technique
[175]
produces high-resolution planar images of undisturbed epidural anatomy. Several observations differ from those in
previous reports when the methods used were more prone to artifact. The epidural contents were found to be located
in circumferentially and metamerically segmented compartments rather than in a uniform layer. Large areas of the
dura were directly in contact with the spinal canal wall. The ligamenta flava were fused in the midline to a variable
degree. The space anterior to the dura was isolated from the rest of the epidural space by a membranous lateral
extension of the posterior longitudinal ligament. This membrane and a midline posterior fat pedicle were the only
observed potential barriers to the spread of epidural solutions. No evidence of a true plica mediana dorsalis was
reported. This could be an explanation of the phenomenon of unilateral epidural blockade. Other researchers have
further researched this phenomenon.
Savolaine and colleagues used computed tomography (CT) to examine the lumbar epidural space in 40 patients. In
[176]
all of these patients, the examinations showed the posterior epidural space to be divided by the plica mediana
dorsalis and an additional transverse connective tissue plane that had not previously been described. However, the
authors were using the term plica mediana dorsalis to describe the fibrous bands and not the true folds of the dura.
This study showed no evidence of a true plica mediana dorsalis. The authors also hypothesized that
compartmentalization was responsible for the occasional entrapment and coiling of epidural catheters. Furthermore,
75% of the patients demonstrated a greater amount of fatty tissue within the junctions of the posterior midline
epidural connective tissue structures, thus producing a bulky triangular-shaped structure that could have been an
impediment to catheterization.
Seeling and associates performed CT epidurography with contrast medium in 30 patients. The authors described a
[177]
plica mediana dorsalis following rapid injection of 10 to 15 mL volumes of iopamidol (5 of 30 patients). In the
majority of the CT scans of the thoracic epidural space, the anterior (ventral) compartment was unfilled by contrast
medium. This suggests that the dura mater and posterior longitudinal ligament had fused to the extent that an
epidural space did not exist in the ventral thoracic segments of the spinal canal. In contrast, in lower thoracic and
lumbar segments, both structures were separate, and a wide anterior epidural space was present and filled with
contrast medium. In other cases, the dorsal and dorsolateral epidural spaces were completely filled, but the contrast
medium stopped behind the spinal nerves and surrounding dural sheaths, suggesting that these structures, together
with the connective tissue strands between them, formed a membrane that spread in a frontal plane.
Using epiduroscopy, Blomberg performed an anatomic study of the lumbar epidural space in 48 cadavers. He
[178]
found a dorsal connective tissue band in the midline of the epidural space between the dura mater and the flaval
ligaments in all cadavers. The appearance of the band varied from strands of connective tissue to a complete
membrane. This connection fixed the dura mater to the flaval ligaments and also narrowed the epidural space in the
midline. Further research was performed in 10 patients, with the aim of comparing the lumbar epidural space of the
patients with the cadaver findings. A complete examination was possible in only eight subjects, and visualization
[179]
was very limited. The authors reported that the dura mater lay very close to the dorsal aspect of the epidural space
and was attached to the flaval ligaments by a dorsomedian connective tissue band. The band was identified in all
eight subjects and was found to cause a dorsal fold in the dura mater.
Unfortunately, techniques requiring the injection of fluid or air into the epidural space may distort the anatomy.
Magnetic resonance imaging (MRI) is the most rapidly advancing of the imaging specialties. The anatomy of the
lumbar epidural space was studied retrospectively using lumbar MRI scans of 39 patients. The authors did not find
[180]
evidence of a plica mediana dorsalis, and therefore concur with other studies that did not involve the injection of
fluid into the epidural region, including the study by Hogan that was described previously. The authors hypothesized
that previous descriptions of the plica mediana dorsalis have been the result of partial collapse of the dural sac
resulting from injected contrast, polyester resin, or the opening of the epidural space at surgery. Under these
circumstances, the fibrous bands support the midportion of the dura, giving the impression of a fold.
Can definitive conclusions be reached? The anatomy of the epidural space has been extensively studied; however,
descriptions are not always concordant. In particular, the reality of a medial partition in the epidural space has been
suggested by epidurography and intraoperative observations. Savolaine and colleagues reported this partition with
[176]
CT epidurography. Luyendijk reported details of a medial fold of the dura mater (which appeared to hold it to the
[181]
posterior vertebral arch) that was collapsed on either side of the midline. Other researchers have attempted to
confirm this experimentally by making casts with polymerizing resins in cadavers; the results have been
unconvincing. Blomberg also tried to examine this space with epiduroscopy in the cadaver and in anesthetized
[182] [178]
patients. However, all these anatomic studies use methods that may alter the natural structures; their results are
therefore questionable. Westbrook and colleagues used a noninvasive MRI scan to further evaluate this question
[180]
and did not find evidence of a plica mediana dorsalis. It appears that the epidural space is segmental in nature, and
140
this may explain the clinical observation that began this review. Variable amounts of fatty tissue in the epidural
space may also partially explain the clinical observation that the elderly patient requires less local anesthetic than a
younger patient to achieve a block at the same level. This is certainly a fascinating demonstration of a research
process in which new techniques are employed to attempt to answer old questions. Unfortunately, as with many
questions that are investigated, we do not yet have definitive answers.
The Postdural Puncture Headache
Spinal anesthesia is commonly used for surgical procedures but may be followed by postdural puncture headache
(PDPH), particularly among young patients and obstetric patients. The first known PDPH is attributed to August
Bier more than a century ago. It is interesting to evaluate the recent research surrounding this well-described
medical problem. Although PDPH is not new and a plethora of publications exist on the topic, two meta-analyses
serve to illustrate how clinical research can be performed when a medical complication occurs relatively
infrequently.
Two strategies have arisen to reduce the incidence of PDPH. The first is to reduce the size of the needle. The second
is to change the design of the needle,
Figure 10-5 A picture depicting the penetration of the dura by a Whitacre (pencil-point) and Quincke (cutting) needle. The Quincke needle cuts
the fibers of the dura, whereas the Whitacre needle separates the fibers without cutting them. The Quincke needle leaves a hole in the dura
through which CSF can leak until it heals several days or weeks later.
presumably to reduce the leak of cerebrospinal fluid. This has been accomplished by using a noncutting rather than a
cutting point ( Figs. 10-5 and 10-6 ). A review of the published literature before 1994 demonstrated that controversy
existed as to whether these strategies were successful in reducing the incidence of PDPH. Some but not all studies
showed a reduction in PDPH when a noncutting needle rather than a cutting needle was used. Similarly, some
studies showed a reduction in PDPH when a small needle was used instead of a larger needle, whereas others
showed no difference. Meta-analysis can be helpful in resolving these issues.
141
Figure 10-6 A close-up of the different shape of a Quincke (cutting) and a Whitacre (pencil-point) needle.
Halpern and colleagues performed a computer search of MEDLINE records from January 1966 to December
[183]
1993. Other evaluated sources included Excerpta Medica, abstracts from major anesthesia meetings from 1989 to
1993, articles in the Scientific Citation Index by the authors of those abstracts, the Oxford database of perinatal
trials, and the International Journal of Obstetrical Anaesthesia (1992 and 1993). A total of 450 articles were
identified by title. Thirty-one abstracts, 25 letters, 44 original articles, and 12 reviews were assessed. Based on this
evaluation, the investigators reported a reduction in the incidence of PDPH when noncutting spinal needles rather
than cutting needles were used. They also reported a reduction in PDPH when a small spinal needle was used rather
than a large needle of the same type. The incidence of PDPH was about 7% with use of control needles and the
incidence of severe PDPH was between 2% and 4%. Individual studies would not have been sufficient to evaluate
the incidence of PDPH. To achieve a power of 0.8, with α equal to 0.05, the sample sizes would have had to be 700
and 2500 per group for PDPH and severe PDPH, respectively, to detect a 50% difference in incidence of these
complications. None of the studies approached that sample size. When combining studies with similar intervention
(noncutting vs. cutting; large vs. small gauge [G]), the required sample size was approached for PDPH but not for
severe PDPH. However, a difference in severe PDPH was detected because the reduction in incidence was more
than 50%. It proved impossible to perform subgroup analysis (e.g., age or sex) because the sample sizes were too
small.
In another prospective, randomized, double-blind study combined with a meta-analysis, Flaatten and associates [184]
compared the incidence of PDPH after spinal anesthesia using two different 27-G spinal needles: a pencil-point
(noncutting) needle and a Quincke (cutting) needle. The researchers investigated the occurrence of PDPH in 301
patients (153 in the pencil-point group and 148 in the Quincke group). Fifteen patients developed PDPH. Of these
patients, 12 were found in the Quincke group and 3 in the pencil-point group. The meta-analysis of 1131 patients
showed a relative risk of developing PDPH of 0.38 (95% confidence interval, 0.19–0.75) in the pencil-point group
compared with the Quincke group. The authors concluded that the use of a pencil-point-shaped spinal needle would
significantly reduce PDPH compared with Quincke-type spinal needles, even when 27-G needles were used. These
are excellent examples of how research from multiple sources may be combined in attempting to resolve a problem
that otherwise would not be clarified.
Equipment and Regional Anesthesia
In the final section of this chapter, the research and innovation pertaining to the development of new equipment for
regional anesthesia and pain management are reviewed. No single chapter could possibly outline the years of
research and the amount of innovation that have brought the technology involved in regional anesthesia to its current
state. It would, in fact, be difficult to determine where to begin.
The development of the syringe and hypodermic hollow needle, which dates back more than a century and a half, is
certainly a major landmark in the history of regional anesthesia. In 1845, Francis Rynd described using gravity, with
the help of a cannula and a trocar, to introduce a solution of morphine into the region of a peripheral nerve. In 1855,
in Edinburgh, Alexander Wood performed a subcutaneous injection with a graduated glass syringe and a hollow
[185]
142
needle provided by William Ferguson. The equipment had actually been manufactured by Ferguson to facilitate the
injection of ferric perchloride into an aneurysm for the purpose of producing a coagulum. Charles-Gabriel Pravaz [186]
had proposed this technique in Lyon in 1853 after the use of a syringe and trocar in animal experimentation.
Another turning point in the history of regional anesthesia, at least insofar as it pertains to invasive pain
management and nerve blocks, is the development of the x-ray machine. This monumental discovery by Wilhelm K.
Röntgen in 1895 paved the way for the development of modern computer equipment that would allow the safe
performance of nerve blocks and other invasive procedures.
Other notable developments include improvements in plastic and silicone materials that facilitate the manufacture of
a variety of catheters for the continuous administration of regional anesthesia and the development of the peripheral
nerve stimulator that assists in the accurate placement of needles and catheters. Three areas are examined, the first of
which is the approval process for new medical devices; the second is the development and ultimate withdrawal of
microcatheters for continuous administration of spinal anesthesia; and the third is infection during chronic epidural
catheterization.
The Approval Process for a New Medical Device
Knowledge of the process required for the approval of a new medical device is a good way of understanding the
research that lies behind innovations in equipment for regional anesthesia. The approval process in the United States
is used as an example of this process. The U.S. Center for Devices and Radiological Health (CDRH) of the FDA
develops and implements national programs to protect the public health in the fields of medical devices and
radiology. These programs are intended to ensure the safety, efficacy, and proper labeling of medical devices; to
control unnecessary human exposure to potentially hazardous ionizing and nonionizing radiation; and to ensure the
safe, efficacious use of such radiation. Similar approval and registration processes exist in most developed countries,
and substantial efforts have been made to coordinate the approval processes in Europe and North America. The
Medical Device Amendments of 1976 to the Federal Food, Drug, and Cosmetic Act established three regulatory
classes for medical devices. The three classes are based on the degree of control necessary to guarantee that the
various types of devices are safe and effective.
Class I—These devices present minimal potential for harm to the user and are often simpler in design than Class II
or Class III devices. Examples include enema kits and elastic bandages.
Class II—Most medical devices are considered Class II devices. Examples of Class II devices include powered
wheelchairs and some pregnancy test kits.
Class III—These devices usually sustain or support life, are implanted, or present potential unreasonable risk of
illness or injury. Examples of Class III devices include implantable pacemakers and breast implants.
If a device falls into a generic category of exempted Class I devices, a premarket notification application and FDA
clearance are not required. Examples of exempt devices include stethoscopes, mercury thermometers, and bedpans.
To market a medical device in the United States, manufacturers must go through one of two evaluation processes:
premarket notification 510(k), unless exempt, or premarket approval. Most medical devices are cleared for
commercial distribution in the United States by the premarket notification 510(k) process. Section 510(k) of the
Food, Drug, and Cosmetic Act requires device manufacturers to notify the FDA of their intent to market a medical
device. This is known as Premarket Notification or 510(k). Under 510(k), before a medical device can be marketed,
the manufacturer must demonstrate to the FDA’s satisfaction that it is “substantially equivalent” to (as safe and
effective as) a device already on the market. A primary safeguard in the way the FDA regulates medical devices is
the requirement that manufacturers submit to the FDA a premarket approval application if they wish to market any
new products that contain new materials or that differ in design from products already on the market. This
submission must provide valid scientific evidence, collected from human clinical trials, showing that the device is
safe and effective for its intended use. Evidence supporting multiple fields of concern needs to be provided,
including chemical, thermal, mechanical, electrical, and radiation safety; the target population; anatomic sites;
design and materials; energy used and/or delivered; performance; compatibility with the environment and other
devices; sterility; biocompatibility; and more. The majority of devices that are currently marketed for use in regional
anesthesia are regulated under these guidelines, and studies and research performed by companies interested in
marketing the devices need to meet or exceed the FDA standards. Physicians or researchers may choose to adapt
other devices or techniques for regional anesthesia, but this is only to be done by an investigational review board in
143
an approved research program. If the device is to become commercially available, the FDA’s approval needs to be
obtained.
Microcatheters for Continuous Administration of Spinal Anesthesia
As previously mentioned, Edward B. Tuohy was the first to describe the technique of continuous spinal anesthesia,
with a 15-G needle and a urethral catheter placed into the subarachnoid space. In 1947, Miguel Martínez
[169] [187]
Curbelo modified Tuohy’s technique and inserted a urethral catheter into the epidural space. Since that time, [170]
continuous epidural anesthesia has become more popular than continuous spinal anesthesia because of its smaller
incidence of PDPH. However, the availability of spinal microcatheters caused a renaissance in the performance of
continuous spinal anesthesia in the late 1980s and early 1990s. These microcatheters were considered
[188] [189] [190]
relatively easy to use, and continuous spinal anesthesia provided a stable block with a more rapid onset of action
than continuous epidural blockade. The drug of choice in 1969 was lidocaine after a multicenter prospective study of
more than 10,000 uses of spinal anesthetics, which established lidocaine’s (5% solution in saline, 40–100 mg)
intrathecal safety and efficacy (no major neurologic complications such as cauda equina injury) and began the
replacement of tetracaine for spinal anesthesia.[191]
Unfortunately, reports began to appear about neurologic deficits associated with continuous spinal anesthesia. These
deficits, characterized by perineal sensory loss and changes in sphincter function, were often severe and
[192]
debilitating. In the immediate postoperative period, the constellation of neurologic deficits included perianal
hypesthesia, lower extremity paresis, urinary retention, and difficulty in defecation. The neurologic deficits could be
permanent, resulting in perianal hypesthesia, sexual dysfunction, and difficulty with defecation and urination. It [193]
was hypothesized that microcatheter continuous spinal anesthesia could convey a unique risk of maldistribution of
the local anesthetic solution and local neurotoxicity. Similarities in these reports included the use of 5% lidocaine,
less than the expected anesthetic effect for a given dose, an initial lidocaine dose of 100 mg or more to establish the
spinal anesthetic, and a total lidocaine dose exceeding 100 mg. Models of the thecal sac demonstrated that if the
catheter tip pointed caudad, there was a strong likelihood of hyperbaric drug pooling at the sacral side of the lordotic
hump, with poor spread to the higher lumbothoracic levels. Poor cephalad spread led in turn to inadequate surgical
anesthesia, encouraging the addition of more solution, with further pooling, and so on. Initially, limitations were
[192]
proposed in the usage of the microcatheters, including recommendations for limiting threading beyond the needle tip
and limiting the dose of lidocaine.
Further problems were noted with microcatheters that were important although not as serious. Hurley and Lambert [188]
published an evaluation of continuous spinal anesthesia with microcatheters. In this evaluation, the issue of the
microcatheter being trapped in the ligamentum flavum was discussed. It was noted that trapping and tearing on
attempted removal of the catheters could occur as a result of their being weaker than epidural catheters. The tensile
strength of 32-G microcatheters was 0.54 kg with a stylet or 0.27 kg alone compared with a 19-G epidural catheter
that had a tensile strength of 1.58 kg.
Eventually, microcatheters were withdrawn from the North American market (FDA Safety Alert: Cauda equina
syndrome associated with use of small-bore catheters in continuous spinal anesthesia; Washington, DC: Food and
Drug Administration, May 29, 1992).
Regrettably, the reports of cases of cauda equina syndrome did not cease. Schneider and colleagues reported four [194]
instances of documented transient lumbosacral monoradiculopathy after one dose of hyperbaric lidocaine spinal
anesthesia in 88 exposures. This demonstrated a potential for neurotoxicity of hyper baric lidocaine that was
unrelated to pericatheter pooling. The authors demonstrated by dissection that the most dorsad lumbosacral dorsal
roots are stretched in the lithotomy position. They noted that stretching compromises neural perfusion and thus
increases neural vulnerability to lidocaine exposure. Further reports of complications continued to surface.
In an editorial in 1994, Rudolph Jong hypothesized that microcatheters contributed to high-density bathing of the
[195]
lumbosacral roots in lidocaine, but he suggested that exposure to a potentially neurotoxic product could compromise
spinal root functionality. Animal studies performed by Ready and coworkers had demonstrated that local
[196]
anesthetic-induced myelotoxicity (in rabbits) was related to water solubility. Highly water-soluble drugs such as
lidocaine and tetracaine could be prepared in concentrations sufficiently potent to cause neural damage, whereas less
water-soluble drugs, such as bupivacaine, could not. Jong noted that the hyperbaric lidocaine formulation appeared
to carry a substantial risk of neurotoxicity when given intrathecally, although the reason was not completely clear.
Possible explanations included the high concentration (5%) of lidocaine; high osmolarity (824 mmol/L) imparted by
144
7.5% dextrose; heavy density (1.033); positional root stretching; or a combination of the above. Jong proposed that
intrathecal lidocaine be used cautiously if at all.
Further studies continue to suggest that hyperbaric lidocaine is a neurotoxic substance and that alternatives should
be developed. Although hyperbaric lidocaine is still available, examining the history of its use gives an interesting
[197]
portrayal of research and studies in the field of regional anesthesia and how developments in devices and technology
can demonstrate potential weaknesses in available drug formulations.
Infection During Chronic Epidural Catheterization
For more than a decade and a half, there has been an increased usage of long-term epidural analgesia for patients
with severe cancer pain and, more recently, even chronic nonmalignant pain. Older studies have reported a high
incidence of positive bacterial culture growth from epidural catheters, without signs of epidural infection at the time
of culture or subsequent follow-up. Du Pen and associates published a report of early signs of infection in 350
[198] [199] [200]
patients in whom long-term epidural catheters had been inserted. Three areas of the catheter track were found to be
involved in infections of the exit site, superficial catheter track infection, and epidural space infection. The bacteria
cultured were most commonly from skin flora contamination, including Staphylococcus epidermidis and
Staphylococcus aureus. All 19 patients who developed deep track or epidural infections were successfully treated
with antibiotics and catheter removal. No surgical spinal cord decompression was required. Catheters were replaced
in 15 of the 19 treated patients who requested them after treatment with no recurrent infections. Patients with
acquired immunodeficiency syndrome may have a higher incidence of epidural catheter infection (compared with
cancer patients); however, the sample size described is probably too small to draw definitive conclusions. Clinical
reports of this nature are important methods of evaluating the risks and benefits of procedures performed in regional
anesthesia and are a means to further expanding our understanding and knowledge.
Conclusion
This chapter is a brief summary of some of the highlights of discovery and development that have made regional
anesthesia what it is today. It is fascinating to attempt to view current medical practice in a historical perspective and
to attempt to understand how its past evolution has brought us to our current status. It is gratifying to know that
current researchers are held to a higher standard of accountability in performing animal and human research than
their predecessors. In reviewing this information, one is often tempted to ask, “Did they really get away with doing
that?” Further developments and improvements are still needed, but much progress has been made.
REFERENCES
1. von Anrep B: Ueber die physiologische Wirkung des cocain. Pflugers Arch 21:38, 1880.
2. Koller K: On the use of cocaine for producing anesthesia on the eye. Lancet 2:990, 1884.
3. Corning JL: Spinal anesthesia and local medication of the cord with cocaine. N Y Med J 42:483, 1885.
4. Quincke H: Die lumbal punction des hydrocephalus. Ber Klin Wochenschr 28:929, 1891.
5. Bier A: Versuche uber Cocainisirung des Ruckenmarkes. Dtsch Z Chir 51:361, 1899.
6. Abel JJ: On the blood-pressure-raising constituent of the suprarenal capsule. Johns Hopkins Hosp Bull 8:151, 1897.
7. Narahashi T, Frazier T, Yamada M: The site of action and active form of local anesthetics. I. Theory and pH experiments with tertiary
compounds. J Pharmacol Exp Ther 171:32–44, 1970.
8. Frazier DT, Narahashi T, Yamada M: The site of action and active form of local anesthetics. II. Experiments with quaternary compounds. J
Pharmacol Exp Ther 171:45–51, 1970.
9. Hille B: The pH-dependent rate of action of local anesthetics on the node of Ranvier. J Gen Physiol 69:475–496, 1977.
10. Hille B: Local anesthetics: Hydrophilic and hydrophobic pathways for the drug-receptor reaction. J Gen Physiol 69:497–515, 1977.
11. Ritchie JM: Mechanism of action of local anaesthetic agents and biotoxins. Br J Anaesth 47(Suppl):191, 1975.
12. Merki F, Buchi J, Perlia X: [Relations between the physico-chemical properties, the chemical reactivity and the local anesthetic activity. 32.
(Part 1): Binding capacity of a structural protein (wool) to local anesthetics]. Arzneimittelforschung 25:997–1004, 1975.
145
13. Aberg G, Dhuner KG, Sydnes G: Studies on the duration of local anaesthesia: Structure/activity relationships in a series of homologous local
anaesthetics. Acta Pharmacol Toxicol (Copenh) 41:432–443, 1977.
14. Schmidt B: [Chemistry of local anesthetics]. Klin Anasthesiol Intensivther 18:1–16, 1978.
15. Reinhard U, Buchi J, Perlia X: [Relations between the physico-chemical properties, the chemical reactivity and the local-anesthetic
activity/part 33: studies on the interactions of local-anesthetically active cinchocaine homologues with phospholipids (author’s translation)].
Arzneimittelforschung 25:1340–1351, 1975.
16. Buchi J, Koller RJ, Perlia X: [Relations between chemical structure, physico-chemical properties, chemical reactivity and effect of various
positionally isomeric local anesthetics. Arzneimittelforschung 25:14–24, 1975.
17. Takman BH: The chemistry of local anaesthetic agents: Classification of blocking agents. Br J Anaesth 47:183–190, 1975.
18. Zaagsma J, Nauta WT: Beta-adrenoceptor studies. 2. Effects of alkyl substitution on beta-adrenoceptor blocking, antiarrhythmic, and local
anesthetic activities of 1,1’-(o-phenylenedioxy)bis(3-isopropylamino-2-propanol). J Med Chem 20:527–531, 1977.
19. Marxer A, Schier O: Fundamental structures in drug research. Prog Drug Res 20:385–432, 1976.
20. Lokhandwala M, Patel DB, Patel H, et al: Stereochemical investigations of local anesthetic action. J Pharm Sci 60:685–689, 1971.
21. Buchi J, Oey LT, Perlia X: [Relations between chemical structure, physico-chemical reactivity and local anesthetic activity of some procaine
isosteres.] Arzneimittelforschung 22:1071–1084, 1972.
22. MerkiF, Buchi J, Perlia X: [Relationship between the physico-chemical properties, the chemical reactivity and the local anesthetic effect: The
binding capacity of structural protein (wool) for local anesthetics]. Arzneimittelforschung 25:1233–1240, 1975.
23. BuchiJ, Koller RJ, Perlia X: [Relationship between chemical structure, physio-chemical properties, chemical reactivity and effect of various
local anesthetics with position isomerism.] Arzneimittelforschung 24:1957–1964, 1974.
24. Pesak
M, Kopecky F, Celechovsky J, et al: Study of local anesthetics. Part 46: Correlations between anesthetic activity and physico-chemical
parameters of some alkoxy substituted esters of phenylcarbamic acids. Pharmazie 31:24–27, 1976.
25. AkermanB, Hellberg IB, Trossvik C: Primary evaluation of the local anaesthetic properties of the amino amide agent ropivacaine (LEA 103).
26. Foster RH, Markham A: Levobupivacaine: A review of its pharmacology and use as a local anaesthetic. Drugs 59:551–579, 2000.
27. Bardsley H, Gristwood R, Baker H, et al: A comparison of the cardiovascular effects of levobupivacaine and rac-bupivacaine following
intravenous administration to healthy volunteers. Br J Clin Pharmacol 46:245–249, 1998.
28. HuangYF, Pryor ME, Mather LE, Veering BT: Cardiovascular and central nervous system effects of intravenous levobupivacaine and
bupivacaine in sheep. Anesth Analg 86:797–804, 1998.
29. Wildsmith JA, Gissen AJ, Gregus J, Covino BG: Differential nerve blocking activity of amino-ester local anaesthetics. Br J Anaesth 57:612–
620, 1985.
30. Bokesch PM, Post C, Strichartz G: Structure-activity relationship of lidocaine homologs producing tonic and frequency-dependent impulse
blockade in nerve. J Pharmacol Exp Ther 237:773–781, 1986.
31. PindelEV, Kedishvili NY, Abraham TL, et al: Purification and cloning of a broad substrate specificity human liver carboxylesterase that
catalyzes the hydrolysis of cocaine and heroin. J Biol Chem 272:14769–14775, 1997.
32. Wildsmith
JA, Gissen AJ, Takman B, Covino BG: Differential nerve blockade: Esters v. amides and the influence of pKa. Br J Anaesth
59:379–384, 1987.
33. Blair MR: Cardiovascular pharmacology of local anaesthetics. Br J Anaesth 47:247–252, 1975.
34. Covino BG: Pharmacology of local anaesthetic agents. British J Anaesth 58:701–716, 1986.
35. Lofstrom JB: Ulnar nerve blockade for the evaluation of local anaesthetic agents. Br J Anaesth 47:297–300, 1975.
36. Owen MD, D’Angelo R, Gerancher JC, et al: 0.125% ropivacaine is similar to 0.125% bupivacaine for labor analgesia using patient-controlled
epidural infusion. Anesth Analg 86:527–531, 1998.
37. Capogna G, Celleno D, Fusco P, et al: Relative potencies of bupivacaine and ropivacaine for analgesia in labour. Br J Anaesth 82:371–373,
1999.
38. Polley LS, Columb MO, Naughton NN, et al: Relative analgesic potencies of ropivacaine and bupivacaine for epidural analgesia in labor:
146
Implications for therapeutic indexes. Anesthesiology 90:944–950, 1999.
39. D’Angelo R, James RL: Is ropivacaine less potent than bupivacaine? Anesthesiology 90:941–943, 1999.
40. Dixon WJ: The up-and-down method for small samples. Am Stat Assoc J 60:967–978, 1965.
41. Eger EI, Saiman LJ, Brandstater B: Minimal alveolar anesthetic concentration: A standard of anesthetic potency. Anesthesiology 26:756–763,
1965.
42. Melzack R: The myth of painless childbirth (the John J. Bonica lecture). Pain 19:321–337, 1984.
43. Bridenbaugh PO: Intercostal nerve blockade for evaluation of local anaesthetic agents. Br J Anaesth 47:306–311, 1975.
44. Ritchie JM, Ritchie B, Greengard P: The active structure of local anesthetics. J Pharmacol Exp Ther 150:152–159, 1965.
45. Galindo
A, Benavides O, De Munos SO, et al: Comparison of anesthetic solutions used in lumbar and caudal peridural anesthesia. Anesth
Analg 57:175–179, 1978.
46. Scott DB, McClure JH, Giasi RM, et al: Effects of concentration of local anaesthetic drugs in extradural block. Br J Anaesth 52:1033–1037,
1980.
47. DiFazio CA, Carron H, Grosslight KR, et al: Comparison of pH-adjusted lidocaine solutions for epidural anesthesia. Anesth Analg 65:760–
764, 1986.
48. Capogna G, Celleno D, Varrassi G, et al: Epidural mepivacaine for cesarean section: Effects of a pH-adjusted solution. J Clin Anesth 3:211–
214, 1991.
49. McClure JH, Scott DB: Comparison of bupivacaine hydrochloride and carbonated bupivacaine in brachial plexus blood by the interscalene
technique. Br J Anaesth 53:523–526, 1981.
50. ZahlK, Jordan A, McGroarty J, et al: Peribulbar anesthesia. Effect of bicarbonate on mixtures of lidocaine, bupivacaine, and hyaluronidase
with or without epinephrine. Ophthalmology 98:239–242, 1991.
51. CandidoKD, Winnie AP, Covino BG, et al: Addition of bicarbonate to plain bupivacaine does not significantly alter the onset or duration of
plexus anesthesia. Reg Anesth 20:133–138, 1995.
52. Stevens
RA, Chester WL, Grueter JA, et al: The effect of pH adjustment of 0.5% bupivacaine on the latency of epidural anesthesia. Reg
Anesth 14:236–239, 1989.
53. BedderMD, Kozody R, Craig DB: Comparison of bupivacaine and alkalinized bupivacaine in brachial plexus anesthesia. Anesth Analg
67:48–52, 1988.
54. Benzon HT, Strichartz GR, Gissen AJ, et al: Developmental neurophysiology of mammalian peripheral nerves and age-related differential
sensitivity to local anaesthetic. Br J Anaesth 61:754–760, 1988.
55. Gissen AJ, Covino BG, Gregus J: Differential sensitivity of fast and slow fibers in mammalian nerve. III. Effect of etidocaine and bupivacaine
on fast/slow fibers. Anesth Analg 61:570–575, 1982.
56. GissenAJ, Covino BG, Gregus J: Differential sensitivity of fast and slow fibers in mammalian nerve. II. Margin of safety for nerve
transmission. Anesth Analg 61:561–569, 1982.
57. Gissen AJ, Covino BG, Gregus J: Differential sensitivities of mammalian nerve fibers to local anesthetic agents. Anesthesiology 53:467–474,
1980.
58. Wong K, Strichartz GR, Raymond SA: On the mechanisms of potentiation of local anesthetics by bicarbonate buffer: Drug structure-activity
studies on isolated peripheral nerve. Anesth Analg 76:131–143, 1993.
59. Bokesch PM, Raymond SA, Strichartz GR: Dependence of lidocaine potency on pH and PCO2 . Anesth Analg 66:9–17, 1987.
60. Bromage PR, Nickel PM: Comparison of lidocaine hydrocarbonate and lidocaine hydrochloride for epidural blockade [letter]. Anesthesiology
64:126–127, 1986.
61. Morison
DH: A double-blind comparison of carbonated lidocaine and lidocaine hydrochloride in epidural anaesthesia. Can Anaesth Soc J
28:387–389, 1981.
62. Eckstein KL, Vicente-Eckstein A, Steiner R, Missler U: [Clinical trial of CO2 -bupivacaine]. Klin Anasthesiol Intensivther 18:185–190, 1978.
63. Johns RA, DiFazio CA, Longnecker DE: Lidocaine constricts or dilates rat arterioles in a dose-dependent manner. Anesthesiology 62:141–
144, 1985.
147
64. Johns
RA, Seyde WC, DiFazio CA, Longnecker DE: Dose-dependent effects of bupivacaine on rat muscle arterioles. Anesthesiology 65:186–
191, 1986.
65. Albert J, Lofstrom B: Bilateral ulnar nerve blocks for the evaluation of local anesthetic agents. Tests with a new agent, prilocaine, and with
lidocaine in solutions with and without epinephrine. Acta Anaesthesiol Scand 9:203–211, 1965.
66. Zaric D, Nydahl PA, Philipson L, et al: The effect of continuous lumbar epidural infusion of ropivacaine (0.1%, 0.2%, and 0.3%) and 0.25%
bupivacaine on sensory and motor block in volunteers: A double-blind study. Reg Anesth 21:14–25, 1996.
67. Cederholm I, Anskar S, Bengtsson M: Sensory, motor, and sympathetic block during epidural analgesia with 0.5% and 0.75% ropivacaine with
and without epinephrine. Regional Anesth 19:18–33, 1994.
68. Hickey
R, Candido KD, Ramamurthy S, et al: Brachial plexus block with a new local anaesthetic: 0.5 per cent ropivacaine. Can J Anaesth
37:732–738, 1990.
69. BrownDL, Carpenter RL, Thompson GE: Comparison of 0.5% ropivacaine and 0.5% bupivacaine for epidural anesthesia in patients
undergoing lower-extremity surgery. Anesthesiology 72:633–636, 1990.
70. Katz JA, Knarr D, Bridenbaugh PO: A double-blind comparison of 0.5% bupivacaine and 0.75% ropivacaine administered epidurally in
humans. Reg Anesth 15:250–252, 1990.
71. Kopacz DJ, Allen HW, Thompson GE: A comparison of epidural levobupivacaine 0.75% with racemic bupivacaine for lower abdominal
surgery. Anesth Analg 90:642–648, 2000.
72. Crews
JC, Hord AH, Denson DD, Schatzman C: A comparison of the analgesic efficacy of 0.25% levobupivacaine combined with 0.005%
morphine, 0.25% levobupivacaine alone, or 0.005% morphine alone for the management of postoperative pain in patients undergoing major
abdominal surgery. Anesth Analg 89:1504–1509, 1999.
73. CorningJ: On the prolongation of the anesthetic effect of the hydrochlorlorate of cocaine, when subcutaneously injected. An experimental
study. N Y Med J 42:317, 1885.
74. Braun
H: Ueber den einfluss der vitalitat der gewebe auf die ortlichen und allgemeinen giftwirkungen localanasthesirender mittel und uber die
bedeutung des adrenalins fur die localanasthesie. Arch Clin Chir 69:541, 1903.
75. ConcepcionM, Maddi R, Francis D, et al: Vasoconstrictors in spinal anesthesia with tetracaine—a comparison of epinephrine and
phenylephrine. Anesth Analg 63:134–138, 1984.
76. Swerdlow M, Jones R: The duration of action of bupivacaine, prilocaine and lignocaine. Br J Anaesth 42:335–339, 1970.
77. Warner MA, Kunkel SE, Offord KO, et al: The effects of age, epinephrine, and operative site on duration of caudal analgesia in pediatric
patients. Anesth Analg 66:995–998, 1987.
78. Sinclair CJ, Scott DB: Comparison of bupivacaine and etidocaine in extradural blockade. Br J Anaesth 56:147–153, 1984.
79. Eisenach
JC, Grice SC, Dewan DM: Epinephrine enhances analgesia produced by epidural bupivacaine during labor. Anesth Analgesia
66:447–451, 1987.
80. BaranowskiAP, Dean Y, Pither CE: The effect of a priming epidural injection of adrenaline on epidural blockade with bupivacaine.
Anaesthesia 46:1023–1029, 1991.
81. Kuhar MJ, Pert CB, Snyder SH: Regional distribution of opiate receptor binding in monkey and human brain. Nature 245:447–450, 1973.
82. Pert CB, Snyder SH: Opiate receptor: Demonstration in nervous tissue. Science 179:1011–1014, 1973.
83. Sabbe MB, Yaksh TL: Pharmacology of spinal opioids. J Pain Sympt Manage 5:191–203, 1990.
84. Mathews ET, Abrams LD: Intrathecal morphine in open heart surgery [letter]. Lancet 2:543, 1980.
85. Kalso E: Effects of intrathecal morphine, injected with bupivacaine, on pain after orthopaedic surgery. Br J Anaesth 55:415–422, 1983.
86. Paterson GM, McQuay HJ, Bullingham RE, Moore RA: Intradural morphine and diamorphine. Dose response studies. Anaesthesia 39:113–
117, 1984.
87. JacobsonL, Chabal C, Brody MC, et al: Intrathecal methadone and morphine for postoperative analgesia: A comparison of the efficacy,
duration, and side effects. Anesthesiology 70:742–746, 1989.
88. Husemeyer RP, O’Connor MC, Davenport HT: Failure of epidural morphine to relieve pain in labour. Anaesthesia 35:161–163, 1980.
89. Hogan Q, Haddox JD, Abram S, et al: Epidural opiates and local anesthetics for the management of cancer pain. Pain 46:271–279, 1991.
148
90. Maves TJ, Gebhart GF: Antinociceptive synergy between intrathecal morphine and lidocaine during visceral and somatic nociception in the
rat. Anesthesiology 76:91–99, 1992.
91. FraserHM, Chapman V, Dickenson AH: Spinal local anaesthetic actions on afferent evoked responses and wind-up of nociceptive neurones in
the rat spinal cord: Combination with morphine produces marked potentiation of antinociception. Pain 49:33–41, 1992.
92. WongCA, Scavone BM, Loffredi M, et al: The dose-response of intrathecal sufentanil added to bupivacaine for labor analgesia.
93. Palmer CM, Van Maren G, Nogami WM, Alves D: Bupivacaine augments intrathecal fentanyl for labor analgesia. Anesthesiology 91:84–89,
1999.
94. Lin BC, Lin PC, Lai YY, et al: The maternal and fetal effects of the addition of sufentanil to 0.5% spinal bupivacaine for cesarean delivery.
Acta Anaesthesiol Sin 36:143–148, 1998.
95. Asokumar B, Newman LM, McCarthy RJ, et al: Intrathecal bupivacaine reduces pruritus and prolongs duration of fentanyl analgesia during
labor: A prospective, randomized controlled trial. Anesth Analg 87:1309–1315, 1998.
96. Dahlgren
G, Hultstrand C, Jakobsson J, et al: Intrathecal sufentanil, fentanyl, or placebo added to bupivacaine for cesarean section. Anesth
Analg 85:1288–1293, 1997.
97. Singh H, Yang J, Thornton K, Giesecke AH: Intrathecal fentanyl prolongs sensory bupivacaine spinal block. Can J Anaesth 42:987–991, 1995.
98. Loper
KA, Ready LB, Downey M, et al: Epidural and intravenous fentanyl infusions are clinically equivalent after knee surgery. Anesth Analg
70:72–75, 1990.
99. Ellis
DJ, Millar WL, Reisner LS: A randomized double-blind comparison of epidural versus intravenous fentanyl infusion for analgesia after
cesarean section. Anesthesiology 72:981–986, 1990.
100. van den Nieuwenhuyzen MC, Stienstra R, Burm AG, et al: Alfentanil as an adjuvant to epidural bupivacaine in the management of
postoperative pain after laparotomies: Lack of evidence of spinal action. Anesth Analg 86:574–578, 1998.
101. Guinard JP, Carpenter RL, Chassot PG: Epidural and intravenous fentanyl produce equivalent effects during major surgery. Anesthesiology
82:377–382, 1995.
102. Salomaki TE, Laitinen JO, Nuutinen LS: A randomized double-blind comparison of epidural versus intravenous fentanyl infusion for
analgesia after thoracotomy. Anesthesiology 75:790–795, 1991.
103. D’Angelo
R, Gerancher JC, Eisenach JC, Raphael BL: Epidural fentanyl produces labor analgesia by a spinal mechanism. Anesthesiology
88:1519–1523, 1998.
104. Cooper
DW, Ryall DM, Desira WR: Extradural fentanyl for postoperative analgesia: Predominant spinal or systemic action? Br J Anaesth
74:184–187, 1995.
105. Baxter AD, Laganiere S, Samson B, et al: A comparison of lumbar epidural and intravenous fentanyl infusions for post-thoracotomy
analgesia. Can J Anaesth 41:184–191, 1994.
106. RostaingS, Bonnet F, Levron JC, et al: Effect of epidural clonidine on analgesia and pharmacokinetics of epidural fentanyl in postoperative
patients. Anesthesiology 75:420–425, 1991.
107. VercauterenM, Lauwers E, Meert T, et al: Comparison of epidural sufentanil plus clonidine with sufentanil alone for postoperative pain
relief. Anaesthesia 45:531–534, 1990.
108. Motsch J, Graber E, Ludwig K: Addition of clonidine enhances postoperative analgesia from epidural morphine: A double-blind study.
109. Mercier FJ, Dounas M, Bouaziz H, et al: The effect of adding a minidose of clonidine to intrathecal sufentanil for labor analgesia.
110. Racle JP, Poy JY, Benkhadra A, et al: [Prolongation of spinal anesthesia with hyperbaric bupivacaine by adrenaline and clonidine in the
elderly]. Ann Fr Anesth Reanim 7:139–144, 1988.
111. Bonnet F, Buisson VB, François Y, et al: Effects of oral and subarachnoid clonidine on spinal anesthesia with bupivacaine. Reg Anesth
15:211–214, 1990.
112. Bonnet F, Diallo A, Saada M, et al: Prevention of tourniquet pain by spinal isobaric bupivacaine with clonidine. Br J Anaesth 63:93–96, 1989.
113. Brunschwiler M, Van Gessel E, Forster A, et al: Comparison of clonidine, morphine or placebo mixed with bupivacaine during continuous
spinal anaesthesia. Can J Anaesth 45:735–740, 1998.
149
114. Nasseri
A, Minneman KP: Relationship between alpha2 -adrenergic receptor binding sites and the functional receptors inhibiting
norepinephrine release in rat cerebral cortex. Mol Pharmacol 32:655–662, 1987.
115. Armand S, Langlade A, Boutros A, et al: Meta-analysis of the efficacy of extradural clonidine to relieve postoperative pain: An impossible
task. Br J Anaesth 81:126–134, 1998.
116. Eisenach JC, Hood DD, Curry R: Intrathecal, but not intravenous, clonidine reduces experimental thermal or capsaicin-induced pain and
hyperalgesia in normal volunteers. Anesth Analg 87:591–596, 1998.
117. GentiliM, Houssel P, Osman M, et al: Intra-articular morphine and clonidine produce comparable analgesia but the combination is not more
effective. Br J Anaesthesia 79:660–661, 1997.
118. Joshi W, Reuben SS, Kilaru PR, et al: Postoperative analgesia for outpatient arthroscopic knee surgery with intraarticular clonidine and/or
morphine. Anesth Analg 90:1102–1106, 2000.
119. ConnellyNR, Camerlenghi G, Bilodeau M, et al: Use of clonidine as a component of the peribulbar block in patients undergoing cataract
surgery. Reg Anesth Pain Med 24:426–429, 1999.
120. Elliott S, Eckersall S, Fligelstone L, Jothilingam S: Does the addition of clonidine affect duration of analgesia of bupivacaine wound
infiltration in inguinal hernia surgery? Br J Anaesth 79:446–449, 1997.
121. Bernard JM, Macaire P: Dose-range effects of clonidine added to lidocaine for brachial plexus block. Anesthesiology 87:277–284, 1997.
122. Kleinschmidt S, Stockl W, Wilhelm W, Larsen R: The addition of clonidine to prilocaine for intravenous regional anaesthesia. Eur J
Anaesthesiol 14:40–46, 1997.
123. Gentili M, Bernard JM, Bonnet F: Adding clonidine to lidocaine for intravenous regional anesthesia prevents tourniquet pain. Anesth Analg
88:1327–1330, 1999.
124. Eisenach
JC, Shafer SL, Bucklin BA, et al: Pharmacokinetics and pharmacodynamics of intraspinal dexmedetomidine in sheep.
125. Coward DM: Tizanidine: Neuropharmacology and mechanism of action. Neurology 44:S6–10, 1994.
126. Fromm GH, Aumentado D, Terrence CF: A clinical and experimental investigation of the effects of tizanidine in trigeminal neuralgia. Pain
53:265–271, 1993.
127. Fogelholm R, Murros K: Tizanidine in chronic tension-type headache: A placebo controlled double-blind cross-over study. Headache 32:509–
513, 1992.
128. Eisenach JC: Muscarinic-mediated analgesia. Life Sci 64:549–554, 1999.
129. Hartvig P, Gillberg PG, Gordh T, Post C: Cholinergic mechanisms in pain and analgesia. Trends Pharmacol Sci (Suppl):75–79, 1989.
130. Abram SE: Alternative neuraxial pain management techniques. Reg Anesth 21:129–134, 1996.
131. Eisenach JC: Three novel spinal analgesics: Clonidine, neostigmine, amitriptyline. Reg Anesth 21:81–83, 1996.
132. Lauretti GR, Mattos AL, Gomes JM, Pereira NL: Postoperative analgesia and antiemetic efficacy after intrathecal neostigmine in patients
undergoing abdominal hysterectomy during spinal anesthesia. Reg Anesth 22:527–533, 1997.
133. Lauretti
GR, Reis MP, Prado WA, Klamt JG: Dose-response study of intrathecal morphine versus intrathecal neostigmine, their combination,
or placebo for postoperative analgesia in patients undergoing anterior and posterior vaginoplasty. Anesth Analg 82:1182–1187, 1996.
134. Klamt
JG, Garcia LV, Prado WA: Analgesic and adverse effects of a low dose of intrathecally administered hyperbaric neostigmine alone or
combined with morphine in patients submitted to spinal anaesthesia: Pilot studies. Anaesthesia 54:27–31, 1999.
135. Lauretti GR, Gomes JM, Reis MP, Pereira NL: Low doses of epidural ketamine or neostigmine, but not midazolam, improve morphine
analgesia in epidural terminal cancer pain therapy. J Clin Anesth 11:663–668, 1999.
136. Lauretti GR, Mattos AL, Reis MP, Pereira NL: Combined intrathecal fentanyl and neostigmine: Therapy for postoperative abdominal
hysterectomy pain relief. J Clin Anesth 10:291–296, 1998.
137. Chung CJ, Kim JS, Park HS, Chin YJ: The efficacy of intrathecal neostigmine, intrathecal morphine, and their combination for post-cesarean
section analgesia. Anesth Analg 87:341–346, 1998.
138. Lauretti
GR, de-Oliveira R, Reis MP, et al: Study of three different doses of epidural neostigmine coadministered with lidocaine for
postoperative analgesia. Anesthesiology 90:1534–1538, 1999.
139. Pan PM, Huang CT, Wei TT, Mok MS: Enhancement of analgesic effect of intrathecal neostigmine and clonidine on bupivacaine spinal
150
anesthesia. Reg Anesth Pain Med 23:49–56, 1998.
140. HoodDD, Mallak KA, Eisenach JC, Tong C: Interaction between intrathecal neostigmine and epidural clonidine in human volunteers.
141. Yang
LC, Chen LM, Wang CJ, Buerkle H: Postoperative analgesia by intra-articular neostigmine in patients undergoing knee arthroscopy.
142. Bone
HG, Van-Aken H, Booke M, Burkle H: Enhancement of axillary brachial plexus block anesthesia by coadministration of neostigmine.
Reg Anesth Pain Med 24:405–410, 1999.
143. Bouaziz H, Paqueron X, Bur ML, et al: No enhancement of sensory and motor blockade by neostigmine added to mepivacaine axillary plexus
block. Anesthesiology 91:78–83, 1999.
144. Dickenson AH: NMDA receptor antagonists: Interactions with opioids. Acta Anaesthesiol Scand 41:112–115, 1997.
145. EdwardsND, Fletcher A, Cole JR, Peacock JE: Combined infusions of morphine and ketamine for postoperative pain in elderly patients.
Anaesthesia 48:124–127, 1993.
146. HartvigP, Larsson E, Joachimsson PO: Postoperative analgesia and sedation following pediatric cardiac surgery using a constant infusion of
ketamine. J Cardiothorac Vasc Anesth 7:148–153, 1993.
147. Trujillo KA, Akil H: Inhibition of opiate tolerance by non-competitive N-methyl-D-aspartate receptor antagonists. Brain Res 633:178–188,
1994.
148. Max MB, Byas-Smith MG, Gracely RH, Bennett GJ: Intravenous infusion of the NMDA antagonist, ketamine, in chronic posttraumatic pain
with allodynia: A double-blind comparison to alfentanil and placebo. Clin Neuropharmacol 18:360–368, 1995.
149. Duncan GE, Miyamoto S, Leipzig JN, Lieberman JA: Comparison of brain metabolic activity patterns induced by ketamine, MK-801 and
amphetamine in rats: Support for NMDA receptor involvement in responses to subanesthetic dose of ketamine. Brain Res 843:171–183, 1999.
150. Harder JA, Ridley RM: The 5-HT1A antagonist, WAY 100 635, alleviates cognitive impairments induced by dizocilpine (MK-801) in
monkeys. Neuropharmacology 39:547–552, 2000.
151. Ilkjaer S, Bach LF, Nielsen PA, et al: Effect of preoperative oral dextromethorphan on immediate and late postoperative pain and hyperalgesia
after total abdominal hysterectomy. Pain 86:19–24, 2000.
152. Davies SN, Martin D, Millar JD, et al: Differences in results from in vivo and in vitro studies on the use-dependency of N-methylaspartate
antagonism by MK-801 and other phencyclidine receptor ligands. Eur J Pharmacol 145:141–151, 1988.
153. Loo
PS, Braunwalder AF, Lehmann J, et al: Interaction of L-glutamate and magnesium with phencyclidine recognition sites in rat brain:
Evidence for multiple affinity states of the phencyclidine/N-methyl-D-aspartate receptor complex. Mol Pharmacol 32:820–830, 1987.
154. Choe H, Choi YS, Kim YH, et al: Epidural morphine plus ketamine for upper abdominal surgery: Improved analgesia from preincisional
versus postincisional administration. Anesth Analg 84:560–563, 1997.
155. Walker
SM, Cousins MJ: Reduction in hyperalgesia and intrathecal morphine requirements by low-dose ketamine infusion [letter]. J Pain
Symptom Manage 14:129–133, 1997.
156. Harada H, Kelly PJ, Cole DJ, et al: Isoflurane reduces N-methyl-D-aspartate toxicity in vivo in the rat cerebral cortex. Anesth Analg 89:1442–
1447, 1999.
157. KristensenJD, Karlsten R, Gordh T, Berge OG: The NMDA antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) has
antinociceptive effect after intrathecal injection in the rat. Pain 56:59–67, 1994.
158. Chaplan
SR, Pogrel JW, Yaksh TL: Role of voltage-dependent calcium channel subtypes in experimental tactile allodynia. J Pharmacol Exp
Ther 1117–1123, 1994.
159. Benedek G, Szikszay M: Potentiation of thermoregulatory and analgesic effects of morphine by calcium antagonists. Pharmacol Res Commun
16:1009–1018, 1984.
160. Contreras E, Tamayo L, Amigo M: Calcium channel antagonists increase morphine-induced analgesia and antagonize morphine tolerance.
Eur J Pharmacol 148:463–466, 1988.
161. Omote K, Sonoda H, Kawamata M, et al: Potentiation of antinociceptive effects of morphine by calcium-channel blockers at the level of the
spinal cord. Anesthesiology 79:746–752, 1993.
162. Chapman DB, Way EL: Modification of endorphin/enkephalin analgesia and stress-induced analgesia by divalent cations, a cation chelator
and an ionophore. Br J Pharmacol 75:389–396, 1982.
151
163. Harris
RA, Loh HH, Way EL: Effects of divalent cations, cation chelators and an ionophore on morphine analgesia and tolerance. J
Pharmacol Exp Ther 195:488–498, 1975.
164. Brose WG, Gutlove DP, Luther RR, et al: Use of intrathecal SNX-111, a novel, N-type, voltage-sensitive, calcium channel blocker, in the
management of intractable brachial plexus avulsion pain. Clin J Pain 13:256–259, 1997.
165. Penn RD, Paice JA: Adverse effects associated with the intrathecal administration of ziconotide. Pain 85:291–296, 2000.
166. Ridgeway B, Wallace M, Gerayli A: Ziconotide for the treatment of severe spasticity after spinal cord injury. Pain 85:287–289, 2000.
167. Barker AE: Clinical experiences with spinal anesthesia in 100 cases. Br Med J 1:665, 1907.
168. Lemmon WT: A method of continuous spinal anesthesia. Ann Surg 111:140, 1940.
169. Tuohy EB: Continuous spinal anesthesia: Its usefulness and technic involved. Anesthesiology 5:142, 1944.
170. Curbelo MM: Continuous peridural segmental anesthesia by means of a ureteral catheter. Anesth Analg 28:13–16, 1949.
171. Cleland JGP: Continuous peridural and caudal analgesia in surgery and early ambulation. Northwest Med J 48:26, 1949.
172. Ramsey RH: The anatomy of the ligamenta flava. Clin Orthop 44:129–140, 1966.
173. Zarzur E: Anatomic studies of the human ligamentum flavum. Anesth Analg 63:499–502, 1984.
174. Parkin IG, Harrison GR: The topographical anatomy of the lumbar epidural space. J Anat 141:211–217, 1985.
175. Hogan QH: Lumbar epidural anatomy: A new look by cryomicrotome section. Anesthesiology 75:767, 1991.
176. Savolaine ER, Pandya JB, Greenblatt SH, Conover SR: Anatomy of the human lumbar epidural space: New insights using CT-epidurography.
177. Seeling W, Tomczak R, Merk J, Mrakovcic N: [CT-epidurography. A comparison of conventional and CT-epidurography with contrast
medium injection through a thoracic peridural catheter]. Anaesthesist 44:24–36, 1995.
178. Blomberg R: The dorsomedian connective tissue band in the lumbar epidural space of humans: An anatomical study using epiduroscopy in
autopsy cases. Anesth Analg 65:747–752, 1986.
179. Blomberg RG, Olsson SS: The lumbar epidural space in patients examined with epiduroscopy. Anesth Analg 68:157–160, 1989.
180. Westbrook
JL, Renowden SA, Carrie LE: Study of the anatomy of the extradural region using magnetic resonance imaging. Br J Anaesth
71:495–498, 1993.
181. Luyendijk W: The plica mediana dorsalis of the dura mater and its relation to lumbar peridurography (canalography). Neuroradiology 11:147–
149, 1976.
182. Morisot P: [Is the posterior lumbar epidural space partitioned?]. Ann Fr Anesth Reanim 11:72–81, 1992.
183. Halpern S, Preston R: Postdural puncture headache and spinal needle design. Metaanalyses. Anesthesiology 81:1376–1383, 1994.
184. Flaatten H, Felthaus J, Kuwelker M, Wisborg T: Postural post-dural puncture headache. A prospective randomised study and a meta-analysis
comparing two different 0.40 mm O.D. (27 g) spinal needles. Acta Anaesthesiol Scand 44:643–647, 2000.
185. Wood A: New method of treating neuralgia by the direct application of opiates to the painful points. Edinburgh Med Surg J 82:265, 1855.
186. Pravaz CG: Sur un nouveau moyen d’opérer la coagulation du sang dans les artères, applicable à la guérison des aneurismes. C R Acad Sci
(Paris) 36:88, 1853.
187. Tuohy EB: The use of continuous spinal anesthesia. JAMA 128:262–264, 1945.
188. Hurley RJ, Lambert DH: Continuous spinal anesthesia with a microcatheter technique: Preliminary experience. Anesth Analg 70:97–102,
1990.
189. SutterPA, Gamulin Z, Forster A: Comparison of continuous spinal and continuous epidural anaesthesia for lower limb surgery in the elderly
patients. Anaesthesia 44:47–50, 1989.
190. Hurley RJ: Continuous spinal anesthesia. Int Anesthesiol Clin 27:46–50, 1989.
191. Phillips
OC, Ebner H, Nelson AT, Black MH: Neurologic complications following spinal anesthesia with lidocaine: A prospective review of
10,440 cases. Anesthesiology 30:284–289, 1969.
152
192. Lambert DH, Hurley RJ: Cauda equina syndrome and continuous spinal analgesia. Anesth Analg 72:817–819, 1991.
193. Schell RM, Brauer FS, Cole DJ, Applegate RL II: Persistent sacral nerve root deficits after continuous spinal anesthesia. Can J Anaesth
38:908–911, 1991.
194. Schneider M, Ettlin T, Kaufmann M, et al: Transient neurologic toxicity after hyperbaric subarachnoid anesthesia with 5% lidocaine. Anesth
Analg 76:1154–1157, 1993.
195. Jong RH: Last round for a “heavyweight”? Anesth Analg 78:3, 1994.
196. Ready LB, Plumer MH, Haschke RH, et al: Neurotoxicity of local anesthetics in rabbits. Anesthesiology 64:364–370, 1985.
197. Carpenter RL: Hyperbaric lidocaine spinal anesthesia: Do we need an alternative? Anesth Analg 81:1125, 1995.
198. Barreto RS: Bacteriological cultures of indwelling epidural catheters. Anesthesiology 23:643–646, 1962.
199. Hunt JR, Rigor BM, Collins J: The potential for contamination of continuous epidural catheters. Anesth Analg 56:222–225, 1977.
200. Du Pen SL, Peterson DG, Williams A, Bogosian AJ: Infection during chronic epidural catheterization: Diagnosis and treatment.
153
Section IV - Chapter 11 - Organization and Function of the Nerve Block Facility
Section IV - Clinical Practice of Regional Anesthesia
Richard L. Rauck
Honorio T. Benzon
161
Chapter 11 - Organization and Function of the Nerve Block Facility
P. PRITHVI RAJ
MOLLY JOHNSTON
A nerve block facility where regional anesthesia and advanced interventional techniques are performed should
provide a comfortable and relaxing area for patients who are scheduled for nerve blocks. Adequate space,
equipment, and comfortable environment are imperative to ensure proper preparation and care of the patient
undergoing such procedures.
Radiologic localization is indicated when difficulty is anticipated because of poor landmarks or anatomic anomalies,
when deep nerves or plexuses are to be blocked, and when neurolytic procedures are planned.
When first seen at the nerve block facility, the acute or chronic pain patient has already been examined by many
professionals in various hospitals and has undergone various tests and procedures. This experience makes the patient
fearful and apprehensive of seeing another new set of medical professionals. Nerve blocks are often foreign to
patients and can be a source of apprehension. The patient must be reassured that nerve blocks are a standard form of
anesthesia for surgery and for therapy in chronic patients and are performed by experts.
It is the responsibility of both the physician and the nurse to inform the patient of the purpose of the procedure, how
it is done, the expected outcome, and the side effects and risks. Unless the procedure is urgent, this explanation is
given on the visit before the procedure. To reinforce the verbal explanation, the patient receives a simple written
explanation of the procedure. Patients who are to have a procedure for chronic pain are told to bring an escort to
accompany them home after it is done. It is the responsibility of the physician to obtain written consent from the
patient.
Facilities
A spacious room is needed ( Figs. 11–1 and 11–2 ) to perform regional anesthesia procedures such as epidural
blocks, brachial plexus block for surgery, celiac plexus blocks, lumbar sympathetic blocks, and stellate ganglion
blocks for chronic pain.
Supplies for the procedure should be readily available in the room. Full monitoring equipment, procedure trays,
needles, catheters, temperature probes, syringes, and medication, including emergency drugs, should be readily
available ( Table 11–1 ). Fluoroscopic equipment is mandatory if advanced interventional techniques are commonly
performed. An alternative is to perform these procedures in the radiology suite of the hospital. The scheduling of
such procedures and safe monitoring of them in the radiology suite have not always been satisfactory. An up-to-date
storage of contrast materials is required. The physician should know the pharmacology of these drugs, and they
should not be injected if the patient has a history of allergy to iodine-containing solutions. Ionic contrast solutions
may inadvertently be injected into the subarachnoid space during the procedure. Although this is usually innocuous,
generalized muscle twitching may occur because of the inaction of contrast solution on the spinal cord. Repeated
doses of diazepam or lorazepam
162
Figure 11-1 The room in which the patient is received and prepared before the procedure and where the patient is taken for recovery after the
procedure.
Figure 11-2 The layout of the nerve block room with fluoroscopy unit and compatible table.
may be needed for 24 hours before the muscle twitching subsides. However, in general, intravascular injection of
any contrast material has not been deleterious.
Nerve stimulators are useful for locating peripheral nerves during placement of catheters, such as sciatic and
brachial plexus catheters. Many stimulators are available. Features needed in the stimulators are constant current, the
ability to stimulate as low as 0.1 mA, and frequencies of less than 5 Hz.
Personnel
The three most important people required for a regional anesthesia procedure are (1) the physician who performs the
procedure, (2) the nurse who has prepared the patient for the procedure, and (3) the radiology technician who assists
during fluoroscopy. On a selected basis, patients in chronic pain may require
163
TABLE 11-1 -- ROUTINE EMERGENCY DRUGS REQUIRED DURING REGIONAL ANESTHESIA PROCEDURES
Drug Suggested Dosage (70-kg adult) Indication
Atropine 0.2 to 0.4-mg IV increments Bradycardia from vagal dominance
Diazepam 2.5 to 5-mg IV increments Local anesthetic; seizure activity
Ephedrine 5- to 10-mg IV increments Hypotension from sympathetic block

Lidocaine 50- to 100-mg IV bolus Ventricular arrhythmias
Thiopental or propofol 50- to 100-mg IV increments Local anesthetic; seizure activity

Succinylcholine or equivalent (Versed, fentanyl, 100-mg IV bolus Muscle relaxation airway control
Naropin)
the expertise of the radiologist to interpret the on-line images for a complex, advanced procedure.
RESPONSIBILITIES OF THE PHYSICIAN
The physician must be trained to perform regional anesthesia or an advanced pain procedure. In a training
institution, a well-trained (regional anesthesia) faculty member should always be present. He or she should
anticipate any difficulties that may occur during the procedure and prepare the team for corrective action. This
person should preselect the needles and special equipment required for the procedure and should have the necessary
solutions drawn and ready to go. The patient, if awake, should receive communication throughout the procedure. At
the end of the procedure, the patient should be told about the procedure, about any side effects, and about what to
expect.
RESPONSIBILITIES OF THE NURSE
Before the procedure, the nurse should obtain a complete nursing assessment, an allergy list, and a record of
baseline vital signs including pulse, oxygen, temperature, and current pain level. During the procedure, the nurse
sets up equipment, positions the patient, monitors vital signs, and assists as required. The nurse should be prepared
to help the patient relax and should anticipate the patient’s needs in case problems arise.
It is important that the patient knows what to expect at each step of the procedure; an informed patient is less likely
to make sudden, unexpected movements. The nurse offers comfort as needed, including proper positioning of
extremities with pillows and premedication if necessary.
The nurse should have a working knowledge of the anatomy and physiology of the region to be blocked and the
pharmacology of the drugs to be used. Knowing drug complications and side effects is imperative in anticipating
problems and dealing with emergencies.
After the procedure, patients are closely monitored as long as necessary, usually 30 minutes after the procedure or 1
hour after administration of the last narcotic.
Verbal and written instructions are given to the patient before discharge if the pain procedure is performed in the
outpatient setting. This instruction includes a list of side effects that commonly occur with the block and the length
of time they may be expected to last. Patients are also informed about how and when to call personnel in the pain
management center should problems arise.
RESPONSIBILITIES OF THE RADIOLOGY TECHNICIAN
Invasive procedures for relieving pain are not automatically learned by the radiology technicians in their training for
certification. On-the-job training is required and technicians should avail themselves of the opportunity to learn
these procedures in the nerve block facility. Safety of the personnel during the fluoroscopic invasive procedure is the
responsibility of the technician. Appropriate lead shields should be available, and no person should be exposed to
radiation without safeguards during the procedure. The technician should be familiar with the fluoroscopy
equipment and should be able to provide clear images to the physician. The technician should also know how to
save and print radiologic images for record keeping and documented interpretation.
164
Equipment
To perform successful regional anesthesia, the correct equipment should be available, including needles, syringes,
and ancillary equipment necessary for the block ( Table 11–2 ). If continuous infusions are planned, adequate tubing
and pumps must be available.
A nerve block tray ( Fig. 11–3 ), whether commercially prepared or supplied by the hospital, should contain
sufficient equipment to perform the regional anesthesia procedure intended. Basic items on each nerve block tray
should include items for sterile skin preparation and draping; containers for sterile antiseptic solution and local
anesthetic; syringes for skin infiltration anesthesia and performance of the block; and an assortment of needles for
skin infiltration and drawing up local anesthetic solutions, preparing the skin, and performing the block. Injection
tubing should be available, and if continuous infusions are planned, appropriate catheters should also be available. If
drugs are to be added to the regional block tray, the hospital pharmacy should be consulted to ensure stability and
potency of the drug so that sterility can be maintained during the sterilization process.
Figure 11-3 The disposable nerve block tray.
TABLE 11-2 -- CONTENTS OF MULTIPURPOSE REGIONAL ANESTHESIA BLOCK TRAY
Routine Items
Preparation tray
Container for antiseptic solution (50 mL)
Antiseptic solution
Preparation sponges (3)
4 × 4 gauze sponges
Ruler (15 cm)
Sterility indicator
Sterile drapes (4)
Intravenous extension tubing
Container for local anesthetic (2, 50 mL)
Local anesthetic solution for infiltration (1.5% lidocaine, 10 mL)
Epinephrine (1 mg/mL)
Syringes
1 mL to dispense epinephrine
3 mL for skin infiltration
Pulsator syringe
10 mL to inject local anesthetic
Needles
165
25 × 2.5 cm (1 in) for skin infiltration of local anesthetic
22 × 7.5 cm (3 in) for deeper skin infiltration
22 × 11.8 cm (4.5 in) for deep skin infiltration
18 × 3.8 cm (1.5 in) to pierce skin and draw up solutions
Contents Specific for Procedure
Block needles
Epinephrine (1 mg/mL)
Spinal
Spinal introducer needle
Epidural
Blunt bevel needles, appropriate size
Radiofrequency needles with electrodes (5, 10, 15 cm long; 5, 10, 15 mm)
Catheter for continuous infusions to spinal, epidural, peripheral nerves
Local anesthetic for nerve block
Contrast agent and container
Neurolytic solution and container
Reusable regional anesthesia trays or commercially available trays are matters of personal preference; ultimate cost
is a consideration, and arguments can be made in favor of either choice. McMahon recently discussed the merits of [1]
reusable trays versus disposable trays.
NEEDLES
Nerve injury can occur after injection of local anesthetic for regional anesthesia and involves one of three
mechanisms:
1. Direct injury may occur to the nerve from the cutting edge of the needle.
2. Local anesthetic injection into the nerve sheath under high pressure can cause direct neural damage or
ischemia of the nerve.
3. A toxic effect resulting from the local anesthetic or its preservative may be responsible for neural toxicity.
During peripheral or plexus nerve block procedures,
a needle having a short, blunt bevel has produced less nerve trauma than the conventional hypodermic needle, which
has a long or cutting bevel. To avoid tissue trauma and undue discomfort, it is important to use the smallest
[2]
diameter needle possible. However, it is essential that the needle be large enough to inject local anesthetics and
aspirate blood easily should an accidental intravascular injection occur; therefore, a 22-gauge (G) needle is
recommended for most nerve blocks. For procedures that require deep penetration, such as a celiac plexus or
hypogastric plexus block, an 18-G or 20-G needle is preferable for better control in guiding the needle and for ease
of aspiration. A 25-G or 27-G needle should be used to infiltrate the skin and subcutaneous tissue before proceeding
with a larger needle for the nerve block. If a catheter is to be used for a continuous infusion technique, the skin
should first be prepared. A nick should be made with a larger (18-G) needle to avoid disrupting the catheter tip as it
is inserted into the skin. If a stylet needle is used, the stylet must fit flush with the bevel of the needle to avoid coring
the tissue and possibly obstructing the needle tip during insertion. Extension tubing can be beneficial when directly
attached to the needle, because the syringe can then be changed when multiple injections are to be used, as when
confirmation of needle placement is required for contrast agents used under fluoroscopy.
CATHETERS
There are a wide variety of catheters available for insertion through both spinal and epidural needles and for
placement on peripheral nerves and plexuses for continuous infusion techniques. The primary differences among
these catheters are the material from which they are made and their physical properties. The ideal material for
catheter construction should have the properties described by Bromage ( Table 11–3 ). The material should be inert,
[3]
166
nonirritating, and supple enough to avoid cracking during placement. It should possess tensile strength to prevent
breakage caused by
TABLE 11-3 -- IDEAL CHARACTERISTICS OF AN EPIDURAL CATHETER

Biochemically inert and nonirritating
High tensile strength

Low coefficient of friction
Resistant to kinking and obstruction

Maneuverable rigidity
Smooth and nontraumatic tip

Indicator of catheter length
Radiopacity
Hurley RJ, Lambert DH: Continuous spinal anesthesia with micro catheter techniques: The experience in obstetrics and general surgery. Reg Anesth
14:S3, 1989.
traction and during insertion and should allow rigid maneuvers. The catheter should be long enough to reach over
the shoulder from the lumbar region, with a sufficient length left over to enter the epidural space. The external
diameter should be small enough to allow it to pass easily through an epidural needle, and the internal diameter
lumen must be large enough to inject fluids and to aspirate blood and cerebrospinal fluid (CSF). The wall of the
catheter must be thick enough to avoid kinking and obstruction. To prevent perforation of veins or dura, the catheter
tip should be smooth, dull, and flexible. Radiopaque catheters can allow verification of correct placement with
radiographic guidance, and graduated markings facilitate control of the depth of catheter insertion into the epidural
space.
Subarachnoid catheters have been used for continuous spinal infusions since the late 1980s. Continuous spinal [4]
catheter infusion is not a new technique of regional anesthesia; it was described by Tuohy in 1944. An epidural [5]
catheter can be used for continuous subarachnoid infusion; however, the incidence of spinal headache with an 18-G
to 20-G catheter would be too high in younger patients. The present subarachnoid catheter is small enough to be
used clinically without an unacceptably high incidence of spinal headache. These catheters are 27-G, 28-G, or 32-
[6]
G, and have internal diameters large enough to allow injection of medications. One of the problems associated with
such a small catheter is the force that must be generated to overcome the resistance of the catheter. However, a study
published in 1990 confirmed that infusion pumps could accurately deliver a continuous infusion into the 32-G
catheter.[7]
Catheters are available for continuous peripheral nerve, plexus, and sympathetic ganglion infusions. They should
have most of the properties of an ideal epidural catheter (see Table 11–3 ), but they should be sufficiently rigid to
maintain their initial placement and avoid migration away from the area to be blocked. The 18-G Longdwel thin-
wall Teflon catheter (available from Becton Dickinson & Co., Franklin Lakes, NJ) has been used for prolonged
infusions of sympathetic ganglia, peripheral nerves, and plexuses. It is available in 4-, 6-, and 8-inch sizes.
[8]
FLUOROSCOPY
Fluoroscopy is an invaluable adjunct in the performance of difficult regional anesthetic procedures in morbidly
obese patients with poor anatomic landmarks or during celiac or hypogastric plexus blocks. Fluoroscopy is essential
to verify accurate needle placement and spread of opaque contrast material before neurolytic agents are injected.
The ideal contrast material should provide opacification of blood vessels and tissue during fluoroscopy, without any
accompanying toxicity or alteration in physiologic function. These agents are commonly used to delineate different
tissue planes and spread of the injected solution before introduction of local anesthetic or neurolytic substances.
They can be used to confirm epidural placement of permanent catheters and to detect subdural or subarachnoid
catheter placement or intravascular location. Because these substances may themselves be injected within the
[9]
central nervous system (CNS) or intravascularly, the potential toxicity of the different agents must be considered.
The amount of contrast agents used during regional anesthesia procedures is usually small; therefore, the clinical
effects described with use of larger volumes during radiographic procedures are usually not produced. The [10]
possibility of a true anaphylactic reaction to contrast agents is extremely rare, but it can occur; therefore, a treatment
167
plan must be prepared in anticipation of such an event. A history should be carefully recorded for any patient
scheduled to receive contrast agents so as to identify any previous adverse reaction to radiographic procedures or
contrast material. It is essential to be able to provide airway support and intravascular volume expansion and to be
able to deliver 100% oxygen and epinephrine to treat the hypotension and hypoxia that could occur from
vasodilation, increased capillary permeability, and bronchospasm resulting from an anaphylactic reaction. Levy [11]
has provided an excellent review of anaphylactic reaction management, and Table 11–4 provides a protocol for
management of anaphylaxis that may occur after injection of contrast material. Emergency drugs and fluids should
be readily available.
The contrast agents that are commonly used have a fully substituted, triiodinated benzene ring structure
TABLE 11-4 -- MANAGEMENT OF ANAPHYLAXIS *

Initial Therapy
1. Stop administration of antigen (contrast agent)
2. Maintain airway with 100% oxygen
3. Start IV volume expansion (2 to 4 L crystalloid with hypotension)

4. Discontinue any supplemental analgesic or sedative agents
5. Give epinephrine (4 to 8 µg IV bolus with hypotension, titrate as needed; 0.1 to 0.5 mg IV bolus with cardiovascular collapse)
Secondary Treatment
1. Antihistamines (diphenhydramine 0.5 to 1 mg/kg)
2. Catecholamine infusions (starting doses: epinephrine 2 to 4 µg/ minute, norepinephrine 2 to 4 µg/minute, or isoproterenol 0.5 to 1 µg/minute as a drip titrate to
desired effects)
3. Aminophylline (5 to 6 mg/kg over 20 minutes with persistent bronchospasm)
4. Corticosteroids (hydrocortisone 0.25 to 1 g; alternately, methylprednisolone 1 to 2 g) *
5. Sodium bicarbonate (0.5 to 1 mEq/kg with persistent hypotension or acidosis)

6. Airway evaluation (prior to extubation)
*Doses are representative for a 70-mg adult. Methylprednisolone may be the drug of choice if the reaction is suspected to be mediated by
complement.
TABLE 11-5 -- RADIOLOGIC CONTRAST AGENTS Metrizamide (Amipaque)NonionicCentral neural blockade

Agent Type Use
Diatrizoate (Renografin, Hypaque) Ionic Nerve plexus blocks
Iothalamate (Conway) Ionic Nerve plexus blocks

Metrizamide (Amipaque) Nonionic Central neural blockade
Iopamidol (Isovue) Nonionic Central neural blockade

Iohexol (Omnipaque) Nonionic Central neural blockade
and may have an ionic or nonionic formulation ( Table 11–5 ). The nonionic contrast agents provide opacification of
the CNS and reduce CNS toxicity after subarachnoid injection. Metrizamide was the first nonionic formulations to
be used and has been used for a number of years to provide state-of-the-art imaging during myelography. However,
it is available in a powder that must be prepared before use, and the frequency of seizures resulting from its use is
unacceptably high in comparison with newer available agents. When contrast agents are used near the central axis,
[12]
with a potential for subarachnoid injection, iopamidol or iohexol should be used, because they have a lower
potential for CNS toxicity, are water-soluble, and are provided in a liquid form that is easy to use. Table 11–5 [13]
provides the names of various ionic and nonionic contrast solutions in common use.
Informed Consent
The doctrine of informed consent establishes the rights of patients to make personal decisions regarding their
medical treatment. Because of the growing emphasis on patients’ rights regarding their medical care and the
obligations of physicians to provide patients with the necessary information to allow them to make treatment
decisions, informed consent issues are becoming more frequent subjects of medical malpractice lawsuits.
Understanding and implementing the requirements for informed consent can improve the pain management
specialist’s relationships with patients, as well as decrease litigation.
168
Physicians in earlier days had no responsibility for informing patients about a proposed treatment, its risks or
benefits, or any alternatives. All that was required was the patient’s agreement to undergo a proposed procedure. If
the patient alleged that no consent was given, the allegation against the physician was one of battery. “Battery” is
defined as the unauthorized touching of another.
The doctrine of informed consent was changed in 1957 when a California court added a requirement that it was
necessary to disclose information regarding the proposed procedure before obtaining consent. The foundation for
requiring that information be provided to patients is based on the following premises:
Patients are generally persons unlearned in the medical sciences and, therefore, except in rare cases, courts may
safely assume that the knowledge of the patient and physician are not in parity.
1. An adult who is competent has the right to exercise control over what medical treatments are personally
rendered.
2. To be effective, a patient’s consent to treatment must be an informed consent.
3. The patient is highly dependent on the physician and must trust that the physician will provide reliable
information during the decision-making process.
In determining whether there is negligence in informed consent issues, there are currently two standards used by the
courts. The professional standard, or old rule, defines the duty to disclose as limited to information that a reasonable
physician would share under the same or similar circumstances. Although this standard has already been challenged
as being paternalistic and authoritarian, it continues to be viable in many courts.
The alternative is the reasonable patient standard, also referred to as the materiality rule or new rule, which is based
on the informational needs of average, reasonable patients. This standard requires disclosing all relevant information
needed for the patient to make a meaningful decision. The key factor is reasonable disclosure.
The test for determining whether information must be disclosed is its materiality to the patient’s decision. However,
establishing the reasonable patient standard is not an easy burden. The following points must be substantiated:
1. The existence of a material risk was unknown to the patient.

2. There was a failure to disclose the risk.
3. The patient’s injury was a direct result of the risk.
The duty for providing the information needed by the patient to make an informed decision has been repeatedly held
to be the responsibility of the person ordering or performing the procedure. The person in this case is usually the
pain management specialist. If the physician delegates to a nurse the responsibility to provide information so that
consent can be obtained, the nurse then becomes legally accountable for the information provided.
Five elements must be considered when obtaining informed consent:
1. The nature and purpose of the proposed treatment

2. The expected outcome and the likelihood of success
3. The material risks
4. The alternatives and supporting information regarding those alternatives
5. The effect of no treatment, including the effect on the prognosis and the material risks associated with no
treatment
The nature and purpose of the proposed treatment should include sufficient information so that the patient
understands what the treatment will involve and whether it is being proposed to provide a cure, to alleviate or
minimize pain, or to provide diagnostic information for purposes of additional treatment.
To evaluate the benefits of the proposed treatment, the patient needs to be told the likelihood of success. No
treatment should ever be guaranteed; rather, there should be a realistic assessment based on general statistics and the
pain management specialist’s personal clinical experience with that treatment.
The fourth element in obtaining informed consent is advising the patient of any reasonable alternatives. In making a
choice, patients are entitled to involve their own value judgments as well as consider social, economic, and personal
factors. For each alternative, information must be provided about the nature and purpose of the proposed treatment,
the expected outcome and likelihood of success, and the material risks.
169
The final element in obtaining informed consent is advising the patient what is likely to occur if no treatment is
undertaken. Courts have held that physicians have a duty to advise patients not only of the risks inherent in the
proposed treatment but also of the risks of a decision not to have the treatment. The failure to give the patient these
alternatives constitutes malpractice.
The individual who provides the information to the patient so that an informed decision can be made must document
exactly what information is provided. A signed consent form is not conclusive for the issue and can readily be
challenged by the patient. The documentation should specifically state the following:
1. What information was given to the patient

2. Whether anyone else was present during that discussion
3. That an opportunity was given to the patient to ask questions
4. That the patient indicated understanding of the procedure
5. The amount of time spent discussing the proposed treatment with the patient
6. Whether any materials were used in providing the information, such as videos, anatomy drawings, or
reading materials
7. Whether further discussions with the patient seemed to be warranted before a decision could be made
The second step of the process for obtaining informed consent is witnessing the giving of consent. Consent may be
obtained verbally or in writing. Consent forms are not required by law in most states; what is required is informed
consent. As a witness, the individual is attesting to the following:
1. The legality and authenticity of the consent

2. The patient’s capacity to give consent at the time
3. The fact that consent was given freely, voluntarily, and without coercion
4. A reasonable belief that the patient has been informed
The person witnessing the giving of consent may also be the person providing the information to the patient. It
should be understood, however, that the witness has two different types of responsibilities pertaining to the two
different functions.
Monitoring
As mentioned earlier, preparation of the patient for invasive procedures should include a complete explanation of
the procedure to be performed and the receipt of informed consent obtained before the patient is brought to the area
where the block will occur. The room should be quiet, undisturbed, of adequate size, and well lit. The characteristics
and design of an ideal regional anesthesia block room have been described by Rosenblatt and Shal. Complete [14]
resuscitation facilities must be available and must include equipment to provide positive-pressure oxygen and
suction, intubation equipment with appropriate laryngoscope blades and handles already tested for working order,
appropriately sized endotracheal tubes and oral airways, and emergency drugs (see Table 11–3 ). Essential
emergency drugs that should be available include succinylcholine, atropine, thiopental or diazepam, ephedrine, and
lidocaine (see Table 11–1 ). A functioning intravenous (IV) catheter is essential for all regional anesthesia
procedures, except for small (2–3 mL) injections of local anesthetics into muscle trigger points or single peripheral
nerve blocks. Minimal monitoring should include continuous electrocardiograph (ECG) monitoring, heart rate,
blood pressure, respiratory rate, oxygen saturation if sedative or narcotic analgesic medications will be given before
or during the block, and level of consciousness. Baseline level of consciousness, pulse oximetry, and vital signs
[15]
should be obtained when the patient is admitted to the pain management center; this information should be used as a
reference during the procedure.
PREPARATION AND MONITORING OF SOME PROCEDURES IN THE NERVE BLOCK

FACILITY
Spinal Anesthesia. Once the patient is taken to the facility where the block will occur, a functioning IV catheter
should be started, and blood pressure and heart rate should be measured before administration of the block. These
measurements must be continued throughout the procedure with continuous ECG monitoring, because the most
important physiologic response to spinal anesthesia involves the cardiovascular system. This response is mediated
primarily by the combined effects of sympathetic denervation and, with higher block (T1–T4), unopposed vagal
nerve dominance. Sympathetic denervation produces arterial and, more important, arteriolar vasodilation. This
vasodilation is not complete, however, because vascular smooth muscle on the arterial side maintains a significant
degree of autonomous tone. The venous system has very little smooth muscle present within its walls and maintains
170
no significant residual tone with complete sympathectomy. Venodilatation and reduced preload result in a reduction
in cardiac output and can cause significant hypotension that needs clinical management after spinal anesthesia. [16]
Bradycardia can occur after spinal anesthesia and may be due to blockade of the cardioaccelerator fibers (arising
from T1–T4) or decreased venous return activation of the great vein and right atrial cardiac receptors, which
reflexively slow the heart rate. [17]
Respiratory rate must be determined before the block, and adequacy of ventilation must be monitored continually
throughout the procedure. It is important to monitor closely the level of consciousness throughout the period of
[18]
spinal anesthesia to detect any change before it becomes a problem. The level of spinal anesthesia should be
[19]
followed in anticipation of an untoward event, such as blockage of the cardioaccelerator fibers with a high thoracic
block (T1–T4).
When spinal narcotics are administered, monitor should be provided for delayed respiratory depression and sedation
or excessive somnolence should be assessed, because these symptoms usually occur before onset of overt respiratory
depression. The respiratory rate and depth of respiration must be followed closely. Pulse oximetry can help detect
inadequate arterial oxygenation. Patients should be monitored for at least 12 hours after the last dose of intrathecal
opioids is administered.[20]
Epidural Blockade. Whenever epidural anesthesia is attempted, there is a potential for local anesthetic toxicity,
because significantly higher volumes of local anesthetic are used to achieve anesthesia.
Before initiation of an epidural block, baseline blood pressure, heart rate, and level of consciousness should be
determined. The anesthesiologist must continuously monitor blood pressure and the ECG. If sedative or narcotic
analgesic medication is given during the block, continuous pulse oximetry is mandatory. Before giving a full dose of
local anesthetic, verify that the needle is in the epidural space by administering a test dose of 3 mL of local
anesthetic with 15 µg of epinephrine while constantly observing the patient. In the event of intravascular injection,
[21]
this dose of epinephrine should elevate heart rate to greater than 30 beats per minute (bpm) within 25 seconds of
injection. If the subarachnoid space has inadvertently been entered and the test dose has been administered, the
patient will have an identifiable level of anesthesia; thus, it is critical to monitor the patient for any signs of nerve
block. There is a continuing controversy over the validity of epidural test doses in obstetrics. Once it has been
[22]
determined that the epidural space has been reached, the volume of local anesthetic to achieve the desired level may
be administered in divided doses of 5 mL each. The patient’s level of consciousness, respiratory rate, blood
pressure, ECG, heart rate, and extent of neural blockade should continue to be monitored.
SYMPATHETIC GANGLION BLOCKS
Stellate Ganglion Blocks. Functioning IV access must be available before the block in the event of an intravascular
injection or occurrence of seizure activity. A system for positive-pressure oxygen delivery and suction should be
[23]
available nearby. Before the block, resting blood pressure, heart rate, and level of consciousness should be
determined. If the patient is to receive sedative or narcotic medications, a pulse oximeter is needed during the block
and throughout the recovery period. Placing temperature probes on a fingertip of each hand before the block allows
a baseline temperature to be monitored, and, after the block, it helps to objectively assess the effectiveness of the
procedure; an elevation of temperature on the blocked side indicates blocked sympathetic fibers. The patient must
[22]
fast for at least 8 hours before the block to prevent intraoperative aspiration.
Because of the proximity of the ganglion to critical vascular structures, a test dose is mandatory. Local anesthetic,
0.25 mL, should be administered and the patient should be constantly monitored for any type of toxic reaction. [23]
After repeat aspiration, the local anesthetic should be injected in divided doses. The patient must be continuously
monitored for any change in the level of consciousness or for toxic reaction. Adequate placement of the local
anesthetic after the block is performed can be confirmed by presence of an elevated temperature on the blocked side
and evidence of a Bernard-Horner syndrome (myosis, ptosis, and enophthalmos). The patient must be instructed
[22]
not to eat or drink for 4 hours after the block.
Lumbar Sympathetic Ganglion Block. A functioning IV catheter must be present in the event of an accidental
intraspinal injection or if sedatives or narcotic analgesics may be needed during the procedure. Baseline blood
pressure, heart rate, level of consciousness, and lower extremity temperatures should be obtained before the block is
performed. There should be continuous monitoring of these parameters while the block is done and during the
recovery period. Inadvertent intravascular injection can cause seizure activity, and subarachnoid placement of local
anesthetic causes complete spinal anesthesia; thus, the anesthesiologist must be prepared for this rare outcome. The
171
patient should fast for at least 8 hours before the block. If the patient receives sedative or narcotic analgesic
medications, a pulse oximeter should be used to monitor arterial oxygenation. It is also important to assess the
patient’s level of consciousness during the injection of local anesthesia and to maintain verbal contact after the block
is complete. The patient should be monitored for lower extremity motor strength and sensation because a somatic
nerve block is possible, and monitoring should be continued after the block is complete.
Use of fluoroscopic assistance can confirm proper needle placement, especially when neurolytic agents are used. If
fluoroscopy is not available, the baseline foot temperatures should be taken as another monitor of correct needle
placement. After needle placement is complete, a small amount of 3% chloroprocaine should be injected and a
temperature elevation of at least 1.5°C should be confirmed before a larger volume of a longer acting local
anesthetic is injected.[22]
Celiac Plexus Block. Before proceeding with the block, an adequate intravenous line should be established and
baseline blood pressure, heart rate, respiratory rate, and level of consciousness should be determined. Resuscitation
facilities should be available in the event of an inadvertent intravascular injection during the block. During the
performance of the block and in the recovery period, the patient’s blood pressure and ECG should be continuously
monitored. Because the sympathetic nervous system supply to the abdominal viscera is interrupted with this block,
hypotension is common and must be anticipated. If sedative or analgesic drugs are used during the block,
[24]
continuous pulse oximetry must be available. Fluoroscopy should be used to monitor correct needle placement and
adequate spread of contrast dye before the block is performed.
SOMATIC NERVE BLOCK
With a somatic nerve block, accurate placement of the needle should be confirmed with a nerve stimulator.
Paresthesia can also be used to monitor proximity to the brachial plexus, but the incidence of peripheral nerve injury
is higher when this technique is used to localize the nerve.
[25]
INTERCOSTAL NERVE BLOCK
The patient should have continuous monitoring of blood pressure, ECG, respiratory rate, and level of consciousness.
Frequently these patients receive intravenous sedation, and, therefore, pulse oximetry should be used. After the
patient has received the block, monitoring should be continued in the recovery period with special attention to
respiratory and hemodynamic status. The incidence of pneumothorax after intercostal nerve block has been reported
to be between 0.0083% and 19%. Any patient complaining of dyspnea and chest pain accentuated by deep
[26]
breathing and coughing should be suspected of having a pneumothorax and should be evaluated by a chest
radiogram.
LUMBOSACRAL PLEXUS AND ITS BRANCHES
Sciatic Nerve Block. Minimal monitoring should include continuous regulation of blood pressure, ECG, and level
of consciousness. If the patient receives any sedative or narcotic medications during the block, a pulse oximeter
should be used. A peripheral nerve stimulator can greatly enhance the success rate of a sciatic nerve block by
helping to avoid significant patient discomfort. The extent of the block can be assessed by examining motor
function, which is primarily governed by a somatic nerve.
Head and Neck Blocks. A functioning IV catheter should be inserted before the block is performed, and
resuscitation facilities must be available if a seizure should occur. Blood pressure, ECG, respiratory rate, and level
[23]
of consciousness should be continuously monitored throughout the block and during the recovery period. If IV
sedatives or narcotics are used, pulse oximetry should be employed.
Guidelines and Protocols
The following guidelines and protocols are used at the authors’ institution for the care of patients undergoing nerve
block procedures.
CARE OF THE PATIENT AFTER SPINAL, EPIDURAL, OR CAUDAL PROCEDURE

STATEMENT OF PURPOSE
172
To make appropriate observations and ensure the safety of the patient after spinal, epidural, or caudal anesthesia.
PROCEDURE
A. Observe the following:

1. Sensory level by means of neurovascular checks
2. Proper body alignment
3. Abdominal distention
4. Urinary bladder distention
5. Shock
6. Bleeding
7. Vital signs
B. Passive range of motion exercises are recommended as indicated and, if not contraindicated by patient
assessment, should be repeated every 30 minutes until the patient has regained sensation and movement of
extremities, if appropriate.
C. Unless otherwise ordered by the physician, the patient should stay at the Institute for Pain Management,
either in Outpatient Surgery or in the Postanesthesia Care Unit until all effects of the block are gone.
D. Chart observations and range of motion exercises as indicated by the nursing assessment on the appropriate
patient care record.
E. Spinal or epidural anesthesia may be administered to outpatients with the approval of the attending
anesthesiologist/pain physician as documented on the Preanesthetic Assessment sheet.
OBJECTIVE PAIN-DISCOMFORT SCALE
Assessment 0 1 2
Blood pressure ± 10% preoperative level ± 10% to 20% preoperative level ± 20% to 30% preoperative level
Crying No crying Crying, but responds to tender loving Crying, does not respond to tender
care loving care
Movement None Restless Thrashing
Agitation Asleep or calm Mild Hysterical
Verbal evaluation or body language Asleep or no pain Mild pain (cannot localize) Moderate pain, expressed verbally or
by pointing
GUIDELINES FOR DISCHARGING PATIENTS

To dismiss those patients who are stable and fully recovered from nerve block or sedation. A member of the
Anesthesia Department evaluates the patient at the time of discharge.
PROCEDURE
A. The patient must meet specific criteria before discharge.

1. The patient must be awake.
2. The patient must be oriented to time, place, and person.
3. The patient must have recovered full muscle control as is normal for that specific person.
4. The patient must have stable vital signs within the normal range.
5. The anesthesiologist must write the discharge order on the Patient Care Record and make a
notation about the patient’s condition. The physician’s signature indicates responsibility for all IV
fluids and drugs administered in the nerve block facility.
B. The patient will go through a period of progressive ambulation. The patient should be able to demonstrate
the following:
1. Dangle legs at the side of the bed without syncope or significant change in vital signs.
2. Ambulate without syncope or significant change in vital signs.
3. Dress with assistance from nurse as needed.
4. Demonstrate full weight bearing.
173
C. Ideally, the patient should be able to retain small amounts of clear liquid before discharge.
D. At the discretion of the anesthesiologist, block patients may be discharged without retaining full muscle
control of the area involved.
E. The patient will be discharged with a responsible adult companion. A responsible adult is someone of legal
age who can act on behalf of the patient.
F. The patient may be taken to the car via wheelchair or ambulation. Either a nurse or a transportation aide
may take the patient out to the car, if necessary.
G. The patient should not be allowed to drive home after narcotic sedation or nerve block.
FOLLOW-UP PHONE CALLS

To contact, by phone, each outpatient after the procedure to ascertain if he or she is well, has any questions, or has
experienced any problems.
PROCEDURE
A. The nurse will phone each outpatient the day after his or her surgery or procedure. If unable to contact the
patient on the first day postsurgery/postprocedure, the nurse will phone the second day
postsurgery/postprocedure. Patients who have Friday surgery dates will be contacted the following
Monday.
B. The nurse will chart a postprocedure phone call note based on the information received and any instructions
given to the patient, including any referrals made on the patient’s chart.
C. Postprocedure phone calls to a patient treated in the pain management center are dependent on the
frequency of treatments received.
D. If positive findings for signs and symptoms of infection are noted, the infection control nurse will be
notified.
REFERENCES
1. McMahon D: Managing regional anesthesia equipment. Probl Anesthesia 1:592, 1987.

2. Selander D, Dhuner KG, Lundberg G: Peripheral nerve injury due to injection needles used for regional anesthesia. Acta Anaesth Scand 21:182,
1977.
3. Bromage BR: Epidural analgesia. Philadelphia, WB Saunders, 1978, p 333.
4. Hurley
RJ, Lambert DH: Continuous spinal anesthesia with microcatheter techniques: The experience in obstetrics and general surgery. Reg
Anesth 14:S3, 1989.
5. Tuohy EB: Continuous spinal anesthesia: Its usefulness and technic involved. Anesthesiology 5:142, 1944.
6. Moote CA, Varkey GP, Komar WE: The incidence of headache is similar after both continuous spinal anesthesia and conventional spinal
anesthesia. Reg Anesth 15(Suppl 1):59, 1990.
7. Flanagan
J, Ringering RL, Black DK, et al: Evaluation of four infusion pumps with a 32-gauge micro spinal catheter for continuous infusion.
Reg Anesth 15(Suppl 1):67, 1990.
8. Brown RE, Johnston L, Raj PP, et al: Continuous peripheral nerve of local anesthetic for management of pain due to reflex sympathetic
dystrophy. Reg Anesth 15(Suppl 1):88, 1990.
9. Mehta M, Maher R: Injection into the extra-arachnoid subdural space. Anesthesia 32:761, 1977.
10. Bettmann MA, Morris TW: Recent advances in contrast agents. Radiol Clin North Am 24:347, 1986.
11. Levy J: Anaphylactic reactions in anesthesia and intensive care. Boston, Butterworth, 1986.
12. Kieffer
SA, Binet EF, David DO, et al: Lumbar myelography with iohexol and metrizamide: A comparative multicenter prospective study.
Radiology 151:665, 1984.
13. Lamb JT: Iohexol vs. iopamidol for myelography. Invest Radiol 20:537, 1985.
14. Rosenblatt RM, Shal R: The design and function of a regional anesthesia block room. Reg Anesth 9:12, 1984.
15. MackeyDC, Carpenter RL, Thompson GE, et al: Bradycardia and asystole during spinal anesthesia: A report of three cases without morbidity.
Anesthesiology 70:866, 1989.
16. Ward RJ, Bonica JJ, Freund FG, et al: Epidural and subarachnoid anesthesia: Cardiovascular and respiratory effects. JAMA 191:275, 1965.
17. Caplan RA, Ward RJ, Posner K, et al: Unexpected cardiac arrest during spinal anesthesia: A closed claim analysis of predisposing factors.
174
18. RawalN, Arner S, Gusustatsson LL, et al: Present state of extradural and intradural opioid analgesia in Sweden. A nationwide follow-up
survey. Br J Anaesth 59:791, 1987.
19. Moore DC, Batra MS: The components of an effective test dose prior to epidural block. Anesthesiology 55:693, 1981.
20. Dain SL, Rolbin SH, Hew EM: The epidural test dose in obstetrics: Is it necessary? Can J Anaesth 6:601, 1987.
21. Korevaar W, Burney RG, Moore PA: Convulsions during stellate ganglion block: A case report. Anesth Analg 58:329, 1979.
22. Benzon HT, Avram MJ: Temperature increases after complete sympathetic blockade. Reg Anesth 11:27, 1986.
23. Kozody R, Ready LB, Barsa JE, et al: Dose requirement of local anesthetic to produce grand mal seizure during stellate ganglion block. Can
Anaesth Soc J 29:489, 1982.
24. Thompson GE, Moore DC: Celiac plexus, intercostal and minor peripheral blockade. In Cousins MJ, Bridenbaugh PO (eds): Neural Blockade
in Clinical Anesthesia and Management of Pain. Philadelphia, JB Lippincott, 1988, p 508.
25. Ellis JC, Ramamurthy S: More problems with the Arrow-Racz epidural catheter. Anesthesiology 65:124, 1985.
26. Bridenbaugh LD: Should regional anesthesia be used during upper abdominal surgery? Probl Anesth 1:567, 1987. 157
175
Section IV - Chapter 12 - Monitoring in Regional Anesthesia
Chapter 12 - Monitoring in Regional Anesthesia
RICARDO S. PLANCARTE
FRANCISCO JAVIER MAYER RIVERA
A traditional definition of monitoring equipment is “a device that records specified data for a given series of events,
[1]
operations, or circumstances.” The definition of monitoring is “to check constantly on a specific condition or
situation.” In a more complex sense, it is the recording of a continuous event, which enables a physician to measure
and compare the data and analyze the elements as a whole as well as develop a conclusion regarding status.
In a medical sense, continuous medical monitoring provides additional information about the patient’s physiologic
status and offers clues for therapeutic decisions, which can improve patient outcome and allow the medical team to
be aware of potential risks during the procedure.
In the current standard of practice, all patients, even those considered to be at low risk, must be monitored carefully
and continuously to evaluate potential adverse reactions from the drugs used and to note significant changes in the
patient’s homeostasis. It is noteworthy that the difference between a good anesthesia practice and a bad one is very
little. The first step must be the basic recording of vital function status. This allows the impact of drug and
[2] [3]
technical interventions to be evaluated.
No matter how safe regional anesthetic techniques are considered to be, there are risks such as hypotension,
arrhythmias, and cardiac arrest when even the simplest procedures are performed. The incidence of complications in
patients under regional anesthesia has been reported for many different surgical procedures and correlated to age
[4]
groups, premorbid states, side effects of drugs, comorbid diseases, and so forth. The absence of premorbid risk
factors is not a sufficient reason to avoid monitoring patients under regional anesthesia. [5]
New regional anesthetic techniques are rapidly developing. The primary reason for this is economic; regional
anesthesia tends to be cheaper than general anesthesia. This is especially significant for underdeveloped countries. [6]
Liability is a major concern of anesthesiologists in current medical practice. Claims are usually associated with
general anesthesia, perhaps because it is used most frequently. In a study from the Maryland Institute of Emergency
Services Systems in the United States, two thirds of all claims alleged (1) failure to attend to changes in the
perioperative status of the patient, which included inadequate monitoring of the patient’s position; (2) failure to
respond to changes in cardiopulmonary status; and (3) problems related to maintaining a safe airway. The most
frequent adverse outcomes were death (21.2%), airway trauma (15.4%), nerve damage (15.4%), and brain damage
(7.7%). [7]
There are different grades of monitoring. They can be invasive (i.e., penetration of the body by needle, catheter, or
surgical incision) or noninvasive (i.e., use of transducers that do not damage skin or mucosa). There are many
options on the monitoring spectrum; for example, cardiac function can be monitored by an electrocardiogram (ECG)
or by pulmonary artery catheter insertion and central venous pressure.
No correlation exists between the number of variables monitored and a satisfactory outcome. It is more useful to
have an appropriate selection than a large number of variables.
Surgical procedures are now being performed with less complex techniques, such as regional blocks and conscious
[8]
sedation, and usually without appropriate surveillance. To make these operations safer, appropriate monitoring
should be available.
For endoscopy, lumbar punctures, bone marrow biopsies, fracture reductions, pacemaker placement, or similar
procedures that are considered “simple,” a technique called sedative analgesia is frequently used. Sedative analgesia
has been described as “a state that allows the patient to tolerate unpleasant procedures while maintaining adequate
vital function and the ability to respond purposefully to verbal command and/or tactile stimulation.” However,
[9] [10]
this situation is very close to monitoring for general anesthesia, and monitoring has to be adequate for assessing vital
functions.
176
Biological Variable Monitoring
Most of the activity of the body can be converted into electrical signals, which can in turn be recorded by
TABLE 12-1 -- MATHEMATICAL EXPRESSIONS OF UNITS

Quantity Name Symbol
BASE UNITS
Length Meter M
Weight Kilogram Kg
Luminous intensity Candle Candle
Electric current Ampere A

Temperature Celsius or Centigrade °C
Time Second S
DERIVED UNITS
Area Square meter M2
Volume Cubic meter M3
Velocity Meters per second M/S

Frequency * Hertz Hz
*
Electrical potential Volt V
*Special names.
transducers, enabling the physician to measure them. All these signals can be measured, and each one has a
mathematical value ( Table 12-1 ). Therefore, the interrelationship between signals can be measured. Base unit
values can be combined, producing derived units that can be expressed in terms of base units. A great diversity
exists in biological measurement, and specific equipment is required for different tasks ( Tables 12-1 and 12-2 ).
The most common values have been recorded, and normal tables have been compiled; thus the problem (patient) can
be compared with the gold standard, making it possible to establish whether the patient is within the normal range.
These values may vary significantly owing to differences in methods and standardization, and every population must
have its own range of values according to regional differences or specific requirements
TABLE 12-2 -- SOME EXAMPLES OF BIOLOGICAL VARIABLES THAT ARE EXPRESSED IN MATHEMATICAL OBJECTIVE
EXPRESSIONS
Objective Values
Breath rate Frequency/min
Oxygen saturation % O2 saturation
ET CO2 % CO2 saturation

Arterial and venous gases % saturation for each gas
Skin color Color scale
Cardiac rate Frequency/min
Cardiac rhythm Regular distribution of events on time

Blood pressure mm Hg
Cardiac pressures mm Hg
Cardiac output Liters/min

Water balance Algebraic addition expressed in liters
Temperature Centigrade
Electro-encephalogram Height, length, and frequency of waves cm, events on
Consciousness Comparative scale expressed numerically

Neuromuscular function Comparative scale expressed numerically
Urinary output Volume/hr expressed in liters
177
of such factors as race, gender, and age groups, among others.
In clinical terms, functions such as arterial tension, temperature, heart and respiratory rates, consciousness, body
weight, and brain waves are initially measured ( Table 12-2 ). Some of these measurements may be obtained in a
specific time frame. Documentation of changes provides data from which a curve can be drawn that establishes a
record of the stability of the patient. Monitoring during surgery is divided into three periods: (1) preoperative, (2)
transoperative, and (3) postoperative.
Monitoring During the Perioperative Period
Data obtained during the preoperative period are considered to be basal. For prevention of deleterious sequelae,
these values need to be maintained during the transoperative and postoperative periods. During the transoperative
time, many of the procedures performed actually disturb homeostasis. Any change capable of putting the patient at
risk should be closely observed.
The preoperative visit is very important. A general examination establishes the patient’s basal data. It is important to
maintain or improve these data during the surgical-anesthetic procedure. At the preoperative visit, a complete
clinical history should be taken in order to establish the actual clinical status of the patient and to determine the
accurate biological values that should be monitored for that person, in particular during the transoperative period.
Monitoring Equipment
Over the last 20 years, technical advances have helped physicians to monitor patients safely and reliably. This
includes regular monitoring; appropriate, reliable documentation of electrical signals; and the ability of different
monitors to calculate parameters, trends, correlation of signals, and self-testing diagnostics. Portable monitors are
helpful during transport of patients.
Monitors have filters capable of blocking electrical interference from other devices, reducing artifacts, and
preventing loss of essential biological signals. The number of physiologic parameters necessary for safe monitoring
has been evaluated and increased. For example, measurement of oxygen saturation (SpO2 ), which was initiated in the
early 1970s and which gained widespread use in the 1980s, is now considered mandatory. Other developments
include the creation of networks that are located in a specific area of the hospital or that are connected to remote
workstations, allowing communication and surveillance by other observers. Monitors capable of automatically
recording data to the physician’s notes in electronic charts can be networked to allow permanent evaluation of data
that correlate with the patient’s clinical status. Also, telemedicine allows patients to be moved within the hospital or
to their homes with permanent surveillance maintained in a central station.
ELECTRONIC DEVICES
Physiologic monitors are either configured or modular. The differences between them are shown in Table 12-3 .
These devices are becoming more complex and use computerization that allows them to expand their functions to
record, analyze, and even offer advice through statistical analyses that compare and review changes in the patient’s
biological status.
Each patient requires an individualized level of monitoring, and the ideal is to accommodate the patient’s changing
needs. A critically ill patient needs a monitor capable of continuous ECG recording and of continuous measurement
of noninvasive blood pressure (NIBP), invasive blood pressure (IBP), temperature, SpO2 , end-tidal carbon dioxide
(ETCO2 ), and cardiac output. Postanesthesia care units usually require only two or three trace monitors or modular
units and a central display. There are color display screens that can differentiate waveforms and numeric displays
that allow faster evaluation, which can be more useful in major procedures. However, it may be confusing if two
separate pieces of equipment show the configuration for the same variable in different color waves.
TABLE 12-3 -- DIFFERENCES BETWEEN CONFIGURED AND MODULAR MONITORS

Configured Modular
Predetermined number of parameters Modules for each parameter
Nonexpandable parameters Interchangeable modules
Less flexibility for variables with similar characteristics (e.g., pressures) Modifiable according to necessities
178
TABLE 12-3 -- DIFFERENCES BETWEEN CONFIGURED AND MODULAR MONITORS

Configured Modular
May be more expensive
If continuous monitoring is necessary, it can be hazardous to move the patient to Can be easily adapted to be compatible with many areas—operating room,
different areas postoperative care unit, cardiac and neonatal care units
If signal acquisition fails, the whole unit must be technically reviewed If signal acquisition fails initially, the specific module must be technically
reviewed while it is still functioning
If signal acquisition fails transoperatively, the whole unit must be technically If signal acquisition fails, the specific module must be exchanged while it is still
reviewed, and replacement with other monitor can be technically hazardous functioning; the transition must be smooth to reduce risk of signal loss
Automated anesthesia information systems can be used to calculate reference limits (population-based normal
values for monitoring vital signs during anesthesia). Population variables such as gender, age, or global status are
considered in determining the percentiles for minimal heart rate, maximal heart rate, minimal arterial
oxyhemoglobin saturation (SaO2 ), minimal mean arterial pressure (MAP), maximal arterial pressure MAP, decreases
and increases in MAP, minimal mean ETCO2 , maximal ETCO2 , decreases in ETCO2 , and increases in ETCO2 , minimal
and maximal mean temperatures, respiratory frequency, and so forth. [11]
Reference limits may play a role, (1) as a way to improve anesthetic practice, and (2) as parameters to consider in
malpractice cases when an expert claims that the care provided by the anesthesiologist was substandard, as shown
by vital signs that were not maintained within the normal range during the critical periods of anesthesia. [12]
Electrical equipment can fail for many reasons; sometimes failures are due to electrical problems, interference from
radio or other electronic sources, overheating, improper installation, incompatible hardware or software, or improper
setting.
Most electronic devices can be programmed with alarms capable of reacting under adverse circumstances. Some
anesthesiologists do not use alarm systems because of the noise that they can make in response to predictable false-
positive alarms (i.e., false-positive or false-negative alarms inherent in a device, such as artifacts, cable [13]
disconnection, wet transducers, and so forth); however, not using alarms is a mistake that must be avoided. A risk
that accompanies the use of electronic monitors is that the physician may pay more attention to the monitor than to
the patient. Some examples of unmonitored observations are the notation of amount of bleeding, anxiety, or skin
color. Even the best monitor cannot substitute for frequent direct observation of a patient.
Analysis of the Data
Tendencies or trends can predict what could happen if the situation is left alone. For example, the observation of a
heart rate of 70 beats per minute (bpm) at 1 minute and a heart rate of 50 bpm at 3 minutes should lead the observer
to realize that something adverse is happening. The ability to evaluate this trend as a whole facilitates the making of
a decision.
INTERPRETATION AND REPORTING
Interpretation of monitoring and clinical signals is a skill that depends on personal experience including familiarity
with the equipment, ability to understand
179
Figure 12-1 Clinical exercise for validation of signals.
the data, knowledge of physiology, and ability to think logically.
Some levels of interpretation have no application in a complex assessment of clinical relevance. Sometimes a single
signal is sufficient, but in most instances, it is necessary to pay attention to many signals to make clinical judgments.
Some electronic devices can detect artifacts or malfunctions and are capable of making recommendations to correct
them; however, practitioners usually do not wait for that information. Instead, they employ their own skills to
determine the validity of the signal and the global status of the patient ( Fig. 12-1 ).
Usually a pattern is recognized first—a flat line on the ECG display—and after that an interpretation of the pattern,
the condition that caused it, and its clinical significance. For example, the flat line may be caused by any of the
following:
1. Stroke
2. Electrode failure
3. Equipment failure
Every interpretation raises many questions, such as the following:
1. What did I do? Is the monitor really reporting a stroke? How is the airway, breathing, and circulation
(ABC) functioning?
180
2. Did I place the monitor correctly? Are the electrodes broken?

3. Is the monitor setting correct? Is the monitor plugged into the correct socket? Could the monitor have
failed?
Information provided by monitoring devices and by observation must be documented in a written record to review
the quality of care for medical and legal purposes. The information must be accurate, complete, legible, and clearly
presented, including times of events; drug dosages and responses; previous and final status of the patient; and
notations of unexpected events, complications, technical or mechanical failures. There must also be written
recommendations about the performance of the monitoring devices. Some machines are capable of reporting not
only signals in real time but trends and tendencies, showing how each signal changes through time. Small,
progressive changes that are potentially harmful to the patient can be continuously tracked.
Risk Factors in Regional Anesthetic Procedures
SAFETY OF EQUIPMENT
All hospitals must have policies for surveillance of equipment to ensure the safety of patients and workers alike,
including maintenance schedules, replacement of worn-out equipment, surveillance of the proper use of equipment,
and training of the personnel who use it. Operating rooms must be designed and maintained according to technically
sound principles to ensure the proper functioning of equipment, which must be “friendly” and ergonomically
correct. Correct monitoring begins with careful planning before purchase medical equipment. Thought must given to
the potential user, the buyer, the biomedical engineer, and any future expectations for regulating its use. Before any
procedure, the equipment must be inspected to detect possible failures. [14]
STANDARDS OF SAFETY
Most hospitals have rules and regulations that reflect local laws that should be observed. Following these procedures
can help to avoid or limit patient liability. Some of them are the following:
• Maintaining equipment according to the schedule

• Checking a list of procedures and inspecting equipment before any anesthetic procedure is done
• Checking a list of procedures and inspecting equipment before any surgical procedure is done
• Obtaining signed consent for performance of the procedure from the patient or a legal representative
HUMAN FACTORS IN THE OPERATING ROOM
Obviously, surgical results depend on the skill of the human beings involved. Various combinations of teamwork
and skills have various outcomes; sometimes, the outcome is better in one situation than another. It is, of course,
beneficial to determine the patient’s prognosis and to evaluate the facts accordingly.
The human team in the operating room can be influenced by many factors, such as personal attitudes,
communication skills, experience, social roles, sharing of information, personal issues, job environment, family
troubles, and fatigue.
The team’s ability to pay attention to the monitoring system can depend on all these factors. Even if there is not
enough evidence to prove it, it is logical to assume that individuals who feel trapped by a routine job, or who are
sick, tired, or distracted by their own troubles could fail to monitor a patient as accurately as individuals who are not
dealing with such circumstances.
In some countries, hospital policies allow family members to be present during the performance of some surgical
procedures, such as cesarean section. In our experience, this intrusion changes the team’s communication dynamics,
adding time to the procedure and causing additional pressure. Moreover, the ability to pay attention to the various
clinical signs and the decision process can be affected, depending on the team’s ability to deal with the situation.
More than two thirds of the accidents and incidents in commercial aviation can be attributed to human error.
Research in this field shows that problems in teamwork, communication, leadership, and decision making play a
larger role than problems in technical competence. To solve this problem, emphasis should be placed on team
training that includes the use of simulation for team practice. This approach has been explored in the field of
medicine, which proved to be successful with strict adherence to management protocols and checklists. [14]
181
LEVELS OF MONITORING IMPLEMENTATION
The medical administrative system evaluates the quality of performance in many ways. One involves review of
clinical records, making it possible to indirectly evaluate the technical anesthetic procedure, which translates into
quality care. Obviously, this ties in with the type of facility where the procedure is done; more complex care
[15]
centers can be expected to have more complex monitoring techniques. In addition, determining how a patient must
be monitored varies from place to place and reflects individual training and institutional recommendations as well as
the advice provided by professional anesthesia societies.
Legislative Liabilities and Claims
For many years, concern about lawsuits has been part of medical practice. Surveillance is key with regard to
avoiding claims. Temporary or permanent damage and death are events that follow loss of clinical control of patient
homeostasis, and such events can be considered as malpractice issues. Clinical control involves effective
management of global hemodynamic and respiratory functions. Complications that start with an incident and end
with some deficit or death fall into the area where law and medical practice coalesce, and the search for errors
includes identifying misjudgment and inadvertent or incorrect interventions. Physicians must do their best to
monitor patients according to the following criteria:
• Global control of homeostasis through close and continuous surveillance of all the biological variables
during monitoring
• Surveillance of the correct use of equipment and continuous evaluation of the appropriate performance of
the equipment
• Anticipation and follow-up of potential complications are essential, and specific treatment must be
provided.
In regional anesthesia procedures, there is an additional risk of injury to the spinal cord and nerves. Such injury
could result from technical errors in inserting needles or use of chemical agents capable of producing neurotoxicity
with central or peripheral nerve damage, which could be temporary or permanent. Other failures are related to the
patient’s experience of pain or discomfort under regional anesthesia during surgical procedures.
The risk of significant damage to patients under regional anesthesia is low; however, many anesthesia-related
injuries are avoidable. The surgical team should be aware of possible pitfalls and take appropriate steps to maintain
patient safety.
Initially, the fear of litigation was probably the most compelling reason behind the widespread acceptance of routine
monitoring. Extensive monitoring may allow anesthesiologists to reduce malpractice liability. However, this does
not ensure an excellent quality of care nor does it abolish anesthesia-related mortality. Besides, there are no clear-cut
studies that prove the cost benefit of monitoring.[16]
Use of Drugs and Choice of Monitoring
Regional anesthesia has been achieved mostly with use of local anesthetic drugs and, sometimes, adjuvant drugs
such as opioids and α-adrenergic receptor agonists or antagonists. The actions and side effects of regional
anesthetics determine the need for appropriate monitoring using either routine automated equipment (blood pressure
[BP], ECG) or more advanced monitors.
Physiologic Changes Caused by Local Anesthetics
Local anesthetics block sodium channels of nerve fibers and thus decrease neuronal conduction. Onset and time of
action are correlated to protein-binding, pK, and lipid solubility. Absorption relates to local blood supply, and
systemic absorption can be slow or fast, depending on its location and on the addition of vasoconstrictive agents
such as epinephrine.
Systemic and toxic effects are determined by dose, site, and agent-specific metabolism and can affect the
cardiovascular system, central nervous system (CNS), respiratory system, and peripheral nervous system.
Cardiovascular effects induced by local anesthetics are caused by decreases in electrical excitability, conduction
rate, and force of contraction, with myocardial contractile reduction inversely related to the concentration of the
182
agent and depression of pacemaker automaticity manifested as prolongation of PR and QRS intervals, with
dysrhythmias, heart blockade, and even fibrillation.
Effects on the CNS are caused by the passage of these agents across the blood-brain barrier, which can produce
symptoms such as dizziness, numbness, vertigo, diplopia, loss of consciousness, coma, respiratory arrest, and
seizures. Headache as well as visual and auditory symptoms can occur because of decreased intracranial pressure
resulting from leakage of cerebrospinal fluid, which is related more to technique (e.g., needle, trauma) than to drugs.
Effects on the peripheral nervous system are the result of direct peripheral and central mechanisms with expected
sensori-motor loss and changes in sympathetic autonomic tone that appear as hypotension, increased gastrointestinal
motility, and reduced uterine muscle tone caused by unopposed parasympathetic action.
Local anesthetic toxicity can produce root damage such as occurs in the cauda equina syndrome. Root damage may
occur after a spinal anesthetic procedure, with loss of sphincter control of the bladder and bowel and a varying
degree of sensory and motor disturbance of low extremities.
The differential diagnosis for a local anesthetic reaction must include the following:
• Local anesthetic toxicity

• Extended neural blockade
• Reaction to adjunctive drugs
• Allergic reaction
• Exacerbation of a concurrent medical condition
Physiologic Changes Caused by Opioids
Opioids have been used in neuroaxis to treat acute and chronic malignant or nonmalignant pain. Adverse effects
include nausea, vomiting, urinary retention, pruritus, and respiratory depression. Delayed symptoms are
constipation, dry mouth, headache, diaphoresis, hyporexia, reduced libido, amenorrhea, myoclonus, arthralgias, and
others. The major concern is the risk of respiratory depression, and this can be related to time, depending on the
chosen agent’s lipophilicity. Times can range from about 6 to 12 hours for morphine and from a few minutes to 4
hours for fentanyl. A significantly greater risk of respiratory depression exists with use hydrophilic opioids such as
morphine. The incidence of respiratory depression is 0.1% to 0.5% for morphine and about 0.6% for fentanyl.
Monitoring opioid use during a regional anesthesia should include clinical assessments of the respiratory rate and
the level of sedation per hour, which have been demonstrated to be the most effective markers. However, other
monitoring techniques, such as carbon dioxide or oxygen saturation monitors, can also be helpful tools.
International Monitoring Recommendations for Regional Anesthesia
The recommended monitoring standards apply equally to general and regional anesthesia. Governments in several
countries have adopted these guidelines.
AMERICAN SOCIETY OF ANESTHESIOLOGISTS: STANDARDS FOR BASIC

INTRAOPERATIVE MONITORING
The American Society of Anesthesiologists (ASA) published guidelines for intraoperative monitoring in 1986, and [17]
the most recent amendment was added in 1996 ( Table 12-4 ). It is noteworthy that the observation of these
guidelines does not necessarily guarantee a good outcome. The guidelines are as follows:
• Standard 1: Qualified anesthesia personnel shall be present in the room throughout the administration of
all general, regional, and monitored anesthesia care.
• Standard 2: Oxygenation, ventilation, circulation, and temperature shall be continually evaluated. (See
Table 12-4. )
183
TABLE 12-4 -- STANDARDS FOR BASIC INTRAOPERATIVE MONITORING

Oxygenation
Oxygen analyzer for inspired gases

Observation of the patient
Pulse oximetry
Ventilation
Auscultation
Observation of the patient
Observation of reservoir bag
ET CO2 analysis
Circulation
Continuous ECG display
Heart rate and BP recorded every 5 min

Evaluation of circulation:
Auscultation of heart sounds, palpation of pulse, pulse plethysmography, pulse oximetry, intra-arterial pressure tracing
Temperature
Core temperature and/or skin temperature
BP, Blood pressure; ECG, electrocardiogram.
From American Society of Anesthesiologists: Standards for Basic Intraop erative Monitoring. Newsletter, Park Ridge, Ill, 1986.
Recommended practices for monitoring of patients include the following:
• Anesthesia personnel must have basic knowledge of the function, use, and interpretation of monitoring
equipment.
• The monitoring record should be an accurate reflection of care.
Risk Assessment and Risk Management in Regional Anesthesia
Risk is defined as the probability of a bad consequence that can be nonfatal (dysfunction) or fatal (death). In other
words, risk can be defined as the chance of a poor outcome and can be applied to any level of care system. Risk
management involves the anticipation of potential bad outcomes, attempting to prevent their occurrence or limit the
extent of the damage.
Promotion of professional development is important. Medical certification and recertification in a specialty can help
to ensure quality care, which includes safe practice. However, certification alone is not enough, and much depends
on the skill and initiative of the physician and the team members. Monitoring deals with risk management.
Specific Perioperative Monitoring
MONITORING OF CARDIOVASCULAR FUNCTION

Heart Rate
Heart rate is widely used as an indicator of activity of the autonomic nervous system. It decreases during and after
spinal and general anesthesia, but sympathovagal balance is more stable during spinal anesthesia, even in the
elderly. However, ischemic heart disease, impact of drugs, failure to keep fluid balance, and the presence of pain
may affect heart rate greatly, making continuous monitoring a priority during the perioperative period. [18]
Electric Cardiac Activity
The ECG, which records the electrical activity of the heart, is one of the most common devices employed under
anesthesia to detect heart rate, myocardial ischemia, dysrhythmias, asystole, and other clinical conditions that
require treatment. It is also necessary to record the heart’s response to the treatment given for those disturbances.
At least three electrodes are required for an ECG lead; two are sensing electrodes and a third acts as a reference to
reduce electrical (ground) interference. Each lead offers a different perspective of the electrical activity of the heart,
184
producing a line to display integration of P waves, QRS complex, and T waves, which can vary in polarity and
amplitude. The duration and amplitude of these pulses correspond directly to the condition of the heart’s conduction
pathways.
A five-lead system is indicated in patients with cardiac disease. Leads II and V5 have high sensitivity for detection
of perioperative ischemic events. The most common lead monitored is lead II, because the P wave is seen more
clearly, allowing the physician to detect changes in it or to define precisely blockade levels in dysrhythmias as well
as inferior wall ischemia.
ECG disturbances can be caused by hypoxemia, ischemia, hypothermia, and drug reactions, but they may also be
triggered by increased metabolic activity, electrolyte anomalies, neurologic changes, and increased metabolic
activity. For example, the use of vasoconstrictors such as epinephrine in local anesthetic procedures increases the
risk of arrhythmias. There is an increase in cardiac vagal activity during the onset of spinal anesthesia, and
arrhythmias can occur. Vasovagal syncope may be present, especially if the patient is in the sitting position.
Knowing that there is a risk of cardiac failure with use of local anesthetics, it is logical to employ adequate
surveillance of cardiac function while considering other causes, such as nervous system stimulation, pain, or
bleeding. The best and most effective noninvasive method of monitoring is the continuous ECG, which shows the
electrical activity of the heart in real time. A three-channel machine is generally used, which is capable of recording
DI, DII, and DIII. When the patient’s cardiac history or the risk of the procedure demands it, one can expand to
other derivations.
The patient under regional anesthesia must be monitored with an ECG before, during, and after the anesthetic-
surgical procedure. The postanesthetic time of surveillance must be determined on an individual basis according to
the trans-surgical outcome and the patient’s previous medical condition. Usually, surveillance is maintained for 2 to
3 hours in the postanesthetic care unit and for 24 to 48 hours if a comorbid state exists that can compromise cardiac
function.
Vascular Response and Intravascular Volume
One of the most frequent risks of regional anesthesia is hypotension. This may be transient and is usually due to
sympathetic blockade, bleeding, or vagal stimulation. Blood pressure is measured every 3 to 5 minutes, especially in
the first hour of the anesthetic-surgical procedure. The major risk times are during the latency period of the drug,
when the position of the patient is changed, during abnormally heavy bleeding, or during surgical stimuli. Blood
pressure can also change after an inadvertent injection of local anesthetics in the epidural, subdural, or subarachnoid
space during regional procedures such as sympathetic nerve blocks or celiac plexus.
Blood pressure, the force exerted by the blood against the blood vessel walls, assesses the effective pumping of
blood by the heart. Blood pressure is expressed in millimeters of mercury (mm Hg), and three blood pressure values
are obtained: systolic (maximal cycle pressure, which occurs during ventricular contraction), diastolic (minimal
cycle pressure, which occurs during the ventricular filling stage between contractions), and MAP (the mean value of
the blood pressure over the cardiac cycle).
Usually, continuous arterial blood pressure is taken with electronic automatic devices using the oscillometric
method, with a cuff that is available in different sizes for adult or pediatric patients. The cuff is wrapped around the
patient’s limb and arterial pressure fluctuations are evaluated. Some use the auscultatory method, using a
microphone to detect Korotkoff sounds.
The blood pressure cuff should be placed around the opposite arm of the surgical procedure to avoid interference
with the surgery procedure or malfunction by inadvertent compression. We recommend an automatic blood pressure
cuff, but if the surgical procedure is multisided, automatic or manual blood pressure cuffs are preferred.
Changes in arterial pressure occur faster and are more marked with spinal than with epidural anesthesia. Continuous,
automated, noninvasive monitoring of blood pressure is necessary.
Monitoring Invasive Blood Pressure
An electronic transducer is usually used; this device converts the pressure to an electronic signal that is amplified
and displayed on a monitor. The transducer, which ideally must be in or close to the artery, employs short, rigid
tubes to obtain a better signal. The system must be free of air bubbles. It is necessary to perform manual flushing
intermittently to prevent clot formation at the end of the cannula. The transducer must be calibrated to zero at any
185
height on air ambience (1 atmosphere); after that, the transducer must always be at the same patient level, usually at
the heart.
The monitor must be programmed with alarms that give warning about dangerous changes in blood pressure levels.
Generally, IBP monitoring in healthy patients should be avoided unless large amounts of bleeding are expected. IBP
monitoring, however, should be performed in all patients under complex regional anesthesia, or in patients with
special risk factors.
The clinical indications for arterial cannulation include the following:
• Hemodynamically unstable patient

• Harmful changes in blood pressure due to cardiac disease, carotid surgery, cranial surgery, controlled
hypotension, uncontrolled hypertension or uncontrolled hypotension [19]
Central Venous Pressure Monitoring
Clinical indications for central venous pressure (CVP) monitoring are as follows:
• Ventricular dysfunction
• Ischemic heart disease
• Valvular heart disease
• Conduction disease
• Multiorgan dysfunction
• Expected large blood loss or liquid exchange
• Risk of venous air embolism (VAE)
CVP can be tested with electronic or nonelectronic devices. Filling pressures in the right side of the heart reflect
intravascular volume and are helpful in determining cardiac output and in preventing air thromboembolism by
aiding to remove air emboli. Cannulations for CVP can be performed via the following access points:
• Internal jugular vein

• Subclavian vein
• Cephalic vein
• Basilic vein
• Auxiliary vein
• Femoral vein
Cannulation techniques and the sizes of the catheters used vary widely, depending on the approach. The correct
placement of the cannula must be tested by fluoroscopy, chest radiograph, or ECG. As in other invasive procedures,
use of a cannula must be evaluated for the risk/benefit ratio. Complications include dysrhythmias, artery puncture,
pneumothorax, hydrothorax, infection, and air embolism.
Monitoring of Pulmonary Artery Pressure
Measurement of pulmonary artery pressure (PAP) is useful for early detection of myocardial or valvular
dysfunction, dysrhythmias, and pulmonary hypertension.
Clinical indications are as follows:
• Ventricular dysfunction
• Valvular heart disease
Monitoring Cardiac Output
This invasive monitoring is not usually employed with regional anesthesia, but there are some cardiovascular or
other surgical procedures that can be done under regional anesthesia for which close surveillance of hemodynamic
values should be observed for surgical reasons. This type of monitoring is more frequent with the use of regional
anesthesia for the cardiac patient. [19] [20]
Use of deliberate hypotensive anesthesia offers many advantages for surgical procedures, such as a dry surgical
field, less blood loss, and briefer surgical time; however, these benefits must be balanced against the risks of
186
ischemic injury, especially to the brain, heart, and kidney. Strict selection criteria are mandatory, especially in older
adults. Regional anesthesia techniques can be employed for this purpose and can be used even in patients with one
or more comorbid medical illnesses. Examples of comorbid diseases include advanced age, cardiac disease marked
by myocardial infarction, history of angina, coronary artery bypass, or history of congestive heart failure that
required continuous pharmacologic therapy, uncontrolled hypertension or hypertension controlled by specific
antihypertensive medication, diabetes controlled by insulin or oral hypoglycemic agents, or an elevated fasting
glucose level on more than one occasion. Deliberate hypotension must be avoided in patients with contraindications
to epidural anesthesia or hypotensive anesthesia, in those with hemodynamically significant aortic or mitral valve
stenosis, in those with severe carotid artery stenosis (>70% occlusion), and in patients with conditions that seriously
affect cognitive testing performance (e.g., deafness, blindness, psychosis, nonfluent language).
The mean arterial blood pressure has one range that varies from 45 mm hg to 55 mm Hg and a greater range of 55
mm Hg to 70 mm Hg. Deliberate hypotension is frequently achieved via mild sedation with midazolam, fentanyl,
thiopental sodium, or propofol. All patients must have central venous catheters, continuous invasive arterial pressure
monitoring, and pulse oximetry. Patients with a history of congestive heart failure or severe renal insufficiency must
also have pulmonary artery catheter monitoring.
Surveillance for cognitive, cardiovascular, and renal outcome tests must be performed daily to monitor for damage
or recovery after severe complications for short- and long-term postoperative cognitive deterioration. Safety has
been demonstrated in elderly patients with comorbid diseases under a similar protocol of surveillance. [20]
Continuous Transcranial Doppler
Doppler measurement has been used to estimate blood flow in small and large vessels, This type of monitoring in
addition to other applications related to flux or air embolism in cardiac cavities in anesthesiology has been used to
determine velocities of cerebral flux and to find emboli (air and particulate transients) during carotid surgery,
especially at the time of carotid cross-clamping and clamp release. Doppler scanning can alter surgical conduct
during carotid endarterectomy. It is also used to identify patients who could benefit from a shunt, preventing
hypoperfusion or hyperperfusion and detecting technical errors during neurosurgery. [21] [22]
MONITORING OF RESPIRATORY FUNCTION
When combined technique of light general anesthesia, regional anesthesia, and sedation is used, a pulse oximeter is
mandatory, especially in patients with a history of sleep apnea or snoring, significant obesity, and orofacial or neck
disturbances. The pulse oximeter can determine the moment when the O2 saturation falls. To prevent this
undesirable situation, respiratory rate interval monitoring can be used to detect the effect of opioids on the
respiratory center. Apnea alarms are also useful if breathing is not detected over a predetermined period of time. A
breath interval varies between 0.9 minute and 1.4 minutes and is a useful and reproducible method of monitoring the
duration of opioid effect in anesthetized patients who can breathe spontaneously when surgical stimulation is not
affecting the CNS. These data can provide information on the duration of action of fentanyl and can help to
determine the correct dosage. [23]
Elderly patients may have an associated decrease in cardiovascular and respiratory reserve. Procedures that make
use of local anesthetics such as ophthalmic surgery and concomitant use of sedative drugs can increase the risk of
respiratory depression. The frequent irrigation of the mouth during oral and dental surgery can cause hypoventilation
and hypoxemia even without sedation.
Respiratory Rate
Respiratory rate can be measured with impedance pneumography by passing a low current, high-frequency carrier
signal between two ECG electrodes on either side of the chest wall. The resistance, or impedance, of the lungs
changes during the respiratory cycle, creating a voltage change that is interpreted and displayed as a respiratory rate.
Another method is use of a pressure-sensitive electrode on the abdomen to detect movements caused by breathing.
Respiratory rate can be measured with impedance pneumo
187
Monitoring of O2 Saturation and CO2 Saturation
PULSE OXIMETRY
Pulse oximetry provides a continuous level of oxygenation as an indicator of effective ventilation and / . It may
reduce the need for arterial samples of blood for evaluating SpO2 and is essential in mechanically or manually
ventilated patients, in neonates, and in sedated patients. [24]
The pulse oximeter, one of the most commonly used perioperative devices, measures the oxygen saturation of red
blood cells. Its importance in regional anesthesia is based on its frequent use in sedated patients. Although many
types of pulse oximeters exist, the third generation of oximeters is theoretically more able to avoid false alarms and
loss of pulse than earlier devices. [13]
This device employs a spectrophotometer to evaluate the changes on light absorption caused by hemoglobin through
the use of two sources of different kinds of light on a vascular bed (ears or fingers). One light source is on the
infrared spectrum and the other is on a visible spectrum. A photodetector at the other side notes changes of each
wavelength, evaluating the difference between them. The final result is a measure of arterial oxygen saturation (SaO2
). A high saturation of oxygen means that oxygen has passed correctly from the lungs to the site of monitoring. A
low saturation may reflect problems with a patient’s gas exchange, or it may signal monitor failure. Causes of
malfunction can occur with interference of cautery equipment or with motion. Poor perfusion can produce low
readings, and patients must then be evaluated by direct samples of arterial blood.
CAPNOMETRY
CO2 increases during exhalation. The capnograph is a device that can measure the values of ETCO2 and its variations,
reflecting, as does the oximeter, the correct pulmonary gas exchange or / . Its normal values of air ambience are
between 24% and 30%. In a patient with a face mask covering the nose and mouth, the measurement can be done at
regular intervals for only a couple of minutes. If the patient cannot tolerate the measurement while awake, it can be
done directly by blowing through the tube of the capnograph. Besides the capnograph, other devices exist that can
measure CO2 by using a noninvasive nasal approach. [25]
Other Ways to Monitor Gases
Transcutaneous oxygen and CO2 —tcPO2 and tcPCO2 — were initially employed in neonates and in other patients as
an alternative to permanent or periodic arterial puncture and blood analysis.
Blood analysis of gases is a method that can be used as a follow-up. The major inconvenience is the invasiveness of
this method and the need for personnel with technical skills.
MONITORING OF TEMPERATURE
Patients may become hypothermic if room temperatures are low, or if there are large exposures that promote
evaporative losses (e.g., patient undergoing surgical procedures, patients with burns who have large amounts of fluid
exchange). Skin temperature is usually 3°C to 4°C below core temperature and is not the most reliable indication.
Hypothermia occurs with use of both general and regional anesthesia.
When temperature is monitored during regional anesthesia, most clinicians use liquid crystal thermometer strips;
surface monitoring; axillary temperature; or thermistor probes, which are semiconductors whose resistance changes
with temperature. Although skin temperature monitoring has limitations, it is the most commonly used method.
Other parts of the body where temperature can be measured are the rectum, the urinary bladder, and the tympanic
membrane. [26] [27] [28]
Normal core temperature is a sign that implies the correct functioning of the organic system and metabolic reactions.
An elevated temperature (fever) indicates a hypermetabolic state that influences many organic functions, including
drug metabolism. A decline in temperature (hypothermia) indicates a hypometabolic state that can also influence the
same functions. The low temperature of the operating room usually produces hypothermia, which can be reinforced
by the use of cold intravenous solutions.
188
Changes of body temperature under regional anesthesia are the result of sympathetic inhibition, which is caused by
dilatation of vessels when there is an increase in regional temperature. This response must be evaluated with skin
temperature transducers in the early phases of the procedure. After that, other variables can affect body temperature,
such as the temperature of administered solutions, room temperature, surgical wash, and surgical exposure.
Sympathetic nerve blocks must be evaluated effectively, and temperature must be monitored by complex
thermostats or plastic strips of liquid crystal.
In the elderly, the speed of temperature change is slower. There is also no difference between epidural and spinal
[29]
anesthesia, and both reduce temperature equally. Monitoring body temperature during the perioperative period has
[30]
value not only in determining the autonomic response to the blockade but also by helping to avoid or diminish the
risk of myocardial ischemia, cardiac morbidity, wound infection, surgical bleeding, and patient discomfort. The
anesthesiologist should be attentive to temperature measurement during general and regional anesthesia. At present,
only 33% of clinicians surveyed routinely monitor body temperature during regional anesthesia. In fact, body
[27]
temperature is often not monitored at all in patients receiving regional anesthesia. It is therefore likely that
significant hypothermia goes undetected and untreated in these patients.
RADIOGRAPHY
The use of fluoroscopy and, occasionally, computed tomography helps in the performance of interventional pain
procedures in the cranial, cervical, thoracic, abdominal, and pelvic regions, thus adding safety and aiding in the
successful completion of neuroablative procedures related to chronic malignant and nonmalignant pain. [31]
In addition, the instillation of opaque contrast material augments the precision of needle placement provided by
radiography. Contrast dyes, especially nonionic formulations, have a lower risk of CNS toxicity when administered
near the neuraxis than ionic agents. Contrast agents may precipitate local and systemic toxicity. Signs of toxicity
may range from rash, or urticaria, to bronchospasm and anaphylaxis.
CENTRAL NERVOUS SYSTEM MONITORING

Conscious State Monitoring
Conscious state monitoring is necessary to detect the impact of drugs, metabolic response, and/or cardiovascular and
respiratory changes. Propofol is frequently used to sedate patients, but methohexital, barbiturates, and other drugs,
[32]
especially benzodiazepines, are also used. Sometimes fentanyl or remifentanil in variable doses is administered as
[33]
a “rescue” analgesic during the operation, because often it is not possible to continue with regional anesthesia. Thus,
the regional anesthetic technique is changed to other complex techniques that must also be monitored.
Hypotension or hypoxemia can cause loss of consciousness (possibly transient) because of sympathetic blockade,
bleeding, vagal stimulation, local anesthetics, drug absorption, or such events as pulmonary or myocardial infarction
or stroke, which are secondary to pathologic complications. One frequent cause of loss of consciousness is
inadvertent pneumocephalus secondary to regional anesthesia techniques (epidural and spinal). [34]
To evaluate and record the level of consciousness, the Glasgow scale can be useful in patients with high risk for loss
of consciousness. Simple scales can be employed such as the alertness/sedation (OAA/S) score, with a range of
responses from 1, which signifies awake/alert to 5, which indicates that the patient is asleep.[32]
The bispectral index (BIS) of the electroencephalogram and middle latency auditory evoked potentials (AEP) are
likely candidates to distinguish between the conscious and unconscious state in all patients during repeated
transitions from consciousness to unconsciousness, which can happen in regional anesthesia with additional
propofol infusion. However, the AEP index offers better discriminatory power in describing the transition from the
conscious to the unconscious state in the individual patient. [35]
Electroencephalography
Electroencephalography (EEG) measures the neuron electric activity of the cerebral cortex and is useful in detecting
ischemia resulting from improper cerebral perfusion. Specific evaluation of cortical, or deep, activity is measured in
neurosurgery to determine specific areas or to map seizure activity spots by means of special electrodes.
189
The EEG waveforms are classified by their frequencies as delta—1 to 3 Hz; theta—4 to 7 Hz; alpha—8 to 13 Hz;
beta—14 to 30 Hz. Loss of fast activity (alpha, beta) and slow activity increase (delta, theta, gamma) are the most
common changes associated with cerebral ischemia. Special waveforms are specific for specific seizure patterns.
An EEG reading is necessary when there is a risk of cerebral hypoxemia, or when the effect of drugs on cerebral
function must be evaluated, especially drugs that are capable of depressing the cerebral function. In many
neurosurgical centers, use of EEG with carotid endarterectomy is a good example, because during this type of
[36]
surgery, the patient is kept awake under regional anesthesia (superficial cervical block plus local infiltration) to
monitor the conscious state and to indicate mental performance as an indirect measure of the neuronal metabolic
state. There are many studies that attempt to show what type of monitoring is best. We think that a mixed
[37]
technique is best, but the data obtained from the EEG reading are more sensitive and are the earliest data obtainable,
with fewer false-positive or false-negative evaluations of transitory ischemic states.
Reports exist that show that there is no significant difference in the outcome of patients who were sedated by either
a general or a regional anesthetic, with low stroke and mortality rates achieved in carotid endarterectomy without
EEG monitoring but with neurologic assessment in awake patients or maintenance of cerebral protection criteria in
patients under general anesthesia.[38]
Bispectral Index
The BIS of the EEG measures the level of unconsciousness and thus may improve the early recovery profile and
guarantee hypnosis under general anesthesia. [39]
Psychomotor agitation can have many causes: emotional, pharmacologic, metabolic, and so forth. It can, therefore,
be very difficult to make a rapid determination between emotional acute disturbance and procedure complications.
We have to take enough time to define the most probable cause, without forgetting the toxicity of local anesthetics
and other drugs, which must be recognized primarily. We must also be mindful of the effect of the drugs on each
[40]
patient of respiratory impairment (muscle paralysis or airway obstruction), especially in patients with premorbid
states (e.g., elderly, hyponatremic, starved). In these patients, the drug impact is far less predictable.
The flexibility of shifting from an initially simple procedure to another much more complex procedure is the daily
challenge of anesthesiologists who practice regional procedures, and they must be prepared to face this ever-
changing situation. A previous emotional excitatory response to pain or other elements related to the illness or
surgical procedure should lead the anesthesiologist to suspect that superficial sedation might be insufficient to
maintain a state of calm in the patient; therefore, the patient must be evaluated to detect early signs or symptoms of
emotional discomfort.
It is expected that some emotional reaction will accompany certain surgical procedures that imply a significant loss
to the patient, such as abortion or hysterectomy.
Generally, children between 6 and 12 years of age are not able to tolerate regional anesthesia without sedation.
Neurologically, we evaluate not only awakeness but also superior cerebral functions such as speech, memory, and
other abilities. This evaluation is more sophisticated when there is risk compromise of the central flow, as in carotid
surgery or during Wada’s test of cerebral dominance under cerebral arteriography. For such procedures, specific
tests are performed, usually by an expert in the field. For regional anesthesia procedures, a continuous record of
[41]
mental status should be kept in the anesthetic record, including the regularly recorded score of anxiety, comfort
level, drowsiness, and pain status; this record should be permanent. [42]
EFFICACY OF PROCEDURE
One of the biggest challenges to the anesthesiologist performing a regional procedure is to be successful in
anesthetizing the patient, in the right area and with enough spread to cover the whole surgical procedure. The
monitoring of efficacy of the block starts with the evaluation of the quality, depth, and extension of the blockade.
This means that different surgical steps and the patient’s responses to them must be monitored.
Sometimes, the blockade may cover a sufficient area, but the quality may be substandard. This means that the
monitoring of the quality of anesthesia must be repeated frequently. It is also necessary to be attentive to other signs
of malfunction, as well as patient complaints, blood pressure, and cardiac function.
190
The combined spinal-epidural technique has been used increasingly since 1990, and it requires special follow-up.
Combined spinal-epidural anesthesia may achieve rapid onset and profound regional blockade, with the ability to
modify or prolong the block and with a variety of techniques and devices. The technique is complex by itself and
cannot be considered simply as a spinal block plus an epidural block, because the fact of combining the techniques
may alter each block. The technique can be performed with needle-through-needle, separate-needle, or combined-
needle techniques, each with different modifications. Causes of failure can vary greatly. If the spinal block is
performed before the epidural blockade is present, there is difficulty in achieving an adequate placing of the epidural
catheter, inability to detect paresthesia during epidural placement, and absence of other sensory elements. All of
these things must be considered in evaluating the performance of the technique. [43] [44]
Other techniques of combined regional and general anesthesia require effective monitoring procedures. EEG can be
used to assess the adequacy of the procedures. IEEG reading can be depressed by sedative hypnotic drugs.
[45] [46]
Another measure includes papillary assessment, in which dilatation of the pupil in response to electric stimulation is
an accurate test of the sensory block level achieved during combined epidural and general anesthesia. [47]
Muscle Relaxation
To determine differences in time of onset and duration of motor block produced by local anesthetics such as
lidocaine, the use of a quantitative and objective method (the measurement of compound muscle action potentials
[CMAPs] with continuous nerve stimulation on a two-channel electromyogram) has been shown to be
experimentally effective. However, it could also be used in vivo because it is the usual diagnostic procedure for
neuropathies and myopathies. Initially, baseline values registering the amplitude of the CMAPs are expressed in
millivolts. The injection of local anesthetic makes the wave diminish. However, this practice is currently not widely
used. The clinical indirect evaluation of muscle relaxation by the assessment of neuromuscular reflexes is much
more common. Depending on the regional procedure, some neuromuscular reflexes are expected to be decreased.
Another way to assess the muscle reponse under regional blockade is by employing a motor block assessment of the
modified Bromage scale. [48]
Sympathetic Blockade
Usually, the sympathetic blockade extends two to five dermatome levels above the limit of cutaneous anesthesia.
Inhibition of preganglionic fibers results in a decrease of peripheral vascular resistance and an increase in venous
pooling, with subsequent hypotension— the clinical sign of blockade effectiveness for thoracic and lumbar levels
but unusual in caudal anesthesia. There is a compensatory increase in the vascular resistance of the upper body that
maintains venous return and cardiac output. However, if the blockade reaches T1, cardiac sympathetic innervation is
blocked with profound hypotension and bradycardia. Hence, monitoring is necessary whenever changes occur in the
patient’s posture. When the patient is set at the recovery room, monitoring should continue until the patient is
discharged to his room.
Dermatome Mapping of Sensory Block
It is necessary to perform dermatome mapping of the sensory block, especially when epidural anesthesia is
employed. It is important to determine the level of blockade and the quality of anesthesia. An anesthetic chart of a
human body with dermatomes must be used to record the extent of neural blockade. The level can be assessed with
light touch, as with pinprick or an ice cube. This assessment should be performed carefully so that tissues are not
damaged and should be reevaluated after the addition of new boluses.
It is necessary to determine the levels of hyposthesia, anesthesia, and analgesia with a visual analogue scale (VAS)
if pain is present before the procedure. The VAS is indispensable in the use of continuous analgesic techniques to
verify efficacy of procedures or while making adjustments of infusions or rescue doses (e.g., postoperative epidural
infusions, anesthesia for cancer pain). The VAS must be updated at scheduled times and must include a record of the
patient’s complaints of pain as well as the drugs used and their effects.
Practical Issues
PREOPERATIVE PERIOD
If surgical intervention is indicated, perioperative anesthesia has to be carefully planned according to the
requirements of each patient. If the patient is classified as high risk at the preoperative anesthetic assessment, the
therapeutic management must aim at optimizing preoperative physical status. The perioperative risk of morbidity
and mortality associated with elective surgical procedures must be evaluated for the individual patient and the best
191
monitoring system for that patient must be chosen. The risks and benefits of invasive monitoring must be discussed
in an interdisciplinary dialogue involving the surgeon, the patient, and the patient’s family.
There are no recommendations about the choice of anesthesia techniques; the decision of whether to use general or
regional anesthesia depends on the site of the operation and is guided by the individual experience of the
anesthesiologist. Patient, surgical personnel, and anesthesiologists should reach a decision on the best technique and
the monitoring requirements should be discussed.
The patient’s neurologic integrity must be evaluated before any regional anesthetic procedure; this is especially
important because some patients may have neurologic deficits that were not noticed previously. Moreover, regional
anesthesia can cause complications. Deafness, blindness, psychosis, or nonfluent language makes this evaluation
[50]
more difficult, and such conditions are probably contraindications to the use of regional anesthesia.
TRANSOPERATIVE PERIOD
Intraoperatively, minimal monitoring standards have to be satisfied by the addition of noninvasive or invasive
monitoring techniques to observe cardiovascular and pulmonary functions according to the patient’s preoperative
disease as well as the course of the surgical-anesthetic procedure.
The principal monitoring function is to measure early events that can produce complications in the anesthetic or
surgical procedure. It is necessary to measure manifestations of toxicity and collateral effects of local anesthetics
and other drugs employed during the procedure. Monitoring can help to prevent administration of drugs at the wrong
site (e.g., entering the subarachnoid in an epidural technique). The patient’s idiosyncratic and allergic responses
must also be assessed for monitoring to be effective.
Frequently, regional anesthesia procedures need to be accompanied by mild to profound sedation and/or systemic
analgesia with an anesthetic technique that can be either combined or mixed. In some circumstances, the
anesthesiologist tries to ensure that the patient is conscious without suffering pain, and is able to respond to verbal
orders and answer questions so that there can be continuous evaluation of response to the regional procedure
through interpretation of tactile or painful stimuli.
A systematic neurologic evaluation is one way to avoid potential skin damage from pinprick puncture used to test
the efficacy and level of anesthesia. The examination must check for pallanesthesia, dysesthesia, motor blockade,
and reflex response. The evaluation must begin after the action of the drug has been initiated. Sensory block to
thermal stimuli, which is one of the early sensations blocked, can be easily done by touching the skin with an ice
cube.
Motor block can be assessed by a modified Bromage scale. The cremasteric reflex in men is a very sensitive
response, which is absent under effective regional anesthesia. In a study of 100 men, sensitivity, specificity, and
positive or negative predictive value for the cremasteric reflex were all 100%. Also, the disappearance of the
cremasteric reflex was affirmed by a simple objective indicator of spinal anesthesia at the first lumbar dermatome.
This test may be useful even in patients who cannot provide reliable answers to conventional tests, such as the
pinprick test. When the patient has pain before the anesthetic procedure, cessation of pain is a measure of
[51]
effectiveness. However, pain relief may be incomplete. This can produce an ineffective level of quality blockade.
The use of the visual or verbal analogue scale of pain and an assessment of the quality of the pain must be done
rather than painful assessments of surgical procedures.
Another concern is a surgical position that can influence the hemodynamic response, especially in operations
performed in the prone or jackknife position. Managing cardiorespiratory complications includes a risk of
[52]
inadvertent increase of sensory motor blockade. Spinal anesthesia is used for lower limb or perianal operations with
limited extension and blood loss; this seems to be a safe, effective, and economical technique for patients without
severe cardiovascular problems. Additional narcotics and sedatives should be avoided, and continuous monitoring of
hemodynamic and respiratory parameters, as well as the level of the blockade, must be methodically maintained. [53]
POSTOPERATIVE PERIOD
The use of continuous epidural infusion techniques employed for pain relief must be documented with a follow-up
similar to that conducted during the operative period. During the postoperative period every high-risk patient must
[54]
be monitored. Ideally, this would take place in the intensive care unit so as to continue intraoperative monitoring and
therapy. The typical recommendation for patients under high risk of postoperative myocardial ischemia or infarction
192
is that they should be closely monitored for 3 to 5 days postoperatively. This must be done regardless of which
anesthetic technique is used. [55]
OBSTETRIC PATIENTS
Usually, the evaluation of the mother in labor is made by the anesthesiologist; the gynecologist undertakes fetal
surveillance. However, the changes that affect the mother reflect on the fetus. Regional anesthesia is frequently
administered to pregnant women for delivery and other surgical procedures, even with complex techniques such as
combined epidural-spinal anesthesia. For the fetus, the usual monitoring includes checking cardiac frequency in
[56]
association with uterine activity. In specific cases, laboratory testing of fetal blood samples and amniotic fluid
(obtained by amniocentesis or amnioscopy) may be necessary to determine the metabolic status (biochemically
compromised or uncompromised) of the fetus.
Other approaches that can be of some help include fetal ECG and assessment of the T/QRS ratio calculated on an
individual basis, which can enhance the detection of fetal compromise during labor and predict poor outcome. [57]
Cardiovascular changes are associated with transport after surgery under spinal anesthesia because the extensively
vasodilated patient may be unable to compensate for postural blood flow. This has been demonstrated in patients
after cesarean section, with approximately 10% of patients exhibiting hypotension when they arrive in the recovery
room. This finding draws attention to the persistence of extensive sympathetic block at the end of cesarean section,
[58]
which is why it is strongly recommended to document the level of sensory block at the end of surgery and to
conduct increased monitoring during transport.
The risk of hypotension is always present in pregnancy. This can be predicted with noninvasive cardiac output
monitoring using thoracic electrical bioimpedance and measurement of systolic blood pressure. A patient with an
increased baseline vascular resistance index or decreased systolic blood pressure is at risk for hypotension under
regional anesthesia. [59]
With use of the head-down position during surgery to obtain better exposure, the heart may be lower than the uterus,
resulting in VAE, which can cause complaints of dyspnea, chest pain, and even death if the air volume is between
400 and 500 mL. Small amounts of air can obstruct pulmonary arteries affecting / expressed as hypoxemia, right
heart failure, cardiac arrhythmias, and cerebral dysfunction. If the uterus is above the level of the heart, this problem
is most noticeable when the uterus is exposed during repair. Some studies have shown a greater than 50% incidence
of VAE. Precordial Doppler monitoring is very sensitive in regard to VAE, detecting bubbles as small as 0.1 mL.
The Doppler scan must be used simultaneously with SaO2 and ECG, especially in patients with placenta previa or
abruptio placentae, conditions which are believed to increase risk for VAE. Patients with these conditions also need
to have a central catheter in the right atrium to remove air and prevent cardiac failure. [60]
PROCEDURES FOR PAIN RELIEF
Nerve blocks are capable of providing excellent analgesia, with minimal systemic effect, in a limited area of the
body. Peripheral nerve blocks are simple to perform, provide excellent analgesia, and have a good record of safety.
In general, appropriate blocks exist for almost all areas of the body. Often, however, there is no single technique that
is effective, and a multimodal approach is necessary.
Pain Control for Patients at the Intensive Care Unit
A number of procedures can prevent pain in patients in the intensive care unit. These procedures improve the
[61]
patient’s comfort and promote consciousness and the hemodynamic response. The techniques include intercostal
nerve blocks, interpleural blocks, paravertebral blocks, brachial plexus blocks, and femoral nerve blocks. A rational
patient evaluation must be made for each case to properly evaluate responses and collateral effects. [62] [63]
Chronic Pain
Many approaches for transient and permanent pain relief exist. The first goal in monitoring pain relief procedures is
a general one, with the monitoring of hemodynamic and metabolic global response to the procedure; the second goal
is to ensure efficacy of pain relief, which requires neurophysiologic monitoring. There is great interest in the long-
term monitoring for patients after neurolytic procedures for determining recovery of neurologic function.
193
Monitoring of chronic pain requires pain relief but also the patient’s well-being, functional restoration, work-status
restoration, and global outcome. These considerations may be very complex, because each case may be managed
with multimodal analgesia techniques ( Table 12-5 ). [64]
TABLE 12-5 -- LOCATION OF PAIN, INTERVENTIONAL PROCEDURE, ASSOCIATED RISKS, AND RECOMMENDED MONITORING
Location, Cause of Pain or
Procedure Intervention Risks Monitoring
Face Trigeminal nerve block Vascular injection, hypertension, Blood pressure, ECG, pulse oximetry,
bradycardia, asystole fluoroscopy, CT scan
Upper extremity Brachial plexus block Vascular injection, pneumothorax, Blood pressure, ECG, pulse oximetry,
phrenic nerve paresis fluoroscopy, respiratory function
Cancer pain Celiac plexus block Vascular injection, hypotension, Blood pressure, ECG, pulse oximetry,
paraplegia, pneumothorax, renal fluoroscopy, CT scan, respiratory
Lumbar sympathetic block puncture, blowel perforation function, neurologic status evaluation
Superior hypogastric plexus block
Ganglion impar block
Central neuroaxial procedures Subarachnoid blockade Vascular injection, hypotension, Blood pressure, ECG, pulse oximetry,
neurologic deficits, pneumothorax, fluoroscopy, CT scan, respiratory
Temporary duration Epidural blockade renal puncture, nerve injury, spinal function
cord damage, undesirable dural
Acute pain PCA
punction or injection, infection,
Chronic pain Epidural steroids hematoma
Differential block Spinal cord stimulation
Diagnostic trial Lysis of epidural adhesions
Disc pathologies Discography Dural puncture/injection Blood pressure, ECG, pulse oximetry,
fluoroscopy, CT scan, respiratory
Nerve injury function, neurologic status evaluation
Vascular injection
Epidural hematoma
Infection (discitis)
CT, Computed tomography; ECG, electrocardiogram; PCA, patient-controlled anesthesia.
Modified from Lake CL, Hines RL, Blitt CD: Clinical Monitoring: Practical Applications for Anesthesia and Critical Care. Philadelphia, WB Saunders, 2001.
Cancer Pain
According to the World Health Organization (WHO), management of cancer pain is principally obtained with
opioids; however, 10% to 20% of patients with advanced disease do not have adequate relief. In this population,
techniques for including temporary or permanent blockades are performed ( Table 12-6 ).
Patient-controlled regional anesthesia (PCRA), which has been used under different circumstances for a long time, [65]
is a method that can be employed at home and monitored. Regular surveillance includes visual analogues scores
(VASs), rescue doses with frequency and total amount used, motor blockade, sphincter function, technical facilities
for user and family, malfunction of the system, and patient and family evaluation of satisfaction with this approach.
Neuroablative techniques are used in the management of intractable malignant pain. Somatic and visceral origins of
pain syndromes are more amenable to neurolysis than neuropathic pain, and usually these techniques are reserved
for patients for whom trials of aggressive pharmacologic therapy and other conservative modalities have been
unsuccessful. Neurolytic modalities include chemical, thermal, and surgical approaches. The lytic agent chosen, site
of administration, adjacent tissue structures at risk for injury, and the level of sedation or anesthetic procedure used
for the procedure determine appropriate monitoring of patients undergoing neurolytic procedures. Chemical
neurolysis is performed with alcohol, phenol, and, in lesser circumstances, ammonium sulfate or glycerol. Alcohol
diffuses rapidly from the injection site after
TABLE 12-6 -- REGIONAL BLOCKADE FOR CANCER PAIN

Temporary
Bolus or infusions of local anesthetics, or mixtures with opioids, ketamine steroids, and other drugs
Peripheral nervous blockade

Epidural
Long Term
Bolus or infusions of local anesthetics, or mixtures with opioids, ketamine steroids, and other drugs
194
Epidural tunnelized catheter

Spinal tunnelized catheter
Long Term
Neurolytic substances, or physical medium—cutting, heating, freezing
Peripheral neurolysis[31]
Sympathetic axis neurolysis
Cervicothoracic (stellate) ganglion

Thoracic chain
Splanchnic nerves
Celiac plexus
Lumbar sympathetic chain

Superior hypogastric plexus
Ganglion of Walther
Data from Plancarte R, Amescua C, Patt RB: Sympathetic neural block ade. In Patt RB (ed): Cancer Pain. Philadelphia, JB Lippincott, 1993, pp 377–425.
injection. The volume is usually small; however, complications including local tissue injuries that range from
irritation to necrosis may occur. Neurolysis is occasionally associated with pain at the site of injection, neuralgia of
variable duration (days to months), and painful anesthesia, or hypoesthesia in the distribution of the chemically
lysed nerve. Lumbar and sacral intrathecal alcohol administration may result in bowel and bladder incontinence or
paraplegia. [31] [66] [67]
Phenol, in comparison with absolute alcohol, yields a less pronounced neurolytic block, and neural degeneration
takes approximately 14 days. Recovery occurs in 14 weeks. In combination, phenol has a high affinity for vascular
tissue, and this fact must be considered when it is applied near major blood vessels as in celiac plexus block.
Monitoring During Chemical Neurolysis
Monitoring of this procedures includes neurologic evaluation with dermatomal mapping to determine hypoesthesic
or anesthetic zones.
ASSESSMENT OF EFFICACY OF TREATMENT FOR SPASTICITY

Pain Due to Spasticity
Spasticity may develop after an injury to the CNS; if sensation is still intact, spasticity may cause pain because of
the prolonged restriction of movement and the difficult positions the body assumes. Management of this condition
usually includes use of benzodiazepines and other oral drugs with antispasmodic effect. However, interventional
therapies for this condition can be helpful, including neurodestructive techniques (surgical or chemical), CNS
stimulation, and continuous infusions of neuraxial drugs (e.g., baclofen, local anesthetics, and morphine).
The ways to monitor spasticity include medical photography to record changes and dynamic records of movement
expressed in angles of extremities. Successful therapies must be based on the subjective clinical assessment by
clinicians or self-reporting by patients, because sometimes spasticity does not improve but pain can be reduced. [68] [69]
MONITORING TO DETERMINE THERAPEUTIC EFFICACY
The patient with a painful condition requires psychological and subjective assessment of pain as a baseline record
and subsequent assessment of responses to therapeutic interventions. The evaluation should include a medical pain
history that contains date of onset; condition at onset; quality, severity, and persistence of pain; associated
symptoms; provocative and mitigating factors; past medical history; medication history; systems review; family,
occupational, and social history. The physical examination should include a thorough evaluation with a focus on the
pain behavior during the examination and with a careful review of neurologic and musculoskeletal structures. The
inclusion of such adjuvant diagnostic modalities as radiographic tests of structure, neurophysiologic tests, and tests
of hematologic and metabolic status augments the establishment of a correct diagnosis. This information must be
compared with the patient’s situation after undergoing procedures, with special attention to pain measurement
195
(numeric pain scales, visual analog scales, or facial drawings). These tools are easily understood by patients and
easily used by pain clinic personnel. They demonstrate reliability and allow assessment of analgesic efficacy.
Self-reporting of pain using multidimensional pain scales such as the McGill Pain Questionnaire can be helpful [70]
also. These devices evaluate pain in more than one dimension. They detect the motivational-affective components
that may have been missed with a single-descriptor pain assessment scale and are probably used more by researchers
than by clinicians. Techniques available for assessment of interventional efficacy include controlled mechanical
stimulation (e.g., algometry, algesimeter, dolorimeter, Frey’s fibers, palpatometer) and quantitative sensory testing
devices.
Assessment of efficacy in sympathetic blockade includes the patient’s perception of complete or partial resolution of
pain or measurement of reduction in sympathetic activity. Measurements of sympathetic activity in an affected limb
include changes in temperature, the sympathogalvanic response, the quantitative sudomotor axon reflex test
(QSART), and thermography. An increase in skin temperature is the most common information obtained. A
temperature probe is applied to the affected region and to the contralateral site as a control measure, both before and
during the sympathetic nerve block. Different degrees of temperature change indicate an effective sympathetic
blockade, with increases of 1.50°C to 7.5°C. Homer’s syndrome is an acceptable marker of sympathetic block in the
stellate ganglion.
The Future of Monitoring
Technology using highly accessible microprocessors and surgical requirements that are becoming increasingly
complex will determine the future of monitoring. The growing importance of RA, along with skilled personnel,
should make this type of anesthesia more safe by ensuring adequate monitoring of the patient’s neuroresponse to
local anesthetics and other drugs used. [71]
Standard reviews of the practice of RA will be done and new additions will be made to the actual parameters to
benefit both patients and practitioners. Monitoring must be reviewed from the perspective of a liability point of view
as well as from improvement of quality and cost-effectiveness of practice and equipment. Training of RA personnel
must be one of the most important factors. An analysis must be made to determine what is clinically useful to
improve the outcome of patients.
Perhaps the development of new neurologic methods, such as functional magnetic resonance imaging and easier
methods for performing neurophysiologic tests, will increase the frequency of these tests. Reduction in costs of
monitoring will increase the practice of monitoring. Telemetric monitoring will reduce costs and provide access to
an expert advisor without concern about distance. [72] [73]
Summary
RA and procedures related to the management of pain, whether acute or chronic, are medical practices that need to
be performed correctly, and this includes regular monitoring. Monitoring should be based on expert
recommendations to improve patient outcome, to achieve the best possible control of pain, and to avoid the risks
associated with therapeutically challenging medical conditions.
The field of interventional pain management requires the development of sensitive, specific, and efficient monitors
with adequate clinical trials of their efficacy.
REFERENCES
1. Stedman’s Pocket Medical Dictionary. London, Lippincott Williams & Wilkins, 1999.
2. Caplan RA, Ward RJ, Posner K, Cheney FW: Unexpected cardiac arrest during spinal anesthesia: A closed claims analysis of predisposing
factors. Anesthesiology 68:5–11, 1988.
3. Knill RL: Cardiac arrests during spinal anesthesia: Unexpected? Anesthesiology 69:629, 1988.
4. Shen CL, Ho YY, Hung YC, Chen PL: Arrhythmias during spinal anesthesia for Caesarean section. Can J Anaesth 47:393–397, 2000.
5. Rosenfeld SI, Litinsky SM, Snyder DA, et al: Effectiveness of monitored anesthesia care in cataract surgery. Ophthalmology 106:1256–1260,
1999.
6. Brooks DM, Hand WR Jr: A cost analysis: General endotracheal versus regional versus monitored anesthesia care. Navy Nurse Corps
196
Anesthesia Program, Bethesda, Md, Mil Med 164:303–305, 1999.
7. Howie WO: Anesthesia-related lawsuits in Maryland: CRNA and anesthesiologist claims. AANA J 66:394–397, 1998.
8. Eige S, Pritts EA, Anesthesia for office endoscopy. Obstet Gynecol Clin North Am 26:99–108, 1999.
9. Christopherson R, Norris EJ: Anesthesia for the cardiac patient. Regional versus general anesthesia. Anesthesiol Clin North Am 15:37–47,
1997.
10. Abeles G, Warmuth IP, Sequeira M, et al: The use of conscious sedation for outpatient dermatologic surgical procedures. Dermatol Surg
26:121–126, 2000.
11. Landry DR, Benett FM, Oriol NE: Analysis of heart rate dynamics as a measure of autonomic tone in obstetrical patients undergoing epidural
or spinal anesthesia. Reg Anesth 19:189–195, 1994.
12. DexterF, Penning DH, Lubarsky DA, et al: Use of an automated anesthesia information system to determine reference limits for vital signs
during cesarean section. Clin Monit Comput 14:491–498, 1998.
13. Rheineck-Leyssius AT, Kalkman CJ: Advanced pulse oximeter signal processing technology compared to simple averaging. II. Effect on
frequency of alarms in the postanesthesia care unit. J Clin Anesth 11:196–200, 1999.
14. Aitkenhead AR, Chopra V, Davies JM, et al: In Bramley I (ed): Clinical Anaesthesiology, International Practice and Research. Quality
Assurance and Risk Management in Anaesthesia, 2nd ed. London, Baillière Tindall W. B. Saunders Ltd, vol 10, 1996.
15. Garcia-Aguado R, Vivo Benlloch M, Arcusa Mon MJ, et al: Systematic recording of perioperative events associated with anesthesia as quality
indicator in ambulatory anesthesia. Rev Esp Anestesiol Reanim 47:101–107, 2000.
16. Brodsky JB: What intraoperative monitoring makes sense? Chest 5:101–105, 1999.
17. American Society of Anesthesiologists: Standards for Basic Intraoperative Monitoring. Newsletter, Park Ridge, Ill, 1986.
18. Backlund M, Toivonen L, Tuominen M, et al: Changes in heart rate variability in elderly patients undergoing major noncardiac surgery under
spinal or general anesthesia. Reg Anesth Pain Med 24:386–392, 1999.
19. Hammer GB: Regional anesthesia for pediatric cardiac surgery. J Cardiothorac Vasc Anesth 13:210–213, 1999.
20. Williams-Russo P, Sharrock NE, Mattis S, et al: Randomized trial of hypotensive epidural anesthesia in older adults. Anesthesiology 91:926–
935, 1999.
21. Ghali R, Palazzo EG, Rodriguez DI, et al: Transcranial, Doppler intraoperative monitoring during carotid endarterectomy: Experience with
regional or general anesthesia, with and without shunting. Ann Vasc Surg 11:9–13, 1997.
22. Mark JB, Steinbrook RA, Gugino LD, et al: Continuous noninvasive monitoring of cardiac output with esophageal Doppler ultrasound during
cardiac surgery. Anesth Analg 65:1013–1020, 1986.
23. Smart JA, Pallett EJ, Duthie DJ: Breath interval as a measure of dynamic opioid effect. Br J Anaesth 84:735–738, 2000.
24. Mackenzie N: Sedation during regional anaesthesia: Indications, advantages and methods. Eur J Anaesthesiol 13 (Suppl):2–7, 1996.
25. Gallacher BP: The measurement of end tidal carbon dioxide concentrations using modified nasal prongs in ophthalmologic patients under
regional anesthesia [letter]. Reg Anest 16(3):189, 1991.
26. Cattaneo CG, Frank SM, Hesel TW, et al: The accuracy and precision of body temperature monitoring methods during regional and general
anesthesia. Anesth Analg 90:938–945, 2000.
27. Frank SM, Nguyen JM, Garcia CM, Barnes RA: Temperature monitoring practices during regional anesthesia. Anesth Analg 88:373–377,
1999.
28. Larue F, Benhamou D, Jullien P, et al: Temperature monitoring during epidural anesthesia for cesarean delivery. Reg Anesth 16:322–324,
1991.
29. Ohe Y, Sotoh K, Tachibana C, et al: The changes of peripheral skin temperature in elderly patients under spinal anesthesia. Masui 48:879–883,
1999.
30. Ozaki M, Kurz A, Sessler DI, et al: Thermoregulatory thresholds during epidural and spinal anesthesia. Anesthesiology 81:282–288, 1994.
31. Plancarte R, Amescua C, Patt RB: Sympathetic neural blockade. In Patt RB (ed): Cancer Pain. Philadelphia, JB Lippincott, 1993, pp 377–425.
32. Sa
Rego MM, Inagaki Y, White PF: The cost-effectiveness of methohexital versus propofol for sedation during monitored anesthesia care.
Anesth Analg 88:723–728, 1999.
197
33. Servin F, Desmonts JM, Watkins WD: Remifentanil as an analgesic adjunct in local/regional anesthesia and in monitored anesthesia care.
Anesth Analg 89(Suppl):S28–S32, 1999.
34. Sherer DM, Onyeije CI, Yun E: Pneumocephalus following inadvertent intrathecal puncture during epidural anesthesia: A case report and
review of the literature. J Matern Fetal Med 8:138–140, 1999.
35. Grundy B: Intraoperative monitoring of sensory-evoked potentials. Anesthesiology 58:72–87, 1983.
36. Wellman BJ, Loftus CM, Kresowik TF, et al: The differences in electroencephalographic changes in patients under carotid endarterectomies
while under local versus general anesthesia. Neurosurgery 43(4):769–773, 1998.
37. Stoughton J, Nath RL, Abbott WM: Comparison of simultaneous electroencephalographic and mental status monitoring during carotid
endarterectomy with regional anesthesia. J Vasc Surg 28:1014–1021, 1998.
38. Hamdan AD, Pomposelli FB Jr, Gibbons GW, et al: Perioperative strokes after 1001 consecutive carotid endarterectomy procedures without an
electroencephalogram: Incidence, mechanism, and recovery. Arch Surg 134:412–415, 1999.
39. Sandin RH, Enlund G, Samuelsson P, Lenmarken C: Awareness during anesthesia: A prospective case study. Lancet 355:707–711, 2000.
40. Kopacz DJ, Allen HW: Accidental intravenous levobupivacaine Anesth Analg 89:1027–1029, 1999.
41. Shah DM, Darling RC, Chang BB, et al: Carotid endarterectomy in awake patients: Its safety, acceptability, and outcome. J Vasc Surg
19:1015–1019, 1994.
42. Marina D, Bizarri-Schmid: [Letter to the editor]. Reg Anesth 15:269, 1990.
43. Fiedler MA: AANA Journal Course: Update for nurse anesthetists—improving the efficacy of subarachnoid and epidural blocks. AANA J
65:451–459, 1997.
44. Cook TM: Combined spinal-epidural techniques. Anaesthesia 55:42–64, 2000.
45. Kiyama S, Tsuzaki K: Processed electroencephalogram during combined extradural and general anaesthesia. Br J Anaesth 78:751–753, 1997.
46. Sloan TB: Anesthetic effects on electrophysiologic recordings. J Clin Neurophysiol 15:217–26, 1998.
47. Larson MD, Sessler DI, Ozaki M, et al: Pupillary assessment of sensory block level during combined epidural/general anesthesia.
48. Atanassoff
PG, Kelly DJ, Ayoub CM, Brull SJ: Electromyographic assessment of ulnar nerve motor block induced by lidocaine. J Clin Anesth
10:641–645, 1998.
49. McCrae AF, Wildsmith JAW: Prevention and treatment of hypotension during central neural block. Br J Anaesth 70:672–680, 1993.
50. Horlocker TT, Wedel DJ: Neurologic complications of spinal and epidural anesthesia. Reg Anesth Pain Med 25:83–98, 2000.
51. Okuda Y, Mishio M, Kitajima T, Asai T: Cremasteric reflex test as an objective indicator of spinal anaesthesia. Anaesthesia 55:587–589, 2000.
52. Standl T, Burmeister MA, Hempel V: Is spinal anesthesia for operations in the prone or jackknife position suitable? Anaesthesist 48:242–250,
1999.
53. Landow L: Monitoring adverse drug events: The Food and Drug Administration MedWatch reporting system. Reg Anesth Pain Med 23(6
Suppl 2):190–193, 1998.
54. Burm AGL, Stienstral R, Brower RP, et al: Epidural infusion of ropivacaíne for postoperative analgesia after major orthopedic surgery.
55. Prause G, List WF: The anesthesiologic risk patient. Preoperative evaluation, intraoperative management and postoperative monitoring.
Chirurg 68:775–779, 1997.
56. Callesen T, Schouenborg I, Nielsen D, Guldager H, Kehlet H: Combined epidural-spinal opioid-free anesthesia and analgesia for
hysterectomy. Br J Anaesth 82:881–885, 1999.
57. van Wijngaarden WJ, Strachan BK, Sahota DS, James DK: Improving intrapartum surveillance: An individualised T/QRS ratio? Eur J Obstet
Gynecol Reprod Biol 88:43–48, 2000.
58. Bandi E, Weeks S, Carli F: Spinal block levels and cardiovascular changes during post-Caesarean transport. Can J Anaesth 46:736–740, 1999.
59. Ouzounian JG, Masaki DI, Abboud TK, Greenspoon JS: Systemic vascular resistance index determined by thoracic electrical bioimpedance
predicts the risk for maternal hypotension during regional anesthesia for cesarean delivery. Am J Obstet Gynecol 174:1019–1025, 1996.
198
60. Vartikar JV, Johnson MP, Datta S: Precordial Doppler monitoring and pulse oximetry during cesarean delivery: Detection of venous air
embolism. Reg Anesth 14:145–148, 1989.
61. Soifer BE: Procedural anesthesia at the bedside. Crit Care Clin 16:7–28, 2000.
62. Burton AW, Eappen S: Regional anesthesia techniques for pain control in the intensive care unit. Crit Care Clin 15:77–88, 1999.
63. Smith DW, Peterson MR, De Berard SC: Regional anesthesia. Nerve blocks of the extremities and face. Postgrad Med 106:69–73, 77–78,
1999.
64. Kehlet H, Dahl JB: The value of “multimodal” or “balanced analgesia” in postoperative pain treatment. Anesth Analg 77:1048–1056, 1993.
65. Amesbury B, O’Riordan J, Dolin S: The use of interpleural analgesia using bupivacaine for pain relief in advanced cancer. Palliat Med
13:153–158, 1999.
66. Rawal N: Patient-controlled regional analgesia (PCRA). Acta Anaesthesiol Belg 50:221–225, 1999.
67. Plancarte R, de León Casasola OA, El-Helaly M, et al: Neurolytic superior hypogastric plexus block for chronic pelvic pain associated with
cancer. Reg Anesth 22:562–568, 1997.
68. Plancarte R, Amescua C, Patt RB: Presacral blockade of the ganglion of Walther (ganglion impar). Anesthesiol Abstr 73:A751, 1990.
69. Neuhluser G: Methods of assessing and recording motor skills and movement patterns. Dev Med Child Neurol 17:369–386, 1975.
70. Chabal C, Schwid HA, Jacobson L: The dynamic flexometer: An instrument for the objective evaluation of spasticity. Anesthesiology 74:609–
612, 1991.
71. Melzack R: The McGill Pain Questionnaire: Major properties and scoring methods. Pain 1:277–299, 1975.
72. MagnúsdóttirH, Kirnö K, Ricksten SE, et al: High thoracic epidural anesthesia does not inhibit sympathetic nerve activity in the lower
extremities. Anesthesiology 91:1299–1304, 1999.
73. Helman JD: Monitoring pain management procedures. In Lake CL, Hines RL, Blitt CD (eds): Clinical Monitoring: Practical Applications for
Anesthesia and Critical Care. Philadelphia, WB Saunders, 2001, pp 539–552. 177
199
Section IV - Chapter 13 - Local Anesthetics
Chapter 13 - Local Anesthetics
LELAND LOU
RAJ SABAR
ALAN D. KAYE
Local anesthetics prevent or relieve pain by interrupting nerve conduction. They bind to a specific receptor site
within the pore of the Na+ channels in nerves and block ion movement through this pore. In general, their action is
restricted to the site of application and rapidly reverses on diffusion from the site of action in the nerve. The
chemical and pharmacologic properties of each drug determine its clinical use. Local anesthetics can be
administered by a variety of routes, including topical, infiltration, field or nerve block, intravenous regional, spinal,
or epidural, as dictated by clinical circumstances. This chapter covers the mechanism of action of local anesthetics,
their physical properties, therapeutic use, and routes of administration.
Nerve Impulse Propagation
Nerve conduction involves the propagation of an electrical signal generated by the rapid movement of small
amounts of several ionic species across the nerve cell membrane. The principal ions involved in generating the
action potential in the nerve membranes are sodium and potassium. The ionic concentration of sodium (Na+ ) is high
extracellularly and low intracellularly; the ionic concentration of potassium (K+ ) is high intracellularly and low
extracellularly. This ionic gradient for sodium and potassium is maintained by a sodium-potassium ion-translocating
adenosine triphosphatase (ATPase) pump mechanism within the nerve. In the resting state, the nerve membrane is
more permeable to potassium ions than to sodium ions. Thus, there is a continual leakage of potassium ions from the
interior of the nerve cell to the exterior. This leakage of a cation leaves the interior of the nerve negatively charged
relative to its outside. In humans, this results in an electrical potential of −60 to −70 mV across the nerve
membrane. [1]
Receptors at the distal end of the sensory nerves are, in effect, transducers of various energy inputs of mechanical,
chemical, or thermal stimuli. These stimuli are converted into tiny electrical currents. For example, chemical
mediators released with a surgical incision react with these receptors and generate small electrical currents. This
alters the electrical potential across a small portion of the nerve membrane near the receptor, making it less negative.
If the threshold potential is achieved, an action potential results, with a sudden increase in the permeability of the
nerve membrane to sodium ions.
The rapid influx of positively charged sodium ions transiently causes a reversal of charge, or depolarization.
Subsequently, repolarization occurs when sodium permeability decreases, then stops, and potassium permeability
increases and results in an efflux of potassium from within the cell, restoring electrical balance. Both ions are
subsequently restored to their initial intracellular and extracellular concentrations by the sodium potassium ATPase
pump mechanism. The depolarization and subsequent repolarization are part of the action potential illustrated in
Figure 13-1 . Depolarization generates a current that sequentially depolarizes the adjacent segment of the nerve, thus
activating the nerve.
The rapid influx of sodium ions that produces the initial upswing of the action potential occurs through specific
sodium channels, or pores, in the cell membrane.
200
Figure 13-1 Sodium and potassium ion movement during the course of an action potential in a nerve.
The sodium channel is a protein structure that penetrates the full depth of the membrane bilayer and is in
communication with the extracellular surface of the nerve membrane and the axoplasm (interior) of the nerve ( Fig.
13-2 ). The sodium channel is limited by size and charge at its opening on the extracellular surface, so that it allows
mainly sodium ions to move through it. Paths such as the sodium channel can change the nerve from being
nonconductive to conductive of an action potential and are thus referred to as gated channels. If the change in
conductance is induced by electrical changes, the channel is said to be voltage-gated. The voltage-gated sodium
channel in the nerve is generally accepted as the site of action for the local anesthetics. Catterall and Ragsdale [2]
dxand colleagues have characterized the sodium channel protein as consisting of four repeating alpha subunits, a
[3]
beta-1 and beta-2 subunit. The alpha subunits are principally involved in the performance of channel function, such
as ion movement and local anesthetic activity. Each of the four repeating alpha subunits is composed of six
transmembrane segments that are repeating amino acid
Figure 13-2 Local anesthetic movement and equilibration of local anesthetic forms across the nerve membrane and into the sodium channel. B,
base; BH+ , cation.
chains ( Fig. 13-3 ). These subunits traverse the nerve membrane and line up to form the sodium channel and the
gating mechanism.
Structure-Activity Relationship of Local Anesthetics
Figure 13-4 shows the structure of a typical local anesthetic, which contains hydrophilic and hydrophobic domains
that are separated by an intermediate ester or amide linkage. A broad range of compounds containing these minimal
structural features can satisfy the requirements for action as local anesthetics. The hydrophilic group usually is a
tertiary amine, but it also may be a secondary amine. The hydrophobic domain must be an aromatic moiety. The
nature of the linking group determines certain of the pharmacologic properties of these agents. For example, local
anesthetics with an ester link are hydrolyzed readily by plasma esterases.
201
The structure-activity relationship and the physiochemical properties of local anesthetics have been reviewed by
Courtney and Strichartz. In brief, hydrophobicity increases both the potency and the duration of action of the local
[4]
anesthetics. This arises because association of the drug at hydrophobic sites enhances the partitioning of the drug to
its sites of action and decreases the rate of metabolism by plasma esterases and liver enzymes. In addition, the
receptor site for these drugs on Na+ channels is thought to be hydrophobic, so that receptor affinity for anesthetic
agents is increased for more hydrophobic drugs. Hydrophobicity also increases toxicity, so that the therapeutic index
actually is decreased for more hydrophobic drugs.
Molecular size also influences the rate of dissociation of local anesthetics from their receptor sites. Smaller drug [4]
molecules can escape from the receptor site more rapidly. This characteristic is important in rapidly firing tissues, in
which local anesthetics bind during action potentials and dissociate during the period of membrane repolarization.
Rapid binding of local
Figur13-3 Schematic of sodium channel protein structure. Linear schematic of the four repeating alpha subunits that form the sodium
channel.(Modified from Heavner JE: Neurophysiology. In Brown DL [ ed]: Regional Anesthesia and Analgesia. Philadelphia, WB Saunders,
1996. By permission of Mayo Foundation for Medical Education and Research.)
Figure 13-4 A, B, C. The four physicochemically important subunits of the structural formula for lidocaine.(From Denson D, Mazoit J:
Physiology, pharmacology, and toxicity of local anesthetics: Adult and pediatric considerations. In Raj PP [ ed]: Clinical Practice of Regional
Anesthesia. New York, Churchill Livingstone, 1991, pp 5, 73–105.)
202
Figure 13-5 Equilibration of lidocaine into base and cationic forms. The amount of available hydrogen ion (pH) determines the equilibrium
concentration of the two forms.
anesthetics during action potentials causes frequency- and voltage-dependence of their action.
An amino group is present at the end of the molecule opposite the benzene ring. This unit determines the
hydrophilic activity and ionization of the drug. The amino group usually has three organic groups attached (tertiary
amine) and becomes charged (ionized) into a cationic form by the addition of a hydrogen ion ( Fig. 13-5 ). The pKa
of the local anesthetic determines the ratio of the ionized (cationic) and the uncharged (base) form of the drug. The
pKa for local anesthetic drugs falls within a narrow range (7.6–9.2). By definition, the pKa is the pH at which 50% of
the drug is ionized and at which 50% is present as the base. The relationship between pH, pKa , and concentration of
the cationic and base forms of the local anesthetic is described by the Henderson-Hasselbach equation
pH = pKa + log base/cation
The pKa generally correlates with the speed of onset of most of the amide local anesthetic drugs; that is, the closer
the pKa is to body pH, the faster the onset. The coexistence of the two drug forms—the charged cation and the
uncharged base form—is important because drug penetration of the nerve membrane by the local anesthetic requires
the base (un-ionized) form to pass through the nerve lipid membrane; once in the axoplasm of the nerve, the base
form can accept a hydrogen ion and equilibrate into the cationic form. The cationic form is predominant and
produces blockade of the sodium channel. The amount of base form that can be in solution is limited by the aqueous
solubility of the base form of the individual local anesthetics.
An ester or an amide linkage exists between the lipophilic end (benzene ring) and the hydrophilic amino end of the
molecule. The type of link present determines the site of metabolic degradation of the drug. The ester-linked local
anesthetics are inactivated in plasma, whereas the amide-linked drugs must reach the liver before inactivation can
take place.
The linkage is also capable of partial ionization, which results in a partial negative charge on the carbonyl oxygen or
nitrogen that, along with the positively charged hydrophilic amino group, facilitates local anesthetic binding within
the sodium channel to ionic portions of the amino acids making up the sodium channel protein. [5]
Small structural modifications can produce major changes in activity, including significant differences in potency,
onset, and duration of action of the local anesthetic drugs. In the mepivacaine series, for example, a change from a
methyl substitution group on the hydrophilic amino group for mepivacaine to a butyl substitution group on the
amino group converts the compound to bupivacaine. Bupivacaine is approximately 30 times more lipid-soluble than
mepivacaine and has four times the potency of mepivacaine. A minor shortening of the four-carbon butyl group of
bupivacaine to a three-carbon substitution (propyl group) on the amino group converts the compound to ropivacaine.
This compound is slightly less potent than bupivacaine for sensory blocks, produces fewer motor blocking effects
than bupivacaine, and is less cardiotoxic than bupivacaine. [6] [7]
203
Mechanism of Action
Local anesthetics prevent the generation and the conduction of the nerve impulse. Their primary site of action is the
cell membrane. Conduction block can be demonstrated in squid giant axons from which the axoplasm has been
removed.
Local anesthetics block conduction by decreasing or preventing the large transient increase in the permeability of
excitable membranes to Na+ that normally is produced by a slight depolarization of the membrane. However, [8]
because the interaction of local anesthetics with K+ channels requires higher concentrations of drug, blockade of
conduction is not accompanied by any large or consistent change in resting membrane potential due to block of K+
channels.
Quaternary analogues of local anesthetics block conduction when applied internally to perfused giant axons of
squid, but they are relatively ineffective when applied externally. These observations suggest that the site at which
local anesthetics act, at least in their charged form, is accessible only from the inner surface of the membrane. [8] [9]
Therefore, local anesthetics applied externally first must cross the membrane before they can exert a blocking
action.
Although a variety of physiochemical models have been proposed to explain how local anesthetics achieve
conduction block, it is now generally accepted that the major mechanism of action of these drugs involves
[4]
Figure 13-6 Schematic representations of the appearance of the sodium channel (anurous pore) formed by repeating subunits in Figure 13-3 .
their interaction with one or more specific binding sites within the Na+ channel. Biochemical, biophysical, and
[10]
molecular biologic investigations beginning in the early 1990s have led to a rapid expansion of knowledge about the
structure and function of the Na+ channel and other voltage-gated ion channels. The Na+ channels of the
[11]
mammalian brain are heterotrimeric complexes of glycosylated proteins with an aggregate molecular size in excess
of 300 kDa; the individual subunits are designated α (260 kDa), β1 (36 kDa), and β2 (33 kDa). The large α subunit of
the Na+ channel contains four homologous domains (I to IV); each domain is thought to consist of six
transmembrane domains or spans in á-helical conformation (S1 to S6; Fig. 13-6 ). The Na+ -selective transmembrane
pore of the channel is presumed to reside in the center of a nearly symmetrical structure formed by the four
homologous domains. The voltage-dependence of channel opening is hypothesized to reflect conformational
changes that result from the movement of “gating charges” (voltage sensors) in response to changes in the
transmembrane potential. The gating charges are located in the S4 transmembrane helix; the S4 helices are both
hydrophobic and positively charged, containing lysine or arginine residues at every third position. It is postulated
that these residues move perpendicular to the plane of the membrane under the influence of the transmembrane
potential, initiating a series of conformational changes in all four domains, which leads to the open state of the
channel (see Fig. 13-6 ).
[11]
The transmembrane pore of the Na+ channel is thought to be surrounded by the S5 and S6 transmembrane helices
and the short membrane-associated segments between them, designated SS1 and SS2. Amino acid residues in these
short segments are the most critical determinants of the ion conductance and selectivity of the channel.
204
After it opens, the Na+ channel inactivates within a few milliseconds due to closure of an inactivation gate. This
functional gate is formed by the short intracellular loop of protein that connects homologous domains III and IV (see
Fig. 13-6 ). The loop may fold over the intracellular mouth of the transmembrane pore during the process of
inactivation. It may bind to an inactivation gate “receptor” formed by the intracellular mouth of the pore.
Amino acid residues that are important for local anesthetic binding are found in the S6 segment in domain IV. [12]
Hydrophobic amino acid residues near the center and the intracellular end of the S6 segment may interact directly
with bound local anesthetics ( Fig. 13-7 ). Experimental mutation of a large hydrophobic amino acid residue
(isoleucine) to a smaller one (alanine) near the extracellular end of this segment creates a pathway for access of
charged local anesthetic drugs from the extracellular solution to the receptor site. These findings place the local
anesthetic receptor site within the intracellular half of the transmembrane pore of the Na+ channel, with part of its
structure contributed by amino acids in the S6 segment of domain IV.
Figure 13-7 Amino acid residues that are important for local anesthetic binding are found in the S6 segment in domain IV. Hydrophobic amino
acid residues near the center and anesthetics.(From Ragsdale DR, McPhee JC, Schever T, et al: Molecular determinants of state-dependent block
of Na+ channels by local anesthetics. Science 265:1724–1728, 1994.)
FREQUENCY- AND VOLTAGE-DEPENDENCE OF LOCAL ANESTHETIC ACTION
The degree of block produced by a given concentration of local anesthetic depends on how the nerve has been
stimulated and on its resting membrane potential. Thus, a resting nerve is much less sensitive to a local anesthetic
than one that is repetitively stimulated; higher frequency of stimulation and more positive membrane potential cause
a greater degree of anesthetic block. These frequency- and voltage-dependent effects of local anesthetics occur
because the local anesthetic molecule in its charged form gains access to its binding site within the pore only when
the Na+ channel is in an open state and because the local anesthetic binds more tightly to and stabilizes the
inactivated state of the Na+ channel. Local anesthetics exhibit these properties to different extents, depending on
[4] [10]
their pEa , lipid solubility, and molecular size. In general, the frequency-dependence of local anesthetic action
depends critically on the rate of dissociation from the receptor site in the pore of the Na+ channel. A high frequency
of stimulation is required for rapidly dissociating drugs so that drug binding during the action potential exceeds drug
dissociation between action potentials. Dissociation of smaller and more hydrophobic drugs is more rapid, so a
higher frequency of stimulation is required to yield frequency-dependent block. Frequency-dependent block of ion
channels is most important for the actions of antiarrhythmic drugs.
Differential Sensitivity of Nerve Fibers to Local Anesthetics
As a general rule, small nerve fibers are more susceptible to the action of local anesthetics than are large fibers. This
was clearly established for the myelinated A fibers by Gasser and Erlanger, who showed that when cocaine is
[13]
applied to a cutaneous nerve, the delta waves (from small cutaneous afferent fibers) are the first and the alpha waves
(from large fibers) are the last to disappear. The smallest mammalian nerve fibers are nonmyelinated and, on the
whole, are blocked more readily than the larger myelinated fibers. However, the spectrum of sensitivity of the
nonmyelinated fibers overlaps that of the myelinated fibers to some extent because myelinated fibers are blocked
205
before unmyelinated fibers of the same diameter. In general, autonomic fibers, small unmyelinated C fibers
(mediating pain sensations), and small myelinated A delta fibers (mediating pain and temperature sensations) are
blocked before larger myelinated A gamma, A beta, and A alpha fibers (carrying postural, touch, pressure, and
motor information. [14]
Smaller fibers are preferentially blocked because the critical length over which an impulse can propagate passively
is shorter. This is related to the shorter space constant for propagation of voltage changes along smaller
unmyelinated nerves and to the shorter internodal distances along smaller myelinated nerves. In the early stages of
development of anesthetic action, small discrete lengths of the most accessible portions of the nerve trunk are the
first to be exposed to the anesthetic as it diffuses inward along various intrafascicular routes. Smaller fibers with
their shorter critical lengths are thus blocked more quickly by anesthetic solutions than larger fibers. The same
reasoning accounts for the slower recovery of larger fibers when the process is reversed during washout of the local
anesthetic.
In addition, the frequency-dependence of local anesthetic action favors block of small sensory fibers. They generate
long action potentials (≤ 5 ms) at high frequency, whereas motor fibers generate short action potentials (< 0.5 ms) at
lower frequency. These characteristics of sensory fibers in general, and of pain fibers in particular, favor frequency-
dependent block. [15]
The sensitivity of a fiber to local anesthetics is not always determined by whether it is sensory or motor. Although
application of local anesthetic to a muscle-nerve trunk leads to blockade of contractions elicited reflexively before
those elicited by electrical stimulation of the nerve, both muscle proprioceptive afferent and motor efferent fibers are
equally sensitive. These two types of fibers have the same diameter, which is larger than the alpha motor fibers that
supply the muscle spindles. It is the more rapid blockade of these smaller motor fibers rather than of the sensory
fibers that leads to the preferential loss of the muscle reflexes. Similarly, in large nerve trunks, motor fibers usually
are located in the outer portion of the bundle and are more accessible to local anesthetic. Thus, motor fibers may be
blocked before sensory fibers in large mixed nerves.
The differential rate of block exhibited by fibers of varying sizes and firing rates is of considerable practical
importance and appears to explain why local anesthetics affect the sensory functions of most nerves in a predictable
order. Fortunately for the patient, the sensation of pain usually is the first modality to disappear; it is followed in
turn by the sensations of cold, warmth, touch, deep pressure, and, finally, by motor function, although variation
among individuals is great.
Effect of pH
Local anesthetics as unprotonated amines tend to be only slightly soluble. Therefore, they are generally marketed as
water-soluble salts, usually hydrochlorides. Inasmuch as the local anesthetics are weak bases (typical pKa values
range from 8 to 9), their hydrochloride salts are mildly acidic. This property increases the stability of the local
anesthetic esters and any accompanying vasoconstrictor substance. Under usual conditions of administration, the pH
of the local anesthetic solution rapidly equilibrates to that of the extracellular fluids.
Although the unprotonated species of the local anesthetic is necessary for diffusion across cellular membranes, the
cationic species apparently interacts preferentially with Na+ channels. This conclusion has been supported by the
results of experiments on anesthetized mammalian nonmyelinated fibers. In these experiments, conduction could
[16]
be blocked or unblocked merely by adjusting the pH of the bathing medium to 7.2 or 9.6, respectively, without
altering the amount of anesthetic present. The primary role of the cationic form also has been demonstrated clearly
by Narahashi and Frazier, who perfused the extracellular and axoplasmic surface of the giant squid axon with
[9]
tertiary and quaternary amine local anesthetics. However, both protonated and unprotonated molecular forms
possess some anesthetic activity. [10]
Modulation of Local Anesthetic Action
pH ADJUSTMENTS
Local anesthetic drugs, as previously described, pass through the nerve membrane in a nonionized lipid-soluble base
form; when they are within the nerve axoplasm, they then equilibrate into an ionic form that is active within the
sodium channel. The rate-limiting step in this cascade is penetration of the local anesthetic through the nerve
membrane, and all of the commercially available local anesthetic solutions contain very little drug in the nonionized
lipid-soluble base form that can penetrate the membrane. The fraction of the nonionized form, as well as the cationic
206
form present, is determined by the pKa of the solution and the pH of the drug solution. Commercially available
solutions are acidic, and the cationic form largely predominates in solution. This form, however, does not cross
biologic membranes readily. Therefore, to increase the amount of drug in the base form, the clinician can alter either
the pH or the pKa of the drug being injected. Changes in pH of the local anesthetic solution injected can produce a
shortening of onset time, with marked decreases paralleling major pH changes. The limiting factor for the pH
adjustment is the solubility of the base form of the drug.
For instance, DiFazio and colleagues demonstrated that a greater than 50% decrease in onset time for epidural
[17]
anesthesia occurred when the pH of commercially available lidocaine with epinephrine was raised from 4.5 to a pH-
adjusted level of 7.2 by the addition of bicarbonate. Similarly, Hilgier reported a marked improvement in the onset
[18]
time for brachial plexus anesthesia when bupivacaine with epinephrine (pH 3.9) was alkalinized to pH 6.4 before
injection. These relatively large changes in pH resulted in major increases in the amount of base available in
solution for nerve penetration and a marked improvement in onset time for anesthesia. However, when only small
changes in pH can be achieved by the addition of bicarbonate because of the limited solubility of the base, only
small decreases in onset time will occur, as when plain bupivacaine or etidocaine is alkalinized. Increases in the
amount of base in solution achieved by increases in pH are limited by the minimal solubility of the free base in
solution. For each local anesthetic, there is a pH at which the amount of base in solution is maximal (a saturated
solution). Further increases in pH result in a precipitation of the drug, and attempts to further increase the pH of the
local anesthetic solution beyond the saturation point, therefore, do not produce decreases in onset time when such
solutions are applied.
CARBONATION
Another approach to shortening onset time for producing surgical anesthesia has been through the use of carbonated
local anesthetic solutions. The local anesthetic salt is the carbonate, and the solution contains large amounts of
carbon dioxide to maintain a high concentration of the carbonate anion. Carbonated solutions are not available in the
United States, but earlier clinical studies by Bromage suggested that the spread of anesthesia was more extensive
[19] [20]
and a better quality of neural blockade occurred with the carbonated rather than the uncarbonated lidocaine solution.
The use of the carbonate salt for other local anesthetics, such as bupivacaine, has not consistently resulted in
significantly improved onset times. [21]
WARMING THE SOLUTION
Warming of the local anesthetic solutions can also bring about a modified onset time. Although the exact
[22]
mechanism is not entirely clear, a major factor appears to be increased pKa of the local anesthetic, which occurs
when the temperature is increased, resulting in increased local anesthetic base in the solution. An increase in the
anesthetic effectiveness and density of block has also been produced by the addition of opiates, such as fentanyl, to
the local anesthetic solutions.
ADDITION OF OPIATES
Combinations of local anesthetic with an opiate are increasingly used in cases for which one desires sensory
blockade without significant motor block, as in obstetric anesthesia and pain management. The addition of epidural
and intrathecal opiates allows use of lower concentrations of local anesthetic (for more information see Chapter 14 ).
Pharmacologically, opiates do not have local anesthetic activity in the concentrations used clinically, with the
exceptions of meperidine and methadone. Therefore, when opiates are combined with local anesthetics and given
epidurally or spinally, the opiate action is at receptors mediating pain in the dorsal horn of the spinal cord, whereas
the action of the local anesthetic is at the dorsal root ganglion. Thus, the effect of combining the two is the
production of a better quality of analgesia with less risk of systemic toxicity or other undesirable side effects than
when the same degree of analgesia or anesthesia is achieved with a single agent. [23] [24]
Physical Properties of Local Anesthetic Affecting Local Anesthetic Action
In correlating the action of local anesthetics with their physical properties one sees that lipid solubility is associated
in a nonlinear manner with potency of the local anesthetic; that is, the more lipid-soluble drugs are the more potent
local anesthetics. The more potent the drug, the lower the drug concentration required to produce equivalent
anesthesia and analgesia. Clinically, however, local anesthetic potency appears to increase until a lipid partition
coefficient of approximately 4 is achieved. Additional increases above this level are not associated with an increase
207
in potency. This plateau effect with lipid solubility results in part from the increased uptake of local anesthetic with
high lipid solubility into non-neural structures (e.g., fat, blood vessels) adjacent to the target nerves.
The time for the onset of action for local anesthetic drugs can be correlated with the ionization of the drugs for
amide-linked local anesthetics; hence, the lower the pKa of the local anesthetic (the closer the pKa is to body pH), the
shorter the onset time of anesthesia.
PROTEIN BINDING
In the body, local anesthetics are in large part bound to proteins such as plasma proteins and tissue proteins. These
drugs are not pharmacologically active in the bound form and are active only in the free, unbound state. The most
important binding proteins for local anesthetics in plasma are albumin and α1 -acid glycoprotein (AAG). The binding
to albumin has been characterized as a low-affinity and high-capacity binding, whereas the binding to AAG is
characterized as a high-affinity but low-capacity binding; hence, local anesthetics bind to AAG preferentially,
compared with albumin. Binding to AAG is easily saturated with clinically achieved blood levels of local
[25]
anesthetics; once AAG saturation occurs, additional binding is to albumin. Because the binding capacity of albumin
for local anesthetic agents is very large, albumin can bind these drugs without saturation at concentrations in plasma
many times greater than those clinically achieved. The fraction of drug bound to protein in plasma correlates with
the duration of local anesthetic activity: bupivacaine/etidocaine > ropivacaine > mepivacaine > lidocaine > procaine
and 2-chloroprocaine. This suggests that the bond between the local anesthetic molecule and the sodium channel
receptor protein may be similar to that of local anesthetic binding to plasma proteins; that is, similar areas of amino
acid sequences are present.
The degree of protein binding of a particular local anesthetic is concentration-dependent. As the transition from
[26]
AAG binding to albumin binding occurs, the degree of protein binding becomes consistently less. For example, the
commonly accepted value for the degree of protein binding in plasma for lidocaine is 65% (see Fig. 13-6 ); this
assumes a concentration of 1 to 2 µg/mL. As the concentration of lidocaine increases to 5 to 10 µg/mL, the protein
binding decreases to 40% to 50%. In the case of bupivacaine, at the usually achieved clinical concentration of 1 to 2
µg/mL, the drug is about 95% bound. As the concentration increases to toxic levels (4 to 6 µg/mL), the binding
decreases to 80% to 85%. Thus, the free active fraction increases from 5% at the low concentrations of bupivacaine
to 15% to 20% at the higher concentrations. Thus, high plasma concentrations of drug potentiate toxicity by
markedly increasing the amount of active available drug.
The amide-linked local anesthetics are, in general, degraded by the hepatic endoplasmic reticulum, by the initial
reactions involving N-dealkylation, and by subsequent hydrolysis. However, with prilocaine, the initial step is
[27]
hydrolytic, forming o-toluidine metabolites that can cause methemoglobinemia. Caution is indicated in the extensive
use of amide-linked local anesthetics in patients with severe hepatic disease. The amide-linked local anesthetics are
extensively (55% to 95%) bound to plasma proteins, particularly α1-acid glycoprotein. Many factors increase the
concentration of this plasma protein (cancer, surgery, trauma, myocardial infarction, smoking, uremia) or decrease it
(oral contraceptive agents). This results in changes in the amount of anesthetic delivered to the liver for metabolism,
thus influencing systemic toxicity. Age-related changes in protein binding of local anesthetics also occur. The
neonate is relatively deficient in plasma proteins that bind local anesthetics and therefore has greater susceptibility to
toxicity. Plasma proteins are not the sole determinant of local anesthetic availability. Uptake by the lung also may
play an important role in the distribution of amide-linked local anesthetics in the body. [4]
Protein binding is also influenced by the pH of the solution (plasma) so that the percentage of drug bound decreases
as the pH decreases. This is important, because with the development of acidosis (as when a seizure occurs), the
[29] [30]
amount of free active drug remains the same. For example, with lidocaine in the adult, binding at pH 7.4 at a
concentration of 5 to 10 µg/mL is 50%, whereas protein binding with a decrease in pH to 7.0 is only 35%.
Compared with lidocaine, the consequences of acidosis on protein binding of bupivacaine are much greater. As the
binding decreases from 95% to 70% with acidosis, the amount of free bupivacaine increases from 5% to 30% (a
factor of 6), even though the total drug concentration is unchanged. Because of this increase in free drug, acidosis
renders bupivacaine markedly more toxic.
AAG plasma concentrations are also decreased in pregnant women and in newborns. This lowered concentration
[31]
effectively increases the free fraction of bupivacaine in plasma, and it may contribute to the observations made
several decades earlier that (1) bupivacaine toxicity was more prevalent in pregnant patients and (2) the number of
cardiac arrests that took place with inadvertent overdoses of bupivacaine was highest in pregnant women. With the
intermediate-duration local anesthetics, such as lidocaine and mepivacaine, smaller changes in protein binding occur
during pregnancy, and these agents are not associated with any increased risk of cardiac toxicity during pregnancy.
208
Plasma Concentration of Local Anesthetics
Plasma concentration is dependent on the following:
• The dose of the drug administered

• The absorption of the drug from the site injected, which depends on the vasoactivity of the drug, site
vascularity, and whether a vasoconstrictor such as epinephrine has been added to the anesthetic solution
• Biotransformation and elimination of the drug from the circulation
Peak local anesthetic blood levels that develop are directly related to the dose administered at any given site.
Doubling of the dose in the same individual at the same site approximately doubles the blood level achieved. [32] [33]
Administration of the same dose, however, at different sites results in marked differences in the peak blood levels
seen ( Fig. 13-8 ). These differences in blood levels result from differences in the vascularity of the site injected and
the vasoactivity of various concentrations of the local anesthetic used.
Generally, the administration of a 100-mg dose of lidocaine in the epidural or caudal space results in approximately
a 1-µg/mL peak blood level in an average adult. When this dose is injected into less vascular areas (e.g., for brachial
plexus blockade using an axillary approach or for subcutaneous infiltration), a peak blood level of approximately 0.5
µg/mL occurs even
Figure 13-8 Peak blood levels of lidocaine. Average blood levels seen with the injection of 400-mg lidocaine at different sites.(From DeFazio C, Woods A,
Rowlingson J: Drugs commonly used for nerve blocking: Pharmacology of local anesthetic. In Raj P [ ed]: Practical Management of Pain, 3rd ed.
though the 100-mg dose has been the same. In contrast, when lidocaine is injected into a highly vascular area (e.g.,
for an intercostal block), a peak blood level of approximately 1.5 µg/mL occurs with administration of this same
100-mg dose. Peak blood levels after injection into extravascular spaces (e.g., brachial plexus, epidural space,
intercostal region) occur 10 to 30 minutes after administration.
Peak blood levels achieved may also be affected by the rate at which the local anesthetic drug undergoes
biotransformation and elimination. In general, this is the case only for very actively metabolized drugs, such as 2-
chloroprocaine, which has a plasma half-life of about 45 seconds to 1 minute. Rapid biotransformation of 2-
chloroprocaine occurs in plasma after absorption, and very low plasma levels result.
For amide-linked local anesthetic drugs, such as lidocaine, peak blood levels achieved with regional anesthesia
primarily result from absorption. Compared with esters, amide local anesthetic biotransformation is much slower
and is a minor contributor to peak plasma levels. Lidocaine biotransformation half-life is approximately 90 minutes.
To undergo biotransformation, these drugs must get to the liver, a factor limited by hepatic blood flow. Most of the
lidocaine absorbed into the blood stream undergoes redistribution to vessel-rich tissues (e.g., muscle, heart, brain),
and only that portion going to the liver is subjected to biotransformation. Renal excretion of lidocaine is small and
amounts to approximately 3% to 5% of an injected dose in a 24-hour period.
It is important to be aware of the systemic effects of the local anesthetic blood levels that result after various routes
of administration. For lidocaine, blood levels of 1 to 5 µg/mL are considered therapeutic in the treatment of patients
209
with cardiac arrhythmias and as a supplement to general anesthesia. Blood levels of 3 to 5 µg/mL produce systemic
symptoms that include circumoral numbness and buzzing or ringing in the ears. The effects of lidocaine blood levels
on the brain are triphasic and are summarized as follows:
• At low blood levels, the drug has an anticonvulsant action.

• As the concentration of the drug in blood and brain increases, seizures occur.
Undesired Effects of Local Anesthetics
In addition to blocking conduction in nerve axons in the peripheral nervous system, local anesthetics interfere with
the function of all organs in which conduction or transmission of impulses occurs. Thus, they have important effects
on the central nervous system (CNS), the autonomic ganglia, the neuromuscular junction, and all forms of muscle. [28]
The danger of such adverse reactions is proportional to the concentration of local anesthetic achieved in the
[34] [35]
circulation.
CENTRAL NERVOUS SYSTEM
After absorption, local anesthetics may cause stimulation of the CNS, producing restlessness and tremor that may
proceed to clonic convulsions. In general, the more potent the anesthetic, the more readily convulsions may be
produced. Alterations of CNS activity are thus predictable from the local anesthetic agent in question and the blood
concentration achieved. Central stimulation is followed by depression; death is usually caused by respiratory failure.
The apparent stimulation and subsequent depression produced by applying local anesthetics to the CNS presumably
is due solely to depression of neuronal activity; a selective depression of inhibitory neurons is thought to account for
the excitatory phase in vivo. Rapid systemic administration of local anesthetics may produce death with no, or only
transient, signs of CNS stimulation. Under these conditions, the concentration of the drug probably rises so rapidly
that all neurons are depressed simultaneously. Airway control and support of respiration are essential features of
treatment in the late stage of intoxication. Benzodiazepines or rapidly acting barbiturates administered intravenously
are the drugs of choice for both the prevention and arrest of convulsions. The benzodiazepines can be administered
as a premedication.
Although drowsiness is the most frequent complaint that results from the CNS actions of local anesthetics, lidocaine
may produce dysphoria or euphoria and muscle twitching. Moreover, both lidocaine and procaine may produce a
loss of consciousness that is preceded only by symptoms of sedation. Whereas other local anesthetics also show
[28]
the effect on the CNS, cocaine has a particularly prominent impact on mood and behavior.
CARDIOVASCULAR SYSTEM
After systemic absorption, local anesthetics act on the cardiovascular system. The primary site of action is the
[28]
myocardium, where decreases in electrical excitability, conduction rate, and force of contraction occur. In addition,
most local anesthetics cause arteriolar dilatation. The cardiovascular effects usually are seen only after high systemic
concentrations are attained and effects on the CNS are produced. However, on rare occasions, lower doses cause
cardiovascular collapse and death, probably due to either an action on the pacemaker or the sudden onset of
ventricular fibrillation. However, it should be noted that ventricular tachycardia and fibrillation are relatively
uncommon consequences of local anesthetics other than bupivacaine. The effects of local anesthetics such as
lidocaine and procainamide, which also are used as antiarrhythmic drugs, are not discussed in this chapter. Finally, it
should be stressed that untoward cardiovascular effects of local anesthetic agents may result from their inadvertent
intravascular administration, especially if epinephrine also is present.
NEUROMUSCULAR JUNCTION AND GANGLIONIC SYNAPSE
Local anesthetics also affect transmission at the neuromuscular junction. Procaine, for example, can block the
response of skeletal muscle to maximal motor-nerve volleys and to acetylcholine at concentrations where the muscle
responds normally to direct electrical stimulation. Similar effects occur at autonomic ganglia. These effects are due
to block of the ion channel of the acetylcholine receptor. [36] [37]
SMOOTH MUSCLE
210
The local anesthetics depress contractions in the intact bowel and in strips of isolated intestine. They also relax
[38]
vascular and bronchial smooth muscle, although low concentrations may initially produce contraction. Spinal and
[28]
epidural anesthesia, as well as instillation of local anesthetics into the peritoneal cavity, cause sympathetic nervous
system paralysis, which can result in increased tone of gastrointestinal musculature. Local anesthetics may increase
the resting tone and decrease the contractions of isolated human uterine muscle; however, uterine contractions
seldom are depressed directly during intrapartum regional anesthesia.
Metabolism of Local Anesthetics
The metabolic fate of local anesthetics is of great practical importance, because their toxicity depends largely on the
balance between their rates of absorption and elimination. As noted earlier, the rate of absorption of many
anesthetics can be reduced considerably by the incorporation of a vasoconstrictor agent in the anesthetic solution.
However, the rate of destruction of local anesthetics varies greatly, and this is a major factor in determining the
safety of a particular agent. Because toxicity is related to the free concentration of drug, binding of the anesthetic to
proteins in the serum and to tissues reduces the concentration of free drug in the systemic circulation and,
consequently, reduces toxicity. For example, in intravenous regional anesthesia of an extremity, about half of the
original anesthetic dose is still tissue-bound 30 minutes after release of the tourniquet; the lungs also bind large
quantities of local anesthetic.
[27]
ESTER LOCAL ANESTHETICS
Ester-linked local anesthetics are hydrolyzed at the ester linkage in plasma by the plasma pseudocholinesterase. This
plasma enzyme also hydrolyzes natural choline esters and the anesthetically administered drug succinylcholine. The
rate of hydrolysis of ester-linked local anesthetics depends on the type and location of the substitution in the
aromatic ring. For example, 2-chloroprocaine is hydrolyzed about four times faster than procaine, which in turn is
hydrolyzed about four times faster than tetracaine. In the case of 2-chloroprocaine, the half-life in the normal adult is
45 seconds to 1 minute. In individuals with atypical plasma pseudocholinesterase, the rate of hydrolysis of all the
ester-linked local anesthetics is markedly decreased, and a prolonged half-life of these drugs results. Therefore,
whereas the potential for toxicity from plasma accumulation of the ester-linked local anesthetics (e.g., 2-
chloroprocaine) is extremely remote with repeated dosing of the drug in normal individuals, this likelihood should
be considered with the administration of large doses or repeated doses to individuals with the atypical
pseudocholinesterase enzyme. [39]
The hydrolysis of all ester-linked local anesthetics leads to the formation of para-aminobenzoic acid (PABA) or a
substituted PABA. PABA and its derivatives are associated with a low but real potential for allergic reactions. A [40]
history of an allergic reaction to a local anesthetic agent should be considered primarily as resulting from the
presence of PABA or derived from ester-linked local anesthetics. Allergic reactions may also develop from the use
of multiple-dose vials of amide-linked local anesthetics that contain PABA as a preservative. Allergic reactions to
amide-linked local anesthetics without preservatives are rare.
AMIDE LOCAL ANESTHETICS
In contrast to the ester-linked drugs, the amide-linked local anesthetics must be transported by the circulation to the
liver before biotransformation can take place. The two major factors controlling the clearance of amide-linked local
anesthetics by the liver are (1) hepatic blood flow (delivery of the drug to the liver) and (2) hepatic function (drug
extraction by the liver). Factors that decrease hepatic blood flow or hepatic drug extraction result in an increased
elimination half-life.
For example, drugs such as general anesthetics, norepinephrine, cimetidine, propranolol, and calcium channel
blockers (e.g., diltiazem) all can decrease hepatic blood flow and increase the elimination half-life of the amide-
linked local anesthetics. Similarly, decreases in hepatic function caused by a lowering of body temperature,
immaturity of the hepatic enzyme system in the fetus, or liver damage (e.g., cirrhosis) lead to a decreased rate of
hepatic metabolism of the amide local anesthetics.
Renal clearance of unchanged local anesthetics is a minor route of elimination. For example, the amount of
unchanged lidocaine excretion in the urine in the adult is small, roughly 3% to 5% of the total drug administered.
For bupivacaine, the renal excretion of unchanged drug is also small but somewhat higher, in the 10% to 16% range
of the administered dose.
211
Lidocaine metabolism occurs after uptake of the drug by the liver. The primary biotransformation step for lidocaine
is a dealkylization reaction in which an ethyl group is cleaved from the tertiary amine ( Fig. 13-9 ). Interestingly,
this primary step in lidocaine’s biotransformation appears to be only slightly slower in the newborn than in the adult,
indicating functional maturity of this particular enzyme system in the newborn. However, an approximately twofold
increase in the elimination half-life of lidocaine is seen in the newborn, which is believed to result not from
enzymatic immaturity but, instead, to reflect the larger volume of distribution for lidocaine in the newborn. A larger
volume of distribution means that a given dose of drug achieves a lower plasma concentration; thus, less drug would
be delivered to the liver for metabolism per unit time and to the kidney for excretion. Thus, it takes longer to clear a
drug from the body when the drug has a larger volume of distribution.
As with the biotransformation of lidocaine, that of
Figure 13-9 Metabolism of lidocaine illustrating a dealkylating reaction.
bupivacaine progresses with a dealkylization reaction as the primary step ( Fig. 13-10 ). Again, in the newborn, an
increased volume of distribution is present for bupivacaine and a longer half-life is thus anticipated compared with
those expected in the adult. Other reactions in the biotransformation of amide-linked local anesthetics include
hydrolysis of the amide-link portion and oxidation of the benzene-ring portion of the drug. The metabolites thus
formed can be cleared by the kidney as unchanged or conjugated compounds. For example, when hydroxy
derivatives are formed from the oxidation of the benzene ring, they are conjugated and excreted as the glucuronide
or sulfate conjugate.
With mepivacaine, the primary metabolic pathway is the oxidation of the benzene ring portion of the molecule,
producing 3-hydroxy and 4-hydroxymepivacaine. Because this oxidation metabolic pathway is less well developed
in the newborn, mepivacaine metabolism occurs more slowly in the newborn than in the adult.
Ropivacaine metabolism in humans has been studied extensively ( Fig. 13-11 ). At low plasma concentrations, the
drug is primarily metabolized by ring oxidation to 3-hydroxyropivacaine, which is conjugated and excreted in the
urine. Significantly less drug is metabolized by dealkylation at low concentrations to PPX. At high concentrations
[41]
in vitro, dealkylation to PPX becomes an important pathway. The metabolites formed are much less active than
[42]
ropivacaine, the parent compound. Renal clearance of ropivacaine also is relatively small, with only about 1% of the
administered dose excreted unchanged in the urine.
212
The metabolism of local anesthetics, as well as that of many other drugs, occurs in the liver by the cytochrome P-
450 enzymes (CYP-450). This enzyme family has been subdivided into a number of isoenzymes, with those
predominantly involved in local anesthetic biotransformation reactions being CYP-1A2 and CYP-3A4. The
predominant cytochrome P-450 isoenzyme present in the human liver is CYP-3A4. This isoenzyme accounts for
approximately 30% to 60% of the total cytochrome P-450 content in the liver. It is primarily responsible for the
dealkylation reaction in drug metabolism, which, in the case of lidocaine, produces monoethylglycinexylidide
(MEGX); with bupivacaine and ropivacaine, PPX is produced.
As noted, the dealkylation reaction is the predominant metabolic reaction in the metabolism of lidocaine and
bupivacaine. This isoenzyme also metabolizes many other drugs, including nifedipine, felodipine, diazepam,
warfarin, and cyclosporine. The other major isoenzyme in the liver is CYP-1A2, which accounts for approximately
10% of the total cytochrome P-450 present in the liver. This isoenzyme produces primarily the hydroxymetabolites
of the local anesthetics through an oxidation of the benzene ring. This is a primary pathway in the metabolism of
mepivacaine and ropivacaine. Despite the presence of large amounts of the CYP-3A4 isoenzyme in the liver, it is
not always the predominant pathway for drug metabolism, because it apparently has a lower affinity for local
anesthetics than CYP-1A2. The higher affinity for ropivacaine has been identified with the CYP-1A2 isoenzymes
and, with ropivacaine, the predominant biotransformation pathway leads to the formation of a 3-hydroxyropivacaine
derivative. Similar predominant CYP-1A2 activity
[41]
Figure 13-10 Metabolism of bupivacaine.
213
Figure 13-11 Schematic diagram showing the two major pathways of ropivacaine metabolism.
is likely for mepivacaine, because the metabolites for this drug are the 3-hydroxy and 4-hydroxy derivatives of the
parent compound.
The possibility of clinical drug interactions at the cytochrome P-450 enzyme level exists when other drugs
administered at the same time are preferentially metabolized by the CYP-1A2 isoenzyme. This probably occurs
because of the low content and high drug affinity of this isoenzyme in the liver. In contrast, the liver has a large
capacity for metabolizing drugs by the CYP-3A4 catalyzed reactions. This makes drug interactions with the CYP-
3A4 isoenzyme very unlikely. The CYP-1A2 isoenzymes also are inducible by many substrates, and the activity of
this isoenzyme may increase after the administration of enzyme inducers. Potent inhibitors of this isoenzyme include
fluvoxamine, which is available in Europe as a psychotropic drug. Coadministration of local anesthetics metabolized
by CYP-1A2 and such inhibitors can lead to marked decreases in drug metabolism. [43]
Biotransformation of local anesthetics such as bupivacaine and lidocaine, which involves a dealkylation reaction as
the primary step produced by the cytochrome CYP-3A4 isoenzyme, can occur in newborns at essentially the same
rate as in adults.
Central Nervous System Toxicity
HISTORY
The long history of spinal anesthesia and the safety of local anesthetics are aptly documented by the
classic studies of Dripps and Vandam, Phillips and coworkers, and, more recently, Horlocker and
[44] [45] [46]
colleagues. The Horlocker study (data collection stopped as of June 1990) reported a frequency of
[47]
persistent sensory and motor deficits in the range of 0.005% to 0.7%, as had the previous, large-survey
studies. None of these reviews encompassed the recent period of time, when serious questions have
surfaced about the neurotoxicity of local anesthetics. Previous consideration had been given to this issue
with regard to 2-chloroprocaine, but this was settled by a change in the drug’s formulation that
eliminated the offending agent. In a 1985 rabbit study of the toxicity of clinically used anesthetics,
[48] [49]
Ready and associates seemed to exonerate the commercial preparations of local anesthetics, although
[50]
supernormal concentrations of lidocaine and tetracaine in their model did produce irreversible neural
injury and histologic change.
Selander argued in 1993, based on a review of reported complications and animal data, that all local
[51]
anesthetics could be neurotoxic and suggested that the concentration of the drug and the time of exposure
were crucial factors in the pathologic changes. He commented that neural trauma and ischemia were
additional factors to be considered (while acknowledging that most cases of alleged neurotoxicity are
multifactorial).
The 1991 sentinel report of Rigler and coauthors concerning cauda equina syndrome (consisting of
[52]
varying degrees of bladder and bowel incontinence, perineal sensory loss, and lower extremity weakness)
after continuous spinal anesthetic genuinely refocused scientific and clinical attention on the significance
214
of local anesthetic neurotoxicity. The practice of placing microbore catheters for continuous spinal
anesthesia had become popular. In this report, three patients who received 175 to 300 mg of intrathecal
lidocaine and one who received a total of 37 mg of tetracaine manifested signs and symptoms of cauda
equina syndrome. The contributory factors highlighted were nonhomogenous spread of the injectate
secondary to slow injections through small needles or catheters, with high concentrations of local
anesthetic subsequently being present secondary to the directional spread of the local anesthetic solution
proportional to the hyperbaricity.
Since the mid-1990s, many reports have been published about the clinical manifestations of local
anesthetic toxicity, variously called transient neurologic syndrome (TNS) or transient radicular
irritation (TRI). Schneider and coworkers published four more cases of possible transient neurologic
[53]
toxicity associated with the use of hyperbaric 5% lidocaine in four women undergoing short
gynecological surgical procedures in the lithotomy position. It was particularly significant that these
patients received low-volume injections of lidocaine that were further diluted in cerebrospinal fluid
rather than the high total doses through microbore catheters received by the patients in the Rigler study.
The etiologic possibilities for TNS were amplified by the Schneider study, which suggested that
positional stretching of the cauda equina was contributory because the position could increase the
vulnerability of certain nerve roots to the drugs. Even after enough data had been accumulated that the
United States (U.S.) Food and Drug Administration (FDA) removed microbore catheters from clinical
practice in May 1992, reports of local anesthetic toxicity did not disappear. [54]
Hampl and colleagues reported on 270 patients who had undergone gynecologic or obstetric procedures
[54]
under spinal anesthesia with either 5% lidocaine in 7.5% glucose or 0.5% bupivacaine in 8.5% glucose.
When TNS symptoms were sought on postoperative day 3, 37% of the patients who had received
lidocaine but only one of 150 patients who had received bupivacaine had such symptoms. It was
suggested that the symptoms were related to a specific drug. More important, a standardized description
of TNS was proposed: “Transient neurologic symptoms were defined as pain and/or dysesthesia in the
buttocks, thighs, or lower limbs occurring after recovery from the anesthetic.” This study was critically
reviewed by Carpenter, who detailed variations in anesthetic technique, surgical procedure, and
[55]
intraoperative management; the lack of randomization of patients in the drug groups; and the nonuse of
equipotent doses of local anesthetics as factors to be considered in the interpretation of the results. He
also raised the pertinent question as to the actual significance of the syndrome, because no neurologic
deficits or functional impairments have been reported and symptoms do not persist.
Pollock and coauthors performed a prospective, randomized, double-blind study of 159 patients
[56]
undergoing arthroscopy or inguinal hernia repair with equipotent doses of 5% hyperbaric lidocaine, 2%
isobaric lidocaine, or 0.5% bupivacaine. TRI symptoms were not present for more than 4 days in any of
the patients. The authors’ findings that only patients who received lidocaine had TRI symptoms and that
the incidence was higher in patients having arthroscopy seemed to maintain attention on spinal lidocaine
and also suggested that surgical positioning might be a factor in the incidence of the syndrome. The
reports documenting that concentrations of lidocaine less than 5% do not eliminate TRI were
[57] [58]
supported by the Pollock study, in that 16% of patients in both groups receiving lidocaine had TRI
symptoms. If one chooses to avoid lidocaine because of concerns about neurotoxicity, it is not
[56]
reassuring to note that TRI has been reported with bupivacaine, tetracaine, and hyperbaric
[59] [60]
mepivacaine. In 1998, Hampl and coinvestigators suggested that prilocaine might be a suitable
[61] [62]
alternative to lidocaine when a short-acting local anesthetic is needed. In their study, the incidence of
TRI was equivalent for bupivacaine and prilocaine and definitely less than that associated with lidocaine.
It is prudent to question whether the additives in the local anesthetics used clinically contribute to
neurotoxicity. Initially, epinephrine was not considered to be associated with TRI, but more recent
[63] [64]
basic science data have raised suspicion. Sakura and coworkers provoked the same concerns about
[65] [66]
phenylephrine (Neo-Synephrine). The glucose that is added to local anesthetics to make them hyperbaric
potentially creates a hyperosmolar injury, but this has not been confirmed in studies by Sakura or Hampl
and their colleagues. [67] [68]
Large-scale studies should be able to continue to chronicle the safety of regional anesthesia. Auroy and
coworkers reported on more than 100,000 regional anesthetic procedures in a survey of French
[68]
anesthesiologists from whom detailed reports of serious complications from regional anesthesia were
sought. In part, the study showed that spinal anesthesia is still associated occasionally with cardiac
[68]
arrest and neural injury. Two thirds of patients with neural injury had pain on injection or paresthesias.
Eisenach, commenting on this report, declared that the data showed that regional anesthesia was safe
[69]
215
and that complications occurred rarely, even when the needle was being placed by an inexperienced
practitioner.
This conclusion reconfirms that when regional anesthesia is attentively provided, most patients
experience little other than the expected effects. Occasionally, and sometimes for reasons not completely
understood, unexpected clinical situations arise. We must then maintain our vigilance to observe such
events, our integrity to report such events, and our scientific curiosity to seek to explain them.
PHARMACODYNAMICS OF CENTRAL NERVOUS SYSTEM TOXICITY
In humans, blood levels of lidocaine associated with the onset of seizures appear to be in the range of 10 to 12
µg/mL. At these blood levels, inhibitory pathways in the brain are selectively impeded, and facilitatory neurons can
function unopposed. The seizures that result appear to originate in the amygdala and hippocampus. With lidocaine,
[70]
prodromal symptoms appear before the onset of seizures and usually include slow speech, jerky movements,
tremors, and hallucinations. Although these prodromal symptoms are diagnostically helpful before lidocaine CNS
toxicity, they are less consistently seen when other local anesthetics approach their seizure threshold. As the blood
levels of lidocaine are increased further, respiratory depression becomes significant at 20 to 25 µg/mL, and at much
higher levels, cardiotoxicity is manifest. In contrast, for bupivacaine, blood levels of approximately 4 µg/mL result
in seizures, and blood levels of approximately 4 to 6 µg/mL are associated with cardiac toxicity. This is reflective of
a much lower therapeutic index for bupivacaine compared with lidocaine in terms of cardiac toxicity.
Treatment of seizures resulting from local anesthetics consists primarily of preventing the detrimental effects of
hypoxia that result from seizure activity. The primary concern should be for adequate ventilation with 100% oxygen.
Secondarily, suppression of the seizures can be achieved by raising the seizure threshold with a small intravenous
dose of either thiopental, 50 to 100 mg, or a benzodiazepine, such as midazolam, 1 to 2 mg, or diazepam, 5 to 10
mg.
Because cardiac output and cerebral blood flow are markedly increased during seizure activity when cardiotoxicity
has not developed, high levels of local anesthetics in the brain rapidly dissipate and are redistributed to other tissue
compartments; however, if drug levels are high enough to cause significant cardiotoxicity, cardiac output is greatly
diminished and redistribution is delayed and less helpful. The use of thiopental in this situation can be of concern
because it may further depress myocardial function and should be administered judiciously if at all.
For patients with severe toxicity, rapid tracheal intubation is performed, usually facilitated by a rapid-acting
neuromuscular blocking drug. An additional benefit of muscle paralysis is the cessation of the acidosis produced by
tonic-clonic seizure muscle activity. Failure to stop seizure activity can lead to progressive acidosis, which can
further potentiate the toxicity of the circulating and intracellular local anesthetic by decreasing the fraction of drug
bound to proteins and thus increasing the active free fraction (and concentration) of the local anesthetic. [71] [72] [73]
Cardiotoxicity
Concern by anesthesiologists for the cardiotoxicity of the long-acting local anesthetics, such as bupivacaine and
etidocaine, followed reports of cardiac arrests with difficult resuscitations in a number of patients. These effects
occurred predominantly in pregnant patients. Apparently, these patients had high blood levels of local anesthetic
[74] [75]
from an unintended intravascular injection of large amounts of drug. Most frequently, this occurred while an
epidural anesthetic was being administered or resulted from tourniquet failure during intravenous regional
anesthesia.
In subsequent animal studies of local anesthetic cardiotoxicity, all local anesthetics caused a dose-dependent
depression of contractility of cardiac muscle. This cardiodepressant effect on contractility paralleled the anesthetic
[76]
potency of the local anesthetic in blocking nerves. Therefore, bupivacaine, which is four times more potent than
[77]
lidocaine in blocking nerves, is also four times more cardiodepressant on cardiac contractility. Cases in which the
patient died with a bupivacaine overdose, however, have been characterized by a progressive prolongation of
ventricular conduction as evidenced by a widening of the QRS complex followed by the sudden onset of
arrhythmias such as ventricular fibrillation. Possibly, the delay in ventricular conduction predisposes the patient to
reentrant phenomena, leading to ventricular dysrhythmias.
Experimental in vitro studies have shown that all local anesthetics can produce a dose-dependent depression of
cardiac conduction velocity, including the intra-atrial, atrioventricular nodal, His-Purkinje, and intraventricular
216
pathways. When the potential for producing this electrophysiologic toxicity was evaluated, bupivacaine was
approximately 16 times more toxic than lidocaine. This effect, therefore, is out of proportion to the anesthetic
[75]
potency of the drug in blocking peripheral nerve conduction.
In studies comparing bupivacaine and ropivacaine, bupivacaine was approximately twice as toxic as ropivacaine in
producing these cardiotoxic effects. Recent experimental studies evaluating the S isomer of bupivacaine, in
[78]
contrast to the racemic mixture of bupivacaine (the commercial preparation), have shown that the S isomer of
bupivacaine also is less arrhythmogenic than the R isomer or the racemic mixture of bupivacaine. Further studies
[79]
are ongoing to assess the commercial potential for the S-bupivacaine.
In vitro studies have demonstrated that local anesthetics block cardiac sodium channels as well as cardiac calcium
channels, and the blockade of these channels is better tolerated for lidocaine than for either bupivacaine or
ropivacaine. The best explanation for the differences in toxicity for the local anesthetics was given by Clarkson and
Hondeghem, who demonstrated that with depolarization, lidocaine rapidly enters and leaves the open cardiac
[80]
sodium channels and thus has little long-term cardiac-blocking effects at slow or normal rates. This is described as a
fast-in, fast-out effect of the drug. In contrast, bupivacaine also rapidly enters the sodium channel, but because of
differences in binding, it is slow to leave and has been classified as a fast-in, slow-out local anesthetic. Thus,
bupivacaine strongly blocks inactivated open cardiac channels, and the unbinding of the drug from the channel
proteins is slow and thus does not allow an adequate time for recovery during diastole. Both slowed and differential
nerve conduction predispose to reentrant dysrhythmias and ventricular fibrillation.
Studies comparing levobupivacaine to racemic bupivacaine indicate that these drugs produce a similar depressant
effect on cardiac contractility but different effects on conduction. At high concentrations, racemic bupivacaine was
associated with QRS widening and ventricular fibrillation, whereas similar doses of levobupivacaine failed to
produce the fatal dysrhythmias seen with the racemic mixture. This has been interpreted as indicating that R-
[79]
bupivacaine is the major culprit in the cardiotoxicity of this drug.
Some investigators have also speculated that cardiac dysrhythmias may be mediated by local anesthetic effects on
the CNS. This is based on animal studies in which the local anesthetic was infused directly into the ventricles of the
brain and cardiac arrhythmias occurred. These arrhythmias were more common when bupivacaine rather than
[81] [82]
lidocaine was used. Although the CNS effects cannot be excluded, these effects are less likely to be the primary
event in the production of arrhythmias. In a separate study using an animal model in which the local anesthetic was
injected directly into the left anterior descending coronary artery (LAD), the direct effects of various drugs on the
left ventricle were evaluated. Independent of the very small CNS effects, local anesthetics administered in the
[75]
LAD caused slowing of ventricular conduction and, with sufficient doses, produced ventricular fibrillation.
Increases in the cardiotoxicity of local anesthetics can also be further enhanced by the presence of acidosis, hypoxia,
hypercarbia, and hyperkalemia. With major overdoses of bupivacaine, a clinical picture of cardiovascular
[72] [73]
collapse may result in which the drug-induced myocardial depression is accompanied by systemic vasodilatation and
extreme hypotension. It is unlikely that this vasodilatation is produced by the circulating local anesthetic, because in
animal studies, these agents produce vasoconstriction at concentrations associated with clinical toxicity. In these
studies, vasodilatation did not occur until the concentrations used were several orders of magnitude higher. It is [83]
more likely that the peripheral vasodilatation resulted from severe hypoxia and acidosis. This makes it all the more
important to take action to reverse these physiologic derangements as rapidly as possible by providing adequate
ventilation, seizure termination, fluid support, vasopressor therapy, antiarrhythmic therapy (i.e., with bretylium or
magnesium), and inotropic support of the myocardium.
As a result of bupivacaine administration, cardiotoxicity may be increased during pregnancy. In one study, lower
doses of bupivacaine were required to produce cardiovascular collapse in pregnant compared with nonpregnant
sheep. When this study was repeated, however, this initial finding was not confirmed.
[78] [84]
CNS convulsions occurred in sheep with significantly lower doses of bupivacaine than with ropivacaine. Similarly,
cardiotoxicity required markedly larger doses of ropivacaine than bupivacaine.
Successful animal resuscitation after massive bupivacaine overdoses has required multiple doses of epinephrine and
atropine. It is beneficial to administer epinephrine directly into the central circulation in patients with shock and
hypoperfusion. In the absence of a central venous catheter, this can be achieved by the administration of more drug
to the heart than when administration is through a peripheral intravenous catheter. Bretylium has also been
suggested for the treatment of serious ventricular tachycardias arising from a local anesthetic overdose of
bupivacaine. [85]
217
Local Anesthetics
These drugs are classified as either ester or amide agents. Clinically useful ester agents are cocaine, procaine, 2-
chloroprocaine, and tetracaine.
COCAINE
Chemistry
Cocaine occurs in abundance in the leaves of the coca shrub and is an ester of benzoic acid and methylecgonine.
Ecgonine is an amino alcohol base closely related to tropine, the amino alcohol in atropine. It has the same
fundamental structure as the synthetic local anesthetics.
Pharmacologic Actions and Preparations
The clinically desired actions of cocaine are the blockade of nerve impulses as a consequence of its local anesthetic
properties, and local vasoconstriction secondary to inhibition of local norepinephrine reuptake. Toxicity and the
potential for abuse have steadily decreased the clinical uses of cocaine. Its high toxicity is due to block of
catecholamine uptake in both the CNS and peripheral nervous system. Its euphoric properties are due primarily to
inhibition of catecholamine uptake, particularly dopamine, at CNS synapses. Other local anesthetics do not block the
uptake of norepinephrine and do not produce the sensitization to catecholamines, vasoconstriction, or mydriasis
characteristic of cocaine. Currently, cocaine is used primarily to provide topical anesthesia of the upper respiratory
tract, where its combined vasoconstrictor and local anesthetic properties provide anesthesia and shrinking of the
mucosa with a single agent. Cocaine hydrochloride is used as a 1%, 4%, or 10% solution for topical application. For
most applications, the 1% or 4% preparation is preferred to reduce toxicity. Because of its abuse potential, cocaine is
listed as a schedule II drug by the U.S. Drug Enforcement Agency.
PROCAINE
Procaine (Novocain), introduced in 1905, was the first synthetic local anesthetic and is an amino ester ( Fig. 13-12 ).
Although it formerly was used widely, its use now is confined to infiltration anesthesia and, occasionally, diagnostic
nerve blocks. This is because of its low potency, slow onset, and short duration of action. Although its toxicity is
fairly low, it is hydrolyzed in vivo to produce PABA, which inhibits the action of sulfonamides. Thus, large doses
should not be administered to patients taking sulfonamide drugs.
2-CHLOROPROCAINE
2-Chloroprocaine (Nesacaine), an ester local anesthetic introduced in 1952, is a chlorinated derivative of procaine
(see Fig. 13-12 ). Its major assets are its rapid onset and short duration of action and its reduced acute toxicity due to
its rapid metabolism (plasma half-life approximately 25 s). Enthusiasm for its use has been tempered by reports of
prolonged sensory and motor block after epidural or subarachnoid administration of large doses.
218
Figure 13-12 Local anesthetic chemical structures illustrating ester linkage.
This toxicity appears to have been a consequence of low pH and the use of sodium metabisulfite as a preservative in
earlier formulations. There are no reports of neurotoxicity with newer preparations of chloroprocaine, which contain
calcium ethylenediaminetetraacetic acid (EDTA) as the preservative, although these preparations also are not
recommended for intrathecal administration. A higher-than-expected incidence of muscular back pain after epidural
anesthesia with 2-chloroprocaine also has been reported. This back pain is thought to be due to tetany in the
[86]
paraspinal muscles, which may be a consequence of Ca2+ binding by the EDTA included as a preservative; the
incidence of back pain appears to be related to the volume of drug injected and its use for skin infiltration.
Pharmacology and Pharmacodynamics
2-chloroprocaine is procaine with the addition of a chlorine group to the benzene ring. This drug has a very rapid
onset of action and a short duration of activity (30–60 min). Once absorbed into the circulation, the drug is rapidly
metabolized. The approximate half-life in plasma in adults is 45 seconds to 1 minute; hence, it is the most rapidly
metabolized local anesthetic currently used. Because of this extremely rapid breakdown in plasma, it has very low
potential for systemic toxicity and has been particularly attractive to obstetric anesthesiologists for use when
elevated maternal blood levels of local anesthetic can cause major problems for the fetus and mother. This drug is
also frequently used for epidural and peripheral blocks in an ambulatory care setting when short duration of
anesthesia is needed and rapid recovery is highly desirable.
The epidural use of this drug, however, has been limited because of several reported problems. Prolonged and
profound motor and sensory deficits occurred with the unintentional subarachnoid injection of the original 2-
chloroprocaine commercial preparation marketed with the preservative bisulfite. The classic work by Gissen and
coworkers and Wang and colleagues demonstrated that bisulfite in the presence of a highly acidic solution
[48] [87]
releases sulfur dioxide (SO2 ), which equilibrates in solution into sulfurous acid, which is neurotoxic. Gissen
postulated that the injection of the highly acidic commercial 2-chloroprocaine (pH 3) solution into the spinal sac
resulted in the slow formation of and prolonged exposure to sulfurous acid, causing spinal cord damage. More
recently, a 2-chloroprocaine preparation was released in which the bisulfite was removed and EDTA was substituted
as the preservative. This change, however, has not been totally satisfactory because there appears to be a significant
occurrence of back muscle spasm after epidural application of this formulation. It has been postulated that the
[88]
EDTA in this commercial preparation binds calcium and causes spasm in the paraspinal muscles.
A new 2-chloroprocaine commercial preparation has been released from which all preservatives have been removed.
Initial studies with this formulation appear to be promising. No preparations of 2-chloroprocaine are recommended
for either spinal or intravenous regional anesthesia.
TETRACAINE
Tetracaine is the butyl amino derivative of procaine (see Fig. 13-12 ). Tetracaine (Pontocaine), introduced in 1932,
is a long-acting amino ester. It is significantly more potent and has a longer duration of action than procaine.
219
Tetracaine has an increased toxicity because it is more slowly metabolized than the other commonly used ester local
anesthetics. Currently, it is widely used in spinal anesthesia when a drug of long duration is needed. Tetracaine also
is incorporated into several topical anesthetic preparations. With the introduction of bupivacaine, tetracaine is rarely
used in peripheral nerve blocks because of its slow onset and toxicity.
The drug is a potent long-acting local anesthetic and has been widely used mainly for spinal anesthesia in a dose of
6 to 15 mg in adults. Clinically, such drug administration produces a high degree of motor blockade. Tetracaine has
also been used as a 0.2% to 0.5% solution for epidural anesthesia; however, it is not consistently considered
adequate for this purpose because of its slow onset of action and its tendency to produce spotty sensory anesthesia.
Many otolaryngologists use this drug to produce topical anesthesia in the upper airway.
Amide Local Anesthetics
LIDOCAINE
Lidocaine (Xylocaine), introduced in 1948, is now the most widely used local anesthetic. The chemical structure of
lidocaine is shown in Figure 13-13 .
Pharmacologic Actions
The pharmacologic actions that lidocaine shares with other local anesthetic drugs have been described widely.
Lidocaine produces faster, more intense, longer lasting, and more extensive anesthesia than does an equal
concentration of procaine. Unlike procaine, it is an aminoethylamide and is the prototypical member of this class of
local anesthetics. It is a good choice for individuals sensitive to ester-type local anesthetics.
Absorption, Fate, and Excretion
Lidocaine is absorbed rapidly after parenteral administration and from the gastrointestinal and respiratory tracts.
Although it is effective when used without any vasoconstrictor, in the presence of epinephrine, the rate of absorption
and the toxicity are decreased, and the duration of action usually is prolonged. Lidocaine is dealkylated in the liver
by mixed-function oxidases to monoethylglycine xylidide and glycine xylidide, which can be metabolized further to
monoethylglycine and xylidide. Both monoethylglycine xylidide and glycine xylidide retain local anesthetic activity.
In human beings, about 75% of xylidide is excreted in the urine as the further metabolite, 4-hydroxy-2,6-
dimethylaniline. [27]
Toxicity
The side effects of lidocaine seen with increasing dose include drowsiness, tinnitus, dysgeusia, dizziness, and
twitching. As the dose increases, seizures, coma, and respiratory depression and arrest will occur. Clinically
significant cardiovascular depression usually occurs at serum lidocaine levels that produce marked CNS effects. The
metabolites monoethylglycine xylidide and glycine xylidide may contribute to some of these side effects.
Clinical Uses
Lidocaine has a wide range of clinical uses as a local anesthetic; it has utility in almost any application in which a
local anesthetic of intermediate duration is needed. Lidocaine also is used as an antiarrhythmic agent.
MEPIVACAINE
Mepivacaine (Carbocaine, others), introduced in 1957, is an intermediate-acting amino amide (see Fig. 13-13 ).
220
Figure 13-13 Local anesthetic chemical structures illustrating amide linkage and indicating an asymmetrical carbon atom (asterisk) when
present.
Its pharmacologic properties are similar to those of lidocaine. Mepivacaine, however, is more toxic to the neonate
and thus is not used in obstetric anesthesia. The increased toxicity of mepivacaine in the neonate is related not to its
slower metabolism in the neonate, but to ion trapping of this agent because of the lower pH of neonatal blood and
the pKa of mepivacaine. Despite its slow metabolism in the neonate, it appears to have a slightly higher therapeutic
index in adults than lidocaine. Its onset of action is similar to that of lidocaine and its duration slightly longer (about
20%) than that of lidocaine in the absence of a coadministered vasoconstrictor. Mepivacaine is not effective as a
topical anesthetic.
PRILOCAINE
Prilocaine (Citanest) is an intermediate-acting amino amide (see Fig. 13-13 ). It has a pharmacologic profile similar
to that of lidocaine. The primary differences are that it causes little vasodilatation and thus can be used without a
vasoconstrictor, if desired, and its increased volume of distribution reduces its CNS toxicity, making it suitable for
intravenous regional blocks (see later). It is unique among the local anesthetics for its propensity to cause
methemoglobinemia. This effect is a consequence of the metabolism of the aromatic ring to o-toluidine.
Development of methemoglobinemia is dependent on the total dose administered, usually appearing after a dose of 8
mg/kg. In healthy persons, methemoglobinemia is usually not a problem. If necessary, it can be treated by the
intravenous administration of methylene blue (1 to 2 mg/kg). Methemoglobinemia after prilocaine administration
has limited its use in obstetric anesthesia because it complicates evaluation of the newborn. Also,
methemoglobinemia is more common in neonates because of decreased resistance of fetal hemoglobin to oxidant
stresses and the immaturity of enzymes in the neonate that convert methemoglobin back to the ferrous state. The
amino amide agents are metabolized primarily in the liver. Patient age may influence the physiologic disposition of
[35]
local anesthetics.
ETIDOCAINE
Etidocaine (Duranest), introduced in 1972, is a long-acting amino amide (see Fig. 13-13 ). Its onset of action is
faster than that of bupivacaine and comparable with that of lidocaine, yet its duration of action is similar to that of
bupivacaine. Compared with bupivacaine, etidocaine produces preferential motor blockade. Thus, although it is
useful for surgery requiring intense skeletal muscle relaxation, its utility in labor or postoperative analgesia is
limited. Its cardiac toxicity is similar to that of bupivacaine (see earlier).
Etidocaine is structurally similar to lidocaine (see Fig. 13-13 ), with alkyl substitution on the aliphatic connecting
group between the hydrophilic amine and the amide linkage. This increases the drug’s lipid solubility and results in
221
a drug more potent than lidocaine that has a very rapid onset of action and a prolonged duration of anesthesia.
Because etidocaine produces rapid profound motor and sensory blockade at all of its clinical concentrations, it is
unacceptable for obstetric anesthesia when motor blockade is undesirable. In addition, motor blockade has been
observed in many instances to far outlast sensory blockade, thus causing significant postoperative patient anxiety
during recovery.
Some practitioners have found it helpful to take advantage of the rapid onset of anesthesia and the significant motor
blocking effect associated with etidocaine administration by using it for lengthy procedures to induce epidural
anesthesia and then substituting bupivacaine or lidocaine for subsequent doses to maintain an adequate sensory level
without undue prolongation of motor block on recovery. The addition of epinephrine to etidocaine solutions
produces a 50% increase in duration of brachial plexus blockade but only a 10% to 15% increase in duration of
epidural blockade. This effect, as with bupivacaine, stems from significant solubility into the high fat content of the
epidural space by a highly lipid-soluble drug. [63]
BUPIVACAINE
Bupivacaine (Marcaine, Sensorcaine), introduced in 1963, is a widely used amide local anesthetic; its structure is
similar to that of lidocaine, except the amine-containing group is a butyl piperidine (see Fig. 13-13 ). It is a potent
agent capable of producing prolonged anesthesia. Its long duration of action plus its tendency to provide more
sensory than motor block has made it a popular drug for providing prolonged analgesia during labor or the
postoperative period. With use of indwelling catheters and continuous infusions, bupivacaine can be used to provide
several days of effective analgesia.
Bupivacaine was developed as a modification of mepivacaine. Its structural similarities to mepivacaine are readily
apparent. Bupivacaine has a butyl (four-carbon substitution) group on the hydrophilic nitrogen.
Bupivacaine has made a contribution to regional anesthesia second in importance only to lidocaine. It is one of the
first of the clinically used local anesthetic drugs to provide good separation of motor and sensory blockade after
administration. The onset of anesthesia and the duration of action are long and can be further prolonged by the
addition of epinephrine in areas with a low fat content. Only small increases in duration are seen when bupivacaine
is injected into areas with a high fat content. For example, a 50% increase in duration of brachial plexus blockade
(an area of low fat content) occurs after the addition of epinephrine to bupivacaine solutions; in contrast, only a 10%
to 15% increase in duration of epidural anesthesia results from the addition of epinephrine to bupivacaine solutions,
because the epidural space has a high fat content.
Toxicity
Bupivacaine is more cardiotoxic than equieffective doses of lidocaine. Clinically, this is manifested by severe
ventricular arrhythmias and myocardial depression after inadvertent intravascular administration of large doses of
bupivacaine. The enhanced cardiotoxicity of bupivacaine probably is due to multiple factors. Lidocaine and
bupivacaine both block cardiac Na+ channels rapidly during systole. However, bupivacaine dissociates much more
slowly than lidocaine during diastole, so a significant fraction of Na+ channels remain blocked at the end of diastole
(at physiologic heart rates) with bupivacaine. Thus, the block by bupivacaine is cumulative and substantially
[80]
greater than would be predicted by its local anesthetic potency. At least a portion of the cardiotoxicity of
bupivacaine may be mediated centrally, because direct injection of small quantities of bupivacaine into the medulla
can produce malignant ventricular arrhythmias. Bupivacaine-induced cardiotoxicity can be very difficult to treat,
[81]
and its severity is enhanced in the presence of acidosis, hypercarbia, and hypoxemia.
Clinical Uses
In the United States, bupivacaine is used mainly for obstetric anesthesia and postoperative pain control when
analgesia without significant motor blockade is highly desirable and achievable with low bupivacaine
concentrations. In contrast to lidocaine, however, when high blood levels occur with bupivacaine, a higher incidence
of cardiotoxic effects is seen. Bupivacaine has a poorer therapeutic index than lidocaine in producing
electrophysiologic toxicity of the heart. Although bupivacaine metabolism is slower in the fetus and newborn than
[89]
in the adult, active biotransformation is accomplished by the fetus and newborn.
A second major role of bupivacaine is in subarachnoid anesthesia. It produces very reliable onset of anesthesia
within 5 minutes, and the duration of anesthesia is approximately 3 hours. In many ways, it is similar to tetracaine;
however, the dose of bupivacaine required is somewhat larger, specifically, 10 mg of tetracaine is approximately
equal to 12 to 15 mg of bupivacaine. The onset of sympathetic blockade after spinal anesthesia appears to be more
222
gradual with bupivacaine than with tetracaine. Also, the sensory blockade produced by bupivacaine lasts longer than
the motor blockade, which is in contrast to what occurs with etidocaine and tetracaine. Bupivacaine can be used for
subarachnoid anesthesia in either the glucose-containing hyperbaric solution (0.75%) or with the isobaric solution
by using the drug packaged for epidural use as a 0.25% or a 0.5% concentration.
Newer Local Anesthetics: Chiral Forms
An area of newfound importance for anesthesiologists is in the use of stereoisomers of drugs to take advantage of
differences in activity or toxicity of the isomers. For stereoisomerism to be present, an asymmetrical carbon (a
carbon atom in the molecule that has four distinctly different substitution groups) must be present in the molecule.
Stereoisomers are possible for the local anesthetics etidocaine, mepivacaine, bupivacaine, prilocaine, and,
ropivacaine, and some of these drugs have differences in potency or toxicity for the isomers. For these local
anesthetics, the asymmetrical carbons are indicated in Figure 13-14 by an asterisk.
In the older literature, isomers were described as L and D on the basis of chemical configuration and as (+) or (−) on
the basis of topical rotation (i.e., L [+] or D [−]). More recent literature describes isomers as R or S, and the optical
rotation is still included in the parentheses as (+) and (−). R and S basically correspond to the D and L in the older
nomenclature.
As a rule, when differences between the activity of isomers are present for local anesthetics, the S form is less toxic
and has a longer duration of anesthesia. For instance, anesthesia produced by bupivacaine infiltration was of
[90] [91]
longer duration compared with the R isomer when the S isomer was used. Also, the S isomer had lower systemic
toxicity. The mean convulsant dose of R-bupivacaine was 57% of the S-bupivacaine convulsant dose. When the [92]
isomers of ropivacaine were evaluated, the S isomer of the drug had a longer duration of blockade and a lower
toxicity than its R isomer. Additionally, when cardiac electrophysiologic toxicity was evaluated in animal studies,
[93]
ropivacaine (the commercial preparation is the S form of drug) at equipotent nerve-blocking doses appeared to have
a safety margin that was almost twice that of commercial bupivacaine, which is a mixture of the R and S isomers. [93]
Studies with the R and S bupivacaine isomers indicate that the R form is apparently more arrhythmogenic and more
cardiotoxic. Further evaluation of the isomers of bupivacaine is necessary before commercial use can be
[79] [94]
achieved.
ROPIVACAINE
The cardiotoxicity of bupivacaine stimulated interest in developing a less toxic, long-lasting local anesthetic.
223
Figure 13-14 Stereoisomers are possible for the aforementioned local anesthetics. The asymmetrical carbons are indicated in this figure by an
asterisk.
The result of that search was the development of a new amino ethylamine, ropivacaine ( Fig. 13-15 ), the S-
enantiomer of 1-propyl-2′,6′-pipecolocylidide. The S-enantiomer, like most local anesthetics with a chiral center,
was chosen because it has a lower toxicity than the R isomer. This is presumably because of slower uptake, resulting
in lower blood levels for a given dose. Ropivacaine is slightly less potent than bupivacaine in producing anesthesia.
In several animal models, it appears to be less cardiotoxic than equieffective doses of bupivacaine. In clinical
studies, ropivacaine appears to be suitable for both epidural and regional anesthesia, with duration of action similar
to that of bupivacaine. Interestingly, it seems to be even more motor-sparing than bupivacaine.
Ropivacaine is a long-acting, enantiomerically pure (S-enantiomer) amide local anesthetic with a high pKa and low
lipid solubility, which blocks nerve fibers involved in pain transmission (A∆ and C fibers) to a greater degree than
those controlling motor function (Aβ fibers). The drug was less cardiotoxic than equal concentrations of racemic
bupivacaine but more so than lidocaine (lignocaine) in vitro and had a significantly higher threshold for CNS
toxicity than racemic bupivacaine in healthy volunteers (mean maximal tolerated unbound arterial plasma
concentrations were 0.56 and 0.3 mg/L, respectively).
Extensive clinical data have shown that epidural ropivacaine (0.2%) is effective for the initiation and maintenance of
labor analgesia, and provides pain relief after abdominal or orthopedic surgery, especially when given in
conjunction with opioids (coadministration with opioids may also allow lower concentrations of ropivacaine to be
used). The drug had efficacy generally similar to that of the same dose of bupivacaine with regard to pain relief but
caused less motor blockade at low concentrations.
224
Lumbar epidural administration of 20 to 30 mL ropivacaine (0.5%) provided anesthesia of a similar quality to that
achieved with bupivacaine (0.5%) in women undergoing cesarean section, but the duration of motor blockade was
shorter with ropivacaine. For lumbar epidural anesthesia for lower limb or genitourinary surgery, comparative data
suggest that higher concentrations of ropivacaine (0.75% or 1.0%) may be needed to provide the same sensory and
motor blockade as bupivacaine (0.5% and 0.75%). In patients about to undergo upper limb surgery, 30 to 40 mL of
ropivacaine (0.5%) produced brachial plexus anesthesia broadly similar to that achieved with equivalent volumes of
bupivacaine (0.5%), although the time to onset of sensory block tended to be faster and the duration of motor block
shorter with ropivacaine.
Ropivacaine had an adverse event profile similar to that of bupivacaine in clinical trials. Several cases of CNS
toxicity were reported after inadvertent intravascular administration of ropivacaine, but only one case of
cardiovascular toxicity has been reported to date. The outcome of these inadvertent intravascular administrations
was favorable.
The conclusion is that ropivacaine is a well-tolerated regional anesthetic with an efficacy broadly similar
Figure 13-15 It is the S-enantiomer r of 1-propyl-2′, -6′-pipecolocylidide.
to that of bupivacaine. However, it may be a preferred option because of its reduced CNS and cardiotoxic potential
and its lower propensity for motor block.
Pharmacodynamic Properties
The amide local anesthetic, ropivacaine, reversibly blocks nerve impulse conduction by reducing nerve cell
membrane permeability to sodium ions. In vitro studies have shown that, because of its high pKa ( 8.2) and low
lipid solubility, the drug preferentially blocks nerve fibers responsible for pain transmission (Aβ and C fibers) rather
than motor function (A∆ fibers). In isolated rabbit vagus nerve, ropivacaine caused significantly less blockade of
motor fibers than bupivacaine (P = 0.0001) but had a similar effect on sensory fibers.
Ropivacaine appears to be less cardiotoxic than equal concentrations of racemic bupivacaine (because of its faster
dissociation from cardiac Na+ channels) but more cardiotoxic than lidocaine (lignocaine). The drug had a smaller
effect on QRS prolongation than bupivacaine in healthy volunteers (+ 2.4 % vs. + 6%: P < 0.05). CNS toxicity
occurs at lower plasma concentrations than cardiotoxicity with all local anesthetics; ropivacaine and bupivacaine
caused seizures at lower concentrations than lidocaine in dogs.
In healthy volunteers, ropivacaine had a significantly higher threshold for CNS toxicity (lightheadedness, tinnitus,
and numbness of the tongue) than bupivacaine, with mean maximum tolerated unbound arterial plasma
concentrations of 0.56 and 0.3 mg/L, respectively (P < 0.001).
Ropivacaine has a biphasic vascular effect, causing vasoconstriction at low concentrations but not at higher
concentrations. Importantly, epidural ropivacaine 0.5% did not compromise uteroplacental circulation in healthy
pregnant women.
Pharmacokinetic Properties
After epidural administration in women undergoing cesarean section, mean maximum plasma concentrations (Cmax )
of 1.1 to 1.6 mg/L were reached after administration of 20 to 28 mL ropivacaine (0.5 or 0.75%). The drug also
underwent a degree of systemic absorption after intercostal, subclavian perivascular, peribulbar, intra-articular, or
225
local administration. However, because ropivacaine is extensively (90%–94%) bound to plasma proteins (mostly α1 -
acid glycoprotein) after systemic absorption. Cmax for unbound drug remained well below the threshold for CNS
toxicity reported in volunteers ( 0.6 mg/L) regardless of the route of administration. Like bupivacaine,
ropivacaine crosses the human placenta.
Mean total body clearance and terminal elimination half-life of ropivacaine after epidural administration in pregnant
women ranged from 13.4 to 19.8 L per hour and 5 to 7 hours, respectively.
Ropivacaine undergoes extensive hepatic metabolism after intravenous administration, with only 1% of the drug
eliminated unchanged in the urine. Two cytochrome P450 (CYP-450) isoenzymes, CYP-1A2 and CYP-3A4, are
responsible for the formation of major (3-hydroxy-ropivacaine) and minor metabolites, respectively. Agents that
inhibit these isozymes (particularly CYP-1A2) have the potential to affect the pharmacokinetic profile of
ropivacaine. Accordingly, coadministration of fluvoxamine, a CYP-1A2 inhibitor, significantly increased total
plasma concentrations of intravenous ropivacaine by 16% and delayed its elimination.
Anesthesia
Lumbar epidural administration of 20 or 30 mL ropivacaine (0.5%) provided anesthesia of a similar quality to that
achieved with bupivacaine (0.5%) in women undergoing cesarean section, without affecting neonatal outcome. The
drugs had comparable effects on sensory blockade, but motor blockade tended to be shorter with ropivacaine.
Lumbar epidural ropivacaine (0.5% to 1%) also provided effective anesthesia for lower limb or genitourinary
surgery, although comparative data suggests that higher doses of ropivacaine (0.75% or 1%) may be needed to
provide the same pattern of sensory and motor blockade as bupivacaine (0.5% and 0.75%) in these patients.
In patients about to undergo upper limb surgery, 30 to 40 mL ropivacaine (0.5%) produced a pattern of brachial
plexus anesthesia broadly equivalent to that achieved with bupivacaine (0.5%) whether administered via the
subclavian perivascular, axillary or interscalenic approach. The onset of sensory blockade tended to be faster and the
duration of motor blockade shorter with ropivacaine, but between-group differences only reached statistical
significance in one study. In noncomparative studies, anesthesia of brachial plexus dermatomes was achieved in
greater than or equal to 86% of patients who received 30 to 33 mL ropivacaine (0.5%) via the subclavian
perivascular route.
Limited data indicate that 25 to 30 mL ropivacaine (0.75%) had an onset of sensory block similar to that of the fast
onset/medium duration local anesthetic mepivacaine 2% ( 25 mL) when used for combined sciatic-femoral nerve
block for lower limb surgery, but ropivacaine provided longer postoperative analgesia. This advantage was offset by
a longer time to resolution of foot motor block. Limited data suggest that ropivacaine (0.5%) has an anesthetic
efficacy similar to that of bupivacaine (0.5%) when used for combined lumbar plexus-sciatic nerve block (for knee
surgery) and 3-in-1 block (for hip surgery after trauma).
Results from a number of well-controlled trials suggest that 5 to 10 mL ropivacaine (1%) (alone or with lidocaine)
provides a quality of peribulbar anesthesia at least similar to that achieved with 5 to 10 mL bupivacaine (0.5% or
0.75%) (alone or with lidocaine) in patients undergoing eye surgery.
Therapeutic Efficacy
Ropivacaine has been extensively evaluated for use as an analgesic (for labor or postoperative pain) and as a
regional anesthetic during a variety of surgical procedures.
Analgesia. Epidural ropivacaine (0.2%) provided adequate pain relief when used for the initiation (10 to 18 mL) and
maintenance (4 to 10 mL/hr) of labor analgesia and had efficacy generally similar to that of the same dose of
bupivacaine with regard to pain relief and motor blockade (mild) in comparative studies. Ropivacaine, like
bupivacaine, had no significant effects on neonatal outcome. Coadministration with opioids such as fentanyl and
sufentanil improved labor analgesia and allowed a lower concentration of the anesthetic to be used (at these lower
concentrations ropivacaine caused less motor blockade than bupivacaine).
Lumbar or thoracic epidural ropivacaine (0.1%, 0.2%, and 0.3%) infused at 10 mL per hour for 24 hours after
abdominal or orthopedic surgery reduced morphine requirements (the primary end-point) compared with placebo.
The incidence of motor block increased with increasing dose but did not differ significantly from that reported in
placebo recipients. Results from comparative studies suggest that epidural ropivacaine (0.2%) is more effective than
226
patient-controlled intravenous morphine for postoperative pain relief. As for labor pain, combination with opioids is
effective and may allow a lower concentration of ropivacaine to be used for the same level of pain relief.
Preoperative (along the intended line of the incision) or postoperative wound infiltration of 30 to 40 mL of
ropivacaine (0.25% or 0.5%) dose-dependently relieved postoperative pain after hernia repair; a higher
concentration (0.75%) was as effective as bupivacaine (0.25%). Evidence published in abstract form suggests that
preoperative infiltration of the incision line using ropivacaine may also provide pain relief after thoracic surgery,
breast reconstruction, or lower back surgery, and postoperative wound infiltration alleviates pain after shoulder
surgery.
Evidence indicates that epidural ropivacaine (0.2% and 0.25%) (2 and 2.5 mg/kg) may provide effective
postoperative analgesia when given via the caudal route in children undergoing minor surgery, and by the lumbar
route in those undergoing major surgery. Importantly, motor block on awakening was minimal with ropivacaine in
these studies.
Tolerability
Ropivacaine was well tolerated in clinical trials, although few studies provided detailed tolerability data.
Hypotension was the most commonly reported adverse event in studies of epidural ropivacaine, but this was most
likely a consequence of sympathetic block (common to all local anesthetics). Other reported events included nausea,
vomiting, paresthesia, urinary retention, and bradycardia. The tolerability profile of ropivacaine was similar to that
of bupivacaine in comparative studies. Limited evidence also suggests that the drug is well tolerated after brachial
plexus block, intrathecal administration, lumbar plexus-sciatic nerve block, local wound infiltration and peribulbar
administration. The clinical experiences from 60 studies involving 3000 patients showed that accidental
intravascular administration of ropivacaine occurred in six patients. Only one patient convulsed and none showed
signs of cardiotoxicity at doses of 75 to 200 mg. The outcome of all six patients to these reactions was good.
Consistent with preclinical evidence that cardiovascular toxicity occurs at higher plasma concentrations than CNS
toxicity, only one case of cardiovascular toxicity after intravascular administration of ropivacaine has been reported
to date.
Dosage and Administration
Ropivacaine (0.2%) is recommended for epidural analgesia administered via either lumbar or thoracic routes (6 to
14 mL/hr) after surgery for postoperative pain and via the lumbar route for labor pain (10 to 20 mL bolus and then 6
to 14 mL/hr plus top-up if required). For anesthesia during cesarean section, ropivacaine 0.75% (15 to 20 mL) is
recommended. This concentration is also recommended for major or minor nerve block and wound infiltration,
whereas ropivacaine (0.75% and 1.0%) can be used for lumbar epidural anesthesia during other types of surgery.
Administration of ropivacaine to children younger than 12 years of age or for spinal anesthesia in adults is not yet
recommended.
LEVOBUPIVACAINE
Levobupivacaine (Chirocaine) injection contains a single enantiomer of bupivacaine hydrochloride, which is

chemically described as (S)-1-butyl-2-piperidylformo-2′,6′-xylidide hydrochloride and is related chemically and
pharmacologically to the amino amide class of local anesthetics ( Fig. 13-16 ).
Figure 13-16 A single enantiomer of bupivacaine hydrochloride

chemically described as (s)-1butyl-2-piperidylformo-2′, 6′-xylidide
hydrochloride.
227
Levobupivacaine hydrochloride, the S-enantiomer of bupivacaine, is a white crystalline powder with a molecular
formula of C18 H28 N2 O − HCl and a molecular weight of 324.9.
The solubility of levobupivacaine hydrochloride in water is about 100 mg per mL at 20°C, the partition coefficient
(oleyl alcohol/water) is 1624, and the pKa of levobupivacaine hydrochloride is the same as that of bupivacaine
hydrochloride and the partition coefficient is very similar to that of bupivacaine hydrochloride (1565).
Levobupivacaine is a sterile, nonpyrogenic, colorless solution (pH 4.0–6.5) containing levobupivacaine

hydrochloride equivalent to 2.5 mg/mL, 5.0 mg/mL, and 7.5 mg/mL of levobupivacaine, sodium chloride for
isotonicity, and water for injection. Sodium hydroxide, hydrochloric acid, or both may have been added to adjust
pH. Levobupivacaine is preservative free and is available in 10-mL and 30-mL single-dose vials.
Clinical Pharmacology
Mechanism of Action.Levobupivacaine is a member of the amino amide class of local anesthetics. Local
anesthetics block the generation and the conduction of nerve impulses by increasing the threshold for electrical
excitation in the nerve, by slowing propagation of the nerve impulse, and by reducing the rate of rise of the action
potential. In general, the progression of anesthesia is related to the diameter, myelination, and conduction velocity of
affected nerve fibers. Clinically, the order of loss of nerve function is as follows: (1) pain, (2) temperature, (3) touch,
(4) proprioception, and (5) skeletal muscle tone.
Pharmacokinetics.After intravenous infusion of equivalent doses of levobupivacaine and bupivacaine, the mean
clearance, volume of distribution, and terminal half-life values of levobupivacaine and bupivacaine were similar. No
detectable levels of R(+ )-bupivacaine were found after the administration of levobupivacaine.
A comparison of the estimates for plasma area under the curve (AUC) and Cmax between levobupivacaine and
bupivacaine in two phase III clinical trials involving short-duration administration of either agent found that neither
total plasma exposure or Cmax differed between the two drugs when they were compared within studies. Between-
study values differed somewhat, likely due to differences in the injection sites, volume, and total dose administered
in each of the studies. These data suggest that levobupivacaine and bupivacaine have similar pharmacokinetic
profiles.
Between 0.5% and 0.75% of levobupivacaine given epidurally at doses of 75 mg and 112.5 mg respectively, the
mean Cmax and AUC0–24 of levobupivacaine were approximately dose-proportional. Similarly, between 0.25% and
0.5% of levobupivacaine used for brachial plexus block at doses of 1 mg/kg and 2 mg/kg respectively, the mean Cmax
and AUC0–24 of levobupivacaine were approximately dose-proportional.
Absorption. The plasma concentration of levobupivacaine after therapeutic administration depends on dose and also
on route of administration, because absorption from the site of administration is affected by the vascularity of the
tissue. Peak levels in blood were reached approximately 30 minutes after epidural administration, and doses up to
150 mg resulted in mean Cmax levels of up to 1.2 µg/mL.
Distribution.Plasma protein binding of levobupivacaine evaluated in vitro was found to be greater than 97% at
concentrations between 0.1 and 1 µg/mL. The association of levobupivacaine with human blood cells was very low
(0%–2%) over the concentration range 0.01–1 µg/mL and increased to 32% at 10 µg/mL. The volume of distribution
of levobupivacaine after intravenous administration was 67 L.
Metabolism.Levobupivacaine is extensively metabolized with no unchanged levobupivacaine detected in urine or

feces. In vitro studies using [14 C]levobupivacaine showed that CYP-3A4 isoform and CYP-1A2 isoform mediate the
metabolism of levobupivacaine to desbutyl levobupivacaine and 3-hydroxy levobupivacaine, respectively. In vivo,
the 3-hydroxy levobupivacaine appears to undergo further transformation to glucuronide and sulfate conjugates.
Metabolic inversion of levobupivacaine to R(+ )-bupivacaine was not evident either in vitro or in vivo.
Elimination.After intravenous administration, recovery of the radiolabeled dose of levobupivacaine was essentially
quantitative, with a mean total of about 95% recovered in urine and feces in 48 hours. Of this 95%, about 71% was
in urine, whereas 24% was in feces. The mean elimination half-life of total radioactivity in plasma was 3.3 hours.
The mean clearance and terminal half-life of levobupivacaine after intravenous infusion were 39 L per hour and per
1.3 hours, respectively.
Pharmacodynamics.Levobupivacaine can be expected to share the pharmacodynamic properties of other local

anesthetics. Systemic absorption of local anesthetics can produce effects on the CNS and the cardiovascular system.
228
At blood concentrations achieved with therapeutic doses, changes occur in cardiac conduction. Excitability,
refractoriness, contractility, and peripheral vascular resistance have been reported. Toxic blood concentrations
depress cardiac conduction and excitability, which may lead to atrioventricular block, ventricular arrhythmias, and
cardiac arrest, sometimes resulting in death. In addition, myocardial contractility is depressed and peripheral
vasodilation occurs, leading to decreased cardiac output and arterial blood pressure.
After systemic absorption, local anesthetics can produce CNS stimulation, depression, or both. Apparent CNS
stimulation is usually manifested as restlessness, tremors, and shivering, progressing to convulsions. Ultimately,
CNS depression may progress to coma and cardiorespiratory arrest. However, the local anesthetics have a primary
depressant effect on the medulla and on higher centers. The depressed stage may occur without a prior excited stage.
In nonclinical pharmacology studies comparing levobupivacaine and bupivacaine in animal species, both the CNS
and the cardiotoxicity of levobupivacaine were less than that of bupivacaine. Arrhythmogenic effects were seen in
animals at higher doses of levobupivacaine than bupivacaine. Animal data comparing the difficulty of resuscitation
from levobupivacaine- and bupivacaine-induced arrhythmia are not available. CNS toxicity occurred with both
drugs at lower doses and at lower plasma concentrations than those doses and plasma concentrations associated with
cardiotoxicity.
In two intravenous infusion studies in conscious sheep, the convulsive doses of levobupivacaine were found to be
significantly higher than for bupivacaine. After repeated intravenous bolus administration mean (± SD) convulsive
doses for levobupivacaine and bupivacaine were 9.7 (7.9) mg/kg and 6.1 (3.4) mg/kg, respectively. The associated
median total serum concentrations were 3.2 µg/mL and 1.6 µg/mL. In a second study after a 3-minute intravenous
infusion, the mean convulsant dose (95% confidence interval) for levobupivacaine was 101 mg (87–116 mg) and for
bupivacaine 79 mg (72–87 mg).
A study in human volunteers was designed to assess the effects of levobupivacaine and bupivacaine on the
electroencephalogram following an intravenous dose (40 mg) that was predicted to be below the threshold to cause
CNS symptoms. In this study, levobupivacaine decreased high alpha power in the parietal, temporal, and occipital
regions, but to a lesser extent than bupivacaine. Levobupivacaine had no effect on high alpha power in the frontal
and central regions, nor did it produce the increase in theta power observed at some electrodes after bupivacaine.
In another study, 14 subjects received levobupivacaine or bupivacaine infusions intravenously until significant CNS
symptoms occurred (numbness of the tongue, light-headedness, tinnitus, dizziness, blurred vision, or muscle
twitching). The mean dose at which CNS symptoms occurred was 56 mg (range 17.5–150 mg) for levobupivacaine
and 48 mg (range 22.5–110 mg) for bupivacaine; this difference did not reach statistical significance. The primary
endpoints of the study were cardiac contractility and standard electrocardiographic parameters. Although some
differences were seen between treatments, the clinical relevance of these is unknown.
Clinical Trials
The clinical trial program included 1220 patients and subjects who received levobupivacaine in 31 clinical trials.
Levobupivacaine has been studied as a local anesthetic in adults; administered as an epidural block for surgical
cases, including cesarean section; and used in peripheral neural blockade and for postoperative pain control.
Although relative potency has not been established, clinical trials have demonstrated that levobupivacaine and
bupivacaine exhibit similar anesthetic effects.
Epidural Administration in Cesarean Section. Levobupivacaine and bupivacaine (0.50%) were evaluated for
epidural block in 62 patients undergoing cesarean section in a randomized, double-blind, comparative trial. The
mean (± standard deviation [SD]) time to sensory block measured at T4 to T6 was 10 ± 8 minutes for
levobupivacaine and 6 ± 4 minutes for bupivacaine. The mean duration of sensory and motor block was 8 ± 1 and 4
± 1 hours for levobupivacaine and 7 ± 1 and 4 ± 1 hours for bupivacaine, respectively. Ninety-four percent of
patients receiving levobupivacaine and 100% of patients receiving bupivacaine achieved a block adequate for
surgery. In a second bupivacaine-controlled cesarean section study involving 62 patients, the mean time to onset of
T4 to T6 sensory block for levobupivacaine and bupivacaine was 10 ± 7 minutes and 9 ± 7 minutes, respectively,
with 94% of levobupivacaine patients and 91% of bupivacaine patients achieving a bilateral block adequate for
surgery. The mean time to complete regression of sensory block was 8 ± 2 hours for both treatments.
Epidural Administration during Labor and Delivery. Levobupivacaine (0.25%) was compared with bupivacaine
(0.25%) in a randomized, double-blind study using intermittent injections via an epidural catheter in 68 patients
229
during labor. The median duration of pain relief in the subset of patients receiving levobupivacaine (0.25%) who
had relief was 49 minutes; for bupivacaine patients, the median duration was 51 minutes. After the first top-up
injections, 91% of patients receiving levobupivacaine and 90% of patients receiving bupivacaine achieved pain
relief.
Epidural Administration for Surgery. Levobupivacaine concentrations of 0.50% and 0.75% administered by
epidural injection were evaluated in 85 patients undergoing lower limb or major abdominal surgery in randomized,
double-blind comparisons with bupivacaine. Anesthesia sufficient for surgery was achieved in almost all patients
with either treatment. In patients having abdominal surgery, the mean (± SD) time to onset of sensory block was 14
± 6 minutes for levobupivacaine and 14 ± 10 minutes for bupivacaine. With respect to the duration of block, the
time to complete regression was 551 ± 88 minutes for levobupivacaine and 506 ± 71 minutes for bupivacaine.
Postoperative Pain Management. Postoperative pain control was evaluated in 258 patients in three studies,
including one dose-ranging study and two studies assessing levobupivacaine in combination with epidural fentanyl
or clonidine. The dose-ranging study evaluated levobupivacaine in patients undergoing orthopedic surgery; the
highest concentration, 0.25%, was significantly more effective than lower concentrations. The combination studies
in postoperative pain management tested levobupivacaine (0.125%) in combination with 4 µg/mL fentanyl and
0.125% levobupivacaine in combination with clonidine (50 µg/hour) for orthopedic surgery. In these studies, the
efficacy variable was time to first request for rescue analgesia during the 24-hour epidural infusion period. In both
studies, the combination treatment provided better pain control than clonidine, opioid, or local anesthetic alone.
Peripheral Nerve Administration. Levobupivacaine has been evaluated for its anesthetic efficacy when used for
peripheral nerve block. These clinical trials included brachial plexus block study (by supraclavicular approach),
infiltration anesthesia studies (for inguinal hernia repair), and peribulbar block studies.
Brachial Plexus Block. Levobupivacaine (0.25% and 0.5%) was compared with bupivacaine (0.5%) in 74 patients
receiving a brachial plexus (supraclavicular) block for elective surgery. In the levobupivacaine (0.25%) treated
group 68% of the patients achieved satisfactory block, and in the other levobupivacaine (0.5%) treated group, 81%
of patients achieved satisfactory block for surgery. In the bupivacaine (0.5%) treated group, 74% of patients
achieved satisfactory block for surgery.
Infiltration Anesthesia. Levobupivacaine (0.25%) was evaluated in 68 patients in two randomized, double-blind,
bupivacaine-controlled clinical trials for infiltration anesthesia during surgery and for postoperative pain
management in patients undergoing inguinal hernia repair. No clear differences between the two drugs were seen.
Peribulbar Block Anesthesia. Two clinical trials were conducted to evaluate levobupivacaine (0.75%) and
bupivacaine in 110 patients who underwent peribulbar block for anterior segment ophthalmic surgery, including
cataract, glaucoma, and graft surgery, and for postoperative pain management. In one study, a 10-mL injection of
levobupivacaine (0.75%) or bupivacaine produced a block adequate for surgery at a median time of 10 minutes. In
the second study, a 5-mL dose of levobupivacaine (0.75%) or bupivacaine injected in a technique more closely
resembling a retrobulbar block resulted in a median time to adequate block of 2 minutes for both treatments.
Postoperative pain was reported in fewer than 10% of patients overall.
Indications and Usage
Levobupivacaine is indicated for the production of local or regional anesthesia for surgery and obstetrics, and for
postoperative pain management. In surgical anesthesia, it is used for epidural, peripheral, and neural blockade, and
for local infiltration. For pain management, levobupivacaine is used for continuous epidural infusion or intermittent
epidural neural blockade as well as continuous or intermittent peripheral neural blockade or local infiltration. For
continuous epidural analgesia, levobupivacaine may be administered in combination with epidural fentanyl or
clonidine.
Contraindications
Levobupivacaine is contraindicated in patients with a known hypersensitivity to this drug or to any local anesthetic
agent of the amide type.
Potency of Bupivacaine Stereoisomers
Chiral local anesthetics, such as ropivacaine and levobupivacaine, have the potential advantage over racemic
mixtures in showing reduced toxic side effects. However, these S-(levo, or “−”) isomers also have reportedly lower
230
potency than their optical antipode, possibly resulting in no advantage in therapeutic index. Potency for local
anesthetics inhibiting Na+ channels or action potentials depends on the pattern of membrane potential as does the
stereopotency ratio. Here, the authors have quantitated the stereopotencies of R−, S−, and racemic bupivacaine,
comparing several in vitro assays of neuronal Na+ channels with those from in vivo functional nerve block, to
establish relative potencies and to understand better the role of different modes of channel inhibition in overall
functional anesthesia.
The binding of bupivacaine to Na+ channels was assessed indirectly by its antagonism of [3 H]-batrachotoxin binding
to rat brain synaptosomes. Inhibition of Na+ currents by bupivacaine was directly assayed in voltage-clamped GH-3
neuroendocrine cells. Neurobehavioral functions were disrupted by bupivacaine percutaneously injected (0.1 mL;
0.0625%–1.0%) at the rat sciatic nerve and semiquantitatively assayed. Concentration-dependent actions of R−, S−,
and racemic bupivacaine were compared for their magnitude and duration of action.
Competitive batrachotoxin displacement has a stereopotency ratio of R:S = 3:1. Inhibition of Na+ currents with
different prepulse potentials shows S > R potency when the membrane is hyperpolarized, and R > S potency when it
is depolarized from normal resting values. Functional deficits assayed in vivo usually demonstrate no consistent
enantioselectivity and only a modest stereopotency (R:S = 1.2–1.3) for peak analgesia achieved at the lowest doses.
Other functions display no significant stereopotency in either degree, duration, or product (AUC) at any dose.
Although the in vitro actions of bupivacaine showed stereoselectivity ratios of 1:3–3:1 (R:S), in vivo nerve block at
clinically used concentrations showed much smaller ratios for peak effect and no significant enantioselectivity for
duration. A primary role for the blockade of resting rather than open or inactivated Na+ channels may explain the
modest stereoselectivity in vivo, although stereoselective factors controlling local disposition cannot be ruled out.
Levo(S−)bupivacaine is effectively equipotent to R− or racemic bupivacaine in vivo for rat sciatic nerve block.
Rarely Used Local Anesthetics
TETRODOTOXIN AND SAXITOXIN
These toxins are two of the most potent poisons known; the minimal lethal dose of each in the mouse is about 8
µg/kg. Both toxins are responsible for fatal poisoning in human beings. Tetrodotoxin is found in the gonads and
other visceral tissues of some fish of the order Tetraodontiformes, to which the Japanese fugu, or puffer fish,
belongs. It also occurs in the skin of some newts of the family Salamandridae and of the Costa Rican frog Atelopus.
Saxitoxin, and possibly some related toxins, are elaborated by the dinoflagellate Gonyaulax catanella and
Gonyaulax tamerensis and are retained in the tissues of clams and other shellfish that eat these organisms. Given the
right conditions of temperature and light, the Gonyaulax may multiply so rapidly as to discolor the ocean—hence
the term red tide. Shellfish feeding on Gonyaulax at this time become extremely toxic to human beings and are
responsible for periodic outbreaks of paralytic shellfish poisoning. Although the toxins are chemically different
[95] [96]
from each other, their mechanism of action is indistinguishable. Both toxins, in nanomolar concentrations,
[96]
specifically block the outer mouth of the pore of Na+ channels in the membranes of excitable cells. As a result, the
action potential is blocked. The receptor site for these toxins is formed by amino acid residues in the SS2 segment of
the Na+ channel á subunit (see Fig. 13-7 ) in all four domains. Not all Na+ channels are equally sensitive to
[11] [97]
tetrodotoxin; the channels in cardiac myocites are resistant, and a tetrodotoxin-resistant Na+ channel is expressed
when skeletal muscle is denervated. Blockade of vasomotor nerves, together with a relaxation of vascular smooth
muscle, seems to be responsible for the hypotension that is characteristic of tetrodotoxin poisoning. Both toxins
[95]
cause death by paralysis of the respiratory muscles; therefore, the treatment of severe cases of poisoning requires
artificial ventilation. Early gastric lavage and therapy to support the blood pressure also are indicated. If the patient
survives paralytic shellfish poisoning for 24 hours, the prognosis is good. [98] [99]
Clinical Uses of Local Anesthetics
Local anesthesia is the loss of sensation in a body part without the loss of consciousness or the impairment of central
control of vital functions. It offers two major advantages. The first is that the physiologic perturbations associated
with general anesthesia are avoided; the second is that neurophysiologic responses to pain and stress can be
modified beneficially. As discussed earlier, local anesthetics have the potential to produce deleterious side effects.
The choice of a local anesthetic and care in its use are the primary deterrents of such toxicity. There is a poor
correlation between the amount of local anesthetic injected and peak plasma levels in adults. The serum level also
depends on the area of injection. It is highest with interpleural or intercostal block and lowest with subcutaneous
infiltration. Thus, recommended doses serve only as general guidelines.
231
The following discussion concerns the pharmacologic and physiologic consequences of the use of local anesthetics
categorized by method of administration. A more comprehensive discussion of their use and administration is
presented in standard anesthesiology texts (e.g., Cousins and Bridenbaugh ). [100]
TOPICAL ANESTHESIA
Anesthesia of mucous membranes of the nose, mouth, throat, tracheobronchial tree, esophagus, and genitourinary
tract can be produced by direct application of aqueous solutions of salts of many local anesthetics or by suspension
of the poorly soluble local anesthetics. Tetracaine (2%), lidocaine (2%–10%), and cocaine (1%–4%) are most often
used. Cocaine is used only in the nose, nasopharynx, mouth, throat, and ear. Cocaine has the unique advantage of
producing vasoconstriction as well as anesthesia. The shrinking of mucous membranes decreases operative bleeding
while improving surgical visualization. Comparable vasoconstriction can be achieved with other local anesthetics by
the addition of a low concentration of a vasoconstrictor such as phenylephrine (0.005%). Epinephrine, topically
applied, has no significant local effect and does not prolong the duration of action of local anesthetics applied to
mucous membranes because of poor penetration. Maximal safe total dosages for topical anesthesia in a healthy 70-
kg adult are 500 mg for lidocaine, 200 mg for cocaine, and 50 mg for tetracaine.
Peak anesthetic effect after topical application of cocaine or lidocaine occurs within 2 to 5 minutes (3–8 min with
tetracaine), and anesthesia lasts for 30 to 45 minutes (30–60 min with tetracaine). Anesthesia is entirely superficial;
it does not extend to submucosal structures. This technique does not alleviate joint pain or discomfort from
subdermal inflammation or injury.
Local anesthetics are absorbed rapidly into the circulation after topical application to mucous membranes or
denuded skin. Thus, it must be kept in mind that topical anesthesia always carries the risk of systemic toxic
reactions. Systemic toxicity has occurred even after the use of local anesthetics to control discomfort associated with
severe diaper rash in infants. Absorption is particularly rapid when local anesthetics are applied to the
tracheobronchial tree. Concentrations in blood after instillation of local anesthetics into the airway are nearly the
same as those that follow intravenous injection.
The introduction of an eutectic mixture of lidocaine (2.5%) and prilocaine (2.5%) (EMLA) bridges the gap between
topical and infiltration anesthesia. The efficacy of this combination lies in the fact that the mixture of prilocaine and
lidocaine has a melting point lower than either compound alone, existing at room temperature as an oil that can
penetrate intact skin. EMLA cream produces anesthesia to a maximal depth of 5 mm and is applied as a cream on
instant skin under an occlusive dressing, which must be left in place for at least 1 hour. It is effective for procedures
involving skin and superficial subcutaneous structures (e.g., venipuncture, skin graft harvesting). The component
local anesthetics are absorbed into the systemic circulation, potentially producing toxic effects. Guidelines are
available to calculate the maximal amount of cream that can be applied and area of skin covered. It must not be used
on mucous membranes or abraded skin, because rapid absorption across these surfaces may result in systemic
toxicity.
INFILTRATION ANESTHESIA
Infiltration anesthesia is the injection of local anesthetic directly into tissue without taking into consideration the
course of cutaneous nerves. Infiltration anesthesia can be so superficial as to include only the skin. It also can
include deeper structures, including intraabdominal organs when these, too, are infiltrated.
The duration of infiltration anesthesia can be approximately doubled by the addition of epinephrine (5 µg/mL) to the
injection solution; epinephrine also decreases peak concentrations of local anesthetics in blood. Epinephrine-
containing solutions should not, however, be injected into tissues supplied by end arteries (e.g., fingers, toes, ears,
nose, penis). The intense vasoconstriction produced by epinephrine may result in gangrene. For the same reason
epinephrine should be avoided in solutions injected intracutaneously. Because epinephrine also is absorbed into the
circulation, its use should be avoided in those for whom adrenergic stimulation is undesirable.
The local anesthetics most frequently used for infiltration anesthesia are lidocaine (0.5%–1.0%), procaine (0.5%–
1.0%), and bupivacaine (0.125%–0.25%). When used without epinephrine, up to 4.5 mg/kg of lidocaine, 7 mg/kg of
procaine, or 2 mg/kg of bupivacaine can be employed in adults. When epinephrine is added, these amounts can be
increased by one third.
The advantage of infiltration anesthesia and other regional anesthetic techniques is that it is possible to provide
satisfactory anesthesia without disruption of normal bodily functions. The chief disadvantage of infiltration
232
anesthesia is that relatively large amounts of drug must be used to anesthetize relatively small areas. This is no
problem with minor surgery. When major surgery is performed, however, the amount of local anesthetic that is
required makes systemic toxic reactions likely. The amount of anesthetic required to anesthetize an area can be
reduced significantly and the duration of anesthesia increased markedly by specifically blocking the nerves that
innervate the area of interest. This can be done at one of several levels: subcutaneously, at major nerves, or at the
level of the spinal roots.
FIELD BLOCK ANESTHESIA
Field block anesthesia is produced by subcutaneous injection of a solution of local anesthetic in such a manner as to
numb the region distal to the injection. For example, subcutaneous infiltration of the proximal portion of the volar
surface of the forearm results in an extensive area of cutaneous anesthesia that starts 2 to 3 cm distal to the site of
injection. The same principle can be applied with particular benefit to the scalp, the anterior abdominal wall, and the
lower extremity.
The drugs used and the concentrations and doses recommended are the same as for infiltration anesthesia. The
advantage of field block anesthesia is that less drug can be used to provide a greater area of anesthesia than when
infiltration anesthesia is used. Knowledge of the relevant neuroanatomy obviously is essential for successful field
block anesthesia.
NERVE BLOCK ANESTHESIA
Injection of a solution of a local anesthetic into or about individual peripheral nerves or nerve plexuses produces
even greater areas of anesthesia than the techniques described earlier. Blockade of mixed peripheral nerves and
nerve plexuses also usually anesthetizes somatic motor nerves, producing skeletal muscle relaxation, which is useful
for some surgical procedures. The areas of sensory and motor block usually start several centimeters distal to the site
of injection. Brachial plexus blocks are particularly useful for procedures on the upper extremity and shoulder.
Intercostal nerve blocks are effective for anesthesia and relaxation of the anterior abdominal wall. Cervical plexus
block is appropriate for surgery of the neck. Sciatic and femoral nerve blocks are useful for surgery distal to the
knee. Other useful nerve blocks before surgical procedures include blocks of individual nerves at the wrist and at the
ankle, blocks of individual nerves such as the median or ulnar at the elbow, and blocks of sensory cranial nerves.
There are four major determinants of the onset of sensory anesthesia after injection near a nerve. These are
proximity of the injection to the nerve, concentration and volume of drug, degree of ionization of the drug, and time.
Local anesthetic never is intentionally injected into the nerve because this is painful and may lead to nerve damage.
Instead, the anesthetic agent is deposited as close to the nerve as possible. Thus, the local anesthetic must diffuse
from the site of injection into the nerve, where it acts. The rate of diffusion is determined chiefly by the
concentration of the drug, its degree of ionization (as ionized local anesthetic diffuses more slowly), its
hydrophobicity, and the physical characteristics of the tissue surrounding the nerve. Higher concentrations of local
anesthetic result in a more rapid onset of peripheral nerve block. The utility of using higher concentrations, however,
is limited by systemic toxicity as well as direct neural toxicity of concentrated local anesthetic solutions. Local
anesthetics with lower pKa values tend to have a more rapid onset of action for a given concentration, because more
drug is ionized at neutral pH. For example, the onset of action of lidocaine occurs in about 3 minutes; 35% of
lidocaine is in the basic form at pH 7.4. In contrast, the onset of action of bupivacaine requires about 15 minutes;
only 5% to 10% of bupivacaine is in the basic form at this pH. Increased hydrophobicity might be expected to speed
onset by increased penetration into nerve tissue. However, it also increases binding in tissue lipids. Furthermore, the
most hydrophobic local anesthetics also are more potent (and toxic) and thus must be used at lower concentrations,
decreasing the concentration gradient for diffusion. Tissue factors also play a role in determining the rate of onset of
anesthetic effects. The amount of connective tissue that must be penetrated can be significant in a nerve plexus
compared with isolated nerves and can serve to slow or even prevent adequate diffusion of local anesthetic to the
nerve fibers.
Duration of nerve block anesthesia depends on the physical characteristics of the local anesthetic used and the
presence or absence of vasoconstrictors. Especially important physical characteristics are lipid solubility and protein
binding. In general, local anesthetics can be divided into three categories: those with a short (20–45 min) duration of
action in mixed peripheral nerves, such as procaine; those with an intermediate (60–120 min) duration of action,
such as lidocaine and mepivacaine; and those with a long (400–450 min) duration of action, such as bupivacaine,
etidocaine, ropivacaine, and tetracaine. Block duration of the intermediate-acting local anesthetics such as lidocaine
can be prolonged by the addition of epinephrine (5 µg/mL). The degree of block prolongation in peripheral nerves
233
after the addition of epinephrine appears to be related to the intrinsic vasodilatory properties of the local anesthetic
and thus is most pronounced with lidocaine.
The types of nerve fibers that are blocked when a local anesthetic is injected about a mixed peripheral nerve depends
on the concentration of drug used, nerve-fiber size, internodal distance, and frequency and pattern of nerve-impulse
transmission. Anatomic factors are similarly important. A mixed peripheral nerve or nerve trunk consists of
individual nerves surrounded by an investing epineurium. The vascular supply is usually centrally located. When a
local anesthetic is deposited about a peripheral nerve, it diffuses from the outer surface toward the core along a
concentration gradient. Consequently, nerves located in the outer mantle of the mixed nerve are blocked first.
[101] [102]
These fibers usually are distributed to more proximal anatomic structures than those situated near the core of the
mixed nerve and are often motor. If the volume and concentration of local anesthetic solution deposited about the
nerve are adequate, the local anesthetic eventually diffuses inward in amounts adequate to block even the most
centrally located fibers. Lesser amounts of drug block only nerves in the mantle and smaller and more sensitive
central fibers. Furthermore, because removal of local anesthetics occurs primarily in the core of a mixed nerve or
nerve trunk, where the vascular supply is located, the duration of blockade of centrally located nerves is shorter than
that of more peripherally situated fibers.
Choice of local anesthetic, as well as the amount and concentration administered, is determined by the nerves and
the types of fibers to be blocked, the duration of anesthesia required, and the size and health of the patient. For
blocks of 2 to 4 hours, lidocaine (1.0%–1.5%) can be used in the amounts recommended earlier (see Infiltration
Anesthesia). Mepivacaine (up to 7 mg/kg of a 1.0%–2.0% solution) provides anesthesia that lasts about as long as
that from lidocaine. Bupivacaine (2 to 3 mg/kg of a 0.25%–0.375% solution) can be used when a longer duration of
action is required. Addition of 5 µg/mL epinephrine prolongs duration and lowers the plasma concentration of the
intermediate-acting local anesthetics.
Peak concentrations of local anesthetics in blood depend on the amount injected, the physical characteristics of the
local anesthetic, and whether or not epinephrine is used. They also are determined by the rate of blood flow to the
site of injection and the surface area exposed to local anesthetic. This is of particular importance in the safe
application of nerve block anesthesia, because the potential for systemic reactions also is related to peak free serum
concentrations. For example, peak concentrations of lidocaine in blood following epidural injection is 7 µg/mL; the
same amount of lidocaine used for block of the brachial plexus results in peak concentrations in blood of
approximately 3 µg/mL. The amount of local anesthetic that can be injected must, therefore, be adjusted
[103]
according to the anatomic site of the nerve or nerves to be blocked to minimize untoward effects. Addition of
epinephrine can decrease peak plasma concentrations by 20% to 30%. Multiple nerve blocks (e.g., intercostal block)
or blocks performed in vascular regions require reduction in the amount of anesthetic that can be given safely
because the surface area for absorption or the rate of absorption is increased.
INTRAVENOUS REGIONAL ANESTHESIA (BIER BLOCK)
This technique relies on using the vasculature to bring the local anesthetic solution to the nerve trunks and endings.
In this technique, an extremity is exsanguinated with an Esmarch (elastic) bandage, and a proximally located
tourniquet is inflated to between 100 and 150 mm Hg above the systolic blood pressure. The Esmarch bandage is
removed, and the local anesthetic is injected into a previously cannulated vein. Typically, complete anesthesia of the
limb ensues within 5 to 10 minutes. Pain from the tourniquet and the potential for ischemic nerve injury limits
tourniquet inflation to 2 hours or less. However, the tourniquet should remain inflated for at least 15 to 30 minutes to
prevent toxic amounts of local anesthetic from entering the circulation after deflation. Lidocaine (40 to 50 mL) (0.5
mL/kg in children) of a 0.5% solution, without epinephrine, is the drug of choice for this technique. For intravenous
regional anesthesia in adults using a 0.5% solution without epinephrine, the dose administered should not exceed 4
mg/kg. A few clinicians prefer prilocaine (0.5%) to lidocaine because of its higher therapeutic index. The
attractiveness of this technique lies in its simplicity. Its primary disadvantages are that it can be used only for a few
anatomic regions, sensation (i.e., pain) returns quickly after tourniquet deflation, and premature release or failure of
the tourniquet can produce toxic levels of local anesthetic (e.g., 50 mL of 0.5% lidocaine contains 250 mg of
lidocaine). For the last reason and because their longer durations of action offer no advantages, the more cardiotoxic
local anesthetics, bupivacaine and etidocaine, are not recommended for this technique. Intravenous regional
anesthesia is used most often for the forearm and hand but can be adapted for the foot and distal leg.
SPINAL ANESTHESIA
Spinal anesthesia follows the injection of local anesthetic into the cerebrospinal fluid (CSF) in the lumbar space.
This technique was first performed in human beings and described by Bier in 1899. For a number of reasons,
including the ability to produce anesthesia of a considerable fraction of the body with a dose of local anesthetic that
234
produces negligible plasma levels, it still remains one of the most popular forms of anesthesia. In most adults, the
spinal cord terminates above the second lumbar vertebra; between that point and the termination of the thecal sac in
the sacrum, the lumbar and sacral roots are bathed in cerebrospinal fluid (CSF). Thus, in this region, there is a
relatively large volume of CSF within which to inject drug, thereby minimizing the potential for direct nerve trauma.
A brief discussion of the physiologic effects of spinal anesthesia and those features relating to the pharmacology of
the local anesthetics used are presented here. The technical performance and extensive discussion of the physiologic
consequences of spinal anesthesia are beyond the scope of this text.[100] [104]
Physiologic Effects of Spinal Anesthesia
Most of the physiologic side effects of spinal anesthesia are a consequence of the sympathetic blockade produced by
local anesthetic block of the sympathetic fibers in the spinal nerve roots. A thorough understanding of these
physiologic effects is necessary for the safe and successful application of spinal anesthetic. Although some of them
may be deleterious and require treatment, others can be beneficial for the patient or can improve operating
conditions. Most sympathetic fibers leave the spinal cord between T1 and L2. Although local anesthetic is injected
below these levels in the lumbar portion of the dural sac, cephalad spread of the local anesthetic is seen with all but
the smallest volumes injected. This cephalad spread is of considerable importance in the practice of spinal
anesthesia and potentially is under the control of numerous variables, of which patient position and baricity (density
of the drug relative to the density of the CSF) are the most important. The degree of sympathetic block is related to
[105]
the height of sensory anesthesia; often, the level of sympathetic blockade is several spinal segments higher, because
the preganglionic sympathetic fibers are most sensitive to block by low concentrations of local anesthetic. The
effects of sympathetic blockade involve both the actions (now partially unopposed) of the parasympathetic nervous
system as well as the response of the unblocked portion of the sympathetic nervous system. Thus, as the level of
sympathetic block ascends, the actions of the parasympathetic nervous system are increasingly dominant, and the
compensatory mechanisms of the unblocked sympathetic nervous system are diminished. As most sympathetic
nerve fibers leave the cord at T1 or below, few additional effects of sympathetic blockade are seen with cervical
levels of spinal anesthesia. The consequences of sympathetic blockade vary among patients as a function of age,
physical conditioning, and disease state. Interestingly, sympathetic blockade during spinal anesthesia appears to be
inconsequential in healthy children.
Clinically, the most important effects of sympathetic blockade during spinal anesthesia are on the cardiovascular
system. At all but the lowest levels of spinal blockade, some vasodilatation occurs. Vasodilatation is more marked
on the venous than on the arterial side of the circulation, resulting in a pooling of blood in the venous capacitance
vessels. At low levels of spinal anesthesia in healthy patients, this reduction in circulating blood volume is well
tolerated. With an increasing level of block, this effect becomes more marked and venous return becomes gravity-
dependent. If venous return decreases too much, cardiac output and organ perfusion precipitously decline. Venous
return can be increased by modest (10 degrees to 15 degree) head-down tilt or by elevating the legs. At high levels
of spinal blockade, the cardiac accelerator fibers, which exit the spinal cord at T1 to T4, will be blocked. This is
detrimental in patients dependent on elevated sympathetic tone to maintain cardiac output (e.g., during congestive
heart failure or hypovolemia), and it also removes one of the compensatory mechanisms available to maintain organ
perfusion during vasodilation. Thus, as the level of spinal block ascends, the rate of cardiovascular compromise can
accelerate if not carefully observed and treated. Sudden asystole also can occur, presumably because of loss of
sympathetic innervation in the continued presence of parasympathetic activity at the sinoatrial node. In the usual
[106]
clinical situation, blood pressure serves as a surrogate marker for cardiac output and organ perfusion.
Treatment of hypotension usually is warranted when the blood pressure decreases to about 30% of resting values.
Therapy is aimed at maintaining brain and cardiac perfusion and oxygenation. To achieve these goals,
administration of oxygen, fluid infusion, manipulation of patient position as mentioned earlier, and the
administration of vasoactive drugs are all options. In particular, patients typically are administered a bolus (500–
1000 mL) of fluid before the administration of spinal anesthesia in an attempt to prevent some of the deleterious
effects of spinal blockade. As the usual cause of hypotension is decreased venous return, possibly complicated by
decreased heart rate, vasoactive drugs with preferential venoconstrictive and chronotropic properties are preferred.
For this reason ephedrine (5–10 mg intravenously) often is the drug of choice. In addition to the use of ephedrine to
treat deleterious effects of sympathetic blockade, direct-acting á1 -adrenergic receptor agonists such as
phenylephrine frequently are administered either by bolus or continuous infusion.
Spinal anesthesia exerts a beneficial effect on the intestine, partially mediated by the sympathetic nervous system.
Sympathetic fibers originating from T5 to L1 inhibit peristalsis; thus, their blockade produces a small, contracted
intestine. This contraction and a flaccid abdominal musculature produce excellent operating conditions for some
types of bowel surgery. The effects of spinal anesthesia on the respiratory system mostly are mediated by effects on
the skeletal musculature. Paralysis of the intercostal muscles reduces a patient’s ability to cough and clear
235
secretions, which may be undesirable in a bronchitic or emphysematous patient and may produce dyspnea. It should
be noted that respiratory arrest during spinal anesthesia is seldom caused by paralysis of the phrenic nerves or by
toxic levels of local anesthetic in the CSF of the fourth ventricle. It is much more likely to be due to medullary
ischemia secondary to hypotension.
Pharmacology of Spinal Anesthesia
Currently, in the United States, the drugs most commonly used in spinal anesthesia are lidocaine, tetracaine, and
bupivacaine. Procaine occasionally is used for diagnostic blocks for which a short duration of action is desired. The
choice of local anesthetic primarily is determined by the duration of anesthesia desired. General guidelines are to use
lidocaine for short procedures, bupivacaine for intermediate to long procedures, and tetracaine for long procedures.
As mentioned earlier, the factors contributing to the distribution of local anesthetics in the CSF have received much
attention because of their importance in determining the height of the block. The most important pharmacologic
factors include the amount and, possibly, the volume of drug injected and its baricity. The speed of injection of the
local anesthesia solution also may affect the height of the block, just as the position of the patient can influence the
rate of distribution of the anesthetic agent and the height of blockade achieved. For a given preparation of local
anesthetic, administration of increasing amounts leads to a fairly predictable increase in the level of block attained.
For example, 100 mg of lidocaine, 20 mg of bupivacaine, or 12 mg of tetracaine usually result in a T4 sensory
block. More complete tables of these values can be found in standard anesthesiology texts. Epinephrine often is
added to spinal anesthetics to increase the duration or intensity of block. Epinephrine’s effect on duration of block is
dependent on the technique used to measure duration. A commonly used measure of block duration is the length of
time it takes for the block to recede by two dermatomes from the maximal height of the block, whereas a second is
the duration of block at some specified level, typically L1. In most studies, addition of 200 µg of epinephrine to
tetracaine solutions prolongs the duration of block by both measures. However, addition of epinephrine to lidocaine
or bupivacaine does not affect the first measure of duration but does prolong the block at lower levels. In different
clinical situations, one or the other measure of anesthesia duration may be more relevant, and this must be kept in
mind when deciding to add epinephrine to spinal local anesthetics. The mechanism of action of vasoconstrictors in
prolonging spinal anesthesia is uncertain. It has been hypothesized that these agents decrease spinal cord blood flow,
decreasing clearance of local anesthetic from the CSF, but this has not been convincingly demonstrated.
Epinephrine, working via α2 -adrenergic receptors, has been shown to decrease nociceptive transmission in the
spinal cord; it is possible that this action contributes to the effects of epinephrine.
Drug Baricity and Patient Position
The baricity of the local anesthetic injected determines the direction of migration within the dural sac. Hyperbaric
solutions tend to settle in the dependent portions of the sac, whereas hypobaric solutions tend to migrate in the
opposite direction. Isobaric solutions usually stay in the vicinity where they were injected, diffusing slowly in all
directions. Consideration of the patient position during and after the performance of the block and the choice of a
local anesthetic of the appropriate baricity is crucial for a successful block during some surgical procedures. For
example, a saddle (perineal) block is best performed with a hyperbaric anesthetic in the sitting position if the patient
remains in that position until the anesthetic level becomes “fixed.” On the other hand, for a saddle block in the
prone, jackknife position, a hypobaric local anesthetic is appropriate. Lidocaine and bupivacaine are marketed in
both isobaric and hyperbaric preparations and, if desired, can be diluted with sterile, preservative-free water to make
them hypobaric.
Complications of Spinal Anesthesia
Persistent neurologic deficits after spinal anesthesia are extremely rare. Thorough evaluation of a suspected deficit
should be performed in collaboration with a neurologist. Neurologic sequelae can be both immediate and late.
Possible causes include introduction of foreign substances (such as disinfectants or talc) into the subarachnoid space,
infection, hematoma, or direct mechanical trauma. Aside from drainage of an abscess or hematoma, treatment
usually is ineffective; thus, careful attention to detail while performing spinal anesthesia is necessary. High
concentrations of local anesthetic can cause irreversible block. After administration, local anesthetic solutions are
diluted rapidly, quickly reaching nontoxic concentrations. However, concern has been raised that 5% lidocaine (i.e.,
180 mM) in 7.5% glucose may be neurotoxic when delivered via small-bore indwelling catheters to areas of
stagnant CSF. Spinal anesthesia sometimes is regarded as contraindicated in patients with preexisting disease of
[52]
the spinal cord. No experimental evidence exists to support this hypothesis. Nonetheless, it is prudent to avoid spinal
anesthesia in patients with progressive diseases of the spinal cord. However, spinal anesthesia may be very useful in
patients with fixed, chronic spinal cord injury.
A more common sequela following any lumbar puncture, including spinal anesthesia, is a postural headache with
classic features. The incidence of headache decreases with increasing age of the patient and decreasing needle
diameter. Treatment usually is conservative, with bed rest and analgesics. If this approach fails, an epidural blood
236
patch can be performed; this procedure usually is successful in alleviating postdural puncture headaches, although a
second blood patch may be necessary. Intravenous caffeine (500 mg as the benzoate salt administered over 4 hours)
also has been advocated for the treatment of postdural puncture headache. However, the efficacy of caffeine is less
than that of a blood patch, and relief usually is transient. If two epidural blood patches are ineffective in relieving the
headache, the diagnosis of postdural puncture headache should be reconsidered.
EPIDURAL ANESTHESIA
Epidural anesthesia is administered by injecting local anesthetic into the epidural space—the space bounded by the
ligamentum flavum posteriorly, the spinal periosteum laterally, and the dura anteriorly. Epidural anesthesia can be
performed in the sacral hiatus (caudal anesthesia) or in the lumbar, thoracic, or cervical regions of the spine. Its
current popularity arises from the development of catheters that can be placed into the epidural space, allowing
either continuous infusions or repeated bolus administration of local anesthetics. The primary site of action of
epidurally administered local anesthetics is the spinal nerve roots. However, epidurally administered local
anesthetics also may act on the spinal cord and on the paravertebral nerves.
The drugs available for epidural anesthesia are similar to those for major nerve blocks. As for spinal anesthesia, the
choice of drugs to be used during epidural anesthesia is dictated primarily by the duration of anesthesia desired.
However, when an epidural catheter is placed, short-acting drugs can be administered repeatedly, providing more
control over the duration of block. Bupivacaine (0.5% to 0.75%) is used when a long duration of surgical block is
desired. Because of enhanced cardiotoxicity in pregnant patients, the 0.75% solution is not approved for obstetric
use. Lower concentrations (0.25%, 0.125%, or 0.0625%) of bupivacaine, often with 2 µg/mL of fentanyl added,
frequently are used to provide analgesia during labor. They also are useful preparations for providing postoperative
analgesia in certain clinical situations. Etidocaine (1.0% or 1.5%) is useful for providing surgical anesthesia with
excellent muscle relaxation of long duration. Lidocaine (2%) is the most frequently used intermediate-acting
epidural local anesthetic. 2-Chloroprocaine (2% or 3%) provides rapid onset and a very short duration of anesthetic
action. However, its use in epidural anesthesia has been clouded by controversy regarding its potential ability to
cause neurologic complications if the drug is accidentally injected into the subarachnoid space. The duration of
action of epidurally administered local anesthetics is frequently prolonged and systemic toxicity decreased by
addition of epinephrine. Addition of epinephrine also makes inadvertent intravascular injection easier to detect and
modifies the effect of sympathetic blockade during epidural anesthesia.
For each anesthetic agent, a relationship exists between the volume of local anesthetic injected epidurally and the
segmental level of anesthesia achieved. For example, in 20- to 40-year-old, healthy, nonpregnant patients, each 1 to
1.5 mL of 2% lidocaine gives an additional segment of anesthesia. The amount needed decreases with increasing
age and also is decreased during pregnancy and in children.
The concentration of local anesthetic used determines the type of nerve fibers blocked. The highest concentrations
are used when sympathetic, somatic sensory, and somatic motor blockade are required. Intermediate concentrations
allow somatic sensory anesthesia without muscle relaxation. Low concentrations block only preganglionic
sympathetic fibers. As an example, with bupivacaine these effects may be achieved with concentrations of 0.5%,
0.25%, and 0.0625%, respectively. The total amounts of drug that can be injected with safety at one time are
approximately those mentioned above in “Nerve Block Anesthesia” and “Infiltration Anesthesia.” Performance of
epidural anesthesia requires a greater degree of skill than spinal anesthesia. The technique of epidural anesthesia and
the volumes, concentrations, and types of drugs used are described in detail in standard anesthesiology texts. [15] [100]
A significant difference between epidural and spinal anesthesia is that the dose of local anesthetic used can produce
high concentrations in blood after absorption from the epidural space. Peak concentrations of lidocaine in blood
following injection of 400 mg (without epinephrine) into the lumbar epidural space average 3 to 4 µg/mL; peak
concentrations of bupivacaine in blood average 1.0 µg/mL after the lumbar epidural injection of 150 mg. Addition
of epinephrine (5 µg/mL) decreases peak plasma concentrations by about 25%. Peak blood concentrations are a
function of the total dose of drug administered rather than the concentration or volume of solution after epidural
injection. The risk of inadvertent intravascular injection is increased in epidural anesthesia because the epidural
[103]
space contains a rich venous plexus.
Another major difference between epidural and spinal anesthesia is that there is no zone of differential sympathetic
blockade with epidural anesthesia; thus, the level of sympathetic block is close to the level of sensory block.
Because epidural anesthesia does not result in the zone of differential sympathetic blockade that is observed during
spinal anesthesia, cardiovascular responses to epidural anesthesia might be expected to be less prominent. In
practice, however, this is not the case; this potential advantage of epidural anesthesia is offset by the cardiovascular
responses to the high concentration of anesthetic in blood that occurs during epidural anesthesia. This is most
237
apparent when, as is often the case, epinephrine is added to the epidural injection. The resulting concentration of
epinephrine in blood is sufficient to produce significant β2 -adrenergic receptor-mediated vasodilation. As a
consequence, blood pressure decreases, even though cardiac output increases owing to the positive inotropic and
chronotropic effects of epinephrine. The result is peripheral hypoperfusion and hypotension. Differences in
cardiovascular responses to equal levels of spinal and epidural anesthesia also are observed when a local anesthetic
such as lidocaine is used without epinephrine. This may be a consequence of the direct effects of high
concentrations of lidocaine on vascular smooth muscle and the heart. The magnitude of the differences in responses
to equal sensory levels of spinal and epidural anesthesia varies, however, with the local anesthetic used for the
epidural injection (assuming no epinephrine is used). For example, local anesthetics such as bupivacaine, which are
highly lipid-soluble, are distributed less into the circulation than are less lipid-soluble agents such as lidocaine.
High concentrations of local anesthetics in blood during epidural anesthesia are of special importance when this
technique is used to control pain during labor and delivery. Local anesthetics cross the placenta, enter the fetal
circulation, and at high concentrations may cause depression of the neonate. The extent to which they do so is
[107]
determined by dosage, acid-base status, the level of protein binding in both maternal and fetal blood, placental [108]
blood flow, and solubility of the agent in fetal tissue. These concerns have been lessened by the trend toward using
more dilute solutions of bupivacaine for labor analgesia.
LOCAL ANESTHETICS FOR SKIN AND MUCOUS MEMBRANES
Some anesthetics are either too irritating or too ineffective to be applied to the eye. However, they are useful as
topical anesthetic agents on the skin, mucous membranes, or both. These preparations are effective in the
symptomatic relief of anal and genital pruritus, poison ivy rashes, and numerous other acute and chronic dermatoses.
They are sometimes combined with a glucocorticoid or antihistamine and are available in a number of proprietary
formulations.
Dibucaine
Dibucaine (Nupercainal) is a quinoline derivative. Its toxicity resulted in its removal from the U.S. market as an
injectable preparation; however, it retains wide popularity outside of the United States as a spinal anesthetic. It
currently is available as a cream and an ointment for use on the skin.
Dyclonine Hydrochloride
Dyclonine hydrochloride (Dyclone) has a rapid onset of action and duration of effect comparable to that of procaine.
It is absorbed through the skin and mucous membranes. The compound is used as 0.5% or 1.0% solution for topical
anesthesia during endoscopy, for oral mucositis pain following radiation or chemotherapy, and for anogenital
procedures.
Figure 13-17 A surface anesthetic agent that is not a benzoate ester. Its distinct chemical structure may help to minimize the danger of cross-
sensitivity reaction in patients allergic to other local anesthetics.
Pramoxine Hydrochloride
Pramoxine hydrochloride (Anusol, Tronothane, others) is a surface anesthetic agent that is not a benzoate ester. Its
distinct chemical structure ( Fig. 13-17 ) may help to minimize the danger of cross-sensitivity reactions in patients
allergic to other local anesthetics. Pramoxine produces satisfactory surface anesthesia and is reasonably well
tolerated on the skin and mucous membranes. It is too irritating to be used on the eye or in the nose. Various
preparations are available for topical application, usually including 1% pramoxine.
Anesthetics of Low Solubility
238
Some local anesthetics are poorly soluble in water and, consequently, too slowly absorbed to be toxic. They can be
applied directly to wounds and ulcerated surfaces, where they remain localized for long periods of time to produce a
sustained anesthetic action. Chemically, they are esters of PABA, lacking the terminal amino group possessed by the
previously described local anesthetics. The most important member of the series is benzocaine (ethyl
aminobenzoate, Americaine, others). Benzocaine is structurally similar to procaine; the difference is that it lacks the
terminal diethylamino group ( Fig. 13-18 ). It is incorporated into a large number of topical preparations.
Benzocaine has been reported to cause methemoglobinemia; consequently, dosing recommendations must be
carefully followed.
LOCAL ANESTHETICS FOR EYE SURGERY
Anesthesia of the cornea and conjunctiva can be obtained readily by topical application of local anesthetics.
However, most of the local anesthetics described earlier are too irritating for ophthalmologic use. The
Figure 13-18 Structurally similar to procaine; the difference is that it lacks the terminal diethylamino group.
Figure 13-19 The most frequently used local anesthetics in ophthalmology.
first local anesthetic used in ophthalmology, cocaine, has the disadvantage of producing mydriasis and corneal
sloughing and has fallen out of favor. The two compounds used most frequently today are proparacaine (Alcaine,
Ophthaine, others) and tetracaine ( Fig. 13-19 ). In addition to being less irritating during administration,
proparacaine has the added advantage of bearing little antigenic similarity to the other benzoate local anesthetics.
Thus, it sometimes can be used in individuals sensitive to the amino ester local anesthetics.
For use in ophthalmology, these local anesthetics are instilled a single drop at a time. If anesthesia is incomplete,
successive drops are applied until satisfactory conditions are obtained. The duration of anesthesia is determined
chiefly by the vascularity of the tissue; thus, it is longest in normal cornea and least in inflamed conjunctiva. In the
latter case, repeated instillations are necessary to maintain adequate anesthesia for the duration of the procedure.
Long-term administration of topical anesthesia to the eye has been associated with retarded healing and pitting,
sloughing of the corneal epithelium, and predisposition of the eye to inadvertent injury. Thus, these drugs should not
be prescribed for self-administration.
REFERENCES
239
1. RangHP, Ritchie JM: On the electrogenic sodium pump in mammalian non-myelinated nerve fibers and its activation by various cations. J
Physiol 196:183–221, 1968.
2. Catterall WA: Structure and function of voltage-gated ion channels. Trends Neurosci 16:500–506, 1993.
3. Ragsdale DS, McPhee JC, Scheuer T, et al: Molecular determinants of state-dependent block of Na+ channels by local anesthetics. Science
265:1724–1728, 1994.
4. Courtney
KR, Strichartz GR: Structural elements which determine local anesthetic activity. In Strichartz GR (ed): Handbook of Experimental
Pharmacology, vol 81, Berlin, Springer-Verlag, 1987, pp 53–94.
5. Hille B: Local anesthetics: Hydrophilic and hydrophobic pathways for the drug-receptor reaction. J Gen Physiol 69:497–515, 1977.
6. Reiz S, Haggmark S, Johansson G, et al: Cardiotoxicity of ropivacaine—a new amide local anesthetic agent. Acta Anaesthesiol Scand 33:93–
98, 1989.
7. Santos AC, Arthur GR, Padderson H, et al: Systemic toxicity of ropivacaine during bovine pregnancy. Anesthesiology 75:137–141, 1994.
8. Strichartz
GR, Ritchie JM: The action of local anesthetics on ion channels of excitable tissues. In Strichartz GR (ed): Handbook of
Experimental Pharmacology, vol 81, Berlin, Springer-Verlag, 1987, pp 21–53.
9. Narahashi T, Frazier DT: Site of action and active form of local anesthetics. Neurosci Res 4:65–99, 1971.
10. Butterworth
JF, Strichartz GR: The molecular mechanisms by which local anesthetics produce impulse blockade: A review. Anesthesiology
72:711–734, 1990.
11. Catterall WA: Cellular and molecular biology of voltage-gated sodium channels. Physiol Rev 72:S15–S48, 1992.
12. Ragsdale
DR, McPhee JC, Scheuer T, et al: Molecular determinants of state-dependent block of Na+ channels by local anesthetics. Science
265:1724–1728, 1994.
13. Gasser HS, Erlanger J: The role of fiber size in the establishment of a nerve block by pressure or cocaine. Am J Physiol 88:581–591, 1929.
14. Raymond SA, Gissen AJ: Mechanism of differential nerve block. In Strichartz GR (ed): Handbook of Experimental Pharmacology, vol 81,
15. CarpenterRI, Mackey DC: Local anesthetics. In Barash PG, Cullen BF, Stoelting RK (eds): Clinical Anesthesia, 2nd ed. Philadelphia, JB
Lippincott, 1992, pp 509–541.
16. Ritchie JM, Greengard P: On the mode of action of local anesthetics. Annu Rev Pharmacol 6:405–430, 1966.
17. DiFazio CA, Carron H, Grosslight KR, et al: Comparison of pH-adjusted lidocaine solutions for epidural anesthesia. Anesth Analg 65:760–
764, 1986.
18. Hilgier M: Alkalinization of bupivacaine for brachial plexus block. Reg Anesth 10:59–61, 1985.
19. Bromage PR: A comparison of the hydrochloride and carbon dioxide salts of lidocaine and prilocaine in epidural analgesia. Acta Anaesth
Scand Suppl XVI:(Suppl)55–69, 1965.
20. Bromage PR, Burfoot MF, Crowell DE, et al: Quality of epidural blockade III: Carbonated local anaesthetic solutions. Br J Anaesth 39:197–
208, 1967.
21. BrownDT, Morison DH, Covino BG, et al: Comparison of carbonated bupivacaine and bupivacaine hydrochloride for extradural anaesthesia.
Br J Anaesth 52:419–422, 1980.
22. Mehta PM, Theriot E, Mehrotra D, et al: A simple technique to make bupivacaine a rapid-acting epidural anesthetic. Reg Anesth 12:135–138,
1987.
23. Fischer
RL, Lubenow TR, Liceaga A, et al: Comparison of continuous epidural infusion of fentanyl-bupivacaine and morphine-bupivacaine in
management of postoperative pain. Anesth Analg 67:559–563, 1988.
24. Chestnut
DH, Owen CL, Bates JN, et al: Continuous infusion epidural analgesia during labor: A randomized double-blind comparison of
0.0625% bupivacaine/0.0002% fentanyl versus 0.125% bupivacaine. Anesthesiology 68:754–759, 1988.
25. Denson
D, Coyle D, Thompson GA, et al: Alpha-1-acid glycoprotein and albumin in human serum bupivacaine binding. Clin Pharmacol Ther
35:409–415, 1984.
26. Tucker GT, Mather LE: Pharmacokinetics of local anesthetic agents. Br J Anaesth 47:213–224, 1975.
27. Arthur GR: Pharmacokinetics. In Strichartz GR (ed): Handbook of Experimental Pharmacology, vol 81, Berlin, Springer-Verlag, 1987, pp
165–186.
240
28. Covino BG: Toxicity and systemic effects of local anesthetic agents. In Strichartz GR (ed): Handbook of Experimental Pharmacology, vol. 81,
29. Burney RG, DiFazio CA, Foster JA: Effects of pH on protein binding of lidocaine. Anesth Analg 57:478–480, 1978.
30. McNamara PJ, Slaughter RL, Pieper JA et al: Factors influencing serum protein binding of lidocaine in humans. Anesth Analg 60:395–400,
1981.
31. Wood M, Wood AJJ: Changes in plasma drug binding and alpha-1-acid glycoprotein in mother and newborn infant. Clin Pharmacol Ther
29:522–526, 1981.
32. Katz
JA, Bridenbaugh PO, Knarr DC, et al: Pharmacodynamics and pharmacokinetics of epidural ropivacaine in humans. Anesth Analg 70:16–
21, 1990.
33. Scott DB, Jepson PJ, Braid DP, et al: Factors affecting plasma levels of lidocaine and prilocaine. Br J Anaesth 44:1040–1049, 1972.
34. Garfield JM, Gugino L: Central effects of local anesthetics. In Strichartz GR (ed): Handbook of Experimental Pharmacology, vol 81, Berlin,
Springer-Verlag, 1987, pp 187–212.
35. Gintant
GA, Hoffman BF: The role of local anesthetic effects in the actions of antiarrhythmic drugs. In Strichartz GR (ed): Handbook of
Experimental Pharmacology, vol 81, Berlin, Springer-Verlag, 1987, pp 213–251.
36. Neher
E, Steinbach JH: Local anesthetics transiently block currents through single acetylcholine receptor channels. J Physiol (London)
277:153–176, 1978.
37. CharnetP, Labarca C, Leonard RJ, et al: An open-channel blocker interacts with adjacent turns of alpha-helices in the nicotinic acetylcholine
receptor. Neuron 4:87–95, 1990.
38. Zipf
HF, Dittmann EC: General pharmacological effects of local anesthetics. In Lechat P (ed): International Encyclopedia of Pharmacology
and Therapeutics, vol 1, Oxford, Pergamon Press, 1971, pp 191–238.
39. Smith
AR, Hur D, Resano F: Grand mal seizures after 2-chloroprocaine epidural anesthesia in a patient with plasma cholinesterase deficiency.
Anesth Analg 66:677–678, 1987.
40. Aldrete JA, Johnson DA: Evaluation of intracutaneous testing for investigation of allergy to local anesthetic agents. Anesth Analg 49:173–183,
1970.
41. Halldin MM, Bredberg E, Arvidsson AT, et al: Metabolism and secretion of ropivacaine in humans. Drug Metab Dispos 24:962–968, 1996.
42. Oda
Y, Furuichi K, Tanaka K, et al: Metabolism of a new local anesthetic, ropivacaine, by human hepatic cytochrome P450. Anesthesiology
82:214–220, 1995.
43. Brosen K, Skjelbo E, Rasmussen BB, et al: Fluvoxamine is a potent inhibitor of cytochrome P450 1A2. Biochem Pharmacol 45:1211–1214,
1993.
44. Dripps RD, Vandam LD: Long-term follow-up of patients who received 10,098 spinal anesthetics: Failure to discover major neurological
sequelae. JAMA 156:1486–1491, 1954.
45. Vandam LD, Dripps RD: A long-term follow-up of 10,098 spinal anesthetics: II. Incidence and analysis of minor sensory neurological defects.
Surgery 38:463–469, 1955.
46. Phillips
OC, Ebner H, Nelson AT, et al: Neurologic complications following spinal anesthesia with lidocaine: A prospective review of 10,440
cases. Anesthesiology 30:284–289, 1969.
47. Horlocker
TT, McGregor DG, Matsushige DK, et al: A retrospective review of 4,767 consecutive spinal anesthetics: Central nervous system
complications. Anesth Analg 84:578–584, 1997.
48. Gissen AJ, Datta S, Lambert D: The chloroprocaine controversy: II. Is chloroprocaine neurotoxic? Reg Anesth 9:135–145, 1984.
49. Wang BC, Hillman DE, Spielholz NI, et al: Chronic neurological deficits and nesacaine-CE: An effect of the anesthetic, 2-chloroprocaine, or
the antioxidant, sodium bisulfite? Anesth Analg 63:445–447, 1984.
50. Ready L, Plumer M, Haschke R, et al: Neurotoxicity of intrathecal local anesthetic in rabbits. Anesthesiology 63:364–379, 1985.
51. Selander D: Neurotoxicity of local anesthetics: Animal data. Reg Anesth 18:461–468, 1993.
52. Rigler MI, Drasner K, Krejcie TC, et al: Cauda equina syndrome after continuous spinal anesthesia. Anesth Analg 72:275–281, 1991.
53. Schneider
M, Ettlin T, Kaufmann M, et al: Transient neurologic toxicity after hyperbaric subarachnoid anesthesia with 5% lidocaine. Anesth
Analg 76:1154–1157, 1993.
54. Hampl KF, Schneider MC, Ummenhofer W, et al: Transient neurologic symptoms after spinal anesthesia. Anesth Analg 81:1148–1153, 1995.
241
55. Carpenter RL: Hypobaric lidocaine spinal anesthesia: Do we need an alternative? Anesth Analg 81:1125–1128, 1995.
56. PollockJ, Neal J, Stephenson C, et al: Prospective study of the incidence of transient radicular irritation in patients undergoing spinal
anesthesia. Anesthesiology 84:1361–1367, 1996.
57. Hampl
KF, Schneider M, Pargger H: A similar incidence of transient neurologic symptoms after spinal anesthesia with 2% and 5% lidocaine.
Anesth Analg 83:1051–1054, 1996.
58. Drasner K: Lidocaine spinal anesthesia: A vanishing therapeutic index? Anesthesiology 87:469–472, 1997.
59. Tarkkila P, Huhtala J, Tuominen M: Transient radicular irritation after spinal anesthesia with hyperbaric 5% lidocaine. Br J Anaesth 74:328–
329, 1995.
60. Sumi
M, Sakura S, Kosaka Y: Intrathecal hyperbaric 0.5% tetracaine as a possible cause of transient neurologic toxicity. Anesth Analg
82:1076–1077, 1996.
61. Lynch
J, zur Nieden M, Kasper S-M, et al: Transient radicular irritation after spinal anesthesia with hyperbaric 4% mepivacaine. Anesth Analg
85:872–873, 1997.
62. Hampl KF, Heinzmann-Wiedmer S, Luginbuehl I, et al: Transient neurologic symptoms after spinal anesthesia: A lower incidence with
prilocaine and bupivacaine than with lidocaine. Anesthesiology 88:629–633, 1998.
63. DiFazioCA, Rowlingson JC: Additives to local anesthetic solutions. In Brown DL (ed): Regional Anesthesia and Analgesia. Philadelphia, WB
Saunders, 1996, pp 232–239.
64. Rowlingson JC: Toxicity of local anesthetic additives. Reg Anesth 18:453–460, 1993.
65. SakuraS, Sumi M, Sakaguchi Y, et al: The addition of phenylephrine contributes to the development of transient neurologic symptoms after
spinal anesthesia with 0.5% tetracaine. Anesthesiology 87:771–778, 1997.
66. SakuraS, Chan VWS, Ciriales R, et al: The addition of 7.5% glucose does not alter the neurotoxicity of 5% lidocaine administered
intrathecally in the rat. Anesthesiology 87:771–778, 1997.
67. Hampl HF, Schneider MC, Thorin D, et al: Hyperosmolarity does not contribute to transient radicular irritation after spinal anesthesia with
hyperbaric 5% lidocaine. Reg Anesth 20:363–368, 1995.
68. AuroyY, Narchi P, Messiah A, et al: Serious complications related to regional anesthesia: Results of a prospective survey in France.
69. Eisenach JC: Regional anesthesia: Vintage Bordeaux (and Napa Valley). Anesthesiology 87:467–469, 1997.
70. Wagman IH, deJong RH, Prince DA: Effect of lidocaine on the central nervous system. Anesthesiology 28:155–172, 1967.
71. Moore DC: Administer oxygen first in the treatment of local anesthetic-induced convulsions. Anesthesiology 53:346–347, 1980.
72. Avery
P, Redon D, Schaenzer G, et al: The influence of serum potassium on the cerebral and cardiac toxicity of bupivacaine and lidocaine.
73. Sage
DJ, Feldman HS, Arthur GR, et al: Influence of bupivacaine and lidocaine on isolated guinea pig atria in the presence of acidosis and
hypoxia. Anesth Analg 63:1–7, 1984.
74. Albright GA: Cardiac arrest following regional anesthesia with etidocaine or bupivacaine [editorial]. Anesthesiology 51:285–287, 1978.
75. Block A, Covino BG: Effect of local anesthetic agents in cardiac conduction and contractility. Reg Anesth 6:55–58, 1981.
76. Lynch C III: Depression of myocardial contractility in vitro by bupivacaine, etidocaine, and lidocaine. Anesth Analg 65:551–559, 1986.
77. FeldmanHS, Covino BG, Sage DJ: Direct chronotropic and inotropic effects of local anesthetic agents in isolated guinea pig atria. Reg Anesth
7:149–154, 1982.
78. Stevens MF, Klement W, Lipfert P: Conduction block in man is stimulation frequency dependent. Anesthetists 45:533–537, 1996.
79. HuangYF, Pryor ME, Mather LE, et al: Cardiovascular and central nervous system effects of intravenous levobupicaine and bupivacaine in
sheep. Anesth Analg 86:797–804, 1998.
80. ClarksonCW, Hondeghem LM: Mechanism for bupivacaine depression of cardiac conduction: Fast block of sodium channels during the
action potential with slow recovery from block during diastole. Anesthesiology 62:396–405, 1985.
81. Thomas RD, Behbehani MM, Coyle DE, et al: Cardiovascular toxicity of local anesthetics: An alternative hypothesis. Anesth Analg 65:444–
450, 1986.
242
82. Heavner JE: Cardiac dysrhythmias induced by infusion of local anesthetics into the lateral cerebral ventricle of cats. Anesth Analg 65:133–
138, 1996.
83. Johns RA, Seyde WC, DiFazio CA, et al: Dose-dependent effects of bupivacaine on rat muscle arterioles. Anesthesiology 65:186–191, 1986.
84. Santos
AC, Arthur GR, Lehning EJ, et al: Comparative pharmacokinetics of ropivacaine and bupivacaine in nonpregnant and pregnant ewes.
Anesth Analg 85:87–93, 1997.
85. Kasten
GW, Martin ST: Bupivacaine cardiovascular toxicity: Comparison of treatment with bretylium and lidocaine. Anesth Analg 64:911–
916, 1985.
86. Stevens RA, Urmey WF, Urquhart BL, et al: Back pain after epidural anesthesia with chloroprocaine. Anesthesiology 78:492–497, 1993.
87. Wang BC, Hillman DE, Spiedholz NI, et al: Chronic neurologic deficits and Nesacaine-CE: An effect of the anesthetic, 2-chloroprocaine, or
the antioxidant, sodium bisulfite. Anesth Analg 63:445–447, 1984.
88. Fibuch EE, Opper SE: Back pain following epidurally administered Nesacaine MPF. Anesth Analg 69:113–115, 1989.
89. Nath
S, Haggmark S, Johansson G, et al: Differential depressant and electrophysiologic cardiotoxicity of local anesthetics: An experimental
study with special reference to lidocaine and bupivacaine. Anesth Analg 65:1263–1270, 1986.
90. Ludena FP, Bogado EF, Tullar BF: Optical isomers of mepivacaine and bupivacaine. Arch Int Pharmacodyn Ther 200:359–369, 1972.
91. Aberg G: Toxicological and local anesthetic effects of optically active isomers of two local anaesthetic compounds. Acta Pharmacol Toxicol
31:273–286, 1972.
92. Akerman B, Hellberg IB, Trossvik C: Primary evaluation of the local anesthetic properties of the amino amide agent ropivacaine (LEA 103).
93. Reiz S, Haggmark S, Johansson G, et al: Cardiotoxicity of ropivacaine—a new amide local anaesthetic agent. Acta Anaesthesiol Scand 33:93–
98, 1989.
94. Graf
BM, Martin E, Bosnjak ZJ, et al: Stereospecific effect of bupivacaine isomers on atrioventricular conduction in the isolated perfused
guinea pig heart. Anesthesiology 86:410–419,1997.
95. Kao CY: Pharmacology of tetrodotoxin and saxitoxin. Fed Proc 31:1117–1123, 1972.
96. Ritchie JM: Tetrodotoxin and saxitoxin and the sodium channels of excitable tissues. Trends Pharmacol Sci 1:275–279, 1980.
97. Terlau H, Heinemann SH, Stühmer W, et al: Mapping the site of block by tetrodotoxin and saxitoxin of sodium channel II. FEBS Lett 293:93–
96, 1991.
98. OguraY: Fugu (puffer-fish) poisoning and the pharmacology of crystalline tetrodotoxin poisoning. In Simpson LL (ed): Poisons of Animal
Origin, vol I, New York, Plenum Press, 1971, pp 139–156.
99. Schantz
EJ: Paralytic shellfish poisoning and saxitoxin. In Simpson LL (ed): Poisons of Animal Origin, vol I, New York, Plenum Press, 1971,
pp 159–168.
100. Cousins MJ, Bridenbaugh PO (eds): Neural Blockade in Clinical Anesthesia and Management of Pain, 3rd ed. Philadelphia, JB Lippincott,
1995.
101. DeJong RH: Local Anesthetics. St. Louis, Mosby–Year Book, 1993.
102. Winnie AP, Tay CH, Patel KP, et al: Pharmacokinetics of local anesthetics during plexus blocks. Anesth Analg 56:852–861, 1977.
103. Covino BG, Vassallo HG: Local Anesthetics: Mechanisms of Action and Clinical Use. New York, Grune & Stratton, 1976.
104. Greene NM, Brull SJ: Physiology of Spinal Anesthesia, 3rd ed. Baltimore, Williams & Wilkins, 1993.
105. Greene NM: Uptake and elimination of local anesthetics during spinal anesthesia. Anesth Analg 62:1013–1024, 1983.
106. Caplan RA, Ward RJ, Posner K, et al: Unexpected cardiac arrest during spinal anesthesia: A closed claims analysis of predisposing factors.
107. Scanlon JW, Brown WU Jr, Weiss JB, et al: Neurobehavioral responses of newborn infants after maternal epidural anesthesia. Anesthesiology
40:121–128, 1974.
108. Tucker GT, Boyes RN, Bridenbaugh PO, et al: Binding of anilide-type local anesthetics in human plasma. II. Implications in vivo, with
special reference to transplacental distribution. Anesthesiology 35:304–314, 1970.
243
Section IV - Chapter 14 - Adjuvant Drugs
Chapter 14 - Adjuvant Drugs
ATHINA N. VADALOUCA
The use of adjuvant drugs for spinal and epidural anesthesia is intended to improve the success of regional
anesthesia by prolonging the analgesia of local anesthetics and preventing the deleterious clinical effects of their
toxic doses.
The nerve blockade produced must be complete and reproducible and must also produce the desired duration of
action. In the past, this goal was attained by means of new local anesthetic drugs with better spread and good
separation of motor and sensory effects. At present, the action of a second drug added to the local anesthetic is
directed toward decreasing sensory input to the central nervous system; thus, a major advance in improving the
success of regional anesthesia has been achieved. These adjuvant drugs act at a secondary site of action different
from that of the local anesthetic. The adjuvant drugs used today range from epinephrine and opiates to α2 -agonist
blockers and N-methyl-D-aspartate-(NMDA)–receptor antagonists, and to cholinergic agonists and
acetylcholinesterase inhibitor receptor agonists. In addition, the role of calcitonin, octreotide (Sandostatin), and
adenosine adjuvant drugs for intraspinal and epidural administration is currently under investigation.
Vasoconstrictors
For many years, vasoconstrictors were the only adjuvant drugs available, and, even today, they are commonly used.
Local anesthetics, with the exception of cocaine, cause peripheral vasodilatation by direct effects on blood vessel
smooth muscle, their vascular absorption being enhanced by the local anesthetic’s vasodilator property. The duration
of a local anesthetic is considered to be proportional to the amount of time that the drug remains in contact with the
nerve. Vascular absorption is delayed with the addition of a vasoconstrictor, with the result that the drug remains in
contact with the nerve tissue longer. This not only prolongs the period of blockade by approximately 50% but also
decreases the systemic absorption of local anesthetics by approximately one third ( Fig. 14–1 ).
In clinical practice, local anesthetic solutions usually contain epinephrine, at a concentration of 5 µg/mL
(1:200,000). With lidocaine, this concentration of epinephrine is optimal. Other concentrations of epinephrine have
[1]
also been evaluated. There is little difference in peak local anesthetic plasma concentration when it is mixed with
epinephrine in proportions of 1:200,000, 1:400,000, or 1:600,000 during epidural administration. Using these data, [2]
in the case of a preeclamptic patient,
Figure 14-1 Addition of epinephrine (adrenaline) to the solution containing lidocaine (lignocaine) or prilocaine decreases systemic absorption of the local anesthetic
by about one third.(From Scott DB, Jebson PJR, Braid B, et al: Factors affecting plasma levels of lignocaine and prilocaine. Br J Anaesth 44:1040–1049, 1972.)
244
a solution containing 1:600,000 proportion of local anesthetic and epinephrine should be a better alternative to the
conventional 1:200,000 solution. In a normal pregnancy, neither vascular resistance in the uteroplacental or fetal
circulation nor fetal myocardial function is affected adversely when epinephrine, 90 to 100 µg, is added to
bupivacaine and administered fractionally for extradural anesthesia. To prevent maternal hypotension, it is, of
course, necessary to administer crystalloid volume rapidly. [3]
In a study reported in 1999 to determine whether epinephrine added to a solution of bupivacaine and injected for
superficial cervical plexus blockade lowers plasma bupivacaine concentration and whether this addition of
epinephrine results in tachycardia, cardiac arrhythmia, or both, the authors found that (1) bupivacaine 0.25% with
epinephrine 1:300,000 consistently produced the lowest plasma bupivacaine concentrations compared with
bupivacaine 0.25% without epinephrine and bupivacaine 0.5% with or without epinephrine; and (2) the use of
epinephrine did not produce untoward cardiac side effects. [4]
Prilocaine with felypressin causes fewer side effects than lidocaine with epinephrine and is therefore the preferred
local anesthetic combination for large loop excision of the transformation zone. [5]
The greater lipid solubility of bupivacaine and etidocaine results in a lesser decrease in systemic absorption and a
greater increase in duration of conduction blockade than those occurring with lidocaine when administered in
conjunction with epinephrine.
When epinephrine or phenylephrine is added to bupivacaine or lidocaine in the spinal space, a greater duration of
sensory anesthesia in the lower extremities is produced. The efficacy of epinephrine in prolonging spinal anesthesia
has been confirmed in the lumbosacral region, and was confirmed in thoracic segments in 1998. In a study reported
in 1998, a dose-dependent response and significant prolongation were confirmed with a 0.6-µg dose of epinephrine
added to hyperbaric lidocaine, 60 mg, in 7.5% dextrose solution for spinal anesthesia in the thoracic dermatomes. [6]
Furthermore, epinephrine added to a low dose of tetracaine (6 mg) increases the rate of success with spinal
anesthesia. [7]
The addition of epinephrine to procaine for spinal anesthesia prolongs sensory and motor blocks by 25%. However,
it is associated with a high incidence of nausea. The decrease of systemic absorption of local anesthetic owing to
[8]
epinephrine’s vasoconstrictive action increases the likelihood that the rate of metabolism may match that of
absorption, thus decreasing the possibility of systemic toxicity.
In clinical practice, the administration of a local anesthetic with vasoconstrictors in the presence of inhaled agents
has the potential for producing enhancement of cardiac irritability. The addition of epinephrine to local anesthetic
[9]
solutions has little, if any, effect on the onset rate of local anesthesia.
The duration of peripheral nerve block anesthesia is prolonged more safely by epinephrine than by increasing the
dose of local anesthetic, which also increases the likelihood of systemic toxicity. Mepivacaine with epinephrine for
axillary block target injections reduces total anesthetic time and provides better spread of analgesia in the hand and
forearm.
Bupivacaine combined with epinephrine may produce peripheral nerve block anesthesia lasting up to 14 hours. The
prolongation of action when epinephrine is added to bupivacaine or ropivacaine has not been documented in
reports.
[10]
There is little available information regarding the effect of epinephrine on plasma lidocaine concentration during
continuous anesthesia. In a study reported in 1999 regarding continuous epidural administration, the addition of
epinephrine to lidocaine solutions was ineffective after 2 hours in reducing the potential for systemic toxicity. This
is the result of the overall plasma lidocaine concentration and of the insignificant decrease of its principal active
metabolite, monoethylglycine xylidide (MEGX). [11]
Opioids
The placement of opioids in the epidural or subarachnoid space to manage acute or chronic pain is based on the
knowledge that opioid receptors are present in the substantia gelatinosa of the spinal cord. Opium is probably the
[12]
oldest known medically useful material. Its psychological effects and usefulness in controlling pain and diarrhea
were known to the ancient Sumerians (4000 BC) and Egyptians (2000 BC). Opiate is the term used for drugs derived
from opium. Morphine was isolated in 1803, followed by codeine in 1832 and papaverine in 1848. Morphine can be
synthesized, but it is more easily derived from opium.
245
The most interesting actions of morphine and related drugs are those affecting the central nervous system, such as
the control of pain and the phenomena of tolerance and physical and psychological dependence,
TABLE 14-1 -- CLASSIFICATION OF OPIOIDS, AGONIST-ANTAGONISTS, AND ANTAGONISTS

Opioids Opioid Agonist-Antagonists Opioid Antagonists
Morphine Pentazocine Naloxone
Meperidine Butorphanol Naltrexone

Sufentanil Nalbuphine Nalmefene
Fentanyl Buprenorphine
Alfentanil Nalorphine
Remifentanil Bremazocine
Codeine Dezocine
Dextromethorphan
Hydromorphone
Oxymorphone
Methadone
Heroin
TABLE 14-2 – EFFECTS OF OPIOID RECEPTORS
Effects µ1 µ2 κ δ
Analgesia (supraspinal, spinal)
Analgesia (spinal)
Euphoria
Depression of ventilation
Dysphoria sedation
Low abuse potential
Physical dependence
Miosis
Constipation (marked)
Constipation (minimal)
Bradycardia
Hypothermia
Urinary retention
Diuresis
which together make up the major undesirable side effect profile of the opiate drugs, namely, narcotic addiction. The
development of synthetic drugs with morphine-like properties has led to the use of the term “opioid” to refer to all
exogenous substances, natural and synthetic, that bind specifically to any of several subpopulations of opioid
receptors and produce at least some agonist (morphine-like) effects. Semisynthetic opioids result from relatively
simple modification of the morphine molecule ( Table 14–1 ).
Synthetic opioids contain the phenanthrene nucleus of morphine but are manufactured by synthetic rather than
chemical modification of morphine. Morphine derivatives (e.g., levorphanol), methadone derivatives,
benzomorphan derivatives (e.g., pentazocine), and phenylpiperidine derivatives (e.g., meperidine, fentanyl) are
examples of groups of synthetic opioids. There are similarities between the molecular weights (236 to 326) and pKs
of phenylpiperidine derivatives and amide local anesthetics.
Fentanyl, sufentanil, alfentanil, and remifentanil, which are semisynthetic opioids, are commonly used as
supplements to general anesthesia, as primary high-dosage cardiac surgery anesthetic drugs, or as adjuvant drugs in
regional anesthesia, despite the fact that the vehicle within remifentanil, when administered epidurally or spinally,
has not yet been demonstrated to be safe. These opioids differ in terms of pharmacokinetics and
pharmacodynamics. The most important pharmacodynamic differences among these drugs are potency and
[13] [14] [15]
rate of equilibration between the plasma and the site of drug effect (biophase).
246
It is not disputed that opioids act in the central nervous system, particularly the brainstem and the spinal cord.
However, several pharmacologic, neurophysiologic, and immunohistologic studies have suggested that exogenous
or endogenous opioids also exert antinociceptive effects by acting at peripheral sites. [16]
THE ENDOGENOUS OPIOID SYSTEM
Opioid receptors are classified as µ, δ, and κ receptors ( Table 14–2 ). [17]

The classification of the effect of opioid
agonists and antagonists on opioid receptors is shown in Table 14–3 .
These opioid receptors belong to a superfamily of guanine (G) protein–coupled receptors that constitute 80% of all
known receptors, including muscarinic, adrenergic, γ-aminobutyric acid, and somatostatin receptors. µ- or
morphine-preferring receptors are principally responsible for supraspinal and spinal analgesia. µ Receptors include a
subpopulation of µ1 and µ2 receptors. The activation of µ1 receptors produces analgesia, euphoria, and miosis,
whereas the activation of µ2 receptors is responsible for hypoventilation, physical dependence, and marked
constipation. Exogenous µ-receptor agonists include morphine, meperidine, fentanyl, sufentanil, alfentanil, and
remifentanil. Activation of calcium channel–linked κ receptors produces less respiratory depression than µ-receptor
activation. However, dysphoria and diuresis may accompany activation of κ receptors. Opioid agonists-antagonists
often act principally on κ receptors.
δ Receptors respond to the endogenous ligands known as enkephalins, and these opioid receptors may serve to
modulate the activity of the µ receptors. Sigma and epsilon receptors were included in the past in the classification
of opioid receptors; however, both of them are no longer considered to be opioid receptors. Nonopioid sigma
receptors may be identical to receptors that bind drugs, such as ketamine. [18]
Three types of opioid receptors have been cloned (µ, δ, κ); these receptors belong to the family of seven
transmembrane G protein–coupled receptors; the molecular basis for the presence of opioid receptor subtypes has
not been demonstrated. Cloning of opioid receptors introduces the potential for development of highly selective
[19]
and subtype-specific receptor agonists. The ideal opioid analgesic would have a high specificity
TABLE 14-3 -- CLASSIFICATION OF THE EFFECT OF OPIOID AGONISTS AND ANTAGONISTS ON OPIOID RECEPTORS
µ1 µ2 Κ δ
AGONISTS Endorphins Endorphins Dynorphins Enkephalins
Morphine Morphine
Synthetic opioids Synthetic opioids
ANTAGONISTS Naloxone Naloxone Naloxone Naloxone
Naltrexone Naltrexone Naltrexone Naltrexone
Nalmefene Nalmefene Nalmefene Nalmefene
for receptors, producing good analgesia with few or no side effects. A new opioid receptor (opioid receptor-like 1,
ORL-1), which is structurally analogous to the κ opioid receptor, has been identified. It has the peculiarity of not
binding to conventional opioids. [20]
ENDOGENOUS OPIOID PEPTIDES
The two pentapeptides, Tyr-Gly-Gly-Phe-Met and Tyr-Gly-Gly-Phe-Leu, given the names methionine enkephalin
and leucine enkephalin, were identified as the first endogenous molecules with opiate-like (opioid) activity and high
affinity for opiate receptors. Approximately 12 peptides with opioid activity have since been discovered, including
the endorphins derived from the previously known pituitary hormone, β-lipotropin, and dynorphin, which is a basic
peptide containing many lysine and arginine residues, having leucine enkephalin at its N-terminal, and bearing no
relation to β-lipotropin. It is now evident that all the known peptides derive from three large precursor proteins:
proenkephalin, pro-opiomelanocortin, and prodynorphin, each coded by a separate gene ( Table 14–4 ).
Therefore, three genetically independent families of endogenous opioid peptides are identified: enkephalin, β-
endorphin, and dynorphin, which include more than 20 peptides with opioid-like activity (transmitters). A new [21]
family of endogenous opioid peptides (endomorphins 1 and 2), with selectivity for the µ opioid receptors, has been
characterized in the brain. After binding to the receptors, endogenous opioid peptides are inactivated in the
[22]
247
extracellular space by nonspecific petptidases. Drugs that block or inhibit these inactivating enzymes have been
developed and shown to produce analgesia in various animal models and in humans. [23] [24]
NEURAXIAL OPIOIDS
The knowledge that opioid receptors are present in the substantia gelatinosa of the spinal cord has led to the [12]
TABLE 14-4 -- OPIOID PEPTIDES AND THEIR PRECURSORS
Precursors Peptides
Proenkephalin Met-enkephalin
Leu-enkephalin
Heptapeptide
Octapeptide
Pro-opiomelanocortin α-Endorphin
γ-Endorphin
β-Endorphin
Prodynorphin α-Neoendorphin
Dynorphin A (1–17)
Dynorphin (1–8)
Dynorphin B (Rimorphin)
TABLE 14-5 -- INTERACTIONS OF OPIOIDS WITH ENDOGENOUS SUBSTANCES
Substance Enhances (↑) or Reduces (↓) Morphine Effect Blocks or Reverses Opiate Tolerance
5-HT agonists ↑ —
α2 -Adrenergic agonists ↑ —
CCK-B ↓ Blocks and reverses
NMDA antagonists No effect Blocks
CCK-B, cholecystokinin-B; NMDA, N-methyl-D-aspartate.
clinical use of opioids in the epidural or subarachnoid space in order to ameliorate acute and chronic pain.
Analgesia that is seen after epidural or spinal administration of opioids, in contrast to regional anesthesia with local
anesthetics, is not associated with sympathetic nervous system denervation, is dose related, and is specific for
visceral rather than somatic pain. The main objective in using spinal opioids is to obtain a reduction in the dose
(compared with systemic administration) that results in effective analgesia and fewer side effects.
The analgesia induced by spinal opioids is produced by several mechanisms and can be summarized as (1) direct
inhibitory action on the dorsal horn of the spinal cord, and (2) indirect effects inducing the release of nonopioid
inhibitory transmitters or modulators. After systemic administration, the binding of opioids to opioid receptors
located in the midbrain and medulla activates descending inhibitory pathways that induce the release of
neurotransmitters in the dorsal horn of the spinal cord.
Several endogenous substances interact with spinal morphine ( Table 14–5 ).
Placing opioids in the epidural space may lead to systemic absorption, with diffusion across the dura into the
cerebrospinal fluid (CSF), or the absorption of the opioid into the epidural fat. Considerable CSF concentrations of
[25]
opioids are produced through epidural administration. The extent of dural penetration is dependent mainly on lipid
solubility, but molecular weight may also play a part. The combination of fentanyl with local anesthetics was
initially reported in 1982 by Justins and colleagues as a means of producing more complete anesthesia. These
[26]
drugs are respectively approximately 800 and 1600 times more lipid soluble than morphine. If CSF concentrations
are compared after epidural administration of morphine, fentanyl and sufentanil, the peak concentration occurs in
about 1 to 4 hours, 20 minutes, and 6 minutes, respectively.
However, it has been questioned whether the epidural administration of lipophilic opioids actually offers any clinical
advantages over intravenous (IV) administration. Opioids, such as morphine, with a low lipid solubility do produce
[27]
248
a slower onset of analgesia, but their duration of effectiveness is much longer. Lipid solubility is the dominant factor
in terms of the cephalad movement of opioids in the CSF. For instance, lipid-soluble opioids such as fentanyl and
sufentanil are restricted in their cephalad movement because of their being drawn into the spinal cord, whereas
morphine, which is not so lipid-soluble, remains in the CSF and is therefore able to reach more cephalad locations.
After epidural administration of highly lipid-soluble opioids, cervical CSF concentrations of the opioids are
minimal. On the other hand, substantial cervical CSF concentrations are present up to 5 hours postinjection after
lumbar intrathecal morphine administration. Coughing or straining but not body position can affect the movement of
the CSF.
Morphine, together with epinephrine, enhances intrathecal analgesia compared with morphine alone. In a study
[28]
reported in 1998, the analysis of the current literature showed that the addition of fentanyl to local anesthetics for
intraoperative epidural analgesia was safe and advantageous. [29]
In obstetric anesthesia, a lower dosage of bupivacaine, combined with sufentanil in epidural analgesia, significantly
improves the obstetric outcome compared with a higher dosage of bupivacaine with adrenaline using an intermittent
bolus technique. In 1999, Joshi and associates recommended the addition of 1 µg/kg of fentanyl in a low
concentration of bupivacaine (0.125%) as the caudal injectate mixture in pediatric patients. Therefore, clinical use
[30]
has been extensively investigated.
In terms of the treatment of acute postoperative and chronic pain, the peripheral administration of opioids has also
been evaluated. The route and site of administration and the type and duration of inflammation appear to be the most
significant factors. A number of different routes and sites have been examined. Opiates have been used individually
or combined with local anesthetics and administered through axillary block, as well as by regional IV, interpleural,
intradermal, intraperitoneal, and intra-articular routes. However, a recent systematic review concluded that only the
intra-articular route produces clinically significant changes in intra- or postoperative analgesic efficacy. One[31]
possible explanation for the ineffectiveness of other routes could be the presence of an intact perineurium, which
may prevent opioids from reaching the opioid receptors presumably present in nerve fibers and terminals. On the
other hand, the administration of opiates intra-articularly does produce some level of analgesia. It must be noted,
however, that the published results are not always consistent. Many of the studies in the literature focus on the use
[32]
of intra-articular morphine after knee arthroscopy in terms of the evaluation of pain intensity and postoperative
analgesic requirements. The results demonstrate that low doses of intra-articular morphine produce no systemic
effects and induce long-lasting analgesia comparable with that of local anesthetics. As the effects are reversed by
intra-articular and systemic naloxone, the conclusion can be drawn that analgesia is mediated through opioid
receptors located in the knee joint. In a study published in 1997, the authors concluded that IV regional anesthesia
using morphine provided no analgesic advantage over the intramuscular route from 6 to 24 hours postoperatively. [33]
However, the addition of alfentanil to lidocaine during axillary brachial plexus anesthesia suggests that alfentanil
may have a peripheral local anesthetic action. [34]
Side Effects
The typical side effects of neuraxial opioids are caused by the presence of the drugs in either the CSF or the
systemic circulation ( Table 14–6 ).
The most serious side effect of neuraxial opioids is respiratory depression, which, after conventional doses of
perispinal opioids, requires intervention at a rate of 1%, which is the same as that after IV or intramuscular opioids.
Obstetric patients appear to be at less risk for ventilatory depression, perhaps because of increased ventilatory
stimulation provided by progesterone. The side effects can be managed by the administration of low doses of
naloxone. Naloxone in an IV dose of 0.25 µg/kg/hr is effective in attenuating the side effects.
Valley and Bailey observed 11 cases of respiratory depression and concluded that “the clinicians should be aware
[35]
of the increased incidence of respiratory depression.” Thus, for opioids to be used safely and effectively as adjuvant
drugs, adequate monitoring of vital parameters is necessary. Controlling respiratory rate is not sufficient by itself to
avoid risks, and a continuous pulse oximetry reading, in order to control the oxygen saturation, together with a
sedation degree evaluation, are essential.
Ketamine
Ketamine is an IV drug with special properties that make it the only agent currently used as anesthetic, sedative,
amnesic, and analgesic.
249
TABLE 14-6 -- SIDE EFFECTS OF NEURAXIAL (EPIDURAL AND SPINAL) OPIOIDS

Nausea and vomiting
Pruritus
Urinary retention
Sedation
Depression of ventilation
Central nervous system excitation

Water retention
Gastrointestinal dysfunction
Sexual dysfunction
Thermoregulatory dysfunction
Ocular dysfunction
Viral reactivation
Neonatal morbidity
Ketamine is a phencyclidine (PCP) derivative, the chloroketone analogue (C1-581) that produces “dissociative
anesthesia,” which is characterized by evidence on electroencephalogram of dissociation between the
thalamocortical and limbic systems. [36]
Ketamine is a water-soluble molecule (10 times more soluble than thiopentone) with a pK of 7.5 at physiologic pH.
Only the racemic form containing equal amounts of the ketamine isomers is available for clinical use; the S(+)
isomer produces more intense analgesia, more rapid metabolism, and, as a consequence, more rapid recovery and a
lower incidence of emergency reactions than the R(−) isomer. [37]
Both S(+) and R(−) isomers of ketamine appear to inhibit the uptake of catecholamines. This inhibition is a cocaine-
like effect and takes place in the postgaglionic sympathetic nerve endings. The fact that the isomers of ketamine
differ in their pharmacologic properties suggests that this drug interacts with specific receptors.
MECHANISM OF ACTION
Glutamate and aspartate are arguably the major excitatory transmitters in the vertebrate central nervous system,
whereas GABA is a major inhibitory transmitter. The cell surface receptors that mediate the effects of glutamate
release can be found at most excitatory synapses throughout the central nervous system. These receptors; they are
divided into the slow, G-protein–coupled metabotropic receptors and the fast, ligand-gated ion channels (ionotropic
receptors). The latter class is again divided according to the agonists originally used to characterize them. (S)-2-
amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionic acid (AMPA) receptors mediate the majority of fast,
excitatory neurotransmission and kainate receptors; they are as yet little understood but are likely to be important in
the future. The NMDA receptor, named after the synthetic glutamate analogue and agonist, N-methyl-D-asparate, is
[38]
perhaps the most interesting glutamate receptor in terms of physiology and pathology. During normal transient
processing of nociceptive signals, the NMDA receptors appear to be unimportant, but with prolonged nociceptive
stimulation, as a result of prolonged release of glutamate or neurokinin-1, the NMDA receptors become activated.
The NMDA receptors are involved in several events, including central sensitization, wind-up, long-term
potentiation, and induction of oncogenes. NMDA receptors generate plasticity in many systems, such as memory,
motor function, vision, and spinal sensory transmission. Activation of NMDA receptors is accompanied by loss of
their Mg2 + plug, followed by calcium influx, which activates several second messenger systems, the most important
of which are protein kinase C and nitric oxide systems. Figure 14–2 shows a schematic representation of dorsal horn
systems with mechanisms that mediate the processing of nociceptive information, as occurs after tissue injury.
Ketamine is a noncompetitive antagonist of the NMDA receptor calcium pore and, in addition, ketamine interacts
with the phencyclidine-binding receptor site, leading to inhibition of NMDA receptor activity. Hurstveit and
[9]
associates reported that ketamine interacts with µ, κ, and δ opioid receptors, whereas other studies suggested that
[39]
ketamine may be an agonist of δ receptors and an antagonist of µ receptors. Results of a study published in 1999
proved that opioid receptor blockade by naloxone does not inhibit ketamine-induced reductions of secondary
hyperalgesia. On the other hand, the anticholinergic symptoms produced by ketamine suggest that this drug has an
[40]
antagonist rather than an agonist effect on muscarinic receptors.
Muscarinic signals play an important role in memory, consciousness and learning and, therefore, the “ketamine
effect” may be the result of muscarinic inhibition. On the other hand, benzethonium chloride, the ketamine
preservative, has also been shown to inhibit cholinergic symptoms. [41]
250
Figure 14-2 Schematic representation of dorsal horn systems with mechanisms that mediate the processing of nociceptive information. AA,
arachidonic acid; COX, cyclooxygenase; EP, epinephine; NK, natural killer; NMDA, N-methyl-D-aspartate; PG, prostaglandin; PKC, protein
kinase C; PLA , phospholipase AZ isoenzymes; sP/CGRP, substance P/calcitonin gene-related peptide.
2
Ketamine interacts with the monoaminergic receptors and voltage-sensitive calcium channels. A study published in
2000 examined the effects of in vitro ketamine on synaptic transmission and long-term potentiation in layers II and
III of the adult rat visual cortex. Primed-burst stimulation was used for induction of long-term potentiation. The
authors concluded that ketamine can interfere with synaptic transmission in the visual cortex through the antagonism
of the NMDA receptors “involved in the induction of long-term potentiation in a rat’s visual cortex.” [42]
Ketamine is metabolized extensively by hepatic microsomal enzymes. The active metabolite of ketamine is
norketamine. Norketamine is eventually hydroxylated and then conjugated to form more water-soluble and inactive
glucuronide metabolites, which are excreted by the kidneys.
The administration of ketamine over a long period has the effect of increasing the activity of enzymes that are
responsible for its metabolism. This accelerated metabolism may partly explain why some patients receiving
repeated doses of the drug develop a tolerance to ketamine’s analgesic properties. Demling and colleagues [43]
suggested that burn patients receiving more than two short-interval exposures to ketamine may develop tolerance.
The development of tolerance has also consistently been observed in cases of ketamine dependence. [44]
NEURAXIAL ANALGESIA
Ketamine has been used for a long time as a supplement for central blocks with a lower incidence of adverse
effects and for IV sedation during regional anesthesia.
[45] [41]
The first study of intrathecal administration of ketamine was in 1984 by Bion. Studies have demonstrated that the
[46]
intrathecal administration of preservative-free ketamine causes no neurotoxicity. [47] [48] [49]
Surgical anesthesia can be achieved by intrathecally injected ketamine. However, further study on this topic is
required. A study comparing the hemodynamic effects of lidocaine or intrathecally injected ketamine on
normoovolemic and hypovolemic pigs showed that the ketamine group had lower hemodynamic alterations than the
lidocaine group. The NMDA antagonist effect may be involved. If this were translated to human practice, ketamine
could be employed in subarachnoid anesthesia for hypovolemic or hemodynamically unstable patients. [50]
Intrathecal ketamine (without preservative) is a promising analgesic alternative for women in labor, although its use
is still at an experimental or very early clinical stage. [51]
251
In the 1980s, a number of studies concerning the use of epidural ketamine in humans began to be published. Good
postoperative analgesia without respiratory depression or other side effects was reported. [52] [53]
The group at my institution concluded that ketamine be recommended for use as a postoperative epidural analgesic
in regional operations, because it offers satisfactory analgesia without any risk to the safety of the patient. More [54]
recent studies have shown good postoperative analgesia with ketamine administered epidurally or caudally. [55] [56]
Semple and associates evaluated the optimal dose of preservative-free ketamine to be added to local anesthetics
[57]
(0.25% bupivacaine, 1 mL/kg) for caudal epidural blockade in children. They demonstrated the duration of
postoperative analgesia to be dose dependent, with the optimal dose being 0.50 mg/kg of ketamine, which produced
no adverse effects, as opposed to a dosage of 1 mg/kg.
To compare the effect of ketamine on onset time of regional anesthesia and the degree of sensory and motor block,
Yanli and coworkers added ketamine, 25 mg (with benzethonium chloride) or saline to 0.5% bupivacaine plus
[58]
adrenaline in a randomized, double-blind study. No differences were demonstrated in hemodynamic parameters.

Onset time decreased by about 8 minutes, and the anesthetic level was higher in two to three segments of the
ketamine group, without differences in motor blockade or postoperative duration of analgesic effects. No adverse
effects were found.
Because NMDA is known to be implicated in central sensitization, it is possible that NMDA antagonists may be
more effective in inducing preemptive analgesia than µ- and κ-agonist opioids. This has been confirmed in several
studies, but all of these studies suffered from a variable number of defects in design. [59] [60] [61]
Ketamine has also been used for patients with chronic pain syndromes such as neuropathic pain, phantom limb pain,
postherpetic neuralgia, and cancer pain. Based on clinical case evaluations, ketamine by spinal route and, on
occasion, by other means of administration, seems to be a promising drug in the armamentarium for treatment of
chronic pain patients whose cases are difficult. [62]
Numerous experiments have shown the synergistic effects of NMDA antagonists and opioids in analgesia, whereas
the development of opioid tolerance was prevented. A possible explanation of the analgesic affinity of ketamine
[63] [64]
is its antioxidative properties, as was shown in a study published in 1998. These results demonstrated that
[65]
memantine and amantadine act as radical scavengers, as inhibitors of the oxidative function of microsomal
cytochrome P450, or as both. The knowledge that antioxidants play a role in pain relief in treatment of patients with
chronic pain may indicate a new horizon for analgesic properties of NMDA-receptor antagonists.
[66] [67] [68]
Another use of ketamine is its topical application. A study reported in 1999 demonstrated that topical morphine
tolerance is mediated, at least in part, through peripheral NMDA receptors, which raises the possibility of the
clinical use of topical NMDA-receptor antagonists. [69]
Clonidine
The centrally acting selective partial α2 -adrenergic agonist clonidine, because of its ability to reduce sympathetic
nervous system output from the central nervous system, acts as an antihypertensive drug. Preservative-free
[9]
clonidine, administered into the epidural or subarachnoid space (150–450 µg), produces dose-dependent analgesia
and, unlike opioids, does not produce depression of ventilation, pruritus, nausea and vomiting, or delayed gastric
emptying. [70] [71] [72]
α2 -Adrenergic drugs such as clonidine, dexmedetomidine, and tizanidine exert action on the descending inhibitory
monoaminergic tracts, resulting in an antinociceptive effect. Clonidine produces analgesia by activating postsynaptic
α2 receptors in the gelatinous substance of the spinal cord. The use of neuraxial clonidine, either to produce
analgesia or to prolong the effects of regional anesthesia, may be accompanied by side effects, namely, hypotension
and dryness of the mouth.
Most evidence about the effectiveness of intrathecal clonidine is provided by studies on postoperative pain. These [73]
studies show the effect of a local anesthetic on the duration and intensity of spinal blockade. Moreover, the addition
of intrathecal clonidine results in a longer period of postoperative analgesia. [74]
Van Elstraete and colleagues, in 2000, assessed the analgesic efficacy and side effects of caudally administered
[75]
clonidine as a mixture of bupivacaine 0.5% with lidocaine, and 2% with epinephrine. They concluded that the
252
addition of 75 µg of clonidine increased the duration of postoperative analgesia in adults without affecting mean
arterial pressure. On the other hand, Ivani and Lampugnani, in 1998, stated that “the use of clonidine as an
[76]
adjuvant drug in the field of regional anesthesia both in adults and children seems to be very effective and in the
pediatric field is safer with respect to opioids and adrenaline.” In contrast, Breschan and coworkers concluded that
[77]
the administration of 2 µg/kg of clonidine caudally in neonates for postoperative analgesia could cause respiratory
depression. Postoperative pain relief by continous epidural infusion of ropivacaine has been improved by the
addition of clonidine.[78]
For spinal anesthesia, motor and sensory blocks are prolonged with the addition of clonidine to local anesthetics, but
the requirement for ephedrine treatment is not increased. [79]
The combination of clonidine, in a dose of 100 to 150 µg with fentanyl, results in prolongation of fentanyl analgesia.
Continuous infusion of clonidine alone produces rate-dependent reduction in the need for other pain medication
after surgery. The importance of these infusion rates is that they are not associated with sedation, although blood
pressure is slightly decreased compared with placebo. The addition of clonidine to other opioids for continuous
epidural infusion reduces the opioid dose by 20% to 60%. It is possible for clonidine to produce postoperative
[79]
analgesia with either systemic or epidural injection, but the epidural dose of clonidine required is lower than the
systemic one. This is in contrast to fentanyl and sufentanil, in which there is no difference in dose between the two
[80]
routes. There is clear evidence that a fixed dose (150 µg) of clonidine intramuscularly, epidurally, or intrathecally
has a clear order of duration: intrathecal > epidural > intramuscular, supporting intraspinal administration.
Eisenach and colleagues carried out a review of the use of clonidine in regional anesthesia as presented in the
[81]
international literature of 1995. Most controlled and uncontrolled trials were concerned with epidural or spinal
administration, primarily in perioperative and obstetric patients. The findings demonstrated that clonidine,
depending on dose and coadministered agents, was able to reduce blood pressure. Furthermore, there have been no
reported cases in the literature of life-threatening hypotension or bradycardia. Eisenach and associates argued that it
was this factor that was the key benefit of clonidine, considering the small but significant incidence of respiratory
depression that occurs with use of epidural and spinal opioids. [71]
However, clonidine fails to produce surgical anesthesia and is therefore not administered alone during surgery or for
the final stages of labor. In addition, clonidine’s side effects, dose-dependent sedation and hypotension, preclude its
administration in large doses and have led to a warning label by the U.S. Food and Drug Administration that it not
be administered routinely in postoperative and obstetric settings. On the other hand, small doses of intrathecal
[82]
clonidine have shown much promise for labor analgesia.
In a study reported in 2000, Paech and coworkers concluded that the addition of clonidine to epidural bupivacaine
[83]
and fentanyl for patient-controlled epidural analgesia in labor improved pain control and the supplementation rate
and shivering. Increased sedation and lower blood pressure were not clinically important.
As a sole agent, clonidine, 50 µg, gives about 45 minutes of good analgesia. At 100 to 200 µg, the analgesia is
longer but hypotension can be profound. When clonidine, 30 µg, was coadministered with sufentanil (2.5 µg and 5
[84]
µg), analgesia was prolonged. The same result happened when clonidine, 50 µg, was added to sufentanil, 7.5 µg,
[85]
and bupivacaine, 2.5 mg. In these situation, no adverse side were noted and the opioid dose was reduced.
[86]
Dexmedetomidine
Dexmedetomidine is a next generation α2 -adrenergic agonist in clinical trials, although it is not yet available for
obstetric use. The blood pressure effects of dexmedetomidine are minimal and there are few systemic side effects,
arguably making it the better analgesic of its class. Compared with clonidine, dexmedetomidine is seven times more
selective for α2 receptors and has a shorter duration of action. In this regard, dexmedetomidine is considered to be a
full agonist among the α2 receptors, whereas clonidine is a partial agonist. However, more research is necessary
before it can be used in parturients. [87]
In the last few years, new routes of administration for α2 -adrenergic agonists have received closer attention. Intra-
articular administration of clonidine has demonstrated a peripherally mediated analgesic effect in preclinical and
clinical trials.
To determine whether clonidine or morphine results in better analgesia and whether their combination would
provide analgesia superior to that of either drug alone, a study evaluating patients undergoing knee arthroscopy of
253
the meniscus under local anesthesia concluded that intra-articular clonidine and morphine improved comfort
compared with either drug alone. [88]
A study published in 2000 reviewed current evidence for the efficacy of adding novel analgesic adjuncts to brachial
plexus block, the goal of which was to prolong the analgesic effect without the disadvantage of systemic side effects
or prolonged motor block. These adjuncts may also allow a reduction in the dose of local anesthetic used. Novel
adjuncts studied to date include opioids, clonidine, neostigmine, and tramadol. Twenty-four studies were reviewed
and assessed by using specific inclusion criteria, and only those studies satisfying these criteria were included in the
final assessment. Clonidine appears to have significant analgesic benefit and to cause minimal adverse effects when
used in doses of 150 µg. [89]
On the contrary, according to a study of Erlacher and colleagues, the addition of clonidine to ropivacaine, 0.75%, for
axillary perivascular brachial plexus block, does not lead to any advantage of the block in regard to onset time,
duration of analgesia, and quality of the block. [90]
A study by Elliott and coworkers has compared local infiltration with clonidine-containing bupivacaine solution
with plain anesthetic solution after inguinal hernia repair. The results of the group who received clonidine were not
[91]
significantly different from those patients in the plain solution group. On the other hand, it has been shown that
during intravenous anesthesia, clonidine improves tolerance of the tourniquet. [92]
The most important use of intrathecal and epidural clonidine is in the treatment of chronic pain. Intrathecal injection
of α2 -adrenergic agonists in preclinical studies maintained or increased potency, whereas intrathecal opioids lost
potency or efficacy in animal models of neuropathic pain. [93]
Clonidine infused epidurally, at a rate of 30 µg/hr, produces analgesia in patients with cancer and neuropathic pain, [81]
and infusion rates of 10 to 40 µg/hr are commonly used in this patient population. Steady state CSF clonidine
concentrations of 12 to 45 ng/mL should be produced by these rates within approximately 6 hours. This time period
concurs with the relatively fast onset of analgesia from the epidural infusion of clonidine in these patients.
In conclusion, the evidence clearly suggests that clonidine should be administered epidurally rather than
systemically for pain relief. Clinical studies have indicated a close relationship between the amount of clonidine in
CSF and the relief of pain, and a spinal site of action of α2 -adrenergic agonists is supported by anatomic and
neurophysiologic experiments in animals. Clonidine is less effective in treating acute pain when administered
intravenously. Analgesia is produced by α2 -adrenergic agonists, partly by stimulating cholinergic systems in the
spinal cord, and, although this mechanism is activated by a small dose of clonidine administered intrathecally, it is
not activated by systemic administration. Epidural clonidine produces effective relief of chronic pain, which
[79]
involves abnormal sympathetic nervous system activity or abnormal responses to sympathetic activity. Thus, it is
clear that clonidine administered epidurally is both more effective as an analgesic and produces fewer side effects
than systemic administration.
Neostigmine
Neostigmine, edrophonium, and physostigmine are the anticholinesterase drugs that are most often administered by
anesthesiologists to facilitate speed of recovery from the skeletal muscle adverse effects caused by nondepolarizing
neuromuscular blocking drugs.
The spinal cholinergic system has gained new interest as a pharmacologic target for accomplishing efficient
antinociception without the limitation of opioid-induced side effects, especially delayed respiratory depression. [94]
Acetylcholine is one of more than 25 neurotransmitters that participate in spinal cord modulation of pain processing.
Acetylcholinesterase is one of the most efficient enzymes known and is normally responsible for the rapid
hydrolysis of the neurotransmitter acetylcholine to choline and acetic acid. Therefore, the use of cholinergic agonists
or acetylcholinesterase inhibitors such as neostigmine were investigated with respect to their specific antinociceptive
activity and to any potential side effects and toxicity after spinal administration. It was demonstrated that
[71] [95] [96] [97]
neostigmine produces analgesia without introducing the ventilatory depression characteristic of neuraxial opioids,
although nausea is common. [98]
The spinal delivery of cholinergic agonists has been shown in animal studies to produce analgesia. This is brought [99]
about by the interaction with spinal noradrenergic-cholinergic neurons corresponding with neurons in laminae I and
II of the spinal dorsal horn. It appears that muscarinic receptors, as opposed to nicotinic receptors, play a part in
[100] [101]
254
producing analgesia. For this reason, it is suggested that M1 and M2 receptors are primarily involved in spinal
antinociception. [102]
Neostigmine administered spinally inhibits nociception in a dose-dependent manner by increasing the endogenous
neurotransmitter acetylcholine, and thus its analgesic potency is enhanced in specific pain states with tonic release
of acetylcholine-like neuropathic pain or inflammatory pain disorders. [103]
In addition, IV opioids stimulate an inhibitory system in the spinal cord that involves the release of acetylcholine,
and intrathecal neostigmine enhances analgesia from intravenous opioids in animals and humans. The large
potentiation observed between neostigmine and α2 -adrenergic agonists such as dexmedetomidine and clonidine
carries important clinical implications. The addition of neostigmine, 50 µg, prolonged the duration of sensory and
motor block. However, a high incidence of side effects and delayed recovery from anesthesia with the addition of
neostigmine, 6.25 to 50 µg, may limit the clinical use of these doses for outpatient spinal anesthesia. [104]
Klamt and coworkers, in 1996, studied the analgesia produced by intrathecal neostigmine in cancer patients.
[105]
Although neostigmine produces analgesia in patients with chronic pain and in the postoperative setting, it produces a
high incidence of nausea and vomiting in the same doses.
Spinal administration of neostigmine as a nonopioid analgesic appears to provide a potent, long-lasting analgesia.
However, its clinical feasibility has still to be assessed with special regard to its side effects, particularly nausea and
vomiting. There is a need, therefore, to investigate the ultralow doses of neostigmine combined with other
analgesics in order to avoid the undesirable side effects. [82]
In 1999, Lauretti and colleagues reported the epidural administration of neostigmine in combination with lidocaine
[107]
for postoperative analgesia. These reports have been encouraging because they demonstrate dose-dependent
analgesia without nausea for 8 to 12 hours after surgery. This route of administration needs further investigation.
Bórkle and coworkers concluded, based on preclinical and clinical studies, that neostigmine can be used as a
[107]
potent peripherally mediated analgesic drug. This action, according to Bórkle’s conclusion, may be mainly due to
enhanced levels of endogenous accetylcholine at the level of the peripheral afferent nociceptor.
The authors of a study reported in 2000 reviewed the efficacy of adding novel analgesic adjuvants to brachial
[89]
plexus block. The novel analgesic adjuvant drugs studied included opioids, clonidine, neostigmine, and tramadol.
Evidence regarding the analgesic benefit of opioid adjuvants remains equivocal, and more evidence is required
before their routine use can be recommended. Clonidine appears to have significant analgesic benefit and causes
minimal adverse effects when used in doses of 150 µg. Data regarding the other drugs, such as tramadol and
neostigmine, are not sufficient to allow any recommendations to be made, and further studies of these agents are
required.[89]
On the other hand, in a previous study, the authors concluded that peripherally administered neostigmine improved
postoperative analgesia in axillary brachial plexus block. [108]
The intrathecal addition of neostigmine and clonidine significantly increased the duration of analgesia with an
intrathecally injected bupivacaine-fentanyl mixture during labor, but neostigmine caused more nausea. [109]
Preclinical investigations have demonstrated that sympathetic activity is increased by spinal neostigmine because of
the enhanced release of norepinephrine. For this reason, neostigmine has been suggested for use in the prevention of
arterial hypotension after delivery of spinal clonidine or bupivacaine. Studies in humans, however, did not
[110] [111]
succeed in demonstrating the beneficial effect of one dose (75 µg) of neostigmine on blood pressure or heart rate
during spinal bupivacaine anesthesia. [112]
Studies in sheep have demonstrated that epidural injection of clonidine can enhance the release of spinal
acetylcholine. For this reason, the analgesic activity of both clonidine and opioids is increased by neostigmine if it is
administered together with these agents. Furthermore, there have been no reports of cross-tolerance in the
[105] [113]
antinociceptive effects for neostigmine, clonidine, or opioids. The only safe conclusion that can be drawn is that the
clinical utility of epidural neostigmine, either alone or with local anesthetics or other agents, awaits further study.
255
Adenosine
Adenosine is an endogenous nucleoside that is present in all body cells. The enzymatic breakdown of either S-
adenosylhomocysteine or adenosine triphosphate produces adenosine. The maintenance of the balance between
oxygen delivery and oxygen demand in the heart and other organs tends to be the main action of adenosine. [114]
Sawynok and coworkers, in 1986, suggested that one of the main mechanisms of analgesia, after intrathecal opioid
[115]
injection, is the release of adenosine by stimulation of its receptors. Adenosine receptors are located in the
superficial layers of the dorsal horn of the spinal cord, and antinociceptive effects of adenosine and adenosine
analogues have been well demonstrated in acute pain models after systemic and intrathecal injections. The
antinociceptive effect of adenosine was also demonstrated in rats after chronic nerve injury. The [116] [117] [118]
antinociceptive effect is likely mediated through the adenosine A1 receptor subtype. [119]
In healthy volunteers, intrathecal adenosine causes a 1000-fold elevation of the CSF concentration. The only [120]
complication observed was a transient lumbar pain after injection of a 2000-µg dose in one of the five subjects. The
use of adenosine in humans for intrathecal analgesia followed preclinical toxicity testing in Sweden and the United
States. The toxicologic studies indicated that adenosine has no toxic effect after weeks of regular
[120] [121]
administration.
Adenosine agonists produce dose-dependent analgesia, motor blockade, and sedation in animal models.
Adenosine reduced, in a non–dose-dependent manner, the areas of secondary allodynia after skin inflammation
(topical mustard oil application) as well as reduced forearm tourniquet ischemic pain ratings.
The use of adenosine in intractable chronic pain was published in 1993 and again in 1995. The two case reports
concerned patients with neuropathic pain whose treatment with spinal adenosine or adenosine A1 receptor agonist
had successfully increased the pain threshold. [122] [123]
Sollevi’s group evaluated the tolerability and efficacy of intrathecally injected adenosine in patients suffering from
[124]
severe neuropathic pain, including tactile hypersensitivity. The results showed reduced pain in the majority of the
patients, with 6 hours’ to 12 days’ duration of clinical beneficial effects of the treatment.
Intrathecal adenosine does not produce hypotension, motor block, or sedation. Adenosine provides analgesia in
hypersensitivity states but has little effect against acute nociceptive stimuli; therefore, adenosine has an uncertain
role in the treatment of acute and obstetric pain. [82]
In a study published in 2000, the authors tried to determine whether the systemic administration of caffeine, a
nonselective adenosine receptor antagonist, would affect the thermal antihyperalgesic efficacy of acute amitriptyline
in a rat model of neuropathic pain. The results of this study suggest that the thermal antihyperalgesic effect of
[125]
acute amitriptyline in this model may involve enhancement of an endogenous adenosine tone. This involvement is
important in light of the widespread consumption of caffeine, which may potentially act to reduce the benefits of
amitriptyline treatment of neuropathic pain. [125]
The knowledge that adenosine produces no side effects and no toxic reaction when administered intrathecally can
lead to the conclusion that adenosine may, in the future, be a useful drug in the treatment of hypersensitivity in
chronic pain and perhaps in the postoperative period. At present, several groups are investigating the diagnostic and
potential therapeutic roles of intrathecally injected adenosine in acute and chronic pain states.
Summary
In this chapter, the use and efficacy of adjuvant drugs in providing analgesia with regional anesthesia has been
examined. The adjuvant agents discussed include vasoconstrictors, opioids, ketamine, clonidine, neostigmine, and
adenosine. Although the primary regional anesthesia is achieved at present by local anesthetics, the novel drugs
described here give hope that better, prolonged analgesia is in store for future generations if the side effects of these
adjuvants can be minimized.
REFERENCES
1. Braid BP, Scott DB: The systemic absorption of local analgesic drugs. Br J Anaesth 37:394, 1965.
256
2. DiFazio CA, Carron H, Grosslight KR, et al: Comparison of pH-adjusted lidocaine solutions for epidural anesthesia. Anesth Analg 65:760–764,
1986.
3. Alahuhta S, Rasanen J, Joupila R, et al: Effects of extradural bupivacaine with adrenaline for caesarean section on uteroplacentral and fetal
circulation. Br J Anaesth 67:678–682, 1991.
4. Harwood TN, Butterworth JF, Colonna DM, et al: Plasma bupivacaine concentrations and effects of epinephrine after superficial cervical
plexus blockade in patients undergoing carotid endarterectomy. J Cardiothorac Vasc Anesth 13:703–706, 1999.
5. Howells RE, Tucker H, Millinship J, et al: A comparison of the side effects of prilocaine with felypressin and lignocaine with adrenaline in
large loop excision of the transformation zone of the cervix: Results of a randomised trial. Br J Obstet Gynaecol 107:28–32, 2000.
6. Kito
K, Kato H, Shibata M, et al: The effect of varied doses of epinephrine on duration of lidocaine spinal anesthesia in the thoracic and
lumbosacral dermatomes. Anesth Analg 86:1018–1022, 1998.
7. Carpenter RL, Smith HS, Bridenbaugh LD: Epinephrine increases the effectiveness of tetracaine spinal anesthesia. Anesthesiology 71:33–36,
1989.
8. Bergeron
L, Girard M, Drolet P et al: Spinal procaine with and without epinephrine and its relation to transient radicular irritation. Can J
Anaesth 46:846–849, 1999.
9. Stoelting RK: Pharmacology and Physiology in Anesthetic Practice, 3rd ed. New York, Lippincott-Raven, 1999.
10. Niesel HC, Eilingsfeld T, Hornung M, et al: Plain ropivacaine 1% versus bupivacaine 0.75% in epidural anesthesia. A comparative study in
orthopaedic surgery. Anaesthestist 42:605–611, 1993.
11. Shin-ichi K, Masayuki M, Yoshihiro K, et al: Plasma concentrations of lidocaine and its principal metabolites during continuous epidural
infusion of lidocaine with or without epinephrine. Reg Anaesth Pain Med 24:529–533, 1999.
12. Cousins MJ, Mather LE: Intrathecal and epidural administration of opioids. Anesthesiology 61:276–310, 1984.
13. Burkle H, Dunbar S, Van Aken H: Remifentanil: A novel, short-acting, opioid. Anesth Analg 83:646–651, 1996.
14. Egan TD, Lemmens JHM, Fiset P, et al: The pharmacokinetics of the new short-acting opioid remifentanil (FI87084B) in healthy adult male
volunteers. Anesthesiology 79:881–892, 1993.
15. Shafer SL, Varvel JR: Pharmacokinetics, pharmacodynamics, and rational opioid selection. Anesthesiology 74:53–63, 1991.
16. Stein C: Peripheral mechanisms of opioid analgesia. Anesth Analg 76:182–191, 1993.
17. Atcheson R, Lambert DG: Update on opioid receptors. Br J Anaesth 73:132–134, 1994.
18. Pleuvry BJ: Opioid receptors and their ligands: Natural and unnatural. Br J Anaesth 66:370–380, 1991.
19. Minami M, Satoh M: Molecular biology of the opioid receptors: Structures, functions and distributions. Neurosci Res 23:121–145, 1995.
20. Akil H, Meng F, Mansour A, et al: Cloning and characterization of multiple opioid receptors. NIDA Res Monogr 161:127–140, 1996.
21. Olson GA, Olson RD, Kastin AJ: Endogenous opiates: 1996. Peptides 18:1651–1688, 1997.
22. Puig MM: Update on the pharmacology of opioids. In De Vera R, Parris W, Erdine S (eds): Bologna, Italy, Monduzzi Editore, 1998, pp 331–
336.
23. Noble F, Smadja C, Valverde O, et al: Pain suppressive effects on various nociceptive stimuli (thermal, chemical, electrical and inflammatory)
of the first orally active enkephalin-metabolizing enzyme inhibitor RB 120. Pain 73:383–391, 1997.
24. Vadalouca A, Kalfakakou V: Zinc and opioid catabolism: A promising new approach to analgesia. Industrial Market Research Association
11:3–7, 1999.
25. Chaney MA: Side effects of intrathecal and epidural opioids, Can J Anaesth 42:891–903, 1995.
26. Justins DM, Francis D, Houlton PG, Reynolds F: A controlled trial of extradural fentanyl in labor. Br J Anesth 54:409–414, 1982.
27. De Leon-Casasola OA, Lema MJ: Postoperative epidural opioid analgesia: What are the choices? Anesth Analg 83:867–875, 1996.
28. Goyagi T, Nishikawa T: The addition of epinephrine enhances postoperative analgesia by intrathecal morphine. Anesth Analg 81:508–513,
1995.
29. Curatolo M, Petersen-Felix S, Scaramozzino P, et al: Epidural fentanyl, adrenaline and clonidine as adjuvants to local anesthetics for surgical
analgesia: Meta-analyses of analgesia and side-effects. Acta Anaesthesiol Scand 42:910–920, 1998.
257
30. Joshi W, Connelly NR, Dwyer M, et al: A comparison of two concentrations of bupivacaine and adrenaline with and without fentanyl in
paediatric inguinal herniorrhaphy. Paediatr Anaesth 9:317–320, 1999.
31. Picard PR, Tramer MR, McQuay HJ, et al: Analgesic efficacy of peripheral opioids (all except intra-articular): A qualitative systematic review
of randomised controlled trials. Pain 72:309–318, 1997.
32. Kalso E, Tramer MR, Carroll D, et al: Pain relief from intra-articular morphine after knee surgery: A qualitative review. Pain 71:127–134,
1997.
33. McSwiney M, Cooper J, Karadia S, et al: Intravenous regional analgesia using morphine. The effect on postoperative pain following total knee
arthroplasty. Acta Anaesthesiol Scand Mar 41:345–347, 1997.
34. Gormley WP, Murray JM, Fee JP, et al: Effect of the addition of alfentanil to lignocaine during axillary brachial plexus anesthesia. Br J
Anaesth 76:802–805, 1996.
35. Valley RD, Bailey AG: Caudal morphine for postoperative analgesia in infants and children: A report of 138 cases. Anesth Analg 72:120–124,
1991.
36. Reich DL, Silvay G: Ketamine: An update on the first twenty-five years of clinical experience. Can J Anaesth 36:186–197, 1989.
37. White PF, Ham J, Way WL, et al: Pharmacology of ketamine isomers in surgical patients. Anesthesiology 52:231–239, 1980.
38. Carpenter KJ, Dickenson AH: NMDA receptors and pain—hopes for novel analgesics. Reg Anesth Pain Med 24:506–508, 1999.
39. Hurstveit O, Maurset A, Oye I: Interaction of the chiral forms of ketamine with opioid, phencyclidine, and muscarinic receptors. Pharmacol
Toxicol 77:355–359, 1995.
40. Mikkelsen S, Ilkjaer S, Brennum J, et al: The effect of naloxone on ketamine-induced effects on hyperalgesia and ketamine-induced side
effects in humans. Anesthesiology 90:1539–1545, 1999.
41. DurieuxME, Nietgen GW: Synergistic inhibition of muscarinic signaling by ketamine stereoisomers and the preservative benzethonium
chloride. Anesthesiology 86:1326–1333, 1997.
42. Salami M, Fathollahi Y, Esteky H, et al: Effects of ketamine on synaptic transmission and long-term potentiation in layer II/III of rat visual
cortex in vitro. Eur J Pharmacol 390:287–293, 2000.
43. Demling RH, Ellerbee S, Jarrett F: Ketamine anesthesia for tangential excision of burn eschar: A burn unit procedure. J Trauma 18:269–270,
1978.
44. White PF, Way WL, Trevor AJ: Ketamine: Its pharmacology and therapeutic uses. Anesthesiology 56:119–136, 1982.
45. Schulte-Steinber O: Ketamine in induction of general anesthesia and regional anesthesia. In Domino EF (ed): Status of Ketamine in
Anesthesiology. Ann Arbor, MI, NPP Books, 1990, pp 473–480.
46. Bion JF: Intrathecal ketamine for war surgery. A preliminary study under field conditions. Anesthesia 39:1023–1028, 1984.
47. Malinovsky JM, Lepage JY, Cozian A, et al: Is ketamine or its preservative responsible for neurotoxicity in the rabbit? Anesthesiology
78:109–115, 1993.
48. Borgbjerg FM, Svensson BA, Frigast C, Gordh T Jr: Histopathology after repeated intrathecal injections of preservative-free ketamine in the
rabbit: A light and electron microscopic examination. Anesth Analg 79:105–111, 1994.
49. Errando CL, Valia JC, Sifre C, et al: Subarachnoid ketamine in swine—pathological findings after repeated doses: Acute toxicity study. Reg
Anesth Pain Med 24:146–152, 1999.
50. Errando CL, Moliner S, Gil F, et al: Haemodynamic effects of subarachnoid lidocaine or ketamine in hypovolemic pigs. Reg Anesth Pain Med
25(Suppl):9, 2000.
51. Mercier FJ, Benhamou D: Promising non-narcotic analgesic techniques for labor. Baillieres Clin Obstet Gynaecol 12:397–407, 1998.
52. Islas JA, Astorga J, Laredo M: Epidural ketamine for control of postoperative pain. Anesth Analg 64:1161–1162, 1985.
53. Naguib M, Adu-Gyamfi Y, Absood GH, et al: Epidural ketamine for postoperative analgesia. Can Anaesth Soc J 33:16–21, 1986.
54. Vadalouca A, Samaras T, Gyftonikolou E, et al: Postoperative analgesic effect of ketamine HCl administrated epidurally in gynecological
procedures. Reg Anesth 13:76, 1988.
55. El-Khateeb OE: Caudal ketamine for relief of pain following anorectal surgery. In Domino EF (ed): Status of Ketamine in Anesthesiology.
Ann Arbor, MI, NPP Books, 1990, pp 411–418.
258
56. El-KhateebOE, Ragab A, Metwalli M, et al: Assessment of epidural ketamine for relief of pain following vaginal and lower abdominal
surgery. In Domino EF (ed): Status of Ketamine in Anesthesiology. Ann Arbor, MI, NPP Books, 1991, pp 403–409.
57. Semple D, Findlow D, Aldridge LM, et al: The optimal dose of ketamine for caudal epidural blockade in children. Anesthesia 51:1170–1172,
1996.
58. Yanli Y, Eren A: The effect of extradural ketamine on onset time and sensory block in extradural anesthesia with bupivacaine. Anesthesia
51:84–86, 1996.
59. Royblat L, Korotkoruchko A, Katz J: Postoperative pain: The effect of low-dose ketamine in addition to general anesthesia. Anesth Analg
77:1161–1165, 1993.
60. Tverskoy M, Oz Y, Isakson A: Preemptive effect of fentanyl and ketamine on postoperative pain and wound hyperalgesia. Anesth Analg
78:205–209, 1994.
61. Fu ES, Miguel R, Scharf JE: Preemptive ketamine decreases postoperative narcotic requirements in patients undergoing abdominal surgery.
Anesth Analg 84:1086–1090, 1997.
62. Takahashi H, Miyazaki M, Nanbu T et al: The NMDA-receptor antagonist ketamine abolishes neuropathic pain after epidural administration
in a clinical case. Pain 75:391–394, 1998.
63. Weber C: NMDA-receptor antagonist in pain therapy. Anasthesiol Intensivmed Notfallmed Schmerzther 33:475–483, 1998.
64. Wiesenfeld-Hallin Z: Combined opioid-NMDA antagonist therapies. What advantages do they offer for the control of pain syndromes?
Drugs 55:1–4, 1998.
65. Lupp A, Kerst S, Karge E, et al: Investigation on possible antioxidative properties of the NMDA-receptor antagonists ketamine, memantine,
and amantadine in comparison to nicanartine in vitro. Exp Toxicol Pathol 50:501–506, 1998.
66. Evagelou A, Kalfakakou V, Georgakos P et al: The effect of antioxidants in painful syndromes [abstract]. First Panhellenic Congress on Free
Radicals and Oxidative Stress. Ioannina, Greece, 84, 1998.
67. Kahlil Z, Liu T, Helme DR: Free radicals contribute to the reduction in peripheral vascular responses and the maintenance of thermal
hyperalgesia in rats with chronic constriction injury. Pain 79:31–37, 1999.
68. Evagelou A, Kalfakakou V, Georgakos P, et al: Ascorbic acid: Effects on withdrawal syndrome of heroin abusers. In Vivo 14:363–366,
2000.
69. Kolesnikov YA, Pasternak GW: Peripheral blockade of topical morphine tolerance by ketamine. Eur J Pharmacol 374:1–2, 1999.
70. Filos KS, Goudas LC, Patroni O, et al: Hemodynamic and analgesic profile after intrathecal clonidine in humans. A dose response study.
71. Eisenach JC, Detweiler DJ, Tong CY, et al: Cerebrospinal fluid norepinephrine and acetylcholine concentrations during acute pain. Anesth
Analg 82:621–626, 1996.
72. Asai T, McBeth C, Stewart JIM: Effect of clonidine on gastric emptying of liquids. Br J Anaesth 78:28–33, 1997.
73. Acalovschi I, Bodolea C, Manoiu C: Spinal anesthesia with meperidine. Effects of added alpha-adrenergic agonists: Epinephrine versus
clonidine. Anesth Analg 84:1333–1339, 1997.
74. Crul PB: Non-opioid spinal analgesia. Highlights in pain therapy and regional anaesthesia. VIII:209–213, 1999.
75. Van Elstraete AC, Pastureau F, Lebrun T, et al: Caudal clonidine for postoperative analgesia in adults. Br J Anaesth 84:401–403, 2000.
76. Ivani G, Lampugnani E: Adjuvants to bupivacaine for surgical anesthesia. Highlights in pain therapy and regional anesthesia. VII:257–265,
1998.
−1
77. Breschan C, Krumplholz R, Likar R, et al: Can a dose of 2 microg.kg caudal clonidine cause respiratory depression in neonates? Paediatr
Anaesth 9:81–83, 1999.
78. De Negri P, Visconti C, DeVivo P, et al: Does clonidine added to epidural infusion of 0.2% ropivacaine enhance postoperative analgesia in
adults? Reg Anesth Pain Med 25(Suppl):39, 2000.
79. Eisenach JC: Spinal non-opioids in pain management: Alpha-2 agonists. In Van Zundert A (ed): Highlights in Pain Therapy and Regional
Anesthesia VII. ESRA and Hadjigeourgiou Printings, Geneva, Switzerland, 1998, pp 132–139.
259
80. Bernard JM, Kick O, Bonnet F: Comparison of intravenous and epidural clonidine for postoperative patient-controlled analgesia. Anesth
Analg 81:706–712, 1995.
81. Eisenach JC, DuPen S, Dubois M, et al: Epidural clonidine analgesia for intractable cancer pain. Pain 61:391–399, 1995.
82. Eisenach JC: Intrathecal clonidine/neostigmine/adenosine. ASRA 25th Annual Meeting and Workshops. Syllabus. Orlando, FL, March 30–
April 2, 2000, pp 277–281.
83. Paech JM, Pavy T, Orlikowski C, et al: Patient controlled epidural analgesia in labor: The addition of clonidine to bupivacaine-fentanyl. Reg
Anesth Pain Med 25:34–41, 2000.
84. Chiari A, Lorber C, Eisenach JC, et al: Analgesic and hemodynamic effects of intrathecal clonidine as the sole analgesic agent during first
stage of labor—a dose-response study. Anesthesiology 91:988–396, 1999.
85. Gautier PE, De Kock M, Fanard L, et al: Intrathecal clonidine combined with sufentanil for labor analgesia. Anesthesiology 88:651–656,
1998.
86. D’Angelo R, Evans E, Dean LA, et al: Spinal clonidine prolongs labor analgesia from spinal sufentanil and bupivacaine. Anesth Analg
88:573–576, 1999.
87. Herman NL: New drugs for labor analgesia. ASRA 25th Annual Meeting and Workshops. Syllabus. Orlando, FL, March 30–April 2, 2000.
88. Joshi W, Reuben SS, Kilaru PR, et al: Postoperative analgesia for outpatient arthroscopic knee surgery with intraarticular clonidine and/or
morphine. Anesth Analg 90:1102–1106, 2000.
89. Murphy DB, McCartney CJ, Chan VW: Novel analgesic adjuncts for brachial plexus block: A systematic review, Anesth Analg 90:1122–
1128, 2000.
90. Erlacher W, Schuschnig C, Orlicek F, et al: The effects of clonidine on ropivacaine 0.75% in axillary perivascular plexus block. Acta
Anaesthesiol Scand 44:53–57, 2000.
91. Elliott S, Eckersall S, Fligelstone L, et al: Does the addition of clonidine affect duration of analgesia of bupivacaine in inguinal hernia repair
surgery? Br J Anaesth 79:446–449, 1997.
92. Gentili M, Bernard JM, Bonnet F: Clonidine and lidocaine vs lidocaine for intravenous regional anesthesia [abstract]. Br J Anaesth 80:A376,
1998.
93. Eisenach JC, Hood DD, Curry R: Relative potency of epidural to intrathecal clonidine differs between acute thermal pain and capsaicin-
induced allodynia. Pain 84:57–64, 2000.
94. Collins JG: Spinally administered neostigmine: Something to celebrate. Anesthesiology 82:327–328, 1995.
95. Hood DD, Eisenach JC, Tuttle R: Phase I safety assessment of intrathecal neostigmine methylsulfate in humans. Anesthesiology 82:331–
343, 1995.
96. Yaksh TL, Grafe MR, Malkmus S, et al: Studies on the safety of chronically administered intrathecal neostigmine. Anesthesiology 82:412–
427, 1995.
97. Lydic R, Baghdoyan HA: Cholinergic contributions to the control of consciousness. In Biebuyck J (ed): Anesthesia: Biologic Foundations.
Philadelphia, Lippincott-Williams & Wilkins, 1997, pp 433–450.
98. Krukowski JA, Hood DD, Eisenach JC, et al: Intrathecal neostigmine for post-cesarean seciton analgesia: Dose response. Anesth Analg
84:1269–1275, 1997.
99. Yaksh T, Dirksen R, Harty G: Antinociceptive effects of intrathecally injected cholinomimetic drugs in the rat and cat. Eur J Pharmacol
117:81–85, 1985.
100. Borges L, Iverson S: Topography of choline acetyltransferase immunoreactive neurons and fibers in the rat spinal cord. Brain Res
362:140–148, 1986.
101. Ribeiro-Da-Silva A, Cuello C: Choline acetyltransferase-immunoreactive profiles are presynaptic to primary sensory fibers in the rat
superficial dorsal horn. J Comp Neurol 295:370–384, 1990.
102. Bouaziz H, Tong CY, Eisenach JC: Postoperative analgesia from intrathecal neostigmine in sheep. Anesth Analg 80:1140–1144, 1995.
260
103. Hood DD, Mallak KA, Eisenach JC, et al: Location and characteristics of nitric oxide synthase in sheep spinal cord. Anesthesiology
85:315–325, 1996.
104. Liu SS, Hodgson PS, Moore JM, et al: Dose-response effects of spinal neostigmine added to bupivacaine spinal anesthesia in volunteers.
105. Klamt JG, Dosreis MP, Neto JB, et al: Analgesic effect of subarachnoid neostigmine in two patients with cancer pain. Pain 66:389–391,
1996.
106. Lauretti GR, Gomes JM, Reis MP, et al: Low doses of epidural ketamine or neostigmine but not midazolam: Improved morphine analgesia
in epidural terminal cancer pain therapy. J Clin Anesth 11:663–668, 1999. 107. Bórkle H, Bantel C, Yang LC, et al: Intra-articular analgesia
techniques: Neostigmine. In Van Zundert (ed): Highlights in Pain Therapy and Regional Anesthesia VII. ESRA & Hadjigeorgiou Printings,
Geneva, Switzerland, 1998, pp 240–242.
108. Bone HG, Van Aken H, Booke M, et al: Enhancement of axillary brachial plexus block anesthesia by coadministration of neostigmine. Reg
Anesth Pain Med 24:405–410, 1999.
109. Owen MD, Ozsarac O, Sahin S, et al: Low-dose clonidine and neostigmine prolong the duration of intrathecal bupivacaine-fentanyl for
labor analgesia. Anesthesiology 92:361–366, 2000.
110. Williams JS, Tong C, Eisenach JC: Neostigmine counteracts spinal clonidine-induced hypotension in sheep. Anesthesiology 78:301–307,
1993.
111. Lauretti GR, Reis MP: Subarachnoid neostigmine does not affect blood pressure or heart rate during bupivacaine spinal anesthesia. Reg
Anesth 21:586–591, 1996.
112. Abram SE, Winne RP: Intrathecal acetylcholinesterase inhibitors produce analgesia that is synergistic with morphine and clonidine in rats.
Anesth Analg 81:501–507, 1995.
113. Bouaziz H, Hewitt C, Eisenach JC: Subarachnoid neostigmine potentiation of alpha2 -adrenergic agonist analgesia: Dexmedetomidine
versus clonidine. Reg Anesth 20:121–127, 1995.
114. Camm AJ, Garratt CJ: Adenosine and supraventricular tachycardia N Engl J Med 325:1621–1629, 1991.
115. Sawynok J, Sweeney MI, White TD: Classification of adenosine receptors mediating antinociception in the rat spinal cord. Br J Pharmacol
88:923–930, 1986.
116. Sjolund K-F, Sollevi A, Segerdahl M, et al: Intrathecal and systemic R-phenylisopropyl-adenosine reduces scratching behaviour in a rat
mononeuropathy model. Neuroreport 7:1856–1860, 1996.
117. Cui J-G, Sollevi A, Lindroth B, et al: Adenosine receptor activation suppresses tactile hypersensitivity and potentiates spinal cord
stimulation in mononeuropathic rats. Neurosci Lett 223:173–176, 1997.
118. Sjolund K-F, von Heijne M, Hao JX, et al: Intrathecal administration of the adenosine A (1) receptor agonist R-phenylisopropyl adenosine
reduces presumed pain behaviour in a rat model of central pain. Neurosci Lett 243:89–92, 1998.
119. Lee Y-W, Yaksh TL: Pharmacology of the spinal adenosine receptor which mediates the antiallodynic action of intrathecal adenosine
agonists. J Pharmacol Exp Ther 277:1642–1648, 1996.
120. Rane K, Segerdahl M, Goiny M, et al: Intrathecal adenosine administration—a phase 1 clinical safety study in healthy volunteers, with
additional evaluation of its influence on sensory thresholds and experimental pain. Anesthesiology 89:1108–1115, 1998.
121. Chiari A, Yaksh TL, Myers RR, et al: Preclinical toxicity screening of intrathecal adenosine in rats and dogs. Anesthesiology 91:824–832,
1999.
122. Lihblom U, Nordfors L-O, Sollevi A, et al: Adenosine for pain relief in a patient with intractable secondary erythromelalgia. Eur J Pain
1:299–302, 1997.
123. Karlsten R, Gordh T: An Al-selective adenosine agonist abolishes allodynia elicited by vibration and touch after intrathecal injection.
Anesth Analg 80:844–847, 1995.
124. Sollevi A: Spinal adenosine for pain relief. In Van Zundert A (ed): Highlights in Pain Therapy and Regional Anesthesia. ESRA and
Hadjigeorgiou Printings, Cyprus, 1998.
125. Esser MJ, Sawynok J: Caffeine blockade of the thermal antihyperalgesic effect of acute amitriptyline in a rat model of neuropathic pain.
Eur J Pharmacol 399:131–139, 2000. 229
261
Section IV - Chapter 15 - Chemical Neurolytic Agents
Chapter 15 - Chemical Neurolytic Agents
SUSAN R. ANDERSON
Prolonged interruption of painful pathways may be accomplished by injection of neurolytic agents. This form of
chemical neurolysis has been performed for many years. Perineural injections have been used therapeutically since
the discovery of cocaine by Koller in 1884. The application of neurolytic substances to provide relief for patients
[1]
with cancer has been practiced since 1930. The first reported injection of a neurolytic solution in the treatment of
pain was probably by Luton, who, in 1863, administered subcutaneous injections of irritant substances into painful
[2]
areas. Levy and Baudouin (1906) were the first to administer the injection of neurolytic agents percutaneously.
[1] [1]
Doppler, in 1925, was the first to report the use of phenol for neurolysis. The first use of phenol for subarachnoid
[1]
neurolysis was reported by Maher in 1955. Today, phenol and ethyl alcohol (ethanol) are the most commonly
[1] [3]
used agents. Subarachnoid neurolysis is indicated for patients with limited life expectancy and patients who still
have recurrent or intractable pain after a series of analgesic blocks. [4]
Important Considerations
Diagnostic blocks are considered of prime importance because neurolytic agents have undesirable side effects and
there is limited duration of analgesia. Potential side effects include neuritis and deafferentation pain, motor deficit
when mixed nerves are ablated, and unintentional damage to nontargeted tissue. Therefore, careful selection of
[4]
patients and clinical expertise are essential. The following criteria should be considered before peripheral neurolysis
is performed. [4]
1. Determine and document that the pain is severe.

2. Document that the pain was not relieved by less invasive therapies.
3. Document that the pain is well localized and in the distribution of an identifiable nerve. [5]
4. Confirm that the pain is relieved with a diagnostic block performed with use of local anesthetic.
5. Document the absence of undesirable deficits after administration of the local anesthetic blocks. [4]
The impermanence of analgesia is thought to be related to the creation by the neurolytic agent of an incomplete
lesion on the targeted nerve. Although local anesthetic injected into the general vicinity of a nerve trunk may
[4] [6]
diffuse through neighboring soft tissue and often result in an effective neural blockade, neurolytic drugs spread
poorly and require precise location of the needle on the targeted nerve. This means that the best results are obtained
when the neurolytic solution is deposed directly onto the nerve. To avoid complications, the volume and
[4]
concentration of the injected neurolytic agent must also be carefully controlled. Controlled comparisons between
different concentrations and volumes of neurolytic agents have not been carried out. The formation of incomplete [4]
lesions and consequent return of partial function may be influenced by these factors. [4]
Neuropathic (causalgic) pain is a feature observed in most ablative procedures.[ ] [ ] [ ] The risk of this type of pain
4 7 8
may be minimized by careful patient selection. A patient with a short life expectancy or one who is unlikely to
survive the duration of pain relief would be considered the best candidates.[ ] If the patient should survive beyond the
4
duration of pain relief, the neurolysis may be repeated at the same site or more proximally. Use of peripheral
neurolysis in patients with benign chronic pain remains controversial. It is imperative that if neurolysis is used in
these patients, the informed consent form must state very clearly pertinent information about undesirable side
effects.
The potential for damage to nontargeted tissue is of concern with any neurolytic procedure. However, it is less likely
to occur with peripheral neurolysis than if central or deep sympathetic neurolytic blocks are undertaken. This is [4]
particularly true when localization is facilitated by electrical stimulation, radiographic guidance, and/or test doses of
local anesthetic. [4] [9] [10] [11]
Postneurolytic neuritis may develop as a result of the incomplete lesion formation caused by chemical neurolytics. [4]
An association between the creation of incomplete or inaccurate lesions and subsequent neuritis is supported
[6] [12]
indirectly by the work of Roviaro and colleagues, who at thoracotomy injected three neighboring intercostal nerves
with 6% phenol in glycerin (1 mL per segment) under direct vision. In the 32 patients treated, neither neuritis nor
[13]
deafferentation pain was reported at the 1-year follow-up, a finding that is in marked contrast to results after
percutaneous neurolytic intercostal blocks. [4] [14]
263
Ethyl Alcohol
Ethyl alcohol is commercially available in 1-mL or 50-mL ampules as a colorless solution that can be injected
readily through small-bore needles. It is hypobaric with respect to cerebrospinal fluid (CSF). However, specific
[4]
gravity is not of concern when the peripheral nerve is injected because the injection takes place in a nonfluid
medium. Ethyl alcohol is usually used undiluted (absolute or higher than 95% concentration). The perineural
[4]
injection of alcohol is followed immediately by severe burning pain along the nerve’s distribution, which lasts about
a minute before giving way to a warm, numb sensation. Pain at injection may be diminished by prior injection of a
local anesthetic. To precede the injection of any neurolytic drug with an injection of local anesthetic optimizes
[4]
comfort and serves as a “test dose.” The alcohol spreads rapidly from the injection site. When injected into the
[4]
cerebrospinal fluid only 10% of the initial dose remains at the site of the injection after 10 minutes, and about 4%
remains after 30 minutes. Between 90% and 98% of the ethanol that enters the body is completely oxidized.
[28] [15]
Oxidation occurs chiefly in the liver and is initiated principally by alcohol dehydrogenase. Denervation and pain [16]
relief accrue within a few days after injection, usually after 1 week. If no pain relief is present after 2 to 3 weeks, the
neurolysis is incomplete and needs repetition. [4]
Various concentrations and mixtures of alcohol have been studied in an attempt to determine selectivity for sensory
nerves. Schlosser studied the effect of alcohol on somatic nerves. He reported that alcoholization was followed
[17] [18]
by degeneration and absorption of all the components of the nerve except the neurilemma. There is general
agreement that with 95% concentration of absolute alcohol, the destruction involves the sympathetic, sensory, and
motor components of a mixed somatic nerve; therefore, it is undesirable to block a mixed nerve with such
concentrations of alcohol. However, there is a great discrepancy in determining the effects when the alcohol is on
motor fibers lower than 80% concentration ( Fig. 15–1 ). [18]
In 1907, Finkelburg tested the presence of inconsistency by injecting 0.5 mL to 1.5 mL of 60% to 80% alcohol into
the exposed sciatic nerve of dogs and rabbits. Persistent paralysis resulted with these concentrations. In 1912,
[18] [19]
May found that the injection of 0.5 mL of alcohol into the exposed sciatic nerve of the cat was followed by motor
paralysis. The duration of the paralysis varied considerably, irrespective of the strength of the alcohol used,
[18] [20]
provided it was greater than 60%. With 80% alcohol concentration, May observed motor paralysis lasting 91 days
[4]
in one case and 19 days in another; with 90% alcohol, paralysis lasted 64 days in one case and 88 days in another.
The paralysis was always followed by recovery. Postrecovery examination revealed that in some cases, the nerve
showed no microscopic evidence of degeneration, whereas in others, there was evidence of degeneration and
regeneration. With absolute alcohol, however, May always found considerable fibrosis at the site of injection into a
normal nerve, with some regenerative process above and intermingled degeneration and regeneration below the
fibrous zone. He also found that a 50% alcohol concentration produced no motor weakness. Gordon, using an
[18] [21]
80% alcohol concentration, found that by the 9th day, there was less evidence of motor involvement than on the
29th day, when he observed partial degeneration in some cases and complete degeneration in others. Nevertheless,
no animal was completely paralyzed. Nasaroff used a 70% alcohol concentration and never observed complete
[18] [21] [22]
paralysis. He did note the onset of a temporary paresis at the end of the second week, at which time he found
progressive and simultaneous degenerative and regenerative processes. These findings seem to indicate that a 70%
alcohol concentration does not cause irremediable damage to somatic nerves. In Labat’s studies, 48% alcohol [18] [22] [23]
(equal parts of 95% alcohol and 1% procaine) and 95% alcohol were compared. Labat observed temporary paralysis
in all animals with use of both concentrations. The period of time required to recover from the paralysis varied and
was inconsistent with the concentration of the alcohol. Thus, in one case, 48% alcohol caused paralysis for 50 days,
the same duration of paralysis as in another case in which 95% alcohol had been used. On microscopic examination
performed after recovery, no demonstrable nerve changes could be seen. Using 33.3% alcohol, Labat and [18] [23]
Greene reported satisfactory clinical results in the management of painful disorders. They did not report any
[8]
muscular paralysis or even paresis.
264
Figure 15-1 A, Effects of alcohol on the peripheral nerve, 15 seconds after application. Electron micrograph shows the sciatic nerve of a mouse after topical
application of 100% alcohol. Note the swelling of unmyelinated nerve fibers; sc indicates Schwann cell cytoplasm that is clumped and granular—Schwann cell
destruction (original magnification ×5000). B, Effect of alcohol on the peripheral nerve, 15 seconds after application. Electron micrograph shows the Schwann cell
after exposure to 100% alcohol. The splitting of the myelin sheath (MS) and the dilated endoplasmic reticulum (ER) indicate acute injury to the Schwann cell and
myelin sheath (original magnification ×4300). C, Effect of alcohol on the peripheral nerve 1 minute after application. Electron micrograph shows splitting of the
myelin sheath after exposure to 100% alcohol (original magnification ×9600). D, Effect of alcohol on the peripheral nerve, 24 hours after a 15-second exposure to
100% alcohol. Note degenerating axons (A) splitting myelin lamellae (M) and beginning of connective tissue reaction (CR) (original magnification ×2200). E, Effect
of alcohol on the peripheral nerve, 4 hours after a 15-second exposure to 100% alcohol. (From Woolsey RM, Taylor JJ, Nagel JH: Acute effects of topical ethyl
alcohol on the sciatic nerve of the mouse. Arch Phys Med Rehabil 53:410, 1972.)
Despite the inconsistency in results with varying concentrations of alcohol, there is better consensus regarding
maximal and minimal concentrations. For complete paralysis, the concentration must be stronger than 95% alcohol.
From Labat and Greene, it may be concluded that a minimal concentration of 33% alcohol is necessary to obtain
[24]
satisfactory analgesia without any motor paralysis.
Histopathologic studies have shown that alcohol extracts cholesterol, phospholipids, and cerebrosides from the
nerve tissue and causes precipitation of lipoproteins and mucoproteins. This results in sclerosis of nerve fibers
[25] [26]
and myelin sheaths. Alcohol produces nonselective destruction of nervous tissue by precipitating cell membrane
[30] [38]
proteins and extracting lipid compounds, resulting in demyelination and subsequent wallerian degeneration. Because
the basal lamina of the Schwann cell tube is often spared, however, the axon often regenerates along its former
course. If a ganglion is injected, it may produce cell body destruction without subsequent regeneration. Topical
[38] [38]
application of alcohol to peripheral nerves produces changes typical of wallerian degeneration. A subarachnoid
injection of absolute alcohol causes similar changes in the rootlets. Mild focal inflammation of meninges and
[26] [27]
patchy areas of demyelination are seen in posterior columns, Lissauer’s tract, and dorsal roots and rootlets. Later,
wallerian degeneration is seen to extend into the dorsal horns. Injection of a larger volume can result in degeneration
of the spinal cord. When alcohol is injected near the sympathetic chain, it destroys the ganglion cells and thus
[26]
blocks all postganglionic fibers to all effector organs. A temporary and incomplete block results if the injection
[31]
affects only the rami communicantes of preganglionic and postganglionic fibers. Histopathologically, wallerian
degeneration is evident in the sympathetic chain fibers. [26]
For subarachnoid block, alcohol concentrations between 50% and 100% are generally selected (Fig. 15–2 (Figure
Not Available) ). Alcohol is hypobaric in nature in relation to CSF. Therefore, the patient must be in the lateral
decubitus position with the painful site uppermost. The patient must then be rolled anteriorly approximately 45
degrees to place the dorsal (sensory) root uppermost. The reported volumes required for neurolysis range from a
[29]
minimum of 0.3 mL to a maximum of 0.7 mL of absolute alcohol per segment and from 0.5 mL to 1 mL to a [28]
maximum of 1.5 mL per segment. For celiac plexus block, volumes of 10 mL to 20 mL of absolute alcohol
[18] [30]
265
bilaterally may be used. Similar volumes have been reported for lumbar sympathetic block. Often, 100% alcohol is
[30]
diluted 1:1 with a local anesthetic before injection. [18]
The most ominous complication associated with the use of alcohol is the possible occurrence of alcoholic neuritis. It
has been postulated that alcoholic neuritis is caused by incomplete destruction of somatic nerves. This seems
plausible, because neuritis has not been observed after an intraneural injection of a cranial or somatic nerve that
produces a complete block. Alcoholic neuritis occurs frequently after paravertebral block of the thoracic
[18]
sympathetics. The cause of the neuritis may be the close proximity of the sympathetic ganglia to the intercostal
[31]
nerves. The alcohol, which is intended for the ganglion, inadvertently bathes and partially destroys the somatic
nerve. During the period of regeneration, hyperesthesia and intense burning pain with occasional sharp shooting
[18] [84]
pain occurs. These pains may be more intense than the original complaint. Fortunately, in most instances, these
symptoms subside within a few weeks or a month. Occasionally, however, this complication persists for many
months, requiring sedation and, in some instances, performance of a subsequent rhizotomy or sympathectomy. As [18]
a prophylactic measure, Mandl recommended the injection of a local anesthetic procaine
Figure 15-2 (Figure Not Available) A, Effect of alcohol on the spinal cord, 4 days after neurolytic block. Cross-section through the spinal cord at
T4 shows degeneration of the dorsal fascicularis (DF) after injection of 100% alcohol several interspaces lower. B, Effect of alcohol on the spinal
cord, 50 days after direct cord injection. Necrosis and degeneration occurred (arrows) after accidental injection of 100% alcohol into the spinal
cord. (From Gallagher HS, Yonexawa T, Hay RC, et al: Subarachnoid alcohol block. II. Histologic changes in the central nervous system. Am J
Pathol 35:679, 1961. © American Society for Investigative Pathology.)
mixture during the insertion of the needle, at the site of injection before the alcohol is injected, and again when the
needle is withdrawn. With use of this technique, he has observed only two instances of alcoholic neuritis.
[32]
Slight cases of alcoholic neuritis are treated conservatively with mild analgesics such as aspirin or with small doses
of codeine. Moderate cases of alcoholic neuritis may require more active therapy. Intravenous histamine, 2.75 mg
[18]
dissolved in 500 mL of 5% glucose in distilled water, administered twice daily, has been employed with some
success. In some cases, the administration of intravenous local anesthetics has been helpful. Bonica determined
[18]
that Pontocaine 250 mg dissolved in 500 mL of fluid was superior to procaine. In one case, when intravenous [33]
procaine had been administered several times with only transient relief of pain, one infusion of tetracaine effected
prolonged pain relief. In some cases, daily sympathetic blocks have been employed with excellent results. In the [18]
case of lumbar nerve neuritis after lumbar sympathetic blocks, serial caudal blocks performed at regular intervals
can effect complete relief of pain. Severe cases of alcoholic neuritis that do not respond to these conservative
[18]
methods may require sympathectomy or rhizotomy. De Takats reported on three such patients who required
[34]
sympathectomy.
Hypesthesia and anesthesia of the dermatomal distribution of nerve roots treated with neurolysis are other
complications associated with alcohol nerve block. The lack of sensation can overshadow the pain relief afforded by
the procedure. Fortunately, this complication is rare, and recovery is relatively quick. Loss of bowel or bladder [26]
sphincter tone, leading to bowel or urinary incontinence, has also been reported with intrathecal alcohol neurolysis
administered to the lower lumbar and sacral areas. To decrease the risk of these complications, it is recommended
[26]
that during sacral neurolysis, only one side should be blocked at a time. A complication of lumbar sympathetic
[26]
neurolysis with alcohol is the development of genitofemoral neuralgia, which can cause severe groin pain. This
referred pain is caused by the degeneration of the rami communicantes from the L2 nerve root to the genitofemoral
nerve. Paraplegia can result if injection of alcohol causes spasm of the artery of Adamkiewicz.
[26] [35] [36] [37] [26]
Alcohol-induced neurolysis causes a disulfiram-like effect. Umeda and Arai reported a case of an individual
[39]
undergoing an alcohol celiac plexus block (15 mL of 67% alcohol) who experienced flushing, sweating, dizziness,
vomiting, and marked hypotension 10 minutes after the infusion ceased. The authors speculated that the reaction
[38]
was due to the patient’s being treated with moxalactam, a type of beta-lactam antibiotic reported to inhibit aldehyde
dehydrogenase. Other agents share this property, including metronidazole (Flagyl); chloramphenicol; the beta-
lactam type antibiotics; the oral hypoglycemic tolbutamide (Orinase) and chlorpropamide (Diabinese); and, of
course, disulfiram (Antabuse). [38] [40]
Phenol
Phenol is a combination of carbolic acid, phenic acid, phenylic acid, phenyl hydroxide, hydroxybenzene, and
oxybenzene. It is not available commercially in the injectable form but can be prepared by the hospital pharmacy.
One gram of phenol dissolves in about 15 mL water (6.67%). It is very soluble in alcohol, glycerol, and a number of
other organic substances. Phenol is usually mixed with saline or glycerin and may be mixed with sterile water or
material used for contrast radiography. Because it is highly soluble in glycerin, phenol diffuses from it slowly. This
[15]
266
is an advantage of intrathecal injection, which allows limited spread and highly localized tissue fixation. Diffusion
also makes phenol hyperbaric relative to CSF. When mixed with glycerin, phenol is so viscid that even when
warmed, injection must be made through at least a 20-gauge needle. This mixture must be free of water, or the
necrotizing effect is much greater than anticipated. When phenol is mixed in an aqueous mixture, it is a far more
[15]
potent neurolytic. Phenol oxidizes and turns red when exposed to air and light. The shelf life of phenol is said to
[26] [15]
exceed 1 year when preparations are refrigerated and not exposed to light. Phenol acts as a local anesthetic at lower
concentrations and as a neurolytic agent in higher concentrations. It has an advantage over alcohol because there is
minimal discomfort on injection.
In 1925, Doppler was the first to use phenol to deliberately destroy nervous tissue. After painting phenol on human
[41]
ovarian vessels, he noted downstream vasodilatation and flush. Later, he reported treating peripheral vascular
disease in the lower extremity by exposing and painting the femoral arteries with a 7% aqueous solution. Twelve
patients were reported to improve, and no failure or complication rate was reported. In 1933, Binet, in France, [41]
reported painting ovarian vessels with 7% phenol. Doppler and Binet attributed their good results to destruction of
perivascular sympathetic fibers. In 1933, Nechaev reported the use of phenol as a local anesthetic. In 1936,
[18] [42]
Putnam and Hampton used an injection of phenol to perform a neurolysis of the gasserian ganglion.
[43]
In 1947, Mandl suggested injecting phenol to obtain permanent sympathectomy. In 1950, he reported its use in 15 [44]
patients, without complications, suggesting that it was preferable to alcohol. The paravertebral injection of
[18] [32]
phenol for peripheral vascular disease was also reported by Haxton and Boyd and colleagues in 1949. In 1955,
[45] [46]
Maher introduced phenol as a hyperbaric solution for intrathecal use in intractable cancer pain, by uttering the
famous remark, “It is easier to lay a carpet than to paper a ceiling.” Thereafter, he reported epidural use as well.
[47] [18]
By 1959, phenol was established as a neurolytic agent for the relief of chronic pain. Kelly and Gautier-Smith and [18] [48]
Nathan then simultaneously reported the use of phenol for the relief of spasticity caused by upper motor neuron
[49]
lesions. Phenol in hyperbaric solution was injected intrathecally, with proper patient positioning to “fix” the drug on
the anterior nerve roots, and thus relieve spasticity (Fig. 15–3 (Figure Not Available) ).
Maher studied various concentrations (3.3%–10%) of phenol in glycerin injected into the subarachnoid space in an
effort to determine the ideal neurolytic strength solution. There was a gradation of block according to the
[47]
concentration. The stronger concentration caused motor damage. Pain was blocked at lower concentrations (5%)
than touch and proprioception. The 3.3% phenol concentration was ineffective. Iggo and Walsh determined that 5%
of phenol in either Ringer’s solution or oil contrast medium produced selective
Figure 15-3 (Figure Not Available) Effect of phenol on the spinal cord. Micrographs of transverse section at levels L2, L3, L4–L5, and S3 show
degeneration of the posterior column after subarachnoid injection of phenol at L3–L4.(From Smith MC: Histological findings following
intrathecal injections of phenol solutions for relief of pain. Br J Anaesth 36:387, 1964.)
block of the smaller nerve fibers in cat spinal rootlets. The same conclusions were drawn from the investigations
[50]
by Nathan and Sears. For a long time thereafter, the idea prevailed that phenol caused selective destruction of
[51]
smaller nerve fibers with slower conduction rates, the C afferents carrying slow pain, the A-delta afferents carrying
fast pain, and the A-gamma efferents controlling muscle tone. [18]
Histopathologic studies by Stewart and Lourie demonstrated nonselective degeneration in cat rootlets, with
[52]
severity parallel to the concentration. Nathan and associates found evidence of A-delta and A-beta damage in their
[18]
electrophysiologic experiments and confirmed the nonselectivity of damage by histologic examination. [53]
At concentrations of less than 5%, phenol produces protein denaturation. Concentrations greater than 5% cause
protein coagulation and nonspecific segmental demyelination and orthograde degeneration (i.e., wallerian
degeneration). Concentrations of 5% to 6% produce destruction of nociceptive fibers with minimal side effects.
[38]
Higher concentrations result in axonal abnormalities, nerve root damage, spinal cord infarcts, and arachnoiditis or
meningitis. These characteristics may explain the long-lasting results of neurolytic blocks performed with 10%
[38] [54]
phenol in the sympathetic axis. [38]
The block produced by phenol tends to be less intense and of shorter duration than that produced by alcohol. Moller
and associates compared various concentrations of alcohol and phenol and concluded that 5% phenol equaled 40%
[55]
alcohol in neurolytic potency. Axons of all sizes are affected by therapeutic concentrations and, as described for
ethyl alcohol, appear edematous. Importantly, the posterior root ganglia are unaffected by phenol. Similar [56]
pathologic changes occur in peripheral nerves when they are exposed to phenol. The process of degeneration takes [18]
about 14 days, and regeneration is completed in about 14 weeks. After intrathecal phenol injection, the
267
concentration decreases rapidly—to 30% of the original concentration in 60 seconds and to 0.1% within 15
minutes. [26] [57]
Phenol is efficiently metabolized by liver enzymes. The principal pathways are conjugation to the glucuronides and
oxidation to equinol compounds or to carbon dioxide and water. It is then excreted as a variety of conjugates via the
kidney. [18]
A higher affinity for vascular tissue than for neuronal tissue has been suggested by Wood. The interference with [54]
blood flow is believed to be the etiology for the observed neuropathy. However, Racz and associates studied the
[58] [59]
morphologic changes that occurred after epidural and subarachnoid injection. They found that massive tissue [60]
destruction was present after subarachnoid injection compared with epidural injection despite intact vasculature in
areas of spinal cord destruction. These findings support a direct neurotoxic effect of phenol rather than an effect
[38]
secondary to vascular destruction. [38] [61]
Large systemic doses of phenol (≥8.5 g) cause convulsions and then central nervous system depression and
cardiovascular collapse. Chronic poisoning results in skin eruptions, gastrointestinal symptoms, and renal toxicity. [38]
Clinical doses between 1 mL and 10 mL of 1% to 10% solutions (up to 1000 mg) are unlikely to cause serious
toxicity. [38] [62]
Glycerol
Glycerol is used mostly for neurolysis of the gasserian ganglion to treat idiopathic trigeminal neuralgia. [63]
Considered a mild neurolytic like other alcohols, it produces localized perineural damage, whereas intraneural
injection results in Schwann cell edema, axonolysis, and wallerian degeneration. In one histologic study, [38]
intraneural injection of glycerol was more damaging than topical application, although significant, localized,
subperineural damage occurred after local application of a 50% glycerol solution. Histologic changes included [38] [64]
the presence of many inflammatory cells, extensive myelin swelling, and axonolysis. Myelin disintegration occurs
weeks after the injury along with ongoing axonolysis during periods of myelin restitution, indicating an ongoing
nerve fiber injury possibly caused by secondary events such as compression of transperineural vessels and
ischemia. Electron microscopy shows evidence of wallerian degeneration; with intraneural injection, all nerve
[38] [64] [65]
fibers are destroyed. [38]
The mechanism of action is not clear. Sweet and colleagues suggested that glycerol affected primarily small
[66]
myelinated and unmyelinated fibers. Bennett and Lunsford, using trigeminal evoked-potential studies, concluded
[38]
that glycerol more specifically affects the damaged myelinated axons implicated in the pathogenesis of trigeminal
neuralgia. Because there is no permanent injury to surrounding structures and facial sensation is preserved in
[38] [67] [68]
most patients, Feldstein considered glycerol superior to radiofrequency rhizotomy for the treatment of tic
douloureux. However, potential spread to the subarachnoid space, risk of neuropathy, and poor control of the
[69]
spread of a fluid agent, have made radiofrequency a continued attractive alternative. With the current use of pulsed
radiofrequency, the advantage of a discrete, controlled lesion remains, without the concern for neuritis or loss of
facial sensation. However, long-term follow-up on its effectiveness has not been reported.
Hypertonic and Hypotonic Solutions
Hypertonic or hypotonic subarachnoid injections have been used for achieving neurolysis. The intrathecal injection [70]
of cold (2°C to 4°C) 0.9% NaCl is supposed to have a specific action on the pain-carrying C fibers, sparing the
larger fibers that subserve sensory, motor, and autonomic functions. The technique requires the spinal fluid to be
[71]
withdrawn and replaced with cold saline as rapidly as possible. Up to 40 mL to 60 mL of saline has been injected.
[18]
Local anesthetic should be used concomitantly or the procedure can be very painful. The pain relief is usually short-
term.[18]
Injections of hypertonic saline can be quite painful; therefore, local anesthetics are generally injected before the
saline. The intrathecal injection of hypertonic saline can produce a variety of complications. Some degree of
[15] [72]
complications occurred in 11% and significant morbidity in 1% of patients. Two deaths were reported secondary to
myocardial infarction. During saline injection, sinus tachycardia or premature ventricular contraction have been
seen, and localized paresis lasting for many hours and paresthesia extending for weeks have been observed. Other
[73] [74]
complications reported include hemiplegia, pulmonary edema, pain in the ear, vestibular disturbances, and loss of
sphincter control with sacral anesthesia. [18] [75]
268
Pathologic changes caused by hypertonic and hypotonic solutions have been extensively studied. Microscopic [18] [76] [77]
changes seen on the peripheral nerves do not correlate with clinical effects of differential C fiber block. [77] [78]
However, application of distilled water on the dorsal root ganglia for 5 minutes produced a differential C fiber block
similar to that seen with in vitro hypertonic saline. The mechanism of action seems to be the intracellular shifts of
water with extracellular change in osmolarity. [18]
Ammonium Salts
In 1935, Judovich used pitcher plant distillate for long-term analgesia. The active component of the distillate was
determined to be ammonium sulfate, ammonium chloride, or ammonium hydroxide, depending on the acid used to
neutralize the distillate and on the pH. Limited pathologic studies suggested that ammonium salts in
[18] [79]
concentrations of greater than 10% caused acute degenerative neuropathy. This degeneration was nonselective,
affecting all types of nerve fibers. More recent in vitro studies with pitcher plant distillate attributed the effects to
[18]
benzyl alcohol contained in the vehicle. Associated complications such as nausea and vomiting, headache,
[18] [80]
paresthesia, and spinal cord injury have led to the clinical abandonment of ammonium salt solutions, including
pitcher plant distillate. [18]
The action of ammonium salts on nerve impulses produces obliteration of C fiber potentials, with only a small effect
on A fibers. Limited pathologic studies suggest that injection of ammonium salts around a peripheral nerve
[81] [82]
causes an acute degenerative neuropathy affecting all fibers. [18]
Hand reported the use of subarachnoid ammonium salts in 50 patients. Transient complications were nausea and
[83]
headache, whereas paresthesias or burning sensation occurred in 30% of patients at doses of 500 mg of ammonium
salt and lasted 2 to 14 days. [18]
Conclusion
The use of chemical neurolytic agents for the interruption of painful pathways is one option for the treatment of
intractable chronic pain. Because of the potential for undesirable side effects, it is imperative that this method be
used by an experienced clinician. The use of fluoroscopic or radiographic guidance is strongly encouraged for
accurate placement of the needle and the injection of the solution because the lesion created is not discrete. The
patients must be carefully selected and given fully informed consent.
REFERENCES
1. Jain
S: The role of neurolytic procedures. In Parris WCV (ed): Cancer Pain Management: Principles and Practice. Boston, Butterworth–
Butterworth-Heinemann, 1997, pp 231–244.
2. Luton A: Études sur la médication substitutive. Première partie, de la substitution parenchymapeuse. Deuxième partie de la
médicationsubstitutive: son Entendue, ses divisions. Archiv Gen Med, ii:57, 1863.
3. Arter OE, Racz GB: Pain management of the oncologic patient. Semin Surg Oncol 6:162, 1990.
4. Raj PP, Patt RB: Peripheral neurolysis. In Raj PP (ed): Pain Medicine: A Comprehensive Review. St. Louis, Mosby-Year Book, 1996, pp 288–
296.
5. Ferrer-Brecher T: Anesthetic techniques for the management of cancer pain. Cancer 63:2343, 1989.
6. Moore DC: Intercostal nerve block and celiac plexus block for pain therapy. In Benedetti C (ed): Recent Advances in the Management of Pain,
vol 4. New York, Raven Press, 1984.
7. Patt R: Neurosurgical interventions for chronic pain problems. Anesthesiology Clin North Am 5:609, 1987.
8. Rammamurthy S, et al. Evaluation of neurolytic blocks using phenol and cryogenic block in the management of chronic pain. J Pain Symp
Manage 4:72, 1989.
9. Pender JW, Pugh DG: Diagnostic and therapeutic nerve blocks: Necessity for roentgenograms. JAMA 146:798, 1951.
10. Raj PP, Rosenblatt R, Montgomery S: Uses of the nerve stimulator for peripheral block. Reg Anesth 5:14, 1980.
11. Rastogi V, Kumar R: Peripheral nerve stimulator as an aid for therapeutic alcohol blocks. Anesthesiology 38:163, 1983.
12. Bonica JJ: Management of Pain. Philadelphia, Lea and Febiger, 1953.
269
13. Roviaro GC, Varoli F, Fascianella A, et al: Intrathoracic intercostal nerve block with phenol in open chest surgery. Chest 90:64, 1986.
14. Moore DC: Regional Block, 4th ed. Springfield, III, Charles C. Thomas, 1965.
15. Heavner JE: Neurolytic agents. In Raj PP (ed): Pain Medicine: A Comprehensive Review. St. Louis, Mosby-Year Book, 1996, pp 285–286.
16. Rall TW: Hypnotics and sedatives: Ethanol. In Gilman AG, Rall TW, Nies AS, Palmer T (ed): The Pharmacological Basis of Therapeutics, 8th
ed. New York, Pergamon Press, 1990.
17. Schlosser H: Erfahrungen in der Neuralgiebehandlung mit Alkoholeinspritzungen. Verh Dtsch Ges Inn Med 24:49, 1907.
18. Raj PP, Denson DD: Neurolytic agents. In Raj PP (ed): Clinical Practice of Regional Anesthesia, New York, Churchill Livingstone, 1991, pp
135–152.
19. Finkelburg R: Experimentelle Untersuchungen uber den Einfluss vom Alkoholinjektionen und periferische Nerven. Verh Dtsch Ges Inn Med
24:75, 1907.
20. May O. Functional and histological effects of intraneural and intraganglionic injections of alcohol. BMJ 2:365, 1912.
21. Gordon A: Experimental study of intraneural injections of alcohol. J Nerv Ment Dis 41:81, 1914.
22. Nasaroff NN: Uber Alkoholinjektionen in Nervenstamine. Zentralbl Chir 52:2777, 1925.
23. Labat G: Action of alcohol on the living nerve. Curr Res Anesth Analg 12:190, 1933.
24. Labat G, Greene MB: Contributions to the modern method of diagnosis and treatment of so-called sciatic neuralgias. Am J Surg 11:435, 1931.
25. Rumbsy MG, Finean JB: The action of organic solvents on the myelin sheath of peripheral nerve tissue—II (short-chain aliphatic alcohols). J
Neurochem 13:1509, 1966.
26. Jain S, Gupta R: Neurolytic agents in clinical practice. In Waldman SD (ed): Interventional Pain Management, 2nd ed. Philadelphia, WB
Saunders, 2001, pp 220–225.
27. Gallagher
HS, Yonezawa T, Hoy RC, Derrick WS: Subarachnoid alcohol block. I: Histological changes in the central nervous system. Am J
Pathol 35:679, 1961.
28. Matsuki M, Kato Y, Ichiyangi L: Progressive changes in the concentration of ethyl alcohol in the human and canine subarachnoid space.
29. Swerdlow M: Neurolytic blocks. In Patt RB (ed): Cancer Pain. Philadelphia, JB Lippincott, 1993, p 435.
30. Dwyer B, Gibb D: Chronic pain and neurolytic blockade. In Cousins MJ, Bridenbaugh PO (eds): Neural Blockade, Clinical Anesthesia and
Management of Pain. Philadelphia, JB Lippincott, 1980.
31. Merrick RL: Degeneration and recovery of autonomic neurons following alcoholic block. Ann Surg 113:298, 1941.
32. Mandl F: Aqueous solution of phenol as a substitute for alcohol in sympathetic block. J Int Coll Surg 13:566, 1950.
33. Bonica JJ: Regional anesthesia with tetracaine. Anesthesiology 11:606, 716, 1950.
34. De Takats G: Discussion of paper by HS Ruth: Diagnostic, prognostic, and therapeutic nerve blocks. JAMA 102:419, 1934.
35. Rocco A: Radiofrequency lumbar sympatholysis: The evolution of a technique for managing sympathetically mediated pain. Reg Anesth 20:3–
12, 1995.
36. Bogduk N, Tynan W, Wilson SS: The nerve supply to the human intervertebral discs. J Anat 132:39–56, 1981.
37. Edwards EA: Operative anatomy of the lumbar sympathetic chain. Angiology 12:184–198, 1951.
38. de Leon-Casasola OA, Ditonto E: Drugs commonly used for nerve blocking: Neurolytic agents. In Raj PP (ed): Practical Management of Pain.
3rd ed. St. Louis, Mosby, 2000, pp 575–578.
39. Umeda S, Arai T: Disulfiram-like reaction to moxalactam after celiac plexus alcohol block. Anesth Analg 64:377, 1985.
40. Lyness WH: Pharmacology of neurolytic agents. In Racz GB (ed): Techniques of Neurolysis. Boston, Kluwer Academic, 1989, p 13.
41. Binet A: Valeur de la sympathectomie chimique en gynécologie. Gynecol Obstet 27:393, 1933.
42. Nechaev VA: Solutions of phenol in local anesthesia. Soviet Khir 5:203, 1933.
43. Putnam TJ, Hampton AO: A technique of injection into the gasserian ganglion under roentgenographic control. Arch Neurol Psychiatry 35:92,
270
1936.
44. Mandl F: Paravertebral Block. Orlando, Fl, Grune & Stratton, 1947.
45. Haxton HA: Chemical sympathectomy. BMJ 1:1026, 1949.
46. Boyd AM, Ratcliff AH, Jepson RP, et al: Intermittent claudication. J Bone Joint Surg 3B:325, 1949.
47. Maher RM: Phenol for pain and spasticity. In Pain: Henry Ford Hospital International Symposium. Boston, Little Brown, 1966, p 109.
48. Kelly RE, Gautier-Smith PC: Intrathecal phenol in the treatment of reflex spasms and spasticity. Lancet 2:1102, 1959.
49. Nathan PW: Intrathecal phenol to relieve spasticity in paraplegia. Lancet 2:1099, 1959.
50. Iggo A, Walsh EG: Selective block of small fibers in the spinal roots by phenol. Brain 83:701, 1960.
51. Nathan PW, Sears TA: Effects of phenol on nervous conduction. J Physiol (London) 150:565, 1960.
52. Stewart WA, Lourie H: An experimental evaluation of the effects of subarachnoid injection of phenol-pantopaque in cats. J Neurosurg 20:64,
1963.
53. Nathan PW, Sears TA, Smith MC: Effects of phenol solutions on the nerve roots of the cat: An electrophysiologic and histologic study. J
Neurol Sci 2:7, 1965.
54. Wood KM: The use of phenol as a neurolytic agent: A review. Pain 5:205, 1978.
55. Moller JE, Helweg-Larson J, Jacobson E. Histopathological lesions in the sciatic nerve of the rat following perineural application of phenol
and alcohol solutions. Dan Med Bull 16:116–119, 1969.
56. Smith MC: Histological findings following intrathecal injection of phenol solutions for the relief of pain. Anaesthesia 36:387, 1964.
57. Bates W, Judovich BD: Intractable pain. Anesthesiology 3:363, 1942.
58. Nour-Eldin F: Uptake of phenol by vascular and brain tissue. Microvasc Res 2:224, 1970.
59. Totoki T, Kato T, Nomoto Y, et al: Anterior spinal artery syndrome—a complication of cervical intrathecal phenol injection. Pain 6:99, 1979.
60. Racz GB, Heavner J, Haynsworth R: Repeat epidural phenol injections in chronic pain and spasticity. In Lipton S, Miles J (eds): Persistent
Pain, 2nd ed New York, Grune & Stratton, 1985, p 157.
61. Heavner, JE, Racz GB: Gross and microscopic lesions produced by phenol neurolytic procedures. In Racz GB (ed): Techniques of Neurolysis.
Boston, Kluwer Academic Publishers, 1989, p 27.
62. Cousins MJ: Chronic pain and neurolytic neural blockade. In Cousins MJ, Bridenbaugh PO (eds): Neural Blockade in Clinical Anesthesia and
Management of Pain, 2nd ed. Philadelphia, JB Lippincott, 1988, p 1053.
63. Hakanson S: Trigeminal neuralgia treated by the injection of glycerol into the trigeminal cistern. Neurosurgery 9:638, 1981.
64. Rengachary SS, Watanabe IS, Singer P, Bopp WJ: Effect of glycerol on peripheral nerve: An experimental study. Neurosurgery 13:681,
1983.
65. Myers RR, Katz J. Neuropathy of neurolytic and semidestructive agents. In Cousins MJ, Bridenbaugh PO (eds): Neural Blockade in Clinical
Anesthesia and Management of Pain, 2nd ed. Philadelphia, JB Lippincott, 1988, p 76.
66. Sweet WH, Poletti CE, Macon JB: Treatment of trigeminal neuralgia and other facial pains by retrogasserian injection of glycerol.
Neurosurgery 9:3647, 1981.
67. Bennett MH, Lunsford LD: Percutaneous retrogasserian glycerol rhizotomy for tic douloureux: Part 2. Results and implications of trigeminal
evoked potentials. Neurosurgery 14:431, 1984.
68. Lunsford LD, Bennett MH: Percutaneous retrogasserian glycerol rhizotomy for tic douloureux: Part 1. Technique and results in 112 patients.
Neurosurgery 14:424, 1984.
69. Feldstein GS: Percutaneous retrogasserian glycerol rhizotomy in the treatment of trigeminal neuralgia. In Racz GB (ed): Techniques of
Neurolysis. Boston, Kluwer Academic Publishers, 1988, p 125.
70. Hitchcock E: Osmolytic neurolysis for intractable facial pain. Lancet 1:434, 1969.
271
71. Lund PC: Principles and Practice of Spinal Anesthesia. Springfield, IL, Charles C. Thomas, 1971.
72. Lucas JT, Ducker TB, Perok PL: Adverse reactions to intrathecal saline injection for control of pain. J Neurosurg 42:557, 1975.
73. McKean MC, Hitchcock E: Electrocardiographic changes after intrathecal hypertonic saline solution. Lancet 2:1083, 1968.
74. Ventafridda V, Spreafico R: Subarachnoid saline perfusion. Adv Neurol 4:477, 1974.
75. O’Higgins JW, Padfield A, Clapp H: Possible complications of hypothermic saline subarachnoid injection. Lancet 1:567, 1970.
76. Hewett DL, King JS: Conduction block of monkey dorsal rootlets by water and hypertonic solutions. Exp Neurol 33:225, 1971.
77. Nicholson MF, Roberts FW: Relief of pain by intrathecal injection of hypothermic saline. Med J Aust 1:61, 1968.
78. Thompson GE: Pulmonary edema complicating intrathecal hypertonic saline injection for intractable pain. Anesthesiology 35:425, 1971.
79. Walti A: Determination of the nature of the volatile base from the rhizome of the pitcher plant., Sarracenia purpurea. J Am Chem Soc
67:22, 1945.
80. Ford DJ, Phero JC, Denson D: Effect of pitcher plant distillate on frog sciatic nerve. Reg Anaesth 5:16, 1980.
81. Davies JI, Steward PB, Fink P: Prolonged sensory block using ammonium salts. Anesthesiology 28:244, 1967.
82. Judovich BD, Bates W, Bishop K: Intraspinal ammonium salts for the intractable pain of malignancy. Anesthesiology 5:341, 1944.
83. Hand LV: Subarachnoid ammonium sulfate therapy for intractable pain. Anesthesiology 5:354, 1944.
84. Woolsey RM, Taylor JJ, Nagel JH: Acute effects of topical ethyl alcohol on the sciatic nerve of the mouse. Arch Phys Med Rehabil 53:410,
1972. 239
272
Section IV - Chapter 16 - Continuous Regional Analgesia
Chapter 16 - Continuous Regional Analgesia
SUSAN R. ANDERSON
Infusion techniques in the epidural space as well as on the peripheral nerves are now commonly used for treatment
of acute and chronic pain. For acute pain, continuous regional infusion has been found to be beneficial for trauma,
after surgery, and in acute medical conditions. Similarly, for chronic pain, the technique has been useful in the
rehabilitation of patients with chronic back pain and in relieving pain from reflex sympathetic dystrophy, peripheral
neuropathy, and cancer.
Continuous epidural analgesia is not a new concept. The first use of this technique was reported in 1949 with a
[1] [2] [3]
description of intermittent boluses of a local anesthetic administered postoperatively for 1 to 5 days. Although
[4]
effective analgesia was obtained, significant sympathetic blockade accompanied the pain relief, with a fluctuating
level of analgesia as the effect of the bolus began to regress. Continuous epidural analgesia with intermittent bolus
injections is labor-intensive and requires skilled personnel to reassess and reinject the patient every few hours.
Because of these shortcomings, continuous infusion (CI) of epidural local anesthetics has now become
commonplace ( Fig. 16–1 ).
Continuous Infusion Versus Intermittent Bolus Injection
Continuous epidural infusion offers many therapeutic advantages over intermittent bolus injection. The primary
advantage is the continuous administration of analgesia compared with intermittent dosages. Although single
boluses of opioids such as epidural morphine may provide 12 hours of pain relief, wide variability has been reported
in the duration of effective analgesia, ranging from 4 to 24 hours. Thus, it becomes difficult to titrate uniform
[5] [6]
levels of pain relief. Continuous infusions provide ease of titration, particularly when shorter acting opioids, such as
fentanyl and sufentanil, are employed. Epidurally administered fentanyl has an onset of action within 4 to 5 minutes
and a peak effect within 20 minutes. This rapidity of onset facilitates adjustment in dosage, because the patient
[7] [8] [9]
can quickly experience pain relief.
A significant disadvantage of the intermittent bolus technique is the need for action when pain relief subsides 4 to 6
hours after epidural administration of morphine. A decision needs to be made about whether to inject a second dose
of epidural opioid or to supplement the bolus through systemic administration of an analgesic. Another disadvantage
of the intermittent technique is that supplementation with parenteral narcotic or sedative drugs increases the risk of
respiratory depression in a patient who has had epidural narcotic administered previously. For the intermittent bolus
technique to be successful, administration of longer acting agents, such as morphine and hydromorphone, is required
to provide a reasonable duration of analgesia. These opioids are associated with a higher risk of delayed-onset
respiratory depression.[6]
A third disadvantage of the intermittent bolus injection technique is the tachyphylaxis that develops with repeat
boluses. In contrast, continuous infusion of the analgesic with the same dose actually increases the intensity of
[10] [11]
the block, and the rate of infusion has to be decreased to maintain the same level of analgesia over time.
Continuous epidural infusion of analgesic agents, especially opioids, has the advantage of fewer fluctuations in
cerebrospinal fluid concentrations of drug. The fact that it takes several hours to infuse enough of a long-acting
opioid such as morphine to provide adequate analgesia represents, however, a major disadvantage. This drawback
can be overcome by administration of a 5- to 10-mL “loading” bolus of epidural local anesthetic solution at the
beginning of the infusion or by injection of a bolus of short-acting opioid such as fentanyl or sufentanil. It usually
takes five half-lives of the infused drug to reach a steady state, which, when calculated for morphine or bupivacaine,
is about 15 to 18 hours.
Catheter Location
Segmental limitation of epidural analgesia mandates placement of an epidural catheter at a site adjacent to
273
Figure 16-1 The assembly of analgesic solution, infusion pump, and catheter connection with a filter for epidural infusion technique.
the dermatome covering the field of pain. This practice reduces dosage requirements and increases the specificity of
spinal analgesia. Suggested interspaces where catheters are usually located for epidural infusion of analgesic
[12] [13]
solutions are shown in Table 16–1 .
Analgesic Agents
Epidural analgesia is commonly provided with one of the following choices:
• Local anesthetic
• Opioid
• Opioid combined with local anesthetic
LOCAL ANESTHETICS
Local anesthetic agents are best used to provide analgesia and anesthesia for patients undergoing surgery to maintain
postoperative pain relief. Lidocaine, bupivacaine, and, more recently, ropivacaine are effective in
TABLE 16-1 -- SUGGESTED INTERSPACES FOR CATHETER INSERTION FOR CONTINUOUS INFUSION OF ANALGESIC
SOLUTIONS AFTER SURGERY
Location of Surgery Interspace(s) for Catheter
Thorax T2–T8
Upper abdomen T4–L1
Lower abdomen T10–L3
Upper extremity C2–C8
Lower extremity T12–L3
achieving and maintaining adequate analgesia. In general, lidocaine is limited to use in a bolus form to establish
[10] [11]
or rescue a block, whereas bupivacaine is used as an infusion. Ropivacaine is becoming more widely used for
infusions owing to its shorter time of onset, shorter duration of motor block, greater selectivity for A delta and C
fibers, and decreased cardiotoxicity compared with bupivacaine. A problem inherent in the use of a
[14] [15] [16] [17] [18] [19] [20]
bolus of local anesthetic through the epidural catheter is the development of tachyphylaxis, which has not been seen
when bupivacaine is administered as an infusion.
274
The CI of dilute local anesthetic solutions has simplified maintenance and improved analgesic uniformity; however,
concentrations sufficient to produce pain relief usually have resulted in progressive sensorimotor blockade. Such
deficits are undesirable because the patient’s ability to ambulate is compromised.
The use of local anesthetic agents alone can cause an accumulation of the local anesthetic agent in the systemic
circulation, which is more pronounced with the shorter acting amides such as lidocaine than with the longer
[10] [21]
acting amides. The decrease in systemic effects with longer acting agents has been attributed to their more
nonspecific binding in the fat of the epidural space compared with that of shorter acting amides. Even when
bupivacaine was infused for 72 hours after abdominal surgery, the serum bupivacaine level increased, peaking at 48
to 60 hours. The toxicity of local anesthetics is less pronounced when the agents accumulate slowly, but there is an
[22]
ever-present risk of central nervous system depression, convulsions, or cardiac arrest.
The concentration of local anesthetic influences the analgesia and the profile of side effects. A constant rate of
infusion of 0.25% or greater concentration of bupivacaine is associated with hypotension, muscle weakness, sensory
block, and the possible accumulation of toxic systemic levels of bupivacaine. Higher plasma levels of the agent
[10]
may occur in the elderly or frail patient. Side effects may be attenuated by the use of lower concentrations of
bupivacaine. The use of a low-dose, constant-rate infusion of epidurally administered bupivacaine (0.03% to
0.06%), close to the dermatomal level desired for pain relief, decreases the incidence of side effects. Although the
low dose of bupivacaine is effective, the level of analgesia it provides is less profound than that achieved by
combining bupivacaine with low concentrations of epidurally administered morphine or with the use of opioid
alone.[10] [23] [24]
OPIOIDS
The ideal intraspinal opiate would be hydrophilic in nature, have a high affinity for the opiate receptor, require
occupation of a small percentage of receptors to provide analgesia, demonstrate a prolonged duration of analgesia,
and be free of side effects. The drugs commonly used spinally are morphine, meperidine, fentanyl, and sufentanil.
Morphine is still the only opiate that has FDA approval for epidural administration. In the postoperative period,
morphine sulfate has been administered by intermittent injection and by continuous infusion. Meperidine has also
been injected epidurally and possesses local anesthetic properties. The accumulation of its metabolite normeperidine
is a cause of concern. Fentanyl has achieved widespread popularity during the past 7 to 10 years. Its advantage over
morphine sulfate is that it spreads rostrally less than morphine. Whether the effect after intraspinal injection is spinal
or systemic, the rapidity with which analgesia is obtained after epidural fentanyl administration makes it the drug of
choice for acute, unacceptable pain.
Sufentanil has been used epidurally. The characteristics of fentanyl, which is lipid-soluble, are magnified with
sufentanil. Its theoretic advantage results from the strong affinity it has for µ receptors. This characteristic has
relevance in cancer management.
COMBINATION OF OPIOID WITH LOCAL ANESTHETIC
In an effort to combine the desirable analgesic properties of local anesthetics with those of epidural opioids, several
investigators studied the concomitant use of morphine-bupivacaine epidural infusions for pain relief. Studies
[25] [26] [27] [28]
have demonstrated either additive or synergistic analgesic activity between a variety of opioids and dilute
concentrations of bupivacaine. Such combinations appear to provide pain relief of greater magnitude than that
[27] [28] [29]
attained with either an opioid or bupivacaine alone, and the incidence and severity of side effects are minimized.
This advantage may be explained by the different analgesic properties of each class of agent and their ability to
block pain at two different sites in the spinal cord. Opioids produce analgesia by specific binding and activation of
opiate receptors in the substantia gelatinosa, whereas local anesthetics provide analgesia by clocking impulse
transmission at the nerve roots and dorsal root ganglia.
Bupivacaine has been used most often, in concentrations ranging from 0.03% to 0.125%, with morphine, fentanyl,
or meperidine. The use of morphine and bupivacaine has resulted in effective analgesia in the management of
patients after thoracic, abdominal, and general surgery. Fentanyl combined with bupivacaine, however, had a
[10] [24] [30] [21]
lower incidence of side effects compared with the morphine-bupivacaine combination. Bupivacaine, 0.03% to
0.125%, mixed with fentanyl, 2 to 3 g/mL, at a rate of 8 to 10 mL/hour in an adult 70-kg patient, usually achieves
excellent analgesia with minimal respiratory depression and sensorimotor blockade. Bupivacaine, 0.03%, with
morphine, 0.005%, or fentanyl, 2 to 3 µg/mL, infused at 8 to 10 mL/hour achieves similar results for patients with
chronic pain. Ropivacaine may be used in place of bupivacaine, in concentrations ranging from 0.1% to 0.2%, with
either morphine or fentanyl. Specific concentrations of drugs and rates of infusion should be tailored to individual
patients. For example, one can treat or prevent significant hypotension in patients by (1) decreasing the local
275
anesthetic concentration, (2) eliminating the local anesthetic, (3) decreasing the rate of a combined local anesthetic-
opioid infusion, or (4) infusing intravenous (IV) fluids. One can treat sedation or carbon dioxide retention by (1)
changing the specific epidurally administered opioid, (2) decreasing the concentration of the opioid, (3) decreasing
the overall infusion rate, or (4) eliminating the opioid from the infusion.
Management of Inadequate Analgesia
Although continuous epidural infusion techniques provide excellent results in most patients, occasional individuals
experience inadequate pain relief. In these cases, the causes of inadequate analgesia should be evaluated and
corrected. Most commonly, placement of the catheter is tested in two stages. First, 5 mL of the epidural infusion
solution is administered, and the patient’s analgesia is reassessed after 30 minutes. Second, if the analgesia remains
inadequate, 5 to 10 mL of 2% lidocaine is administered in two fractionated doses. This test dose generally yields one
of three results:
1. If bilateral sensory block occurs in a few segmental dermatomes, correct catheter placement is confirmed.
In this case, insufficient volume of the infusion mixture was the likely cause of inadequate analgesia. This
problem can be rectified by increasing the rate of infusion.
2. A unilateral sensory block most likely indicates that the catheter tip was placed too far laterally into the
epidural space (i.e., at the foramen). The catheter can be withdrawn 1 to 2 cm, and the test dose repeated.
3. Finally, lack of any sensory block indicates that the epidural catheter is no longer in the epidural space. The
catheter is then removed, and the options are placement of another epidural catheter or administration of an
alternative therapy.
Complications of Continuous Infusion Epidural Anesthesia
Complications of continuous epidural anesthesia include accidental intrathecal administration of the analgesic drug,
infection, epidural hematoma, and respiratory depression. To decrease the incidence of these complications, the
following guidelines are advocated:
1. The use of appropriate concentrations of local anesthetics (e.g., bupivacaine, 0.03% to 0.125%) prevents
serious hypotension and facilitates diagnosis of subarachnoid catheter migration more readily by providing
progressive levels of sensory blockade where none would have been expected. Another safety feature is the
combination of dilute local anesthetic solution with half the usual dose of an opioid, such as oral morphine,
0.005% to 0.01%, with fentanyl, 3 µg/mL.
2. Daily examination of catheter insertion sites, monitoring of temperature, and periodic check for neurologic
signs of meningism are essential. If findings consistent with infection are present, the catheter should be
removed and the patient should be treated appropriately. I have had experience with one case of epidural
abscess in 2000 epidural infusion cases. The patient’s infection resolved in 6 weeks with aggressive
antibiotic therapy. Infections limited to the cutaneous and subcutaneous tissues can develop and resolve
with local conservative therapy.
3. If epidural catheters are placed at least 1 hour before heparinization, the incidence of epidural hematoma is
not significant. Epidural catheters may be inserted safely in patients who receive warfarin postoperatively,
as long as their coagulation status is normal at the time of catheter insertion.
Limitations of Continuous Epidural Analgesia
There are limitations to epidural infusion analgesia. First, this type of analgesia cannot independently control pain
that stems from multiple sites. Epidural analgesia normally can provide analgesia for five to seven dermatomal
regions in continuity, such as L4 to S5 or T2 to T8. Patients with multiple injuries may require other forms of pain
control management.
The placement site of the epidural catheter influences the adequacy of pain relief and the maintenance of normal
vital function. In general, placing the epidural catheter within the dermatomal distribution of the pain achieves the
best result with the smallest amount of drug. For example, pain from a thoracotomy is best treated with a thoracic
epidural infusion, and pain in the lower extremity requires a lumbar epidural infusion.
276
Patient-Controlled Epidural Analgesia
Patient-controlled epidural analgesia (PCEA) has been offered to patients with acute postoperative pain after intra-
abdominal, major orthopedic, or thoracic surgery and has also been given to patients with chronic pain states such as
occur with cancer. The technique has several potential advantages. The patient has the ability to titrate analgesic
doses in amounts proportional to the level of pain. Given the large individual variation in the perception of pain and
its relief, this control is an important factor in optimizing spinal opioid analgesia. Most of the published work
[32]
describing PCEA comes from Europe. Chrubasik and colleagues[32]

used PCEA technique in comparing three
[33] [34]
different epidural opioids. These studies were remarkable in that the morphine dosage required to provide effective
analgesia with PCEA was much smaller than the amount used with continuous epidural infusion and IV patient-
controlled analgesia (PCA). Serum morphine levels used in these studies were very low. Table 16–2 lists
[35] [36] [37]
various studies and the opioids used, along with their hourly consumption. Sjostrom and colleagues evaluated [32]
morphine PCEA and demonstrated its efficacy. They employed intermittent boluses of 1 mg with a 30-minute
lockout period. The average consumption was about 0.5 mg/hour, and serum morphine levels were well below the
minimum effective plasma concentrations usually associated with parenteral delivery. Marlowe and coworkers [38]
compared constant infusion of epidural opioid with PCEA. They found that the self-administration technique was
superior because less
TABLE 16-2 -- CONSUMPTION OF OPIOIDS USED WITH PATIENT-CONTROLLED ANALGESIA

Study * Epidural Opiates Average Consumption (mg/hour)
[32]
Sjostrom et al Morphine sulfate 0.52
[38]
Marlowe et al Demerol 18.0
Walmsley et al[39] † Hydromorphone 0.1
[33] †
Chrubasik and Wiemers Morphine sulfate 0.47
Morphine sulfate 0.25
*Superscript number refers to reference number in chapter.
†Infusion and patient-controlled epidural anesthesia were both used.
opiate was required to provide similar levels of analgesia. Walmsley and associates reported the high efficacy of [39]
PCEA in their evaluation of more than 4000 surgical cases.
The following advantages are given for PCEA over conventional epidural CI analgesia:
• Increased efficiency
• Higher satisfaction
• Decreased sedation
• Reduced opioid usage
The following advantages are given for PCEA compared with IV PCA:
• Self-adjustment by patient
• Self-satisfaction and resulting decrease in anxiety
• Reduced opioid requirement
PCEA TECHNIQUE USING MORPHINE
The following techniques are used for patient-controlled epidural analgesia. [31]
Loading Dose
Lower thoracic or upper lumbar catheters are placed preoperatively or intraoperatively with use of standard
techniques. Patients are “loaded” with preservative-free morphine, 2 to 3 mg, and given a basal infusion of 0.4
mg/hour with a 0.02% solution. Patients are allowed to self-administer morphine, 0.2 mg, every 10 to 15 minutes
with a maximum dose of 1 to 2 mg/hour. The “load” is administered only after a local anesthetic test dose (lidocaine
2%, 2 to 3 mL) has demonstrated that the catheter is not located in a subarachnoid space. The optimal loading dose
size and the timing of the administration have yet to be determined; however, given morphine’s latency to peak
277
effect, one needs to “load” as early as possible. Breakthrough pain is common in these patients during the first 6 to 8
hours postoperatively.
Breakthrough pain is treated with epidural morphine boluses, 0.5 to 1.0 mg/hour. If two doses are inadequate to
provide analgesia, the catheter needs to be retested with local anesthetic to confirm the epidural placement and to
rule out dislodgment. The loading dose can be augmented with epidurally administered fentanyl, 50 to 100 µg. This
drug speeds the onset of the analgesia, possibly because of dual action (i.e., rapid vascular uptake) and rapid spinal
cord neural uptake. Residual levels of intraoperatively administered local anesthetics augment initial epidural
morphine analgesia and contribute to subsequent postoperative pain relief.
Lockout
The short lockout period usually set with PCEA is somewhat controversial in view of the longer latency of
morphine’s epidural effect. Sjostrom and coworkers thus chose 30 minutes as the lockout period. There are few
[32]
problems with morphine’s longer latency to peak epidural effect, however, provided that a suitable loading dose has
been administered 90 to 120 minutes before PCEA is begun. It is possible that patients perceive early analgesic
benefits from the small rise in serum morphine levels occurring soon after a PCA bolus. The shorter latency of
response to a single PCA bolus may be related to the “primed” or “loaded” state of spinal cord tissues during
infusion and an optimal interval between the load and the initiation of PCEA opioid. Alternatively, patients may be
satisfied by the placebo effect associated with all self-administration techniques.
The size of the intermittent PCEA dose should be limited in order to avoid excessive accumulations of morphine.
Small boluses with short lockouts are safe and do not lead to accumulation of excessive drug before the initial dose
becomes effective.
Continuous Infusion
A continuous infusion provides the major portion of epidurally administered morphine. Tolerance to morphine does
not develop when continuous infusions are added to PCEA in the typical postoperative patient. Several authors
believe that continuous infusions, by avoiding peaks and valleys in cerebrospinal fluid levels, provide more uniform
levels of analgesia while reducing the incidence of side effects. [35] [36]
Serum levels at 24 hours are low, with 90% of 20 samples studied being less than 6.5 ng/mL. This finding
[39]
indicates that the systemic absorption of morphine provides a minimal contribution to the overall levels of analgesia.
Breakthrough pain is treated with small morphine boluses. Changing the rate of infusion alone has little effect in the
short term, because it requires five half-lives to reach the new equilibrium.
ALTERNATIVE ANALGESIC AGENTS FOR PCEA

Lipophilic Opioids
Fentanyl, sufentanil, and hydromorphone may be used with a PCEA infusion technique; however, the amount of
drug necessary to provide effective analgesia appears to be much greater than equivalent doses of morphine. The
administration of lipophilic opioids by continuous infusion, PCEA, or both has been questioned by several authors. [40]
E stok and coworkers showed that fentanyl administered by IV PCA or PCEA provided equivalent analgesia.
[41] [41]
Epidurally administered lipophilic opioids are most appropriately administered via thoracic epidural catheters. They
may be of special use in the following circumstances:
• To speed the onset of epidural opioid analgesia.

• In large volumes of dilute solution or combined with local anesthetics. (Cohen and associates[42] [43]
compared combinations of fentanyl bupivacaine and buprenorphine-bupivacaine for PCEA. The average
hourly doses of opioid were minimized, presumably because of the effective analgesia provided by
concurrently administered bupivacaine; therefore, 24-hour serum concentrations were low.)
• For breakthrough pain, especially in the first few hours postoperatively.
Local Anesthetics
The use of PCEA with local anesthetics during labor has been reported to be safe and effective. The technique was
first described in 1988 by Gambling and colleagues, who compared bupivacaine (0.125%) PCEA with CI alone.
[44]
They found that PCEA was better for controlling pain than continuous epidural infusion of bupivacaine. Patients in
278
the PCEA group required significantly smaller doses of bupivacaine to provide similar analgesia. The technique was
believed to be safe and reliable and was not associated with excess sensory blockade.
Lysak and associates evaluated bupivacaine, 0.125%, in combination with three different concentrations of
[45]
fentanyl to find the optimal regimen for PCEA. The control group received continuous infusion of plain
bupivacaine. Hemodynamics, sensory level, and duration of labor were monitored. The results suggested that PCEA
was safer than plain bupivacaine, and the researchers concluded that the optimal concentration of fentanyl for PCEA
hourly dosage was 1 ng/mL.
Bupivacaine-fentanyl administered by PCEA with infusion also demonstrated greater safety and efficacy (i.e., fewer
“top-ups” and lower infusion rates) than when administered by CI. Naulty and coworkers used bupivacaine-
[48]
sufentanil combinations for relief of labor pain. They demonstrated no particular benefits of PCEA with this
combination of drugs; in fact, total drug requirements were higher in the PCEA group. Whether this finding was
attributable to the drugs employed or to the PCEA regimen (small volume of self-administered dose) remains to be
seen.
Dilute local anesthetic solutions (bupivacaine, 0.03%–0.06%) can be used in selected postoperative patients. So that
patients may avoid avoid interference with ambulation, the use of local anesthetics should be limited to the first 12
to 24 hours postoperatively. Local anesthetics are probably best employed with segmentally placed catheters in
patients recovering from major upper abdominal or thoracic surgery. A small but definite incidence of hypotension
and lower extremity weakness is associated with the PCEA technique.
CONCLUSION
Compared with IV PCA, PCEA is a relatively new technique that may offer adequate analgesia with a lower opioid
dosage. PCEA provides greater control and higher patient satisfaction than CI. There is also a potential decrease in
dose-dependent side effects with use of PCEA. The clinical advantages of PCEA may outweigh the greater cost and
invasiveness of the technique. More data need to be analyzed, however, so that the best choice among IV PCA, CI,
and PCEA may be made for analgesia in patients with acute and chronic pain.
Continuous Peripheral Regional Analgesia
A prolonged peripheral nerve block may be placed as a continuous technique to provide perioperative pain relief for
patients with trauma and postoperative pain. This continuous technique is very similar to a single-injection
[49]
technique. After the needle is placed in the correct position, a catheter may be threaded into the perivascular
[50]
compartment and secured for up to 7 to 10 days. In addition to perioperative pain relief, these catheters may be
placed for a sympathetic block in patients with vascular compromise, intractable pain from complex regional pain
[51]
syndrome (CRPS) I and II, or phantom limb pain. [52]
CONTINUOUS BRACHIAL PLEXUS INFUSION [53]
Indications for continuous brachial plexus infusion include perioperative pain for trauma and postoperative pain
relief, vascular compromise, intractable pain from CRPS I and II, and phantom limb pain.
Anatomy
The brachial plexus is an ideal location for a continuous regional technique because of its well-defined perivascular
compartment and the close approximation of the large number of nerves supplying the upper extremity. All
techniques of brachial plexus blockade have been described as continuous techniques, but some are easier to achieve
than others. The infraclavicular approach is preferred owing to the advantage of maintaining the catheter in the
[53]
same position for long periods, sometimes as long as 3 weeks. [53]
Technique
The patient lies supine, with the head turned away from the arm to be blocked ( Fig. 16–2 ). The arm is abducted to
90 degrees and allowed to rest comfortably. The physician stands on the opposite side of the arm to be blocked. The
whole length of the clavicle is identified after palpation or fluoroscopic imaging. The midpoint of the clavicle is
marked. The brachial artery is palpated in the arm and marked. The C6 tubercle on the same side is palpated in the
neck and marked. A line is drawn from the C6 tubercle to the brachial artery in the arm. This line goes through the
midpoint of the clavicle and is the surface marking of the brachial plexus. The ground electrode of a peripheral
279
nerve stimulator is attached to the opposite shoulder. A skin wheal is raised 2 cm below the inferior border of the
clavicle at its midpoint. An 18-gauge (G) needle is used to pierce the skin. A 19-G B-D Longwell needle/catheter (or
a 16-G R-K epidural needle with appropriate epidural catheter to follow) is introduced through the skin wheal. The
needle point is directed laterally toward the brachial artery (see Fig. 16–2 ). The exploring needle is then attached to
either the stem or the hub of the needle with a sterile alligator clip. The current of the peripheral nerve stimulator is
set to deliver 3 mA, and the needle is advanced at an angle of 45 degrees to the skin. As the needle approaches the
fibers of the brachial plexus, movements of the muscles supplied by those fibers occur. The forearm and hand are
carefully observed for these movements. Flexion or extension of the elbow, wrist, or digits confirms that the needle
point is close to nerve fibers of the brachial plexus. The current of the impulse is decreased to 0.5 mA. The needle is
then advanced. The muscle movement previously seen increases as the needle tip moves closer to the brachial
plexus. The needle is advanced until the muscle movements start to decrease. When this happens, the needle tip has
passed the nerve. The needle is withdrawn slowly until maximal muscle movements are observed. The needle is
held in that position. Water-soluble contrast medium may be injected (approximately 3 mL) to observe the spread in
the nerve sheath; lidocaine, 2 mL of 2%, is then injected through the needle, with the 1 impulse per second button on
the peripheral nerve stimulator activated (Fig. 16–3 (Figure Not Available) ). If the needle is placed correctly on the
nerve fibers, there is a loss of previously seen muscle movements within 30 seconds. If not, the needle should be
withdrawn slightly and the process repeated. The catheter is then threaded through the needle and approximately
[54]
Figure 16-2 Raj’s technique of the infraclavicular approach. The drawing illustrates the surface markings of the brachial plexus. The needle is
directed laterally at 45 degrees to the skin at the point of entry. The point of entry is 1 inch inferior to the midpoint of the clavicle. The artery is
identified in the upper arm, and the needle is directed toward it.(From Raj PP, Pai U, Rawal N: Techniques of regional anesthesia in adults. In
Raj PP [ed]: Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991.)
Figure 16-3 (Figure Not Available) A, Radiograph shows needle in final position after infraclavicular block. Note that the needle tip approaches
the scapula as it goes deeper. B, The spread of the contrast material (20 mL) when the needle is on the brachial plexus in the infraclavicular
region. (From Raj PP, Montgomery SJ, Nettles D, et al: Infraclavicular brachial plexus block: A new approach. Anesth Analg 52:897-904,
1973.)
3 to 5 cm beyond the needle tip. Further confirmation of placement of the catheter can be made with contrast dye.
Ropivacaine 0.2%, 20 to 30 mL, is then injected through a bacteriostatic filter in divided doses for immediate pain
relief (Fig. 16–4 (Figure Not Available) ). The needle
Figure 16-4 (Figure Not Available) Details of 20 mL of contrast solution injected into the infraclavicular region. Note the cephalad spread under
the midclavicular region and the filling of the axillary sheath in the upper arm (caudad spread). The spilling of the solution in the midportion
suggests a sievelike brachial plexus sheath in the infraclavicular region. The spilling of contrast solution outside the sheath at this level usually
blocks the intercostobrachial nerve, an obvious advantage of this block.(From Raj PP, Montgomery SJ, Nettles D, et al: Infraclavicular brachial
plexus block: A new approach. Anesth Analg 52:897-904, 1973.)
280
is then withdrawn under direct fluoroscopic guidance. The catheter is sutured into place. The site is covered with
antibiotic ointment and a bio-occlusive dressing. The brachial plexus catheter is then connected to a constant
infusion of ropivacaine, 0.1%, with fentanyl, 5 µg/mL, at 6 to 10 mL/hour. Occasional bolus doses may be required
and may be administered by the patient (patient-controlled with 3 mL of the dosage, 15-minute lockout, and a
maximum of 6 mL/hour). The CI is reliably efficacious for up to 48 hours. After that period, the efficacy drops
precipitously, for A-delta fiber blocking. Sympathetic blocking can still be maintained for up to 2 to 3 weeks with
ropivacaine, 0.1% to 0.2%, in a reliably anchored catheter. [53]
Complications
The complications of a continuous brachial plexus infusion are similar to those of a brachial plexus block. They
include bleeding, infection, intravascular injection, intrathecal injection, pneumothorax, and phrenic nerve paralysis.
The severity and length of phrenic nerve paralysis are related to site of catheter placement (e.g., interscalene,
supraclavicular) and choice of local anesthetic. The plasma concentration and pharmacokinetics of the
[55] [56] [57] [58] [59] [60] [61]
constant infusion in steady state are similar to those observed in epidural infusion. Once steady state is reached, the
drugs infused do not accumulate if they are infused at the same rate. The metabolites also remain at an insignificant
level without causing any deleterious effect. [54]
CONTINUOUS SCIATIC NERVE INFUSION

Indications
Patients with CRPS I and II, vascular insufficiency, and unilateral leg edema from many causes are frequently
managed with lumbar epidural catheters. There are, however, inherent risks with long-term placement of an epidural
catheter. The sciatic catheter can be an alternative in such patients. It can eliminate the risk of epidural abscesses,
hematoma formation, or catheter erosion of the dura. The unilateral affected limb can be specifically treated without
numbing or weakening the opposite limb. Thus, ambulation can be maintained. Contraindications include (1)
anticoagulant therapy, (2) septicemia, (3) local infection, (4) recent injury at the site of injection to the nerve, and (5)
inability of the patient to lie in the prone position.
Anatomy
The sciatic nerve is formed from the nerve roots of L4 to L5 and S1 to S3. After formation at the sciatic notch, the
nerve passes through the gluteal region between the greater trochanter and the ischial tuberosity. In the buttocks, it
runs posterior to the gemelli and the obturator internus. It lies anterior to the piriformis muscle as it descends to the
thigh, as first described by Labat in 1923. My approach is based on the identification of the piriformis muscle and
[62]
the placement of the catheter on the sciatic nerve in the gluteal region.
Technique
The patient is placed in the prone position. The gluteal regional ipsilateral to the affected side is sterilized and
draped. The following landmarks are located by fluoroscopy: (1) posterior superior iliac spine, (2) greater
trochanter, and (3) ischial tuberosity ( Fig. 16–5 ). A line is drawn connecting the posterior iliac spine and the
greater trochanter. The midpoint is identified and a perpendicular line is drawn in a caudal direction. A second line
is drawn from the greater trochanter to the ischial tuberosity. This line is divided into thirds. A line is drawn
vertically from the medial third mark upward to intersect the other line. The point of entry is where the two lines
meet ( Fig. 16–6 ). A skin wheal is raised at the site with a 25-G needle. A larger needle (16-G or 18-G) can pierce
the skin. A blunt, 16-G, 7-inch needle is introduced perpendicularly, approximately 1 cm through the skin to reach
the piriformis muscle ( Fig. 16–7 ). A 22-G needle is inserted subcutaneously and attached to a positive lead from
the Medtronic test stimulator (or equivalent peripheral nerve stimulator). The Medtronic test stimulator should be set
to deliver 6 to 8 V at 1 impulse per second. (If a peripheral nerve
281
Figure 16-5 Drawing depicting the landmarks to be identified by fluoroscopy. A, Posterior superior iliac spine. B, Greater trochanter. C, Ischial
tuberosity. (From Racz G, Raj P, Lou L, et al: Posterior sacral approach to the sciatic nerve for continuous lidocaine infusion: A new technique.
Presented at 1997 ASA Annual Meeting, San Diego, CA.)
Figure 16-6 Surface landmarks and entry point of needle. A, Posterior superior iliac spine. B, Greater trochanter. C, Ischial tuberosity. D,
Insertion site. (From Racz G, Raj P, Lou L, et al: Posterior sacral approach to the sciatic nerve for continuous lidocaine infusion: A new
technique. Presented at 1997 ASA Annual Meeting, San Diego, CA.)
stimulator is used, the current should be adjusted from 3 to 0.5 mA at 1 impulse per second.) The needle is slowly
advanced anteriorly until the piriformis muscle, which is identified by contrast solution, is twitching ( Fig. 16–8 ).
The needle is further advanced until the piriformis muscle stimulation stops and foot twitching (dorsiflexion) is
observed in the affected limb. A stimulating catheter is then inserted through the needle. The
282
Figure 16-7 Surface view of the catheter after placement.(From Racz G, Raj P, Lou L, et al: Posterior sacral approach to the sciatic nerve for
continuous lidocaine infusion: A new technique. Presented at 1997 ASA Annual Meeting, San Diego, CA.)
Figure 16-8 Fluoroscopic image of catheter with the piriformis muscle superficially and with contrast solution over the sciatic nerve.(From Racz
G, Raj P, Lou L, et al: Posterior sacral approach to the sciatic nerve for continuous lidocaine infusion: A new technique. Presented at 1997 ASA
Annual Meeting, San Diego, CA.)
negative lead of the stimulator is attached to the distal connecting wire of the catheter. The catheter is passed to the
level of the lesser trochanter for foot movement. The needle is then removed, and the catheter is attached to the hub
connector. Confirmation of placement can be made with 3 mL of contrast dye via the catheter ( Fig. 16–9 ). An
additional 3 mL of local anesthetic (ropivacaine 0.2%) may be injected, and stimulation of the sciatic nerve should
cease. Ropivacaine 2%, 15 to 30 mL, is injected through an attached bacteriostatic filter in divided doses for
[63]
283
immediate pain relief and nerve blockade. The constant infusion of ropivacaine 0.1% with fentanyl 5 µg/mL may
range from 4 to 10 mL/hour. Occasional bolus doses may be required and may be delivered by the patient through
the pump with a bolus of 5 mL and a 30-minute lockout. The catheter may be connected to a drug infusion balloon
[64]
(DIB) for outpatient care through home health services. This DIB delivers 4 mL/hour of the drug to the patient for
24 hours. (The volume of the DIB reservoir is 100 mL.)
Complications
Potential complications with the CI sciatic catheter include bleeding, infection, hematoma, intravascular injection,
and residual dyschesia.
Figure 16-9 Fluoroscopic image of the catheter with contrast solution following the sciatic nerve sheath.(From Racz G, Raj P, Lou L, et al:
Posterior sacral approach to the sciatic nerve for continuous lidocaine infusion: A new technique. Presented at 1997 ASA Annual Meeting, San
Diego, CA.)
LUMBOSACRAL PLEXUS CATHETERIZATION
Placement of a lumbosacral catheter with an epidural needle has been reported by Vaghadia and colleagues. [65]
Successful blockade of the lumbar and sacral plexuses was achieved for unilateral lower extremity surgery. The
catheter is placed between the quadratus lumborum and psoas muscles between the transverse processes of L4 and
L5. The technique is not difficult and seems highly successful. The main disadvantage is the volume of local
anesthetic needed, which is between 40 and 70 mL. [66]
FEMORAL NERVE CATHETERIZATION
Continuous techniques for the femoral nerve have been used for various surgeries. Edwards and Wright, in 1992, [67]
reported significantly lower postoperative pain scores and reduced opioid requirements in patients who underwent
total knee replacement with CI (0.125% bupivacaine at 6 mL/hour) within the femoral sheath compared with
patients who received analgesia from conventional intramuscular injections of opioids.
The drugs administered for lower extremity infusions follow the same principles as those used for brachial plexus
infusions. The concentration of drug infusion depends on the need to block A-alpha, A-delta, or C fibers, and the
rate of infusion is usually 10 to 15 mL/hour. Complications include peripheral neuropathy, motor weakness,
dysesthesias, and decubitus ulcers secondary to sensory loss. [66]
284
Technically, lower extremity infusion is difficult and unreliable. At best, this technique is an alternative to lumbar
epidural infusion (when it cannot be performed because of infection or coagulation abnormality). Postoperative knee
pain and CRPS I and II may be the best indications for these procedures. [66]
CONTINUOUS SYMPATHETIC INFUSION
Some clinicians routinely perform continuous sympathetic infusions, such as continuous stellate ganglion and
[68]
continuous lumbar sympathetic infusions. The stellate ganglion infusion is often unreliable because of catheter
dislodgment. Continuous splanchnic and lumber sympathetic infusions are successful even in outpatients with no
significant problems. These techniques are most useful for treatment of patients with visceral pain secondary to
[66]
cancer, CRPS I, and sympathetically maintained pain. [69]
DRUGS
The drugs administered for sympathetic infusions follow the same principles as those for brachial plexus infusion.
The drug of choice has been bupivacaine (0.125%–0.25%), usually without a narcotic. With the introduction of [66]
less cardiotoxic local anesthetics, ropivacaine (0.1%–0.2%) and chirocaine (0.125%), are becoming the drugs of
choice. Morphine, fentanyl, and sufentanil have been mixed with the local anesthetic to prolong the analgesia. A
solution of 6 mL (stellate ganglion) to 20 mL (splanchnic nerve or celiac plexus [bilateral]) is continuously
infused. [66]
EFFICACY
The stellate ganglion infusion is unreliable because of catheter dislodgment. Lumbar sympathetic infusion is quite
reliable, although the lumbar plexus is eventually blocked by the diffusion of the local anesthetic solution into the
psoas muscle. Hypotension and nausea are rare complications of bilateral celiac plexus infusion. Not enough data
are currently available to state that continuous sympathetic infusion is a safe, reliable, and efficacious technique. [66]
Conclusion
Continuous regional analgesia, whether central or peripheral, is a safe and efficacious technique. The infusions may
use local anesthetics, opioids, or a combination of both. These infusions are performed when prolonged analgesia is
required for moderate to severe acute, chronic, or cancer pain. [53]
BIBLIOGRAPHY
Lubenow TR: Epidural analgesia: Considerations and delivery methods. In Sinatra RS, Hord AH, Ginsberg B,
Preble LM (eds): Acute Pain: Mechanisms and Management. St. Louis, Mosby-Year Book, 1992, pp 233–242.
Walmsley PNH: Patient controlled epidural analgesia, In Sinatra RS, Hord AH, Ginsberg B, Preble LM (eds): Acute
Pain: Mechanisms and Management. St. Louis, Mosby-Year Book, 1992, pp 312–320.
REFERENCES
1. Green R, Dawkins CJM: Postoperative analgesia: The use of continuous drip epidural block. Anaesthesia 21:372, 1966.
2. Sponerel WE, Thomas A, Gerula GR: Continuous drip analgesia: Experience with mechanical devices. Can Anaesth Soc J 17:37, 1970.
3. Rosenblatt RM, Raj PP: Experience with volumetric infusion pumps for continuous epidural analgesia. Reg Anaesth 4:3–5, 1979.
4. Cleland JG: Continuous peridural causal analgesia in surgery and early ambulation. Northwest Med 48:266, 1949.
5. Akerman B, Arwenstrom E, Post C: Local anesthetics potentiate spinal morphine anti-nociception. Anesth Analg 59:473–480, 1980.
6. Bromage PR, Camporseli E, Chestnut D: Epidural narcotics for postoperative analgesia. Anesth Analg 59:473–480, 1980.
7. Cousins MJ, Mather LE: Intrathecal and epidural administration of opioids. Anesthesiology 61:276–310, 1984.
8. Rutler DV, Skewes DG, Morgan M: Extradural opioids for postoperative analgesia. Br J Anaesth 53:915–920, 1981.
9. Vander Auwera D, Verborgh C, Camu F: Analgesic and cardiorespiratory effects of epidural sufentanil and morphine in humans. Anesth Analg
66:999–1003, 1987.
285
10. Scott ND, Mogensen T, Bigler D, et al: Continuous thoracic extradural 0.05% bupivacaine with or without morphine: Effect on quality of
blockade, lung function and the surgical stress response. Br J Anaesth 62:253–257, 1989.
11. Raj PP, Denson D, Finnason R: Prolonged epidural analgesia: Intermittent or continuous? In Meyer J, Nolten H (eds): Die Kontinuerliche
Peridural Anesthesia. 7th International Symposium uber die Regional Anaesthesia AM, Jan. 7, 1982, Minden, Germany. Stuttgart, George
Thieme, 1983, pp 26–38.
12. Lubenow TR, Durrani Z, Ivankovish AD: Evaluation of continuous epidural fentanyl/butorphanol infusion for postoperative pain.
13. Rosseel PMJ, Van Der Broeck J, Boer EC, Prakash O: Epidural sufentanil for intraoperative and postoperative analgesia in thoracic surgery: A
comparative study with intravenous sufentanil. Acta Anaesthesiol Scand 32:193–198, 1988.
14. Scott DB, Lee A, Fagan D, et al: Acute toxicity of ropivacaine compared with that of bupivacaine. Anesth Analg 69:563–569, 1989.
15. Markham A, Faulds D: Ropivacaine: A review of its pharmacology and therapeutic use in regional anaesthesia. Drugs 52(3):429–449, 1996.
16. Akerman B, Hellberg IB, Trossvic C: Primary evaluation of the local anaesthetic properties of the amino amide agent ropivacaine. Acta
17. Feldman HS, Covino BG: Comparative motor blocking effects of bupicavaine and ropivacaine, a new amino amide local anesthetic, in the rat
and dog. Anesth Analg 67:1047–1052, 1988.
18. Reuz S, Haggmark S, Gohansson G, Nath S: Cardiotoxicity of ropivacaine—A new amide local anesthetic agent. Acta Anaesthesiol Scand
33:93–98, 1989.
19. Finucane BT: Ropivacaine—A worthy replacement for bupivacaine? Can J Anaesth 37(7):722–725, 1990.
20. Authur
GR, Feldman HS, Covino BG: Comparative pharmacokinetics of bupivacaine, a new amide local anesthetic. Anesth Analg 67:1053–
1058, 1988.
21. Tucker GT, Cooper S, Littlewood D, Buckley SP: Observed and predicted accumulation of local anesthetics during continuous extradural
analgesia. Br J Anaesth 49:237, 1977.
22. Schweitzer
SA, Morgan DJ: Plasma bupivacaine concentrations during postoperative continuous epidural analgesia. Anaesth Intensive Care
15:425–430, 1987
23. Gregory MA, Brock-Utne JC, Bux S, Downing JW: Morphine concentration in brain and spinal cord after subarachnoid morphine injection in
baboons. Anesth Analg 64:929–932, 1985.
24. Rawal N, Sjostrand U, Dahlstrom B: Postoperative pain relief by epidural morphine. Anesth Analg 60:726–731, 1981.
25. Chestnut DH, Owen CL, Bates JN, et al: Continuous infusion epidural analgesia during labor: A randomized double-blind comparison of
0.0625% bupivacaine/0.0002% fentanyl versus 0.125% bupivacaine. Anesthesiology 68:754–759, 1988.
26. Cullen M, Staren E, Ganzouri A, et al: Continuous thoracic epidural analgesia after major abdominal operations: A randomized prospective
double-blind study. Surgery 98:718–728, 1985.
27. Fisher R, Lubenow TR, Liceaga A, et al: Comparison of continuous epidural infusion of fentanyl-bupivacaine and morphine-bupivacaine in
the management of postoperative pain. Anesth Analg 67:559–563, 1988.
28. Logas WG, El-Baz NM, El-Ganzouri A, et al: Continuous thoracic epidural analgesia for postoperative pain relief following thoracotomy: A
randomized prospective study. Anesthesiology 67:787–791, 1987.
29. Hjorts NC, Lunc C, Mogensen T, et al: Epidural morphine improves pain relief and maintains sensory analgesia during continuous epidural
bupivacine after abdominal surgery. Anesth Analg 65:1033–1036, 1986.
30. Magora F, Olshwand DL, Eimei D, et al: Observation on extradural morphine analgesia in various pain conditions. Br J Anaesth 52:247–252,
1980.
31. Rutberg
H, Hakannson E, Anderberg B, et al: Effects of extradural administration of morphine or bupivacaine on the endocrine response to
upper abdominal surgery. Br J Anaesth 56:233–238, 1984.
32. Sjostrom S, Hartvig D, Tamsen A: Patient controlled analgesia with extradural morphine or pethidine. Br J Anaesth 60:358, 1988.
33. Chrubasik J, Wiemers K: Continuous-plus-on demand epidural infusion of morphine for postoperative pain relief by means of a small,
externally worn infusion device. Anesthesiology 62:263, 1985.
34. Chrubasik J, Wust H, Schulte-Monting J, et al: Relative analgesic potency of epidural fentanyl, alfentanil and morphine in treatment of
postoperative pain. Anesthesiology 68:929, 1988.
286
35. DowningJE, Stedman PM, Busch EH: Continuous low volume infusion of epidural morphine for postoperative pain. Reg Anesth
13(Suppl):84, 1988.
36. Planner RS, Cowie RW, Babarczy AS, et al: Continuous epidural morphine analgesia after radical operations upon the pelvis. Surg Gynecol
Obstet 166:229, 1988.
37. Rauck R, Knarr D, Denson D, Raj P: Comparison of the efficacy of epidural morphine given by intermittent injection or continuous infusion
for the management of postoperative pain. Anesthesiology 65:A201, 1986.
38. Marlowe S, Engstrom R, White PF: Epidural patient-controlled analgesia (PCA): An alternative to continuous epidural infusion. Pain 37:97,
1989.
39. Walmsley PNH, McDonnell FJ, Colclough GW, et al: A comparison of epidural and intravenous PCA after gynecological surgery.
Anessthesiology 73:A684, 1989.
40. Loper KA, Ready LB, Sandler AN: Epidural and IV fentanyl infusions are clinically equivalent following knee surgery. Anesthesiology
71:A1149, 1989.
41. Estok PM, Glass PSA, Goldberg JS, et al: Use of PCA to compare IV to epidural administration of fentanyl in the postoperative patient.
42. Cohen
S, Amar D, Pantuck CB: Continuous epidural-PCA post-cesarean section: Buprenorphine-bupivacaine 0.03% vs. fentanyl-bupivacaine
0.03%. Anesthesiology 73:A230, 1987.
43. Cohen S, Amar D, Pantuck CB: Continuous epidural-PCA for cesarean section: Buprenorphine-bupivacaine 0.015 with epinephrine vs
fentanyl-bupivacaine 0.015 with and without epinephrine. Anesthesiology 73:A918, 1990.
44. Gambling DR, Yu P, Cole C, et al: A comparative study of patient controlled epidural analgesia analgesia (PCEA) and continuous infusion
epidural analgesia (CIEA) during labour. Can J Anaesth 35:249–254, 1988.
45. Lysak SZ, Eisenach JC, Dobson CE: Patient-controlled epidural analgesia during labor: A comparison of three solutions with a continuous
infusion control. Anesthesiology 72:44–49, 1990.
46. Gambling DR, McMorland GH, Yu P, et al: Comparison of patient controlled epidural analgesia and conventional intermittent “top-up”
injections during labor. Anesth Analg 70:256–261, 1990.
47. Viscomi C, Eisenach JC: Patient-controlled epidural analgesia during labor. Obstet Gynecol 77:A685, 1989.
48. Naulty
JS, Barnes D, Becker R, et al: Epidural PCA vs. continuous infusion of sufentanil-bupivacaine for analgesia during labor and delivery.
49. Fisher A, Meller Y: Continuous postoperative regional analgesia by nerve sheath block for amputation sugery—A pilot study. Anesth Analg
72:300–303, 1991.
50. Raj P: Continuous brachial plexus analgesia In: Abstract Book, 21st Annual Meeting, American Society of Regional Anesthesia, San Diego,
1996, pp 501–502.
51. Matsuda M, Kato N, Hosoi M: Continuous brachial plexus block for replantation in the upper extremity. Hand 14:129–34, 1982.
52. Hartrick C: Pain due to trauma including sports injuries. In Raj PP (ed): Practical Management of Pain, 2nd ed. St. Louis, Mosby-Year Book,
1992, pp 409–433.
53. Raj PP: Continuous regional analgesia. In Raj PP (ed): Practical Management of Pain, 3rd ed. Philadelphia, WB Saunders, 2000.
54. Raj PP, Moontgomery SJ, Nettles D, et al: Infraclavicular brachial plexus block—A new approach. Anesth Analg 52(6):897–904, 1973.
55. Pere P, Pitkanen M, Rosenberg PH, et al: Effect of continuous interscalene brachial plexus block on diaphragm motion and on ventilatory
function. Acta Anaesthesiol Scand 36:53–57, 1992.
56. Urmey WF, Talts KH, Sharrock NE: One hundred percent incidence of hemidiaphragmatic paresis associated with interscalene brachial plexus
anesthesia as diagnosed by ultrasonography. Anesth Analg 72:498–503, 1991.
57. Urmey WF, McDonald M: Hemidiaphragmatic paresis during interscalene brachial plexus block: Effects on pulmonary function and chest wall
mechanics. Anesth Analg 74:352–357, 1992.
58. Knoblanche GE: The incidence and etiology of of phrenic nerve blockade associated with supraclavicular brachial plexus block. Anaesth
Intensive Care 7:346–349, 1979.
59. Dhuner KG, Moberg E, Onne L: Paresis of the phrenic nerve during brachial plexus block analgesia and its importance. Acta Chir Scand
109:53–57, 1955.
287
60. Farrar MD, Scheybani M, Nolte H: Upper extremity block: Effectiveness and complications. Reg Anesth 6:133–134, 1981.
61. Kulenkampff D: Die Anasthesia des plexus brachialis. Zentralbl Chir 38:1337–1340, 1911.
62. Adriani J: Labat’s Regional Anesthesia: Techniques and Clinical Applications. Philadelphia, WB Saunders, 1967.
63. Racz G, Raj P, Lou L, et al: Posterior sacral approach to the sciatic nerve for continuous lidocaine infusion: A new technique. Presented at
1997 ASA Annual Meeting, San Diego, CA (and the 1997 PGA, New York, NY and 1998 IARS, Orlando, FL.)
64. Racz G, Raj P, Lou L, et al: Posterior sacral approach to the sciatic nerve for continuous ropivacaine infusion: A new technique. Presented at
1998 PGA, New York, NY.
65. VaghadiaH, Kapnoudhis P, Jenkins LC, Taylor D: Continuous lumbosacral block using a Tuohy needle and catheter technique. Can J Anaesth
39:75–78, 1992.
66. Raj P: Nerve blocks: Continuous regional analgesia. In Raj PP (ed): Practical Management of Pain, 3rd ed. St. Louis, Mosby-Year Book, 2000,
p 719.
67. Edwards ND, Wright EM: Continuous low-dose 3-in-1 nerve blockade for postoperative pain relief after total knee replacement. Anesth Analg
75:265, 1992.
68. Rauck R: Sympathetic nerve blocks: Head and neck and trunk. In Raj PP (ed): Practical Management of Pain, 3rd ed. St. Louis, Mosby-Year
Book, 2000, pp 677–678.
69. Racz GB, Noe C, Colvin J, et al: Sympathetic nerve block: Pelvic. In Raj PP, (ed): Practical Management of Pain, 2nd ed. St. Louis, Mosby-
Year Book, 1992, pp 813–817.
288
Section IV - Chapter 17 - Aids to Localization of Peripheral Nerves
Chapter 17 - Aids to Localization of Peripheral Nerves
P. Prithvi Raj
Jose De Andrés
Paolo Grossi
Ronald Banister
Xavier Sala-Blanch
An increasing number of patients in daily clinical practice who are undergoing surgery or who have acute or chronic
pain receive nerve blocks for anesthesia, analgesia, or both. The continued popularity of regional anesthesia depends
on a high success rate with these blocks. The peripheral nerve stimulator (PNS) can achieve this success rate. In
addition to the PNS, other aids to the success of nerve blocks are appearing on the horizon: for example,
ultrasonography, radiologic imaging, and “anesthetic line.” This review describes these techniques in some detail.
PERIPHERAL NERVE STIMULATION FOR NERVE BLOCKS

P. Prithvi Raj
Ronald Banister
HISTORY
In 1912, von Perthes became the first to describe the technique of peripheral nerve stimulation. He used an
[1]
induction apparatus as the source of faradic current. The current was transmitted through a pure nickel needle that
was coated with lacquer down to the tip to provide insulation. The following is the original excerpt of von Perthes’
paper translated into English.
About Nerve-Block/Conduction Anesthesia with the Help of Electrical Stimulation

Our procedure is based on the following facts: If one pushes forward a cannula coated with an isolating varnish until
the furthest/outermost point onto a nerve which exists out of motoric and sensitive fibers, and when one sends a
faradic electricity through the needle whereby the electricity is so low that it can only be realized as a very sensitive
stimulus, then, when one’s tongue gets in contact with the needle-shaped electrode, a muscle spasm happens. Only
there, however, where the nerve is directly touched by the cannula. If the point of the needle is just 1 mm away from
the nerve, then the electrical stimulus with the indicated strength of the electric current is ineffective. The spasms
that occur when the nerve gets touched do not affect the whole area, which is provided by the nerve with motoric
fibers. Rather, one just sees spasms in single muscles or sees the spasms in some fascicles of fibers when a fine
cannula is used. This is proving that only these nerve fibers that are directly touched by the point of the needle get
stimulated. Those facts were determined at the nerve ischiadicus in the drugged dog and at the open laying nerve
peroneus in a human being. Several experiences with patients and a test with my own nerve ulnaris revealed that the
electricity of the indicated strength of the electric current is, on the one side, strong enough to cause spasms and
abnormal feeling; on the other side, one does not see it as pain.
On the basis of these facts, it is possible to inject the anesthetizing solution in the same moment when the spasm of
muscle proves that the point of cannula touches the nerve stem.
The cannula, which is connected with the cable, is already put onto the Novocaine solution filled jab during the
injection so that one can inject the anesthesia as soon as the muscle spasms occur. During the injection, the spasms
get weaker or disappear. When this first occurred, there was concern that the cannula point slipped off the nerve
during the injection. The beginning of anesthesia, however, convinced me that this was not the case. The test at the
open laying ischiadicus of the dog revealed that as soon as 2% of the Novocaine solution touched the fibers, the
motoric sensitivity of the fibers toward the electricity at once vanished as soon as the point touched the fibers. It is
recommended not to push forward the solution immediately before the injection through the whole cannula or the
solution may affect the nerve stimulus.
Block of Nervus Ischiadicus

In order to block the nervus ischiadicus , I usually did it in the following way: while the patient was lying on his/her
stomach, the tuber ischii was examined. When the patient bends his/her knee, one can feel the muscles that arise
from the tuber ischii . At the very least, one can feel the nervus ischiadicus with his/her fingers and move it back and
forth. If one starts its injection parallel to the central axis and at the height of the cleft between the buttocks, at the
side of the musculus biceps , he can reach the nervus ischiadicus 5 to 6 cm under the skin surface. While pushing the
needle forward, one can start the electric current; this causes the nervus ischiadicus to start spasms in the calf or to
289
lightly bend the knee. At the same time when the spasms occur, 15 cc of 3% of the Novocaine-suprarenin solution
are injected.
Anesthesia of the Plexus Brachialis with the Aid of Electric Stimulus

Borchers explains that the method of Kuhlenkampff is perfect in its recent form. I, however, have to confess that
following Kuhlenkampff’s method, I did not always receive a satisfying plexus anesthesia. One point of this method
I think is not quite right: that the operating doctor has to depend on what the patient tells him. Following
Kuhlenkampff’s method, one injects above the clavicula ; one knows that it hits the plexus when the patient tells the
doctor that he feels it in his arm. It seems this is something the patient can do, but I realized that most patients are
not able to do this. Some patients are so nervous and get so excited when the hives get attached that they are no
longer able to express what they feel in their muscles. Sometimes, when the electric stimulus proved that the plexus
was reached, the patient still claimed he/she did not feel anything. It seems more appropriate to use the objective
method—the motoric stimulus—instead of depending on the word of the patient. Another advantage of this method
is that one can put very nervous patients into a doze.
I did the plexus anesthesia with the stimulus needle about seven times. I can, however, prove that operations at
fingers, hands, and arms, amputations of the lower arm because of sarcoma , etcetera can be done without any pain
with an injection—following Kuhlenkampff—of 10 cc of 3% Novocaine-suprarenin. When one touches the plexus
with the stimulus cannula, there are spasms of different muscle groups possible when moving the needle a little bit;
therefore, it is still open to figure out which position of the cannula is the best for anesthetizing different areas; for
example, the hand or the elbow joint.
There are also more tries necessary in order to answer the question if the electric current will help to find pure
sensitive nerves. I started those tries already in 1905, but, unfortunately, didn’t pursue them. The method is
important insofar as a very fine cannula stimulates only a few fibers; therefore, this method can help to figure out
the exact topography of the cross-section through the nerve, especially when one thinks of the operation following
Stoffel for the Little-disease. At a discussion following Stoffel’s presentation in 1911, I suggested to him my
method; he explained that he had already used this method in order to identify the fibers. In his publication one can
read that he uses the galvanic current and that he isolates single beams in a radius of 2 cm from their neighbors. At
the Congress of 1911, I also suggested to Mr. Foerster the use of electrical stimulus in order to differentiate the
motoric and sensitive muscles for the Foerster-operation. Mr. Foerster was very positive toward my suggestion. We
finally found a method to treat sciatica with the injection following Jerome Lange after having found the nervus
ischiadicus through the unhurt skin.
Postscript: After having finished this essay I did some more experiences with this method. Unfortunately, beside
good results I also had two partially bad ones and two completely bad ones. This method can, therefore, not yet be
called totally successful. I think, however, I should not keep my experiences to myself, since there is no doubt that,
thinking of the good results, this principle is very much of high value.
In 1955, Pearson located motor nerves by electrical stimulation with an insulated needle, using a heavy
[2]
transformer, a vacuum-tube stimulator, and an electrophrenic stimulator. In 1962, Greenblatt and Denson
[3] [3]
constructed a portable transistorized nerve stimulator as a “needle nerve stimulator-locator.” It delivered a square
wave impulse of 0.001 second’s duration at 1-second intervals. Its output could be varied from 0.3 to 30 volts. One
pole of the output voltage was grounded to a metal plate or needle connected to the patient’s extremity. The negative
pole consisted of a clip that was fastened to the metal Luer lock of a standard syringe. A standard needle of the
desired size, insulated with plastic paint except at the tip, completed the circuit. To localize the motor nerve, the
insulated needle was placed in the vicinity of the nerve to be blocked. The needle then was used as a stimulator
probe with 10 volts until motor stimulation of the nerve was initiated. Voltage was decreased progressively and the
needle advanced, redirected, or both until the lowest voltage that produced motor stimulation was obtained, usually
in the range of 2 to 5 volts. An injection of 2 to 4 mL of local anesthetic agents usually terminated the motor
response. If, after further probing, nerve fibers remained that responded to low voltage, they also were injected with
2 to 4 mL of drug. Paresthesias were not sought.
In 1969, Wright modified the commercially available Block-Aid monitor for use as a PNS. His modification
[4]
consisted of two wires with an Eyenard adapter soldered to each end of one of the wires and one end of the second
wire and an alligator clamp at the other end of the second wire. The needle was inserted proximal to the nerve and
the monitor connected to it. The monitor was switched to the tetanus position and turned on. The voltage selector
was turned about midway. If the voltage produced discomfort, it was reduced and the needle advanced further. As
the nerve was approached, the current produced stronger paresthesias. However, if the needle was positioned wrong,
paresthesia was not elicited or became weaker as the needle was advanced.
In the same year, Koons introduced the Rochester plastic cannula as a needle probe, and Magora and colleagues
[5] [6]
evaluated the technique of electrical stimulation by comparing obturator nerve blocks either with blind anatomic
technique and radiography or electrical stimulation alone. They concluded that electrical nerve stimulation was
preferable to blind or radiographic technique (used singly or in combination) for location of the obturator nerve.
290
All the early reports of the use of the PNS for regional anesthesia noted the use of insulated needles. Some of these
were intravenous cannulae ; others were specially constructed by insulating a conventional needle with Teflon or
[5]
lacquer. In 1973, worrying that such needles might alter the feel of the tissues or that the insulation might peel off,
[3]
Montgomery and colleagues tried using conventional un-insulated needles. They demonstrated the efficacy of the
[7]
technique and did some experimental work to show that most of the current leaves from the tip of such a needle. [7]
They believed that use of coated needles in plastic cannulas could alter the feel of tissues, making accurate anatomic
location more difficult than with standard needles. The coating occasionally tears off or curves back and could lead
to errors in performance of the block.
ELECTROPHYSIOLOGY OF PERIPHERAL NERVE STIMULATORS
Before the middle of the 19th century, nerve fiber conduction was thought to be instantaneous. In 1850, von
Helmholz, in a classic series of experiments with an isolated nerve muscle preparation, demonstrated the temporal
[8]
nature of nerve fiber conduction and paved the way for the elucidation of most of the relevant physiology of
peripheral nerve stimulation. Of particular importance is the relationship between the strength and duration of the
current and the polarity of the stimulus.
There is a threshold stimulus that must be applied to a nerve fiber to cause it to propagate a nerve impulse. Below
this threshold, no impulse is propagated; above this threshold, no increase is produced in the impulse. If a square
pulse of current is used to stimulate the nerve, the total charge applied to the nerve is the product of the current
(strength) and the length of the pulse (duration).
The relationship between the strength and the duration of the charge needed to stimulate a nerve can be expressed by
the familiar strength-duration curve. Figure 17–1 shows such a curve obtained from a preparation of cat sciatic
nerve. The rheobase is the minimum current required to stimulate the nerve with a long pulse width, whereas the
chronaxy is the duration of stimulus required to just stimulate at twice the rheobase. Generally, strength duration
curves follow this formula:
I is the current required, Ir is the rheobase, C is the chronaxy and t is the duration of the stimulus. Thus, the
Figure 17-1 Strength-duration curve. Stimulus strength is plotted against the duration of the pulse. The rheobase is
the smallest current to stimulate the nerve with a long pulse width. The chronaxy is the pulse duration at a stimulus
strength twice that of the rheobase. The curve was obtained from cat sciatic nerve, with the stimulating needle
touching the nerve.(From Pither CE, Raj PP, Ford DJ: The use of peripheral nerve stimulators for regional
anesthesia: A review of experimental characteristics, technique, and clinical applications. Reg Anesth 10:50, 1985.)
291
TABLE 17-1 -- CHRONAXIES OF MAMMALIAN PERIPHERAL NERVES

Cat sural nerve A Alpha fiber 50–100 µsec[10]
A Delta fibers 170 µsec[9]
Cat saphenous nerve C fibers 400 µsec[12]
current needed to stimulate a nerve depends on the pulse width or the duration of the stimulus.
The chronaxie can be used as a measure of the threshold for any particular nerve and is useful when comparing
different nerves or nerve fiber types. Table 17–1 shows values obtained for chronaxies for mammalian peripheral
nerves. Note that smaller unmyelinated fibers have larger chronaxies. This supports the observation that the larger
the fiber, the easier it is to stimulate at any given distance. Thus, it is possible to stimulate the larger A alpha motor
[9]
fibers without stimulating the smaller A delta or C fibers responsible for pain. In practical terms, this means that a
mixed peripheral nerve can be located by a twitch in the muscles it supplies without causing pain (see Table 17–1 ).
MINIMUM VOLTAGE
Raj and colleagues raised several questions during their studies of nerve blocks with electrical stimulation. The
[13]
first question was: What is the minimal voltage of current necessary to stimulate a peripheral mixed nerve for
muscle contraction? During axillary block, the needle tip was placed on the median nerve as confirmed by
paresthesia. The needle was stimulated with varying voltage, and the muscle contraction in the median nerve
distribution was observed. When the compound potential from one of these muscles was recorded, it appeared that
the voltage necessary for optimal potential was 2 volts; there was no action potential below 1.5 volts. Amplitude
increased with increasing voltage up to 2 volts, but increasing voltage from 2 to 3 volts did not increase the
amplitude any further.
MINIMUM CURRENT
Magora and colleagues reported that 0.5 mAmp was required for direct stimulation of the obturator nerve. If 1 to 3 [6]
mAmp were needed, the block usually was ineffective and delayed.
OPTIMAL DISTANCE OF NEEDLE TIP TO THE NERVE
Study 1
Greenblatt and Denson performed experiments to determine the relationship between voltage and the distance of
[3]
the needle tip from the nerve. During above-knee amputation, a probing needle was inserted through soft tissue
TABLE 17-2 -- DISTANCE–VOLTAGE RELATIONSHIP

Touching nerve 1–2 volts
3 mm 3–5 volts
6 mm 10 volts
8 mm 15–20 volts
>8 mm No stimulation at higher voltage
and the minimal voltages needed to produce motor stimu lation at various distances from the exposed nerve were
recorded. Table 17–2 shows the voltage needed to stimulate the motor fibers at varying distances.
Study 2
The second question Raj and coworkers asked was: How can one tell that the needle tip is on the nerve? His group
[13]
recorded the twitch height of contracting muscles while performing infraclavicular blocks with a PNS. In Figure 17–
2 , it appears that as the needle tip nears the nerve, the twitch height increases and, as it moves away, the twitch
292
height decreases. The tip of the needle is presumed to be on the nerve if the twitch height is greatest at the lowest
voltage.
Study 3
To confirm that the needle tip was within 5 mm of the nerve, Raj and coworkers performed the following
[13]
experiment in a group of five anesthetized dogs. Three spinal needles were introduced toward the sciatic nerve at the
gluteal region via electrical stimulation. After it appeared that the muscle contraction was maximal at the lowest
voltage with all of the needles, one needle was left undisturbed. The second needle was pulled back 1 cm
proximally, the third needle was pushed 1 cm deeper, and 0.2 mL of methylene blue stain was injected through each
needle. With the needles in place, the stained areas were explored through careful dissection. It was found that the
needle that was presumed to be on the nerve, did, in fact, stain the nerve sheath. The other needles, 1 cm distal or
proximal to the nerve, stained tissues similar distances away from the nerve.
DISCUSSION
The fundamental principle of clinical importance is the variation of stimulus current (at a fixed stimulus duration)
with distance from the nerve. As the stimulating tip moves away from the nerve, the relationship between stimulus
intensity and distance from the nerve is governed
TABLE 17-3 -- CALCULATED VALUES FOR CURRENT REQUIRED TO STIMULATE NERVE AT VARIOUS DISTANCES FROM THE
NERVE
Distance
On Nerve 0.5 cm 1 cm 2 cm
Stimulus 0.1 2.5 10 40
Current 0.5 12.5 50 200
In milliamperes 1.0 25.0 100 400
by Coulomb’s law, E=K(Q/r2 ). E is the current required, K is a constant, Q is the minimal current, and r is the
distance. The presence of the inverse square means that a very high stimulus is needed once the tip is some distance
away from the nerve. Table 17–3 shows some calculated figures to demonstrate the magnitude of the rise. This can [14]
be of clinical concern, because stimulation of the nerve from more than 2 cm can require currents in the region of 50
mA (depending on the pulse width) and currents smaller than this have been reported to cause ventricular fibrillation
when applied directly to the heart (so-called microshock); however, if appropriate care is taken in any patient who
may have intracardiac electrodes (e.g., pacemaker, Swan-Ganz catheter), currents of these magnitudes are perfectly
safe in most individuals. They do become painful, however, presumably because of direct stimulation of nerve
endings in the tissues being penetrated and are not recommended for this reason.
PROGNOSTIC VALUE OF MUSCLE TWITCH FOR BLOCK SUCCESS
During electrical stimulation to locate nerves, it was observed by Montgomery and others that after good muscle
[13]
contraction was obtained, 2 mL of local anesthetic would diminish or abolish that muscle contraction within 10
seconds in successful blocks ( Fig. 17–3 ). Conversely, if the muscle contraction did not diminish within 10 seconds,
the block usually was patchy and inadequate ( Fig. 17–4 ). It appeared that a 2-mL test dose would indicate the
success of the block if muscle twitch was abolished immediately. The mechanism was intriguing because twitch
abolition was too rapid for the nerve to be blocked by the injected local anesthetic.
293
Figure 17-2 The twitch height recorded during infraclavicular block as the needle tip approaches the nerve.(From Raj PP, Rosenblatt R,
Montgomery SJ: Use of the nerve stimulator for peripheral blocks. Reg Anesth 5:14–21, 1980.)
Figure 17-3 The arrow shows the effect of 2 mL of lidocaine, 2%, to the twitch height. This indicates that the needle tip is close to the
nerve.(From Raj PP, Rosenblatt R, Montgomery SJ: Use of the nerve stimulator for peripheral blocks. Reg Anesth 5:14–21, 1980.)
DETERMINATION OF THE MECHANISM OF ABOLITION OF TWITCH HEIGHT
Raj and associates performed several experiments to clarify this mechanism. In the first experiment, the needle tip
[13]
was placed on the femoral nerve by the PNS. When the twitch height was maximal at the lowest voltage, 2 mL of air
were injected and the twitch was recorded. A decrease in the amplitude of the twitch height occurred within 2
seconds ( Fig. 17–5 ). With continued impulses at 1-second intervals, the twitch height reappeared in 10 seconds.
Similar abolition occurred with 2 mL of saline (see Fig. 17–5 A), and the twitch started to reappear at 15 seconds.
With 1 mL of 2% lidocaine (Xylocaine), not only did the twitch disappear within 1 to 2 seconds, but it did not
reappear for 1½ minutes and then only with a 50-fold increase in the voltage (see Fig. 17–5 B).
These results indicate that the disappearance of twitch with 2 mL of air, saline, or local anesthetic is caused by
physical displacement of the nerve via the pressure executed during injection. This removes the nerve from the
influence of voltage at the tip of the needle. The reappearance of the amplitude within 30 seconds after air or saline
is introduced suggests that this pressure is dissipated very quickly and that the influence of the voltage at the tip of
the needle is regained. Delayed reappearance, with the increased voltage necessary supplied with local anesthetic,
294
Figure 17-4 The arrow shows that 2 mL of lidocaline, 2%, does not have any effect on the twitch height, which indicates that the needle tip is not
close to the nerve.(From Raj PP, Rosenblatt R, Montgomery SJ: Use of the nerve stimulator for peripheral blocks. Reg Anesth 5:14–21; 1980.)
suggests that not only is there physical displacement but that the 2 mL of local anesthetic does, in fact, anesthetize
the neural surface.
ELECTRICAL CHARACTERISTICS OF PERIPHERAL NERVE STIMULATORS

CURRENTLY AVAILABLE IN CLINICAL PRACTICE [15]
To determine which electrical characteristics of the PNS contributed to the localization of a peripheral nerve, the
electrical properties of eight commercially available peripheral nerve stimulators and a Grass S-88 stimulator were
measured. The PNS was then used in the laboratory to locate a peripheral nerve in an anesthetized cat. The
controlled environment in the laboratory allowed each PNS to be used under nearly identical conditions.
Experiment I: Determination of Output Characteristics of Peripheral Nerve Stimulators
To determine the shape and duration of the stimulating pulse, the linearity of the output, and the change in the output
in response to a change in load resistance, the peripheral nerve stimulators were connected to a variable resistance
and an oscilloscope (Tektronix Type 564B) as shown in Figure 17–6 . The shape, duration, and amplitude of the
output were measured on the oscilloscope screen. The linearity of the output was determined by correlating the
current output of the PNS with the dial (or slide) setting of the same PNS. The change in the output of the PNS as
the load resistance was changed from 1000 Ω to 2000 Ω was monitored on the oscilloscope. The current output of
the peripheral nerve stimulator was calculated from the relation, V=I×R. V is the voltage output as measured on the
oscilloscope and R is the known load resistance. The known resistance in this experiment is approximately that
encountered when the PNS is connected to a patient.
Result. The effect of increasing the load resistance on the current and voltage output was determined first. For a
twofold increase in resistance, the current delivered by the PNS dropped an average of 10% (range: 1%–24%). Next,
the linearity of the peripheral nerve stimulators was determined. A completely linear PNS delivered X5 of its
maximal output when the dial was set at x%. As can be seen from Figure 17–7 , some PNSs deviated greatly from
being linear, whereas others were quite linear. Finally, all but one of the PNSs studied delivered a square wave of
duration between 200 µsec and 1000 µsec. The exception delivered a triangular pulse.
295
Figure 17-5 A, Effect of 2 mL of air on amplitude of the compound potential. B, Effect of 2 mL of saline on the median nerve in infraclavicular
block. C, Effect of 1 mL of lidocaine on the same nerve. (From Raj PP, Rosenblatt R, Montgomery SJ: Use of the nerve stimulator for peripheral
blocks. Reg Anesth 5:14–21, 1980.)
Experiment II
To determine how the different electrical properties of the PNS affected the localization of a peripheral nerve, the
peripheral nerve stimulators were used in the laboratory to locate a peripheral nerve in an anesthetized cat. Six cats
of either sex weighing between 2.5 kg and 3.5 kg were used for this study. The cats were obtained from Kaiser
Lake, St. Paris, Ohio, and housed in the Department of Laboratory Animal Medicine until used. On the day of the
experiment, the cat was given 100 mg of ketamine and 0.1 mg of atropine intramuscularly. After the appropriate
areas for surgery were shared, the cat was intubated and placed on a respirator. Anesthesia was maintained with
0.2% to 0.5% methoxyflurane, 67% N2 O, and the balance of O2 . Venous and arterial lines were established in the
external jugular vein and carotid artery, respectively. Blood pressure and heart rate were monitored continuously.
Blood gases were taken every 60 minutes to ensure that normal acid-base status was maintained.
To monitor evoked muscle twitches produced by the PNS, the sciatic nerve–tibialis muscle preparation of the cat
was chosen as a model. The superficial tendons of the tibialis muscle on the dorsal surface of the right hind paw
were exposed. After clamping the quadriceps muscle and the paw to immobilize the leg, the most lateral tendon
Figure 17-6 Schematic diagram of the apparatus used in experiment I. The oscilloscope (left), variable resistance (center), and the peripheral
nerve stimulator (right) are connected in parallel. (From Ford D, Pither C, Raj P: The use of peripheral nerve stimulators for regional
anesthesia. A review of experimental characteristics, technique, and clinical applications. Reg Anesth 9:73–77, 1984.)
was attached to an F-1000 Microdisplacement Muograph, transducer (Norco Biosystems, Inc.). Then the remaining
tendons and the Achilles tendon were severed. Finally, the force transducer was connected to a strip recorder
(Physiography, Model DMP-4B) to record the evoked muscle twitches ( Fig. 17–8 ).
The needle (6.3 cm×22 gauge [G] spinal needle, uninsulated) was mounted in a one-dimensional manipulator and
aligned to approach the sciatic nerve through the hamstring muscle. The needle was advanced through the
296
Figure 17-7 Linearity of the peripheral nerve stimulators. The percentage of output delivered at a given setting was plotted along the Y axis, and the percentage of
dial setting was plotted along the X axis. A linear response is shown by a straight line starting at the origin and going to the (100%) point.(From Ford D, Pither C, Raj
P: Electrical characteristics of peripheral nerve stimulators: Implications for nerve localization. Reg Anesth 9:73–75, 1984.)
Figure 17-8 Schematic diagram of the apparatus used in experiment II. The cathode of the peripheral nerve stimulator was attached to the needle
(arrow) and the anode to the cat through a 1000 Ω resistance. To measure the current delivered by the peripheral nerve stimulator, the voltage
drop across the 1000 Ω resistance was measured on the oscilloscope and related to current by: Current = V/1000. To measure the voltage drop
delivered by the peripheral nerve stimulator, the line labeled “Current” was disconnected and connected as shown by the dashed line labeled
“Voltage.” The tibialis muscle was attached to a force transducer and the muscle twitches recorded on a strip recorder. (From Ford D, Pither C,
Raj P: Electrical characteristics of peripheral nerve stimulators: Implications for nerve localization. Reg Anesth 9: 73–75, 1984.)
skin and each PNS was connected in sequence to the cat and the needle. The voltage output, current output, and dial
setting, along with the muscle twitch strength, were recorded. The needle was advanced in 0.5-cm increments and
the recording repeated until the femur was reached or the needle was clearly past the nerve.
Next, the needle was moved in and out until the position was found where the minimum current caused a muscle
twitch. This maneuver simulated the clinical situation of manipulating the needle to find the closest approach to the
nerve.
At the conclusion of this experiment, with the needle 1 to 2 cm beyond the sciatic nerve, a cutdown to the nerve
revealed how closely the needle approached the nerve ( Table 17–4 ). By withdrawing the needle until the tip was
again even with the nerve, the depth of the nerve was determined. A repeat series of measurements was made 2 to 3
cm distally on the nerve.
297
Result. In rotating the PNS through this series of experiments, five favorable electrical characteristics were
discerned. They were (1) a linear output, (2) high and low output ranges, (3) a short stimulation pulse, (4) clearly
TABLE 17-4 -- POLARITY OF STIMULATION

Anodal vs cathodal current required to stimulate peripheral nerve
× 4.57
× 4.3
Data from Ford DJ, Pither CE, Raj PP: Electrical characteristics of periph eral nerve stimulators: Implications for nerve localization. Reg Anesth 9:73–77, 1984;
and from BeMent SL, Ranck JB Jr: A quantitative study of electrical stimulation of central myelinated fibers. Exp Neurol 24:147–170, 1969.
marked polarity, and (5) constant current output. In addition, three design features that also contributed to finding a
peripheral nerve were noted. These were a large, easily turned dial; a digital output meter; and a battery check.
Experiment III: Strength Duration Curve
Because all of the commercial PNSs examined used a stimulus pulse width between 2000 microseconds and 1000
microseconds, it was not possible to determine the effect of a shorter pulse (<200 µsec) on the peripheral nerve
localization procedure used in Experiment II. Therefore, to determine the effect of pulse width, the Grass stimulator,
which has a variable pulse width, was used to construct a strength-duration curve.
Result. The results of this experiment are shown in Figure 17–9 . The Y-intercept is the rheobase and the pulse
duration corresponding to twice the rheobase is the chronaxy. The dotted lines in Figure 17–9 show the change in
stimulating current as the needle is advanced toward the nerve from 1 cm away. The shorter the pulse duration, the
greater the change. For a short pulse (40 µsec), there was a change of approximately 29 mA. For a long pulse (1000
µsec), the change was 2.6 mA. Uninsulated needles gave the same qualitative results, but more current was required
(data not shown).
SIGNIFICANCE OF POLARITY
Study 1
Another important principle of electrical peripheral nerve stimulation is preferential cathodal stimulation ( Fig. 17–
10 ).
Figure 17-9 Strength-duration curve. The Y axis is the current that produced a small muscle twitch (2%–5% of the maximum). The X axis is the reciprocal of the
duration of the stimulating pulse. The actual duration is also shown below the X axis. The error bars are the standard deviation. The top line is the strength-duration
curve with the needle 1 cm from the nerve. The lower line is the strength-duration curve with the needle touching or very close to the nerve. The dashed lines show the
change in stimulating current as the needle approaches the nerve for a 40-µsec pulse and 1000-µsec pulse.(From Ford D, Pither C, Raj P: Electrical characteristics of
peripheral nerve stimulators: Implications for nerve localization. Reg Anesth 9: 73–75; 1984.)
298
Figure 17-10 Preferential cathodal stimulation. A, With the needle as the cathode, electron flow is toward the needle. This causes an area of
depolarization around the needle tip. B, With the needle as the anode, the area adjacent to the nerve is hyperpolarized, with a zone of
depolarization in a ring distant to the needle. This arrangement requires more current to stimulate the nerve. (From Pither CE, Ford DJ, Raj PP:
The use of peripheral nerve stimulators for regional anesthesia: A review of experimental characteristics, technique, and clinical applications.
Reg Anesth 10:49–58; 1985.)
If a nerve is stimulated by an electrode until a muscle twitch occurs, it is found that much less current is needed to
generate a muscle twitch if the cathode (negative) rather than the anode (positive) is adjacent to the nerve. When the
stimulating needle is the cathode, the current flow alters the resting membrane potential adjacent to the needle to
produce an area of depolarization, which easily triggers an action potential. If the stimulating needle is the anode,
the current causes an area of hyperpolarization adjacent to the needle and a ring of depolarization distal to the needle
tip. This arrangement is less efficient. This phenomenon is of clinical importance. Table 17–4 shows the differences
in current required when the polarity is reversed. [15] [16]
Clearly marked polarity extending to the ends of the connecting cords is important. The stimulating needle should be
attached to the cathode (−) and the patient attached to the anode (+). When the polarity was reversed, 4.3±0.4
(AVE±SD, No.=6) times as much current was required to produce a muscle twitch as when the polarity was correct.
Study 2
Tulchinsky and colleagues did a clinical study to determine whether needle polarity significantly affects nerve
[17]
stimulation during peripheral nerve block. They performed a randomized, double-blinded study of 10 patients
undergoing axillary block for upper extremity surgery. Using insulated needles, they determined the minimal
amount of current necessary to elicit muscle contraction with positive and negative needle polarity at two needle
placements: (A) where stimulation was first observed and (B) where stimulation was maximal. At position A,
stimulation required significantly more current when the needle was positive (2.32±0.45 mA, mean±SEM) than
when it was negative (1.05±0.23 mA P<0.001). Similarly, at position B, stimulation required more current when the
needle was positive (1.49±0.49 mA) than when it was negative (0.47±0.15 mA, P<0.001). The mean ratio of
positive to negative threshold stimulation current at position B (3.11±0.20) was significantly greater than that at
position A (2.37±0.19, P<0.05). Their results emphasize the importance of attaching the negative terminal of the
nerve stimulator to the stimulating electrode.
Use of the positive terminal could lead to abandoning a block if stimulation were not obtained at a low enough
current; alternatively, motor contraction might not be observed before neutral contact or vascular puncture occurred.
299
NERVE STIMULATION WITH INSULATED AND UNINSULATED NEEDLES
Bashein and colleagues addressed the question of nerve stimulation with two in vitro stimulation models, one
[18]
digital and one analogue. In both models, they considered a square region of “tissue” with a needle connected to one
electrode and inserted perpendicular to the free border representing the “skin,” whereas the other three sides were
connected to the so-called indifferent electrode. Their model differed from that of Montgomery and coworkers in [7]
that the region was large compared with the needle length, so that it more accurately represents the situation in vivo.
With the digital computer, Bashein and colleagues solved for the electrical potential over the region (Laplace’s
equation) and then graphed the contours of constant electric field strength. The contour delineating where the field
exceeds some threshold value defines a zone of depolarization (ZD), and any nerve located within that zone
presumably would be depolarized.
For the analogue solution, these investigators constructed a similar region by spreading polyacrylamide gel
containing bromphenol blue dye uniformly in a thin layer on a glass plate. A DC power supply caused the dye to
migrate away from the needle under the influence of the electric field.
In both stimulations, they observed the following: (1) with a noninsulated needle (NIN), the ZD is broadened at the
tip of the needle, but it extends proximally along the entire shaft. The widest dimension of the ZD is slightly
proximal to the needle tip (and presumably away from the stream of local anesthetic); (2) with an insulated needle
(IN), the ZD is almost circular and is displaced, with its center slightly distal to the needle tip; (3) (analogue
simulation only) they also found that the stimulator current setting necessary to obtain a ZD of a given area was
highly dependent on the depth of needle insertion with NIN but only slightly so with IN.
They concluded that the ZD for an insulated needle has a more favorable geometry for successful nerve block, and
that with an insulated needle, nerve proximity can be inferred by response to stimulation with a current that is
largely independent of the depth of insertion. Further investigation, with a uniform-resistance conductive paper and
a Wheatstone bridge as a two-dimensional model for a volume conductor, revealed that the density of a stimulating
current leaving an unshielded hypodermic needle was greatest at the tip.
Figure 17-11 Computer-stimulated models for zones of current density around the tips of insulated (A) and uninsulated (B) needles. Note how the
center of B is just proximal to the tip of the needle and most of the zone extends up to the needle shaft. (From Pither CE, Ford DJ, Raj PP: The
use of peripheral nerve stimulators for regional anesthesia: A review of experimental characteristics, technique, and clinical applications. Reg
Anesth 10:49–58, 1985.)
Figure 17–11 illustrates the experimental model in which isocurrent lines measured from appropriately placed
electrodes show the patterns of current flow. The stippled area adjacent to the needle represents current density, the
intensity of the stippling being proportional to the current density. The isocurrent lines were determined by
increments of 10% of the total current. Accordingly, the size of this segment represents current density, which is
inversely proportional to the distance between the lines. If each segment represents 10% of the total current, the
three segments making up the tip of the needle account for 30% of the current discharged. The diameter-to-length
ratio for this needle is more than double that of any of the needles actually used in the study, which means it is a
300
conservative estimate of the percentage of current flow from the tips of those needles.Because of the symmetry of
the model, it could be rotated mathematically to generate a three-dimensional model, with a similar approximation.
Thus, with at least 30% of the total current coming from the very tip of the needle, a vastly greater stimulation came
from the tip rather than from the sides of the needle with low voltage.
Preferably, the needles should have metal hubs, but plastic hubs may be used if the needle is of sufficient length to
allow attachment of the alligator clamp to the shaft of the needle. The most commonly used needles are a 25-G, 1-
inch needle; a 22-G, 1½ -inch needle; a 22-G 3½ -inch spinal needle; and a 22-G, 6-inch standard block needle (
Table 17–5 ).
TABLE 17-5 -- SUMMARY OF DIFFERENCES BETWEEN INSULATED AND UNINSULATED NEEDLES

Insulated Uninsulated
Greater accuracy Accurate
Expensive Very cheap
Often unobtainable Readily available
No stimulation from shaft Local stimulation from shaft
Less current Slightly more current required
Minimum current on nerve Minimum current just past nerve
Can alter feel of tissues No alteration in feel of tissues
Both insulated and uninsulated needles have been used with nerve stimulators for peripheral nerve blockade. Pither
and colleagues have developed an in vivo cat model to compare nerve stimulators and to assess the electrical
[19]
behaviour of both types of needles.
Study in CAT Model
Two sets of experiments were performed. In the first, the needle was advanced toward the sciatic nerve in the thigh,
and stimulation of the nerve was assessed by twitches of the tibialis muscle attached to a force transducer. In the
second, the saphenous nerve was used and the compound action potential recorded distal to the stimulation. In both
cases, the needle was mounted on a mechanical platform that enabled its exact position to be determined. The
minimal current needed to produce stimulation by a 100 microsecond pulse delivered by a Grass S-88 stimulator
was recorded at various distances from the nerve. The current was measured by recording the voltage drop across a
known resistance by a Tektronic 564B storage oscilloscope. The effect on the twitch of a small injection of saline
was investigated at various positions of the needle. At the end of each experiment, a cutdown was performed to
verify the exact position of the needle in relation to the nerve.
Results. The graph shows the mean and standard deviations for five experiments on the saphenous nerve. The
current was plotted against distance from the nerve ( Fig. 17–12 ). Minimal current for the insulated needle occurs
with the tip adjacent to the nerve and requires 0.57±0.26 mA (mean±1 SD). For the uninsulated needle, this
minimum is 1.33±0.38 mA and occurs 0.5 cm past the nerve. Similar results were obtained from the sciatic nerve.
Injections of 0.1 to 0.3 mL of saline stopped the twitch when the needle tip was on the nerve or 1 cm past the nerve
but had no effect on the twitch when the tip was 1 cm proximal to the nerve.
Conclusions. Both insulated and uninsulated needles can be used to locate peripheral nerves in the cat. For insulated
needles, the nerve can be simply and accurately located at the point of minimal current. For uninsulated needles, the
tip is likely to be past the nerve at this point, and would not be indicated by an injection of saline. Optimal
placement of uninsulated needles can be obtained if the needle is withdrawn until the stimulus current is just above
minimum.
Figure 17-12 Comparison of current required to stimulate the nerve versus distance from the nerve for insulated and uninsulated needles (cat
saphenous nerve). Both needles behave similarly approaching the nerve, but the uninsulated needle reaches a plateau once it has passed the nerve.
The insulated needle requires less current throughout and is minimally on the nerve. The uninsulated needle is minimally (0.6) cm past the
nerve.[19] (From Pither CE, Ford DJ, Raj PP: Peripheral nerve stimulation with insulated and uninsulated needles: Efficacy of characteristics.
301
Reg Anesth 9:42, 1984.)
EFFICACY OF CLINICALLY USED PERIPHERAL NERVE STIMULATORS
Study 1
Accurate delivery of current is important in the use of nerve stimulators for nerve location. A nerve stimulator that
overestimates the current output is likely to lead the operator to assume the needle is further away from the nerve
than it is. This could lead to penetration of the nerve by the needle and intraneural injection. Conversely, a
stimulator that underestimates the current output is likely to mislead the operator by indicating that the needle is
nearer the nerve than it is. This could lead to injection of local anesthetic too far from the nerve for effective neural
blockade.
Kaiser and colleagues produced a list of desirable properties in peripheral nerve stimulators, which included
[20]
adjustable constant current at resistances of 500 Ω to 10k Ω; a monophasic square wave initial impulse; selectable
impulse duration of 0.1 and 1.0 ms; unequivocal scale graduation or current indicator, especially over the range of
0.5 to 1.0 mA; and impulse frequency of 1 to 2 Hz. They also made recommendations on self-test and safety
features for nerve stimulators, which included an alarm at high impedance and check on electrical circuit; battery
test; unequivocal assignment of load end; high-quality connections and cable; instructions for use; and design
operating parameters. [20]
The general procedure of nerve localization involves producing a small evoked muscle twitch with the PNS, moving
the needle in a direction that causes an increase in the twitch strength, and then reducing the stimulus strength to
restore the twitch to its previous tension. This procedure is repeated until minimal stimulus strength is obtained. It is
important for the operator to be able to produce a discriminating change in the stimulus strength. The specific
features of the PNS that affect the operator’s ability to produce discriminating changes in the stimulus strength were
(1) linear output; (2) high and low output; and (3) a large, easily turned dial. A nonlinear output was most
detrimental when a small movement of the dial produced a large change in the output (curve B; see Fig. 17–7 ) and
when the output did not start at zero (curve A; see Fig. 17–7 ). The nonlinear response shown in curve C of Figure
17–11 did not affect the ability to locate a peripheral nerve. The dual output ranges allowed a muscle twitch to be
stimulated when the needle was several centimeters from the nerve (high scale) and still produce small changes in
the output when the needle was close to the nerve (low scale). Furthermore, all the PNSs used for this study could
also be used to monitor neuromuscular blockade. The high output scale was well suited for this purpose.
The digital scale was very useful for approximating the position of the needle relative to the nerve. In the two PNSs
with a digital scale, the reading was in milliamperes. When the needle was not close to the nerve (>1 cm), the
minimal amount current required to produce a twitch was large. This was easily observed with a digital scale. With a
dial only, the larger amount of current was not easily detected.
There was a wide response in current output to a twofold change in resistance (1%–24% decrease). A constant
current instrument delivers the same current through 1000 Ω as through 2000 Ω . Therefore, the drop in current is
0%. A constant voltage instrument (Grass S-88) delivers half as much current through a 2000 Ω resistance as
through a 1000 Ω resistance; therefore, the drop in current is 50%. A 24% decrease is a compromise between
constant current and constant voltage. The advantage of a constant current instrument lies in its stability to changes
in resistance. Movement of the patient or drying of the electrode can alter the resistance in the patient-needle circuit.
With a constant voltage instrument, an increase in resistance causes a decrease in the stimulus strength. On the other
hand, a sudden drop in resistance creates an increase in stimulus strength, causing the patient pain.
The significance of a short stimulus pulse is that it increases the ability to produce a discriminating change in the
stimulation current. At 40 µsec, the ratio of current required to stimulate the nerve when the needle is 1 cm away
from the nerve to the current when the needle is on the nerve is approximately 100 (32/3.0). At 200 µsec, the ratio is
about 8 (8.5/1.1), and at 1000 µsec, the ratio is about 5 (3.5/0.7). Therefore, as the needle approaches the nerve, the
relative changes in the current increase for shorter pulses ( Table 17–6 ).
Study 2 [21]
This study set out to examine the PNSs available in one hospital. Six different models were identified (Braun
Stimuplex, Braun Stimuplex DIG, Digistim 3, Digistim 3 Plus, Regional Master Corporation Nerve Finder, Bard
750 Digital),
302
TABLE 17-6 -- PERFORMANCE OF COMMERCIALLY AVAILABLE NERVE STIMULATORS AS TESTED BY THE AUTHORS
Maximal Output
Pulse
Constant Width
at 2000 Ω Meter (M, Output: High Battery
Current Linearity Polarity µsec) Pulse Interval and Low Indicator
Output ++ Poor (A) — 200 1 Hz — —

Dupaco + Good — 500 2 Hz — —
Bard High+ Good Yes 200 1 Hz Yes Yes
High 4.3
Low++ None of the
Low 17.5 instruments
tested had
the ideal
labeling of
“needle”
and —
“grounding” 500 5 Hz Yes 21.5
Anaesthesia Associates ++ OK 500 5 Hz — Yes 21.5
Professional Instruments ++ Poor (D) 150 1 Hz — —
Neuro Technology High++ Good Yes 200 1 Hz Yes Yes High 66
Low+++ Low 22
†
Welcome ++ Poor (B) — 1 Hz — — 25
Nerve Finder +++ Poor© Yes 1000 1 Hz Yes 15
†Hyperbolic pulse.
and the output characteristics were measured for each stimulator with use of a twin-beam, calibrated storage
oscilloscope. Target current output values from 0.3 mA to 3 mA and load resistances from 560 Ω to 10 k Ω were
selected to model the normal ranges of operating current and skin electrode-needle impedance performing regional
anesthesia. Only half of the PNSs tested were able to complete the test and deliver a target current to ± 20%
accuracy. The variation in performance of PNSs means that for a safe and successful nerve block it is important for
the operator to be aware of the design and functional limitations of any stimulator being used in clinical practice.
Of the six test machines, only three were able to complete the full range of output tests within an accuracy of ± 20%
(Braun Stimuplex DIG, Digistim 3, and Digistim 3 Plus). The Braun Stimuplex appears to perform poorly for the
higher combinations of output current and load resistance; however, it is accurate over the critical range of 0.05 to
1.0 mA and does perform well in clinical use.
The main conclusion to be drawn from this study is that some PNSs give misleading current readings. This means
that to ensure a safe and successful nerve block, it is important for the operator to be aware of the design limitations
and the degree of inaccuracy in the stimulator being used.
TABLE 17-7 -- DESIRABLE CHARACTERISTICS OF PERIPHERAL NERVE STIMULATORS

Constant current output
Clear meter reading to 0.1 mA (preferably digital)
Variable output control
Linear output
Clearly marked polarity
Short pulse width
Pulse of 1 Hz
Battery indicator
High and low output
High quality alligator-type clips
303
DESIRABLE CHARACTERISTICS OF PERIPHERAL NERVE STIMULATORS
Many specialized PNSs are now commercially available, and most contain complex and sophisticated electronics
that are far from the primitive machines of the early pioneers. The desirable features of PNSs have been elucidated
by Galindo and by Ford and colleagues. Table 17–7 lists the features PNSs should include for optimum
[22] [15]
efficiency.
Technical Considerations
1. The device should have a constant level of current output. This implies that the stimulator should have a
high internal resistance. Because it is a particular current (not voltage) that stimulates the nerve, it is
important that the current should not vary with changes in resistance of the external circuit. The resistance
of tissue, needles, connectors, and such, when a nerve stimulator is used, may vary from 1 K Ω to 20 K Ω .
For a constant voltage instrument, this change in resistance can cause a 20-fold change in the current
delivered and may easily be the difference between a painful and nonpainful stimulus.
2. The current delivered should be displayed on a clear reading meter, preferably digital. The importance of
this is emphasized later, but, from the foregoing discussion, it may be appreciated that with the stimulating
needle on the nerve only a very small current (in the region of 0.5 mA) is needed to stimulate the nerve.
Knowledge of the amount of current is vital for accurate location. Older PNSs without meters cannot be
recommended.
3. The device should have an easily moved variable output control with a linear scale. This means that if the
dial is turned to 50%, the output should be 50% of the maximum.
4. The polarity of the leads should be clearly marked. It is not enough to color the leads or to label them
positive and negative, because few practitioners are aware of the importance of attaching the anode to the
needle. Furthermore, as the anode is conventionally colored black, common sense may suggest that this
should be attached to the ground, which is incorrect. The matter can be further complicated if the
manufacturer has compensated for the possible misunderstanding by reversing the color coding. The
answer is for the negative end of the electrode to be clearly marked “needle” and the positive end of the
electrode to be marked “ground.”
5. The pulse width should be short; a pulse of 50 to 100 µsec is ideal. This corresponds to the chronaxies of A
delta fiber in mammalian mixed peripheral nerves. The importance of this is emphasized by reexamining
the strength duration curves. Figure 17–9 shows strength-duration curves obtained from a cat sciatic nerve
preparation, with the needle on the nerve and at 1 cm distal to the nerve. The reciprocal of the duration is
used to obtain a straight line. It can be seen that with a pulse width of 40 µsec, the change in stimulation
strength as the needle moves from 1 cm away to the nerve is 10-fold. If the pulse width is increased to 1
ms, the change is only double. Notice that the change in required current is minimal for all pulse widths
with the needle on the nerve. Because the current is being read continuously from a meter, the shorter pulse
width provides better discrimination of the distance between needle and nerve. Although a shorter pulse
requires a greater current when distant from the nerve than a longer pulse, the actual change delivered is
less because the time for which the current flows is so much shorter.
6. The device should have both high and low outputs. This is especially important if the instrument is also
used for monitoring neuromuscular block, for which the high currents required are best provided by a
separate output. The optimal frequency is between 0.5 and 2 Hz.
7. A battery indicator should be provided. If there are problems in eliciting a response, it is important to know
if the battery is in good condition.
8. The connectors should be made of a high-quality, alligator-type clip of low resistance. Any major increase
in resistance at the connectors can cause an inappropriate current reading.
Procedure for the Use of Peripheral Nerve Stimulation for Nerve Location
1. The ground electrode is attached to the electrocardiogram pad and placed away from the region to be
stimulated ( Fig. 17–13 ).
2. The syringe containing the anesthetic solution is attached to an extension set filled with anesthetic solution.
3. The end of the extension set is connected to a 22-G, 3.75-cm needle.
4. The needle is inserted through the skin.
5. The exploring electrode is connected to the hub of the needle via the alligator clamp ( Fig. 17–14 ).
6. The ampere control is set so that the current flows at 4 or 5 mA at a frequency of one pulse per second (
Fig. 17–15 ).
7. The needle is advanced slowly, while the forearm and hand are observed carefully for muscle movements.
Flexion or extension of the elbow, wrist, or digits confirms that the needle is in close proximity to nerve
304
fibers of the brachial plexus. The best results are obtained if the movements occur as distally as possible;
for example, with brachial plexus block, in the hand or fingers ( Fig. 17–16 ).
8. The current is then reduced ( Fig. 17–17 ) and the needle is moved deeper to find maximal contraction.
This process is continued until a point is reached where there is maximal stimulation with minimal current
(0.5 mA–1 mA) ( Fig. 17–18 ).
9. After careful aspiration, 1 to 2 mL of anesthetic solution are injected through the needle, which should
result in the cessation of muscle movement within a few seconds ( Fig. 17–19 ).
10. If a reduction in muscle movement does not occur, the stimulation is probably coming from the side of the
needle, in which case the needle should be repositioned and the procedure repeated.
11. Immediately after muscle movement has ceased, the remaining anesthetic solution should be injected
through the needle.
Figure 17-13 Ground electrode is placed in a region away from the block; here, for example, it is placed on the opposite shoulder.(From Raj PP,
Nolte H, Stanton-Hicks Md’A: Principles of management. In Raj PP, Nolte H, Stanton-Hicks Md’A: Illustrated Manual of Regional Anesthesia.
New York, Springer-Verlag, 1988, p 10. Copyright 1988 Springer-Verlag.)
Figure 17-14 The needle penetrates the skin with the exploring electrode connected to the hub of the needle.(From Raj PP, Nolte H, Stanton-
Hick Md’A: Illustrated Manual of Regional Anesthesia. New York, Springer-Verlag, 1988, p 10. Copyright 1988 Springer-Verlag.)
305
Figure 17-15 Initially, the stimulator is set at 5 mA and 1 pulse per second.(From Raj PP, Nolte H, Stanton-Hicks Md’A: Illustrated Manual of Regional Anesthesia.
New York, Springer-Verlag, 1988, p 10. Copyright 1988 Springer-Verlag.)
Figure 17-16 Flexion of medial 1½ digits is seen as the needle approaches the nerve trunk in brachial plexus block.(From Raj PP, Nolte H,
Stanton-Hicks Md’A: Illustrated Manual of Regional Anesthesia. New York, Springer-Verlag, 1988, p 11. Copyright 1988 Springer-Verlag.)
Figure 17-17 The current is reduced to between 0.5 and 1 mA and the needle is stabilized when maximal stimulation of the contracting muscles
is achieved.(From Raj PP, Nolte H, Stanton-Hicks Md’A: Illustrated Manual of Regional Anesthesia. New York, Springer-Verlag, 1988, p 11.
Copyright 1988 Springer-Verlag.)
Figure 17-18 Maximal flexion of digits supplied by the median nerve is seen here with stimulation at 0.5 mA; this suggests that the needle is in
close proximity to the median nerve fibers.(From Raj PP, Nolte H, Stanton-Hicks Md’A: Illustrated Manual of Regional Anesthesia. New York,
Springer-Verlag, 1988, p 11. Copyright 1988 Springer-Verlag.)
306
Figure 17-19 Complete cessation of movement within a few seconds is seen after 2-mL local anesthetic solution is injected.(From Raj PP, Nolte H, Stanton-Hicks
Md’A: Illustrated Manual of Regional Anesthesia. New York, Springer-Verlag, 1988, p 11. Copyright 1988 Springer-Verlag.)
Helpful Hints
Ground Electrode. Conventional electrocardiogram-type electrodes are suitable, but care must be taken to ensure
that they make good contact with clean, dry skin. The current flows between the two electrodes (needle and ground);
therefore, it is preferable not to position the ground over a superficial peripheral nerve. The passage of current
through the myocardium should also be avoided. The shoulder and buttocks, respectively, are good sites for upper
and lower extremity blocks.
It should be emphasized that the peripheral nerve stimulator is not a substitute for sound anatomic knowledge and
adroit technique but is rather an adjunct to them. The fundamentals of premedication, kindness, and asepsis should
naturally be followed and are not detailed here.
The Needle. The needle is inserted through the skin and advanced a short distance. The assistant connects the nerve
stimulator with the anode (black) to the needle. The stimulator is turned on with a current of 5 mA to 10 mA shown
on the meter. This often produces a localized muscle twitch, especially with uninsulated needles. The needle is
advanced toward the nerve and movement is looked for in the appropriate muscle groups. Once movement is elicited
in the appropriate muscles, the needle tip is likely to be 1 to 2 cm from the nerve. As the needle is advanced toward
the nerve, the twitch increases in intensity. The assistant reduces the current strength. If the twitch decreases with
advancement of the needle, the needle is probably to one side of the nerve and should be redirected to a more
suitable approach. The needle is manipulated until a muscle twitch occurs at minimal current. This level should be
between 0.5 mA and 1 mA. The figures reported by Yasuda and colleagues of 0.09 mA probably reflect the long
[23]
pulse width (5 ms) that they used.
Once the point of optimal muscle twitch at minimal current has been obtained, a test injection of 2 mL of the local
anesthetic agent is given. The immobile needle technique advocated by Winnie is particularly appropriate at this
[24]
point. Within 10 seconds after the test injection, the twitch should diminish considerably or disappear. If it does not,
the needle should be withdrawn slightly. If the twitch is stopped by the test injection, the full dose of local anesthetic
is given. If the twitch is not eliminated completely by the injection, the needle should be removed and redirected
until the muscle twitch is maximal at 0.5 mA to 1 mA and until the 2 mL-test dose immediately eliminates the
twitch height. Only then should the full calculated dose of the local anesthetic be injected. It is often possible to
restore the muscle twitch at this point by increasing the stimulating current to the region of 10 mA. This does not
imply that the block has failed, but, if further contractions are elicited at low current, it is worth injecting more local
anesthetic.
The onset of the block occurs initially in the region supplied by the nerve to the muscles that were twitching ( Table
17–8 ). For example, if the radial three and a half fingers were flexing at digital joints with each pulsation, the onset
of the block is seen in the median nerve distribution. It has also been our experience that proximal muscle groups are
paralyzed earlier than the occurrence of sensory loss or sympathetic block. de Jong has explained that this [25]
phenomenon is the result of anesthesia developing in the mantle fibers earlier than in the core fibers.
When stimulation of pure sensory nerves (e.g., maxillary or saphenous nerve) is performed, confirmation of the
needle tip location at the nerve is obtained by eliciting from the patient a radiating paresthesia with every pulsation
[2]
in the distribution of the nerve. The quality of pulsation felt by the patient is also very important. It should occur at
307
low current (0.5 mA–1 mA) and should be stopped instantaneously with, a 1 mL-test dose. Sensory loss occurs quite
quickly in these nerves and one may not be able to appreciate the sympathetic block.
That a small dose of anesthetic can eliminate the twitch was first noted by Greenblatt and Denson and subsequently [3]
investigated by Raj and colleagues in anesthetized dogs. They found that an injection of air or saline also stopped
[13]
the twitch and suggested that the mechanism was due to physical displacement of the nerve. Pither and associates, [19]
using anesthetized cats and injecting saline, confirmed the mechanism and found not only that the twitch always
disappeared with the needle on the nerve, but that it also disappeared with the needle tip just past the nerve. The
injection test should thus be regarded as a helpful but not infallible aid to needle placement. If the second injection
does not affect the twitch, the needle should be withdrawn or repositioned; if the twitch disappears, the likelihood is
that the needle is on or in close proximity to the nerve, but it could be past it.
The importance of the amount of current required to stimulate the nerve at the end point is emphasized in Figure 17–
20 . Note that the characteristics of the passes that missed the nerve are very similar to those that found the nerve
(compare with Fig. 17–12 ), with the exception of the amount of current. With the needle touching or very close to
the nerve, only 0.5 mA to 1 mA is required; if the current is more than this, the needle is unlikely to be on the nerve.
PNSs without meters are unable to make this discrimination.
Occasionally, during the course of an experiment, the muscle twitch ceased because of a loose connection, a worn-
out battery, an improperly placed needle, or some other unknown cause. Under such circumstances, it was very
useful to be able to check the condition of the battery. In the literature, results of minimal stimulation strength are
reported in volts and milliamperes. Two points need to be made concerning the significance of such numbers. First,
it is current that stimulates a nerve and that should be reported. Furthermore, in practice, the voltage that produces a
[9]
particular current is a function of the resistance
Figure 17-20 Compare with Figure 17–10 . Graph of the stimulus current against a needle positioned for approaches to the sciatic nerve in a cat.
The needle missed the nerve by the distances stated. Notice how the current troughs at the point nearest the nerve are similar to the dotted line in
Figure 17–10 , but the current required is very much greater, emphasizing the importance of an accurate meter on a nerve stimulator.(From Pither
CE, Ford DJ, Raj PP: The use of peripheral nerve stimulators for regional anesthesia: A review of experimental characteristics, technique, and
clinical applications. Reg Anesth 10:49–58, 1985.)
between the needle and the second electrode. Therefore, the quality of the electrical connection between the
electrode pad and the patient’s skin affects the voltage required to stimulate the nerve but does not affect the current.
In addition to reporting the minimal current, the duration of the stimulating pulse should also be reported. In Figure
17–7 , a 40-µsec pulse required 2.86 mA, whereas a 1000-µsec pulse required only 0.68 mA to produce a small
muscle twitch when the insulated needle was on the nerve.
CLINICAL APPLICATIONS
PNS is useful in patients who have undergone trauma or surgery as well as those who have postoperative or chronic
pain. The technique can be used for nearly all common blocks. Localization of purely sensory nerves can be
accomplished by eliciting pulsating paresthesias with the stimulator. When mixed nerves containing motor fibers are
blocked, the patient has a more passive role; therefore, minimal patient cooperation is required. Thus, patients who
308
are compromised because of injury, alcoholic intoxication, drugs, or medications can be effectively treated with
little cooperation. It also enables adequate premedication to be given for painful blocks in pediatric practice, because
children can be anesthetized before the block is performed. Table 17–8 lists the blocks that can be performed with
the PNS. Even though the use of the PNS for regional anesthesia is still practiced by a minority, there is little doubt
about its efficacy in the hands of those familiar with its use. Few studies exist in the literature comparing the
technique with other methods of nerve location. Magora and coworkers compared obturator
[6]
TABLE 17-8 -- BLOCKS THAT CAN BE PERFORMED WITH THE PERIPHERAL NERVE STIMULATOR
Nerve and Root Elicited Area of
Block Value Movement Muscles Involved Paresthesia Comments
Trigeminal V3 Jaw clench Masseter temporalis Lower jaw pinna
Pterygoids
V2 − Purely sensory Cheek, nose, upper
jaw
V1 − Purely sensory Front of scalp
Accessory XI Shoulder Trapezius − Sometimes encountered when
shrug cervical plexus block is
performed
Glossopharyngeal IX − Purely sensory Back of tongue,
throat
Phrenic C3–C5 Hiccup Diaphragm − Sometimes encountered when
interscalene block is performed
Cervical C2–C5 (Arm Mainly sensory (deltoid) Back of neck and Paresthesia often obtained rather
abduction) head than muscle twitch
Brachial plexus Musculocutaneous Elbow Biceps brachialis Lateral side of
flexion and forearm
supination
C5–C6 Elbow, wrist, Triceps common extensors Back of arm +
and finger forearm
extension
Radial C7–C8 Base of thumb
Median Wrist flexion Common flexors pronators Lateral 2½ fingers
and pronation of palm
C5–C8 Finger Opponents
flexion +
opposition
Ulnar C8T1 Wrist flexion Long flexors 1½ medial fingers
with medial of palm and
deviation dorsum
Small muscles of hand
Intercostal T1–T12 − Intercostal muscles Segmental band; Muscle movement not observed
usually clinical
Lumbar plexus L1 Inguinal region Electrolocation not ideal as sole
means of identification but
helpful to confirm proximity to
nerve once anatomic or
radiographic approach made
L2 Front of thigh
L3 Hip flexion Hip abduction Medial knee
L4 + extension Inside calf
L5 Hip Knee flexion Great toe
adduction
Sacral plexus S1 Plantar Little toe
flexion
S2 Sphincters Back of leg
S3
309
TABLE 17-8 -- BLOCKS THAT CAN BE PERFORMED WITH THE PERIPHERAL NERVE STIMULATOR
Nerve and Root Elicited Area of
Block Value Movement Muscles Involved Paresthesia Comments
S4 Saddle
S5
Pudendal S2–S4 Pelvic floor Perineum (labia, Muscle twitch not usually
scrotum) elicited
Femoral L2–L4 Knee Quadriceps, pectineus sartorius Inside of leg Contraction of sartorius alone
extension not sufficient
Obturator L2–L4 Hip Hip adductors Patch on inside of
abduction knee
Lateral Femoral L2 − Purely sensory Patch on outside of
Cutaneous thigh
Sciatic L4–L5 Knee flexion Hamstrings, gastrocnemius, Back of leg Any movement may be
soleus, peroneus, etc. elicited— foot movements are
preferable as they preclude
direct stimulation of muscles
S1–S3 Foot and toe Back and lateral
side of calf
Dorsiflexion Most of foot
Plantar
Flexion
Knee Tibial Foot and toe Gastrocnemius Dorsolateral side
flexion, of leg and foot,
inversion and and sole
adduction
L4–L5; S1–S3 Foot flexors
Saphenous − Purely sensory Inside of lower leg
L2–L4 Foot and toe, Peroneus, tibial anterior Top of foot
dorsiflexion
and eversion
Peroneal Long extensors
Ankle Tibial Toe flexion Small muscles of foot Sole of foot
Deep and − Purely sensory Dorsum of foot
superficial
peroneal
blocks by nerve stimulation and by fluoroscopic control and, although the series was small, they concluded that the
nerve stimulator was more accurate. Chapman found the technique “very useful, being easy and quick to use with a
[26]
high degree of certainty and causing little discomfort,” but Chapman made no comparisons with alternative methods
of nerve location. Yasuda and coworkers had a 98% success rate using a stimulator for supraclavicular block, but,
[23]
again, made no comparisons with other techniques. On the other hand, Smith supervised the performance of a
[27]
number of upper and lower limb blocks by residents and concluded that “the stimulator was not a useful adjunct for
nerve location.” However, an optimal stimulator or technique may not have been used. It would be useful to see the
results of a larger series comparing different methods of nerve location with optimal equipment and methods.
In the treatment of patients with chronic pain, there are indications for neurolysis of peripheral nerves (e.g., cancer,
paraplegia, and phantom pain). This can be accomplished by a routine single-shot injection of the neurolytic agent
as one would do for surgical anesthesia; the use of the nerve stimulator is also recommended. Some physicians,
ourselves included, prefer to localize the nerves objectively and to test with local anesthetics before injecting the
neurolytic agents. To accomplish this one can introduce a catheter onto those nerves. The PNS can be extremely
useful in introducing catheters onto the peripheral nerves. Special catheters are required for such localization with
the PNS. For the current to flow to the tips of the catheters, the alligator clip of the PNS should be attached to the
metal hub of the catheter. BD-Longdwel catheters (4-, 6-, and 8-inch) have been useful for such purposes because
they have metal hubs and transparent Teflon sheaths.
310
EVALUATION OF CLINICAL PRACTICE OF PERIPHERAL NERVE STIMULATOR
Since the early 1970s, clinical reports have been appearing that detail use of the PNS for various blocks. These are
mostly report series of patients on whom a block has been performed via the PNS technique. Many blocks have been
described, the most common being the brachial plexus, femoral, obturator, and sciatic blocks.
Most of these reports have noted excellent results, with success rates greater than 90%. Most workers have
recommended the technique and have often implied that the use of the PNS was the reason for publishing the series.
A number of these studies describe the technique in anesthetized children and claim high success rates in this group
of patients who benefit considerably from the postoperative level of analgesia that can be achieved with neural
blockade but that is virtually impossible to attain without nerve stimulation.
Only one noncomparative study concludes that the PNS is not useful. This study examined the use of the device as
[27]
an adjunct to teaching upper and lower limb block techniques to residents, but the study may not have used optimal
equipment or technique.
Unfortunately, the number of comparative studies is limited. Magora and colleagues compared the PNS with a
[6]
radiographic technique of blocking the obturator nerve and found the former superior. Smith and Allison compared [28]
sciatic nerve block performed with a paresthesia technique with nerve stimulation. They concluded that “the
stimulator significantly improves . . . the success rate in establishing sciatic nerve block.”
Four studies examined the role of the PNS in brachial plexus anesthesia. In a study comparing the perivascular
approach with nerve stimulation, the latter technique was found to be superior, and the authors concluded that the
PNS could increase the success rate. Goldberg and coworkers compared a transarterial approach with paresthesis
[29]
and with nerve stimulation and found the last to be the least successful, although this difference was not statistically
significant. Baranowski and Pither compared paresthesias with catheter and PNS techniques in 100 patients.
[30]
Although they again found no significant difference in success, they concluded that the PNS was the technique of
choice because of the minimal risk of damage to nerves and because of the occasional problems encountered when
inserting catheters. A further study comparing paresthesia with the PNS in interscalene block found no significant
difference between the two techniques. [31]
Some attention has been directed toward examination of the details of the technique to assess whether manipulations
can improve the success rate. There are no studies comparing insulated and uninsulated needles, although this topic
has been the subject of some correspondence, and data would provide interesting information. Kaiser and
colleagues have shown that the block can be enhanced if the stimulus current is kept to a minimum, implying that
[32]
the needle can be brought closer to the nerve if the stimulus current is 0.5 mA or less.
Overall, there are insufficient data to draw unequivocal conclusions about the superiority of PNS techniques, but
there is no doubt that it is the method of choice for many practitioners and that success rates are greater than 90%.
RECENT DATA ON EFFICACY
In one study, data from 1001 consecutive subclavian perivascular blocks were prospectively gathered over 2.5
years. All blocks were performed according to Winnie’s technique, using a stimulator instead of a paresthesia.
[33]
When an adequate response was obtained, 35 to 40 mL of local anesthetic solution was injected.
Nine hundred seventy-three blocks (97.2%) were completely successful; 16 blocks (1.6%) were incomplete and
needed supplementation; and 12 blocks (1.2%) failed and required general anesthesia, giving a success rate to
regional anesthesia of 98.8%.
The authors concluded that the subclavian perivascular block consistently provides an effective block for surgery of
the upper extremity. With this technique, at the site of injection, the plexus is reduced to its smallest components and
the sheath is reduced to its smallest volume, which explains in great part the success obtained with this block. They
believed that the PNS technique was both highly successful and safe; no clinical pneumothorax was found nor did
any other major complications develop.
Sia and colleagues conducted a prospective study to compare the onset time and the success rate of a multiple-
[34]
injection axillary brachial plexus block performed by using two methods of nerve localization: paresthesia elicitation
or nerve stimulation. Each of the major nerves of the plexus was located by elicitation of a paresthesia (Group
[34]
PAR; No. = 50) or by nerve stimulation (Group PNS; No. = 50) and injected with 10 mL of local anesthetic solution.
311
Time to perform the block, onset time of the primary block, time to achieve readiness for surgery, and total
anesthetic time were significantly shorter in group PNS than in Group PAR. The incidence of complete block was
larger in Group PNS than in Group PAR (91% vs. 76%; P <−0.05), and this was related to a larger success rate for
anesthetizing the radial and musculocutaneous nerves (P < 0.05). The frequency of venous puncture was larger in
Group PAR (P < 0.05). For multiple-injection axillary brachial plexus block, the authors concluded that nerve
stimulation resulted in a greater success rate and a faster onset than paresthesia elicitation, and that the former
technique should be considered when the radial and musculocutaneous nerve distributions were involved in the
surgical area.
This was the first study in which a higher success rate was obtained by the use of a PNS than with the paresthesia
method. The discrepancy between the results of the few previous studies comparing paresthesia elicitation with
nerve stimulation performed in this study may be explained by the relevant differences between the protocols.
Goldberg and colleagues compared a single-paresthesia technique with single-nerve stimulation and with the
[29]
transarterial approach, concluding that the success rates were no different. The lack of difference between the groups
in their study may be explained by the limitations of the single-injection technique. The success rates of a single-
injection axillary block are small and are not affected by the method of identification of the neurovascular
compartment. This is probably not related to an insufficient proximal spread of the local anesthetic, as
[29] [35] [36] [37] [38]
initially postulated, but to an insufficient circumferential spread to the various nerves of the plexus.
[39] [40] [41]
The efficacy of the different methods of identification of the nerves in producing a successful block may be better
shown by the multiple-injection technique, in which the individual nerves of the plexus are located and injected with
small volumes of local anesthetic, rather than in the single-injection technique, in which a large volume of local
anesthetic is injected into one point of the neurovascular compartment and must spread to all nerves of the plexus.
Baranowski and Pither showed that there was no difference in success rates between catheter, multiple-paresthesia,
[30]
and multiple-stimulation techniques. In this study, one to three nerves were located. Three nerves were located in
only 12 patients in the paresthesia group and four in the stimulation group. Baranowski and Pither defined a block[30]
as complete when three nerves were blocked after 30 minutes. In Sia’s study, blockade of all four terminal nerves
[34]
of the brachial plexus was required. Again, it may be hypothesized that with the multiple-injection technique, the
difference in efficacy of the nerve localization techniques in producing a successful block is better demonstrated. A
possible explanation of the results of this study may lie in the higher objectivity of the PNS in localizing the various
nerves than is possible with paresthesia elicitation. The use of a PNS requires no input from the patients who,
because of anxiety, fear, or lack of knowledge, may not adequately report a paresthesia when one is sought. [42]
The significantly shorter onset time in the Group PNS patients suggests that the local anesthetic was delivered closer
to the nerves. Another important contribution to the faster onset of surgical anesthesia in Group PNS was the
reduced need for supplementary blocks. The onset time of the primary block in Group PNS was similar to that
recorded in other studies using the same technique. [37] [43] [44]
The shorter time for the block performance found in Group PNS can be explained by the easier localization of the
four nerves and by the fact that no input from the patient was required. The time for block performance in Group
PNS was shorter than in other similar studies, probably because the blocks were performed with the aid of a
[37] [43] [44]
second person and because the subcutaneous tissue overlying the artery was infiltrated before the block
performance. The saving of 9 minutes in Group PNS amounted to a 26% reduction in total anesthetic time.
The difference in the incidence of complete block was related to a larger success rate for anesthetizing the radial and
musculocutaneous nerves in Group PNS. A muscular response related to the stimulation of the musculocutaneous
nerve was very easy to obtain in all the patients of Group PNS, whereas a blind injection into the body of the
coracobrachialis muscle was used in Group PAR. Although a successful block of the musculocutaneous nerve was
obtained in 85% of Group PAR patients, we believe that the use of a PNS permitted a more reliable and simpler way
of separately localizing and blocking the nerve, and this fact represents one of the main advantages of the technique.
The different success rates for blocking the radial nerve in the two groups were more difficult to understand. The
nerve was located in all of the Group PAR patients. It may be that the median and ulnar nerves, which lie in a more
superficial plane, were more easily reached by the spread of the local anesthetic, even if the nerve localization had
not been precisely made. Otherwise, the deeper position of the radial and musculocutaneous nerves might have
required a precise localization to obtain a satisfactory block in a large percentage of cases.
Several practical conclusions can be inferred from the results of this study. The multiple-injection technique via a
PNS resulted in a preparation of the surgery with fewer supplementary blocks than the same technique when
localization of the nerve trunks was made by eliciting paresthesia; therefore, the former technique may be preferred
when a rapid onset of the block is required. When surgery involves the palmar area, supplied by the median and
ulnar nerves, both techniques may be successfully used. When several nerves have to be blocked (especially if the
312
radial and/or the musculocutaneous nerves are involved, as in the case of surgery of the wrist or of the forearm), a
PNS may be helpful.
EFFICACY OF THE PERIPHERAL NERVE STIMULATOR IN STIMULATING

SENSORY NERVE
Regional block of the lateral femoral cutaneous nerve often has disappointing success rates despite the large
volumes of local anesthetic used. Shannon and coworkers undertook this study to investigate the utility of a PNS in
[45]
localizing and blocking the lateral femoral cutaneous nerve (a sensory nerve). The authors proceeded with a two-
stage study. In stage 1, 20 ASA 1 volunteers underwent lateral femoral cutaneous nerve block with both a fan and a
PNS technique in a prospective, randomized, crossover study employing strict criteria for success and extent of
block. To predict clinical utility, 20 patients underwent lateral femoral cutaneous nerve block by the PNS technique
with the same assessment criteria (stage 2). The PNS technique significantly improved the success of lateral femoral
cutaneous nerve block over the fan technique (100% vs. 40%, P = 0.00002). The number of successful blocks was
no different with the two techniques. Success in stage 2 was similar to that in stage 1 (85%) in predicting clinical
utility. The authors concluded that a PNS can be used to localize a purely sensory nerve, such as the lateral femoral
cutaneous nerve, and improve success rates in regional anesthesia. [45]
SUMMARY
The use of the PNS as an aid to nerve localization has an accepted place in the practice of regional anesthesia.
Several good stimulators are now commercially available, with many features to aid successful blockade. These
include a constant current output with clear reading meter, variable linear output, clearly marked polarity, and short
pulse width. For these devices to be used optimally, however, a sound knowledge of the electrophysiology of the
technique is important. This includes an appreciation of the strength-duration curve, current distance relationship,
and preferential cathodal stimulation. Good technique is necessary to optimize the successful performance of the
PNS; therefore, attention should be given to the electrical behavior of the type of needle used, the minimal current
required to stimulate the nerve, and the correct use of the injection of a small test dose of local anesthetic.
ULTRASOUND AND ANESTHETIC BLOCK

Jose de Andrés
Xavier Sala-Blanch
Neurostimulation is the most commonly used technique for locating the brachial plexus, thanks to its simplicity,
versatility, and low cost associated with a higher success rate than afforded by performance of other methods. [30]
Nevertheless, neurostimulation is a blind technique in which performance of percutaneous puncture is based on

external references or landmarks. The use of imaging techniques, specifically ultrasonography (US), has produced a
conceptual change in the way the brachial plexus is located. This change is based on the fact that the technique is
performed under direct puncture visualization and, therefore, constitutes a much more anatomic approach. During [46]
US guidance, the structures through which the needle is inserted are identified, and the plexus is directly localized;
consequently, a reduction in complications and side effects is more likely attributable to optimized puncture than to
an actual improvement in the clinical results. This characteristic will make US highly attractive in performance of
brachial plexus localization in the near future.
Advantages and Inconveniences of Ultrasonography in Relation to Neurostimulation
US shares many of the characteristic that have made neurostimulation so popular ( Table 17–9 ). The echograph is
easy to use once the necessary US knowledge has been gained, and the apparatus can be moved around in the
operating room. Moreover, although the systems that require performance of high-resolution US studies are
expensive, rapid technical developments and decreased discardable material costs (special neurostimulation needles)
could make the technique more accessible in the not too distant future. Nevertheless, the technique does require
thorough knowledge of the anatomic details and of US.
Familiarity with the anatomy of the zone in which the brachial plexus is found, knowledge of the US technique, and
technical developments will award US the importance it deserves in locating the brachial plexus.
313
Principles of Ultrasonography
Ultrasonography (or echography) is the result of technical developments in the application of US to imaging
diagnosis. Sound is a vibratory phenomenon by which frequency defines the number of vibrations, oscillations, or
cycles per second (measured in Hertz: 1 HZ = one oscillation per sound). US is defined as sound at a
TABLE 17-9 -- COMPARATIVE ANALYSIS OF NEUROSTIMULATION VERSUS ULTRASONOGRAPHY AS GUIDANCE

TECHNIQUE FOR BRACHIAL PLEXUS BLOCK
Neurostimulation (NS) Ultrasonography (US)

Puncture Based on external landmarks Direct visualization
Technical simplicity Yes Yes
Versatility Yes Yes
Cost
Apparatus Intermediate High
Discardable materials Intermediate Low
Learning Simple Complex
Teaching method Good Excellent
Clinical results Good Good
Clinical experience Great Limited (initial)
Expected complications Few Minor
Application to difficult patients Good Excellent
frequency above the human anditory threshold (greater than 20,000 Hz). The piezoelectric principle allows the
generation of ultrasound waves with applications to imaging techniques. This effect is based on the capacity of
certain crystals (piezoelectric crystals) to generate mechanical energy in the form of ultrasound waves in response to
the application of electric energy and vice versa.
The physical characteristics of US are defined by the wavelength, period amplitude, frequency, and velocity of the
waves. The wavelength is the distance traveled by sound in the course of a single cycle, and is measured in
millimeters (mm). The period is the time required to complete a full cycle, and is measured in seconds (sec),
whereas the amplitude corresponds to the square root of the energy of the wave, and frequency is the number of
periods per second. Frequency in turn depends on the generating piezoelectric material used. The frequencies
employed in clinical practice range from 1 to 20 MHz, whereas in application to brachial plexus block, the range is
typically 3.5 to 10 MHz. Wave velocity is the displacement of sound per unit time (measured in m/s), and depends
on the medium through which the sound travels—approximately 1540 m/s in the case of biological tissues.
Echogenicity is the capacity of structures standing in the way of the ultrasound beam to reflect the waves toward
their source. This capacity depends not only on the characteristics of the ultrasound waves but also on the properties
of the medium through which the sound travels. The interface is the limit or contact zone between two distinct
media that transmit sound at different velocities. The acoustic impedance is in turn defined as the resistance of the
medium to the passage of sound. When an ultrasound beam penetrates a given structure, the beam intensity
decreases as a result of attenuation on the one hand and wave reflection on the other. Attenuation represents the loss
of wave amplitude (energy) on traveling through a medium and depends on the wavelength, the density of the
medium or tissue, and the heterogeneity (number and type) of the interfaces present (attenuation being 1dB/MHz on
average). Wave reflection in turn conditions the formation of ultrasound images; it is proportional to the differences
in acoustic impedance between two media that form an interface standing in the way of the ultrasound beam. In
terms of reflectivity, the resulting images can be regarded as hyperechogenic, normoechogenic, or hypoechogenic.
In turn, hypoechogenic structures may appear anechogenic (anechoic) when US is completely attenuated or trans-
sonorous when the waves are neither attenuated nor reflected toward the emitting source.
A characteristic of ultrasound echoes applied in the clinical setting is the so-called Doppler effect, which occurs
when the ultrasound beam encounters a moving structure in its path. As a result of such contact, the
314
TABLE 17-10 -- ULTRASONOGRAPHY IMAGES OF THE TISSUES IDENTIFIABLE DURING SONOGRAPHIC STUDY OF THE
BRACHIAL PLEXUS TERRITORIES
Tissues Ultrasound Image Artifacts
Venous vessels Compressible, anechoic
Arterial vessels
Fat Pulsatile, anechoic
Muscle: Hypoechoic
Perimysium Hyperechoic
Muscle tissue Hypoechoic
Tendons Intensely hyperechoic Anisotropy (hypoechoic)
Cartilage Fine band, anechoic
Nerves Hyperechoic Anisotropy (hypoechoic)
Bone Intensely hyperechoic line, with acoustic shadow
Air (lung) Anechoic
frequency of the reflected echo is modified, and an analysis of the corresponding frequency difference can inform us
of the velocity of the moving structure (e.g., blood within the vascular lumen).
The images seen on the echograph screen can depend on the tissue through which the sound travels (tissue images),
or on the separation zones between tissues (contour images). In turn, contour images can be (1) anatomic (or wall)
images when two tissues are separated by an anatomically identifiable structure with a distinct acoustic impedance;
or (2) interface (or separation) images, in the presence of different acoustic impedances without any actual anatomic
separation between them. On the other hand, tissue images can exhibit (1) fluid patterns, characterized by the
absence of echoes with posterior enhancement and lateral shadowing (e.g., blood vessels); (2) solid patterns,
characterized by dispersed internal echoes that can be either homo- or heterogeneous; (3) mixed patterns; and (4)
acoustic shadows, beyond which echoes are no longer generated. Acoustic shadowing occurs when US crosses
interfaces with great differences in acoustic impedance (e.g., air and bone interfaces).
The US characteristics of the different body tissues are shown in ( Table 17–10 ). Water is the body element that
[47] [48]
best transmits ultrasound waves, generating a black (anechoic) image. Thus, highly cellular tissues containing
abundant water can be expected to be hypoechoic, whereas more fibrous tissues containing less water and a larger
number of interfaces are characteristically hyperechoic.
Anatomic Considerations and Ultrasonography Puncture Techniques
An essential requirement for applying US in locating the brachial plexus is a detailed classic topographic (i.e.,
structures by planes) and sectional anatomic
TABLE 17-11 -- ANATOMIC CHARACTERISTICS OF INTEREST FOR ACCESSING THE BRACHIAL PLEXUS UNDER
ULTRASONOGRAPHC GUIDANCE
Interscalene Supraclavicular Infraclavicular Axillary

Anatomic Supraclavicular fossa Supraclavicular fossa Pectoral Arm
zone
Plexus Roots and trunks Trunks and divisions Divisions and cords Terminal nerves
zone
Landmarks
Bony Clavicular transverse processes Collarbone Collarbone, coracoid process Humerus
Vascular Carotid + vertebral artery Subclavian artery + Axillary artery + vein Humeral artery + vein
Internal jugular vein vein
Muscular Sternocleidomastoid, anterior, Greater and smaller pectoral Greater pectoral, coracobrachial,
middle, and posterior scalene biceps, triceps
315
TABLE 17-11 -- ANATOMIC CHARACTERISTICS OF INTEREST FOR ACCESSING THE BRACHIAL PLEXUS UNDER
ULTRASONOGRAPHC GUIDANCE
Interscalene Supraclavicular Infraclavicular Axillary

Depth 1–3 cm 1–3 cm 3–6 cm 1–3 cm
knowledge of the region in which the plexus is found. The topographic anatomy of the zone allows us to identify the
successive structural layers down to the actual plexus and facilitates identification of near-lying related elements.
Sectional anatomy in turn facilitates identification of the structures seen on screen during US guidance.
The different brachial plexus anesthetic approaches involve puncture in quite distinct anatomic zones that must be
familiar to the anesthetist to ensure a safe and successful technique. From its origin in the neck, the brachial plexus
ends in the form of terminal or end-nerves in the arm, running through three anatomically differentiated zones that
in turn correspond to the different anesthetic approaches used: the supraclavicular region, the infraclavicular (or
anterior shoulder) region, and the axillary (or arm root) region. The supraclavicular region is used to perform
interscalene and supraclavicular punctures, whereas the infraclavicular region is used to perform infraclavicular
techniques, and the axillary, or armpit and root part of the arm region is used for access to the brachial plexus (
Table 17–11 ).
SUPRACLAVICULAR REGION
Topographic Anatomy
The supraclavicular region has well-defined limits, with the collarbone located at the base, the posterior margin of
the sternocleidomastoid muscle located anteriorly, and the trapezius muscle located posteriorly. This triangle is
identified by the skin depression found within its limits: the supraclavicular fossa.
The supraclavicular fossa is covered by the skin, the subcutaneous lax tissue, and the cutaneous supra-acromial and
supraclavicular branches of the superficial cervical plexus. The second layer comprises the superficial cervical
aponeurosis, or fascia, that envelops the muscles defining the limits of the supraclavicular region (i.e., the
sternocleidomastoid and trapezius muscles). A third anatomic layer in turn contains the middle cervical aponeurosis,
enveloping the omohyoid muscle that crosses the supraclavicular region; the muscle can be easily identified by
palpation, and the external jugular vein runs along its surface.
The deep zone of the middle cervical aponeurosis contains structures that the anesthetist should know and be able to
associate with the corresponding sectional anatomic characteristics. The anterior scalene muscle originates in the
anterior tubercles of the fourth, fifth, and sixth transverse processes of the cervical vertebrae, and inserts in
Lisfranc’s tubercle on the anterior aspect of the first rib. At its insertion, the anterior scalene muscle divides two
important vascular structures—the subclavian artery (located posterior to the muscle) and the subclavian vein (lying
anterior to the muscle). Posterior to the subclavian artery is the brachial plexus, which lies on the anterior belly of
the middle and posterior scalene muscles. The middle scalene muscle originates in the posterior tubercles of the
transverse processes of four to five of the first cervical vertebrae and inserts in the external margin of the first and
second ribs. The posterior scalene muscle in turn originates in the posterior tubercles of the fourth, fifth, and sixth
cervical vertebrae, and inserts in the external aspect of the second and third ribs.
This zone possesses an important vascular component. The subclavian artery gives rise to the cervical artery, which
penetrates through the intertransverse foramina (from the sixth cervical vertebra) located anterior to the outlet of the
spinal nerves through the conjugate foramina. The thyrocervicoscapular trunk gives rise to the inferior thyroid
artery, the ascending and superficial cervical artery, and the suprascapular artery. Finally, the superior scapular (or
coracoid) artery crosses the supraclavicular region to become the axillary artery.
Sectional Anatomy
The sectional anatomy depends on the level at which the ultrasound image is acquired, which is in turn dependent on
the specific anesthetic technique employed. When the interscalene technique is performed, the region of interest is
the neck, whereas in the case
316
Figure 17-21 Two-dimensional ultrasonography image across the transverse interscalene at the C6 level, identifying the different muscles and
vascular structures in the neck region (A). Three hypodense nodular structures located between the scalene muscles (arrows) (B) and
corresponding to the trunks of the brachial plexus can be observed. A, Carotid artery; V, internal jugular vein.
of the supraclavicular anesthetic approach, ultrasound imaging focuses on the supraclavicular region.
The cross-sectional anatomy at the level of the sixth cervical vertebra allows us to identify the sternocleidomastoid
muscle, whereas medial to the latter lies the common carotid artery and the internal jugular vein. Posterior to these
vessels are the scalene muscles—the anterior scalene muscle posterior to the vessels, followed posteriorly by the
middle and posterior scalene muscles that conform to a single muscle mass. Between the scalene muscles, small
round or oval nodules corresponding to the nerve roots and/or trunks of the brachial plexus can be identified. More
medial to the interscalene region lies the transverse process of the sixth cervical vertebra, with the vertebral artery
and vein located anterior to the latter structure.
A sagittal study at the level of the supraclavicular fossa enables identification of the collarbone, with the subclavian
muscle lying caudad and the subclavian vein on the first rib. In a posterior plane are the omohyoid muscle and the
subclavian artery. In the posterosuperior portion of the artery lies the brachial plexus. These structures are easily
identified by US with the exception of the elements located posterior to the collarbone (because of the acoustic
shadowing effect of the bone).
Ultrasonographic Anatomy Applied to Plexus Anesthesia
The interscalene techniques are performed over the cervical region, in the interscalene sulcus or groove. US
assessment of the neck region requires the use of high-resolution devices because of the anatomic complexity of the
zone. The availability of Doppler imaging in turn facilitates identification of the vascular structures, thereby greatly
facilitating localization of the different anatomic spaces. The ultrasound transducer should operate at 7.5 MHz to 10
MHz to identify and evaluate the important muscle and vascular references found superficially. The global anatomy
can be identified by cross-sectional imaging at the level of the sixth cervical vertebra ( Fig. 17–21 ). Superficially,
there is the clavicular belly of the sternocleidomastoid muscle, and internal to the latter muscle lie the internal
jugular vein and the carotid artery, along with the anterior and middle-posterior interscalene muscles. Between the
anterior and middle scalene muscles can be seen a separation with US characteristics corresponding to fatty tissue,
where hypodense nodules (trunks of the brachial plexus) can be identified. At a deeper level, there is the acoustic
[46]
shadowing effect (i.e., bone pattern) of the cervical transverse process; here, Doppler imaging can help to identify
the vertebral vessels.
To perform the anesthetic technique, the needle should be inserted deep into the interscalene space under direct
visual guidance. The injected anesthetic solution floods the interscalene space but also spreads around the anterior
317
scalene muscle to reach the carotid artery, thereby inducing the most constant undesirable effect associated with
[49]
interscalene block of the brachial plexus: phrenic nerve paralysis. [50]
The supraclavicular techniques are performed over the supraclavicular space, where the superior, middle, and
inferior primary trunks divide into their respective anterior and posterior branches. The plexus runs very
superficially at this level; high-frequency (10 MHz) transducers should, therefore, be used to identify the
Figure 17-22 Sagittal supraclavicular cross-section. There is a sectional image at the level of the first rib, showing the different vascular
structures of the supraclavicular region (A), and identifying hypodense nodular structures in the superoposterior portion of the subclavian artery,
corresponding to the divisions of the brachial plexus (arrows) (B). A, subclavian artery; V, subclavian vein.
structures. In addition, technical difficulties are found when the supraclavicular zone is studied, owing to the
presence of the supraclavicular depression, which complicates manipulation of the transducer and the puncture.
Finally, although the important primary trunks of the brachial plexus are easily identified in the interscalene space,
identification is more difficult in the supraclavicular zone. Although color Doppler imaging is not necessary to
identify the subclavian vein, it greatly facilitates identification of the brachial plexus by differentiating between the
nerves (hypoechogenic structures with no Doppler effect) and arterial and venous branches located in the zone
(likewise hypoechogenic although producing a Doppler effect). The US anatomy of the supraclavicular region can
be seen in Figure 17–22 .
In performing the anesthetic technique, identification of the nerve branches is an important consideration. In effect,
when the nerves have been identified, the needle is inserted into the depth of the plexus along its vertical axis. This
insertion takes place under visual guidance to avoid medial displacement and the risk of pleural puncture. However,
if the nerves have not been identified, half of the anesthetic solution should be injected into the zone posterior to the
subclavian artery; the other half of the solution should be reserved for the posterosuperior zone of the artery below
the omohyoid muscle. [51]
INFRACLAVICULAR REGION
Topographic Anatomy
The limits of the infraclavicular region are well defined, with the collarbone above, the lower margin of the greater
pectoral muscle below. The deltopectoral sulcus is external, and the vertical line is traced from the center of the
collarbone to the lower margin of the greater pectoral muscle internally.
The infraclavicular region is covered by skin and subcutaneous lax tissue. The second layer in turn contains the
superficial aponeurosis of fascia that covers the greater pectoral muscle and extends toward the deltoid muscle
through the deltopectoral sulcus. The third layer, or plane, contains the greater pectoral muscle, whereas a fourth
318
anatomic layer presents the middle axillary aponeurosis or clavipectoral fascia, containing the subclavian muscle
and extending past the smaller pectoral muscle to the axillary fascia. The deep zone of the clavipectoral fascia
contains the axillary fossa (of which it forms the anterior wall). The axillary fossa in turn contains the neurovascular
bundle. The most medial structure of the latter is the axillary vein, followed by the axillary artery and the three cords
or fascicles of the brachial plexus laterally. On reaching the region of the smaller pectoral muscle, the neurovascular
bundle runs deeper, and the nerve fascicles are found around the artery. The axillary vein is formed as a result of the
joining of the brachial veins, receiving the cephalic vein along its axillary trajectory at the level of the deltopectoral
triangle. The axillary artery in turn gives rise to the thoracoacromial, long thoracic, subscapular, and humeral
circumflex arteries.
Sectional Anatomy
The sagittal plane sectional anatomy of the infraclavicular region corresponds to the anterior wall of the axillary
space, or fossa. Consequently, the collarbone and greater pectoral muscle are found here anteriorly, followed
medially by the subclavian muscle, the clavipectoral fascia, and the smaller pectoral muscle. Within this muscle-
aponeurotic wall can be identified the neurovascular bundle—the vein lying caudad, the artery medial, and the
secondary trunks of the brachial plexus cranial. If the imaging section is acquired at the distal infraclavicular level
(i.e., in the subacromial zone), the acromion can be identified, with the insertion of the smaller pectoral muscle and
the neurovascular bundle lying immediately posterior to this muscle. At this level, the secondary trunks and end
branches of the brachial plexus are distributed around the axillary artery.
Ultrasound Anatomy Applied to Plexus Anesthesia
The infraclavicular techniques are performed over the pectoral region, which is easily evaluated by US in view of
the simplicity of its anatomic structures. Doppler imaging in turn allows identification of the vascular components,
particularly the divisions of the axillary vessels; thereby accidental vascular puncture (the most common
complication of the infraclavicular techniques) is avoided. Because of the greater depth at which the brachial
[32]
plexus is found in this territory compared with other anesthetic approaches, a lower frequency (5 to 7.5 MHz)
transducer may be indicated to identify the structures.
The proximal infraclavicular techniques are performed over the midclavicular point. At this level, the plexus is
relatively superficial (3 cm–5 cm), and is located beneath the subclavian muscle and clavipectoral fascia. The plexus
lies cranial and external to its most important reference—the axillary artery. At this level, the anterior and posterior
divisions of the plexus group or merge to form the secondary trunks. Doppler US can identify the thoracoacromial
branch of the axillary artery, which arises at this level. To perform puncture, most of the local anesthetic volume
should be injected into the posteroexternal part of the axillary artery; however, Ootaki and colleagues obtained
[53]
excellent clinical results (95% success rate) by administering equivalent 30-mL volumes at both sides of the axillary
artery.
The distal (or coracoid) infraclavicular techniques are performed in the distal zone of the infraclavicular plexus, at
the level where the terminal nerves are formed. The anatomic zone corresponds to the axillary neurovascular bundle,
which runs beneath the smaller pectoral muscle. At this level, the neurovascular bundle depth is 4 to 5 cm; therefore,
lower frequency (3.5 MHz–7.5 MHz) transducers are required for US imaging. At this level ( Fig. 17–23 ), the thick
muscle space of the greater and smaller pectoral muscles can be identified, separated by a hyperechogenic band
corresponding to the perimysium. The end branches of the brachial plexus are located at this level, around the
axillary artery. The branches of the brachial plexus are difficult to visualize at this level; consequently, the local
anesthetic solution should be administered around the axillary artery. The technique proposed by Ootaki and
colleagues is, therefore, not applicable here.
[53]
PROXIMAL REGION OF THE ARM AND THE AXILLARY FOSSA

Topographic Anatomy
In the region of the arm, the neurovascular bundle is located in the internal bicipital sulcus, or groove,
319
Figure 17-23 Sagittal infraclavicular cross-section. Sectional image corresponding to the pectoral zone (anterior wall of the axilla), showing the
different muscles and vascular structures in the region (A); hypodense nodular structures are seen around the axillary artery (B) (arrows),
corresponding to the cords of the brachial plexus. A, axillary artery; V, axillary vein.
separating the flexor muscle mass (biceps) from the extensor muscle (triceps). Here, again, the first layer comprises
the skin and subcutaneous lax tissue, whereas a second layer contains the superficial aponeurosis or fascia that
covers the medial bicipital sulcus and continues with the aponeuroses of the flexor and extensor muscles of the arm.
Following the superficial aponeurosis and within the bicipital sulcus lies the neurovascular bundle, with vein and
nerves on the surface and the brachial artery in depth. Beyond the superficial aponeurosis lies the flexor muscle
layer, composed ventrally and superficially of the inferior insertions of the deltoid and biceps muscles, and with the
coracobrachial and anterior brachial muscles located more in depth. In the posterior or extensor region of the arm,
there is a single muscle layer corresponding to the three portions of the triceps muscle. The humerus is in turn
located in the deepest region.
Sectional Anatomy
The sectional anatomy of the zone medial to the insertion of the deltoid muscle presents the internal bicipital sulcus
(seen as a hyperdense structure on US scan), with two humeral vessels—the vein superficially and the artery lying
inernal to the latter. At this level, the end branches of the brachial plexus separate, terminating in their
corresponding innervation territories. The radial nerve is located in the depth of the sulcus, whereas the median and
ulnar nerves accompany the artery over its more superficial portion ( Fig. 17–24 ).
Ultrasound Anatomy Applied to Plexus Anesthesia
The axillary techniques are performed in the region of the internal bicipital sulcus. US assessment requires the use
of high-resolution and high-frequency (10 MHz) transducers, because of the superficiality of the neurovascular
structure (1–2 cm). Color Doppler imaging provides little additional information, because the vascular elements are
easily indentifiable and palpable at this level. Puncture under US guidance consists of distribution of the local
anesthetic solution both behind and in front of the humeral artery. However, Kapral and colleagues obtained their [51]
best results by placing the anesthetic volume between the humeral artery and vein, an observation that can be
explained by their choice of puncture site, located very close to the root of the arm.
Clinical Trials with Ultrasound-Guided Plexus Anesthesia
Friedl and Fritz presented a technique for accessing the brachial plexus at axillary level, using a linear 7.5 MHz
[54]
transducer. They recommended application of this technique if the brachial artery could not be well identified by
320
clinical examination, thereby avoiding neurologic deficits resulting from direct puncture and injection of anesthetic
into the nerves.
Yang and coworkers, using high-resolution US guidance with a broadband L10 5-MHz transducer (HDI 3000;
[49]
ATL Bothell, Wash), inserted a catheter into the interscalene brachial plexus sheath and evaluated location using
radiography and computed tomography (CT) after the injection of contrast material. Successful neural blockade at
20 minutes and postoperative analgesia were achieved in all patients. On the other hand, 6 of 15 patients who
consented to regional anesthesia required general anesthesia because blockade proved incomplete.
Figure 17-24 Axillary transverse cross-section. Sectional image corresponding to the proximal zone of the arm, showing the different muscles
and vascular structures (A), and identifying hypodense nodular structures around the axillary artery (B) (arrows), corresponding to the terminal
nerves of the brachial plexus. A, humeral artery; V, humeral vein.
Kapral and coworkers, using a 5- to 7-MHz transducer, reported a 95% surgical anesthesia rate with both the
[51]
supraclavicular and axillary technique, whereas anesthesia was only partial in the remaining 5% of cases. No
complications attributable to the techniques were observed.
More recently, Ootkai and coworkers, using real-time US guidance for plexus block at the infraclavicular level,
[53]
concluded that the approach could be used as an alternative to the anatomic references or landmark-guided
technique. Attached to the US transducer (7.0 MHz), and for effective needle manipulation, we used a needle guide,
keeping needle pass within the US beam (UAGV021A-Toshiba). For plexus block, a 23-G, 60-mm needle was
inserted toward the medial aspect of the subclavian artery under real-time US guidance, and the local anesthetic was
injected near the subclavian artery, 15 mm medial and 15 mm lateral to the vessel. Complete sensory block was
achieved in 100% of patients for the musculocutaneous and medial antebrachial cutaneous nerves; in 96.7% for the
median nerve; and in 95% for the ulnar and radial nerves. In turn, complete motor block was achieved in 100% of
patients for the musculocutaneous nerve; in 96.7% for the median nerve; in 90% for the ulnar nerve; and in 93.3%
for the radial nerve. No complications were recorded.
In conclusion, US guidance for accessing the brachial plexus will undoubtedly find a place in plexus anesthesia for
the teaching of anesthetic techniques, application to concrete clinical situations (involving patients in whom the
classic anatomic landmarks for blind puncture are difficult to identify), or for systematic application in clinical
practice.
321
3-in-1 Block
Recently it has been demonstrated that the use of US improves the onset time and the quality of sensory block for 3-
in-1 blocks compared with conventional PNS technique. The present study was designed to evaluate whether US
[55]
guidance for 3-in-1 blocks reduces the amount of local anesthetic required compared with blocks conducted by PNS
guidance ( Fig. 17–25 ).
TECHNIQUE
Sixty patients undergoing hip surgery after trauma were randomly assigned to three groups of 20 patients each. In
group A, the 3-in-1 block was performed using US guidance with 20 mL of bupivacaine, 0.5%. Group B received 20
mL of bupivacaine, 0.5%, and group C received 30 mL bupivacaine, 0.5%, during PNS guidance. The quality of the
block and the onset time were assessed by pinprick test in the central sensory region of each of the three targeted
nerves and compared with
Figure 17-25 Ultrasonographic picture of the major anatomic structures of the 3-in-1 block (right side). N, femoral nerve; A, femoral artery; IPF,
iliopectineal fascia; S, skin surface.(From Marhofer P, Schrogendorfer K, Wallner T, et al: Reg Anesth Pain Med 23:584–588, 1998.)
the contralateral leg every 10 minutes for 1 hour by a blinded observer. The rating was undertaken using a scale
from 100% (uncompromised sensibility) to 0% (no sensation).
RESULTS
Overall success rates for the 3-in-1 block were 95% in group A, 80% in group B, and 80% in group C. Onset time
was significantly shorter in the US-guided compared with both PNS-guided groups (group A 13 ± 6 min; group B
27 ± 12 minutes; and group C 26 ± 13 min; <.01 to groups B and C). Quality of sensory block was significantly
better in group A (4% ± 5% of initial value) compared with groups B and C (group B 21% ± 11% of initial value,
<.01 to group A; group C 22% ± 19%, <.01 to group A).
322
Conclusion
The authors of this study concluded that the amount of local anesthetic for 3-in-1 blocks could be reduced by using
US guidance compared with the amount required in the convention PNS-guided technique. [55]
AIDS TO NERVE LOCATION BY RADIOLOGIC IMAGING

P. Prithvi Raj
Fluoroscopy
Lanz and Theiss reported that the brachial plexus block near the first rib at the level of the trunks and divisions
[56]
provided the most reliable efficacy. Despite this advantage, the use of the approach near the first rib is limited
because of the risk of pneumothorax. Eliciting paresthesias is also important to obtain a high degree of
[57] [58] [59] [60] [61]
success. However, paresthesias are uncomfortable for patients and may result in nerve injury.
[57] [62]
To [63] [64] [65] [66] [67]
perform the brachial plexus block safely and quickly while obtaining a reliable effect and without making patients
uncomfortable, Theiss performed the supraclavicular approach using the contrast medium under fluoroscopic
guidance. He advanced the needle near the first rib and posterior to the subclavian artery, which he thought was in
the interscalene space (Figs. 17–26 (Figure Not Available) and 17–27 (Figure Not Available) ). The subclavian
artery was identified by the groove where the first rib starts to curve posteriorly. During injection, Theiss corrected
the
Figure 17-26 (Figure Not Available) The part of the first rib that the tip of the needle should touch defined by plotting the points that the tip of
the needle touched in the first 80 successful blocks. a, artery; v, vein; m, muscle.(From Nishiyama M, Naganuma M, Amaki Y, et al: A new
approach for brachial plexus block under fluoroscopic guidance. Anesth Analg 88:91–97, 1999.)
placement of the tip of the needle, because the direction of the needle depends on the patients’s anatomic
characteristics, such as size of the first rib and its angle to the vertebra. Whether eliciting paresthesias causes nerve
injury remains controversial. However, it is an uncomfortable experience for the patient. Avoiding
[63] [64] [65] [66] [67]
paresthesias is one of the advantages of the supracostal approach. Theiss believed that the needle could be advanced
to touch the first rib within 5 to 10 seconds; therefore, the risk from radiation exposure was minimal.
More than 2000 blocks have been reported by Theiss, with no clinically significant complications. There is,
however, the possibility that the practitioner who has little experience in performing nerve blocks under fluoroscopic
guidance may improperly advance the needle and insert it into the lung or the subclavian artery.
There were four failures in the study by Lanz and Theiss. The placement of the tip of the needle did not correspond
to the proper part of the first rib. In two blocks, the needle was too far to the outside of the rib; in one block, it was
too close to the subclavian artery; and in one block, it was too close to the vertebra. To avoid puncturing the
subclavian artery and the brachial plexus, the authors recommended that the needle insertion be 1 cm lateral to the
palpated subclavian artery and 1 to 2 cm above the clavicle. Under fluoroscopic guidance, one should be able to
advance the needle and place the tip on the proper part of the first rib.
Computed Tomography Guidance
The role of imaging-guided therapy for delivery of regional anesthesia for pain management and treatment of
patients with brachial plexopathies is an important area that has received little attention. Causes of [69] [70] [71] [72] [73] [74] [75]
such chronic brachial plexopathies include stenosis of the cervical neural foramina, which causes a
mononeuropathy; neoplastic invasion of the brachial plexus by Pancoast’s tumor or metastases; and plexopathies
that result from prior treatment. Treatment for such patients often includes percutaneous nerve root block. The site
of needle insertion is based on palpation of surface anatomic landmarks. At times, the normal surface
[76] [77] [78] [79] [80]
landmarks may be difficult to palpate in patients who have short, thick necks or who have undergone surgery or
radiation therapy. These conditions often result in an inability to properly localize
Figure 17-27 (Figure Not Available) A, Brachial plexus block for pain relief of recurrent Pancoast’s tumor. Coronal nonenhanced T1-weighted
image (repetition time, 600 msec; echo time, 14 msec) depicts a mass situated in the apex of the left lung, as well as obliteration of the apical fat
323
and encasement of the left brachial plexus. On the contralateral side, note the normal appearance of the apical fat and brachial plexus. B,
Transverse computed tomography scan obtained after injection of the solution of local anesthetic and contrast material shows the majority of the
solution to be distributed between the anterior and the middle scalene muscles. C, Transverse computed tomography scan at the thoracic inlet
depicts contrast material extending along the neurovascular bundle of the subclavian artery and vein, which indicates that the solution is to
contact the brachial plexus. The patient experienced approximately 50% reduction in pain immediately after the injection. (A–C from Nishiyama
M, Naganuma M, Amaki Y, et al: A new approach for brachial plexus block under fluoroscopic guidance. Anesth Analg 88:91–97, 1999.)
the anatomic site for needle insertion and may cause incorrect needle placement. The result is often inadequate pain
control.
Imaging guidance may be used to guide percutaneous nerve root block by helping to localize the optimal site of
needle insertion and to identify the extent of analgesic distribution that would provide optimal pain relief. Mukherji
described a technique for brachial plexus block guided with CT and reported initial results for regional pain
management in patients with chronic pain referable to the brachial plexus and surface landmarks that cannot be
palpated.
Technique
Six brachial plexus block procedures guided by CT in five patients (three male and two female; age range, 33 to 72
years; mean age, 52.2 years) were performed. All patients had chronic neuropathic pain that was believed to
originate from the brachial plexus. Because the surface landmarks were difficult to palpate on clinical examination
in these patients, the procedures were done with imaging guidance.
The second and third patients had cervical mononeuropathies, and the blocks were performed as diagnostic
procedures before foraminotomy to help confirm that the pain was originating from nerve root components of the
brachial plexus ( Fig. 17–28 ). One procedure was performed in the fifth patient, who had recurrent Pancoast’s
tumor ( Fig. 17–29 ); he underwent a second procedure 6 weeks after the original diagnostic block to duplicate the
pain relief received from the initial procedure.
Even though CT guidance is not commonly indicated, this technique should be kept in mind for difficult patients,
especially when neurolytic techniques have to be used (e.g., for trigeminal or sphenopalatine gangliolysis).
324
Figure 17-28 A, Brachial plexus block to treat a left C7 mononeuropathy. Transverse contrast-enhanced computed tomography (CT) scan, obtained after the skin over
the brachial plexus was marked with barium (arrows), was acquired to help identify the locations of the common carotid artery (C), internal jugular vein (J), and
vertebral artery (V). A, anterior scalene muscle; M, middle scalene muscle. B, Transverse CT scan demonstrates the tip of the needle inserted into the plane separating
the anterior (A) and middle (M) scalene muscles. C, Transverse CT scan helps to confirm that the solution (2 mL) (arrow), which contains lidocaine and water-soluble
contrast material and is injected through the needle, is located between the planes of the anterior and middle scalene muscles and thereby must involve the
supraclavicular brachial plexus. The patient experienced complete pain relief immediately after the injection. (A–C from Mukherji S, Wagle A, Armao D, Dogra S:
Brachial plexus nerve block with CT guidance for regional pain management: Initial results. Radiology 216: 886–890, 2000.)
325
Figure 17-29 A, Brachial plexus block for pain relief for recurrent Pancoast’s tumor. Coronal nonehanced T1-weighted image (repetition time, 600 msec; echo time, 14 msec) depicts a mass (M)
situated in the apex of the left lung, as well as obliteration of the apical fat and encasement of the left brachial plexus. On the contralateral side, note the normal appearance of the apical fat
(arrowhead) and brachial plexus (arrows). B, Transverse computed tomography (CT) scan obtained after injection of the solution of local anesthetic and contrast material shows the majority of
the solution to be distributed between the anterior (A) and middle (M) scalene muscles. C, Transverse CT scan at the thoracic inlet depicts contrast material (small arrows) extending along the
neurovascular bundle (large arrow) of the subclavian artery and vein, which indicates that the solution is in contact with the brachial plexus. The patient experienced approximately 50%
reduction in pain immediately after the injection. (A–C from Mukherji S, Wagle A, Armao D, Dogra S: Brachial plexus nerve block with CT guidance for regional pain management: Initial
results. Radiology 216:886–890, 2000.)
THE ANESTHETIC LINE

Paolo Grossi
Placing the patient in the position most frequently employed for the interscalenic, supraclavicular, and
infraclavicular blocks, with the head turned to the side opposite to the procedure site and the arm abducted at a 45-
degree angle to the trunk, it can be seen that all the cutaneous landmarks used in these approaches are on a straight
[79]
line from the apex of the triangle of the scalene muscles and ending with the axillary artery in the axilla. This line
may be denoted as the “anesthetic line” ( Fig. 17–30 ). The line is drawn to connect the following landmarks: (1) the
apex of the scalene triangle at C5, (2) the midpoint of the clavicle, (3) the sulcus of the deltoid and pectoralis located
between the coracoid process and the chest, and (4) the axillary artery’s pulse in the axilla.
This observation of the correlation of the three-dimensional structure of the brachial plexus, with a straight line
connecting various fixed anatomic landmarks, allows the anesthesiologist to select from a number of different
standard techniques of blocking the brachial plexus. Moreover, the ability to view the brachial plexus as a single
three-dimensional linear unit extending from the cervical column to the arm simplifies the instruction process and
lends itself to a
326
Figure 17-30 The anesthetic line. The top is the apex of the scalenic triangle; it then passes through the middle point of the clavicle, the deltopectoral sulcus, to the
point of palpation of the axillary artery.
safer and more consistent method of performing the blocks of the brachial plexus.
In addition, through the use of anesthetic line technique, I have developed several variations of this method based on
the inclination of the needle. These variations use a vertical or tangential inclination of the needle with respect to the
plexus to control the preferential spread of the local anesthetic to higher or lower segments. Also, this control of the
inclination of the needle and an understanding of the three-dimensional anatomy of the anesthetic line aids in the
catheterization of the brachial plexus.
The Anesthetic Line and the Interscalene Approach
A new approach to the interscalene block of the brachial plexus, which departs from Winnie’s classic approach to [79]
blockade of the brachial plexus, is proposed. This approach uses the anesthetic line as its point of perspective in the
performance of the block. With the patient placed supine and the skin prepared and draped in a sterile manner, the
[80]
anesthetic line is traced on the skin of the patient with the arm abducted at a 45-degree angle. Next, with the needle
positioned parallel to the anesthetic line, the needle is advanced cranially and medially into the scalene triangle
approximately 2 cm lower than in Winnie’s point of entry. After entering the skin at this point, the sheath of the
fascia of the brachial plexus is entered in a smooth and precise manner. At a shallow depth of approximately 1 cm to
2 cm, it is possible to elicit twitches of the deltoid muscle with the use of a PNS. This guides and confirms needle
placement within the brachial plexus. It should be noted that with this technique the needle is a relatively long
distance from the major vessels and there is a greatly decreased risk of Horner’s syndrome
327
Figure 17-31 The cephalad direction of the needle follows the anesthetic line; the hub is placed on the firm surface of the clavicle and the entry
point is 1 cm below the apex of the scalenic triangle.
because there is less risk of perforating the posterior fascia of the brachial plexus. The superficial cervical plexus
can be blocked by pulling the catheter tip subcutaneously ( Figs. 17–31 and 17–32 ).
The Anesthetic Line and the Infraclavicular Approach
Figure 17–33 illustrates what has been mentioned regarding the interscalene approach that is valuable for optimizing
the infraclavicular approach to the brachial plexus.
The patient is placed with the arm abducted 45 degrees from the body, and the anesthetic line is drawn on the skin as
described. The difference from the original Raj technique is the position of the arm, which is not abducted to 90
[80]
degrees. The original position favors a more superficial localization of the plexus that, at the same time, is more
widened and much easier to detect. With the help of the line, the technique offers the chance to enter the plexus in a
vertical way with a variety of possible approaches (immediately under the clavicle and at every single point from the
coracoid process to the base of the axilla). It is comfortable for the patient if the operator raises a skin wheal before
introducing the stimulating needle, which elicits peripheral twitches including the typical ones related to the
innervation of the musculocutaneous nerve.
LOWER LIMB: FEMORAL NERVE
The block of the femoral nerve at the inguinal ligament is usually obtained by first locating the femoral artery
328
Figure 17-32 Represents the block of the posteroinferior branch of the superficial cervical plexus. The needle, after having blocked the brachial plexus through the
interscalene route, is withdrawn to the subcutaneous tissues and directed posteriorly, behind the sternocleidomastoid muscle, at a distance of 2 cm, where the local
anesthetic solution of 3 to 4 mL is injected.
Figure 17-33 Infraclavicular approach. Perpendicular to the anesthetic line and 2 cm distal to the coracoid process, the brachial plexus is blocked,
including the musculocutaneous nerve.
along a line that connects the anterior superior iliac spine to the pubic tubercle. After the pulsation of the artery is
detected, a needle is inserted perpendicularly, or parasaccularly, with a cranial direction, until the typical twitches of
the patella are elicited using an electrical PNS.
In some cases, it is difficult to detect the nerve, which, after a wide lateral or medial scanning, may appear to be
more medial or lateral to the expected site. This may be relative to individual anatomic variation, but, more often,
the cause is incorrect positioning of the patient. The patient must be placed in a supine position with the limb at zero
degree of frontal rotation; this means that the point of pulsation of the femoral artery, the center of the patella at the
middle point between the malleolus, must be on a single line. If the limb is extrarotated, the nerve will be dislocated
more laterally; the opposite occurs when the limb is intrarotated, with the nerve nearer to the artery.
329
If a line is traced between the described points, the anesthesiologist can obtain a more anatomically correct
positioning of the structures, and the “line” will assist entry near the nerve with a correct perpendicular or vascular
technique ( Fig. 17–34 ).
SCIATIC NERVE: POSTERIOR APPROACH (THE LABAT POSITION)
The patient is placed in a lateral position, with the thigh flexed at a 90-degree angle to the body, to let the sciatic
nerve localize in the iliac bone incisura, or in a fixed-bone position. This position avoids the flotation of the nerve in
the soft tissues that are surrounding it, thus determining more difficulties in the localization with an insulated needle.
The contralateral limb rests in a position that is comfortable for the patient, usually half-flexed. A line is drawn
connecting the central point of the condylus lateralis of the femur, the central point of the femoral great trochanter,
and the hiatus sacralis. At the middle point of the segment of the line between the great trochanter and the hiatus
sacralis, the needle (120 mm–150 mm) is directed perpendicular to the line, at a 90-degree angle to the skin. When
the nerve is approached, the typical peripheral twitches are elicited. Usually, a higher percentage of results is
obtained with multiple twitch elicitation ( Fig. 17–35 ).
A posterior view of the patient, showing an anatomic preparation of the sciatic nerve, exhibits a longitudinal
pathway of the nerve from the exit point of the foramen ischiadicus to the superior angle of the popliteal fossa,
where it divides into the two main branches: popliteal nerve and external sciaticus popliteus.
When the patient is prone, a line is drawn from the middle point of a line connecting the great trochanter and the
hiatus sacralis to the apex of the popliteal fossa. All along this line, at a variable depth (8 cm–2 cm) an insulated
needle inserted perpendicular to the skin may reach the sciatic nerve ( Fig. 17–36 ).
Conclusion
The anesthetic line, which clearly describes the straightforward relationship of the brachial plexus structure with a
straight line and several superficial, easily noted landmarks, leads to a better understanding of how the plexus is
positioned. This is particularly important for beginners and greatly aids their localization of the brachial plexus,
increasing their chances of achieving successful blocks, whether they are attempting to block the brachial plexus
from above or below the clavicle. Following the described technique reduces the risk of pleural or vessel injuries
and decreases the trainees’ fears of complications. This concept may be extended to blocks of the lower limb. The
aim in this case is not simply to represent an anatomic drawing on the skin, reproducing the underlying nerve
pathways, but to give a guide for a correct, topographic introduction of the localizing needle.
330
Figure 17-34 Anterior approach to the femoral nerve. The line indicates normal rotation of the limb: (A) The intermalleolar middle point, (B) the
middle point between the femoral epicondylar processes, and (C) the femoral artery pulsation.
Figure 17-35 Posterior approach to the sciatic nerve. The thigh is flexed at a 90-degree angle to the body. The line connects: (A) The central
point of the lateral femoral condylus, (B) the central point of the great trochanter (GT), (C) the middle point between the GT and the HS, and (D)
the hiatus sacralis.
331
Figure 17-36 Posterior approach to the sciatic nerve. The patient is prone, and the line indicates the direction of the sciatic nerve to the popliteal
fossa: (A) The middle point between the GT and the HS, (B) the great trochanter (GT), (C) the hiatus sacralis (HS), (D) the intercondylar middle
point in the popliteal fossa, and (E) the intermalleolar middle point.
REFERENCES
1. Perthes VG: Uker leitungsanästhesie unter zuhilfenahme elektrischer reizung. Munch Med Wochenschr 47:2545–2548, 1912.
2. Pearson RB: Nerve block in rehabilitation: A technic of needle localization. Arch Phys Med Rehabil 36:631, 1955.
3. Greenblatt GM, Denson JS: Needle nerve stimulator-locator. Anesth Analg 41:599–602, 1962.
4. Wright BD: A new use for the Block-Aid Monitor. Anesthesiology 30:236–237, 1969.
5. Koons RA: The use of the Block-Aid Monitor and plastic intravenous cannulas for nerve blocks. Anesthesiology 31:290–291, 1969.
6. Magora E, Rozin R, Ben-Menachem Y, et al: Obturator nerve block: An evaluation of technique. Br J Anaesth 41:695–698, 1969.
7. Montgomery SJ, Raj PP, Nettles D, et al: The use of the nerve stimulator with standard unsheathed needles in nerve blockade. Anesth Analg
52:827–831, 1973.
8. Von Helmholz H: Messungen uber den zeitlichen verlaug der Zuchung animalischer Muskern und die Fortphanzungageschwindigkeit der
Reizung in den Nerven. Archiv Anat Phisiol 277, 1850.
9. Ranck JB: Which elements are excited in electrical stimulation of mammalian central nervous system: A review. Brain Res 98:417–440, 1975.
10. Shaefer H: Elktrophysiologie I, vol 2. Germany, Wein franz Deuticke, 1940.
12. Koslow M, Bak A, Li DL: C fiber excitability in the cat. Exp Neurol 41:745–753, 1973.
13. Raj P, Rosenblatt R, Montgomery SJ: Use of the nerve stimulator for peripheral blocks. Reg Anesth 5:14–21, 1980.
14. Pither CE, Raj PP, Ford DJ: The use of peripheral nerve stimulators for regional anesthesia. A review of experimental characteristics,
332
technique, and clinical applications. Reg Anesth 10:49–58, 1985.
15. Ford DJ, Pither CE, Raj PP: Electrical characteristics of peripheral nerve stimulators: Implications for nerve localization. Reg Anesth 9:73–77,
1984.
16. BeMent SL, Ranck JB Jr: A quantitative study of electrical stimulation of central myelinated fibers. Exp Neurol 24:147–170, 1969.
17. Tulchinsky A, Weller RS, Rosenblum M, et al: Nerve stimulation polarity and brachial plexus block. Anesth Analg 77:100–103, 1993.
18. Bashein G, Ready LB, Haschke RH: Electrolocation: Insulated versus non-insulated needles. Reg Anesth 9:31, 1984.
19. Pither CE, Ford DJ, Raj PP: Peripheral nerve stimulation with insulated and uninsulated needles: Efficacy of characteristics. Reg Anesth 9:42,
1984.
20. Kaiser H, Niesel HC, Hans V: Fundamentals and requirements of peripheral electric nerve stimulation. An improvement of safety standards in
regional anesthesia. Reg Anesth 13:143–147, 1990.
21. Barthram CN: Nerve stimulators for nerve location—are they all the same? A study of stimulator performance. Anaesthesia 52:761–764, 1997.
22. Galindo A: Electrical localization of peripheral nerves: Instrumentation and clinical experience [abstract]. Reg Anesth 8:49–50, 1983.
23. Yasuda I, Hirano T, Ojima T, et al: Supraclavicular brachial plexus block using a nerve stimulator and an insulated needle. Br J Anaest
52:409–411, 1980.
24. Winnie AP: An “immobileneedle” for nerve blocks. Anesthesiology 31:577–578, 1969.
25. de Jong RH: Local Anesthetics, 2nd ed. Springfield, Ill, Charles C Thomas, 1977, pp 72–84.
26. Chapman GM: Regional nerve block with the aid of a nerve stimulator. Anaesthesia 27:185–193, 1972.
27. Smith BL: Efficacy of a nerve stimulator in regional analgesia: Experience in a resident training programme. Anaesthesia 31:778–782, 1976.
28. Smith BE, Allison A: Use of a low power nerve stimulator during sciatic nerve block. Anaesthesia 42:296–298, 1987.
29. Goldberg ME, Gregg C, Larijani GE, et al: A comparison of three methods of axillary approach to brachial plexus blockade for upper
extremity surgery. Anesthesiology 66:814–816, 1987.
30. Baranowski AP, Pither CE: A comparison of three methods of axillary brachial plexus anaesthesia. Anaesthesia 45:362–365, 1990.
31. McClaine DA, Finucane BT: Interscalene approach to the brachial plexus: Paraesthesae versus nerve stimulator. Reg Anesth 12:80, 1987.
32. Kaiser H, Niesel HC, Klimpel L; Ischiadikusblockade durch nervenstimulation. Reg Anesth 11:92–97, 1988.
33. Franco CD, Vierira ZEG: 1,001 subclavian perivascular brachial plexus blocks: Success with a nerve stimulator. Reg Anesth Pain Med 25:41–
46, 2000.
34. Sia S, Bartoli M, Lepri A, et al: Multiple-injection axillary brachial plexus block: A comparison of two methods of nerve localization-nerve
stimulation versus paresthesia. Anesth Analg 91:647–651, 2000.
35. Youssef MS, Desgrand DA: Comparison of two methods of axillary brachial plexus anaesthesia. Br J Anaesth 60:841–844, 1988.
36. Hill DA, Campbell WI: Two approaches to the axillary brachial plexus loss of resistance to saline or paraesthesia. Anaesthesia 47:207–209,
1992.
37. Koscielniak-Nielsen ZJ, Stens-Pedersen HL, Lippen FK: Readiness for surgery after axillary block: Single or multiple injection techniques.
Eur J Anaesthesiol 14:164–171, 1997.
38. Lavoie J, Martin R, Tetrault JP, et al: Axillary plexus block using a peripheral nerve stimulator: Single or multiple injections. Can J Anaesth
39:583–586, 1992.
39. Winnie AP, Radonjic R, Akkineni SR, et al: Factors influencing distribution of local anesthetic injected into the brachial plexus sheath. Anesth
Analg 58:225–234, 1979.
40. Koscielniak-Nielsen ZJ, Quist CI, Stens-Pedersen HL, et al: Effect of digital pressure on the neurovascular sheath during perivascular axillary
block. Br J Anaesth 75:702–706, 1995.
41. Yamamoto K, Tsubokawn T, Ohmura S, Kobayashi T: The effects of arm position on central spread of local anesthetics and on quality of the
block with axillary brachial plexus block. Reg Anesth Pain Med 24:36–42, 1999.
42. VadeBoncouer TR, Riegler FX: In defense of the nerve stimulator [letter]. Reg Anesth Pain Med 23:229–230, 1998.
333
43. Koscielniak-Nielsen Z, Hesselbjerg L, Fejlberg V: Comparison of transarterial and multiple nerve stimulation techniques for an initial axillary
block by 45 mL of mepivacaine 1% with adrenaline. Acta Anaesthesiol Scand 42:570–575, 1998.
44. Koscielniak-NieslenZJ, Nielsen PR, Nielsen SL, et al: Comparison of transarterial and multiple nerve stimulation techniques for axillary block
using a high dose of mepivacaine with adrenaline. Acta Anaesthesiol Scand 43:398–404, 1999.
45. Shannon J, Lang SA, Yip RW, et al: Lateral femoral cutaneous nerve block revisited. Reg Anesth 20:100–104, 1995.
46. Sheppard DG, Iyer RB, Fenstermacher MJ: Brachial plexus: Demonstration at US. Radiology 208:402–406, 1998.
47. Fornage BD: Musculoskeletic ultrasound. In Mittelstaldt CA (ed): General Ultrasound. New York, Churchill Livingstone, 1994, pp 1–17.
48. Van Holsbeeck M, Introcaso JH: Musculoskeletal ultrasonography. Radiol Clin North Am 30:907–925, 1992.
49. YangWT, Chui PT, Metreweli C: Anatomy of the normal brachial plexus revealed by sonography and the role of sonographic guidance in
anesthesia of the brachial plexus. AJR 171:1631–1636, 1998.
50. Sala-Blanch X, Lázaro JR, Correa J, Gomez-Fernandez M: Phrenic nerve block caused by interscalene brachial plexus block: Effects of digital
pressure and a low volume of local anesthetic. Reg Anesth Pain Med 24:231–235, 1999.
51. Kapral S, Krafft P, Eibenberger K, et al: Ultrasound-guided supraclavicular approach for regional anesthesia of the brachial plexus. Anesth
Analg 78:507–513, 1994.
52. Kilka HG, Geiger P, Mehrkens HH: Infraclavicular vertical brachial plexus blockade. A new method for anesthesia of the upper extremity. An
anatomical and clinical study. Anaesthesist 44:339–344, 1995.
53. Ootaki C, Hayashi H, Amano M: Ultrasound-guided infraclavicular brachial plexus block: An alternative technique to anatomical landmark-
guided approaches. Reg Anesth Pain Med 25:600–604, 2000.
54. Friedl W, Fritz T: Ultrasound assisted brachial plexua anesthesia. Chirurg 63:759–760, 1992.
55. Marhofer P, Schrogendorfer K, Wallner T, et al: Ultrasonographic guidance reduces the amount of local anesthetic for 3-in-1 blocks. Reg
Anesth Pain Med 23:584–588, 1998.
56. Lanz E, Theiss D: The extent of blockade following various techniques of brachial plexus block. Anesth Analg 62:55–58, 1983.
57. Winnie AP, Collins VJ: The subclavian perivascular technique of brachial plexus anesthesia. Anesthesiology 24:353–363, 1964.
58. Dalens B, Vanneuville G, Tanguy A: A new parascalene approach to the brachial plexus in children: Comparison with the supraclavicular
approach. Anesth Analg 66:1264–1271, 1987.
59. Moorthy SS, Schmidt SL, Dierdorf SF, et al: A supraclavicular lateral parascalene approach for brachial plexus regional anesthesia. Anesth
Analg 72:241–244, 1991.
60. Brown DL, Cahill DR, Bridenbaugh LD: Supraclavicular nerve block: Anatomic analysis of a method to prevent pneumothorax. Anesth Anal
76:530–534, 1993.
61. Vongvises P, Boekhaimook N: Computed tomographic study of parascalene block. Anesth Anal 84:379–382, 1997.
62. Winnie AP: Subclavian perivascular technique of brachial plexus block. In Winnie AP (ed): Plexus Anesthesia, vol 1. New York, Churchhill
Livingstone, 1984, pp 145–166.
63. Selander D, Dhuner KG, Lundborg G: Peripheral nerve injury due to injection needles used for regional anesthesia. Acta Anaesthesiol Scand
21:182–188, 1977.
64. Selander D, Edshage S, Wolf T: Paresthesiae or no paresthesia? Acta Anaesthesiol Scand 23:27–33, 1979.
65. Selander D: Axillary plexus block: Paresthetic or perivascular? Anesthesiology 66:726–728, 1987.
66. Partridge BI, Katz J, Benirschke K: Functional anatomy of the brachial plexus sheath: Implications for anesthesia. Anesthesiology 66:743–747,
1987.
67. Bartell C, Vical F, Raich M, et al: A neurological complication following interscalene brachial plexus block. Anaesthesia 35:365–367, 1980.
68. Passannante AN: Spinal anesthesia and permanent neurologic deficit after interscalene block. Anesth Analg 82:873–874, 1996.
69. Lewin JS: Interventional MR imaging: Concepts, systems, and applications in neuroradiology. AJNR 20:735–748, 1999.
70. LewinJS, Merkle EM, Duerk JL, Rarr RW: Low flow vascular malformations in the head and neck: Safety and feasibility of MR imaging-
guided percutaneous sclerotherapy—preliminary experience with 14 procedures in three patients. Radiology 211:566–570, 1999.
71. Merkle
EM, Lewin JS, Duerk JL: Magnetic resonance imaging-guided intervention in the head and neck. In Mukherji SK, Castelijns JA (eds):
Modern Head and Neck Imaging. Heidelberg, Germany, Springer-Verlag, 1998, pp 17–24.
72. Vogl TJ, Mack MG: MR-guided therapy of head and neck cancers. In Mukherji SK, Castelijns JA (eds): Modern Head and Neck Imaging.
Heidelberg, Germany, Springer-Verlag, 1998, pp 25–30.
73. Zennaro H, Dousset V, Viaud B, et al: Periganglionic foraminal steroid injections performed under CT control. AJNR 19: 25–30, 1998.
74. Quinn SF, Murtaugh FR, Chatfield R, Kari SH: CT-guided nerve root sleeve block and ablation. AJNR 151:1213–1216, 1988.
75. Murtaugh FR: The neuroradiologist as pain therapist. AJNR 19:353–354, 1998.
334
76. Brown DL, Bridenbaugh LD: The upper extremity. In Cousins MJ, Bridenbaugh PO (eds): Neural Blockade in Clinical Anesthesia and
Management of Pain, 3rd ed. Philadelphia, Lippincott-Raven, 1998, pp 345–371.
77. Warfield CA (ed): Principles and Practices of Pain Management. New York, McGraw-Hill, 1993, pp 29–30.
78. Iocolano CF: Total spinal anesthesia after interscalene block. J Perianesth Nurs 12:163–170, 1997.
79. Winnie AP: Interscalene brachial block: Description of the interscalene block. Anesth Analg 49:455–466, 1970.
80. Raj PP, Montgomery SJ, Nettles D, Jenkins MT: Infraclavicular brachial plexus block: A new approach. Anesth Analg 52:897–904, 1973.
81. Grossi P, Coluccia R, Tassi A, et al: The infraclavicular brachial plexus block. Techniques in Regional Anesthesia and Pain Management.
3:217–221, 1999. 285
335
Section IV - Chapter 18 - Conduction Blocks
Chapter 18 - Conduction Blocks
P. PRITHVI RAJ
Anatomy of the Spinal Column
The spinal column is made up of vertebral bodies joined together as cervical (7), thoracic (12), lumbar (5), sacral
(5), and coccygeal vertebrae (4), named as such by their location. A typical vertebra consists of two essential parts:
the anterior vertebral body and the dorsal vertebral arch. The vertebral bodies along with the intervertebral discs
form a strong column for the support of the head and trunk, and the vertebral arch protects the spinal cord. The
vertebral column presents two primary curves in the thoracic and sacrococcygeal regions and two compensatory
curves in the cervical and lumbar regions.
In the midline of the dorsal surface of the vertebral column, one can identify and feel the spinous processes. In the
cervical region, they are short and horizontal, whereas, in the thoracic region, they are vertical, and in the lumbar
region they are again nearly horizontal. The interval between the spinous processes is wide in the lumbar region
compared with the thoracic region where they are approximately close ( Figs. 18-1 and 18-2 ).
On either side of the spinous process, a vertebral groove is formed by the laminae in the cervical and lumbar regions
and by laminae and transverse processes in the thoracic region. Lateral to the laminae are the articular processes and
the transverse processes. The transverse processes are located ventral to the articular processes, lateral to the pedicle,
and between the intervertebral foramina ( Figs. 18-3 , 18-4 , and 18-5 ).
The vertebral canal follows the different curves of the column. It is triangular in the regions in which there is greater
movement (e.g., cervical and lumbar regions) and smaller and round in the thoracic region, where there is the least
movement.
The sacrum is a large, triangular bone, situated below the fifth lumbar vertebra ( Fig. 18-6 ). Its apex articulates with
the coccyx and its anterior surface is concave. Anteriorly, its median part is crossed by four transverse ridges. The
portions of the bone between the ridges are the bodies of the sacrum. There are four anterior sacral foramina through
which the sacral nerves exit and the lateral sacral arteries enter. The posterior surface of the sacrum is convex. There
are rudimentary spinous processes from the first three or four sacral segments in the midline. The laminae unite to
form a sacral groove. The laminae of the fifth sacral vertebra fail to unite posteriorly to form a sacral hiatus. The
tubercles that represent the inferior articular processes make up the sacral corona and are connected inferiorly to the
coccygeal cornua. Laterally, one can identify four dorsal sacral foramina. They transmit the posterior divisions of
the sacral nerves. The sacrum may have many variations. The bodies of the first and second may fail to unite or the
sacral canal may be open throughout its length ( Fig. 18-7 ).
MENINGES OF THE SPINAL CORD
In the vertebral canal, the spinal cord is covered by three membranes: (1) the dura mater is the tough, outer,
protective membrane; (2) the pia mater is the inner, delicate, fibrous membrane that contains the blood vessels to the
spinal cord; and (3) the arachnoid
336
Figure 18-1 Normal curvature of the vertebral column. In the supine position, lumbar and cervical lordosis decreases (as shown by the arrows).
Local anesthesia injected in the lumbar region settles around the T5 level because of the curvature at the thoracic region.
Figure 18-2 Surface landmarks identifying the vertebral levels in the cervical, thoracic, lumbar, and sacral regions.
337
membrane is the intermediate spidery, weblike structure containing the cerebrospinal fluid. The spinal duramater
forms a loose sheath around the spinal cord and corresponds to the meningeal layer of the cranial dura. The outer, or
periosteal, layer is interrupted at the foramen magnum and appears below as the periosteum of the vertebrae.
The epidural space is formed between the spinal dura and the vertebral canal. It contains loose areolar tissue and a
plexus of veins. The dura mater is attached to the foramen magnum and, by a fibrous slip, to the posterior
longitudinal ligament. The subarachnoid space occupies most of the tubular space of the duramater.
Figure 18-3 Posterior boundary of the spinal canal, showing the ligamentum flavum and the laminae.
Figure 18-4 Cross-sectional view of the vertebral column, showing the boundaries of the spinal canal with the contents.
338
It ends at the level of the second sacral vertebra and continues as the filum terminale to be attached to the back of
the coccyx. The lower part of the subarachnoid space from the second lumbar vertebra to the second sacral vertebra
is occupied by the cauda equina. The dura covers the spinal nerves as they pass from the cauda equina to the
intervertebral foramina. The spinal arachnoid membrane loosely invests the spinal cord. It is continuous with the
cranial arachnoid membrane and caudally encloses the cauda equina, ending at the second sacral vertebra (see Fig.
18-6 ).
Subarachnoid Block
ANATOMY
The subarachnoid space extends to the level of S, and the enclosed spinal cord usually extends down to L1. A needle
inserted below L should not encounter the substance of the spinal cord, but it might encounter the cauda equina. In
the midline, the spinal needle traverses the skin, the supraspinous ligament, the interspinous ligament, the
ligamentum flavum, and the epidural
Figure 18-5 Sagittal section of the lumbar region shows the spine’s interspinous and supraspinous ligaments and ligamenta flava
Figure 18-6 Anatomy of the sacral hiatus and dorsum of the sacrum.
339
Figure 18-7 Sagittal section through the lumbosacral section of the vertebral column, showing the termination of the spinal cord and dural sac
and the course of the lumbar and sacral nerves.
340
Figure 18-8 Diagrammatic representation of the sagittal section showing needle placements in both the subarachnoid and the epidural space.
space before entering the subarachnoid space. In the lateral approach, the needle passes through skin, subcutaneous
fat, lumbar aponeurosis, paravertebral muscles, ligamentum flavum, and epidural space before entering the
subarachnoid space ( Fig. 18-8 ).
EQUIPMENT
Many disposable trays are available on the market. Reusable trays should be sterilized and checked before use.
Anesthesiologists have their own ideas of what is essential in a block tray. It is important that the smallest gauge (G)
of spinal needle be used to decrease the incidence of postdural puncture headache. The anesthetizing area and the
operating room should be fully equipped to provide total patient care, with an anesthetic machine, anesthetic
equipment, suction, and monitoring devices.
MONITORING OF PHYSIOLOGIC CHANGES

• Blood pressure (a decrease in systolic blood pressure of ≥20% is considered hypotension)
• Pulse
• Respiration
341
• Overall appearance
• Electrocardiogram
Note that an intravenous infusion via an indwelling plastic cannula is absolutely essential to expand the intravascular
volume preblock and administer intravenous agents as necessary.
TECHNIQUE
Position
The lateral decubitus position, the sitting position, and the jackknife position are most frequently used for spinal
anesthesia.
LATERAL POSITION
The line of the spinous processes should be parallel to the table. To open up the vertebral interspaces, the patient is
asked to flex the back by drawing the knees up toward the chest and flexing the neck so the chin touches the chest.
The head should be supported by a small pillow. An assistant should support and calm the patient.
SITTING POSITION
The patient sits on the edge of the table with the feet resting on a stool. The neck is flexed so that the chin touches
the chest, with the arms folded across the upper thighs or resting on a pillow, a Mayo tray, or the shoulders of the
assistant who is supporting the patient from the front.
JACKKNIFE POSITION
This position is used mainly for anorectal surgery with a hypobaric solution. Care must be taken with the patient’s
position during the procedure to avoid pressure points on the pelvis, thighs, or lower legs.
Procedure
The gloved anesthetist prepares the skin of the lumbar area with a bactericidal preparation, wiping off the excess
solution. The field is draped with sterile towels. The appropriate interspace is located. Depending on the special
anatomic features of the patient, the second, third, or fourth lumbar interspace may be found to be most suitable.
After the most prominent point of the right and left iliac crests is located, an imaginary line is drawn between the
two points that usually cross the L4 spinous process or the L4 interspace (the interspace between the L4 and L5
vertebrae) ( Figs. 18-9 and 18-10 ).
With the lateral position, the line of the spinous processes must be parallel to the table and the surface of the back
must be vertical. This approach aligns the spinous processes in the horizontal plane. The selected entry point is
infiltrated with a small amount of local anesthetic injected from a 25-G needle. In addition, a small amount (1–2
mL) of local anesthetic may be injected into the subcutaneous tissue and the interspinous ligament. When
satisfactory analgesia of the entry point has been created, an 18-G needle is used as an introducer and is inserted
through the skin wheal. The index and the middle fingers of the free hand straddle the interspace to fix the tissues of
the underlying structures.
342
Figure 18-9 A, Transverse section at the level of L3 to L4, showing the direction of the needle in the median and paramedian approaches. B,
Surface landmarks of the point of entry of the needle in a midline and paramedian (lateral) approach.
The introducer is used for passage of the fine spinal needle and, theoretically, it prevents a plug of skin or fat from
entering the subarachnoid space. However, some operators prefer not to use an introducer. An improperly inserted
introducer makes it impossible to point the needle in the correct direction. It is preferable to select a thin-gauged
(French [Fr] 25- or 26-G) spinal needle for spinal anesthesia. However, a 22-G spinal needle can also be used
without an introducer.
343
Figure 18-10 A, Median approach. Angle and the direction of the needle for the median and paramedian approaches for spinal and
epidural techniques. B, Paramedian approach. Angle and the direction of the needle for the median and paramedian approaches for spinal
and epidural techniques.
The needle must first be examined for any imperfections. It should be noted that the bevel of the needle is on the
same side as the key notch for the stylet in its hub. Once the physician is satisfied with the needle, it should be
inserted in such a fashion that the bevel does not cut across the longitudinal fibers of the dura. The bevel should,
therefore, face laterally during its passage through the dura.
The spinal needle is held between the index and middle fingers by the thumb and inserted through the introducer.
The thumb exerts pressure on the stylet to prevent its displacement as the needle is pushed through the tissues. The
ring fingers and the little fingers support the anesthetist’s hand by resting on the patient’s back. The spinal needle is
then slowly advanced. Its progress through the tissues is followed by noting the variations in resistance as the
various structures are crossed. First, the firm resistance of the interspinous ligament and the ligamentum flavum is
felt. Next, a lessening of resistance is observed as the needle crosses the epidural space. This is followed by the
344
characteristic “pop”—an abrupt disappearance of resistance as the needle pierces the dura to enter the subarachnoid
space. The physician should now check the needle position by withdrawing the stylet to see whether cerebrospinal
fluid appears at the hub of the needle. When a 25-G needle is used, aspiration with a 2-mL syringe may be needed.
If the cerebrospinal fluid does not appear at the hub of the needle, several possible causes should be considered.
A nerve root or the dura may be blocking the bevel of the needle. After the stylet is withdrawn, an attempt should be
made to rotate the needle between 90 and 180 degrees to see whether the bevel can be freed of this obstruction. The
cerebrospinal fluid (CSF) pressure may be too low to push the fluid through the needle. The anesthetist can confirm
the needle’s position by aspirating the cerebrospinal fluid with a syringe. A tissue plug may be blocking the bevel.
This also may be dislodged by an aspiration attempt. The bevel may still be at least partially in the epidural space.
The anesthetist should, therefore, replace the stylet in the needle and then slowly advance the needle. The earlier
maneuvers are then repeated.
If contact with bone is made, the procedure should be stopped. The needle must not be forced against this resistance,
because the lumen of the needle can easily be blocked and the needle point can become barbed. If the needle lumen
seems to be plugged, the needle should be taken out and flushed with normal saline or local anesthetic solution.
Contact with bone usually means that the vertebral lamina has been encountered. This necessitates a small change in
the direction of the spinal needle. To do this effectively, the needle point is withdrawn completely into the
introducer and a fresh puncture attempt is made in a different direction. Success is indicated by the appearance of
CSF in the hub of the spinal needle. When this is achieved, the hub of the spinal needle is held firmly between the
index finger and thumb of one hand to prevent any displacement of the needle from its proper location. The back of
the anesthetist’s hand is steadied against the patient’s back. A syringe filled with an appropriate dose of local
anesthetic solution is attached to the spinal needle ( Table 18-1 ).
TABLE 18-1 -- RELATIVE MERITS OF SUBARACHNOID VERSUS EPIDURAL ANESTHESIA FOR CESAREAN SECTION
Subarachnoid Epidural
Speed of onset Very rapid Delayed
Upper limit of block Variable, unpredictable Usually satisfactory to T4
Lower limit of block Usually satisfactory to S4 Variable, sacral sparing
Density of block Profound Variable, agent dependent
Duration of motor block Agent dependent; may be prolonged Agent dependent; not usually prolonged
Systemic absorption Negligible Substantial; toxicity possible
Hypotension Common, rapid onset Variable; gradual onset
Shivering Rare Common
Dural puncture headache Variable, unpredictable Nil
Provision for postoperative analgesia Nil Ideal route for continuous analgesia
From Cousins MJ, Bridenbaugh PO (eds): Neural Blockade in Clinical Anesthesia and Management of Pain. Philadelphia, JB Lippincott, 1988,
p. 629
Negative pressure is applied to the syringe, enabling a small amount of CSF to be drawn up; this ascertains that the
proper position of the needle bevel has been maintained. Local anesthetic solution in the syringe is then injected
slowly to prevent a jet effect in the subarachnoid space. Some prefer a small amount of aspiration and reinjection in
the middle of the procedure, after the local anesthetic has been injected, to rule out inadvertent movement of the
needle during the instillation of the drug. The patient is turned gently after the needle is removed. Vital signs are
monitored continuously at this point. Verbal contact with the patient is essential. Early signs of hypotension appear
during the change in position and should be prevented or the patient should be treated as soon as possible.
When the patient is resting comfortably, the spread of anesthesia is frequently checked by gentle repeated pinpricks
or by a cotton swab moistened with alcohol. Because loss of pain and loss of temperature sensation progress
simultaneously, the use of alcohol to check the spread of anesthesia is more pleasant for the patient. Repeated
pinpricks may not accurately differentiate the area of complete loss of pain sensation from that of partial analgesia (
Fig. 18-11 A, B).
When the anesthesia reaches the desired segmental level, the patient is positioned so as to prevent any further spread
of the anesthetic. Usually, the local anesthetic drug becomes fixed to the neuronal elements, so that no further spread
345
of anesthetic effect is seen after a fixation time of approximately 20 minutes. The spread of the local anesthetic
depends on specific gravity, which is the basicity between the local anesthetic solution used and that of CSF.
A hyperbaric solution has a higher specific gravity than that of cerebrospinal fluid; therefore, it moves to low-lying
parts of the subarachnoid space. This technique is recommended for surgical and obstetric procedures performed in
the supine or sitting position.
A hypobaric solution has a specific gravity lower than that of CSF, and it therefore spreads to areas lying higher in
the subarachnoid space. However, some believe that the block is produced by displacement of the cerebrospinal
fluid from the superior part of the subarachnoid space by the hypobaric solution. This technique is primarily used for
pelvic, perineal, and lower extremity procedures performed in the lateral, prone, or jackknife positions. One
advantage of using a hypobaric technique is that the patient is placed in the position in which the operation will be
performed; therefore, after the block is established, no further movement of the patient is necessary. One needs to
keep the operative site uppermost and the table in a 20-degree head-down position.
An isobaric solution with a specific gravity matching that of CSF, tends to remain at the injection point, even during
the fixation time. Although this technique is rarely used at present, it is gaining popularity with the introduction of
bupivacaine as a spinal agent.
With hyperbaric solutions, it is possible to attempt to block one leg (the dependent extremity). However, on
resuming the supine or prone position, there is sufficient mixing to obtain a bilateral block, although it may be less
intense in the superior extremity.
PREVENTION OF DELETERIOUS EFFECTS
To ensure the safety and success of spinal anesthesia, several precautions should be taken. The entry point for the
needle should be below the level of L2 to avoid injury to the spinal cord.
On occasion, the spinal needle may puncture one of the epidural vessels, resulting in a blood-tinged return of CSF at
the hub of the needle. If this occurs, the procedure should be halted until the return clears completely. If the CSF
return fails to clear, an attempt should be made to repeat the block through another interspace. The vital signs must
be monitored continuously, especially during the initial 10 minutes in which the block is being fixed, with close
attention paid to any drop in blood pressure.
CONTRAINDICATIONS
Circumstances that make spinal anesthesia inadvisable include conditions that may potentiate bleeding into
346
Figure 18-11 A, Anterior view with dermatomal distribution of the body wall. B, Posterior view with dermatomal distribution of the body wall.
the central nervous system (blood dyscrasia, coagulopathies), which may cause infection of the meninges of the
spinal cord (septicemia, local cutaneous infections at the puncture site), or a condition in which preexisting central
nervous system pathology may be aggravated by the pharmacologic action of the local anesthetic (e.g.,
poliomyelitis, amyotrophic lateral sclerosis).
Deformities of the lumbosacral spine may make spinal anesthesia technically difficult. In these patients, the
potential for trauma may become unacceptably high.
CONTINUOUS (INTERMITTENT) SPINAL ANESTHESIA
Continuous spinal block is rarely used because of the increased use of continuous epidural anesthesia. The incidence
of spinal headache after this block can be expected to be unacceptably high because it may cause a clinically
significant loss of CSF. Spinal anesthesia inevitably requires a large-gauge needle, and thereby producing a
relatively large dural defect. The pressure of the catheter inserted through the dura also potentiates the loss of CSF
by capillary action.
347
Epidural Block
ANATOMY
Anatomically, the epidural space is the area between the dura mater and the ligaments and periosteum lining the
vertebral canal and extending from the foramen magnum to the sacrococcygeal membrane. This has been described
as a potential space, because it is normally completely filled with a loose type of adipose tissue, lymphatics, and
blood vessels. It is particularly rich in venous plexi. No free fluid exists in the epidural space, in contradistinction to
the CSF, which is found in the subarachnoid space. However, solutions injected into the epidural space spread in all
directions owing to the loose tissue structure that occupies this area. Epidural anesthesia is usually subdivided into
the following three categories, depending on the site of injection: thoracic epidural, lumbar epidural, and caudal
anesthesia. Cervical epidural anesthesia is possible but rarely performed. Thoracic epidural anesthesia is employed
mainly for production of a segmented band of analgesia involving the middle and lower thoracic dermatomes. This
technique has proved beneficial for relief of pain after thoracic or upper abdominal surgery. Lumbar epidural
anesthesia is useful as an adjunct to surgical procedures involving the lower abdomen, pelvis, perineum, and lower
extremities, and for obstetric procedures. Caudal anesthesia is usually reserved for pelvic and perineal surgery and
for vaginal deliveries.
TECHNIQUE
Procedure
Awareness of the three-dimensional anatomic relationships that exist among the bony spine, the soft tissues of the
back, and the ligamentum flavum allows the anesthesiologist to become familiar with midline or paramedian
approaches to the epidural space. Both techniques, performed correctly, should elicit no real discomfort from the
patient in spite of the varying depth of penetration of the 16- to 18-G needles. The primary advantage of the median
approach is its position in the middle of the epidural space, allowing the operator to feel the definite resistance of the
ligamentum flavum and the loss of resistance when the needle is past it. For the paramedian approach, the advantage
is the paramedial point of penetration of the skin, which allows final entry of the needle just off the midline at the
interspace one level above skin entry. This approach enables and promotes ease of catheter insertion and reduced
incidence of dural penetration during catheter insertion.
MIDLINE APPROACH
The patient can be positioned in a lateral decubitus or sitting position. The position chosen depends on the ease with
which the intervertebral spaces are palpated and identified. If the operator is not sure of the midline connecting the
spinous processes, a sitting position for the patient has the decided advantage.
The technique up to this point of needle entry is the same as that for spinal anesthesia. A 16- to 18-G Tuohy needle
with a Huber point is generally used for the midline approach. After the needle is engaged in the interspinous
ligament, the stylet is removed. The needle tip is usually directed cephalad. A syringe filled either with air, air and
saline, or saline alone is attached for loss of resistance. The technique for confirming loss of resistance with air or air
and saline is different from that used with saline alone. The testing with air or air and saline is done intermittently (a
stop-test-push maneuver), with advances of a few millimeters at a time. The saline-filled syringe must continuously
be pushed inward at a steady pace, with constant pressure maintained at all times. When the air-filled syringe
approaches the ligamentum flavum, an increase in bounce of the barrel is observed, which suddenly decreases with
entry into the epidural space. With the saline-filled syringe, there is a sudden surge of the saline into the epidural
space.
The syringe is then removed. The following points are determined at this stage: (1) The needle appears to have its
tip in the midline; (2) there is no leakage of CSF through the needle hub, and fluid or blood is not aspirated with a 2-
mL syringe. A test dose of 3 mL of local anesthetic with epinephrine is injected through the needle at a steady state
(usually 2% lidocaine with 1:200,000 epinephrine). If there is increased radicular pain with the injection, the needle
is withdrawn slightly rotated, or removed altogether. No further injection should be made if radicular pain reappears
and gets worse on injection. Radicular pain denotes intraneural injection and may cause a prolonged nerve lesion or
spread of the solution into the subarachnoid space. When the test dose fails to produce spinal anesthesia at 5 minutes
or shows no systemic toxicity on an electrocardiogram, the calculated amount of local anesthetic is injected. If a
catheter is inserted, the test dose should be given via a catheter. The needle is removed over a catheter, with constant
inward pressure on the catheter. The catheter must be secured properly to maintain the position for prolonged use.
The patient is again positioned gingerly in the surgical position and testing is done for onset of anesthesia, as in
spinal block.
348
PARAMEDIAN APPROACH
The patient is placed in the left lateral decubitus position, with the shoulder and pelvic girdle perpendicular to the
plane of the flat bed. The lumbar spinous processes are palpated, and one of the most prominent processes in the
lumbar 3 to 4 area is identified. A small circle is drawn immediately over the spinous process, and an imaginary
lamina is drawn on the skin of the back. After careful preparation of the aniodine (Betadine) solution, a 1-cm skin
wheal is raised with a 25-G needle 3 cm from the midpoint of the spinous process on the dependent side. Lidocaine,
0.5%, is used for analgesia of the skin and the deeper tissues. A 22-G, 1½ inch needle is then used to inject 3 to 5
mL of lidocaine very slowly from the skin wheal through the subcutaneous tissue and muscle down to the lamina.
During the slow penetration of the needle, the syringe is gradually emptied, with deposition of the local anesthetic
along the pathway through the superficial and deeper tissues. An assistant discusses the procedure with the patient as
it is being performed and explains the technique in detail in a calm and reassuring manner. Next, an 18-G, thin-
walled Crawford-point needle, or the epidural needle preferred by the performer, is inserted along the path of
analgesia down to a contact point with the lamina. During insertion of the needle, the administrator’s fingers become
sensitive to penetration of the needle through each tissue layer. The lamina is approached and touched very gently to
prevent undue discomfort from periosteal irritation. Because this anatomic depth also identifies the plane at which
the ligamentum attaches to the leading edge of the lamina, the administrator now simply brings the needle back into
the soft tissue. The needle is then carefully and gently directed medially and cephalad through one, two, and perhaps
even three probes, until it is ascertained that the end of the needle has securely engaged the ligamentum. The stylet
is removed and a plastic, 12-mL syringe containing 10 mL of saline, or air, if one prefers, is attached to aid in
achieving a careful and safe entry into the epidural space by loss of resistance. Constant, unremitting pressure is
maintained on the syringe with saline until the needle enters freely into the epidural space. A gentle pressure test is
done intermittently using air. There is a sudden release of pressure from the barrel of the syringe. The presence of
saline in the syringe promotes the characteristic and readily identifiable entry into the epidural space, simultaneously
releasing saline into the space and gently pushing the dura away from the tip of the needle. This serves as another
protection against inadvertent dural puncture. The syringe is removed and the needle examined to see whether there
is momentary return of the saline that has been injected into the epidural space. If the needle has mistakenly
penetrated the dura and entered the subarachnoid space, it is easily identified by a continuous return of fluid from
the needle. A catheter is then gently placed in the epidural space for a distance of 3 cm. The needle is withdrawn and
the catheter taped in place for subsequent injection.
Combined Spinal-Epidural Block
Epidural and spinal anesthesia are major regional anesthetic techniques. Both blocks have many potential
advantages over general anesthesia, especially for surgery involving the lower abdomen, perineum, and lower
extremities. Both techniques also have disadvantages. Spinal anesthesia is easy to perform, has a rapid onset, and
[1]
requires small doses of local anesthetic to provide reliable surgical anesthesia and good muscle relaxation. The
disadvantages are the unpredictability of the upper level of block, precipitous hypotension, inability to extend the
block once it is fixed (unless a catheter technique is employed), and the risk of postdural puncture headache. These
disadvantages are particularly conspicuous in the patient undergoing cesarean section (see Table 18-1 ). In contrast,
epidural block is less easy to perform, has a significantly slower onset, and does not reliably guarantee adequate
analgesia or good muscle relaxation. The catheter technique is often used to extend the block and prolong its
duration. This technique also enables provision of high-quality postoperative pain relief using local anesthetics or
opioids in the epidural catheter. Although the choice between epidural and spinal block is often determined by local
tradition and preference, there are significant differences between the two techniques, as shown in Table 18-2 .
[1]
A combined spinal-epidural (CSE) technique can be used to reduce or eliminate some of the disadvantages of spinal
and epidural anesthesia while preserving their advantages. The combined technique has been used for major lower
extremity, urologic, and colorectal surgery ( Table 18-3 ). The CSE technique is particularly appropriate in
[2] [3] [4] [5]
patients undergoing cesarean section. Provision of safe and effective analgesia for abdominal surgery in the
[6] [7]
awake obstetric patient has been described as one of the most challenging problems for the anesthetist. It is [8]
generally recognized that an S5 to T4 block is necessary to provide adequate analgesia during cesarean section. Such
an extensive block by the epidural route requires large doses of local anesthetic drugs and may be associated with a
relatively high incidence of hypotension and potential risk of toxic complications.
[9] [10]
Furthermore, in spite of
[11] [12]
these large doses, the block may be inadequate in 10% to 25% of patients, mainly because of difficulty in blocking
sacral roots. Spinal anesthesia is more reliable than epidural anesthesia because of more intense motor block,
[11] [13] [14]
but the technique may be associated with a high risk of precipitous maternal hypotension, which may be harmful for
the neonate. Because the catheter technique is not used, there is no possibility of providing postoperative pain
[15] [16]
relief with spinal block.
349
TABLE 18-2 -- ASSESSMENT OF SURGICAL ANALGESIA BY PATIENT, NURSE ANESTHETIST, AND SURGEON
CSE Block
Group A Group B Epidural Block
Surgical Analgesia Number of Patients Percentage (%) Number of Patients Percentage (%)
Excellent 13 87 10 67
Good 2 13 1 7
Fair 0 - 2 13
Poor 0 - 2 13
From Rawal N, Schollin J, Wesström G: Epidural versus combined spinal epidural block for cesarean section. Acta Anesthesiol Scan,
32:6146,1988.
The combined technique was introduced by Brownridge in 1981 to exploit the advantages of epidural and spinal
[17]
block for cesarean section. An epidural catheter was introduced at L1 to L2 and 2 mL of 2% lidocaine with
epinephrine injected through it as a test dose. This was followed by a spinal block at the L3 to L4 interspace. In
about 90% of patients, the spinal block alone was adequate for cesarean section. The epidural catheter was available
to extend the block if necessary and for providing postoperative analgesia. [17]
A modification of the technique for orthopedic surgery was reported by Coates and by Mumtaz and colleagues in
[2] [5]
1982. These authors described a single space “needle-through-needle” technique in which a 16-G epidural needle
served as an introducer for a fine (26- or 27-G) spinal needle. Rawal described a sequential CSE technique for
[7]
cesarean section, which was performed in a single interspace.
In the only controlled trial to date, Rawal and associates compared CSE block with epidural block for cesarean
[18]
section. Thirty healthy parturients were randomly divided into two groups. In both groups, a T4 block was the
chosen approach. Bupivacaine was used to provide analgesia in both groups. All patients receiving CSE block had
good to excellent analgesia, whereas only 74% receiving epidural block had similar pain relief (see Table 18-2 ).
This was reflected in the
TABLE 18-3 -- REPORTED INDICATIONS FOR COMBINED SPINAL-EPIDURAL TECHNIQUE

Orthopedic surgery (major hip and knee surgery)
Obstetrics (cesarean section, labor pain)
Urologic surgery *
Colorectal surgery *
Gynecologic surgery *
*Combined spinal-epidural block alone or in combination with light general anesthesia.
requirement for additional analgesics, sedatives or N2 O anesthesia. Muscular relaxation was also better after CSE
block. The total dose of bupivacaine for a T4 block was three times larger in patients receiving only epidural block.
The maternal and fetal blood bupivacaine levels were correspondingly about three times higher in the epidural group
( Table 18-4 ). In addition, the incidence of maternal hypotension was higher in patients receiving epidural block.
Apgar scores, blood gases, and neurobehavioral evaluation did not show any differences between the two groups of
neonates. The authors demonstrated that CSE block was superior to epidural block for cesarean section and
concluded that CSE block combined the reliability of spinal block and the flexibility of epidural block while
minimizing their drawbacks. [18]
The segmental technique for cesarean section is as follows: With the patient in the sitting position, a 16- or 18-G
Tuohy needle is inserted at the L2 to L3 interspace and the epidural space is identified. A long 26- or 27-G (or finer)
spinal needle is introduced through the Tuohy needle and advanced until the tip of the spinal needle is felt to
penetrate the dura ( Fig. 18-12 ). A stylet for the spinal needle is unnecessary because the spinal needle passes
through the dura only. The finer the spinal needle, the longer it takes for CSE to appear at the hub. This may cause
uncertainty about the correct position of the needle tip. At our institution, we prefill 26-G or finer diameter spinal
needles with saline to overcome this problem. Because the spinal needle is held in place only by the dura, there is a
risk of displacement of the needle position at the time of connecting it to the syringe or during injection of the local
anesthetic. This is a critical stage in the CSE technique. A steadying hand against the back of the patient as shown in
350
Figure 18-13 may be helpful. Alternatively, a somewhat cumbersome but more effective method described by
Nikalls and Dennison may be used to avoid spinal needle displacement. The authors recommended clamping the
[10]
spinal needle, at the point where it enters the Tuohy needle, with a sterile, lightweight, toothed artery clip. After [10]
correct placement of the spinal needle is confirmed by the appearance of CSF at the hub, 1.5 mL of 0.5% hyperbaric
bupivacaine
Figure 18-12 Technique of combined spinal and epidural anesthesia for cesarean section. A fine spinal needle is introduced through the Tuohy
needle and advanced until the tip of the needle is felt to penetrate the dura. The appearance of cerebrospinal fluid confirms that the needle is in
the subarachnoid space.
TABLE 18-4 -- TOTAL DOSE AND MATERNAL AND FETAL BLOOD LEVELS OF BUPIVACAINE
CSE block Group A (Mean ± s.e. Epidural block Group B (Mean
Bupivacaine mean) ± s.e. mean) Statistical Significane
*
Total dose of bupivacaine (mg) 40.2 ± 4.24 125.0 ± 2.67 P < 0.001
Maternal blood concentration 205.3 ± 33.6 604.9 ± 51.2 P < 0.001
(rig/g)
Fetal blood concentration (rig/g) 45.8 ± 8.5 186.0 ± 20.3 P < 0.001
From Rawal N, Schollin J, Wesström G: Epidural versus combined spinal epidural block for cesarean section. Acta Anesthesiol Scand 32:61-
66,1988
*Mean total dose of 8 mg for spinal block in addition to mean total dose of 32.0 mg for epidural block.
351
Figure 18-13 This figure shows the importance of steadying the spinal needle in position after its introduction through the Tuohy needle. Note
that one hand stays in contact with the skin in the back and the other steadies the syringe attached to the spinal needle.
is injected into the spinal needle, which is then withdrawn. The aim is to achieve a block from S5 to T8 and T9.
Next, a catheter is introduced about 4 cm into the epidural space through the Tuohy needle ( Fig. 18-14 ). After
aspiration for blood or spinal fluid, 0.5 to 1 mL of saline is injected into the epidural catheter to test its patency. The
catheter is secured firmly by tape and the patient placed supine with a left lateral tilt. No local anesthetic is injected
into the epidural catheter at this stage. After the spinal block is “fixed” (usually 15–20 min), it is extended to T4 by
injecting fractionated doses (1.5–2 mL per unblocked segment) of plain bupivacaine, 0.5%, into the epidural
catheter ( Fig. 18-15 ). The objective of the two-stage technique is to reduce the severity and frequency of maternal
hypotension. The less extensive block of sympathetic vasomotor activity resulting from low spinal block, combined
with the slower onset of epidural block (and waiting for about 15 min) allows more time for compensatory
mechanisms to be effective. It should be remembered that the preoperative management of patients undergoing
cesarean section under regional anesthesia is similar whether the block is epidural, spinal, or CSE. This includes
preloading with 1 to 2 L of fluids, left lateral tilt (see Fig. 18-15 ), frequent monitoring of blood pressure, and
aggressive treatment of maternal hypotension with vasopressors such as ephedrine.
352
Figure 18-14 A catheter is introduced into the epidural space through the Tuohy needle. Before this step, the spinal needle that was introduced in
the Tuohy needle was removed.
For the nonobstetric patient, the CSE block is simpler because the two-stage technique is unnecessary. Indeed, in the
literature the commonest indication for CSE block is major surgery for the hip and knee. The CSE technique for
orthopedic and lower abdominal surgery is similar to that described earlier. The main difference is that the total dose
of spinal local anesthetic is given as a single injection. For the nonpregnant patient, CSE block may be performed
with the patient in the lying or sitting position, depending on the anesthesiologist’s preference. In a majority of
cases, the epidural catheter does not have any function during surgery. However, in about 10% to 15% of patients,
spinal anesthesia alone may not be adequate because of unanticipated prolonged surgery or inadequacy of block.
General anesthesia can be avoided in such situations by using the epidural catheter to extend the block. The presence
of an epidural catheter also provides the anesthesiologist with a choice regarding postoperative pain management.
Local anesthetics, opioids, or a combination of these drugs may be given as intermittent injections or continuous
infusion depending on available resources for postoperative surveillance. This is not possible with a single injection
spinal technique.
Although the CSE technique is being increasingly used, internationally (Axel Spanholtz, B. Braun, Melsungen AG,
Sweden, personal communication), there
Figure 18-15 It is noteworthy that for cesarean delivery with CSE (or any other conduction technique), one has to keep the patient in a semilateral position to prevent
pressure on the aorta. The figure also shows the level of analgesia produced by spinal block and extended by epidural block.
353
TABLE 18-5 -- COMBINED SPINAL-EPIDURAL BLOCK-UNANSWERED QUESTIONS

Is there an increased risk of catheter penetration through the dural hole?
What is the mechanism of extensive spread of block after small doses of local anesthetics?
What are the reasons for the extremely low incidence of postdural puncture headache?
What are the advantages and disadvantages of single versus two interspace CSE block?
CSE, combined spinal-epidural block.
is a scarcity of literature, and several aspects need clarification ( Table 18-5 ). One of the questions that needs to be
addressed is the potential risk of epidural catheter penetration through the dural hole made by the spinal needle. Also
unclear is how relatively small doses of local anesthetic injected into the epidural space can result in a considerable
elevation of the upper level of spinal block. In experimental studies on isolated human dura at our institution, it was
impossible to force an 18-G Portex epidural catheter through dural holes made by 26- or 27-G spinal needles. Also,
it was quite difficult to force the catheter through holes made by spinal needles of diameters from 22-G through 26-
G. Needles of 22-G or spinal needles of larger diameter made holes large enough to permit passage of the catheter. [18]
This is reflected in the experience of workers with extensive experience in CSE blocks. Thus, only one catheter
penetration occurred during 6 years in which about 4000 CSE blocks were performed (Svante Lindén, Uddevalla,
Sweden, personal communication). However, it should be noted that there are several reports in the literature of
spontaneous intrathecal catheter migration in patients who received epidural catheters. Clearly, the risk of
[19] [20]
catheter migration can be expected to be greater if there is a hole in the dura. Therefore, the routine for
administration of “top-up” doses in the epidural catheter is similar with epidural and CSE blocks and includes
confirmation of the catheter position by aspiration as well as frequent assessment of the block after injection of
fractionated doses of local anesthetics. Clearly, the CSE technique is not for the novice.
In an attempt to reduce the risk of catheter penetration while performing CSE block, various modifications of the
technique or needle design have been reported.
In the modification of CSE block described by Eldor and Olshwang, a Tuohy needle is placed in the epidural space,
[3]
after which a fine spinal needle is introduced alongside the outer wall of the epidural needle ( Fig. 18-16 ). After
injection of local anesthetic, the spinal needle is withdrawn. The epidural catheter is then introduced through the
Tuohy needle. The authors claimed that this modification eliminates the risk of damage to the bevel of spinal
[3]
needle when it is introduced through the epidural needle. However, this complication has not been reported in the
literature. Furthermore, the new disposable CSE sets include specially designed spinal needles that can be
introduced into the dura without coming in contact with the internal wall of the epidural needle (B. Braun,
Melsungen AG, Sweden). These authors have modified the combined needle further by brazing with silver alloy the
epidural and spinal nerves. The needle also allows the CSE block to be performed in reverse order (i.e., the spinal
[21]
block is performed after the epidural catheter is in place). However, using two fixed parallel needles may be
associated with local back pain and a high risk of spinal headache should dural puncture occur accidentally.
The “TA-pair” needle consists of an 18-G epidural and a 22-G spinal needle welded together. The distal ends of the
needles make a common tip. The epidural needle points cephalad and permits the passage of a 20-G epidural
catheter, whereas the bevel of the spinal needle points caudad and allows the passage of a 26-G or finer spinal
needle through it ( Fig. 18-17 ). Both needles have a stylet. The authors have used the needle in over 60 patients
undergoing lower abdominal or orthopedic surgery (Torreiri and Aldrete, 1988, personal communication). No
complications were noted. This combined needle appears similar to the needle described above, and spinal block can
also be performed after the epidural catheter is in position.
Disposable combined spinal epidural sets have been available since 1986 ( Fig. 18-18 A, B). The manufacturers have
modified the Tuohy and spinal needles to reduce the risk of catheter penetration through the dura and to reduce the
risk of damage to the bevel of the spinal needle. A hole at the angle of the Tuohy
354
Figure 18-16 Eldor and Olshwang describe a technique in which they first place a Tuohy needle in the epidural space, then introduce a fine spinal needle alongside
[3]
the Tuohy needle into the subarachnoid space.
Figure 18-17 The T-A pair needle for CSE anesthesia.
needle near its bevel permits the passage of the spinal needle ( Fig. 18-19 ). As mentioned earlier, the spinal needle
enters the hole easily. The point of dural contact by the epidural catheter is thus at some distance from the dural hole
(B. Braun, Melsungen AG, Sweden).
The two-segment CSE block appears to be safest because the spinal block is performed at an interspace that is below
the level of the epidural block. The technique can be modified by using a thoracic epidural catheter combined with
[17]
conventional lumbar spinal block. The obvious disadvantage of the double interspace technique is that introduction
of needles at two separate sites can be expected to increase the potential risks compared with a single injection site.
Also, the incidence of local back pain may be higher.
355
The mechanism by which small doses of local anesthetics administered in the epidural catheter result in rather
extensive CSE block is unclear. This phenomenon has not been reported in the nonpregnant patient. Thus, in the
study mentioned earlier, an average of only 30 to 50 mg of epidurally injected bupivacaine extended the upper level
of block from T8 to T4 in patients undergoing cesarean section. It is generally accepted that the sympathetic block
extends some segments above the sensory block after epidural or spinal anesthesia. Carrie has speculated that there [8]
may be a similar zone of subclinical analgesia above the level of block demonstrated by pinprick. With CSE block,
small increments of epidural local anesthetic may then be perineurally spread to bring the block up to full analgesic
strength. Another possibility is that the hole in the dura may allow a transfer of epidurally injected local anesthetic
[8]
through it into the intrathecal space. Alternatively, the spinal block continues to rise in spite of the 20-minute wait in
the previously mentioned study. Furthermore, it is conceivable that the pressure changes in the epidural space
(resulting from the presence of the catheter and the injection of local anesthetic) may
Figure 18-18 A and B, Disposable CSE needle sets.
Figure 18-19 The Tuohy needle modified to reduce the risk of catheter penetration through the dura and damage to the bevel by B. Braun, Melsungen AG, Sweden.
356
lead to a more extensive spread because of changes in volume and circulation of CSF.
Although there are no data from controlled studies, several workers have commented on the very low incidence of
post dural puncture headache after CSE block. Dennison reported only two spinal headaches in the first 400
[2] [5] [7] [18] [22]
patients who received CSE block for cesarean section. The possible mechanisms could be the following:
1. Because the Tuohy needle in the epidural space serves as an introducer, the spinal block is easier to
perform. Multiple attempts at identifying the subarachnoid space are thus avoided.
2. The technique allows the use of spinal needles with very fine diameter.
3. There is decreased risk of CSF leakage through the dura due to increased pressure in the epidural space
resulting from the presence of an epidural catheter and from administration of epidural local anesthetics
and opioids.
4. Epidural opioids may have a prophylactic effect against postdural puncture headache.
CSE has been used for urological, gynecological and colorectal surgery either alone or with light general anesthesia
( Table 18-5 ). Kehlet has developed a concept of total surgical and postoperative pain relief for suppression of
[23]
stress response. The authors believe that current methods of intraoperative and postoperative analgesia do not
attenuate the stress response completely and that a combination of analgesic modalities can provide total pain relief
and improve outcome after major surgery. To achieve this goal they studied patients undergoing colorectal surgery
under CSE block plus a postoperative CSE local anesthetic and morphine regime. Additionally, the patients received
systemic piroxecam. This technique prevented postoperative pain in all patients during rest and mobilization. Thus, [24]
the role of CSE block in the provision of total surgical and postoperative pain relief and in improving outcome after
surgery requires further study.
CSE technique has also been used for management of labor pain. Sixty-two women in labor were randomly divided
into three groups. For pain relief, they received 0.2 mg of intrathecal morphine, 0.125% of bupivacaine, or a
combination of both using CSE technique. Neither intrathecal morphine nor bupivacaine, 0.125%, provided
effective pain relief. However, all patients receiving the combination were pain free. It was also demonstrated that
the use of intrathecal morphine might lead to prolongation of the duration of labor (Abouleish, personal
communication, 1992).
In summary, although epidural and spinal blocks will continue as major regional anesthetic techniques, CSE block,
which combines the reliability of spinal block and the flexibility of epidural block, may be a superior alternative in
selected patients. However, further controlled studies are needed to clarify some of the unanswered questions. Until
such data are available, this technique should be used only by experienced anesthesiologists.
Caudal Technique
The caudal epidural technique is very difficult to perform because of the many variations in anatomic structure from
patient to patient, and because it is often hard to palpate the sacral coccygeal hiatus. The technique is quite different
from that described for the lumbar epidural technique. The patient can be placed in the lateral decubitus or prone
position. In the left lateral position, the left leg is straightened, and the right leg, or upper leg, is flexed, with the
right foot placed in the popliteal space of the left leg ( Figs. 18-20 and 18-21 ). The patient’s upper buttock is
slightly rotated off the perpendicular placement so that the gluteal fold does not prolapse over the lower middle
portion of the sacrum, where palpation of the sacral coccygeal hiatus is performed. The thumb and second finger are
placed on the prominent sacral tuberosities just below the articular processes of the fifth lumbar vertebrae, and the
middle finger is swept downward and medial to palpate the sacral cornua. If the sacral cornua can be easily
identified, the technique for needle placement is rather simple. With the finger in place over the sacral cornua, the
skin is moved slightly cephalad a few millimeters and a 25-G needle is inserted for skin analgesia. An amount less
than 0.125 to 0.25 mL is needed for a 1-cm wheal. The 25-G needle is inserted down toward the inferior lateral
angle of the sacral cornua and another 0.50 mL are injected on each side to obtain analgesia of the fifth sacral nerve,
which
357
Figure 18-20 Caudal block in a lateral position showing the penetration of the needle through the sacrococcygeal membrane with the thumb at the shelf of the sacral
hiatus.
exits near this point. A 22-G, 2½ inch needle is then used to puncture the skin. The area is gently palpated to
ascertain precisely the sensation of the needle piercing through the sacral coccygeal membrane. With consideration
of the needle angle, the 22-G needle is removed and an 18-G, thin-walled 2½ inch needle is inserted through the
sacral coccygeal membrane into the caudal-epidural space. At this point, extreme care must be taken to avoid tearing
the periosteum, which covers the dorsal aspect of the ventral plate of the sacrum. The needle is gently and carefully
manipulated cephalad into the caudal epidural space, with the needle between the dorsal and ventral plates of the
sacrum. As an added precaution, saline is carefully injected while advancing the needle, to avoid damaging the large
collection of venous channels lying within the caudal-epidural space. A calculated amount of the local anesthetic of
choice can then be injected after the last dose of 3 mL, as is done for the lumbar epidural space.
358
Figure 18-21 Caudal block in prone position. Arrow shows the position of sacral hiatus. Inset: The technique of
359
Figure 18-22 Catheter placement for continuous caudal technique. A, Large cannula or Tuohy needle inserted in the caudal canal. B, Epidural
catheter threaded through the needle. C, Needle removed and catheter anchored.
Catheter Placement
If a catheter needs to be placed, special Crawford-tip caudal needles can be chosen, with an understanding that only
1 to 1½ inches of the needle is inserted in the caudal canal. The catheter insertion is shown in Figure 18-22 . In most
instances, this should place the catheter at an ideal location, between S2 and S3. The catheter is taped in place, and
the injection tip of the catheter is placed either on the abdomen for subsequent injection or is brought to the
shoulder. It is most important when performing either the lumbar epidural or the caudal epidural technique that the
catheter be injected with saline soon after placement, so that any blood that may have collected at the tip of the
catheter does not form a clot and prevent subsequent injections.
Mechanism of Action of the Epidural Block (Bromage)
360
The possible sites of action of local anesthetic agents administered epidurally are the paravertebral nerve trunks, the
dorsal root ganglia, the dorsal and ventral spinal roots, and the spinal cord. Radiopaque material injected into the
epidural space exits through the intervertebral foramina. It is therefore possible that anesthetic agents could leave the
epidural region via these foramina to inhibit conduction in the paravertebral nerve trunks. Under these conditions,
epidural anesthesia would be analogous to multiple paravertebral blocks. Because the intervertebral foramina are
patent only in young people, it is suggested that there is an inverse relationship between the size of the foramina and
the spread of epidural anesthesia. All investigators have not observed such a relationship. Hence, paravertebral block
probably plays only a minor role in the production of epidural anesthesia.
The dorsal root ganglia appear to be a local site of action because of their anatomic location in the epidural space.
Tissue distribution studies of local anesthetic agents administered into the subarachnoid space have revealed
minimal concentration of lidocaine in dorsal root ganglia compared with other subdural neural structures, suggesting
that dorsal root ganglion inhibition is not a primary determinant of epidural anesthesia.
The intradural spinal roots show a high concentration of local anesthetic agent after either subarachnoid or epidural
injection. The dermatomal progression of anesthesia after epidural administration is also consistent with conduction
block of the spinal roots. The anatomic characteristics of the neural membranes in the region of the spinal roots
favor the diffusion of anesthetic drugs. In this area, the dura mater is relatively thin and there are numerous
arachnoid villi that increase the surface area available for diffusion of anesthetic agents from the epidural space. A
concentration of analgesic drug localized in the dural sleeves containing the spinal roots would soon exceed the
minimum effective anesthetic level required for conduction blockade of these spinal roots.
The spinal cord itself also takes up the anesthetic drug. The concentration within the cord, however, is less than that
in the spinal roots. Moreover, a greater quantity of drug is located in the periphery than at the center of the cord. The
dermatomal onset pattern of epidural anesthesia and the physiologic differences observed between subarachnoid and
epidural anesthesia indicate that the spinal cord is not the initial site of action after epidural administration.
However, the regression of epidural anesthesia does not follow the same segmental distribution observed at the
onset of analgesia. During the recovery phase, the cranial level of analgesia appears as a straight line encircling the
body like a belt, which is analogous to a transverse action through the cord. This suggests that spinal cord blockade
does occur after epidural administration of local anesthetic agents but only after inhibition of conduction in the
spinal roots. It therefore appears that the mechanism of epidural anesthesia is primarily caused by sensory and motor
spinal root inhibition, followed by spinal cord blockade and, possibly, in young people, conduction block in the
paravertebral nerve trunks.
DRUGS FOR EPIDURAL ANESTHESIA
The basic pharmacologic properties of the various local anesthetic agents influences the resultant quality of epidural
anesthesia. The drugs used for epidural anesthesia may be classified according to their intrinsic anesthetic potency
and duration of action. Procaine, chloroprocaine, lidocaine, mepivacaine, and prilocaine are commonly administered
as 1% to 3% solutions, whereas tetracaine, bupivacaine, and etidocaine are employed in concentrations of 0.25% to
1.5%. These agents can be divided into three categories on the basis of analgesic duration:
1. For short-duration block (30–90 min): procaine and chloroprocaine

2. For moderate-duration block (60–180 min): lidocaine, mepivacaine, and prilocaine
3. For prolonged block (180–360 min): tetracaine, bupivacaine, and etidocaine
Initial onset usually occurs within 5 to 10 minutes after epidural administration of the various agents and complete
onset commonly occurs 10 to 20 minutes after injection of the anesthetic solution. Differences in epidural onset time
between the various agents are significantly less than observed after other regional anesthetic techniques, such as
brachial plexus blockade. For example, an average difference of approximately 10 minutes’ onset time was observed
between mepivacaine and bupivacaine in brachial plexus blocks, whereas an average difference of only 1.5 minutes
was found when these agents were used for epidural anesthesia. Marked variations in onset of epidural anesthesia
have been reported by various investigators studying the same agent. Such variations are probably related to the
method of evaluation.
Analgesic duration is commonly divided into (1) two-segment regression, that is, the time required for analgesia to
regress two dermatomes from the highest level of block; and (2) total duration, that is, the time for complete
disappearance of analgesia from all dermatomes. The interval between two-segment regression and total recovery
from analgesia is considerably longer for the long-acting agents compared with the agents of moderate total
duration. In general, the duration of epidural anesthesia is markedly shorter than the duration of major nerve
blockade. However, the difference in duration between epidural and major nerve blockade is less for agents such as
361
lidocaine and mepivacaine than for compounds possessing an intrinsically longer duration of action (e.g.,
bupivacaine and tetracaine). Considerable variation also exists in the values for anesthetic duration reported by
different investigators for the same agent, which again reflects differences in the method of analgesic evaluation.
Duration of anesthesia may be influenced by the concomitant use of vasoconstrictor agents. In general, the duration
of agents of short or moderate activity is significantly prolonged by the use of epinephrine-containing solutions,
whereas the long-acting agents benefit little from the addition of epinephrine. The optimal concentration of
epinephrine required to retard the vascular absorption of local anesthetic agents from the epidural space and thus
prolong the duration of anesthesia may vary depending on the relative vasodilator properties of the different
analgesic drugs. The optimal concentration of epinephrine for each anesthetic agent has not been well elucidated. A
1:200,000 (5-µg/mL) concentration of epinephrine is usually employed with all epidurally administered anesthetic
drugs. This concentration of epinephrine has been demonstrated to be optimal for lidocaine and etidocaine.
CARDIOVASCULAR EFFECTS OF SPINAL AND EPIDURAL ANESTHESIA
Central neural blocks of the lumbar epidural or subarachnoid type are frequently associated with a fall in systemic
blood pressure. For example, Moore reported hypotension in 39% to 45% of patients after spinal or epidural
[25]
anesthesia. Subarachnoid anesthesia to the T5 level causes a decrease in stroke volume, cardiac output, and
peripheral vascular resistance, undoubtedly accounting for the rather high rate of hypotension. Because the doses
used for spinal anesthesia are quite small, such cardiovascular changes during subarachnoid anesthesia appear
related solely to the sympathetic blockade produced by this procedure rather than to a direct effect of the local
anesthetic agent.
Hypotension may also occur after epidural anesthesia, but the mechanism appears to be more complex. The degree
of hypotension after peridural blockade is related in part to the level of anesthesia, the local anesthetic agent, the
concomitant use of vasoconstrictor drugs, and the status of the patient. For example, Bonica and associates [26]
reported that epidural anesthesia extending to the first thoracic segment or higher was associated with a fall in mean
arterial blood pressure of 16%, a decrease in total peripheral resistance of 18%, and little change in cardiac output.
However, analgesia to T4 or below failed to produce a significant change in blood pressure, peripheral resistance, or
cardiac output. These differences were related in the extent of the sympathetic blockade. T1 blocks resulted in a
significant increase in both upper and lower limb blood flow and a fall in total peripheral resistance, indicating
widespread sympathetic blockade and peripheral vasodilation. T4 blockade produced an increase in lower limb
blood flow, a fall in upper limb flow, and little change in total peripheral resistance, suggesting a compensatory
vasoconstriction in the upper half of the body.
Because relatively large doses of local anesthetic agents are employed for epidural anesthesia, the drug itself may be
responsible for some of the cardiovascular alterations observed after epidural blockade. For example, lidocaine
blood levels of 4 to 7 µg/mL occurred in some of the subjects involved in the epidural study conducted by Bonica
and associates. In these subjects, a fall in total peripheral resistance was offset by an increase in cardiac output,
[26]
such that little change in mean arterial blood pressure occurred. The increased cardiac output was believed to be
caused by a direct effect of lidocaine on the vasomotor center in the central nervous system. The use of excessive
amounts of local anesthetic drug for regional anesthesia results in blood levels that may produce direct cardiac and
peripheral vascular depression, exaggerating the hypotensive state caused by sympathetic blockade.
The specific local anesthetic agent employed can influence the changes in cardiovascular function produced by the
regional anesthetic procedure. A comparison of drugs of different inherent anesthetic duration (i.e., lidocaine and
etidocaine) in epidural analgesia revealed that the magnitude of cardiovascular changes was similar for these two
agents, but the duration of hypotension after etidocaine blockade was significantly prolonged. This prolonged
hypotensive action was directly related to the longer duration of epidural anesthesia and sympathetic blockade
produced by etidocaine.
Anesthetic solutions employed for epidural analgesia frequently contain a vasoconstrictor drug, usually epinephrine,
which influences the circulatory changes associated with the anesthetic procedure. Epidural blockade to the T5 level
with plain lidocaine produced a 5% to 10% change in cardiac output, peripheral resistance, and arterial pressure. In
contrast, lidocaine with epinephrine resulted in a 49% increase in cardiac output, a 37% decrease in total peripheral
resistance, and a 10% decrease in mean arterial pressure. The marked increase in cardiac output and decrease in total
peripheral resistance was ascribed to the β-adrenergic receptor-stimulating effect of absorbed epinephrine.
The physiologic status of the patient also influences the circulatory changes after regional anesthesia. The use of
lidocaine-epinephrine solutions to induce epidural analgesia in hypovolemic subjects caused a 23% decrease in
arterial pressure compared with a 10% fall in normovolemic volunteers. This difference was due to the absence of a
362
compensatory increase in cardiac output in the hypovolemic subjects. Epidural administration of plain lidocaine in
the presence of hypovolemia produced signs of severe cardiovascular depression, believed to be related to a greater
myocardial uptake of lidocaine and leading to a significant decrease in cardiac contractility.
The direct cardiovascular effect of local anesthetic agents and the circulatory alterations resulting from epidural
blockade can be compared in the following manner: The blood level of lidocaine after the administration of 400 mg
of this agent into the lumbar epidural space is similar to that produced by the intravenous injection of 1 mg/kg
lidocaine. However, the cardiovascular effects are quite different. Little or no change in blood pressure, peripheral
vascular resistance, cardiac output, and heart rate occurs after the intravenous administration of 1 mg/kg of
lidocaine. On the other hand, epidural anesthesia results in a significant fall in arterial blood pressure, caused
primarily by a decrease in peripheral vascular resistance, with little or no change in cardiac output and a slight rise
in heart rate. These cardiovascular effects are obviously the result of sympathetic blockade and a subsequent
reduction in peripheral vascular tone rather than a direct vasodilator effect of the local anesthetic agent.
The complications of epidural anesthesia occur because of poor patient selection for the particular surgical
procedure, the condition of the patient, and improper technique. Improper technique could result in dural puncture,
total spinal anesthesia, epidural venous injection of the local anesthetic, and local anesthetic toxicity. These
complications are preventable by following simple guidelines: (1) Know the anatomy of the area well; (2) Exercise
careful sterile technique; (3)If in doubt, take it out; (4) Aspirate and avoid injection into a needle or catheter
containing blood or other fluid; (5) Inject small test dose (if epinephrine is added to the test dose the cardiac
response will act as an alert to probable venous injection) and wait an appropriate interval for possible response.
Some anesthesiologists believe that the use of a straight Crawford needle aids in placement of the epidural catheter
without significant risk of dural puncture. The Tuohy needle with Huber point may not afford such protection.
Other complications include infection or epidural hematoma. Care must be taken to prevent contamination of the
catheter by avoiding puncture near a site of active infection, protecting the puncture site with sterile dressings,
frequently inspecting and redressing the site for long-term maintenance. Epidural hematomas can be prevented by
avoiding the use of epidural catheters in patients with clotting abnormalities, such as severe liver disease, uremia, or
thrombocytopenia, or in patients on heparin therapy. Patients who are receiving low-dose heparin to prevent deep
vein thrombosis should be evaluated as to the more important indication, that for prevention of deep vein thrombosis
or that for epidural anesthesia. Should epidural anesthesia prove to be a greater indication, heparin therapy should be
stopped 12 hours before surgery, and a partial thromboplastin time within the normal range should be obtained
before starting the epidural placement. One important consideration is that epidural anesthesia seems to improve
blood flow in the lower extremities and prevent occurrence of deep vein thrombosis. The development of epidural
hematoma is signaled by severe back pain and rapid onset of neurologic deficits. Such signs should lead to further
evaluation of a patient with an epidural catheter or of a patient after epidural block.
Spinal cord injury and the development of arachnoiditis or transverse myelitis are extremely rare complications,
which are preventable by careful placement of needles and during injection of noncontaminated recommended drugs
into the epidural space.
It is generally accepted that the benefits of epidural anesthesia for abdominothoracic surgery far outweigh the
complications; therefore, the anesthesiologist must gain experience and skill in the use of this technique.
REFERENCES
1. BridenbaughPO, Greene NM: Spinal (subarachnoid) neural blockade. In Cousins MJ, Bridenbaugh PO (eds): Neural Blockade in Clinical
Anesthesia and Management of Pain. Philadelphia, JB Lippincott, 1988; pp 213–251.
2. CoatesM: Combined subarachnoid and epidural techniques. A single space technique for surgery of the hip and lower limb. Anaesthesia 37:89–
90, 1982.
3. Eldor J, Olshwang D: Combined spinal-epidural anaesthesia for prostatectomy. Br J Anaesth 60:121–122, 1988.
4. Forster SJ: Combined subarachnoid and epidural techniques. Anaesthesia 38:72, 1983.
5. Mumtaz MH, Daz M, Kuz M: Combined subarachnoid and epidural techniques. Anaesthesia 37:90, 1982.
363
6. Brownridge P, Cohen SA: Neural blockade for obstetrics and gynecologic surgery. In Cousins MJ, Bridenbaugh PO (eds): Neural Blockade in
Clinical Anesthesia and Management of Pain. Philadelphia, JB Lippincott, 1988, pp 593–634.
7. Rawal N: Single segment combined subarachnoid and epidural block for caesarean section. Can Anaesth Soc J 33:254–255, 1986.
8. Carrie LES: Epidural versus combined spinal-epidural block for caesarean section. Acta Anaesthesiol Scand 32:595–596, 1988.
9. Lewis M, Thomas P, Wilkes RG: Hypotension during epidural analgesia for caesarean. Anaesthesia 38:250, 1983.
10. Nikalls RWD, Dennison B: A modification of the combined spinal and epidural technique. Anaesthesia 39:935–936, 1984.
11. Kileff ME, James FM, Dewan DM, et al: Neonatal neurobehavioral responses after epidural anesthesia for cesarean section using lidocaine and
bupivacaine. Anesth Analg 63:413–417, 1984.
12. Thorburn J, Moir DD: Bupivacaine toxicity in association with extra-dural analgesia for caesarean section. Br J Anaesth 56:551–553, 1984.
13. Larsen JV: Obstetric analgesia and anaesthesia. Clin Obstet Gynaecol 9:685–710, 1982.
14. Morgan BM, Aulakh JM, Barker JP, et al: Anaesthesia for caesarean section. Br J Anaesth 55:885–889, 1983.
15. Clark RB, Thompson DS, Thompson CH: Prevention of spinal hypotension associated with cesarean section. Anesthesiology 45:670–674,
1976.
16. Datta S, Alper MH: Anesthesia for cesarean section. Anesthesiology 53:142–160, 1980.
17. Brownridge P: Epidural and subarachnoid analgesia for elective caesarean section. Anaesthesia 36:70, 1981.
18. Rawal N, Schollin J, Wesström G: Epidural versus combined spinal epidural block for cesarean section. Acta Anaesthesiol Scand 32:61–66,
1988.
19. Crawford JS: Some maternal complications of epidural analgesia for labour. Anaesthesia 40:1219–1225, 1985.
20. Phillips DC, MacDonald R, Lyons G: Possible subarachnoid migration of an epidural catheter. Anaesthesia 41:653–654, 1986.
21. Eldor J, Chaimsky G: Combined spinal-epidural needle (CSEN). Can J Anaesth 35:537–539, 1988.
22. Dennison B: Combined subarachnoid and epidural block for caesarean section. Can J Anaesth 34:105–106, 1987.
23. Kehlet H: Modification of responses to surgery by neural blockade. Clinical implications. In Cousins MJ, Bridenbaugh PO (eds): Neural
Blockade in Clinical Anesthesia and Management of Pain. Philadelphia, JB Lippincott, 1988; pp 129–175.
24. Dahl JB, Rosenberg J, Dirkes WE, et al: Prevention of postoperative pain by intraoperative spinal + epidural blockade and postoperative
combined low-dose epidural bupivacaine + morphine and systemic piroxecam. Proceedings of European Society of Regional Anaesthesia, Oulu,
Finland, 1989, p 87.
25. Moore DC: Complications of regional anesthesia. In Bonica JJ (ed): Regional Anesthesia. Philadelphia, FA Davis, 1971.
26. Bonica JJ, Akamatsu TJ, Berges PU, Morikawa K: Circulatory effects of peridural block. II. Effects of epinephrine. Anesthesiology 34:514,
1971.
364
Section IV - Chapter 19 - Subarachnoid and Epidural Anesthesia
Chapter 19 - Subarachnoid and Epidural Anesthesia
MIGUEL ANGEL REINA

JOSE DE ANDRÉS
ANDRES LÓPEZ
The meninges envelop the brain and spinal cord and consist of three membranes (external to internal): dura mater,
arachnoid, and pia mater, respectively. In association with their cellular and fibrillar components, these membranes
constitute an organ in their own right. The cellular and fibrillar components in turn are morphologically and
physiologically implicated in the mechanical, immunologic, and thermal protection of the brain and spinal cord.
They also play an important role in the passage of substances to the brain tissue and in the elimination of waste
products. These functions are made possible by the multiple communications between the cerebrospinal fluid (CSF)
and the intercellular space of the central nervous parenchyma.
The spinal meninges—particularly the dura mater— provide mechanical protection during dural sac displacement
owing to (1) the elasticity of their ultrastructure, which consists of collagen fiber bundles that interweave at different
angles, yielding a scissors-like appearance, and (2) the presence of an important number of elastic fibers. This
system is protected by the epidural tissue, which contains abundant fat, and by the vertebral venous plexuses. Unlike
the dura mater, the arachnoid mater constitutes a physiologic barrier that functions in diffusion processes and in the
exchange of fluids and solutes through the dural sac. [1] [2] [3]
In this chapter, the functions of each of the meningeal components are analyzed, although all three layers form a
single structure with combined functions.
Dura Mater
The dura mater consists of a cranial portion and a spinal portion. The former is composed of a richly vascularized
and innervated external periosteal layer that adheres to the internal surface of the skull and an internal squamous cell
layer. In certain places, these two layers separate to form large venous sinuses. Although the spinal dura mater is
firmly fixed to the anterior and posterior walls of the vertebral canal in the upper cervical region, the anchor of the
dural sac below this segment is made up of connective tissue bundles with structures similar to that of the dura
mater.[4]
The dural nerve plexuses contain sympathetic and parasympathetic nerve fibers and abundant sensory fibers, most of
which are not myelinated. The sensory fibers are found either as free nerve endings within the dura mater, or lying
in close proximity to the blood vessels. Immunohistochemical studies have revealed the presence of a great variety
of transmitters and neuropeptides in the dural nerves, including acetylcholine,serotonin, substance P, calcitonin
peptide-related gene, neuropeptide Y, vasoactive intestinal peptide, and so forth. On the other hand, a great number
of free cells are present.
[1] [2] [3]
From the perspective of histology, the dura mater has been described as the most external of the meningeal
membranes, with a dense structure composed of collagen tissue. Although the collagen fibers were thought to be
arranged longitudinally and in parallel, electron microscopy studies have shown them to possess a complex
organization, with interspaced elastic fibers and some fibroblasts ( Figs. 19–1 , 19–2 , 19–3 , 19–4 ).
[5]
In 1989, Fink used transmission electron microscopy to study samples of dura mater from cadavers of different
[6]
ages. The collagen fibrils typically measured 0.06 micron (µm) in diameter, were arranged in wavy interlacing
bundles oriented in various directions, and had elastic fibers measuring 1 to 2 µm in diameter.
365
Figure 19-1 Full thickness of the dural sac at the lumbar level. The dural laminas take up concentric positions parallel to the spinal cord. The subdural space is an
artifact that was produced during dissection. Scanning electron microscopy. (Original magnification ×300. Bar: 100 µm.)(From Reina MA, Dittmann M, López Garcia
A, van Zundert A: New perspectives in the microscopic structure of human dura mater in the dorsolumbar region. Reg Anesth 22:161–166, 1997.)
[7] [8]
In 1996, Reina discovered that collagen fibers form wavy bands that intercross at different angles, generating
different patterns depending on the region examined in a given sample. Three fiber patterns were defined: type 1, a
lax weaving of easily individualized fibers distributed in different directions ( Fig. 19–5 ); type 2, fibers forming
bundles in a given direction, with each bundle consisting of dozens of fibers separated by ground substance ( Fig.
19–6 ); and type 3, which are type 2 fibers that merge to form compact plaques of similar width.
The collagen and elastic fibers form concentric laminas surrounding the spinal cord and have a global thickness
equivalent to many concentric laminas (78 to 82) parallel to the spinal cord. Each lamina of the dura mater measures
4 µm to 5 µm and consists of 8 to 12 thin subunits known as thin dural laminas ( Figs. 19–7 and 19–8 ). [8]
At the lumbar level, the average dura mater is 320 µm thick, with variations in the anterior, lateral, and posterior
portions at different vertebral levels. [9]
Figure 19-2 Partial thickness of the dural sac at the lumbar level, with detail of the dural laminas. The dural laminas take up concentric positions parallel to the
spinal cord. Scanning electron microscopy. (Original magnification ×3700.)(From Reina MA, López A, Dittmann M, de Andrés JA: Análisis estructural del
espesor externa e interna de la duramadre humana por microscopia electrónica de barrido. Rev Esp Anestesiol Reanim 43:135–137, 1996.)
366
Figure 19-3 Elastic fiber in the epidural surface of the dura mater. Scanning electron microscopy. (Original magnification ×3700. Bar: 10 µm.)(From Reina MA,
López A, Dittmann M, de Andrés JA: Análisis de la superficie externa e interna de la duramadre por microscopia electrónica de barrido. Rev Esp Anestesiol Reanim
43:130–134, 1996.)
The dura mater enveloping the spinal nerve roots at the conjugate foramina has a more lax and disorganized fiber
structure, with a gradual decrease in thickness to 80 µm in some areas.
Collagen fibers are cylindrical and smooth; they average 0.1 µm in thickness. The elastic fiber surfaces are
comparatively rough and can anchor a number of collagen fibers. The diameter of the fiber surfaces is
Figure 19-4 Partial thickness of the dural sac at the lumbar level. Detail of sectioned collagen and elastic fibers. Transmission electron microscopy. (Original
magnification ×7000.)
367
Figure 19-5 Epidural surface of the dura mater. Packed fibers grouped in bands adopting different directions, type 1. Scanning electron microscopy. (Original
magnification ×1000. Bar: 10 µm.)(From Reina MA, López A, Dittmann M, de Andrés JA: Análisis de la superficie externa e interna de la duramadre por microscopia
electrónica de barrido. Rev Esp Anestesiol Reanim 43:130–134, 1996.)
about 20 times greater than that of the collagen fibers (i.e., average of 2 µm). Longitudinal sections of the collagen
[7]
fibers show striations at intervals of 67 nanometer (nm) ( Fig. 19–9 ). Each elastic fiber has a central structure of
amorphous material surrounded by a thin lamina of microfibrils measuring 10 nm in thickness. In addition to fibers,
the dura mater also contains diffuse fibroblasts in parallel arrangement. These fibroblasts are flattened and measure
about 1 µm; the nuclei are flattened and contain finely dispersed chromatin. Thecytoplasm is rich in organelles
(especially mitochondria), with a scarce granular endoplasmic reticulum, free ribosomes, and a number of plasma
membrane involutions suggestive of pinocytosis or ectocytic processes. Macrophages are present in the thickness of
the dura mater ( Fig. 19–10 ).
Figure 19-6 Epidural surface of the dura mater. Bundles of fibers in a given direction, type 2. Scanning electron microscopy. (Original magnification ×8000. Bar: 1
µm.)(From Reina MA, López A, Dittmann M, de Andrés JA: Análisis de la superficie externa e interna de la duramadre por microscopia electrónica de barrido. Rev
Esp Anestesiol Reanim 43:130–134, 1996.)
368
Figure 19-7 Partial thickness of the dural sac at the lumbar level. Detail of four dural laminas. The dural laminas take up concentric positions parallel to the spinal
cord. Each dural lamina measures 5 µm. Note the presence of 10 to 12 small dural laminas with fibers organized in different directions within each dural lamina.
Scanning electron microscopy. (Original magnification ×4000.)(From Reina MA, López A, Dittmann M, de Andrés JA: Análisis estructural del espesor externa e
interna de la duramadre humana por microscopia electrónica de barrido. Rev Esp Anestesiol Reanim 43:135–137, 1996.)
Arachnoid
From the macroscopic perspective, the arachnoid layer is a delicate membrane occupying the intermediate zone of
the three meningeal components. Its external surface in vivo has been considered to be in contact with, but not
adhered to the internal surface of the dura mater—with only a virtual space between them, known as the subdural
space. It has been postulated that this membrane is in contact with the dura mater as a result of the hydrostatic
pressure exerted by the
Figure 19-8 Partial thickness of the dural sac at the lumbar level. Detail of sectioned dural laminas. Transmission electron microscopy. (Original magnification
×20,000.)
369
Figure 19-9 Thickness of the dura mater. Detail of collagen fibers. Note the characteristic striations of the collagen fibers. Transmission electron microscopy.
(Original magnification ×50,000.)
CSF, and that diminished pressure in the cadaver can cause separation of the arachnoid from the dura mater, giving
rise to an artificial space.
In histologic terms, the arachnoid membrane has been classically described as a tissue composed of leptomeningeal
cells with an aqueous cytoplasm forming long and irregular pseudopodia that mingle with the pseudopodia of the
adjacent cells. The accuracy of this concept, however, is currently under investigation.
It is now thought that the arachnoid mater is formed by the barrier arachnoid lamina, the reticular arachnoid lamina,
and the trabecular arachnoid component ( Fig. 19–11 ). [10] [11]
Figure 19-10 Macrophage in the thickness of the dura mater. Note phagosomes containing foreign particles. Transmission electron microscopy. (Original
magnification ×7000.)
370
Figure 19-11 Diagram of the dura mater, subdural compartment, arachnoid laminas, and arachnoid trabecular component.(From Reina MA, López A, de Andrés JA, et
al: Existe el espacio subdural? Rev Esp Anestesiol Reanim 45:367–376, 1998.)
BARRIER ARACHNOID LAMINA
Inside the cellular level of the subdural compartment lies a cellular component forming a layer 5 µm thick. These
cells are composed of epithelial-like tissue and are not as flat as those of the external layer, which consists of
neurothelial cells.
The cellular lamina is distinct from the rest of the arachnoid mater because of the compact junctions between its
cells and because of the presence of a basal membrane separating the more external arachnoid cells of the barrier
lamina from the internal arachnoid cells that occupy the reticular arachnoid lamina.
RETICULAR ARACHNOID LAMINA
Inside the barrier arachnoid lamina lies the reticular arachnoid lamina, between 10 µm and 20 µm thick and
composed of irregularly interweaving cells alternating with an increased amount of collagen fibers and intercellular
lacunar spaces of various sizes, which are filled with amorphous foreign material ( Fig. 19–12 ).
371
Figure 19-12 Arachnoid sheath surrounding a vessel within the subarachnoid space. Scanning electron microscopy. (Original magnification ×250. Bar: 100 µm.)
TRABECULAR ARACHNOID COMPONENT
The trabecular arachnoid component occupies the innermost region of the arachnoid and is in direct contact with the
subarachnoid space. It is composed of true leptomeningeal cells and represents the cellular complement of the
trabecular component, which contributes to the formation of the spider web pattern that is located within the
subarachnoid space. The leptomeningeal cells line the vessels in the subarachnoid space and fuse with their
adventitial component ( Fig. 19–12 ). In many places, numerous connective tissue fibrils are connected wi th these
cells, forming sheaths that surround small spaces. On the functional level, it has been found that when foreign
substances are injected into the subarachnoid space, the cells of the
Figure 19-13 Dural lesion with 25-gauge Whitacre Becton-Dickinson needle in the arachnoid surface. Note that the arachnoid lesion is
larger than the dura mater lesion. Scanning electron microscopy. (Original magnification ×200. Bar: 100 µm.)(From Reina MA, López A, de
Andrés JA, et al: Estudio en cadáveres mediante microscopia electrónica de barrido de la lesión dural producida por la aguja Whitacre y
Quincke. Rev Esp Anestesiol Reanim 44:56–61, 1997.)
372
Figure 19-14 Dural lesion with 25-gauge Quincke Becton-Dickinson needle in arachnoid surface. Note that the arachnoid lesion is larger than the dura mater lesion.
Scanning electron microscopy. (Original magnification ×200. Bar: 100 µm.)(From Reina MA, de Leon-Casasola OA, López A, et al: An in vitro study of dural lesions
produced by 25-gauge Quincke and Whitacre needles evaluated by scanning electron microscopy. Reg Anesth Pain Med 25:393–402, 2000.)
trabecular arachnoid component swell and engage in phagocytic activity—ingesting the foreign particles and even
detaching from the trabecula to become freely displaced macrophages.
Pia Mater
The pia mater is a fine layer of vascular connective tissue that directly envelops the spinal cord and its nerve roots.
Below the conus medullaris, the pia mater is continuous with the filum terminale, which progressively thins and
descends into the cauda equina, perforating the terminal portions of the dura mater and arachnoid, and ultimately
fusing with the connective tissue beyond the first coccygeal segment. The denticulate ligament is composed of 22
lateral prolongations extending from the pia mater to the dura mater. The pia mater is the most internal of the
[4]
meningeal membranes and constitutes the last barrier to the glioneuronal tissue of the central nervous system.
However, this membrane is known to be highly permeable, allowing rapid passage of local anesthetics, morphine-
like compounds, and other molecules introduced into the subarachnoid space and, in some cases, affording an
almost instantaneous analgesic response. The existence of natural fenestrations in the surface of the pia mater could
account for these characteristics.
Dural Sac
The wall of the dural sac consists of the dura mater with the arachnoid layer lining its internal surface. The lateral
projections of the dural sac envelop each pair of spinal nerve roots, and the sac extends from the occipital foramen
to the inferior margin of the second sacral vertebra, where it continues as the filum terminale of the first coccygeal
segment. In a small proportion of individuals, the dural sac extends below the sacrum, 2 to 3 cm from the
sacrococcygeal membrane; this infrequent anatomic variant increases the risk of accidental dural puncture during
caudal anesthesia. The epidural space is a concentric cavity located between the dural sac and the bony spinal
[12] [13] [14]
canal. It is formed by superpositioning of the vertebrae and the arcuate ligaments occluding the vertebral
interlaminar spaces. Grouped collagen bundles containing hundreds of fibers form bridgelike structures
[12] [13] [14]
through the epidural space; at one extremity, these fibers mingle with the dural fibers; at the other, they merge with
the collagen lining covering the periosteal surface of the spinal canal. In some individuals, these collagen bridges
tend to incompletely divide the anterior epidural space into two longitudinal compartments. [11] [12] [13] [14]
The lateral dural prolongations envelop each pair of spinal nerve roots and include a small subarachnoid fundus that
intimately adheres to the distal portion of the corresponding spinal ganglion, at the point where the anterior and
posterior roots fuse to form the conjugate nerve, or the first portion of the mixed nerve. Here, the dura mater is
slightly thinner posteriorly.
From this point, the dura runs contiguous to the epineurium. The dural sheaths terminate at different positions in
relation to the intervertebral foramina at their various levels.
In the cervical region, this termination lies within the foraminal striae, whereas in the dorsal zone it is related to the
internal aspect of the foramen, and in the lumbar and sacral zone it lies entirely within the vertebral canal.
373
Anatomic Implications for Subarachnoid and Epidural Anesthesia
PERMEABILITY OF THE DURAL SAC
Different types of molecules are able to penetrate the dural sac. In this context, opioids and local
[15] [16] [17] [18] [19] [20] [21] [22] [23]
anesthetics were among the molecules most frequently studied by Bernards and colleagues. These [15] [16] [17] [18] [19] [20] [21] [22] [23]
authors found that although the arachnoid lamina occupies only 10% of the internal thickness of the dural sac, it
constitutes the main barrier against the free diffusion of molecules. Arachnoid resistance to the free passage of
molecules may be about 90%. In contrast, the dura mater is highly permeable, particularly to hydrophilic
[16]
substances, because of the presence of abundant amorphous material between the dural fibers. This amorphous
substance is composed of proteoglycans and contains a large amount of water; as a result, it is quite permeable to
hydrosoluble molecules. Arachnoid resistance to diffusion is in turn attributed to the multiple cellular planes and
strong intercellular junctions that inhibit passage of substances through the lipidic cell membranes. From the
physiologic perspective, this barrier effectively seals off the dural sac and limits water and solute loss from the CSF.
It contributes a certain volume to help maintain the equilibrium regulated by CSF production and reabsorption. The
histologic characteristics of the arachnoid and dura mater may explain why intermediately liposoluble molecules are
more permeable than other highly liposoluble or hydrophilic substances. [18] [21] [24] [25]
Regarding the metabolic capacity of the dural sac, Bernards and colleagues found that exogenous substances such as
epinephrine or endogenous neurotransmitters such as acetylcholine could be metabolized at the level of the
arachnoid. However, these processes, which can be implicated in pain suppression at the spinal level, are little
[24]
known at present.
Bernards and colleagues suggested that the hypothesis of molecular passage from the epidural space to the
subarachnoid space through the so-called arachnoid granulations based on retrograde flow phenomena was not
valid, because such movement through the granulations is strictly unidirectional, allowing the passage of water and
solutes from the CSF to the epidural space and thereby contributing to the physiologic process of CSF clearance. [17]
These authors likewise argued against the passage of molecules from the epidural space to the spinal cord through
radicular arterial perfusion. [26]
Meningeal permeability in relation to lipophilic substances has been defined in terms of the octanol:buffer partition
coefficient; in this context, it was found that the permeability of the dural sac increases exponentially up to a
coefficient value of 129, after which it gradually decreases. This discovery showed that very hydrophilic
[15]
substances with an octanol:buffer partition coefficient of 1 (e.g., morphine) show practically no differences in dural
sac permeability than substances with an octanol:buffer partition coefficient of 1737, such as sufentanil ( Table 19– [15]
1 ).
In contrast to these results, Mc Ellistrem and Benmington found the permeability of different molecules to be
[28]
independent of liposolubility, corresponding to a simple diffusion process. However, the validity of the method used
by these authors was questioned by Bernards and colleagues. The results of Mc Ellistrem and Benmington can be
[29]
explained if the arachnoid is partially detached during dissection. Moreover, these results corresponded to analysis
of the permeability of the dura mater isolated from the arachnoid, whereas the work of Bernards and colleagues
focused
TABLE 19-1 -- PARTITION AND PERMEABILITY COEFFICIENTS
Partition Coefficients Permeability Coefficient

Octanol: Buffer (cm/min × 10−3 )
Alfentanil 129 2.30
R-Bupivacaine 560 1.60
S-Bupivacaine 1.60
Lidocaine 110 1.45
Fentanyl 955 0.92
Sufentanil 1737 0.75
Morphine 1 0.62
[15] [22] [23] [27]
Data from references , .
on permeability through the full thickness of the dural sac.
374
With regard to the comparative spinal distribution and clearance kinetics of intrathecally administered morphine,
fentanyl, alfentanil and sufentanil, Unmenhofer found that full exposure of the spinal cord to morphine is high in
[19]
comparison with fentanyl, alfentanil, and sufentanil after subarachnoid injection. This high exposure to morphine[19]
is justified because of its small volume of distribution in the medulla and its slow clearance into the systemic
circulation. The effect of other opioids is different. In effect, alfentanil is rapidly taken up by the systemic
[19]
circulation, whereas fentanyl partly remains in the epidural fat. The nature of sufentanil is that it is highly
[19]
lipophilic and has limited free drug availability within the medulla. [19]
DURAL LESIONS INDUCED BY QUINCKE- AND WHITACRE-TYPE BEVELED NEEDLES
The studies published in the literature on postdural puncture headache (PDPH) have analyzed the use of
[30] [31] [32] [33] [34]
needles with different tip designs and different external diameters. Most authors agree that needles with small
external diameters—pencil point designs cause fewer cases of PDPH because such needles (e.g., Sprotte,
[35] [36]
Whitacre types) produce less damage by separating rather than sectioning the dura mater fibers. However, [30] [31] [32] [33] [34]
when the morphology is examined in detail concerning the damage produced by needles with various tip or bevel
designs, the results obtained tend to contradict the clinical findings.
In 1988, Dittmann and associates reported that the fibers are not uniformly parallel, and that the thickness of the
[37]
dural sac can vary. These authors described the so-called “tin lid” phenomenon: The needle perforation resembles
the top of an almost completely opened tin with the lid hinged at one point. The hole tends to be ellipsoidal when the
needle is inserted through a thick part of the dura; after a short time, it tends to shrink. In comparison, when a
thinner part of the dura is penetrated by a needle of the same size, the resultant hole is larger and shrinks much more
slowly. [37]
In 1993, Celleno and colleagues reported that the gross morphology of the holes produced through the dura by
[38]
needles reveals that puncture hole size depends on the size of the needles used. In this context, Quincke needles
were seen to produce an oval or ellipsoidal hole, whereas pencil point needles (Sprotte or Whitacre needles) produce
a more rounded hole. In all cases, the puncture hole tends to retract after 5 to 15 minutes. Patterns of compressed but
not sectioned fibers are more frequently observed with the pencil point needles.
In 2000, Reina and coworkers studied the effects of dural lesions in recently deceased individuals ( Fig. 19–15 ;
[39]
see also Figs. 19–13 and 19–14 ). The area of the dural lesions produced by Quincke 25G needles 15 minutes after
dural puncture was found to be 0.023 mm2 in the epidural surface and 0.034 mm2 in the arachnoid surface of the
dural sac. In turn, the area of the lesions produced by Whitacre 25-gauge (G) needles was 0.026 and 0.030 mm2 in
the external and internal surfaces of the dural sac, respectively. There were no significant differences in the cross-
sectional area of the punctures produced by Quincke 25-G or Whitacre 25-G needles in the dura or arachnoid ( Fig.
19–16 ; see also Figs. 19–13 , 19–14 , 19–15 ). With Quincke needles, lesion closure was 88.3% and 82.7% of the
original size in the dural and arachnoid surfaces, respectively, whereas in the case of the Whitacre needle, closure
reached 86.8% and 84.8%, respectively. Differences in the morphology of these lesions were observed, however.
Thus, Whitacre
Figure 19-15 Dural lesion with 25-gauge Quincke Becton-Dickinson needle in the epidural surface. The punctures were made with the bevel parallel to the long axis
of the spinal cord. Scanning electron microscopy. (Original magnification ×150. Bar: 100 µm.)(From Reina MA, de Leon-Casasola OA, López A, et al: An in vitro
study of dural lesions produced by 25-gauge Quincke and Whitacre needles evaluated by scanning electron microscopy. Reg Anesth Pain Med 25:393–402, 2000.)
375
needles produced coarse lesions with significant destruction of the dural fibers, whereas the Quincke needles
typically produced U-shaped lesions or flaps resembling the open lid of a tin can, regardless of the direction of the
needle tip. Depending on needle positioning with respect to the spinal cord axis, the size of the lesions produced
[39] [40]
by Quincke needles in the epidural surface was 0.023 mm2 and 0.024 mm2 for parallel and perpendicular
orientations, respectively. In the arachnoid surface, the lesions measured 0.035 mm2 and 0.034 mm2 with these same
respective orientations. No significant differences in terms of lesion size were observed between the two puncture
methods ( Figs. 19–14 , 19–15 , 19–16 ). On analysis of the dural sac lesions in terms of closure, or sealing, and CSF
loss, the characteristics and size of the arachnoid lesions were possibly more important than those of the
corresponding dura mater lesions.
Figure 19-16 Dural lesion with 25-gauge Quincke Becton-Dickinson needle in the epidural surface. The punctures were made with the bevel perpendicular to the long
axis of the spinal cord. Scanning electron microscopy. (Original magnification ×150. Bar: 100 µm.)(From Reina MA, de Leon-Casasola OA, Lopez A, et al: An in
vitro study of dural lesions produced by 25-gauge Quincke and Whitacre needles evaluated by scanning electron microscopy. Reg Anesth Pain Med 25(4):393–402,
2000.)
The occurrence of PDPH has been clinically related to the type of needle employed and to the bevel position or [41] [42]
angle of puncture. The conclusions are based on the classical anatomic description of the dura mater. Studies [41] [43] [44] [45]
have indicated, however, that the lesion produced by a needle in the dura-arachnoid cannot be attributed to the
elastic behavior defined by a synthetic lamina or interwoven cloth model. Scanning electron microscopy studies
have actually suggested a complex viscoelastic behavior in the formation of a dural lesion, influenced by the
characteristics of the perforated dural component on one hand, and of the arachnoid component on the other. The
resulting orifice and its rapid retraction were largely influenced by the arachnoid component, which limits CSF
leakage from the subarachnoid space to the epidural space. This lesion is in turn influenced by the diameter of the
needle used, its tip design, and the repair processes set in motion in response to the structural damage.
Based mainly on clinical evidence, it has been suggested that pencil-tip needles cause less dural damage. The
concept of dural lesions associated with the Quincke-type needles that were developed in the 1940s may no longer
be valid, because the lack of an adequate bevel edge in the old needles produced larger lesions more by a tearing
[45]
action than as a consequence of sectioning. Modern needles, however, produce clean, U-shaped lesions or flaps
resembling the open lid of a tin can and formed by the superpositioning of damaged laminas. On withdrawing the
needle, the U-shaped flap tends to return to its original position, favored by CSF pressure and the viscoelastic
properties of the dura mater—thereby almost completely occluding the dural orifice after 15 minutes. On the other
hand, the lesions produced by pencil-tip needles respond not only to the dural fiber separation theory but possibly
also involve a complex fiber tearing, sectioning, and separation mechanism in which needle design may be of capital
importance.
The maximal extent of the dural lesion depends on the external diameter of the needle, dural sealing mechanism,
percentage effectiveness of sealing, needle tip design, and quality of needle polishing. In this context, needles [46] [47]
with the same tip design but less refined levels of polishing associated with the presence of microfractures or
imperfections would undoubtedly modify the mechanism underlying the dural lesion, resulting in increased fiber
tearing and larger residual lesions ( Fig. 19–17 ).
Needle deformation on impact with vertebral bone or other resistant structures modifies the original tip design.
[48] [49] [50]
In addition to yielding a larger dural lesion, this phenomenon can ultimately lead to the iatrogenic introduction of
376
skin fragments into the subarachnoid space [51] [52] [53] [54]
( Fig. 19–18 ). Holst in 1998, showed images of dural lesions
[55]
produced by different needle designs.
López and coworkers used scanning electron microscopy to study the quality of 200 new needles from different
[47]
manufacturers (see Fig. 19–17 ). In some cases, the authors observed metal surface imperfections and fractures in
pencil point needles.
Figure 19-17 Defective pencil-point needle. New, unused needle. Presence of rough edge in proximity to lateral hole. This rough edge acts as a razor blade or as
multiple microknives upon puncture entry and exit. Such defects produce an indeterminate increase in hole size. Scanning electron microscopy. (Original
magnification ×40).
In these instances, Quincke- and Atraucan-type needles deform easily when they impact on bone. The actual
[48] [49] [50]
amount of deformation is dependent on the puncture angle and the force applied ( Fig. 19–19 ). Such deformation
yields a more damaging needle tip (see Fig. 19–19 ). In contrast, pencil point needles do not deform easily on impact
with bone. Series that assess dural PDPH generally involve many anesthesiologists; therefore, it is difficult to detail
the technique used in each patient, including aspects such as tip impact on bone or modifications in puncture angle
within a resistant ligament, which are situations that can modify the shape of a Quincke-type beveled needle.
Reconsideration should probably be given to whether CSF loss (within the range expected with the use of modern
needles with different tip designs) plays a decisive role in the development of PDPH, or whether multiple variables
are actually involved. In this sense, as yet unknown factors associated with needle insertion into the dural sac may
exert an influence in addition to CSF loss.
Figure 19-18 Defective pencil-point needle used after two contacts with a bony structure during dural puncture. This happens in previously defective needles.
Scanning electron microscopy. (Original magnification ×200. Bar: 100 µm.)
377
Figure 19-19 Defective Atraucam 26-gauge needle after one contact with a bony structure during dural puncture at different incidence angles. Scanning electron
microscopy. (Original magnification ×22. Bar: 1 mm.)
Up to the present, most studies conducted in an attempt to establish a direct relationship between development of
PDPH and CSF loss have employed needles that are extremely thick by current standards. However, it should [56] [57] [58]
be taken into account that not all cases of CSF hypotension have been related to headache. As an example, Iqbal [59]
and coworkers, in 1995, employed magnetic resonance imaging techniques to study CSF loss after lumbar
[60]
puncture and observed no correlation between the volume of CSF leakage and the incidence of PDPH.
With regard to needle bevel alignment parallel or perpendicular to the spinal axis, most clinical studies have
reported fewer patients with PDPH; the needle bevel was aligned parallel to the axis during dural puncture. [41] [42]
These results have been related to the hypothesis that such a bevel alignment causes a smaller dural lesion.
However, examinations of dural lesions in human cadavers do not provide evidence to support this hypothesis.
In 2000, Reina and associates studied the dural lesions produced by Quincke-type 26-G, 25-G, and 22-G needles,
[39] [40]
and observed no differences in the morphology and size of the residual dural lesions ( Fig. 19–20 ). In 1999,
Zetlaoui hypothesized that during movement and when traction is exerted along the longitudinal axis of the dura
[61]
mater, the dynamic dimensions of the hole change. When the hole is made with the bevel parallel to the longitudinal
axis, there is a tendency to close the hole and reduce the CSF leakage. However, when the hole is the result of a
transverse bevel, longitudinal traction makes the hole larger and the CSF leakage greater.
If the dural lesion aperture is analyzed in isolation, the limiting factor is represented by the arachnoid component,
Figure 19-20 Arachnoid surface with dural lesion produced with Quincke 22-gauge needles. There are no significant differences in the cross-sectional areas of the
punctures made with the bevel directions parallel or perpendicular to the axis of the spinal cord. Scanning electron microscopy. (Original magnification ×100. Bar:
100 µm.)
378
which exerts increased resistance to the diffusion of fluids because of its thickness (i.e., it hermetically seals the
dural sac). The external, or dural, component of the lesion affords mechanical resistance to the fragile arachnoid
[10] [62]
membrane but does not prevent fluid diffusion owing to the large percentage of interfibrillar material present,
largely composed of mucopolysaccharides. Hence, early closure of the dural component does not resolve the
leakage of CSF. Fluid loss effectively depends on retraction of the arachnoid lesion. Strictly speaking, dural lesions
should be called dura-arachnoid lesions, because the arachnoid component is comparatively more important than the
dura in sealing off CSF loss. Arachnoid aperture with rupture of the neurothelial cells allows CSF passage toward
the interstice between the neurothelial cells and the collagen fibers of the dural laminas. In the event of important
arachnoid damage, the leaked fluid is taken up by the neurothelial cells, which swell in response and become more
fragile. This situation facilitates neurothelial cell rupture and may, with the accumulation of fluid, give rise to the
formation of a subdural space of variable extent. In patients with such a condition, magnetic resonance studies
[62]
have shown an increase in spinal and cranial meningeal thickness, an increase in hypophyseal size, and,
occasionally, subdural fluid accumulations. These phenomena have received no clear explanation, although the
intervention of reflex vasodilatation has been postulated. Perhaps neurothelial cell edema, dilatation of
[63] [64] [65] [66] [67]
vessels located among the arachnoid cells, and meningeal traction (which causes global central nervous structures to
descend during CSF hypotension episodes) contribute to the appearance of fluid in the recently formed subdural
space, with subdural hematomas caused by rupture of the vessels within the thickness of the arachnoid. The
[68] [69]
extent may be proportional to the intensity of the factors triggering PDPH and may form part of the multiple
variables underlying PDPH.
BIOMECHANICAL PROPERTIES OF THE HUMAN DURA MATER
The dura mater may be well defined as a viscoelastic material; namely, a material possessing viscosity. Viscosity is
defined as the relative resistance to, or ease of, flow and elasticity, which is defined as the tendency of a material to
come back to its original form after an applied force. In vitro models of dural puncture facilitate understanding of
[70]
viscoelastic behavior’s influence in this tissue on hole defects. The force applied by a distracted tissue is a measure
[70]
of the readily available mechanical energy stored in the tissue. In a viscoelastic lamina, there is a loss of restoring
force in the region around the point of a needle that has punctured the dura mater. If different regions of the dural
sac are analyzed, the thickness and strength are greater in the regions of the spine that have greater flexibility. In [70]
1993, Patin and colleagues researched stretch samples in either the longitudinal or transverse direction. Peak
[70]
tensile forces necessary for tissue failure of posterior dura samples of cadavers were 66 to 98 newtons (N) in
longitudinal orientation and 6.9 to 19.6 N in transverse orientation. The relaxation values reflecting behavior of the
dura as viscoelastic material were 15% to 33% in longitudinal orientation and 22% to 25% in transverse orientation.
Longitudinal forces are 5 times to 11.4 times greater than transverse forces. [70]
The viscoelastic properties show the tendency of the dura mater to go back to a less energetic state when tissue
distraction is stopped. According to the studies of Patin and associates, the dura mater possessed resistance-
[70]
affording fibers of a predominantly longitudinal orientation in the samples studied. The force vectors applied to the
dural sac in a given patient depend on the CSF pressure changes and the flexion or extension of the spine, or on the
tension transmitted by flexion of the neck. Physiologically, the dural sac contracts transversely to increase CSF
pressure and thus compensate for a drop in such pressure.
In 1993, Zarzur studied samples of human dura mater and found transverse extensibility (32.0%–53.2%) to be
[71]
greater than longitudinal extensibility (25.8%–43.7%); on the other hand, CSF pressure was seen to induce increased
transverse extensibility of the dural sac, and such changes in turn transmitted increased pressure.
The diffusion of local anesthetics introduced within the epidural space can be modified to the tension of the dural
sac. Nishimura found that diffusion is modified by the pressure changes within the epidural space (e.g., whether
[72]
the patient is sitting or lying down). In 1999, Runza and colleagues recorded a significantly lower ultimate stress
[73]
level in the circumferential direction of human tissues than in the longitudinal direction.
RESISTANCE OF THE DURAL SAC TO NEEDLE PENETRATION
In order to investigate dural sac resistance to puncture and the effects of the tentorial effect, Zarzur correlated dural [74]
sac resistance to the increased tentorial effect that can occur before perforation of the dura mater. Puncture with a
Quincke-type 21-G BD needle with a long 2-mm bevel was carried out in 15 patients. The distance between contact
with the dura mater and the maximal tentorial advance to perforation was 4 ± 1.3 mm, and the negative pressure
generated at maximal tentorial effect was −12.9 ± 6.3 cm of water (range −2 to −25).
379
Westbrook and associates, in 1994, compared, in vitro, the force required to puncture using different needles:
[75]
Tuohy 16-G Steriseal (230 g), Quincke 20-G Steriseal (240 g), Whitacre 22-G Vygon (210 g), Quincke 25-G Becton
Dickinson (BD) (40 g), Whitacre 25-G BD (120 g), pencil-point 26-G Portex (110 g), Quincke 26-G Steriseal (150
g), Quincke 26-G BD (30 g), Whitacre 27-G BD (90 g), and Quincke 29-G Vygon (40-g). A 100-g force being the
equivalent of 0.98 N, these authors stressed that needle manufacturers do not all follow the same gauge standards,
and needles labeled as the same gauge may not have the same external diameter. On close examination of the tip,
Westbrook and associates found that the bevel of the Steriseal needle is significantly shorter, and therefore blunter,
than that of the BD needle. This could explain why the Steriseal needle required significantly more force to puncture
the dura than the BD needle.
In 2000, Lewis and coworkers studied the effects of needle bevel orientation and CSF pressure on dural
[76]
displacement and the force required to penetrate in vitro cadaveric dura using a Tuohy 17-G needle. These authors
required greater force to penetrate the dura with the needle orientated perpendicular to the axis.
IN VITRO STUDIES OF CEREBROSPINAL FLUID LOSS THROUGH DURAL LESIONS PRODUCED BY DIFFERENT NEEDLES
A number of authors, including Cruickshank and associates, Ready and colleagues, Janes and coworkers,
[77] [78] [79]
Westbrook and colleagues, Morrison, and Holst and associates, have conducted in vitro studies of CSF loss
[75] [80] [55]
through dural lesions produced by different needles. The aim of such research has been to indirectly determine the
size of the dural lesions produced by different needles. The results measure the volumes of real or artificial CSF that
escape through the dural lesions produced. The leakage observed exhibited a nonlinear decreasing trend; in effect,
the largest losses occurred in the first few minutes, when lesion size was similar to the cross-sectional area of the
needle used. The CSF flow subsequently decreased exponentially as the lesion retracted and sealed. In analyzing
these studies, it is important to note the method employed in order to draw conclusions that can be extrapolated to
the clinical setting and to compare results among different studies. [77]
Cruickshank found CSF flow to decrease abruptly after the first five minutes to between 5% and 15% of the
[77]
original flow rate. Such in vitro studies can give an idea of the true life situation, but they in no way reflect the
actual CSF losses that occur in patients in the hours and days after dural puncture and are responsible for the
different clinical presentations of PDPH.
On the other hand, the results of different studies published in the literature cannot be compared, because the
methods involved were not exactly the same. In effect, most such studies were conducted on human cadavers,
although some used bovine dura mater. A further problem is that age at the time of death and the time elapsed after
death were rarely specified. The way in which the anatomic structures were dissected has also often been omitted.
The mode of dissection is important consideration, because the arachnoid mater lines the dural sac internally and
constitutes the main barrier component against fluids and solutes. Depending on how arachnoid dissection is
performed, it can be either partially or entirely detached as a result of rupture of the neurothelial cells, which are
very fragile. A dural lesion involving a previously manipulated arachnoid affects the final results obtained. The
thickness and distribution of the elastic and collagen fibers vary in the different regions of the dural sac.
Consequently, depending on whether the study samples are obtained from the anterior, posterior or lateral zones, or
from different levels, the values obtained may vary due to differences in retraction capacity. If fluid pressure on the
lesion differs (as has been observed) and ranges from 12 to 15 to 25 to 30 cm of water, the resulting flow also varies.
From the morphologic perspective, and in order to assess the impact of dural puncture with use of different needle
designs, it is necessary to evaluate fluid loss not only in the first few minutes but over periods of 24 to 48 hours. In
this context, the results recorded in the first minutes reflect the action of the initial retraction mechanisms after
needle withdrawal, and these conclusions cannot be extrapolated to the global situation. On the other hand, as the
study sample is an isolated specimen with the interruption of vascularization, both edema and inflammation around
the lesion are either altered or annulled.
Cruickshank evaluated fluid loss in the first 5 minutes after puncture and observed no significant differences
[77]
between punctures produced by different tip designs or with the bevel oriented either parallel or perpendicular to the
long axis when using Quincke 22-G, 26-G, and 29-G types of needles. Such findings are in conflict with those of
Ready and colleagues, who, in a similar study, determined the time required to accumulate 1 mL of fluid,
[78]
extrapolating the results to flows in milliliters per minute. Based on a different design for flow assessment,
significant differences were observed between the lesions produced by Whitacre 22-G and Quincke 22-G needles,
and between Quincke needle bevel orientation in different directions (parallel or perpendicular to the axis). Janes
and associates, in a follow-up study over 24 and 48 hours, considered orientation of the Quincke needle bevel to be
[79]
of only relative importance. Morrison and colleagues, after accumulating the fluid lost over a 6-minute period,
[80]
concluded that the lesions produced by Whitacre, Sprotte, and Atraucan needles led to less fluid loss than when
Quincke needles were used. Holst and coworkers in turn assessed fluid loss over a period of 5 hours. The
[55]
accumulated volumes were 116 mL with the Quincke 22-G needle; 54.6 mL with the Quincke 25-G needle; 31.2 mL
380
with the Quincke 27-G needle; 16.2 mL with the Quincke 29-G needle; 40.3 mL with the Sprotte 24-G needle; 25.5
mL with the Whitacre 25-G needle; 22.5 mL with the Sprotte needle; 17.2 mL with the Whitacre 26-G needle; 11.8
mL with the Whitacre 27-G needle; and 9.4 mL with the Atraucan 26-G needle. Analysis of these results revealed
significant differences between the different needle tip designs and diameters. In effect, pencil-point needles caused
two to three times less fluid loss than the Quincke beveled needles. No significant differences were recorded
between the Sprotte and Whitacre types of needles. The Atraucan needles yielded the least amount of fluid loss. In
general, all investigators reported less fluid loss with smaller external diameter needles. As regards the Atraucan
needles, it should be taken into account that the results were obtained after isolated puncture of the dura mater,
whereas in the clinical setting, this type of needle has been found to offer very little mechanical tip resistance to
contact with bone or a resistant yellow ligament and can suffer variable tip deformation that leads to dural lesions
quite different from those initially expected (see Fig. 19–19 ).
ARACHNOID AND SUBDURAL COMPARTMENT MORPHOLOGY: ACCIDENTAL SUBDURAL BLOCK
The existence has been postulated of a serous fluid-filled virtual space (the so-called subdural space) between the
dura mater and the arachnoid. The introduction of contrast media into this space during radiologic procedures, or [81] [82]
the accidental positioning of epidural catheters, has confirmed the existence of the subdural space. However, it is
[83] [84]
not certain whether the latter is natural or acquired. In this context, new concepts relating to the arachnoid have
made it possible to study its ultrastructure and question a number of classical anatomic conceptions. [85] [86] [87] [88] [89] [90] [91]
The dura-arachnoid complex is formed from the epidural to the subarachnoid space by ultrastructurally distinct
laminar structures corresponding to the dura mater, the subdural compartment, and the arachnoid ( Fig. [85] [86] [87] [88] [89] [90] [91]
19–21 ; see also Fig. 19–10 ). The subdural compartment is a particularly important element for analyzing the novel
conceptions of the subdural space. In effect, this compartment (also called the dural border cell layer or subdural
mesothelium) is composed of the neurothelial cells located between the last dural laminas and the barrier arachnoid
lamina ( Fig. 19–22 ). These neurothelial cells are flat, displaying long and intermingling prolongations ( Fig. 19–23
). In contrast to the neighboring laminas, the dura mater and the arachnoid, there is a total absence of collagen fibers
among the cells of this compartment. In the event that a separation plane is produced during sample preparation, it is
generally found at this level (i.e., in the thickness of the subdural compartment) but never in the dura mater–
subdural compartment-limiting plane.
Aperture of the subdural space occurs as a result of tearing in the thickness of the subdural compartment,
particularly between the neurothelial cells contiguous to the collagen fibers of the dura mater ( Fig. 19–24 ). On the
other hand, the intercellular junctions are more disseminated in this plane and not as strong as those in the
neighboring cellular plane. In turn, large extracellular lacunar structures are observed, separated by
Figure 19-21 Human arachnoid cells in a barrier arachnoid lamina. Transmission electron microscopy. (Original magnification ×4400.)
381
Figure 19-22 Human interface dura-arachnoid occupied by neurothelial cells. Between the neurothelial cells, there are amorphous materials. No space exists between
the last dural lamina and the barrier arachnoid lamina. In this interface between the neurothelial cells, the subdural space would be produced. Transmission electron
microscopy. (Original magnification ×5000.) (Anesth Analg, 2002, in press.)
thin cytoplasmic bridges. These spaces are filled with a low-resistance amorphous material of uncertain
composition ( Fig. 19–25 ).
[85] [87] [88]
The combination of all of these factors accounts for a considerably diminished cohesion in the external zone of the
dural border cell layer, allowing tearing in response to minimal traction forces. The tendency always to tear along
such a narrow plane in multiple samples corresponds to the presence of collagen in the planes adjacent to the tearing
plane, coinciding with the dura mater and the barrier arachnoid lamina, where strong intercellular junctions are
found.
Up to this point, we have mentioned that the subdural space is produced along a tear plane. However,
Figure 19-23 Neurothelial cell. Detail of soma and prolongations. Scanning electron microscopy. (Original magnification ×15,000. Bar: 10 µm.)(From Reina MA,
López-García A, de Andres JA, et al: Does the subdural space exist? Rev Esp Anestesiol Reanim. 45(9):367–376, 1998.)
382
Figure 19-24 Diagram of the origin of the subdural space.(From Reina MA, López A, de Andrés JA, et al: Existe el espacio subdural? Rev Esp Anestesiol Reanim
45:367–376, 1998.)
in our samples, we have observed the simultaneous formation of a number of parallel and concentric tears within the
subdural compartment. Moreover, the characteristics of the tissue and the distribution of the applied forces can lead
to incomplete tear planes or secondary subdural spaces, whereas other tears can extend to form the so-called
principal subdural space (see Fig. 19–25 ). All such tearing occurs within a thickness of 5µm to 10 µm. When the
[10] [62]
portion of the subdural compartment adhering to the dura mater is observed from within the subdural space,
adherent cytoplasmic fragments can be identified, originating from torn neurothelial cells. [7] [10]
Considering these observations, it may be concluded that the subdural space exists naturally in some patients. There
seems to be no other explanation for
Figure 19-25 Subdural space that has been produced at the dura-arachnoid interface by rupture between neurothelial cells. Multiples of concentric subdural spaces are
initially observed, although only the principal subdural space actually grows. Scanning electron microscopy. (Original magnification ×180. Bar: 100 µm.)(From Reina
MA, López A, de Andrés JA, et al: Existe el espacio subdural? Rev Esp Anestesiol Reanim 45:367–376, 1998.)
The subdural space may also be present in patients susceptible to aperture of the space due to as yet unidentified
pathologic disorders. Confusion is generated by the ease with which this space can be produced in cadavers as a
result of dissection or manipulation. In most individuals, however, the subdural space is not present naturally.
Blomberg attempted to evaluate the subdural space by using endoscopic methods in cadavers but could not
[92]
visualize it in all cases. Moreover, in the light of recent histological studies, doubts have been raised about whether
or not the space described by this author was produced artificially with the introduction of endoscopic lenses and
irrigation fluid. In all cases, the interpretation of such affirmations has been macroscopic.
383
Subdural anesthetic block occurs as a complication of epidural anesthesia resulting from the accidental
[93] [94]
introduction of local anesthetic, partially or totally outside the epidural cavity, into the subdural space. This type of
block causes local accumulation of anesthetic between the dura mater and the arachnoid, with the dissection of a
new subdural space as the solution is injected. The extent of the block is unpredictable, because it depends on the
volume of local anesthetic injected into the subdural space and on whether dissection of the space is predominantly
cephalad or circumferential; in the former case, only a few milliliters of anesthetic solution can cause exaggerated
extension of the block.
MORPHOLOGY OF ARACHNOID SHEATHS AND A NOVEL HYPOTHESIS ON THE ORIGIN OF CAUDA EQUINA
SYNDROME AND TRANSIENT ROOT IRRITATION SYNDROME
The trabecular arachnoid component arises from the reticular arachnoid lamina and merges with the cellular plane of
the pia mater. This trabecular component emits arachnoid projections to all the structures that traverse the
subarachnoid space. Variable diameter vessels and nerves are in turn enveloped by this component (see Fig.
[95] [96] [97]
19–11 ). In this way, the nerve roots enveloped by the pia mater are not found free within the dural sac but are
[14]
surrounded by arachnoid structures known as arachnoid sheaths ( Figs. 19–26 and 19–27 ).
[98]
Figure 19-26 Arachnoid sheath surrounding a nerve root within the subarachnoid space. Scanning electron microscopy. (Original magnification ×100. Bar: 100
µm.)(From Reina MA, López A, de Andrés JA: Hypothesis concerning the anatomical basis of cauda equina syndrome and transient nerve root irritation after spinal
anesthesia. Rev Esp Anestesiol Reanim 46:99–105, 1999.)
These sheaths envelop the nerve roots and contribute to keeping them structurally organized within the dural sac,
limiting positional shifts with respect to the neighboring roots during spinal movements. The mechanical resistance
of the sheaths with respect to the enveloped nerve roots and vessels is very low; that is, the sheaths are ineffective as
protection against trauma and are, in fact, the first structures to tear during dissection. The thickness and
characteristics of these arachnoid sheaths within the cauda equina vary. Thus, although some sheaths are lax,
[98]
allowing visualization of fibrous bridges and leptomeningeal cells, others are formed by superimposed planes of the
same components, thereby affording a more compact appearance. Sheath thickness ranges from 10 to 60 µm,
[98]
depending on the abundance of the arachnoid filaments forming them (see Fig. 19–27 ). In some cases, one or more
nerve roots can be observed enveloped by a single arachnoid sheath, whereas in other cases, the nerve roots have no
sheath at all.
384
Figure 19-27 Thickness and characteristics of the arachnoid sheath. Scanning electron microscopy. (Original magnification ×100. Bar: 100 µm.)
These findings and the observation that a microcatheter can be inserted into the subarachnoid sheaths, causing
temporary distention after injection of a saline solution, suggested a hypothesis to explain cauda equina syndrome
and transient root irritation syndrome. In effect, an anesthetic solution can accidentally be injected into the
subarachnoid sheaths. In such a case, dilution of the anesthetic would be hindered, and the nerve tissue located
within the sheaths would be exposed for some time to higher anesthetic concentrations than initially expected ( Fig.
19–28 ). Local anesthetics enter contact with the spinal roots and the spinal cord at concentrations 10 to 25 times
lower than the concentration of the solution injected into the subarachnoid space. [99] [100]
The high local anesthetic concentration and the osmolarity of the solution would give rise to deleterious effects
within the arachnoid sheath, as would slow administration through a microcatheter; in contrast, injection of the same
anesthetic solution into the dural sac, but outside the arachnoid sheaths, would elicit only minimal effects ( Fig. [98]
19–29 ).
Part of the CSF is found within the arachnoid sheaths; consequently, the nerve roots or vessels contained within the
sheaths come into contact with the fluid. In this way, a significant volume of free CSF is located within the sheaths,
where substance dissolution is faster. Outside the arachnoid sheaths, the CSF mixing dynamics are slower.
Achievement of equilibrium between the two compartments requires some time, because the arachnoid sheaths exert
a buffering effect between the different concentrations in the two compartments. Local anesthetic injection into the
sheaths in such complications may explain the absence of antecedents
Figure 19-28 Model explaining why arachnoid sheaths complicate the dilution of local anesthetic solution after its subarachnoid administration.(From Reina MA,
López A, de Andrés JA: Hypothesis concerning the anatomical basis of cauda equina syndrome and transient nerve root irritation after spinal anesthesia. Rev Esp
Anestesiol Reanim 46:99–105, 1999.)
385
Figure 19-29 Arachnoid sheath surrounding a nerve root within the subarachnoid space. Note on the left that the arachnoid barrier lamina was separated from the
dural sac during dissection. Scanning electron microscopy. (Original magnification ×30. Bar: 1 mm.)(From Reina MA, López A, de Andrés JA: Hypothesis concerning
the anatomical basis of cauda equina syndrome and transient nerve root irritation after spinal anesthesia. Rev Esp Anestesiol Reanim 46: 99–105, 1999.)
of trauma during puncture. Local anesthetic injection into the arachnoid sheaths during a single puncture or through
a microcatheter can be the triggering cause, and the remaining factors analyzed to date, including concentrated local
anesthetic and hyperbaric solutions, can aggravate the situation. [98]
Microcatheters can easily erode and traverse the arachnoid sheaths, without directly damaging a nerve root or the
spinal cord. The resulting neurotoxic effect can be greater in the case of fractionated dosage and small volumes,
whereas the administration of larger volumes may facilitate partial leakage of the local anesthetic out of the sheath. [98]
According to this anatomic hypothesis, transient root irritation syndrome would constitute an intermediate condition,
with lesser toxic involvement and clinical repercussion than cauda equina syndrome. Drug concentration would be
less important in proximity to the nerve structures contained within the arachnoid sheaths, as a result of the lesser
amount of local anesthetic deposited. This situation could arise due to the variable thickness of the sheaths, their
incomplete catheterization, and/or local anesthetic administration at a pressure sufficient to ensure extravasation
from the arachnoid sheaths. [98]
The injection of local anesthetic into the arachnoid sheaths in zones close to the spinal cord or the conus medullaris
could affect various nerve roots, whereas injection into distal zones in proximity to the dural sheaths would affect
only individual nerve roots, with more limited clinical repercussions (see Fig. 19–29 ).
Pia Mater
The thickness of the pia mater at the spinal cord level ranges from 160 to 200 µm, of which 10 to 15 µm
[101]
correspond to the cellular plane, and 150 to 185 µm to the subpial compartment. The thickness of the cellular plane
is more uniform, although the subpial connective compartment can vary slightly from one zone to another; thus, it is
thinner in the region of the lower lumbar vertebrae, and reaches a thickness of 70 to 100 µm at the conus medullaris
( Fig. 19–30 ). At the different levels studied, the subpial compartment is occupied by collagen fibers oriented in
[101]
different directions and with an average diameter of 0.1 µm. The external surface of the cellular plane of the pia
mater is smooth, brilliant, and mamillated in appearance, with small elevations measuring 10 to 20 µm. The pial
cells are smooth and flat, with perfect junctions on the surface that make it almost impossible to identify the limiting
zone between two adjacent cells.
Natural perforations, or fenestrations, are found over the entire surface of the pia mater, distributed in variable
proportions. Some samples have revealed 1000 to 1400 fenestrations per square millimeter, forming circular,
elliptic, or ovoid shapes. Although the dimensions of the fenestrations vary, most of them measure 5 to 10 µm ( Fig.
19–31 ).
386
At nerve root level within the dural sac, the pia mater appears as a wrinkled or folded sheath running parallel to
[102]
the main axis of the root. The thickness between the cellular plane and the subpial compartment at the nerve root
level varies from 3 to 4 µm, whereas the subpial compartment measures 10 to 12 µm. The pia mater at this level [102]
has natural fenestrations similar to those found in the pia mater enveloping the spinal cord, although of smaller size.
The fenestrations measure between 1 and 4 µm in diameter, with a density between 18,000 and 32,000 perforations
per square millimeter. These fenestrations facilitate faster diffusion in the nerve roots by local anesthetics and
[102]
Figure 19-30 Medullar pia mater. The cellular plane of the pia mater was separated during dissection. Under the pia mater lies the subpial compartment occupied by
collagen fibers. The space between the pia mater and the subpial compartment is an artifact. Beneath the subpial compartment lies the medulla. Scanning electron
microscopy. (Original magnification ×100. Bar: 100 µm.)
Figure 19-31 Natural fenestrations in the surface of the medullar pia mater. Within the fenestration, note the collagen fibers of the subpial compartment. Scanning
electron microscopy. (Original magnification ×1000. Bar: 10 µm.)(From Reina MA, López Garcia A, de Andrés JA: Anatomical description of a natural perforation
present in the human lumbar pia mater. Rev Esp Anestesiol Reanim 45:4–7, 1998.)
other substances following injection into the subarachnoid space.
The pia mater in general was thought to form a complete cellular lamina, establishing a barrier between the central
nervous system and the subarachnoid space. However, the existence of these fenestrations would demonstrate the
absence of such a barrier. In humans, no such fenestrations have been described to date. Their identification and the
resulting absence of a true barrier would explain the high permeability of this membrane, allowing rapid diffusion
toward the nerve roots and the spinal cord of substances administered into the CSF ( Fig. 19–32 ). Under such
circumstances, the basal membrane would constitute the only intact structure separating the glial tissue of the spinal
cord.
387
Figure 19-32 Pia mater cells of the nerve root. Under the pial cells lie myelinic axons. Transmission electron microscopy. (Original magnification ×7000.)
REFERENCES
1. Zenker W, Bankoul S, Braun JS: Morphological indications for considerable diffuse reabsortion of cerebrospinal fluid in spinal meninges
particulary in the areas of meningeal funnels. Anat Embryol 189:243–258, 1994.
2. Zenker W, Rine B, Bankoul S, et al: 5′Nucleotidase in spinal meningeal compartments in the rat. An immuno- and enzyme-histochemical study.
Histochemistry 98:135–139, 1992.
3. Braun JS, Kaissling B, Le Hir M, Zenker W: Cellular components of the immune barrier in the spinal meninges and dorsal root ganglia of the
normal rat: Immunohistochemical (MCH class II) and electron microscopic observations. Cell Tissue Res 273:209–217, 1993.
4. Williams PL, Bannister LH, Berry MM, et al: Anatomía de Gray, vol 2, 38th ed. Madrid, Churchill Livingstone, 1998, pp 1209–1218.
5. ReinaMA, Dittmann M, López A, van Zundert A: New perspectives in the microscopic structure of human dura mater in the dorsolumbar
region. Reg Anesth 22:161–166, 1997.
6. Fink BR, Walker S: Orientation of fibers in human dorsal lumbar dura mater in relation to lumbar puncture. Anesth Analg 69:768–772, 1989.
7. ReinaMA, López A, Dittmann M, de Andrés JA: Análisis de la superficie externa e interna de la duramadre humana por microscopia
electrónica de barrido. Rev Esp Anestesiol Reanim 43:130–134, 1996.
8. Reina MA, López A, Dittmann M, de Andrés JA: Análisis estructural del espesor de la duramadre humana por microscopía electrónica de
barrido. Rev Esp Anestesiol Reanim 43:135–137, 1996.
9. Reina MA, López A, de Andrés JA: Variación del espesor de la duramadre humana. Rev Esp Anestesiol Reanim 46:344–349, 1999.
10. Reina MA, López A, de Andrés JA, et al: Existe el espacio subdural? Rev Esp Anestesiol Reanim 45:367–376, 1998.
12. Blomberg R, Olsson SS: The lumbar epidural space in patients examined with epiduroscopy. Anesth Analg 68:157–160, 1989.
13. Hogan QH: Lumbar epidural anatomy. A new look by cryomicrotome section. Anesthesiology 75:767–775, 1991.
14. HoganQ: Reexamination of anatomy in regional anesthesia. In Brown DL: Regional Anesthesia and Analgesia. Philadelphia, WB Saunders
Co, 1996, pp 50–83.
15. Bernards
CM, Hill HF: Physical and chemical properties of drug molecules governing their diffusion through the spinal meninges.
388
16. Bernards
CM, Hill HF: Morphine and alfentanil permeability through the spinal dura, arachnoid and pia mater of dog and monkeys.
17. Bernards
CM, Hill HF: The spinal nerve root sleeve is not a preferred route for redistribution of drugs from epidural space to the spinal cord.
18. Bernards
CM: Effect of hydroxypropyl-B-cyclodextrin on flux of morphine, fentanyl, sufentanil and alfentanil through the spinal meninges of
the monkey. J Pharm Sci 83:620–622, 1994.
19. Unmenhofer WC, Arends RH, Shen DD, Bernards CM: Comparative spinal distribution and clearance kinetics of intrathecally administered
morphine, fentanyl, alfentanil and sufentanil. Anesthesiology 92:739–753, 2000.
20. Bernards
CM: Epidural and intrathecal opioids. Which drugs should we choose and how should they be used? In Schwartz AJ: ASA Refresh.
Am Soc Anesthesiol 27:13–30, 1999.
21. Bernards
C, Kern C: Palmitoylcarnitine increases the transmeningeal flux of hydrophilic but not hydrophobic compounds in vitro.
22. Strichartz
GR, Sánchez V, Arthur GR, et al: Fundamental properties of local anesthetics: II. Measured octanol: Buffer partition coefficients
and pKa values of clinically used drugs. Anesth Analg 71:158–170, 1990.
23. Mather LE: Clinical pharmacokinetics of fentanyl and newer derivatives. Clin Pharmacokinet 8:422–446, 1983.
24. Kern C, Mautz DS, Bernards CM: Epinephrine is metabolized by the spinal meninges of monkey and pigs. Anesthesiology 83:1078–1081,
1995.
25. UnmenhoferW, Bernards CM: Acylcarnitine chain length influences carnitine enhanced drug flux through the spinal meninges in vitro.
26. Bernards
CM, Sorkin LS: Radicular artery blood flow does not redistribute fentanyl from epidural space to the spinal cord. Anesthesiology
80:872–878, 1994.
27. Bernards CM, Ulma G, Kopacz DJ: The meningeal permeability of R- and S-bupivacaine are no different. Anesthesiology 93:896–897, 2000.
28. McEllistrem RF, Benmington RG: In vitro determination of human dura mater permeability to opioids and local anesthetics. Can J Anaesth
40:165–169, 1992.
29. Bernards CM: Human dura mater permeability. Can J Anaesth 40:1125, 1992.
30. Buettner J, Wresch KP, Klose R: Postdural puncture headache: Comparison of 25-Gauge Whitacre and Quincke needles. Reg Anesth 18:166–
169, 1993.
31. Tarkkila
PJ, Heine H, Tervo RR: Comparison of Sprotte and Quincke needles with respect to postdural puncture headache and backache. Reg
Anesth 17:283–287, 1992.
32. de Andrés JA, Bolinches R, Nalda MA: Importancia de la aguja en anestesia regional. Rev Esp Anestesiol Reanim 37:71–74, 1990.
33. Gielen M: Postdural puncture headache (PDPH): A review. Reg Anesth 14:101–106, 1989.
34. Halpern S, Preston R: Postdural puncture headache and spinal needle design. Metaanalyses. Anesthesiology 81:1376–1383, 1994.
35. Hart JR, Whitacre RJ: Pencil-point needle in prevention of postspinal headache. JAMA 147:637–638, 1951.
36. Sprotte G, Schedel R, Pajunk H, Pajunk H: Eine “atraumatische” Universalkanüle für einzeitige Regionalanaesthesien. Reg Anaesth 10:104–
108, 1987.
37. DittmannM, Schäfer HG, Ulrich J, Taylor WB: Anatomical re-evaluation of lumbar dura mater with regard to postspinal headache. Effect of
dural puncture. Anaesthesia 43:635–637, 1988.
38. Celleno
D, Capogna G, Constantino P, Catalano P: An anatomic study of the effects of dural puncture with different spinal needles. Reg
Anesth 18:218–221, 1993.
39. ReinaMA, de Leon-Casasola OA, López A, et al: An in vitro study of dural lesions produced by 25-gauge Quincke and Whitacre needles
evaluated by scanning electron microscopy. Reg Anesth Pain Med 25:393–402, 2000.
40. Reina
MA, López A, de Andrés JA, et al: Estudio en cadáveres mediante microscopia electrónica de barrido de la lesión dural producida por la
aguja Whitacre y Quincke. Rev Esp Anestesiol Reanim 44:56–61, 1997.
41. Mihic DN: Postspinal headache and relationship of needle bevel to longitudinal dural fibers. Reg Anesth 10:76–81, 1985.
42. Flaatten
H, Thorsen T, Askeland B, et al: Puncture technique and postural postdural puncture headache. A randomised, double-blind study
comparing transverse and parallel puncture. Acta Anesthesiol Scand 42:1209–1214, 1998.
389
43. Greene
HM: A technique to reduce the incidence of headache following lumbar puncture in ambulatory patients, with a plea for more frequent
examination of cerebrospinal fluids. Northwest Med 22:240–241, 1923.
44. Greene HM: Lumbar puncture and prevention of postpuncture headache. JAMA 86:391–392, 1926.
45. Franksson C, Gordh T: Headache after spinal anesthesia and a technique for lessening its frequency. Acta Chir Scand 94:443–445, 1946.
46. De Andrés J, Reina MA, López-García A: Risks of regional anaesthesia: Role of equipment needle design, catheters. In Van Zundert A:
Highlights in Pain, Therapy and Regional Anaesthesia. VII. Barcelona. Permanyer Publications, 1998, 175–183.
47. López-GarcíaA: A scanning electron microscopy and analysis of the latest spinal needle design. In Van Zundert A: Highlights in Regional
Anesthesia and Pain Therapy, 4th ed. Barcelona, Publicidad Permanyer SL, 1995, pp 115–118.
48. JokinenMJ, Pitkänen MT, Lehtonen E, Rosemberg PH: Deformed spinal needle tips and associated dural perforations examined by scanning
electron microscopy. Acta Anaesthesiol Scand 40:687–690, 1996.
49. Parker RK, White PF: A microscopic analysis of cut-bevel versus pencil-point spinal needles. Anesth Analg 85:1101–1104, 1997.
50. Benham M: Spinal needle damage during routine clinical practice. Anaesthesia 51:843–845, 1996. in Regional Anaesthesia and Pain Therapy,
4th ed. Barcelona, Publicidad Permanyer SL, 1995, pp 115–118.
51. Reina
MA, López A, Dittmann M, et al: Tumores epidermoides espinales iatrogénicos. Una complicación tardía de la punción espinal. Rev
Esp Anestesiol Reanim 43:142–146, 1996.
52. Reina
MA, López A, Manzarbeitia F, et al: Arrastre de fragmentos epidérmicos mediante agujas espinales en cadáver. Rev Esp Anestesiol
Reanim 42:383–385, 1995.
53. RosembergPH, Pitkänen MT, Hakala PH, Andersson LC: Microscopic analysis of the tips of thin spinal needles after subarachnoid puncture.
Reg Anesth 21:35–40, 1996.
54. PuolakkaR, Andersson LC, Rosemberg PH: Microscopic analysis of three different spinal needle tips after experimental subarachnoid
puncture. Reg Anesth Pain Med 25:163–169, 2000.
55. Holst
D, Möllman M, Ebel C, et al: In vitro investigation of cerebrospinal fluid leakage after dural puncture with various spinal needles.
Anesth Analg 87:1331–1335, 1998.
56. Kadrie
H, Driedger AA, McInnis W: Persistent dural cerebrospinal fluid leak shown by retrograde radionuclide myelography: Case report. J
Nucl Med 17:797–799, 1976.
57. LiebermanLM, Tourtellote WW, Newkirk TA: Prolonged post lumbar puncture cerebrospinal fluid leakage from lumbar subarachnoid space
demonstrated by radioisotope myelography. Neurology 21:925–929, 1971.
58. Kunkle CE, Ray BS, Wolff HG: Experimental studies on headache. Arch Neurol Psychiatry 49:323–358, 1943.
59. Marshall J: Lumbar puncture headache. J Neurol Neurosurg Psychiatry 13:71–74, 1950.
60. Iqbal J, Davis LE, Orrison WW Jr: An MRI study of lumbar puncture headaches. Headache 35:420–422, 1995.
61. Zetlaoui PJ: Bevel orientation and postdural puncture headache. A new possible explanation? Acta Anaesthesiol Scand 43:967–968, 1999.
62. Reina MA, De León Cassasola OA, López A, et al: The origin of the spinal subdural space. Ultrastructure finding. Anesth Analg 2002, in
press.
63. Fishman RA, Dillon WP: Dural enhancement and cerebral displacement secondary to hypotension. Neurology 43:609–611, 1993.
64. MockriB, Piepgras DG, Miller GM: Syndrome of orthostatic headaches and diffuse pachymeningeal gadolinium enhancement. Mayo Clinic
Proc 72:400–413, 1997.
65. Mockri
B, Parisi JE, Scheithauer BW, et al: Meningeal biopsy in intracranial hypotension: Meningeal enhancement on MRI. Neurology
45:1801–1807, 1995.
66. Sable SG, Ramadan NM: Meningeal enhancement and low CSF pressure headache: An MRI study. Cephalalgia 11:275–276, 1991.
67. Alvarez-Linera
J, Escribano J, Benito-León J, et al: Pituitary enlargement in patients with intracranial hypotension syndrome. Neurology
55:1895–1897, 2000.
68. Pavlin DJ, McDonald JS, Child B, Rusch V: Acute subdural hematoma: An unusual sequel of lumbar puncture. Anesthesiology 51:338–340,
1979.
390
69. Newrick P, Read D: Subdural haematoma as a complication of spinal anaesthetic. BMJ 285:341–342, 1982.
70. Patin DJ, Eckstein EC, Harum K, Pallares V: Anatomic and biomechanical properties of human lumbar dura mater. Anesth Analg 76:535–540,
1993.
71. Zarzur E: Some mechanical properties of the human spinal dura mater. Reg Anesth 18(Suppl 1):26, 1993.
72. Nishimura N: Effect of position on spread of radionuclide in epidural space. Reg Anesth 17(Suppl 1):87, 1992.
73. RunzaM, Pietrabissa R, Mantero S, et al: Lumbar dura mater biomechanics: Experimental characterization and scanning electron microscopy
observations. Anesth Analg 88:1317–1321, 1999.
74. Zarzur E, Goncalves JJ: The resistance of the human dura mater to needle penetration. Reg Anesth 17:216–218, 1992.
75. Westbrook JL, Uncles DR, Sitzman BT, Carrie LES: Comparison of the force required for dural puncture with different spinal needles and
subsequent leakage of cerebrospinal fluid. Anesth Analg 79:769–772, 1994.
76. Lewis MC, Lafferty JP, Sacks MS, et al: How much work is required to puncture dura with Tuohy needles? Br J Anaesth 85:238–241, 2000.
77. Cruickshank RH, Hopkinson JM: Fluid flow through dural punctures sites. An in vitro comparison of needle point types. Anaesthesia 44:415–
418, 1989.
78. Ready LB, Cuplin S, Haschke RH, Nessly M: Spinal needle determinants of rate of transdural fluid leak. Anesth Analg 69: 457–460, 1989.
79. Janes EF, Pennefather S, Wilkinson K: Fluid flow through dural punctures sites. Anaesthesia 44:1011, 1989.
80. Morrison LMM, McCrae AF, Foo I, et al: An in vitro comparison of fluid leakage after dural puncture with Atraucan, Sprotte, Whitacre and
Quincke needles. Reg Anesth 21:139–146, 1996.
81. Mehta M, Maher R: Injection into the extra-arachnoid subdural apace. Anaesthesia 32:760–766, 1977.
82. Ralph CJ, Williams MP: Subdural or epidural? Confirmation with magnetic resonance imaging. Anaesthesia 51:175–177, 1996.
83. Hartrick CT, Pither CE, Umeshraya P, et al: Subdural migration of an epidural catheter. Anesth Analg 64:175–178, 1985.
84. SmithGB, Barton FL, Watt JH: Extensive spread of local anaesthetic solution following subdural insertion of an epidural catheter during
labour. Anaesthesia 39:355–358, 1984.
85. Orlin
JR, Osen K, Hovig T: Subdural compartment in pig: A morphologic study with blood and horseradish peroxidase infused subdurally.
Anat Rec 230:22–37, 1991.
86. Schachenmair W, Friede RL: The origin of subdural neomembranes. I. Fine structure of dura-arachnoid interface in man. Am J Pathol 92:53–
68, 1978.
87. Frederickson RG: The subdural space interpreted as a cellular layer of meninges. Anat Rec 230:38–51, 1991.
88. Haines DE: On the question of a subdural space. Anat Rec 230:3–21, 1991.
89. Rascol MM, Izard JY: The subdural neurothelium of the cranial meninges in man. Anat Rec 186:429–436, 1976.
90. Lopes CAS, Mair WGP: Ultrastructure of the arachnoid membrane in man. Acta Neuropathol (Berlin) 28:167–173, 1974.
91. Vandenabeele F, Creemers J, Lambrichts I: Ultrastructure of the human arachnoid mater and dura mater. J Anat 189:417–430, 1996.
92. BlombergRG: The lumbar subdural extraarachnoid space of humans: An anatomical study using spinaloscopy in autopsy cases. Anesth Analg
66:177–180, 1987.
93. Boys JE, Norman PF: Accidental subdural analgesia. Br J Anaesth 47:1111–1113, 1975.
94. ManchandaVN, Murad SHN, Shilyansky G, Mehringer M: Unusual clinical course of accidental subdural local anesthetic injection. Anesth
Analg 62:1124–1126, 1983.
95. Nicholas
DS, Weller RO: The fine anatomy of the human spinal meninges. A light and scanning electron microscopy study. J Neurosurg
69:276–282, 1988.
96. Hogan Q, Toth J: Anatomy of soft tissues of the spinal canal. Reg Anesth Pain Med 24:303–310, 1999.
97. Nauta HJ, Dolan E, Yasargil MG: Microsurgical anatomy of spinal subarachnoid space. Surg Neurol 19:431–437, 1983.
98. ReinaMA, López A, de Andrés JA: Hipótesis sobre las bases anatómicas del síndrome de cauda equina e irritación radicular transitoria
postanestesia espinal. Rev Esp Anestesiol Reanim 46:99–105, 1999.
391
99. Fink BR, Maravilla KR, Richards TL, Sloan R: Regional spinal cerebrospinal fluid (CFS) volumes. Anesthesiology 81:A–231, 1994.
100. Hogan
Q, Prost R, Kuller A, et al: Magnetic resonance imaging of cerebrospinal fluid volume and the influence of body habitus and
abdominal pressure. Anesthesiology 84:1341–1349, 1996.
101. Reina MA, López A, de Andrés JA: Perforaciones naturales en la piamadre humana. Rev Esp Anestesiol Reanim 45:4–7, 1998.
102. Reina
MA, De Andrés JA, López-García A: Anatomía. Implicación en la práctica de las técnicas de conducción espinal. In Torres LM, ed:
Tratado de Anestesia, Reanimación y Tratamiento del Dolor. Madrid, Aran Ed, 2001, 1: 1135–1155.
392
Section IV - Chapter 20 - Peripheral Nerve Blocks
Chapter 20 - Peripheral Nerve Blocks
ROY GREENGRASS
SUSAN STEELE
GENE MORETTI
STEWART GRANT
STEVEN KLEIN
KAREN NIELSEN
It is important that any patient who is to undergo a regional anesthesia procedure for surgery be adequately
evaluated preoperatively for physical status and anatomic anomaly present at the site where the block is to be
performed. The responsibilities of physicians and assistant nurses and the organization of a nerve block facility are
described in detail in Chapter 11 .
In this chapter, somatic peripheral nerve blocks such as cervical plexus blocks, blocks of the brachial plexus and its
branches, intercostal and interpleural blocks, pudendal nerve blocks, blocks of the lumbosacral plexus and its branch,
and intravenous regional anesthesia of upper and lower extremity blocks are described.
Field Blocks Including Local Infiltration
LOCAL INFILTRATION
One of the simplest and earliest techniques of providing anesthesia is local infiltration or field block, which is used
primarily by the surgeon. The objective of local infiltration is to provide somatic sensory analgesia at the site of
incision by infiltrating a field of local anesthetic agent subcutaneously. The infiltration should be carried deeper into
the muscle layer and parietal serosal layer as well as the periosteum to provide incisional analgesia ( Figs. 20–1 and
20–2 ). The local anesthetic agent can be combined with a vasoconstrictor agent, such as epinephrine, to provide a
relatively dry field and improve hemostasis. The amount of epinephrine should not exceed 8 µg/kg in any 1-hour
period and is effective in concentrations as low as 1:200,000 to 1:400,000. The amount of epinephrine should be
reduced to 1.5 µg/kg over a 10-minute period and to no more than 4.5 µg/kg per hour in the presence of an
inhalation agent such as halothane. Other inhalation agents (enflurane, desflurane, sevoflurane, and isoflurane) do
not seem to predispose or sensitize the myocardium to epinephrine-induced arrhythmias to the same extent. It would
seem prudent to find ways to provide hemostasis other than adding epinephrine to the infiltration solution in the face
of halothane administration.
Another advantage of using local infiltration as an anesthetic technique is the ability to use large volumes of dilute
local anesthetic solutions. Lidocaine in the range of 0.55% or bupivacaine in the range of 0.2% to 0.25% is
sufficient to provide incisional analgesia during the postoperative period. One should stay below the maximum dose
of lidocaine 5 mg/kg without epinephrine, 7 mg/kg with epinephrine and ropivacaine or bupivacaine 2 mg/kg, for
infiltration. Ropivacaine and bupivacaine have the added advantage of long duration of action that is more evident in
the higher concentration ranges. Simple mathematical calculations show a maximum allowable volume of 100 mL
of 0.5% lidocaine with epinephrine or 60 mL of 0.25% bupivacaine, which should provide adequate volume for the
most prodigal surgeon.
The most commonly encountered complication of this technique is systemic toxicity from inadvertent
Figure 20-1 Technique of subcutaneous infiltration.(From Raj PP (ed): Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, p 272.)
393
overdose. Often, this is associated with a poor choice of patient or procedure for local infiltration anesthesia.
Supplementation of local infiltration with sedatives, narcotic analgesics, or light inhalation anesthesia may decrease
the inadvertent obligatory overdosage and thus the potential for neurologic or cardiovascular toxicity of local
anesthetic agents. The addition of sedation or light general anesthesia may make the technique of local infiltration
more acceptable to patient and surgeon alike.
FIELD BLOCK
Field block is a special form of local infiltration that takes advantage of the subcutaneous course of many of the
somatosensory cutaneous nerve branches. Blockade of a larger area can be accomplished by infiltrating the
subcutaneous courses of these branches more proximally than the incision area. This technique allows less volume
of a more concentrated solution of local anesthetic to block a larger area. It also permits the incision site to remain
virgin, without distortion of dermal contour or possibility of spread of infection or malignant cells ( Fig. 20–3 ).
Gastrostomy
INDICATIONS
The technique is indicated for surgical feeding in a high-risk, debilitated patient.
Figure 20-2 Infiltration technique. The needle penetrates multiple times deeper to subcutaneous tissue in the muscle, fascia, or serosal layer.(Redrawn from Labat:
Regional Anesthesia—Its Technic and Clinical Application, General Principles of Technic. Philadelphia, WB Saunders, 1922. From Raj PP: Clinical Practice of
Regional Anesthesia. New York, Churchill Livingstone, 1991, p 273.)
ANATOMY
The lower intercostal nerves T7 to T11 innervate the upper part of the skin of the anterior abdominal wall. The
celiac plexus innervates the viscus (stomach) and the peritoneum.
DRUGS
For local infiltration, 1–1.5% lidocaine (Xylocaine) or mepivacaine (Carbocaine) are used.
For intercostal or paravertebral block, 0.5% bupivacaine or ropivacaine.
394
Figure 20-3 Technique of field block.(Redrawn from Labat: Regional Anesthesia—Its Technic and Clinical Application, General Principles of Technic. Philadelphia,
WB Saunders, 1922. From Raj PP: Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, p 273.)
395
Figure 20-4 Method of regional block for gastrostomy.(From Raj PP: Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, p 274.)
TECHNIQUE
The patient lies in the prone or lateral position. The procedure is performed in the following manner ( Fig. 20–4 ):
1. Intercostal nerve block of T6 to T11 is performed approximately 8 to 10 cm from the midline on the left
side with 3 mL of local anesthetic agent for each nerve (see section under Intercostal Nerve Block).
2. Paravertebral block of T6 to T11 is performed 2.5 cm from the midline on the left side using 3 mL of local
anesthetic for each nerve.
3. Local subcutaneous infiltration approximately midline from the xiphoid process to the umbilicus is used to
block the crossed nerve fibers from the opposite side; 7 to 8 mL of local anesthetic are injected via a 25-
gauge (G) spinal needle.
4. Local infiltration occurs along the line of incision; 5 to 10 mL of local anesthetic is injected with a 25-G
spinal needle.
UNSUCCESSFUL BLOCK
1. The block is repeated if time is available, and the therapeutic range of the dose is not exceeded.
2. Supplemental intravenous sedation is provided if the area is partially blocked and if it is considered to be
safe.
3. General anesthesia is given; if this is not possible, the procedure should be abandoned.
CONTRAINDICATIONS
396
If a patient is receiving anticoagulant therapy, that is a contraindication to this technique. Treatment of side effects is
as follows:
1. Hypotension: Vasopressors are given and IV fluids, if tolerated.

2. Central nervous system toxicity: Oxygen is administered; the patient is given the same treatment as for
local systemic toxicity.
3. Cardiovascular system toxicity: same treatment as for systemic toxicity.
4. Pneumothorax: See the section under Intercostal Nerve Block.
HERNIORRHAPHY
Indications
The technique is indicated for patients in whom general anesthesia or spinal anesthesia is contraindicated and for
patients who choose to have regional anesthesia.
ANATOMY
The inguinal region is innervated by the subcostal (T12), iliohypogastric (L1), and ilioinguinal (L1) nerves, with
overlap by T11 in the upper part. These nerves are closely related to the anterosuperior iliac spine. After passing
between the internal oblique and transversus muscles, these nerves pass from the internal oblique medial to the
anterosuperior iliac spine (about 3 cm) and then pass between the internal oblique and the aponeurosis of external
oblique. The ilioinguinal nerve then accompanies the spermatic cord beyond the midinguinal point. The spermatic
cord is associated with the genitofemoral nerve and sympathetic fibers in its course.
DRUGS
1–1.5% lidocaine (Xylocaine) or mepivacaine (Carbocaine) are used for short duration; for long duration, 0.5%
bupivacaine or ropivacaine is used.
TECHNIQUE
Skin wheals are raised with a 27-G needle (A) 3-cm medial and inferior to the anterior superior iliac spine, and (B)
at the superficial inguinal ring. A 22-G, 2-inch spinal needle is attached to a Luerlok syringe. The needles are
introduced upward laterally and inward from a point 3 cm inferomedial to the anterosuperior iliac spine until the tip
touches the iliac crest. On its way in, the needle passes through skin and superficial fascia. On its way out, it passes
through external oblique/internal oblique muscles. Three mL of local anesthetic is injected as the needle is slowly
withdrawn. This blocks the T12 area ( Figs. 20–5 and 20–6 ).
Through the same skin wheal, the needle is introduced medially, parallel to and above the inguinal ligament around
the anticipated line of incision; about 5 to 6 mL of local anesthetic is injected.
Through a second skin wheal, at about the pubic symphysis, the 22-G spinal needle is introduced laterally above and
parallel to the inguinal ligament around the line of incision; 5 to 6 mL of local anesthetic is injected as the needle is
withdrawn. Through the same skin wheal, the needle is inserted upward toward the umbilicus with subcutaneous
tissue to block the nerves crossing from the opposite side.
Once the spermatic cord is exposed, 3 to 4 mL of local anesthetic is injected under direct vision at the deep inguinal
ring to anesthetize the genitofemoral nerve and sympathetic fibers in and around the cord.
Alternatively, paravertebral block of T11 to L2 can be used for this surgery. The spinal processes of T11 to L2 are
identified at their most superior margins. Skin surface points are marked 2.5 cm lateral to the spinal processes. After
skin infiltration, a 22-G Tuohy needle is inserted perpendicular to the skin until it touches the transverse process.
The needle is then walked caudally off the transverse process and inserted a further .5 cm, with 6 mL of local
anesthetic injected at each level.
CONTRAINDICATIONS
397
The technique is not indicated if the patient is uncooperative, has infection at the site of needle insertion, or is
grossly obese.
Hemorrhoidectomy
INDICATIONS
The technique is indicated for patients who prefer to have regional anesthesia and for those in whom general
anesthesia is a relative contraindication.
Figure 20-5 Field block for the inguinal region. Note the position of the needles. Needle A is medial to the anterosuperior iliac spine to block the iliohypogastric and
ilioinguinal nerves. Needle B is at the superficial inguinal ring to block the spermatic cord.(From Raj PP: Clinical Practice of Regional Anesthesia. New York,
Churchill Livingstone, 1991, p 276.)
398
Figure 20-6 Field block for the inguinal region and the lower part of the anterior abdominal wall.(From Raj PP: Clinical Practice of Regional Anesthesia. New York,
ANATOMY
The region of the anal canal and the surrounding area is innervated by branches of the pudendal nerve and the
perineal branch of the fourth sacral nerve and by the perineal branch of the posterior femoral cutaneous nerve of the
thigh. The mucosal aspect is also innervated by sympathetic fibers.
DRUGS
1. For short-duration block: 1–1.5% mepivacaine (Carbocaine) or lidocaine.

2. For prolonged block and postoperative analge sia: 0.5% bupivacaine/ropivacaine.
TECHNIQUE
1. Low spinal subarachnoid block (saddle)

2. Caudal epidural block
3. Pudendal nerve block (see section under Pudendal Nerve Block)
4. Local infiltration of the anus
MANAGEMENT OF UNSUCCESSFUL BLOCK
399
1. The block should be repeated.

2. An alternate technique should be chosen.
Head and Neck Blocks
The structures of the head and neck are supplied by twelve cranial and four cervical nerves. A large proportion of
the nerve supply to the head and neck is of a specialized sensory or secretomotor nature and is of minimal relevance
to the practice of regional anesthesia. Another unique feature is the separation of sensory and motor functions,
which allows anesthesia of the
Figure 20-7 Line drawing of innervation of the face, head, and neck.
oral cavity without loss of control of the airway muscles. In order to provide regional anesthesia, knowledge of the
sensory supply to the skin, mucous membranes, airway, and head and neck is required ( Fig. 20–7 ).
OPHTHALMIC NERVE AND ORBIT ANATOMY

Anatomy
The globe of the eye is a sphere 20 to 30 mm in diameter ( Fig. 20–8 ). The globe sits within a bony pyramid with a
square base that tapers to a tight apex: the orbit. The orbit ranges from 40 to 50 mm in depth in
400
Figure 20-8 The extraocular muscles, which can move the eye in all directions. The extraocular muscles include four recti muscles (superior, inferior, medial, and
lateral) and two oblique muscles (superior and inferior).
the adult. The intraorbital part of the optic nerve averages 30 mm in length and charts a sinuous course from the
posterior pole of the globe to the optic foramen. With the eye in primary gaze, the optic nerve (CN II) exits the globe
3 mm to the nasal side of midline; during its intraorbital course, it lies closer to the medial than the lateral rectus
muscle. The ophthalmic nerve is covered with dura. The dura fuses with the sclera anteriorly. Within the dural
covering, cerebrospinal fluid flows freely. Additionally within the orbit lie (1) the ophthalmic nerve, the smallest
division of the trigeminal nerve and (2) the nerves supplying motor function to the extraocular muscles ( Fig. 20–9 ).
The ophthalmic division of the trigeminal nerve (CN V) is examined in more detail in the next section. Nerves
Figure 20-9 The rich nerve supply of the eye, including the optic nerve and the oculomotor nerve (which has a superior division), a branch to the inferior oblique
muscle, and a short root to the ciliary ganglion. The ciliary ganglion has several branches: the short ciliary nerve, the long ciliary nerve, and the nasociliary nerve.
supplying the oculomotor muscles are (1) the oculomotor nerve (CN III), which supplies the superior rectus, medial
rectus, inferior rectus and inferior oblique; and (2) the abducens nerve supplying the lateral rectus muscle.
Sympathetic and parasympathetic nerve supply to the eye passes through the ciliary ganglion. The ciliary ganglion is
located within the muscular cone. The levator muscle is supplied by the oculomotor nerve (CN III). The orbicularis
oculi is supplied by the facial nerve (CN VII). The blood supply of the orbital contents is predominantly from the
ophthalmic artery. The ophthalmic artery is a branch of the internal carotid artery. The main venous drainage of the
orbit runs backward in a connective tissue septum below the superior rectus muscle. The principal vein is the
superior ophthalmic vein.
TRIGEMINAL NERVE (CN V) ANATOMY ( Fig. 20–10 )
401
The gasserian ganglion is formed from two roots emerging at the midpontine level. These roots pass in the posterior
cranial fossa laterally across the border of the petrous temple bone. These roots enter Meckel’s cave, which is
formed by an invagination of dura mater. Behind the ganglion is a dural pouch called the trigeminal cistern, which
contains cerebrospinal fluid (CSF). The ganglion gives rise to the three peripheral branches exiting its anterior
aspect; these are the ophthalmic, maxillary, and mandibular branches.
OPHTHALMIC DIVISION (CN VI) ANATOMY
The ophthalmic nerve is the most superior and the smallest of the three divisions. It runs lateral to the cavernous
sinus and exits the cranium through the medial aspect of the superior orbital fissure. This nerve is sensory and
supplies the eye, conjunctiva, eyelids, and lacrimal glands. The frontal nerve is the major branch, which divides into
supraorbital, medial, and lateral branches supplying sensation from the upper eyelid as far posteriorly as the vertex
of the scalp. The supratrochlear nerve passes over the superior oblique muscle to exit the orbit medial to the
supraorbital nerve. It supplies sensation to the medial section of the forehead.
MAXILLARY DIVISION (CN V2) ANATOMY
The maxillary nerve is a purely sensory nerve that leaves the cranium via the foramen rotundum and
Figure 20-10 Anatomy of the trigeminal

nerve.(From Raj PP: Clinical Practice of
Regional Anesthesia. New York: Churchill
Livingstone, 1991, p 201.)
enters the sphenopalatine fossa. It branches here, giving off the zygomatic, nerve and supplying the posterolateral
face and the superior posterior alveolar nerve, which supplies the maxilla, part of the oral mucosa, and the upper
dentition. The maxillary nerve then travels into the infraorbital fissure. When it passes through the infraorbital
foramen, it becomes the infraorbital nerve, which supplies sensation from the lower eyelid to the upper lip, including
the underlying mucosa.
MANDIBULAR DIVISION (CN V3) ANATOMY
The mandibular division is the largest division of the trigeminal nerve and is a mixed sensory and motor nerve. It
exits the cranium through the foramen ovale, just posterior to the lateral pterygoid muscle. The nerve divides into
anterior and posterior branches. The anterior branch supplies motor fibers to the muscles of mastication and only
supplies sensation to the lateral face and underlying mucosa via the buccal nerve. The posterior nerve, which is the
auriculotemporal nerve, emerges from behind the temporomandibular joint to supply sensation to the external
auditory meatus and temple. The inferior dental nerve enters the foramen on the medial side of the ramus of the
mandible to run through the bone and emerge at the mental foramen as the mental nerve. The lingual nerve runs
402
between the ramus of the mandible and the medial pterygoid muscle to lie on the deep surface of the mandible at the
third molar, at which point it is covered only by the mucous membrane. The lingual nerve supplies sensation to the
anterior two thirds of the tongue and the mucous membrane.
FACIAL NERVE (CN VII)
The facial nerve exits the cranium at the stylomastoid foramen. Its motor component supplies the muscles of facial
expression, eyelid closure, and oral competence. The facial nerve runs within the substance of the parotid gland and
divides into five main branches that fan out to supply respective areas of the face: temporal, zygomatic, buccal,
mandibular, and cervical. The sensory root of CN VII conveys taste fibers from the chorda tympani nerve to the
anterior two thirds of the tongue and soft palate and provides secretomotor preganglionic parasympathetic
innervation to the submandibular and sublingual glands.
SPHENOPALATINE GANGLION ANATOMY ( Fig. 20–11 )

The ganglion receives afferent sensory input from fibers of the maxillary division of the trigeminal nerve and motor
input via the greater superficial petrosal nerve, which is a branch of the facial nerve. Afferent sympathetics are
received from the carotid plexus. Efferent fibers are divided into an orbital branch, which subdivides into the
posterior superior nasal nerve (supplying the posterior septum) and the nasal palatine nerve (supplying the upper
gingiva, the hard and soft palate, and part of the tonsil). Efferents also interface with the trigeminal nerve, facial
nerve, carotid plexus, and superior cervical ganglion. The sphenopalatine ganglion is located in the pterygopalatine
fossa, posterior to the middle turbinate.
GLOSSOPHARYNGEAL NERVE (CN IX) ANATOMY
The glossopharyngeal nerve exits the skull with the vagus and spinal accessory (CN XI) nerves via the jugular
foramen and passes between the internal jugular vein and the internal carotid artery ( Fig. 20–12 ). It then descends
anterior to the internal carotid artery and deep to the styloid process, where it turns toward the tongue, dividing into
its terminal branches. The glossopharyngeal nerve is both motor and sensory. Sensory innervation is from the
middle ear, the posterior third of the tongue, and the tonsils and pharynx, cephalad from the level of the true vocal
cords. Motor fibers supply the stylopharyngeus muscle and parasympathetic secretomotor fibers to the parotid gland.
Figure 20-11 The nerve of the right lateral nasal wall. Note the site and distribution of the sphenopalatine ganglion.(Redrawn from Bononi SR: The trigeminal nerve.
In Bennett CR: Manheim’s Local Anesthesia and Pain Control in Dental Practice, 7th ed. St. Louis, CV Mosby, 1984. From Raj PP: Clinical Practice of Regional
Anesthesia. New York, Churchill Livingstone, 1991, p 207.)
403
VAGUS NERVE (CN X) ANATOMY
The branches of importance are those supplying sensory and motor innervation to the pharynx and larynx. The
superior laryngeal nerve arises from the inferior ganglion of the vagus to run caudad and medial to the greater cornu
of the hyoid, where it divides into branches. The internal branch pierces the thyrohyoid membrane to supply
sensation to the larynx above the level of the true vocal chords The external branch supplies the cricothyroid muscle,
which tenses the cords. The recurrent laryngeal nerve, after looping
Figure 20-12 Anatomy and relation of glossopharyngeal nerve as it exits from the base of the skull.
around the aorta on the left and the subclavian artery on the right, ascends into the groove between the esophagus
and the trachea to enter the larynx at the inferior cornu of the thyroid cartilage. It provides sensation to the larynx
below the level of the true vocal cords and motor supply to all the laryngeal muscles except the cricothyroid.
SPINAL ACCESSORY NERVE (CN XI) ANATOMY
The accessory nerve is a motor nerve consisting of spinal and cranial roots. It supplies motor fibers to both the
sternocleidomastoid and trapezius muscles.
HYPOGLOSSAL NERVE (CN XII) ANATOMY
The hypoglossal nerve is the motor nerve to the tongue. It leaves the cranium in close relation to the
glossopharyngeal and vagus nerves. At the angle of the mandible, it crosses both internal and external carotid
arteries to run superior to the greater cornu of the hyoid, where it enters the tongue. Motor fibers innervate the
thyrohyoid, styloglossus, hyoglossus, geniohyoid, and genioglossus.
CERVICAL NERVES ANATOMY
Skin of a great proportion of the dorsal scalp, the neck, and the shoulders is supplied by sensory branches of the
upper four cervical nerves ( Fig. 20–13 ). The dorsal rami of C2 to C4 supply the back of the neck and the scalp as
the greater occipital nerve. The ventral rami of C1 to C4 form the cervical plexus. The deep branches supply the
muscles of the neck and the diaphragm. The superficial cervical plexus pierces the posterior border of the
sternocleidomastoid at its midpoint to fan out and supply sensation from the lower border of the mandible to as low
as the second rib. The terminal branches are the lesser occipital, great auricular, transverse cervical, and
supraclavicular nerves.
GENERAL INDICATIONS
Regional anesthesia of the head and neck can allow a reduction in postoperative opioid analgesic requirements,
reduce intraoperative blood loss, and also provide an autonomic block to augment microsurgical blood flow after
reconstructive surgery. It is important to note that every anesthesiologist encounters patients with complex airway
anatomy that requires awake fiberoptic tracheal intubation.
404
All cranial nerves may be blocked as they leave the base of the skull, but, more frequently, the block is confined to
the more distal branches. More distal blocks offer the advantages described earlier without the serious sequelae of
the more central methods. They are also technically less demanding and allow any anesthesiologist to apply them
successfully in daily practice.
Figure 20-13 Formation of the cervical plexus and its branches.(From Raj PP: Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, p
278.)
Careful preoperative preparation is essential to success. A full medical history should be taken, including a history
of allergy, current medications, and previous anesthetics. Many metabolic and congenital diseases involve head,
neck, and airway pathology. Diabetes mellitus is a common cause of blindness. Also of importance are
homocysteinuria, sickle cell disease, and dystrophia myotonica. Relevant syndromes include Apert, Crouzon, Down,
and Marfan. Further discussion of these conditions is not within the scope of this chapter, but appropriate texts are
405
readily available. Physical examination including airway assessment should be undertaken. Appropriate
[1]
investigations and optimization of preexisting medical conditions should occur. An empathetic discussion with the
patient of the planned anesthetic management should be undertaken. Anxiolysis with either oral premedication or
titration of intravenous agents such as midazolam can assist block placement if appropriate. The very young or
elderly, confused patients may be unsuitable candidates for regional techniques alone. This does not preclude the use
of distal simple neural blockade techniques for postoperative analgesia. It is important to remember that sedation
does not replace an inadequate block. A careful assessment of success is required after block placement but before
surgery commences. Head and neck regional techniques offer specific clinical advantages in the following groups of
patients:
1. Ambulatory surgery
2. Poor medical risk patients
3. Carotid artery surgery
4. Thyroid and parathyroid surgery
5. Intractable head and neck pain
6. Awake intubation of the trachea and anticipated postoperative airway problems.
Side effects and hazards of specific blocks are listed with the description of block technique.
OPHTHALMIC SURGERY BLOCKS

Regional Anesthetic Techniques
Regional anesthesia for ophthalmology originated in 1884 when Carl Koller introduced the use of cocaine for
topical anesthesia of the conjunctiva. At present, regional techniques are used for surgery of the anterior and
posterior segments of the eye, cataract extraction, and lens implantation. Nerve blocks with neurolytic agents are
also used in the management of chronic eye pain.
Most ophthalmic operations are not urgent and patients should be optimized medically before surgery. Patients
requiring ophthalmic surgery are often elderly and suffer from coincidental medical conditions, including diabetes,
cardiorespiratory disease, and renal impairment. Conditions such as trauma, retinal detachment, or malignant
[1]
glaucoma necessitate emergency surgery, and all present challenges for the anesthesiologist. Before planning the
anesthetic care for surgery, the anesthesiologist must have a good understanding of ocular anatomy and physiology. [2]
In addition, the anesthesiologist must understand the ophthalmologist’s preferred conditions for the procedure.
Ophthalmic surgeries can broadly be subdivided into intra-and extraocular procedures. Intraocular surgery usually
requires globe and conjunctival anesthesia, globe and orbital hypotonia, and extraocular muscle and orbicularis
muscle akinesia. With advances in surgical techniques for cataract surgery, nonakinetic methods of regional
anesthesia have been popularized, these are subconjunctival, episcleral (sub-Tenon), and topical.
TECHNIQUE OF RETROBULBAR ANESTHESIA
HISTORY
Knapp (1884) first used cocaine for retrobulbar block, but the technique failed to gain popularity until
[2]
the 1930s, after the discovery of procaine. Atkinson described a cone injection technique, which
[3] [4]
became standard teaching ( Fig. 20–14 ). In the Atkinson method, the patient directs the gaze upward and
inward; however, this technique results in many complications, including damage to the optic nerve. To
[5]
avoid contact with the orbital nerve, the needle should not pass more than 31 mm beyond the orbital rim
with the eye in the primary gaze position. A conventional retrobulbar block does not cause paresis of the
[6]
eyelids; therefore, Van Lint developed a technique of periorbital anesthesia. Many ophthalmologists have
since described techniques for blocking the facial nerve. [7]
The conjunctiva is anesthetized and the local anesthetic solution prepared. The patient looks straight
406
Figure 20-14 The position of the needle during placement of a retrobulbar block. The needle is first directed straight backward until a loss of
resistance is experienced, indicating that the point of the needle is at the cone. The needle is then pointed upward toward the apex of the eye and
the local anesthetic is placed into the muscle cone.(From Raj PP: Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone,
1991, p 214.)
ahead and a 25-G, 40-mm needle is inserted either transconjunctivally or transcutaneously. The needle is injected in
line with the lateral limbus at the junction of the inferior and lateral limbus of the orbit. The needle is advanced
tangentially to the sclera and directed cephalad 10 degrees and posteriorly. Once the globe equator is passed, the
needle is also directed medially to puncture the intermuscular septum and enter the muscle cone. The eye
momentarily turns down and then returns to the neutral position as the septum is penetrated. The needle should not
penetrate beyond 31 mm. After negative aspiration for blood and cerebrospinal fluid, 3 to 4 mL of local anesthetic is
injected over 1 to 2 minutes. A superior rectus block is then performed by injecting 3 mL of solution through the
upper eyelid above the center of the eye. The needle is inserted to a depth of 15 mm and 2 mL of solution is injected.
The facial nerve may then be blocked by injection of 3 mL of local anesthetic through a 25-G needle over the
condyle of the mandible.
PERIBULBAR (PERICONE OR PERIOCULAR) ANESTHESIA
Peribulbar anesthesia was first described by Davis and Mandel in 1986. Many variations have been described.
[8]
Local anesthetic mixtures are deposited within the orbit but not within the cone of the rectus muscles. Hyaluronidase
assists the spread of solution to all compartments of the eye. Spread of the local anesthetic through the intermuscular
septum into the cone is required for full akinesia of the extraocular muscles. The onset is slower than retrobulbar
block and there is a 10% failure rate of akinesia. The conjunctiva is anesthetized and the anesthetic solution for
injection is prepared. Single and dual injection techniques have been described. Commonly, local anesthetic
[9] [10]
solution is injected in two places. A 27-G, 20-mm needle is inserted through the skin and enters the orbit at the
junction of the lateral and inferior rims ( Fig. 20–14 ). The needle is passed in a posterior direction parallel to the
orbital floor to a depth of 18 mm, and 5 mL of local anesthetic solution is slowly injected. More local anesthetic is
injected as the needle is withdrawn. A medial pericone block is then performed. On the medial side of the caruncle,
a 27-G, 25-mm needle is inserted posteriorly and slightly medially toward the medial orbital wall. The needle is
inserted 25 mm, and up to 5 mL of the solution is injected.
407
Complications
Complications of these techniques include subconjunctival edema (ecchymosis, retrobulbar hemorrhage, globe
penetration, temporary loss of acuity or light perception, or complete loss of vision. Inadvertent intravascular
injection can result in systemic toxicity, including confusion, convulsions, coma, and cardiorespiratory arrest. Optic
nerve injection can result in CSF spread, resulting in total spinal blockade. Allergic reactions have been reported
after injection of hyaluronidase.
TECHNIQUE OF TRIGEMINAL NERVE (CN V) BLOCK
The details and radiographic images of the trigeminal block are given in Chapter 41 .
GASSERIAN GANGLION BLOCK
This approach is useful in the management of painful conditions of the face and head, including pain of malignant
origin, intractable cluster headaches, and neuropathic pain syndromes.
Regional Anesthetic Technique
The patient is supine with the head resting on a donut to provide stability. A point is marked 3 cm lateral to the
corner of the mouth, and, through this point, a 25-G spinal needle is advanced toward the base of the skull ( Fig. 20–
15 A–C). The plane of insertion of the 25-G spinal needle is in line with the pupil in a neutral position in an anterior
plane and 1 cm anterior to the midpoint of the zygoma in the horizontal plane. The needle strikes the sphenoid
anterior to the foramen ovale. If the needle enters the oral cavity on insertion, a new needle should be used. It should
be walked 1 to 1.5 cm posteriorly, maintaining a line with the pupil to enter the foramen ovale. Paresthesia of the
mandibular branch may be encountered on passage through the foramen ovale. Fluoroscopy can assist in checking
needle passage through the foramen ovale. Before injection, an aspiration check for blood or CSF should be
performed. A total of 1 to 2 mL of local anesthetic should be injected in 0.25-mL increments for therapeutic or
diagnostic procedures. Radiographic confirmation of needle placement should always be performed before injection
of any neurolytic substance. Injection of neurolytic substances is being replaced largely by the newer technique of
thermogangliolysis. [11]
Side Effects and Complications
This approach to the trigeminal nerve divisions has a high risk of serious complications. The gasserian ganglion is
partially bathed in CSF, and even a very small amount of local anesthetic injected through the needle may lead to
total spinal blockade. Significant hematomas of the face and subscleral hematoma occur commonly. It is
recommended that this approach be used by experienced personnel. If neurolytic block is performed, fluoroscopy
should be used to check the needle position. All divisions of the nerve may be blocked as they emerge from the
foramina on the base of the skull.
408
Figure 20-15 Trigeminal (gasserian ganglion) block. A, Lateral view showing posterior clinoid process. B, Bony sphenoid ridge. C, Site of foramen ovale for the base of skull and needle entry.
(A and B, From Katz J: Somatic nerve blocks. In Raj PP (ed): Practical Management of Pain, 2nd ed. St. Louis, Mosby, 1992. C, From Raj PP, Lou L, Erdine S, Staats PS. Radiographic
Imaging for Regional Anesthesia and Pain Management. [in press].)
OPHTHALMIC (VI) DIVISION OF CN V BLOCK
Retrobulbar nerve block, when performed, blocks the first divisions together with the oculomotor nerve, the
trochlear nerve, the abducens nerves, and the ciliary ganglion (see earlier) (see Fig. 20–14 ).
MAXILLARY (CN V2) DIVISION OF CN V BLOCK
A 22-G spinal needle is introduced through the coronoid notch below the midpoint of the zygomatic arch ( Fig. 20–
16 ). The needle should be directed at an angle of 45 degrees, aiming for the apex of the orbital cone. The needle
strikes the medial edge of the lateral pterygoid plate or the body of the maxilla. Once the needle is positioned, 2 to 4
mL of local anesthetic can be
409
Figure 20-16 Extraoral posterior approach for nerve block of the maxillary division of the trigeminal nerve.(From Bennett CR: Manheim’s Local Anesthesia and Pain
Control in Dental Practice, 7th ed. CV Mosby, St. Louis, 1984. Also from Raj PP, Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, p
205.)
injected carefully in increments. An intraoral approach via the greater palatine canal has also been reported. This [12]
also blocks the sphenopalatine ganglion. We have used this block for postoperative analgesia after hard palate
surgery.
Caution must be exercised to prevent the needle from entering the infraorbital fissure and possibly damaging the
optic nerve. Diplopia can occur with correct block placement. Paresthesia is not essential for this block. Careful
[13]
aspiration should prevent inadvertent intravascular or subarachnoid injection, but because of the vascularity of the
region, bruising is common.
MANDIBULAR (V3) DIVISION OF CN V BLOCK
To block the mandibular nerve, the same landmarks are used as with the maxillary division. In this instance, the
needle is advanced perpendicularly in all planes until it strikes the posterior edge of the lateral pterygoid plate ( Fig.
20–17 ). This should be at a distance of approximately 5 cm. The needle is then walked
410
Figure 20-17 The technique for the extraoral block of the mandibular nerve is essentially the same as that for the maxillary block, except that the needle is directed
upward and posteriorly; thus, the mandibular nerve is contacted as it exits from the foramen ovale.(From Bennett CR: Manheim’s Local Anesthesia and Pain Control
in Dental Practice, 7th ed. St. Louis, CV Mosby, 1984.)
posteriorly until it slips off the posterior edge of the plate 1 cm further. This step may be omitted because enough
[14]
local anesthetic diffuses to the nerve around the border of the pterygoid. Once the needle is positioned, 2 to 4 mL of
local anesthetic can be injected. Paresthesia is not essential for this block. Dentists prefer the intraoral approach, [15] [16]
although this is not without complications, including temporary complete paralysis of cranial nerves III, IV, and
VI. [17]
As for the maxillary block, careful aspiration is required to prevent inadvertent intravascular or subarachnoid
placement.
TECHNIQUES OF DISTAL TRIGEMINAL BLOCK
The supraorbital, infraorbital, and mental foramina lie on a line 1.5 cm lateral to the alar margin. With the patient in
a supine position, a 30-G needle is used. Paraesthesia may be sought, but it is not essential for entering the foramina.
SUPRAORBITAL AND SUPRATROCHLEAR NERVE BLOCKS
Both of these nerves can be blocked from a single injection site on the nasal bridge. The injection should be given
continuously as the needle is advanced from a point on the bridge of the nose under the orbital rim to a point 1 cm
411
beyond the supraorbital notch. The needle should be directed downward and laterally toward the medial canthus.
One or 2 mL of local anesthetic should be sufficient for both blocks.
INFRAORBITAL NERVE BLOCK
The infraorbital nerve is located 1.5 cm lateral to the nasal bone and 1 cm below the orbital rim. The skin can be
punctured directly. Alternatively, it can be approached by entering the buccal sulcus at the upper premolar with the
needle directed upward toward the foramen. Entry of the foramen may lead to puncture of the orbital floor. Damage
to the infraorbital artery can cause ulceration of the infraorbital skin.
MENTAL NERVE BLOCK
The mental foramen lies halfway between the lower border of the mandible and the gum margin below the first
premolar. Application of an anesthetic-soaked pledget in the buccal sulcus allows for a painless injection through
the oral mucosa. Injection can also be performed through the skin.
ZYGOMATICOFACIAL AND LACRIMAL NERVE BLOCK
The zygomaticofacial nerve exits the zygomatic foramen 1 to 2 cm below the lower lateral border of the orbit.
Injection of 1 to 2 mL of local anesthetic around the foramen should be sufficient. From the same site, injection to
the outer third of the lateral canthus anesthetizes the lacrimal nerve.
INFERIOR DENTAL AND LINGUAL NERVE BLOCKS
The foramen is located in the center of the medial aspect of the ascending ramus of the mandible. The foramen is
found by rolling the index finger over the concavity of the retromolar trigone. With the barrel of the syringe resting
on the contralateral premolars, the needle is directed to a point just beyond the midpoint of the palpating finger.
While anesthetic is injected, the needle is directed medially and more posteriorly for a distance of 1 to 2 cm. A
column of 2 mL blocks both nerves.
BUCCAL NERVE BLOCK
The needle is inserted into the mucous membrane of the cheek at the level of the first mandibular premolar. The
needle is advanced parallel to the lateral aspect of the mandibular ramus. A volume of 2 to 3 mL should be sufficient
to block the nerve.
AURICULOTEMPORAL NERVE BLOCK
The landmark for this branch is the midpoint between the superficial temporal artery and the ear. Injection of 2 mL
of local anesthetic is usually sufficient to block this branch.
SPHENOPALATINE GANGLION BLOCK
Block of the sphenopalatine ganglion may be used to provide regional anesthesia for nasal and dental surgery or for
fiberoptic airway management. It may also be used in the management of acute migraine, acute cluster headache,
and facial neuralgia.
For the transnasal approach, the patient is placed supine. With a cotton tip soaked in 4% lidocaine or 10% cocaine,
the first applicator is passed along the upper border of the first turbinate until contact is made
412
Figure 20-18 Approaches for the sphenopalatine (pterygopalatine) ganglion block. (I) Intraoral technique, in which the needle enters the
pterygopalatine canal via the greater palatine foramen. (II) Intranasal approach (Sluder’s technique).
with the posterior pharyngeal wall. A second soaked cotton tip is passed along the upper border of the middle
turbinate. These should be left in place for 20 minutes.
For the greater palatine foramen approach ( Fig. 20–18 ), the greater palatine foramen is located in the hard plate
medial to the third molar. A fine needle is advanced 3 to 5 cm through the foramen in a caudad and slightly posterior
trajectory. The maxillary nerve lies just superior to the ganglion and a paresthesia may be elicited. After aspiration,
2 mL of local anesthetic is injected incrementally.
GLOSSOPHARYNGEAL (CN IX) BLOCK
With the peristyloid approach, owing to the presence of anatomic structures close to the glossopharyngeal nerve,
there is an extremely high risk of accidental intravascular injection or spread to the vagus, hypoglossal, and
accessory nerves.
With the patient in a supine position, the head is rotated to the side opposite the one to be blocked ( Fig. 20–19 ).
The landmark for needle insertion is a point between the posterior border of the mandible and the tip of the mastoid
process. A 23-G needle is advanced until the styloid process is contacted. The needle is then withdrawn slightly and
walked off the styloid process a further depth of 1 cm. After careful aspiration, 3 to 4 mL of local anesthetic is
injected in increments. An alternative technique has been described using an ultrasonically guided needle directed at
the glossopharyngeal nerve as it runs anterior to the internal carotid artery. This is intended to reduce the risk of
puncture of the vessels. An intraoral approach has been described. This requires adequate mouth opening, a tongue
depressor, and a long 22-G (spinal) needle. The needle is inserted submucosally in the caudad portion of the
posterior tonsillar pillar, or, alternatively, to a depth of 5 mm through the anterior tonsillar pillar. After aspiration, 5
mL of local anesthetic is injected. This approach can also be used during topical anesthesia of the airway.
Alternatively, Krause’s forceps holding local anesthetic soaked pledgets are rested in the piriform fossae for 3
minutes. This also blocks the superior laryngeal nerve.
Superior and Recurrent Laryngeal Nerve (CN X) Blocks Including Airway Blocks. All anesthesiologists
encounter patients with difficult airways. Regional airway blocks are essential in managing these situations safely.
Superior Laryngeal Nerve Block. With the patient supine, the hyoid bone is displaced to the side to be blocked,
which makes the hyoid bone more prominent. A short, fine needle is directed toward the lateral aspect of the hyoid
bone and walked off the inferior margin a depth of 1 to 2 mm until it pierces the thyrohyoid ligament. Aspiration is
performed to ensure that the airway has not been entered. Injection of 2 to 3 mL of local anesthetic is sufficient. This
process should be repeated on the other side to anesthetize the glottis above the true vocal cords ( Fig. 20–20 ).
413
Recurrent Laryngeal Nerve Block. Transtracheal injection anesthetizes the airway below the true vocal cords. A
22-G needle is inserted through the cricothyroid membrane in the midline. Once air is freely aspirated, 4 mL of 4%
lidocaine is injected rapidly and the needle withdrawn. This usually produces coughing. The coughing spreads the
anesthetic above the vocal cords, often making a separate superior laryngeal nerve block unnecessary. Coughing
could be undesirable in someone with raised intracranial pressure, and hematoma may occur if injection is not made
in the midline. Pulmonary aspiration may also theoretically be a risk once the block has been performed.
Anterolateral Approach to the Recurrent Laryngeal Nerve. Blockade of both sides would produce bilateral
vocal cord paralysis and should not be performed. Block of the recurrent laryngeal nerve can be undertaken for pain
due to malignancy at the level of the first tracheal ring. A 22-G needle is passed to the posterolateral margin of the
tracheal ring and 3 to 5 mL of local anesthetic is injected.
Figure 20-19 Point of entry on the skin for glossopharyngeal nerve block just
posterior to the mandible and anterior to mastoid process.
Figure 20-20 The internal and external branches of the superior laryngeal nerve are
blocked below the apex of the hyoid bone. (I) The needle penetrates the thyrohyoid
membrane and is directed toward the greater cornu of the hyoid bone for superior
laryngeal nerve block. Through the same point of entry, the needle can be directed into
the larynx for transtracheal spray. (II) The needle enters at the greater cornu of the
hyoid bone. (III) The usual approach for transtracheal spray is to insert the needle into
the larynx through the thyrohyoid membrane.
Stellate Ganglion Block. Stellate ganglion block is indicated in circulatory disturbances of the upper limb (e.g.,
Raynaud’s phenomenon). The stellate ganglion is approached most readily from the front via a paratracheal
approach (see Chapter 33 ). The sympathetic chain lies on both the C6 and the C7 transverse processes and can
easily be reached using a short, 3-cm needle. The position of the C7 transverse process is determined by placing a
mark 3 cm lateral to the middle of the clavicular notch and 3 cm vertical to the clavicle. The carotid sheath and
sternomastoid are retracted laterally as the needle is inserted perpendicularly through the mark to contact the bone.
The needle is then slightly withdrawn, and, after aspiration, a small test dose of local anesthetic is injected. Stellate
ganglion blocks carry the significant risk of total spinal anesthesia. [18]
414
CERVICAL NERVE BLOCKS
Great Auricular Nerve Block. This divides into pre- and postauricular branches to supply the greater part of the
ear. The landmark for this block is the tip of the mastoid process. Infiltration of 2 mL of local anesthetic in an
anterior and 2 ml in a posterior direction from this landmark is sufficient to block both branches.
Greater and Lesser Occipital Nerve Blocks. Occipital nerve block is indicated for posterior scalp anesthesia or
relief of headache associated with muscular tension or spasm. With the patient seated and the head flexed slightly
[19]
forward, both the greater and lesser occipital nerves can be blocked. Introducing a fine needle (approximately 30
mm long) lateral to the insertion of the trapezius muscle at the base of the skull blocks the greater occipital nerve.
The needle is advanced in a cephalad direction until the skull is contacted and then withdrawn 2 mm. After negative
aspiration for blood, 3 mL of local anesthetic is injected. The lesser occipital nerve is blocked by introducing the
needle medial to the origin of the sternocleidomastoid muscle at the mastoid process. The needle is aimed in a
cephalad and medial direction until it contacts the skull. The needle is withdrawn 2-mm and aspirated, after which
approximately 3 mL of local anesthetic should be injected.
Deep and Superficial Cervical Plexus Blocks. There are numerous surgical indications for these blocks, including
thyroid and parathyroid procedures, cervical lymph node biopsy, carotid endarterectomy, and pain management.
Superficial Cervical Plexus Block. The patient is placed supine with the head on a pillow and rotated to the
opposite side. The patient is asked to raise the head off the pillow to accentuate the borders of the
sternocleidomastoid muscle. The midpoint of the posterior border of the sternocleidomastoid muscle, at the level of
the cricoid cartilage, is the point of injection. A long, fine needle is advanced caudad along the middle third of the
posterior border of the sternocleidomastoid muscle. From the same insertion point, the needle is then aimed
cephalad and advanced again along the posterior border of the sternocleidomastoid muscle. A volume of 10 to 20
mL of local anesthetic is usually sufficient.
Deep Cervical Plexus Block. Using the classical method ( Fig. 20–21 ), with the patient in the same position as for
the superficial cervical plexus block, a line is drawn from the tip of the mastoid process to the transverse process of
C6, which is readily palpable. The transverse processes of C2, C3, and C4 lie approximately 0.5 cm posterior to this
line. C2 is palpable 2 cm caudad to the mastoid process. C3 and C4 can be palpated and lie a further 1 to 1.3 cm
apart and slightly anterior. A 23-G needle is advanced perpendicularly to all skin planes to rest on the transverse
process. The needle should be kept in contact with bone as the injection is performed. Alternatively, the needle may
elicit a paresthesia, or a discernible click may be felt as it enters the prevertebral fascia. After negative aspiration, 5
mL of local anesthetic should be injected incrementally at each site.
Using an alternate technique, a single needle can be placed at C3 or C4, and the corresponding nerve root can be
identified as described earlier. Ten mL of local anesthetic solution is injected after negative aspiration, with a finger
pressing at the C5 transverse process to prevent caudal spread.
415
Figure 20-21 Position and surface landmarks for the cervical plexus block.(From Raj PP: Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone,
1991, p 279.)
A nerve stimulator can be attached to the needle and used as described in Chapter 17 by placing the needle at C5.
Deltoid muscle contraction confirms placement of the needle at the C5 nerve root. Ten mL of local anesthetic
solution is injected, with distal digital pressure maintained.
Brachial Plexus and Its Branches
HISTORY
Brachial plexus block was first performed in 1889 by William Stewart Halsted, who used cocaine and
direct exposure in the neck to accomplish the block. In 1911, Hirschel described the first percutaneous
brachial plexus block. Since these historic reports, the efficacy of brachial plexus blockade has been
confirmed, and the block is now commonly used to provide upper extremity anesthesia.
The four usual sites of approach ( Fig. 20–22 ) for brachial plexus block are the interscalene space, the
supraclavicular region, the infraclavicular region, and the axillary region (see later discussion of each of these
approaches). Although all of these approaches have certain limitations or disadvantages, they offer the
anesthesiologist the opportunity to select from a variety of techniques the one that is most appropriate for the
intended surgical or therapeutic procedure. In general, supraclavicular and interscalene blocks are used when the
surgical operation is around the shoulder above the elbow. An axillary block is considered the best choice for
operations on the hand and medial side below the elbow. The infraclavicular block may be preferable for operations
in the forearm and around the elbow (see later discussion of each of these types of block).
416
ANATOMY
The brachial plexus is formed by the ventral rami of C5 to C8 and T1 (with minor contributions from C4 and T2).
From the proximal to the distal part of the plexus, it is described as having the following subdivisions ( Fig. 20–23 ):
1. Roots. These enter the interscalene groove between the scalenus anterior and scalenus medius. The C5 to
C6 nerve roots form the upper trunk. The C7 nerve root continues as the middle trunk, and the C8 to T1
nerve roots unite to form the lower trunk at the lateral border of the scalenus anterior muscle. The brachial
plexus is ensheathed by the prevertebral fascia and lies in the same plane as the subclavian artery. The
upper and middle trunks lie above the subclavian artery, and the lower trunk lies posterior to the subclavian
artery, close to the first rib.
2. Trunks and Divisions. Each trunk divides into anterior and posterior divisions.
3. Cords. The posterior, lateral, and medial are so named because of their relationship to the second part of the
axillary artery behind the pectoralis minor muscle. The posterior cord is formed by the union of posterior
divisions of all the trunks. The lateral cord is formed by the anterior divisions of the upper and middle
trunks. The medial cord is formed by the anterior division of the lower trunk.
Branches. Several branches arise from the brachial plexus. From the roots: C5 contributes branches to the phrenic
nerve; C5 to C7 contributes branches to the serratus anterior; and C8 to T1 contributes branches to the rhomboids,
and levator scapulae. From the trunks: The upper trunk C5 and C6 contributes a branch to the subclavius, and the
suprascapular nerve to the supraspinatus and infraspinatus. From the cords: the lateral cord contributes the lateral
pectoral nerve, the musculocutaneous nerve, and the lateral head of the median nerve; the medial cord contributes
the medial pectoral nerve, the medial cutaneous nerve of the arm and forearm, the medial head of the median nerve,
and the ulnar nerve; and the posterior cord contributes the upper and lower subscapular nerve, the nerve to the
latissimus dorsi, the axillary nerve to the shoulder joint (which innervates the deltoid and the teres minor), and the
radial nerve. Except for the innervation of the skin over the upper part of the shoulder (C3, C4) and the upper part of
the medial arm (T2), all motor and sensory innervation of the upper extremity is derived from the brachial plexus.
Sympathetic innervation is derived from the T1 to T5 spinal segments. The T1, T2 postganglionic fibers traverse the
brachial plexus via the stellate ganglion, and the T3 to T5 postganglionic fibers join the vascular branches of the
subclavian artery to the arm.
CLINICAL APPLICATIONS OF BRACHIAL PLEXUS BLOCK
More proximal surgical procedures usually use more proximal brachial plexus approaches (e.g., interscalene block
for shoulder procedures). Clinical applications of interscalene block include all shoulder surgical procedures,
including arthroscopic and open procedures, management of frozen shoulder, repair of humeral fracture, elbow
[20] [21] [22]
procedures, carotid endarterectomy, vascular shunts, chronic pain syndromes, pain of the arm and forearm, and
cancer pain management. Supraclavicular, infraclavicular, and axillary blocks are used for elbow, forearm, and
[23] [24] [25]
hand surgery.
417
Figure 20-22 Anatomy of the brachial plexus, showing the interscalene, supraclavicular, infraclavicular, and axillary approaches.
Figure 20-23 Anatomy of the brachial plexus.
418
Equipment. We primarily use nerve stimulator techniques for performance of regional anesthesia. It is
recommended that a high-quality nerve stimulator with digital readout be used. It is also highly recommended that
[26]
needles specifically designed for regional anesthesia be used because sharp needles may be associated with more
neurologic complications. We currently use the Stimuplex Digital nerve stimulator and Stimuplex insulated
[27]
needles (B. Braun Medical, Bethlehem, Pa.). The authors prefer nerve stimulation techniques because they obviate
the need for patient cooperation, thereby allowing the use of sedation titrated to each patient’s need, which gives
enhanced patient satisfaction. The use of sedation does not prevent diagnosis of inadvertent intraneural injection,
which is diagnosed by pain and movement on injection of a ½ mL test dose of local anesthetic. Injection of this
small dose of local anesthetic intraneurally is generally innocuous; however, larger volumes may cause neural injury,
probably by interfering with the vasa nervosa. Thus, if patient discomfort occurs with ½ mL, the needle should not
be “repositioned” as suggested in various articles but removed from the patient (because in repositioning, the nerve
is simply drawn back with the needle) and the block performed at a more distal site. We do not perform nerve blocks
in anesthetized adults because of the dangers of inducing neurologic damage. It is interesting, however, that in
[28]
pediatric patients, large series of blocks have been performed during general anesthesia without any documentation
of nerve injury. This is most probably due to the rich vasa nervosa in pediatric patients.
LOCAL ANESTHETICS USED FOR BLOCKS
For short procedures associated with mild postoperative pain, one can use mepivacaine or lidocaine 1% to 1.5%
with freshly added epinephrine 1:400,000. For longer procedures associated with significant postoperative pain, we
use ropivacaine 0.5% with 1:400,000 epinephrine. We inject 30 to 40 mL of local anesthetic for interscalene,
supraclavicular, and infraclavicular blocks and 40 to 50 mL for axillary blocks in adults. In pediatric patients, lesser
volumes appropriate for age are given. For continuous peripheral nerve blocks, we inject 0.2% ropivacaine at
[29]
infusion rates of 5 to 10 mL per hour.
RATIONALE FOR THE CHOICE OF LOCAL ANESTHETICS FOR BRACHIAL PLEXUS BLOCK
Surgical procedures are superficial or deep and of short or long duration. Superficial procedures usually require a
local anesthetic agent of short duration in lesser concentration, whereas deeper operations usually require a local
aesthetic agent of long duration in higher concentration. For successful brachial plexus block, one needs to use an
adequate volume and concentration of the chosen local anesthetic.
Ten milliliters of local anesthetic is necessary to produce a consistently good surgical block on each mixed
peripheral nerve. Because the brachial plexus block involves four major nerves, it requires 40 mL of local anesthetic.
The site of needle entry does not change the volume requirement. (Higher needle entry in the brachial plexus sheath,
such as that used for the interscalene, supraclavicular, or infraclavicular techniques, causes the motor block to
appear earlier than the sensory block. A more distal needle entry, such as that used for the axillary technique, is
associated with greater sensory block and poorer motor block.)
For consistent motor block of the brachial plexus, the recommended agents include 0.5% ropivacaine, 3%
chloroprocaine, 1.5% mepivacaine, and 2% lidocaine. For success with sensory block alone, lesser concentrations of
local anesthetic, such as 2% chloroprocaine or 1% lidocaine, may be used.
When choosing a local anesthetic for brachial plexus block, one should select an agent that does not exceed safe
blood concentrations when used in the volume required to produce a consistently good block.
PATIENT MONITORING
An intravenous infusion should be started. Blood pressure, EKG, and O2 saturation monitoring should be initiated.
ANATOMY: INTERSCALENE APPROACH
The brachial plexus in the interscalene region consists of roots and trunks covered by prevertebral fascia and
enclosed between fascia of the anterior and middle scalene muscles.
Equipment. The following items are required: Two 20-mL syringes, a 27-G local infiltration needle with a 2-mL
syringe, a nerve stimulator, and a 50-mm, 22-G insulated needle.
419
Drugs. For short-duration block (<1 hr) 2% to 3% 2-chloroprocaine, 40 mL, is used. For medium-duration block (3
hr): 1% to 1½% lidocaine or mepivacaine, 30 to 40 mL, is given. For prolonged block (>3 hr), ropivacaine 30 to 40
mL is the dosage used.
Technique. The patient lies in the supine position with the head turned to the opposite direction. The arm rests on
the side, trying to reach the knee. The anesthesiologist stands on the side to be blocked at the level of the neck. The
landmarks are as follows ( Fig. 20–24 A):
• The patient is asked to touch the ipsilateral knee (to depress the shoulder and decrease the amount of
redundant tissue in the neck)
• The cricoid cartilage (C6 level) should be palpated and a line drawn laterally from it, parallel to the skin
creases.
• The patient is asked to lift the head, thereby enhancing palpation of the lateral border of the clavicular
head of the sternomastoid muscle.
• Two fingers are placed under the muscle, and the patient is then asked to return the head to the examining
table (facilitating movement of the fingers onto the anterior scalene muscle). The fingers are then rolled
laterally until they fall into the interscalene groove.
• The point of entry of the needle is close to the point where the external jugular vein crosses the
sternomastoid (C6 level).
• The two examining fingers are moved apart approximately 2 cm. This splays the groove and decreases the
distance from the skin to the brachial plexus. Between the anterior and middle scalene muscles is the
interscalene groove. This is the point of needle insertion.
After skin preparation and local anesthetic infiltration, a stimulating needle is placed through the insertion point
perpendicular to the skin in all planes and slightly caudad. The slight caudad direction is to minimize the chance of
inadvertent spinal or epidural placement. The needle is inserted, looking for contractions of muscles at or below the
shoulder at an initial current of 1.5 mA. Once an appropriate contraction is elicited at a current of less than 0.5 mA,
30 to 40 mL of local anesthetic is incrementally injected. We prefer
Figure 20-24 A, Interscalene block. B, Interscalene space bounded by the anterior scalene and middle scalene muscles, containing the nerve root and covered by the
prevertebral fascia. (B, From Raj PP: Clinical Practice of Regional Anesthesia. New York Churchill Livingstone, 1991, p 287.)
420
that muscular contractions below the shoulder be elicited; however, deltoid contractions have been documented to
result in blocks adequate for shoulder surgery. Deltoid paresis ensures a successful block. Surgical placement of an
[30]
arthroscope anteromedially at the shoulder often results in patient discomfort and interferes with an otherwise
successful interscalene block. This area is innervated by dermatomes from T2 and T3, which are not part of the
brachial plexus. Thus, to ensure adequate surgical anesthesia, we routinely place 5 to 10 mL of local anesthetic
subcutaneously along a line from the axilla to the clavicle. It was previously thought that digital pressure applied
immediately above the injection site during interscalene block would prevent cephalad extension of local anesthetic
to the lower cervical plexus; however, this has been disproved. [31]
ASSOCIATED EFFECTS OF INTERSCALENE BLOCK
Ipsilateral diaphragmatic paresis secondary to phrenic nerve block occurs in 100% of patients, with associated
[32]
effects on breathing patterns and chest wall mechanics. These effects are innocuous in the vast majority of patients,
[33]
and as long as the contralateral diaphragm is functioning, they are not contraindications to brachial plexus block. It
has been suggested that severe respiratory dysfunction is a contraindication to interscalene block; however, in many
patients with severe dysfunction, (e.g., chronic obstructive pulmonary disease), the diaphragms are flat and the
accessory muscles of breathing are utilized more; thus, phrenic block may be less significant in these patients. We
thus use this block in patients with chronic obstructive pulmonary disease, realizing that intubation and ventilation
of these patients is associated with high morbidity and that any opportunity to avoid intubation would be beneficial
to these patients, whereas the worst case scenario, if phrenic block did result in some compromise, would be
intubation. Another associated effect of interscalene block is hoarseness secondary to recurrent laryngeal nerve
paresis. Ipsilateral sympathetic block resulting in Horner’s syndrome occurs in 50% of patients.
[34]
Complications of Interscalene Block
Activation of the Bezold-Jarisch reflex has been reported in the literature ; however, we have not experienced it in
[35]
our performance of interscalene blocks. Total spinal anesthesia due to inadvertent intrathecal injection either directly
or via extension along a dural cuff has been reported. Brachial plexopathy and permanent spinal cord injury
[36] [29]
(block performed under general anesthesia in an adult) have been among the neurologic injuries reported after
[37]
interscalene block.
AIDS TO BLOCK PERFORMANCE
In patients with difficult anatomy (e.g., morbidly obese), in whom the interscalene groove is difficult to palpate, the
interscalene groove may be located by drawing lines laterally from the cricoid and along the lateral border of the
clavicular head of the sternocleidomastoid muscle as described. Where these lines intersect, a mark should be made
2 cm laterally along the line from the cricoid. The insulated needle should be inserted at this mark perpendicular to
skin planes, and slightly caudad. If phrenic stimulation occurs (diaphragmatic stimulation), the needle has been
placed too far anteriorly and should be redirected more posteriorly. If posterior shoulder contractions occur, the
needle should be redirected more anteriorly.
PHYSIOLOGIC CHANGES
Monitoring should be performed for anesthesia of the shoulder, elbow, forearm, and hand. There is usually no
anesthesia of the inner aspect of the upper arm or elbow. The ulnar nerve is blocked only 50% of the time.
The following measures should be undertaken:
1. Aspiration before injection to prevent vascular or cerebrospinal fluid spread

2. A test dose of 1 to 2 mL of local anesthetic to observe central nervous system toxicity or total spinal block
3. Injection discontinued with appearance of early signs of toxicity
MANAGEMENT OF UNSUCCESSFUL BLOCK
This can be done with the following interventions:
1. Supplementation with propofol or midazolam
421
2. Supplementary narcotics intravenously if the block is partial but surgery is short or if the patient complains
of tourniquet pain
3. Supplemental nitrous oxide–oxygen (50:50) as analgesia if needed
4. Full general anesthesia with airway control if block is not present
ANATOMY OF THE SUPRACLAVICULAR APPROACH
The three trunks emerge from the interscalene space and continue their anterolateral and inferior direction to
converge toward the upper surface of the first rib. At the lateral edge of the rib, each trunk divides into an anterior
and posterior division. The divisions then enter the axilla through its apex. The trunks and divisions on the first rib
are closely grouped together and are thus accessible for block at this site ( Fig. 20–25 ).
Equipment
The following items are required: a 27-G ½-inch needle for skin infiltration, 2 × 20 mL syringes, a nerve stimulator,
and a 50-mm, 22-gauge insulated needle.
Drugs
For short-duration block (<1 hr): 2% to 3% 2-chloroprocaine, 40 mL, is used. For medium-duration block (2 hr), 40
mL of 1% to 1½% lidocaine, is given. For prolonged block (>3 hr): 40 mL of 0.5% ropivacaine is given.
SUPRACLAVICULAR BRACHIAL PLEXUS BLOCKS
HISTORY
Kulenkampff first described the classic supraclavicular approach to the brachial plexus. Subsequent
studies reported a high incidence of pneumothorax (2%–6%) with use of this technique, and
because of this complication, the Kulenkampff method is infrequently performed today. Various
modifications of the supraclavicular technique have been developed in an effort to decrease the
incidence of pneumothorax. The subclavian perivascular block was first described by Winnie and
Collins with a reported incidence of pneumothorax of less than 1%. Indeed, data regarding this
[23]
technique in 1001 patients reported no pneumothoraces. This technique is attractive in terms of

[38]
rapid onset of a dense block. These attributes probably reflect the fact that at the point of
[39]
subclavian perivascular block the plexus is contracted to its smallest volume at the level of the
trunks. Other brachial plexus supraclavicular approaches described include the plumb bob
technique and the classical technique, developed by Pham and associates.
[40] [41]
1. The midpoint of the clavicle is located midway between the prominence of the top of the shoulder
(acromial end of the clavicle) and the sternal end of the clavicle.
2. The point of entry is the lateral border of the anterior scalene muscle at the midpoint of the clavicle.
PROCEDURE
After a sterile preparation of the region, the needle is inserted at the point of entry above the midpoint of the clavicle
in the backward-inward-downward direction (BID) (see Fig. 20–25 ). This looks as if it is at right angles to all
planes at this level of the neck. Although the direction of the needle is toward the first rib, it is not necessary to
touch the rib. Stimulation of the forearm or hand is elicited. If stimulation is obtained, after negative aspiration for
air or blood, 1 to 3 mL of test dose of local anesthetic should be injected. This is followed by the total calculated
volume of local anesthetic after 5 minutes if there are no systemic effects. If stimulation is not obtained and the
needle touches the first rib, it usually touches it at the subclavian groove. The needle is walked posteriorly to elicit
stimulation. If stimulation is not obtained, contact with the rib is lost. Contact with the rib should be regained, and
the needle should be walked toward the vertebra. If no stimulation is obtained at this point, the procedure is repeated.
422
Figure 20-25 Supraclavicular approach to the brachial plexus. Note the insertion of the needle 1 to 2 cm superior to the midclavicular point in a backward-inward-
downward direction toward the first rib.(From Raj PP: Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, p 288.)
SUPRACLAVICULAR PLUMB BOB TECHNIQUE
The patient’s head is turned slightly to the contralateral side. The patient is asked to raise the head slightly off the
table so that the lateral border of the clavicular head of the sternocleidomastoid muscle can be identified as it inserts
onto the clavicle. This point is marked as the entry point. After skin preparation, an insulated needle is inserted at
the entry site as if it were a weight (“plumb bob”) under gravitational pull (i.e., in a parasagittal direction) ( Fig. 20–
26 ). If appropriate nerve stimulation of the forearm or hand is not obtained, the needle is returned to the skin and
redirected cephalad in small steps through an arc of 20 degrees. If this is not successful, the needle is returned to the
skin and redirected through an arc of 20 degrees in a caudal direction. Once muscle contraction in the forearm or
hand is elicited at an mA less than 0.5, 30 mL of local anesthetic is incrementally injected.
ALTERNATIVE TECHNIQUE: PERIVASCULAR SUBCLAVIAN APPROACH
423
The subclavian perivascular approach ( Fig. 20–27 ) to the brachial plexus has the point of entry at the interscalene
Figure 20-26 Supraclavicular block, “plumb bob” technique.
groove, where the subclavian artery pulsation is felt. A 22-G, 50 mm, insulated needle is directed caudad at this
point tangential to the dorsal aspect of the subclavian artery. The needle point is seeking the trunks at this position.
An associated side effect is that phrenic nerve block occurs in 30% to 50% of patients.
Complications
As with other supraclavicular blocks, pneumothorax can occur with an incidence between 0.5% and 5%. The
incidence may be higher in patients in whom the apex of the lung is positioned more cephalad (e.g., patients with
COPD, pediatric patients). Another possible complication is subclavian artery puncture.
Physiologic Changes
Anesthesia occurs in the whole arm up to the shoulder, except inside the upper third of the upper arm. There is
sympathetic block in the same regions along with loss of sweating and increased temperature.
Prevention of Deleterious Effects
1. Puncture of the subclavian artery or lung or entering epidural and subarachnoid space should be avoided.
2. The stellate ganglion may be blocked, especially with large volumes.
Figure 20-27 Subclavian perivascular block. Subclavian-perivascular approach to the brachial plexus. Note the point of entry at the interscalene groove, where the
subclavian artery pulsation is felt. A 22-gauge 1½-inch needle is directed caudad at this point tangential to the dorsal aspect of the subclavian artery. The needle point
is seeking the trunks at this position.(From Raj PP: Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, p 289.)
INFRACLAVICULAR BRACHIAL PLEXUS BLOCK
The infraclavicular block was developed to avoid the side effects and complications of supraclavicular blocks,
particularly pneumothorax. It also has advantages over axillary block in that this block may be performed with the
424
patient’s arm in any position. It provides a more consistent block of the axillary and musculocutaneous nerves than
the axillary block. Infraclavicular brachial plexus block was first described by Raj. [24]
RAJ INFRACLAVICULAR BLOCK
The length of the clavicle must first be defined by finding the acromioclavicular junction and the sternoclavicular
junction and determining the midpoint between them. From this point, a mark is made 2.5 cm caudal to the clavicle.
The brachial artery is then palpated in the axilla. A stimulating needle is inserted through the skin, marking below
the clavicle and directed toward the brachial artery pulse ( Fig. 20–28 A, B). After appropriate nerve stimulation at
an mA less than 0.5, local anesthetic is incrementally injected at a dose of 30 to 40 mL.
LATERAL INFRACLAVICULAR BLOCK
The lateral infraclavicular block was developed in an effort to present a more constant landmark, the coracoid
process. The coracoid process is identified and marked (shrugging should enhance palpation of the coracoid
process). From the medial aspect of the coracoid process, a mark 1 cm medial and 1 cm caudad is made. This is the
[42]
point of needle insertion. A stimulating needle is inserted directly perpendicular to the skin ( Fig. 20–29 ). After an
appropriate muscle contraction at an mA less than 0.5 is elicited, 30 to 40 mL of local anesthetic is incrementally
injected. The mean depth of insertion varies from 2.26 to 7.75 cm depending on body habitus. Side effects include
Horner’s syndrome secondary to ipsilateral sympathetic block. Complications include vascular puncture and (rarely)
pneumothorax.
Note that for both the Raj and coracoid approaches to the brachial plexus, shoulder stimulation (axillary nerve) or
biceps stimulation (musculocutaneous nerve) implies that the needle has been inserted too far superiorly. It should
be reinserted from a point 1 cm inferior to the initial inserting point and directed as described.
Figure 20-28 Infraclavicular approach to the brachial plexus. A, Note the entry of a 22-gauge 3.5-inch needle 1 inch below the midclavicular
point. It is directed laterally toward the axillary artery at an angle 45 degrees to the skin with the patient’s arm abducted to 90 degrees. B,
Transverse section of the axilla showing the relationship to the needle as it penetrates the pectoralis major and minor before entering the brachial
plexus sheath. Note the relationship of the neurovascular structures within the brachial plexus sheath. (From Raj PP: Clinical Practice of
Regional Anesthesia. New York, Churchill Livingstone, 1991, pp 290, 291.
Figure 20-29 Infraclavicular block: Lateral coracoid technique.
425
AXILLARY BRACHIAL PLEXUS BLOCK
The axillary brachial plexus block is the most commonly performed technique of brachial plexus anesthesia. This
technique was first described by Hirschel in 1911. Techniques to perform axillary brachial plexus block include the
transarterial, paresthetic, and nerve stimulation techniques. In good hands, all of these techniques have high success
rates and minimal complications.
At the level of the axilla, the position of the nerves in the neurovascular bundle in 75% to 80% of patients is as
follows: (1) musculocutaneous nerve: lateral aspect of the artery (in the coracobrachialis muscle); median nerve:
lateral/anterior aspect of the artery; ulnar nerve: medial aspect of the artery; radial nerve: posterior aspect of the
artery ( Fig. 20–30 ).
AXILLARY PERIVASCULAR BLOCK
The single injection perivascular axillary technique as described by Winnie is performed in the following manner.
[43]
The patient lies supine, with the arm to be blocked abducted to 90 degrees and flexed 90 degrees at the elbow.
Abduction beyond 90 degrees can compress the brachial pulse against the humerus and lead to obliteration of the
pulse. The axillary arterial pulse is palpated as proximally as is convenient and marked. Two fingers are placed
along the artery separated by 1 to 2 cm. Pressure is applied distally. Placing two palpating fingers on the vessel
minimizes the chance of inadvertent lateral or medial placement of the needle outside the sheath. The insulated
needle is inserted at the lateral aspect of the pulse at a 45-degree angle to the skin and directed cephalad while
searching for wrist flexion (median nerve stimulation). Once a muscular contraction at an mA less than 0.5 is
elicited, 40 to 50 mL of local anesthetic is incrementally injected. After injection, the needle is removed and
continuous digital pressure is maintained as the arm is adducted alongside the patient’s body. Digital pressure is
continued for 1 minute. The arm adduction removes the effect of humeral head pressure on the neurovascular sheath,
which might limit proximal spread of the local anesthetic solution.
TRANSARTERIAL AXILLARY APPROACH
This technique identifies the plexus by direct puncture of the axillary artery. Entry into the axillary artery is detected
by the aspiration of bright red blood through the needle. Various descriptions of this technique have been given,
including anterior placement of a large-volume injection, posterior placement of large-volume injection, or anterior
and posterior placement of equal volumes of injection with no significant differences in success rates. With the usual
technique, the needle is advanced through the anterior and posterior wall of the artery until aspiration of blood
ceases. At this point, it is assumed that the tip of the needle lies within the neurovascular bundle posterior to the
artery. After negative aspiration, local anesthetic is incrementally injected. If desired, half the volume can be
injected posteriorly and half anteriorly (total 40 to 50 mL). Side effects and complications include axillary
tenderness and bruising, hematoma formation with compression of the neurovascular bundle, infection secondary to
hematoma, pseudoaneurysm of the axillary artery, transient vasospasm, nerve injury, and unintentional arterial
[44] [45] [46]
catheterization during continuous catheter techniques.
Aids to Block Performance
If the axillary pulse is difficult to palpate (e.g., in morbidly obese patients), the following technique can often
successfully identify it. First, the biceps muscle is identified, moving medially the groove between the biceps and
coracobrachialis. Then the coracobrachialis muscle is identified. Immediately medial to the coracobrachialis muscle
is the arterial pulse. In our experience, it is not unusual for the musculocutaneous nerve to be missed after
performance of an axillary block. The coracobrachialis muscle is identified as described at the level of the pectoralis
muscle and is grasped between the thumb and index finger. An insulated needle is inserted perpendicular to skin into
the coracobrachialis muscle in a search for a contraction of the biceps/brachialis muscle. After successful
stimulation at an mA less than 0.5, 5 to 10 mL of local anesthetic is incrementally injected.
426
Figure 20-30 Axillary approach to the brachial plexus. A, Position of the arm, showing digital compression of the axillary artery and direction of the needle in the
brachial plexus sheath. B, Cross-section of the point of entry of the needle. (From Raj PP: Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone,
1991, p 293.)
MIDHUMERAL BLOCK
The midhumeral block was developed as a method of isolating and blocking each peripheral nerve individually. This
block is performed at the junction of the upper and middle third of the arm. The relationship of the peripheral nerves
relative to the brachial artery for midhumeral block is similar to the relationship for axillary block in that the median
nerve is anterior to the artery, the radial nerve is posterior, the ulnar nerve is medial, and the musculocutaneous
nerve is lateral. The brachial artery is palpated and marked. For median nerve stimulation, the needle is inserted
toward the pulse, and after flexion of the wrist and fingers is obtained, 10 mL of local anesthetic is incrementally
injected. The ulnar nerve is stimulated at the anterior medial aspect of the vessel and 10 mL of local anesthetic is
injected. The radial nerve is found posterior to the artery and 10 mL is injected. The musculocutaneous nerve is
found by directing the stimulating needle under the biceps for 2 to 4 cm until elbow flexion is noted. Ten mL of
local anesthetic is then injected. [47]
INTERCOSTAL BRACHIAL BLOCK
The intercostal brachial nerve is the only nerve in the upper extremity that does not originate from the
brachial/cervical plexus. It is conveniently anesthestized with a subcutaneous injection from the axillary arterial
pulse 2 to 3 cm medially. The intercostal brachial nerve (or medial brachial cutaneous nerve) supplies sensation to
the medial aspect of the arm.
LATERAL AND MEDIAL ANTEBRACHIAL CUTANEOUS NERVE BLOCKS
The lateral antebrachial cutaneous nerve (cutaneous branch of the musculocutaneous nerve), if not blocked as part of
the musculocutaneous block in the coracobrachialis, can be conveniently blocked at the elbow by a subcutaneous
ring of local anesthetic from the lateral aspect of the biceps tendon to the brachioradialis muscle. The medial
antebrachial cutaneous nerve (branch of T1) can be conveniently blocked by finding the olecranon, moving 4 cm
proximally, and injecting a 5 to 7 mL subcutaneous ring of local anesthetic along the medial aspect of the arm.
427
These two subcutaneous blocks of the antebrachial cutaneous nerves have been used successfully for creation of
arterial venous fistulas and as rescue techniques for incomplete brachial plexus blocks.
ULNAR, MEDIAN, AND RADIAL NERVE BLOCKS
Clinical applications of ulnar, median, and radial nerveblocks include surgical procedures on the hand and
supplementation of incomplete brachial plexus block.
NERVE BLOCKS AT THE ELBOW ( Fig. 20–31 )
Note that blockade at the elbow only gives sensory/motor anesthesia in the hand (anesthesia of the medial forearm
requires a medial antebrachial cutaneous nerve block as described). At the elbow, the ulnar nerve is located in the
intercondylar groove, which is a bony canal between the medial epicondyle of the humerus and the olecranon. The
median nerve is located medial to the brachial artery, which lies medial to the biceps tendon. The radial nerve lies
between the brachialis and brachioradialis muscles.
Equipment
Elbow blockade requires 25-G, 35-mm needles and 3 to 5 mL of local anesthetic for each nerve to be blocked.
ULNAR NERVE BLOCK
The patient is positioned supine with the forearm flexed on the upper arm to facilitate identification of the ulnar
groove (intercondylar groove). The olecranon process and medial epicondyles are identified and a line is drawn
between them. A needle is inserted at a 45-degree angle to enter the skin at a point 1 cm proximal to this line aiming
cephalad; 3 to 5 mL of local anesthetic is injected.
MEDIAN NERVE BLOCK
The patient is supine with the arm supinated. A line is drawn connecting the medial and lateral epicondyles of the
humerus. The brachial artery is identified medial to the biceps tendon. The needle is inserted medial to the brachial
artery pulse and 3 to 5 mL of local anesthetic is injected.
RADIAL NERVE BLOCK
The patient is positioned as for median nerve block. Identification of the biceps tendon is made along the line
between the medial and lateral humeral epicondyles. A skin mark is made 1 to 2 cm lateral to the biceps tendon. The
needle is inserted posterolaterally and 3 to 5 mL of local anesthetic is injected.
428
Figure 20-31 Deep anatomy for elbow and wrist block of musculocutaneous, radial, ulnar, and median nerves.(From Raj PP: Clinical Practice of
429
NERVE BLOCKS AT THE WRIST ( Figs. 20–32 and 20–33 )
At the level of the wrist, the median nerve is located between the flexor carpi radialis and the palmaris longus
tendon. The ulnar nerve is located medial to the ulnar artery and lateral to the flexor carpi ulnaris tendon. The radial
nerve has cutaneous branches supplying the lateral side of the dorsum of the hand and the proximal dorsal parts of
the three and a half digits.
Technique
The patient is asked to close the hand and flex the wrist to identify the palmaris longus and flexor carpi radialis
tendons. The needle is inserted between these tendons 2 cm proximal to the flexor crease, and 3 to 5 mL of local
anesthetic is injected.
At the level of the ulnar styloid the needle is inserted from the ulnar side of the flexor carpi ulnaris tendon and
directed laterally one centimeter, following which 3 to 5 mL of local anesthetic is injected. Alternatively, the needle
can be inserted perpendicular to the
Figure 20-32 Anatomy and needle position for the wrist block of the ulnar and median nerves.(From Raj PP, Clinical Practice of Regional
430
Figure 20-33 Anatomy of the superficial radial nerve at the level of the wrist. Note the needle directions for subcutaneous infiltration to block the
nerve.(From Raj PP: Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, p 299.)
skin just lateral to the flexor carpi ulnaris tendon and 3 to 5 mL of local anesthetic is injected.
The needle is inserted parallel to the wrist across the radial ulnar sulcus, and a subcutaneous injection is performed
using 2 to 3 mL of local anesthetic.
DIGITAL NERVE BLOCK

Clinical Application
This block is used for surgical procedures on the fingers.
Anatomy
The digital nerves run at the dorsal lateral borders of the proximal phalanges. Digital vessels run with the digital
nerves on the ventral and lateral aspects of the fingers. The common digital nerves divide the palmar and dorsal
branches. Palmar digital nerves are branches of the medial nerve. Dorsal digital nerves are branches from the radial
nerve and supply the back of the fingers.
Procedure
The patient’s hand and affected finger should be extended.
Equipment
A 25-G, 16-mm needle is used. Up to 2 mL of local anesthetic can be injected for each side. Note that epinephrine-
containing solutions are contraindicated because of possible ischemia (digital vessels are end vessels).
Technique
The needle should be inserted at the level of the metacarpal head on the dorsal surface of the hand. The needle is
advanced until resistance of the palmar dermis is appreciated. An injection of 1 mL of local anesthetic is then
performed on each side. Large volumes of local anesthetic should be avoided because mechanical pressure in a
confined space can result in vascular insufficiency and gangrene.
Complications
Complications of the technique include vascular puncture and hematoma.
431
Intravenous Regional Anesthesia
Intravenous regional anesthesia (IVRA), first used by Bier in 1908, enjoys continuous popularity because of its
simplicity, reliability, and safety for a variety of peripheral procedures. [48] [49]
Note the anatomy of the venous system in the upper and lower extremities in Figure 20–34 A and 20–34B.
Indications
IVRA is indicated for short (<1–1½ hr) procedures of the upper extremity below the elbow and the lower extremity
below the knee. [50] [51]
Choice of Agents
Many local anesthetic agents have been used for IVRA; however, because of side effects (e.g., chloroprocaine:
venous thrombosis; prilocaine: methemoglobinemia; bupivacaine: cardiotoxicity). Lidocaine is currently the local [52]
anesthetic of choice in a usual concentration of 0.5% with volumes, in adults, of 30 mL (upper
Figure 20-34 A, The superficial veins of the upper limb. B, The great saphenous vein and its tributaries. (A and B, From Gray H, Gross CM: Anatomy of the Human
Body. Philadelphia, Lee & Febiger, 1973, pp 700–717. C, Illustration of patient position with intravenous needle at the wrist and correct placement of dual cuff at the
upper arm, with individual monitor of pressure for each.
extremity forearm tourniquet) and 50 mL (upper extremity arm tourniquet or lower extremity leg tourniquet).
[53]
Volumes used can be modified for smaller patients by keeping within the guidelines of dosages of 1.5 to 3 mg/kg.
Method
Although conjectural, the suggested mechanisms of anesthesia include diffusion from the veins into small branches
of peripheral nerves or blockade of nerves accompanying the veins. [54]
432
The suggested method of IVRA performance, as with all regional anesthetic procedures, is to apply standard ASA
monitors and insert an intravenous. An intravenous cannula with attached extension tubing is then placed into the
operative extremity as distally as possible, with care taken to place it away from the site where the surgical incision
will be made. If necessary, more proximal veins to may be accessed, including antecubital veins, with the caveat that
more than 2 minutes of injection time must be allotted when injecting into such veins to allow for dispersion and to
prevent excessive tourniquet pressures resulting in release into the systemic circulation. Adequate but not excessive
padding is applied over the site where the tourniquet will be placed. A double-cuffed orthopedic tourniquet, as wide
as possible, is applied to the limb and secured. Proximal and distal tubings are noted. (Note that a large, single
tourniquet is used by many practitioners.) It is essential to preinflate the tourniquet and check it for leaks before
beginning the procedure because the commonest complication of IVRA is tourniquet failure. The tourniquet
pressure must be adequate to ensure limb ischemia.
Methods used include tourniquet inflation to 100 mm above the patient’s systolic pressure or 100 mm above
obliteration of a pulse oximeter signal. This is correlated with cessation of the radial pulse. After the tourniquet is
checked, the limb is elevated to allow venous drainage. An Esmarch bandage is then applied as distally as possible
and wrapped tightly up to the level of the tourniquet. The distal tourniquet is then inflated to act as an extension of
the Esmarch bandage, after which the proximal tourniquet is inflated. (Both tourniquets are left inflated for the
duration of the procedure; however, if tourniquet pain is not resolved with sedation or if narcosis occurs, it can
sometimes be alleviated by releasing the distal tourniquet to allow spread of the local anesthetic under the tourniquet,
with re-inflation of the distal tourniquet and then deflation of the proximal tourniquet.) Once the tourniquets are
inflated, the Esmarch bandage is removed and the limb is checked for ischemia (pale, white) before injection of
local anesthetic. If the limb appears cyanotic, ischemia is inadequate. The tourniquet should be deflated and the
whole system rechecked and reapplied. Once ischemia is confirmed, the local anesthetic is slowly injected over 2
minutes. The cannula is then removed and firm pressure is applied to the cannula site to prevent hematoma
formation. Anesthesia usually ensues within a few minutes.
The method of postprocedure tourniquet deflation for surgical procedures lasting more than 20 minutes allows safe,
single tourniquet deflation because most of the local anesthetic is bound to tissues distal to the tourniquet. For
procedures less than 20 minutes, the tourniquet should be alternately deflated for 10 seconds and re-inflated for 1
minute, with the cycle repeated so that a small bolus of local anesthetic is periodically released to the systemic
circulation.
Adjuvants
Over the years, many drugs, including low-dose neuromuscular blockers, α2 agonists, narcotics, and so forth have
been added to the local anesthetic to try to improve anesthesia; however, side effects have precluded their use. At
present, low-dose ketorolac (e.g., 20 mg in an adult) has been shown to have some benefit in improving analgesia. [55]
Newer local anesthetics are now available. Hartmannsgruber and colleagues have recently investigated the use of
[56]
low-dose ropivacaine and found it to result in less CNS excitation after tourniquet release, with the added benefit of
prolonged postoperative analgesia.
INTERCOSTAL NERVES
Indications
The intercostal nerve technique is indicated for surgery of the upper abdominal region in conjunction with celiac
plexus block, for postoperative pain in thoracoabdominal surgery, and for trauma in the chest wall—especially for
fracture of the ribs and for neurolytic blocks.
Anatomy
The spinal nerve in the paravertebral region divides into a dorsal branch, innervating the muscle and skin of the back,
and ventral branch that forms intercostal nerves for the 11 intercostal spaces and the subcostal nerve below the last
rib.
433
The first thoracic ventral branch contributes to the formation of the lower trunk of the brachial plexus. Only a small
part continues as the first intercostal nerve. The second intercostal nerve becomes the lateral cutaneous branch and
the intercostobrachial nerve, innervating the medial side of the arm. Each of the other intercostal nerves becomes a
lateral branch, innervating the skin of the lateral body wall and an anterior cutaneous branch of the anterior body
wall—the upper six branches up to the xiphisternum and then from T7, T8, T9, T10, and T11 to the skin of the
anterior abdominal wall. T10 is around the umbilicus. The anatomy of the formation of an intercostal nerve is
illustrated in Figure 20–35 .
Figure 20-35 Anatomy of the intercostal nerve and its distribution with its branches along the ribs.(From Raj PP: Clinical Practice of Regional Anesthesia. New York,
The upper six intercostal nerves innervate the muscle in the intercostal space. The lower five intercostal nerves and
subcostal nerves innervate the abdominal muscles in addition to the intercostal muscles. The nerve runs in the
neurovascular plane between the internal intercostal muscle and the innermost layer (subcostalis, sternocostalis,
innermost intercostal), protected by a costal groove in the intermediate part of the rib in the region where the
innermost layer of the muscle is deficient.
Equipment
The requirements for this procedure are a 22-G 1½-inch (3.8 cm) needle, a 23-G ½-inch needle, 10-mL syringes,
and the usual preparation tray.
Drugs
For this procedure 3 to 5 mL of drug are required per intercostal nerve. For short-duration block, lidocaine, 1% to
1.5%, is given. For prolonged block, ropivacaine, 0.5% is the drug of choice. The neurolytic agent used is phenol,
6% to 8%, in Renografin.
Procedure
434
The intercostal block ( Figs. 20–36 and 20–37 ) can be done at (1) the angle of the rib posteriorly, (2) the posterior
axillary line and midaxillary line laterally, (3) the anterior axillary line anteriorly. The patient usually lies prone for
bilateral intercostal blocks. After the usual skin preparation, the needle entry is made over the rib selected for the
block. It should touch the lower half of the rib subcutaneously. At this point, with one hand holding the needle and
syringe, the other hand moves the skin caudally over the rib, in such a way that the needle point slips off the rib. The
needle is pushed about 3 mm deeper until a click is felt. The hub is now turned downward and the needle tip is
directed under the lower edge of the rib cephalad about 2 to 3 mm. Aspiration for air or blood is performed. If
aspiration is negative, 3 mL of local anesthetic is injected. For one intercostal space to be blocked, three intercostal
nerves (the one to be blocked and one above and below) have to be injected.
Complications
The complications arising from intercostal blockade involve primarily two separate issues. One is the inadvertent
pleural puncture leading to pneumothorax. The technique should be performed carefully using thin needles. The
pneumothorax should be recognized and dealt with as necessary, and the patient should be reassured. With the use
of a 22-G, short-bevel needle, even in relatively inexperienced hands, such as in a resident teaching program, the
incidence is less than 1%. If pneumothorax occurs, it can be easily treated with simple aspiration and observation.
Only a very small percentage of these pneumothoraces require chest tube drainage. In the case of a unilateral
thoracotomy with chest tube drainage, concern over pleural puncture is a moot point.
The second concern—intravascular injection leading to toxicity—is much more problematic. Because the intercostal
space is supplied by a rich network of vascular anastomosis and because of the high metabolic activity of the
intercostal muscles, there is much greater absorption of the local anesthetic, leading to high plasma levels. The blood
levels are higher and peak sooner than occurs with the same amount of local anesthetic injected elsewhere, such as
the axillary sheath or other nerve blocks. This may lead to toxic reactions; therefore, careful attention must be paid
to the maximum dosage allowed and the addition of a
Figure 20-36 Technique of intercostal block at the angle of the ribs. Note the finger palpating the inferior edge of the rib. The needle is inserted below it.(From Raj
PP: Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, p 302.)
435
Figure 20-37 Intercostal nerve compartment bounded by external intercostal and internal intercostal muscle superficially and innermost intercostal muscle on the
deeper aspect. Between the ribs, the solutions can spread into adjacent spaces and flow medially into the epidural space.(From Raj PP, Clinical Practice of Regional
vasoconstrictor in small concentrations (1:200,000– 1:400,000).
The existence of a third complication associated with intercostal block has actually been proved with dye studies:
the development of spinal anesthesia. A rare but noteworthy complication results from the fact that the dura
occasionally extends out along the intercostal nerve a variable distance before it adheres to the nerve as the
neurilemma or nerve sheath. The fact that anesthetic drug deposited in this potential space can dissect back into the
subarachnoid space has been shown and results in a spinal anesthetic. Certainly, in view of this, all the precautions
necessary to support the patient should be present (airway equipment, breathing bag, intravenous fluids, and
vasopressors). Any block done under anesthesia by the anesthesiologist, or especially by the surgeon (from within
the thoracic cavity), which results in significant hypotension not otherwise explained should be considered as
resulting from inadvertent spinal anesthesia, and the patient’s respiration and blood pressure should be supported
until the block dissipates.
INTERPLEURAL BLOCK
Interpleural administration of local anesthetic for the control of pain was described initially by Reiestad in 1984 [57]
and has been the subject of several investigations in the past several years. Indications for the technique have
expanded and include postoperative pain relief after thoracic and upper abdominal surgical procedures including
cholecystectomy, nephrectomy, unilateral breast surgery, and gastric fundoplication. Additionally, the technique has
been used for treatment of patients with pain after blunt chest trauma and the multiple rib fractures associated with
flail chest. Treatment of patients with acute herpes zoster and those with postherpetic neuralgia are other possible
applications. Bilateral catheters have been used but are limited by the risk of systemic toxicity.
Contraindications
436
Contraindications to the technique appear to include significant pleural injury or thickening because of difficulty in
identifying the pleural space with a loss-of-resistance method; presence of pleural fluid collections because of the
dilutional effect they may have on the local anesthetic; systemic sepsis; localized pleural infection or inflammation
because pleural inflammation may allow rapid absorption of local anesthetic and ensuing toxicity; and a bleeding
diathesis because of the risk of hemorrhage.
Complications
Complications of the procedure thus far reported in the literature have been surprisingly few, with one report of a
seizure after bolus administration of 33 mL of 0.5% bupivacaine solution with 1:200,000 epinephrine. There has
[58]
been a report of a pneumothorax in a ventilated patient after catheter insertion.[59]
Pharmacokinetics
The pharmacokinetics of interpleural infusions have been studied using a variety of solutions, but bupivacaine
solutions with and without epinephrine have been the most common ones used in these investigations. Arterial and
venous bupivacaine plasma levels in the presence and absence of epinephrine were 1.1 to 3.3 µg/mL, peaking 20
minutes after bolus administration of 30 mL of bupivacaine, 0.5%,. One patient with a recent pleural infection had
peak levels of 4.9 µg/mL and displayed seizure activity. It was thought that the pleural inflammation allowed more
rapid absorption in this case. Another group reported levels peaking at a range of 1.1 to 2.38 µg/mL after 20 mL of
bupivacaine, 0.5%, with and without epinephrine. Another study demonstrated a significant lowering of peak blood
levels when epinephrine-containing solutions were used. A 20-mL bolus of bupivacaine, 0.5%, produced peak levels
of 0.32 µg/mL in the epinephrine-containing group and 1.7 µg/mL mean peak serum levels in the group without
epinephrine.
Duration of action has also been studied after bolus injection; duration of analgesia after a single bolus injection of
20 mL of bupivacaine, 0.5%, with epinephrine was 6 to 27 hours (mean time 10 hr).
Technique
The technical aspect of the procedure is quite simple. The patient is placed in the lateral decubitus position with the
affected side uppermost. Sterile preparation of the skin area is performed, and a skin wheal is raised with a 25-G
needle between the 7th and 8th ribs and the angle of the ribs, approximately 8 to 10 cm from the midline posteriorly
( Fig. 20–38 ). This corresponds well to the interspace felt just beneath the scapular angle with the arm held at the
side. After the skin is nicked with an 18-G needle, a 17-G Tuohy needle with the bevel directed towards the head is
walked off the superior border of the rib and advanced about 3 mm. A definite resistance may be felt at this point,
corresponding to perforation of the posterior intercostal membrane. The stylet is removed and a lubricated glass
syringe is attached to the hub of the needle. The needle and syringe are then carefully advanced until perforation of
the parietal pleura is accomplished, with subsequent loss of resistance and a definite clicking feeling noted. The
syringe is then removed and the hub covered by a finger until an epidural catheter is readied for insertion. The
catheter is fixed into position and dressed with a transparent plastic dressing to allow easy visibility of the puncture
site. After aspiration and a suitable test dose, local anesthetic is administered by bolus and followed by continuous
infusion.
437
The mechanism of action of the analgesic effect of the technique is not known. One possible explanation is diffusion
of the anesthetic retrograde through the parietal pleura, causing intercostal nerve block. Another, more likely
explanation is diffusion of the local anesthetic posteriorly to the paravertebral area, effecting blockade of thoracic
nerve roots and sympathetic ganglia. Still other possibilities include systemic local anesthetic effect, blockage of the
nerve endings of the pleural surface itself. More studies are needed to
Figure 20-38 Interpleural block. The epidural needle is introduced at the T7 to T8 interspace at the inferior angle of the scapula. The needle-tip position in the
interpleural space is confirmed by the hanging drop technique, and catheter placement is performed.(From Raj PP, Clinical Practice of Regional Anesthesia. New
York, Churchill Livingstone, 1991, p 305.)
explain the mechanism of action of intrapleural anesthesia.
The intrapleural catheter technique has certain limitations but also several distinct advantages over the more
traditional intercostal nerve block, thoracic epidural blockade, and parenteral narcotic administration. The procedure
is technically simple to perform. Only one needlestick is needed in contrast to intercostal nerve block, which, if done
at multiple levels, can result in relatively high local anesthetic blood levels and systemic toxicity. Use of parenteral
narcotics may provide pain relief at the expense of the central nervous system and respiratory depression. Thoracic
epidural blockade can produce sympathetic block and result in systemic hypotension along with pruritus and urinary
retention if opiates are being used.
Paravertebral Block
Paravertebral somatic nerve blockade (PVB) is a technique that was first described in 1905 by Hugo Sellheim. It
was initially used as an alternative to spinal anesthesia to minimize the cardiovascular and respiratory effects of
central neuraxial block. However, after initial enthusiasm, PVBs have been used sparingly to provide anesthesia
[60]
and analgesia. New enthusiasm for paravertebral blocks has occurred along with new enthusiasm for other forms of
regional anesthesia in the hope of decreasing the side effects associated with general anesthesia and opioids. [61]
Anatomy
The paravertebral space is a wedge-shaped anatomic compartment adjacent to the vertebral bodies. The space is
defined anterolaterally by the parietal pleura, posteriorly by the superior costotransverse ligament (thoracic levels),
medially by the vertebrae and interverbal foramina, and superiorly and inferiorly by the heads of the ribs. Within
this space, the spinal root emerges from the intervertebral foramen and divides into dorsal and ventral rami. In
addition, sympathetic fibers of the ventral rami enter the sympathetic trunk via the preganglionic white rami
communicantes and the postganglionic gray rami communicantes in this space. Because of the multiple neurologic
structures confined within this compact space, local anesthetics introduced here can produce unilateral motor
sensory and sympathetic blockade.
438
Indications
Paravertebral blocks (PVBs) are used for various types of surgery and for patients with acute pain : [62]
1. In breast surgery, paravertebral block can provide anesthesia and excellent postoperative analgesia for
every breast procedure from biopsy to modified radical mastectomy and axillary dissection. Paravertebral
block is particularly suited for those patients who have significant medical comorbidity (e.g.,
cardiorespiratory disease related to treatment of cancer, adriamycin cardiotoxicity, bleomycin pulmonary
toxicity) because it produces anesthesia to be administered without the side effects of general or central
neuraxial anesthesia.[63] [64] [65]
2. In thoracic surgery, for chest wall procedures (e.g., rib resections), paravertebral block can provide
excellent anesthesia. For pulmonary surgery, continuous paravertebral catheters can provide highly
successful postoperative analgesia with minimal effects on pulmonary function. Thoracoscopic surgery
[66] [67]
is an excellent indication for PVBs.

3. PVBs provide excellent postoperative analgesia for open procedures such as cholecystectomy and
nephrectomy. There is some evidence that thoracic PVBs, because of their effect on the sympathetic chain,
may provide visceral analgesia also, (e.g., liver capsule pain) , and thus they may also be useful for
[68]
laparoscopic cholecystectomy.
4. PVBs provide excellent operative conditions and prolonged postoperative analgesia for inguinal, ventral,
[69] [70]
or umbilical hernia surgery.

5. PVBs at T11 to L3 provide excellent anesthesia/analgesia for iliac crest bone graft harvest. This is
particularly helpful in patients with significant spinal abnormalities such as ankylosing spondylitis because
in these patients, spinal or epidural procedures may be difficult to perform.
6. Continuous thoracic paravertebral block either unilaterally or bilaterally has been useful in minimally
invasive cardiac surgery to provide excellent anesthesia and analgesia while allowing early ambulation. [71]
There is also a potential advantage of avoiding central neuraxial hematoma with this technique.
7. In patients with trauma, PVBs provide excellent analgesia for rib fractures, particularly upper rib fractures,
when the thoracic spine has not been cleared for performance of an epidural injection. PVBs have
advantages over intercostal blocks because it takes three intercostal injections to provide analgesia to one
nerve, whereas paravertebral injection can spread to adjacent dermatomes and thus enhance success rates.
Because of decreased vascularity in the paravertebral space, it is probable that PVBs provide much longer
analgesia than intercostal blocks, although this has not been studied as yet.
8. Paravertebral block is being used for patients with chronic postherpetic neuralgia and other chronic pain
syndromes. PVB may have an advantage over other techniques in treating this type of pain because
blockade of the sympathetic ganglia as well as excellent somatic blockade is provided by this technique.
9. For other somatic malignant or nonmalignant chronic pain syndromes, PVB can be useful both
diagnostically and therapeutically. Both single-shot and continuous catheter techniques are being evaluated
in the treatment of reflex sympathetic dystrophy.
10. For obstetric analgesia, when PVBs are performed at the L2 level, interruption of afferent impulses from
the cervix occurs and thus excellent analgesia can be obtained. [72] [73]
The usual contraindications to regional anesthesia, such as infection at the site of injection or coagulopathy, apply to
performance of PVBs; however, paravertebral catheters may be useful in patients about to undergo anticoagulation
because PVBs are outside the central neuraxis.
Technique
As with all regional anesthetic techniques, adequate hemodynamic monitoring and resuscitation equipment should
be available. At our institution, blocks for both thoracic and lumbar PVB are carried out with patients in the sitting
position. To maximize operating room efficiency, block placement is usually performed in a monitored pre-
operative holding area. After application of monitors and administration of supplemental oxygen, patients are
usually sedated with midazolam, 1 to 3 mg, and fentanyl, 50 to 150 µg intravenously.
Equipment
The supplies required for this type of block are a 22-G Tuohy needle (B. Braun Medical, Bethlehem, Pa.), extension
tubing, a skin marker, and local anesthetic skin wheal antiseptic solution (Betadine).
Levels
The dermatomes that will be involved in the operative field must be selected. For mastectomy with axillary
dissection, we routinely block T1 to T6. For breast biopsy, we usually make one injection at the dermatome
439
corresponding to the needle localization plus injections one dermatome above and below this site. When we perform
the block for inguinal herniorrhaphy, levels from T11 to L2 are blocked.
Technique
The patient is seated with the neck flexed, back arched, and shoulders dropped forward (similar to the positioning
for thoracic epidural placement). The spinous process of each level is identified and a mark is placed at its most
superior aspect. From the midpoint of these marks, a needle entry site is designated 2.5 cm laterally ( Fig. 20–39 ).
These marks should overlie the transverse process of the immediately caudal vertebra (because of the extreme
angulation of the thoracic spinous processes). In the lumbar area, the transverse process is at the same level as the
spinous process or even one level above the spinal process.
Employing aseptic technique, a skin wheal is placed at each landmark. Using a 22-G, 3.5-inch Tuohy epidural
needle attached via extension tubing to a syringe, the shaft of the needle is grasped by the dominant hand of the
operator. The needle is inserted through the skin wheal and advanced anteriorly 2 to 5 cm (depending on the body
habitus of the patient) in the parasagittal plane (perpendicular to the back in all directions) until it contacts the
transverse process. As a safety measure, to prevent inadvertent deep placement, the needle is grasped at a point from
its tip that is equal to the estimated depth from the skin to the transverse process. Inserting the needle 1 cm past this
predicted depth is allowed. If the transverse process is not identified at an appropriate depth, it is assumed that the
needle tip lies between adjacent transverse processes. The needle is then redirected cephalad and caudad until the
transverse process is successfully contacted. This depth is noted as the estimated distance to subsequent transverse
processes. The needle is then withdrawn to the subcutaneous tissue and angled to walk off the caudad edge of the
transverse process 1 cm. At thoracic levels, it is common to appreciate a loss of resistance or a subtle “pop” as the
needle passes through the superior costotransverse ligament. After aspiration of the syringe, 2 to 5 mL of local
anesthetic is injected at each level. It is important to note that in the lumbar region, the transverse process is very
thin. Hence, the needle should be inserted only ½ cm past the transverse process. In addition, there is no superior
costotransverse ligament in this region. If a distinct pop is felt here, the needle has likely punctured the psoas fascia
and should be withdrawn to a more shallow depth. For both thoracic and lumbar blockade, the local anesthetic
solution should inject easily with little resistance.
Drug
The selection of local anesthetic, as with other regional techniques, should be based on available agents, onset,
duration, and side effects. We routinely use ropivacaine, 0.5% (with 1:400,000 epinephrine as the intravascular
Figure 20-39 A, Paravertebral block

technique. B, Paravertebral space:
anatomy.
marker) and achieve sensory blockade within 15 minutes.
440
Complications
Potential complications from paravertebral nerve blockade involve inadvertent needle penetration of adjacent
structures. [74]
As with all regional anesthesia techniques involving local anesthetics, inadvertent intravascular injection, or
excessive doses can result in local anesthetic toxicity. However, despite the close proximity to the epidural space,
systemic absorption of local anesthetic appears to occur less than with conventional epidural techniques.
Ropivacaine doses of 3 mg/kg have been administered safely. As always, incremental injection techniques are
essential.
Because of the close relationship of the paravertebral space to the parietal pleura, incorrect needle placement may
result in lung injury. In skilled hands this complication is rare. In one study examining our early experience with
thoracic paravertebral block for breast cancer surgery, the authors found that a pneumothorax occurred in only 1
patient in 319. We believe walking caudad off the transverse process gives an added margin of safety; if the rib
(deeper) is initially contacted, the needle almost always contacts the caudad transverse process (more superficial)
and thus avoids the lung.
Because of the close proximity of the paravertebral space with central neuraxial structures, inadvertent medial
needle insertion can result in epidural or spinal blockade. Even a properly placed PVB can result in medial spread of
local anesthetic because of dural cuffs extending from the midline. Despite the close relationship of these structures,
bilateral anesthetic spread at the thoracic level is relatively rare.
Bilateral sympathetic blockade from epidural spread can result in hypotension similar to that occurring with thoracic
epidural anesthesia. In general, unilateral and bilateral PVBs do not result in significant hypotension.
“Pearls” Pertaining to Paravertebral Block
The following points should be noted regarding PVBs:
1. For thoracic PVBs the midpoint of the superior aspect of each spinous process should be found and
measured 2.5 cm laterally; these points should be marked. The points generally overlie the caudad portion
of the transverse process of the vertebra below. Because of the extreme angulation of the thoracic spinous
process, a lateral line overlies the transverse process of the vertebra below. For example, a line lateral to the
T3 spinous process overlies the transverse process of T4.
2. The block should begin with the most superficial transverse process (e.g., T3, T4) and work up and down
from there.
3. The Tuohy needle should be inserted perpendicular to the skin a distance of 2 to 4 cm (more in the obese)
to contact the transverse process. If the transverse process is not contacted at an appropriate needle depth,
the operator should not proceed because the needle is probably between two transverse processes. The
needle should be returned to the skin point and a search conducted either cranially or caudad until a
transverse process is successfully contacted. If bone is contacted at a point that seems too deep, this is rib,
which is anterior to the transverse process—again, a return should be made to the skin and the a search
should be conducted cranially or caudad for bone contact that is more superficial.
If while attempting to walk caudally off the transverse process, too much angulation of the needle is required,
the transverse process has probably been contacted at its cephalad rather than its caudad aspect. The needle
should be returned to the skin and reinserted at a skin site 1 cm more caudal. If further attempts continue to
result in an extreme angulation, an attempt should be made to walk cephalad off the transverse process, and the
operator should recognize that the block may be at a root one level higher than anticipated.
4. If many attempts result in continued bony contact, the operator may be too medial (walking along laminae)
or, more commonly, contacting transverse processes that are much closer together (e.g., from degenerative
disease in the elderly, resulting in vertebral body collapse). In these patients, slight caudad or cephalad
insertions after a perpendicular insertion resulting in bony contact usually results in successfully passing
the transverse process. If this is not the case, it may be possible to flex the patient’s spine further to increase
the distance between the transverse processes.
5. Scoliosis may require that the needle be inserted parallel to the spinous process (i.e., at an angle) because
the spines are rotated.
6. For hernia surgery, blockade of T11, T12, L1, and L2 is made. In the lumbar area, the same technique is
used as for thoracic block; however, because the transverse processes are much thinner in the lumbar area,
441
the needle is walked off the transverse process only 0.5 cm before local anesthetic is injected. Deep
insertion of the needle beyond the transverse process puts the needle into the psoas muscle, which results in
decreased effect.
Lower Extremity Regional Blockade
Regional blockade can be carried out for virtually every surgical procedure involving the lower extremity. It is
efficacious when central neuraxial blockade is contraindicated and also is a superb adjunct to general anesthesia for
providing excellent intraoperative and postoperative analgesia.
Anatomy
The lower extremity is innervated by two major nerve plexuses, the lumbar plexus and the lumbosacral plexus. The
lumbar plexus forms deep within the psoas muscle, residing anterior to the transverse processes of the lumbar
vertebrae. It is formed from the ventral rami of the first three lumbar nerves (L1–L3), with a contribution from the
fourth lumbar nerve (L4). The first lumbar nerve is joined by a branch of the 12th thoracic nerve, in 50% of people
( Fig. 20–40 ). The lumbar plexus distributes primarily to the ventral aspect of the lower extremity. The cephalic
portion of the lumbar plexus, which is made up of the the first lumbar nerve and a portion of the 12th thoracic nerve,
splits into superior and inferior branches. The superior branch then further divides into the iliohypogastric and
ilioinguinal nerves, whereas the small inferior branch combines with a small superior branch of the second lumbar
nerve to form the genitofemoral nerve.
The iliohypogastric nerve enters the transverse abdominal musculature near the iliac crest and supplies motor fibers
to the muscles of the abdomen. It terminates in an anterior branch to the skin of the suprapubic region and a lateral
cutaneous branch to the hip.
The ilioinguinal nerve lies somewhat inferior to the iliohypogastric nerve. It crosses the inguinal canal and
442
Figure 20-40 Lumbar plexus anatomy.
terminates by supplying branches to the skin of the upper and medial regions of the thigh and to the anterior scrotal
nerves that supply the skin at the root of the penis and anterior scrotum. Comparable anatomic structures in the
female are the anterior labial nerves supplying the skin of the mons pubis and the labia majora.
The genitofemoral nerve divides into genital and femoral branches. The smaller genital branch enters the inguinal
canal at the deep inguinal ring, supplying the cremaster muscle, small branches to the skin and fascia of the scrotum,
and adjacent parts of the thigh. The femoral branch is more medial and travels under the inguinal ligament on the
anterior surface of the external iliac artery. It then penetrates the femoral sheath inferior to the inguinal ligament and
travels through the saphenous opening to supply the skin overlying the femoral triangle lateral to that supplied by
the ilioinguinal nerve.
The lateral femoral cutaneous, femoral, and obturator nerves are the three major nerves of the lumbar plexus that
exit the pelvis anteriorly and innervate the lower extremity. The lateral femoral cutaneous nerve passes under the
lateral end of the inguinal ligament. It lies either superficial or deep to the sartorius muscle and travels deep to the
fascia lata. Here, it provides cutaneous innervation to the lateral portion of the buttock distal to the greater femoral
trochanter and to the proximal two thirds of the lateral aspect of the thigh.
The femoral is the largest nerve of the lumbar plexus. It passes through the fibers of the psoas muscle at its lower
lateral border and descends in the groove between the psoas and iliacus muscles. It then passes inferior to the
inguinal ligament within this groove. Just before, or right at the entrance into the femoral triangle, it divides into
several branches, supplying the muscles and skin of the anterior thigh, knee, and hip joints.
The lumbosacral plexus innervates the dorsal aspect of the lower extremity. It is formed by the ventral rami of the
fourth and fifth lumbar vertebrae, and the first, second, and third sacral nerves ( Fig. 20–41 ). Sometimes, a part of
the fourth sacral nerve contributes to the sacral plexus. The only nerve of this plexus of major interest to the clinical
anesthesiologist is the sciatic nerve. This nerve is formed by the combination of two major nerve trunks. First is the
tibial nerve formed by the anterior branches of the ventral rami of the fourth and fifth lumbar and the first, second,
and third sacral nerves. The second major nerve trunk of the sciatic nerve is the common peroneal nerve, which is
composed of the dorsal branches of the ventral rami of the same five nerves. These two nerve trunks leave the pelvis
443
through the greater sciatic foramen, after which the sciatic nerve enters the thigh by passing between the greater
trochanter and the ischial tuberosity. It descends from the upper thigh to the popliteal
Figure 20-41 Sacral plexus anatomy.
fossa, where it divides into its terminal branches, the tibial and common peroneal nerves.
INGUINAL PERIVASCULAR BLOCK
The inguinal perivascular (“3-in-1”) nerve block was originally described by Winnie in 1973. This technique
[75]
provides anesthesia for multiple lower extremity procedures. It has been shown to be particularly useful for femoral
shaft and neck fractures, knee procedures, and procedures involving the anterior thigh. Chronic pain uses include,
[76] [77]
among others, treatment of herpes zoster. At the level of the inguinal ligament, the femoral nerve has the iliacus
[78]
muscle fascia as its lateral border, the psoas major fascia as its medial border, and the transversalis fascia anteriorly.
The “3-in-1” technique purports to utilize the fascial wrapping as a conduit, thus allowing local anesthetic to ascend
to the level of the lumbar plexus, which is located between the quadratus lumborum and the psoas major muscles,
thus bathing the lateral femoral cutaneous, femoral, and obturator nerves—“3-in-1.” Unfortunately, the lateral
femoral cutaneous and obturator nerves are not consistently blocked by this technique.
Evidence has demonstrated that when obturator and lateral femoral cutaneous blocks do occur, it is often because of
lateral spread of local anesthetic along fascial planes rather than ascent to the roots of the lumbar plexus.
In the technique of inguinal perivascular block, the inguinal ligament is defined and marked from the anterosuperior
iliac spine to the symphysis pubis. The midpoint of this line is determined. Just caudal to the
444
Figure 20-42 Inguinal perivascular “3-in-1” block.
midpoint should lie the femoral arterial pulse. Once the femoral arterial pulse is determined, a mark is made 1 cm
below the inguinal ligament and 1 cm lateral to the pulse. This is the point of needle insertion ( Fig. 20–42 ). An
insulated needle is inserted through the skin and directed cephalad at approximately a 60-degree angle. Quadriceps
movements involving the patella (i.e., “patellar snap”) at an mA less than 0.5 confirms successful needle placement,
after which 30 mL of local anesthetic is incrementally injected. If only medial thigh movements are made on initial
insertion, the needle is directed slightly laterally, and if there are lateral movements, the needle is inserted slightly
medially. Isolated medial or lateral movements are caused by branches of the femoral nerve and injection does not
result in adequate anesthesia. If, in spite of movement lateral and medial, only peripheral branches are stimulated,
the needle has been inserted too far caudally and should be reinserted 1 cm more cephalad for a “patellar snap.” The
block is tested for anesthesia of the anterolateral thigh and weakness of the quadriceps muscle.
LATERAL FEMORAL CUTANEOUS BLOCK
The lateral femoral cutaneous nerve is a pure sensory nerve providing sensation to the lateral aspect of the thigh.
This nerve is often blocked as an adjunct to other nerve blocks to provide anesthesia for surgical procedures
involving the thigh (e.g., analgesia for tourniquet pain and superficial procedures involving the lateral thigh).
Chronic pain applications include diagnosis and treatment of meralgia paresthetica, a chronic pain syndrome
involving this nerve.
For this technique, the patient is placed supine and a point 2 cm medial and 2 cm inferior to the anterior superior
iliac spine is marked ( Fig. 20–43 A, B). A 3- to 5-cm, 22-G blunt-tip needle is inserted perpendicular to the skin and
advanced through the fascia lata (appreciated by a loss of resistance as the fascia is penetrated). After careful
aspiration, 10 to 15 mL of local anesthetic is incrementally injected above and below the fascia lata in a medial-to-
lateral fanlike direction.
BLOCKADE OF THE OBTURATOR NERVE
The obturator nerve has both motor and sensory components. The anterior division provides sensory innervation to
the medial aspect of the distal thigh. The posterior division provides sensation to the medial aspect of the distal thigh
as well as to the hip and knee joints. The obturator nerve also provides motor innervation to the thigh adductors.
Clinical applications of obturator block include use as an adjunct with lateral femoral cutaneous, femoral, and sciatic
nerve blocks for surgical procedures on the lower extremity. The obturator block is also used as a diagnostic adjunct
in the treatment of pain syndromes involving the hip, because the articular branch of this nerve is involved in pain
transmission from the hip. Obturator block is also used to relieve adductor spasms of the hip.
Technique
The patient is placed supine with the affected thigh in slight abduction. The tip of the pubic tubercle is palpated. A
point 1.5 cm caudal and 1.5 cm lateral to the tubercle is marked ( Fig. 20–44 ). A 22-G, 7- to 8-cm needle is inserted
perpendicular to the skin until the horizontal ramus of the pubis is identified. This usually occurs at a depth of 1.5 to
445
4 cm. The depth is noted and the needle is withdrawn and redirected laterally to a point 2 to 3 cm deeper than the
pubic ramus. The needle should now be in close proximity to the obturator canal. After careful aspiration, 10 to 15
mL of local anesthetic is injected in a fanlike fashion to ensure adequate distribution of local anesthetic in the area of
the obturator nerve.
PSOAS LUMBAR PLEXUS BLOCK
The lumbar plexus was previously described as being between the quadratus lumborum and psoas major muscles.
Current information, however, suggests that the lumbar plexus lies within the substance of the psoas major itself. [79]
This has been confirmed by a combined cadaver and computed tomography study. Cadaveric dissections have [80]
determined that the femoral nerve lies between the lateral femoral cutaneous and obturator nerves. Although the
lateral femoral cutaneous nerve is in the same fascial plane as the femoral nerve, the obturator nerve can be found in
the same plane as the other two nerves or in its own muscular fold. Computed tomographic data revealed the
following measurements: The femoral nerve is at a depth of
Figure 20-43 A, Lateral femoral cutaneous nerve, anterior view. The patient is in the supine position, showing needle direction for the lateral femoral cutaneous nerve
block. Needle entry is at a point 1 inch below and medial to the anterosuperior iliac spine. The needle penetrates up to the iliac bone. The solution is infiltrated from
that point to the skin. B, Lateral femur cutaneous nerve block, lateral view, showing needle direction for the lateral femoral cutaneous nerve block. Patient is in the
supine position. Needle entry is at a point 1 inch below and medial to the anterior superior iliac spine. The needle penetrates up to the iliac bone, and solution is
infiltrated from that point to the skin. (From Raj PP: Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, p 324.)
Figure 20-45 Psoas compartment block.
446
Figure 20-44 Anatomy of the obturator nerve. The nerve emerges from the obturator foramen along with the obturator arteries. It can be blocked
at the foramen, as is shown in this figure.
9.01 ± 2.43 cm; the psoas major medial border is at 2.73 ± 0.64 cm from the medial sagittal plane; and the lateral
border is at 6.41 ± 1.61 cm from the same plane.
The psoas lumbar plexus block in combination with a proximal sciatic nerve block can be used for virtually any
procedure in the lower extremity. For the psoas block, the patient is placed in the lateral position with the operative
site upright. The upper thigh is maximally flexed at the hip and the knee flexed (Sims position). A line is drawn
between the iliac crests (intercristal line). A line through the lumbar spines is drawn. The posterosuperior iliac spine
is identified and marked. A line parallel to the lumbar spines through the posterosuperior iliac spine is drawn. The
point at which the intercristal line intersects the line through the posterosuperior iliac spine is the point of needle
insertion ( Fig. 20–45 ). After skin preparation and local anesthetic infiltration a 21-G, 4 to 6-inch insulated needle is
inserted at the skin wheal perpendicular to all planes, looking for a quadriceps muscle contraction. The needle is
inserted 4 to 9 cm, depending on body habitus. If a contraction is not found at the initial insertion, from the same
skin point the needle is inserted to the same depth toward an imaginary point in 1-cm increments more medially.
After contraction of the quadriceps is elicited at an mA of less than 0.5, 30 mL of local anesthetic is incrementally
injected. Weakness of the quadriceps and anesthesia of the anterolateral thigh confirms successful block placement.
Complications
With older methods of psoas block (e.g., psoas sheath block), the needle is inserted closer to the central neuraxis,
with a resultant incidence of epidural spread of 20%.
FASCIA ILIACA LUMBAR PLEXUS BLOCK
The fascia iliaca block was first described by Dalens and colleagues, who hypothesized that sufficient amounts of a
[81]
solution injected just posterior to the fascia iliaca could spread at the inner surface of this fascia and contact the
femoral, lateral cutaneous, genitofemoral, and obturator nerves that run, for part of their course, just behind the
fascia. It is important to remember that the fascia iliaca represents a potential space, the so-called “fascia iliaca
compartment.” Inferior to the inguinal ligament, this space is continuous with the lacuna musculorum, covered by
447
the fascia iliaca, the fascia lata, and the skin covering the femoral triangle. Injecting the desired amount of a solution
into the lacuna musculorum and favoring its upward migration toward the iliacus muscle should result in spread of
the solution within the entire fascia iliaca compartment, hence allowing the local anesthetic solution access to all of
the structures contained within the potential space.
The indications for the fascia iliaca compartment block of the lumbar plexus parallel those of the femoral 3-in-1
block.
Technique
The patient is placed in the dorsal recumbent position. The course of the inguinal ligament from the pubic tubercle
to the anterior superior iliac spine is drawn and divided into three equal parts. At the junction of the middle and
lateral thirds, a point is marked 1 cm below the inguinal ligament. A blunt needle is inserted through this mark
perpendicular to the skin. An initial loss of resistance (pop) is appreciated as the needle tip penetrates the fascia lata.
A second loss of resistance is appreciated as the needle penetrates the fascia iliaca ( Fig. 20–46 ). Thirty mL of local
anesthetic is then incrementally injected while caudal pressure is maintained
Figure 20-46 Fascia iliaca block.
to facilitate cephalad spread to the fascia iliaca compartment. After the needle is withdrawn, any swelling in the
groin is massaged in a cephalad direction to again facilitate spread.
SCIATIC NERVE BLOCK
Sciatic nerve block is used for procedures involving the posterior thigh as well as all procedures involving the leg
(complemented by a saphenous block when necessary).
POSTERIOR (LABAT) SCIATIC BLOCK
This approach was first described by Labat in 1930. The patient is placed in the lateral (Sim’s) position, operative
[82]
site up, thigh maximally flexed, and knee flexed. The greater trochanter of the femur is identified and marked. The
posterior superior iliac spine is identified and marked. A line connecting these two bony landmarks is made. The
448
midpoint of the line is marked and a perpendicular line from the midpoint drawn caudally. A line is drawn from the
sacral hiatus to the trochanter. Where the line from the midpoint of the greater trochanter and the posterior superior
iliac spine intersects the line from the hiatus to the trochanter is the point of needle insertion ( Fig 20–47 ). A 21-G,
4- to 6-inch, insulated needle is inserted perpendicular to the skin, searching for movements in the leg and foot. If
initial insertion is not successful, the needle is inserted either cranially or caudally along the line from the trochanter
and posterior spine. After successful leg or foot stimulation with an mA less than 0.5, 20 to 25 mL of local
anesthetic is incrementally injected.
If intense contractions of the hamstrings occur, the needle has been placed too far medially and should be
reintroduced at a point 1 cm more lateral.
Figure 20-47 Classic (Labat) sciatic block.
PARASACRAL SCIATIC NERVE BLOCK
The parasacral approach was first described by Mansour in 1993. With this approach, the sciatic nerve is blocked
[83]
as it exits the greater sciatic foramen.
Technique
The patient is positioned as for the posterior approach, with the extremity to be blocked uppermost and with a
greater inclination of the trunk to a semiprone position. The dependent limb should be straightened at the knee and
hip and the limb to be blocked should be flexed at both the knee and hip. A line is drawn between the posterior
superior iliac spine and the lowest point of the ischial tuberosity. A mark at a point three finger breadths inferior to
the posterosuperior iliac spine is made on this line, which represents the surface marking of the posteroinferior iliac
spine. A 21-G, 4- to 6-inch insulated needle is inserted at this mark perpendicular to all planes. If bone is contacted,
the needle is reintroduced along the line more caudally until it misses bone. It should then be inserted 2 cm deeper,
searching for dorsal or plantar flexion of the foot ( Fig. 20–48 ). After successful stimulation at an mA less than 0.5,
20 to 30 mL of local anesthetic is incrementally injected.
SUPINE SCIATIC (RAJ) BLOCK
This technique was first described by Raj in 1975. The approach is attractive because the sciatic nerve is more
[84]
superficial with this approach than with any of the other gluteal approaches; thus, it is particularly useful in
morbidly obese patients or patients with abnormal posterior anatomy. It is also useful as a “rescue” block when
more proximal approaches have failed.
449
Figure 20-48 Parasacral sciatic nerve block.
Figure 20-49 A, Supine (Raj) sciatic block. B, Cross-sections at the gluteal region show the depth of the sciatic nerve from the supine sciatic
approach. (From Raj PP: Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, p 311.)
Technique
The patient is placed supine and the operative extremity maximally flexed at the hip and flexed 90 degrees at the
knee. This maneuver decreases redundant tissue in the buttock and thins the gluteus maximus muscles, making the
sciatic nerve more superficial. The greater trochanter and ischial tuberosity are identified and marked. The midpoint
of a line joining the trochanter and tuberosity is determined at the level of the gluteal crease. A 21-G, 4- to 6-inch
insulated needle is inserted perpendicular to the skin and directed cephalad, searching for contractions of the
peroneal (toes up) or tibial (toes down) nerves ( Fig. 20–49 A, B). If, after insertion of the needle, no stimulation is
determined, the needle is inserted at the same skin point and directed 1 cm laterally or medially until appropriate
contractions occur. Upon successful sciatic nerve stimulation at an mA of less than 0.5, 20 to 25 mL of local
anesthetic is incrementally injected.
450
ANTERIOR SCIATIC BLOCK
The anterior sciatic block first described by Beck in 1962 offers advantages. It requires no change in the patient’s
[85]
position to accomplish this or accompanying blocks (e.g., femoral), and it offers no hazard to an injured patient
incident to being turned into a lateral or prone position. The time required for a combination of blocks is lessened,
because only one area of the skin needs to be prepared.
Technique
With the patient in the supine position, the inguinal ligament is identified between the anterosuperior iliac spine and
the symphysis pubis and a line drawn along its distribution. This line is then divided into three equal segments. The
junction of the middle and medial segments is identified and a line perpendicular to this junction is extended down
the thigh. The greater trochanter is identified and a line extended from it medially across the anterior surface of the
thigh parallel to the line through the inguinal ligament. Where the perpendicular line from the inguinal ligament
intersects the trochanteric line is the point of needle insertion ( Fig. 20–50 ). After skin preparation and local
anesthetic infiltration, a 21-G, 4- to 6-in insulated needle is inserted at the surface landmark in a slightly lateral
direction until the anterior medial surface of the femur is contacted. The needle depth at this point is noted. The
needle is then withdrawn to the skin and redirected in a more perpendicular direction to bypass the femur
approximately 5 cm beyond the depth at which the femur was first encountered. Dorsal or plantar flexion of the foot
at an mA of less than 0.5 confirms successful stimulation, after which 20 to 30 mL of local anesthetic is then
incrementally injected.
The disadvantage of this approach is that it is a technically more difficult block to perform.
Figure 20-50 Sciatic nerve block: Anterior approach.
Once the femur is contacted, lateral rotation of the hip may bring the neurovascular bundle more in line with the
stimulating needle, and this maneuver should be entertained if there is difficulty in locating the nerve.
LATERAL SCIATIC BLOCK
The lateral sciatic block was first described by Ichiyanaghi in 1959 as another supine approach to sciatic block. An
[86]
alternate approach as described by Guardini and associates was introduced in 1985.

[87]
Technique
The patient is placed in the supine position with the hip in neutral position. A point 3 cm distal to the point of
maximal lateral prominence of the trochanter is identified along the posterior profile of the femur. After skin
preparation and local anesthetic infiltration, a 21-G, 4- to 6-inch insulated needle is inserted though a wheal
perpendicular to the skin until bone is encountered. The needle is reintroduced to the skin and angulated
approximately 20 degrees posteriorly to slide under the surface of the femur approximately 5 cm deeper than the
depth at which the femur was originally contacted. The nondominant hand may be positioned under the patient to
palpate the ischial tuberosity. This gives the operator a medial reference point for performance of the block. After
451
successful plantar or dorsiflexion of the foot at an mA less than 0.5, 20 to 30 mL of local anesthetic is incrementally
injected.
POPLITEAL FOSSA BLOCK
The popliteal fossa block was first described by Labat in 1923 and subsequently by others. This block is
[88] [89] [90] [91]
used primarily for procedures on the foot and ankle. The nerves blocked in the popliteal fossa, namely, the tibial and
peroneal nerves, are extensions of the sciatic nerve. Classical performance of this block requires the patient to be
placed in the prone position, although it may also be approached from the supine position. The cephalad borders of
[92]
the popliteal fossa are the semimembranosus and semitendinosus muscles medially and the biceps femoris muscle
laterally. Caudal borders are defined by the gastrocnemius muscles both medially and laterally. The larger of the two
nerves in the popliteal fossa is the tibial nerve, which separates from the common peroneal nerve at the upper limit
of the popliteal fossa; however; it may separate much more proximally. The tibial nerve maintains a linear course
and runs lengthwise through the popliteal fossa. Inferiorly, it passes between the heads of the gastrocnemius
Figure 20-51 Sciatic nerve block: Popliteal approach.
muscles. The common peroneal nerve follows the biceps femoris tendon along the cephalad lateral margin of the
popliteal fossa. After exiting the popliteal fossa, it travels around the head of the fibula and divides into the
superficial peroneal and deep peroneal nerves.
Technique
The patient is placed prone and asked to flex the knee. A line is made at the flexion crease. Approximately 8 to 10
cm proximal to the flexion crease, the groove between the semitendinosus and biceps femoris muscles is marked. A
22-G, 50-mm insulated needle is inserted perpendicular to the skin in a slight cephalad direction, looking for
movement of the toes ( Fig. 20–51 ). If initial insertion is unsuccessful, the needle is returned to the skin and
reinserted from the same entry site to an imaginary point 1 cm lateral. After successful stimulation at an mA less
than 0.5, 30 mL of local anesthetic is incrementally injected.
Disadvantages of this block include possible blockade of only one branch because of proximal separation of the
tibial and common peroneal nerves. Because the popliteal fossa is filled with fat, dispersion of local anesthetic is
452
frequent, and larger volumes of local anesthetic are required for successful block. Clinical onset is also longer than
that of more proximal sciatic blocks. To obviate these problems, some clinicians block both branches of the sciatic
nerve.
LATERAL POPLITEAL SCIATIC BLOCK
Using anatomic studies performed by Vloka and colleagues and Zetlaovi and associates, the patient is asked to
[93] [94]
slightly flex the knee, which enhances palpation
Figure 20-52 Sciatic nerve block: Lateral popliteal approach.
of the groove between the vastus lateralis and biceps femoris muscles. After the groove is identified, the leg is
straightened. Where the lateral line from the patella intersects the groove is the point of needle insertion. A 50-mm
insulated needle is inserted at the marking perpendicular to skin until it contacts the femur. This distance is noted. It
is then returned to skin and redirected at a 20- to 30-degree angle posteriorly, to bypass the femur, searching for both
the common peroneal (more internal, toes up) and tibial, toes down nerves ( Fig. 20–52 ). After successful
stimulation at an mA less than 0.5, each nerve is incrementally injected with 15 mL of local anesthetic.
SAPHENOUS NERVE BLOCK AT THE KNEE

Anatomy
The saphenous nerve descends through the femoral canal to accompany the femoral artery into the adductor canal. It
then becomes superficial by passing between the sartorius and gracilis muscles and passes anteroinferiorly to supply
the skin and fascia of the anteromedial aspects of the knee, leg, and foot.
The saphenous nerve is the only branch of the lumbar plexus (femoral nerve) below the knee. Thus, a saphenous
nerve block at the knee combined with a sciatic block can be used for leg and foot procedures.
Technique
The medial femoral condyle is grasped between two fingers at its anterior and posterior aspects. From the midpoint
between the fingers, 8 to 10 mL is injected in a fanlike direction 3 cm posteriorly ( Fig. 20–53 ).
TRANS-SARTORIAL SAPHENOUS NERVE BLOCK
The trans-sartorial block, described by Van der Wal and coworkers uses the consistent location of the saphenous
[95]
nerve lateral to the sartorius muscle above the knee.
Technique
453
With the patient supine, the superior aspect of the patella is palpated and a line drawn posteriorly from it. The
patient is asked to raise the extended leg from the bed, and the sartorius muscle is identified and marked as it lies
between the biceps femoris and vastus medialis muscles. Two centimeters superior to where the line through the
patella intersects the line along the sartorius is the point of needle insertion ( Fig. 2–54 ). A blunt needle is inserted
through the skin marking and directed at a 45-degree angle posteriorly with a slight caudal direction. Two losses of
resistance are appreciated, first at the medial and then at the lateral fascia of the sartorius muscle, after which 10 mL
of local anesthetic is incrementally injected.
ANKLE BLOCK
The ankle block is useful for surgical procedures of the foot. However, for procedures requiring high tourniquet
pressures, more proximal techniques should be considered. There are five nerves that innervate the foot. The number
of nerves blocked for any particular procedure depends on the site of the surgery and whether or not a tourniquet
will be used. Four of the nerves are branches of the sciatic nerve; the fifth, the saphenous nerve, is the terminal
branch of the femoral nerve ( Figs. 20–55 and 20–56 ).
Generally, infiltration techniques are used for ankle blocks; however, the posterior tibial nerve can be blocked by a
nerve stimulator technique. All blocks are performed at the upper levels of the malleoli.
SAPHENOUS NERVE BLOCK
The saphenous nerve runs in the superficial fascia in front of the medial malleolus accompanying the saphenous
vein and innervates the medial side of the foot.
Technique
For saphenous nerve block, 3 to 5 mL of local anesthetic is injected subcutaneously on either side of the saphenous
vein at the superior aspect of the medial malleolus.
TIBIAL NERVE BLOCK
The tibial nerve lies under the flexor retinaculum at the midpoint between the medial malleolus and calcaneus.
454
Figure 20-53 Saphenous nerve block at the knee. The needle is placed at the level of the patella on the medial condyle of the femur between the tendons of the
sartorius muscle and the gracilis muscle.(From Raj PP: Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, p 321.)
455
Figure 20-54 Trans-sartorial saphenous nerve block.
It lies posterior to the posterior tibial artery and innervates the skin and muscles of the plantar aspect of the foot.
A point is marked midway between the medial malleolus and calcaneus. If the posterior tibial artery is palpated, the
needle is inserted just posterior to the pulse, following which 3–5 mL of local anesthetic is injected. Conversely, a
25-mm stimulating needle can be inserted at the skin mark and directed posterior to the tibial arterial pulse, looking
for plantarflexion of the toes.
SURAL NERVE BLOCK
For sural nerve block, 3 to 5 mL of local anesthetic is injected at a point deep between the lateral malleolus and
calcaneus.
DEEP PERONEAL NERVE BLOCK
A needle is inserted perpendicular to skin just lateral to the extensor hallucis longus tendon to contact the
456
Figure 20-55 The course of the saphenous, sural, superficial, and deep peroneal nerves at the ankle.(From Raj PP: Clinical Practice of Regional Anesthesia. New
York, Churchill Livingstone, 1991, p 316.)
tibia. It is then withdrawn a few millimeters and 3 mL of local anesthetic is injected.
SUPERFICIAL PERONEAL NERVE BLOCK
Subcutaneous infiltration of 5 to 7 mL of local anesthetic from the lateral to the medial malleolus is performed.
DIGITAL BLOCKS OF THE TOES
Digital blocks of the toes follow the same general principles as digital blocks of the fingers. (For anatomy and
technique, see the section on upper extremity digital blocks.)
PUDENDAL NERVE BLOCK

Indications
A pudendal nerve block is indicated for perineal surgery, such as obstetric vaginal procedures (vaginal delivery,
forceps delivery) and for hemorrhoidectomy.
457
Figure 20-56 Transverse section through the ankle showing the needle placement for blocking the superficial and deep peroneal, saphenous, sural,
and posterior tibial nerves.(From Raj PP: Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, p 317.)
458
Figure 20-57 Passage of pudendal nerve with its relationship to the sacrospinous and sacrotuberous ligaments. The terminal branches of the
pudendal nerve arise in Alcock’s canal.
Figure 20-58 A, Point of entry and direction of needle for the transperineal approach to pudendal nerve. Transvaginal palpation of the spinous
process is shown. B, Position of the hand during insertion of a Kobak-type needle for block of the left pudendal nerve.
459
Figure 20-59 Pudendal nerve block, perineal approach. Deep structures of the perineum with the course and distribution of the
pudendal nerve. The needle is placed 1 inch medial to the ischial tuberosity on the side of the anus.
Anatomy
The pudendal nerve (S2–S4) arises from the sacral plexus ( Fig. 20–57 ). After crossing the ischial spine and the
sacrospinous ligament, the pudendal nerve enters the lesser sciatic foramen. It then runs on the medial side of the
ischium with the vessels in the pudendal canal (Alcock canal), branching to the perineal region. The first branch is
the inferior hemorrhoidal nerve, which innervates the anal region. At the anterior part, the branches innervate the
urogenital region.
Equipment
Requirements are a 12- to 14-G needle and an Iowa trumpet.
Technique
The patient lies in the lithotomy position. The landmarks are the ischial spine, sacrospinous ligament, and ischial
tuberosity.
For the transvaginal route, the sacrospinous ligament is pierced. The needle is guided within the Iowa trumpet along
the index and middle fingers, which leads transvaginally toward the ischial spine. The local anesthetic (10 mL) is
injected at this site ( Fig. 20–58 A, B).
For the perineal route a skin wheal is made 2 to 3 cm posteromedial to the ischial tuberosity ( Fig. 20–59 ). A 20 G,
12- to 15-cm needle attached to a 10-mL syringe is introduced through the skin wheal in a posterior and lateral
460
direction, guided by a finger in the rectum or vagina toward the ischial spine. After the sacrospinous ligament is
pierced, 10 to 15 mL of local anesthetic is injected around the ligament.
Contraindications
The technique is contraindicated in the presence of infection or by previous perineal surgery.
REFERENCES
1. Stoelting RK, Dierdorf SF: Anesthesia and Co-Existing Disease, 3rd ed. New York, Churchill Livingstone, 1993.
2. Knapp H: On cocaine and its use in ophthalmic and general surgery. Arch Ophthalmol 13:402–448, 1884.
3. Feibel RM: Current concepts in retrobulbar anesthesia. Surv Ophthalmol 30:102–110, 1985.
4. Atkinson WS: The development of ophthalmic anesthesia. Am J Ophthalmol 51:1–14, 1961.
5. Unsold R, Stanley JA, DeGroot J: The CT-topography of retrobulbar anesthesia. Graefes Arch Clin Exp Ophthalmol 217:125–136, 1981.
6. Kastev DA, Drews RC, Rose BT: An anatomic study of retrobulbar needle path length. Ophthalmology 96:1221–1224, 1989.
7. Wong DHW: Regional anesthesia for intraocular surgery. Can J Anesth 40:635–657, 1993.
8. Davis DB. Mandel MR: Posterior peribulbar anesthesia: An alternative to retrobulbar anesthesia. J Cataract Refract Surg 12:182–184, 1986.
9. Hamilton RC: Techniques of orbital regional anesthesia [see comments]. Br J Anesth 75:88–92, 1995.
10. Ripart J, Lefrant J, Lalourcey L, et al: Single injection periocular anesthesia. Anesth Analg 83:1234–1238, 1996.
11. Loeser JD: What to do about tic douloureux. JAMA 239:1153–1155, 1978.
12. WongJD, Sved AM: Maxillary nerve block anesthesia via the greater palatine canal: A modified technique and case reports [see comments].
Aust Dent J 36:15–21, 1991.
13. Kronman JH, Kabani S: The neuronal basis for diplopia following local anesthetic injections. Oral Surg, Oral Med, Oral Pathol 58:533–534,
1984.
14. Raj
P, Nolte H, Stanton-Hicks M: Illustrated Manual of Regional Anesthesia. Head and Neck Blocks, vol 6. New York, Springer-Verlag, 1988,
pp 67–76.
15. Gow-GatesGA: Mandibular conduction anesthesia: A new technique using extraoral landmarks. Oral Surg, Oral Med, Oral Pathol 1973;
36:321–328, 1973.
16. Kafalias
MC, Gow-Gates GA, Saliba GJ: The Gow-Gates technique for mandibular block anesthesia. A discussion and a mathematical
analysis. Anesth Prog 34:142–149, 1987.
17. Fish
LR, McIntire DN, Johnson L: Temporary paralysis of cranial nerves III, IV and VI after a Gow-Gates injection [published erratum]. J Am
Dent Assoc 119:127–128, 1989.
18. Stannard CF, Glynn CJ, Smith SP: Dural puncture during attempted stellate ganglion block. Anesthesia 45:9522–9524, 1990.
19. Anthony M: Headache and the greater occipital nerve. Neurol Neurosurg 94:297–301, 1992.
20. Conn RA, Cofield RH, Byer DE, et al: Interscalene block anesthesia for shoulder surgery. Clin Orthop 216:94–98, 1987.
21. De Beer JF, v RK: Arthroscopic capsulotomy and continuous interscalene block for managing frozen shoulder. J Bone Joint Surg 79B, 46,
1997.
22. Heffington CA, Thompson RC: The use of interscalene block anesthesia for manipulative reduction of fractures and dislocations of the upper
extremities. J Bone Joint Surg 55A:83–86, 1973.
23. Winnie AP, Collins VJ: The subclavian perivascular approach of brachial plexus anesthesia. Anesthesiology 25:353–363, 1964.
24. Raj PP: Infraclavicular brachial plexus block—a new approach. Anesth Analg 52:897–904, 1973.
25. Pearce H, Lindsay D, Leslie K: Axillary brachial plexus block in two hundred consecutive patients. Anaesth Intensive Care 24:453–458, 1996.
26. Barthram CN: Nerve stimulators for nerve location—are they all the same? A study of stimulator performance. Anaesthesia 52:761–764, 1997.
461
27. Sleander D, Dhuner KG, Lundborg G: Peripheral nerve injury due to injection needles used for regional anesthesia. An experimental study of
the acute effects of needle point trauma. Acta Anaesthesiol Scand 21:182–188, 1977.
28. Bromage PR, Benumof JL: Paraplegia following intracord injection during attempted epidural anesthesia under general anesthesia. Reg Anesth
Pain Med 23:104–107, 1998.
29. Winnie AP: Determination of volume of local anesthetic. In Plexus Anesthesia. Philadelphia, WB Saunders, 1983, p 208.
30. SaiyedMU, Silverstein, WB, Brown AR: Interscalene block with a peripheral nerve stimulator: A deltoid twitch is as successful an indicator of
correct needle placement as a biceps twitch. Reg Anesth Pain Med. 23:(Suppl):31, 1998.
31. UrmeyWF, et al: Digital pressure during interscalene block is clinically ineffective in preventing anesthetic spread to the cervical plexus.
Anesth Analg 83:366–370, 1996.
32. Urmey WF, Talts KH, Sharrock NE: One hundred percent incidence of hemidiaphragmatic paresis associated with interscalene brachial plexus
anesthesia as diagnosed by ultrasonography. Anesth Analg 72:498–503, 1991.
33. UrmeyWF, McDonald M: Hemidiaphragmatic paresis during interscalene brachial plexus block: Effects on pulmonary function and chest wall
mechanics [see comments]. Anesth Analg 74:352–357, 1992.
34. Seltzer JL: Hoarseness and Horner’s syndrome after interscalene brachial plexus block. Anesth Analg 56:585–586, 1977.
35. D’Alessio JG, Weller RS, Rosenblum M: Activation of the Bezold-Jarisch reflex in the sitting position for shoulder arthroscopy using
interscalene block [see comments]. Anesth Analg 80:1158–1162, 1995.
36. Dutton RP, Eckhardt WF III, Sunder N: Total spinal anesthesia after interscalene blockade of the brachial plexus. Anesthesiology 80:939–941,
1994.
38. Franco CD, Vieira ZEG: 1,001 subclavian perivascular brachial plexus blocks: Success with a nerve stimulator. Reg Anesth Pain Med, 25:41–
46, 2000.
39. Brown DL: Brachial plexus anesthesia: An analysis of options. Yale J Biol Med 66:415–431, 1993.
40. Brown
DL, Cahill DR, Bridenbaugh LD: Supraclavicular nerve block: Anatomic analysis of a method to prevent pneumothorax. Anesth Analg
76:530–534, 1993.
41. Pham DC, Gunst JP, Poirier P, et al: A novel supraclavicular approach to brachial plexus block. Anesth Analg 85:111–116, 1997.
42. Wilson
JL, Brown DL, Wong GY, et al: Infraclavicular brachial plexus block: Parasagittal anatomy important to the coracoid technique.
Anesth Anal 87:870–873, 1998.
43. Winnie AP: Axillary perivascular block. In Plexus Anesthesia. Philadelphia, WB Saunders, 1983; pp 58, 121.
44. Groh GI, et al: Pseudoaneurysm of the axillary artery with median-nerve deficit after axillary block anesthesia. A case report. J Bone Joint
Surg 72:421, 1990.
45. Zipkin M, et al: False aneurysm of the axillary artery following brachial plexus block. J Clin Anesth 3:143–145, 1991.
46. Stan
TC, et al: The incidence of neurovascular complications following axillary brachial plexus block using a transarterial approach. A
prospective study of 1000 consecutive patients [see comments]. Reg Anesth 20:486–492, 1995.
47. Bouaziz
H, Narchi P, Mercier FJ, et al: Comparison between conventional axillary block and a new approach to the midhumeral level. Anesth
Anal 84:1058–1062, 1997.
48. Brown EM, McGriff JT, Mainowski RW: Intravenous regional anesthesia (Bier block): Review of 20 years experience. Can J Anesth 36:307,
1989.
49. Davies JAH, Gill SS, Weber JCP: Intravenous regional analgesia. Anesthesia 39:416, 1984.
50. Roven AN: The Bier block for hand surgery. Plast Reconstr Surg 89:769, 1992.
51. Davies, JAH Walford AJ: Intravenous regional anesthesia for foot surgery. Acta Anaesthesiol Scand 30:145, 1986.
52. Heath ML: Deaths after intravenous regional anesthesia. Br Med J, 285:931, 1982.
53. Chan CS, Pun, WK, Chan YM: Intravenous regional analgesia with a forearm tourniquet. Can J Anaesth 34:21, 1987.
54. Lillie PE, Glynn CJ, Fenwick DG: Site of action of intravenous regional analgesia. Anesthesiology 61:507, 1984.
462
55. Steinberg RB, Reuben SS, Gardner G: The dose-response relationship of ketorolac as a component of intravenous regional anesthesia with
lidocaine. Anesth Analg 86:791–793, 1998.
56. Hartmannsgruber MWB, Silverman DG, Halaszynski TM, et al: Comparison of ropivacaine 0.2% and lidocaine 0.5% for intravenous regional
anesthesia in volunteers. Anesth Analg 89:727–731, 1999.
57. Reiestad F, Stromskag KE: Interpleural catheter in the management of postoperative pain. A preliminary report. Reg Anesth 11:89, 1986.
58. Seltzer JL, et al: Intrapleural bupivacaine—a kinetic and dynamic evaluation. Anesthesiology 67:798–987,
59. RoccoA, et al: Intrapleural administration of local anesthetics for pain relief in patients with multiple rib fractures. Preliminary report. Reg
Anesth 12:10, 1986.
60. Mandl F: Paravertebral Block. New York, Grune & Stratton, 1947.
61. Eason MJ, Wyatt R: Paravertebral thoracic block—a reappraisal. Anaesthesia 34:638, 1979.
62. Greengrass R, Steele S: Paravertebral blocks for breast surgery. Tech Reg Anesth 2:8–12, 1998.
63. Greengrass R, O’Brien FO, Lyerly K, et al: Paravertebral block for breast surgery. Can J Anaesth 43:858–861, 1996.
64. Greengrass R, Weltz C, Lyerly K: Ambulatory surgical management of breast cancer using paravertebral block. Ann Surg 222:1, 19–26, 1995.
65. Coveney E, Weltx CR, Greengrass R, et al: Use of paravertebral block anesthesia in the surgical management of breast cancer: Experience in
156 class. Ann Surg 227:496–501, 1998.
66. Richardson J, Lonnqvist PA: Thoracic paravertebral block. Br J Anaesth 81:230–238, 1998.
67. Richardson J, Sabanathan S, Jones J: A prospective randomized comparison of preoperative and continuous balanced epidural or paravertebral
bupivacaine on post-thoracotomy pain, pulmonary function and stress responses. Br J Anaesth 83:387–392, 1999.
68. Hall H, Leach A: Paravertebral block in the management of liver capsule pain after blunt trauma. Br J Anaesth 83:819–821, 1999.
69. KleinAM, Greengrass RA, Weltz C, Warner DS: Paravertebral somatic nerve block for outpatient inguinal herniorrhaphy: An expanded case
report of 22 patients. Reg Anesth 23:306–310, 1998.
70. MedhatR, Wassef MB, Randazzo T, Ward W: The paravertebral nerve root block for inguinal herniorrhaphy—a comparison with the field
block approach. Reg Anesth 23:451–456, 1998.
71. GanapathyS, Murkin J, Boyd D et al: Continuous percutaneous paravertebral block for minimally invasive cardiac surgery. J Cardiothorac
Vasc Anesth 13:594–596, 1999.
72. Suelto M, Shaw B: Labor analgesia with paravertebral lumbar sympathetic block. Reg Anesth Pain Med 24:179–181, 1999.
73. Leighton
B, Halpern S, Wilson D: Lumbar sympathetic blocks speed early and second stage induced labor in nulliparous women. Anesthesia
90:1039–1046, 1999.
74. Lönnquist PA, Mackenzie J, Soni AK, Conacher ID: Paravertebral blockade: Failure rate and complications. Anesthesia 50:813–815, 1995.
75. Winnie
AP, Ramamurthy, S, Durrani Z: The inguinal paravascular technique of lumbar plexus anesthesia: The “3-in-1 block.” Anesth Analg
52:989–996, 1973.
76. Tarkkila
P, Tuominen M, Huhtala J, Lindgren L: Comparison of intrathecal morphine and continuous femoral 3-in-1 block for pain after major
knee surgery under spinal anesthesia. Eur J Anesthesiol. 15:6–9, 1998.
77. SingelynFJ, Deyaert M, Jrois D, et al: Effects of intravenous patient controlled analgesia with morphine, continuous epidural analgesia and
continuous three-in-one block on postoperative pain and knee rehabilitation after unilateral total knee arthroplasty. Anesth Analg 87:88–92, 1998.
78. Hadzic A, Vloka JD, Saff GN, et al: The three-in-one block for treatment of pain in a patient with acute herpes zoster infection. Reg Anesth
22:480–485, 1997.
79. Farny J, Drolet P, Girard M: Anatomy of the posterior approach to the lumbar plexus block. Can J Anesth 41:480–485, 1994.
80. DietemannJL, Sick H, Wolfram-Gabel R, et al: Anatomy and computed tomography of the normal lumbosacral plexus. Neuroradiology
29:58–68, 1987.
81. Dalens
B, Vanneuville G, Tanguy A: Comparison of the fascia iliaca compartment block with the 3-in-1 block in children. Anesth Analg
69:705–713, 1989.
82. Labat G: Regional Anesthesia, Its Technique and Clinical Application, 2nd ed. Philadelphia, WB Saunders, 1930, p 330.
463
83. Mansour NY: Reevaluating the sciatic nerve block: Another landmark for consideration. Reg Anesth 18:322–323, 1993.
84. Raj PP, Parks RI, Watson TD, Jenkins MT: A new single position supine approach to sciatic femoral nerve block. Anesth Analg 54:489–493,
1975.
85. Beck GP: Anterior approach to sciatic nerve block. Anesthesiology 24:222–224, 1962.
86. Ichiyanaghi K: Sciatic nerve block: Lateral approach with patient supine. Anesthesiology 20:601–604, 1959.
87. Guardini R, Waldron A, Wallace WA: Sciatic nerve block: A new lateral approach. Acta Anaesthesiol Scand 29:515–519, 1985.
88. Rorie DK, Byer DE, Nelson DO, et al: Assessment of block of the sciatic nerve in the popliteal fossa. Anesth Analg 59:371–376, 1980.
89. Gouverneur JM: Sciatic nerve block in the popliteal fossa with atraumatic needles and nerve stimulation. Acta Anaesthesiol Belg 36:391–399,
1985.
90. Kempthorne PM, Brown TC: Nerve blocks around the knee in children. Anesth Intensive Care 12:14–17, 1984.
91. Benzon HT: Popliteal sciatic nerve block: Posterior approach. Tech Reg Anesth Pain Manag 3:23–27, 1999.
92. Vloka JD, Hadzic A, Koorn R, Thys D: Supine approach to the sciatic nerve in the popliteal fossa. Can J Anaesth 43:964–967, 1996.
93. Vloka
JD, Hadzic A, Kitain E, et al: Considerations for sciatic nerve block in the popliteal fossa through the lateral approach. Reg Anesth
21:414–418, 1996.
94. Zetlaoui PJ, Bouaziz H: Lateral approach to the sciatic nerve in the popliteal fossa. Anesth Analg 87:79–82, 1998.
95. Van der Wal M, Lang S, Yip RW: Transarterial approach for saphenous nerve block anaesthetic technique. Can J Anesth 40:542–546, 1993.
464
Section IV - Chapter 21 - Regional Anesthesia in Children
Chapter 21 - Regional Anesthesia in Children
Claude Ecoffey
The rekindling of interest in the use of regional anesthesia has been due, in part, to the fact that regional anesthesia
is a feasible and safe alternative to general anesthesia in the pediatric population, and to an increasing awareness of
the need for adequate postoperative analgesia. It is, therefore, not surprising that the use of regional anesthetic
techniques, particularly caudal and peripheral blocks, has gradually increased in pediatric anesthesia.
In addition, regional anesthesia with longer acting local anesthetics provides postoperative pain relief with
preservation of consciousness and normal ventilatory control. This is so despite the fact that general anesthesia is
necessary in most children for the regional block to be performed easily, safely, and effectively. Indeed, the
benefit/risk ratio is excellent, especially for femoral, iliofascial, ilioinguinal, axillary, and penile blocks. These
blocks can be performed by beginners. All of the regional blocks require comprehensive knowledge of anatomic
landmarks, and the training of interventionalists should be supervised by specialists in pediatric anesthesiology.
General Conditions
ADVANTAGES OF REGIONAL ANESTHESIA
Regional anesthesia, in combination with light general anesthesia, provides several advantages for the pediatric
patient, the most significant of which, as demonstrated by several authors, is intra- and postoperative pain relief.
[4] [5] [6] [7]
[1] [2] [3]
First, this means that the use of regional blocks suppresses undesirable reflexes such as laryngospasm. In addition,
when regional anesthesia is administered to obtain intraoperative analgesia, the regional block permits the use of
minimal amounts of inhalation agents. In patients who are breathing spontaneously, there is a decrease in
physiologic dead space and respiratory rate, with maintenance of a normal end-tidal CO2 , compared with patients
receiving general anesthesia alone. On the other hand, the use of intraoperative caudal anesthesia has not been
[8]
shown to decrease the incidence of postoperative nausea and vomiting.
Second, regional blocks with a long-acting agent induce prolonged postoperative pain relief. During the first
postoperative days, repeated injections of local anesthetics or narcotics through an epidural catheter provide
[4] [5] [7] [9]
prolonged postoperative analgesia. Other advantages include earlier ambulation, earlier hospital discharge,
decreased need for non-narcotic analgesics after discharge, and a more rapid return to the child’s usual bright and
alert state. Finally, neural blockade may modify the “stress response.” Children who receive neural blockade wake
up rapidly at the end of surgery and are calm in the postoperative period, without signs of discomfort. This pain-free
period provides ideal psychological conditions for the recovering child and the family. In the recovery room,
effective neural blockade lowers the risk of bleeding, dislodgment of the dressing, or both. In the same way, a limb
can be immobilized after delicate surgery such as nerve tendon repair.
Regional anesthesia is also useful when general anesthesia is technically difficult or is associated with an increased
morbidity and mortality such as the ex-premature infant with the risk of postanesthetic apnea, the child with
[10]
chronic respiratory disease, or the child with myopathy.

[7]
Regional anesthesia may offer an alternative to general
[11] [12]
anesthesia in children with a history of malignant hyperthermia.
DISADVANTAGES OF REGIONAL ANESTHESIA
Regional anesthesia requires extra time to perform the block and allow it to become effective. Therefore, the use of
an induction room can smooth work in the operating room. If general anesthesia is needed to perform the block, it is
helpful to have an assistant to support the airway and monitor the patient during performance of the block. Critics of
the combined technique suggest that one may be exposing the child to the risks and complications inherent in both
techniques. This fear, however, is more a theoretical consideration than a practical one. [13]
Pediatric anesthesiologists now view regional anesthesia as an adjunct to general anesthesia, in much the same way
that a neuromuscular blocking agent or intravenous narcotic supplements general anesthesia with a volatile agent.
465
CONTRAINDICATIONS
Absolute contraindications to regional anesthesia include (1) infection at the site of the block, (2) ongoing
degenerative axonal disease, and (3) a coagulopathy. In addition, a myelomeningocele is a relative contradiction to
spinal or epidural blocks.
CHOICE OF REGIONAL ANESTHESIA IN CHILDREN [14] [15] [16] [17]
Although blocks that are commonly used in adults are not always suitable for children, some regional blocks are
particularly useful for pediatric patients. These include the central blocks—caudal, lumbar, thoracic epidural, and
spinal blocks for thoracic, abdominal, urologic, and lower limb orthopedic surgery; and the peripheral blocks—
ilioinguinal and iliohypogastric blocks for herniorrhaphy, paraumbilical block for repair of umbilical hernia, dorsal
nerve block of the penis for circumcision, axillary and parascalene blocks and intravenous regional anesthesia for
upper limb surgery, sciatic nerve block, femoral nerve block for lower limb surgery, and, sometimes, intrapleural
analgesia for cholecystectomy and thoracic surgery. It should not be assumed that these techniques are the only ones
suitable for use in pediatric patients. Others may be used with appropriate modifications, provided that the
anesthesiologist has experience with the particular block and that it can be successfully and safety performed in
anesthetized subjects. However, the choice should be made with regard to the benefit/risk ratio ( Table 21–1 ) and [17]
to the fact that some blocks cause less morbidity, especially peripheral nerve blocks ( Table 21–2 ). [13]
Peripheral nerve blocks have the advantage of providing a more localized area of anesthesia, which may still be
perfectly adequate for some operations. There are virtually no side effects, no lower limb motor block, and usually a
lower dose is required than for caudal or epidural block. However, serious problems can occur. A child under
general anesthesia is unable to report paresthesia when a needle is advanced toward a nerve. Neural damage from
needle trauma is, therefore, a possible hazard when peripheral nerve blocks are attempted. The risk of needle trauma
can be lowered by the use of a nerve stimulator, and now, the use of a nerve stimulator is mandated in pediatric
practice. Indeed, eliciting paresthesia by means of an electrical nerve stimulator is necessary for localizing nerve
trunks. It is difficult to explain the concept of paresthesia to a child younger than 8 or 9 years of age, and it is also
difficult to enlist a good level of cooperation. The nerve stimulator should deliver electrical current in short pulses
for 50 to 100 ms, with consistent intensity adjusted from 1.5 mA to 0.7 mA (0.5 mA if the patient is awake), and
emitted at a frequency of 1 to 2 Hz. The needle is connected to the negative pole of the generator, whereas the skin
electrode is connected to the anode.
REGIONAL BLOCKADE WITHOUT OR WITH GENERAL ANESTHESIA
Without General Anesthesia
Most children do not like needles or injections. Small, frightened children are unlikely to keep still unless they are
well sedated. Thus, local anesthetic techniques alone are not usually used in children younger than 8 to 10 years of
age. After age 10 years, a cooperative child who has had the procedure explained may tolerate a block for such
procedures as laceration suturing, fracture reduction, or minor procedures on the extremity. Adequate sedation, the
presence of a reassuring parent, or both may facilitate the procedure.
When a child has a fractured femur, the insertion of a block to relieve the pain may be of less concern to the patient
than the painful fracture. A skilled, sympathetic assistant and continual reassurance of the child are necessary.
TABLE 21-1 -- BENEFITS AND RISKS OF EACH OF THE MAIN REGIONAL BLOCKS IN PEDIATRICS
Technique Practical Usefulness Benefit : Risk Ratio Catheter
CENTRAL BLOCKS
Spinal ++ +++ No
Caudal ++++ +++ Sometimes
Sacral +++ +++ Yes
Lumbar ++ +++ Yes
Thoracic + + Yes
Cervical 0 0 0
PERIPHERAL BLOCKS
Subclavicular ++ 0 to +++ * No
466
TABLE 21-1 -- BENEFITS AND RISKS OF EACH OF THE MAIN REGIONAL BLOCKS IN PEDIATRICS
Technique Practical Usefulness Benefit : Risk Ratio Catheter
Axillary ++++ ++++ Sometimes
Lumbar plexus + + No
Femoral/3-in-1 ++++ ++++ Sometimes
Sciatic +++ +++ No
Penile ++++ ++++ No
Intercostal ++ + No
Ilioinguinal +++ +++ No
†
Paravertebral ++ + to +++ Yes
Distal limbs + to ++ +++ No
IVRA + ± No
From Murat I: Anesthésie locorégionale chez l’enfant. Conférence d’experts. Ann Fr Anesth Reanim 16:985, 1997.
*Parascalene approach.
†Surgical approach.
When a child requires an emergency procedure such as a fracture reduction or suturing of a laceration, preoperative
sedation is usually helpful. If an appropriate choice is made, local anesthesia is usually well tolerated. For selected
procedures, the use of neuroleptanalgesia with midazolam and fentanyl can produce satisfactory conditions. New
methods of administering sedatives, opioids, and local anesthetics transdermally greatly facilitate the[18]
administration of peripheral local anesthetics in the conscious child.
If a nerve stimulator is to be used, the child must be well sedated. A nerve stimulator facilitates the use of neural
blockade in an anxious child, because motor responses can be obtained without causing discomfort if sedation is
adequate.
With General Anesthesia
In children, regional anesthesia is often combined with light general anesthesia, but there must be justifiable
TABLE 21-2 -- INCIDENCE OF CRITICAL EVENTS FOR EACH TECHNIQUE OF REGIONAL ANESTHESIA
Technique Blocks (No.) Events (No.) Incidence Per 1000
*
Peripheral blocks 9396 0 0
Central blocks 15013 23 * 1.5
Caudal 12111 12 1
Epidural 2396 10 4.2
Spinal 506 1 2
From Giaufré E, Dalens B, Gambert A: Epidemiology and morbidity of regional anesthesia in children: A one year prospective survey of the
French Language Society for Pediatric Anesthesiologists. Anesth Analg 83:904, 1996.
*Intrathecal puncture = 8; intravascular injection = 6.
advantages for the child. Such potential advantages are summarized earlier. In addition, general anesthesia decreases
central nervous system (CNS) toxicity caused by local anesthetics. A competent assistant is required to maintain the
airway and ventilation while the block is performed. The decision to intubate or to use a laryngeal mask airway
should be based on the usual criteria, such as a full stomach, upper abdominal surgery, or the need to maintain
adequate ventilation. If intubation is indicated it should be completed before the block is begun.
Blocks that do not require paresthesia are ideal for use with general anesthesia. In lieu of paresthesia, a nerve
stimulator can be used to locate the nerve. Induction of general anesthesia by mask with halogenated agents and
nitrous oxide 70% in oxygen can be supplemented with intravenous thiopental or intramuscular ketamine (2 mg/kg).
Basal anesthesia during the operation can be maintained with nitrous oxide, oxygen, and, if necessary, low
concentrations of an inhalation agent such as halothane or sevoflurane, or with ketamine, which can be given
intramuscularly or intravenously.
467
Techniques for Performing Central Regional Anesthesia
ANATOMIC AND PHYSIOLOGIC CONSIDERATIONS
First, there are some differences in the anatomy of spinal cord meninges between a neonate and an adult. The tip of
the spinal cord is at L3 at birth and L1 to L2 at 1 year. In the same way, the meninges are at S3 at birth and S4 to S5
at 1 year ( Fig. 21–1 ). In addition, infants and children who weigh less than 15 kg have a relatively high volume of
cerebrospinal fluid (CSF)—4 ml/kg of body weight—compared with adult values of 2 ml/kg body weight.
Figure 21-1 Age-related differences in the anatomy of the spinal cord and the dura mater in the newborn and the adult.
The contents of the epidural space in infants differ from those of adults. Instead of having mature, densely packed
fat lobules divided by fibrous strands, infants have spongy, gelatinous lobules with distinct spaces permitting the
wide longitudinal spread of injected solutions. Furthermore, the relative resistance to epidural blockade of the L5 to
S1 nerve roots observed in adults does not occur in pediatric patients because of the smaller diameter of their nerve
fibers. Myelination begins during the fetal period and continues to the age of 3 years. In an infant, the fiber diameter
is smaller, the myelin sheath thinner, and the internodal distance smaller, so a lower concentration of local anesthetic
is needed, leading to fewer toxic effects. The local distribution is excellent because of several factors: volume,
concentration, and presence and thickness of the aponeuroses and sheaths around the nerves.
Second, there are important differences between small children and adults in the physiologic effects of central
blocks. It is a constant finding that the incidence of clinically significant hypotension after spinal or epidural
anesthesia is less than in adult patients. However, despite the absence of prior intravenous volume loading and the
[19]
high level of sympathetic blockade, neither blood pressure nor cardiac index are modified by the block. [20]
GENERAL TECHNICAL CONSIDERATIONS
As with any anesthetic, appropriate equipment must be at hand (and checked) to treat a patient with any potential
complication. This means that an oxygen source and appropriately sized airway equipment (bag, mask,
laryngoscope, endotracheal tube, laryngeal mask airway, and oral airway) must be readied in advance. Drugs to
rapidly induce general anesthesia and paralysis (thiopental and succinylcholine) are required, as is a functioning
source of suction.
Before the administration of the regional anesthetic, an intravenous catheter with an appropriate infusion solution
should be in place. Hypotension that is secondary to sympathetic block is very common in adults but exceedingly
rare in children. Indeed, blood pressure, cardiac output, and carotid blood flow as measured by pulsed Doppler
scanning are well maintained during caudal anesthesia in 6-month-old infants. [20]
468
CAUDAL BLOCK
This is the most useful pediatric block, because it is widely applicable and technically simple. Indeed, caudal
anesthesia is very easy to administer to a child rather than an adult in whom the caudal block is often difficult and
occasionally impossible. The caudal block can provide analgesia for surgery up to and including the umbilicus. This
technique can be used successfully in neonatal rectal surgery. [21]
Performance of a Caudal Block
The anesthetic agent is injected through the sacral hiatus, which is formed by failure of fusion of the fifth sacral
vertebral arch. The hiatus is easily palpated in children as a triangular depression bounded on either side by the
sacral cornua ( Fig. 21–2 ). After induction of general anesthesia, the child is placed in the lateral position with the
knees drawn up, the upper knee being flexed more than the lower. The best sacral hiatus is found at the apex of an
equilateral triangle based on a line drawn between the two posterior superior iliac spines ( Fig. 21–3 ). A short
beveled 22-gauge (G) needle is inserted at 45 degrees to the skin ( Fig. 21–4 ). When the needle pierces the
sacrococcygeal membrane and enters the sacral canal, a distinct “pop” is felt. The needle is then advanced an
additional 0.5 to 1 cm depending on the child’s age, on a plane parallel to the spinal axis.
After aspiration to exclude bone marrow, dural puncture, or venipuncture, a test dose of local anesthetic, 0.1 ml/kg
with epinephrine, 1:200,000, is injected. However it has been shown that the use of pretreatment with atropine
enhances the magnitude and the
Figure 21-2 Cutaneous landmarks for a caudal block.
duration of increase in heart rate resulting from epinephrine injection. To minimize the risks associated with large
[22]
volumes of local anesthetic, epinephrine should be injected in incremental doses and the T wave or ST segment
changes should be monitored to detect the beginning of intravascular injection. [23] [24]
When there is difficulty in identifying the sacral hiatus, the technique of intervertebral sacral blockade has been
performed in children. The puncture of the ligamentum flavum is performed in the S2 to S3 interspace, which is
[25]
easily identified because it is the interspace just below the level of the posterior superior iliac spines.
469
Figure 21-3 Bone marrow landmarks for a caudal block.
Local Anesthetic Dosage
Several dosage regimens have been recommended, but I prefer the body weight method. Thus, 0.25% bupivacaine
0.5 mL/kg for lumbosacral areas (e.g., orthopedic surgery of lower limb) and 1 mL/kg for thoracolumbar area (e.g.,
herniorrhaphy and orchidopexy) were administered. The postoperative pain relief was more prolonged with
[26]
addition of 1/200,000 epinephrine, especially in children younger than 5 years, in whom it may double the
duration. It was noted that the mean maximum bupivacaine concentration after administration of 2.5 mg/kg (1
[27]
mL/kg of 0.25%) bupivacaine by the caudal route was less than 1.3 µg/mL and the highest value obtained was 1.6
µg/mL. These values
[28]
Figure 21-4 Angles of the needle during caudal puncture: (1) first stage and (2) second stage.
are far below the plasma bupivacaine concentration levels considered toxic in adults. Just two major differences
were reported on the pharmacokinetics of bupivacaine in children. First, the terminal half-life was longer in children
470
than in adults because of the larger volume of distribution. Second, the free fraction of bupivacaine was more
[28]
important in infants less than 3 months old than in adults. However, the free fraction level has no clinical
[29]
implication without intravenous injection. Nonetheless, the risk of cardiac arrest because of intravascular injection
of local anesthetics is always present as reported by Morray and colleagues. Therefore, the use of ropivacaine
[30]
seems safer, with fewer cardiotoxic effects, e.g., 0.2% ropivacaine 1.25 mL/kg for a caudal block.
[31]
Specific Considerations
Caudal blocks in children are notable for their simplicity, safety, and effectiveness. The two main reasons for failure
of caudal block are (1) not identifying the hiatus and (2) using an insufficient volume of local anesthetic. [32] [33]
Complications are uncommon. The disadvantages are the possible residual motor block and the risk of urinary
retention. Both of these disadvantages can be avoided if a low concentration of bupivacaine (i.e., 0.25%) is used. In
addition, the incidence of intravenous needle insertion can be minimized if a precise technique is used, and dural
puncture is much less common than the anesthetist’s anxiety about it.
On the other hand, I do not recommend the use of caudal epidural catheters because of the risk of sepsis owing to
the proximity of the anus. Therefore, caudal block is a single-shot technique. The lumbar epidural route is preferred
if reinjection is needed, or in children weighing more than 20 to 25 kg to reduce the total amount of local anesthetic
used. In this group of patients, the lumbar epidural block may be used as a single-shot technique. Moreover, to
prolong caudal block and to avoid lumbar technique, clonidine (1–2 µg/kg) may be used. [34]
EPIDURAL BLOCK
Epidural block is an effective technique for intra- and postoperative pain relief. However, general anesthesia is
almost always required if the epidural and surgical procedures are to be performed under satisfactory conditions.
The greatest advantage of epidural block is the long-term analgesia after major surgery of the chest and abdomen
and some orthopedic procedures. In these cases, a combination of light general anesthesia with endotracheal
[4] [6] [7]
intubation and epidural anesthesia is used to obtain a good intraoperative analgesia. In addition, the addition of[4] [6] [7]
continuous bupivacaine injection or administration of narcotics permits prolonged postoperative analgesia.

[5] [9]
Performance of an Epidural Block
General anesthesia is first induced in the same way as caudal block, which was discussed earlier in this chapter. The
technique of lumbar epidural anesthesia in children is similar to that in adults. The smaller the patient, the narrower
the epidural space, and modifications of equipment are thus required if the epidural needle and catheter are to be
placed safely and dural puncture avoided. The midline approach is preferred. However, the distance between skin
and epidural space depends on the age of the child. ( Figs. 21–5 and 21–6 ) I use an 18-G Tuohy needle (10 cm
[35]
long) with a 20-G epidural catheter in children older than 2 years of age
Figure 21-5 Distance from the skin to the epidural space in children.(From Kosaka Y, Sato I, Kawaguchi R: Distance from skin to epidural space in children. Jpn J
Anesthesiol 23:874, 1974.)
471
Figure 21-6 Distance from the skin to the epidural space in infants.
and a 19-G Tuohy needle (5 cm long) with a 21-G epidural catheter in children younger than 2 years of age. The
puncture is performed at L3 to L4 or L4 to L5 interspace to decrease the potential risk of trauma to the spinal cord
(see Fig. 21–1 ). Indeed, in infants, the spinal cord may extend lower than the L2 to L3 interspace. Nevertheless,
thoracic epidural blocks can be performed by skilled practitioners. The correct positioning of the Tuohy needle is
[6] [7]
ascertained by the loss-of-resistance technique with a syringe filled with air instead of saline to avoid diluting the
very small volumes of anesthetics used. Nonetheless, a patchy analgesia has been reported with use of a large
volume of air. The catheter tip should be placed as close as possible to the spinal nerves innervating the area of the
[36]
surgical field. Indeed, when surgery is performed in the thorax and the upper abdomen, the catheter is advanced into
the epidural space to obtain thoracic levels of analgesia. Because of the absence of mature, densely packed fat
lobules, the best placement of an epidural catheter in a child is in a cephalad direction. Bacteriostatic filters are
[6]
connected to the free end of the catheter.
Local Anesthetic Dosage
After a test dose, bupivacaine, 0.25% with epinephrine, 1:200,000, 0.5 mL/kg (bupivacaine, 0.75 mL/kg, for infants
younger than 18 months of age) is used for an initial loading dose, and bupivacaine 0.25 mL/kg is used for
subsequent “top-up” to obtain intraoperative analgesia. Sometimes, to provide better muscle relaxation, it is
[4] [6] [7]
possible to use intravenous muscle relaxants. Despite the relatively high dose used in children, plasma bupivacaine
concentrations are far below the concentrations considered toxic in adults. If lidocaine is used instead of
[5]
bupivacaine, the benefit of prolonged postoperative analgesia is lost.
The effective dose of bupivacaine needed to provide pain relief in the postoperative period may be given as a
continuous infusion (bupivacaine, 0.1 to 0.125% given at a rate of 0.3–0.4 mL/kg/hr). A higher infusion rate would
[5]
expose the patient to neurologic and/or cardiac complications. The disadvantages of continuous bupivacaine
[37]
epidural infusion are a high risk of urinary retention and motor blockade of the legs. The latter can cause anxiety in
children between 4 and 8 years of age, who may not understand why they cannot move their legs. Ropivacaine can
be useful to decrease the risk of motor blockade. [38]
SPINAL BLOCK
Spinal block is an effective technique in the ex-premature infant scheduled for inguinal herniorrhaphy, because it is
the only form of pediatric regional anesthesia in which the block is routinely performed and the operation carried out
on a conscious patient. It is well known that ex-premature infants are more prone to complications, such as
[10] [39] [40]
apnea, hypoxia, and bradycardia during the first postoperative hours after general anesthesia. Moreover, [41] [42]
premature infants with a history of bronchopulmonary dysplasia may be at even greater risk of developing
postanesthetic complications because of the depressant effects of halothane or sevoflurane on intercostal muscles,
lung volumes, and chemo- and baroreceptor responses. Avoiding general anesthesia in these patients is a good
policy.
Performance of a Spinal Block
472
As discussed earlier with epidural block, the subarachnoid puncture should be made caudal to L3 to avoid possible
damage to the spinal cord. The puncture is performed with the child in the lateral position, with lower extremities
flexed and the neck extended. Indeed, it has been shown that hypoxemia has occurred during lumbar puncture in the
sick neonate when the infant’s neck was flexed for the spinal tap. A 22-G, 3.5-cm stylet-type (or a 25-G 1.5 cm
[43]
stylet-type) lumbar puncture needle is inserted in a midline position. A non–stylet-type needle increases the patient’s
risk of developing an epidermoid tumor. The needle is advanced slowly, and the stylet is frequently removed,
[44]
checking for free-flowing return of CSF.
Local Anesthetic Used
Tetracaine, 0.5%, with dextrose, 5%, is the most common local anesthetic preparation used: 0.13 mL/kg in infants
weighing less than 4 kg and 0.07 mL/kg in infants weighing more than 4 kg. I use isobaric bupivacaine, 0.5%, 0.75
[10]
mL for infants weighing less than 5 kg and 1 mL for infants weighing more than 5 kg. [40]
The dead space of the needle is 0.04 mL, which should be taken into account when the dose is being calculated and
drawn up. Duration of spinal block with either tetracaine or bupivacaine is shorter in infants than in adults, probably
because of the larger adult volume of CSF. A relationship between duration of motor blockade and age has been
reported. Moreover, timing of the administration of the block in conjunction with the baby’s feeding schedule is
[19]
important for two reasons. First, the crying of a hungry baby makes hernia repair much more difficult. A pacifier can
usually be used to help keep the baby quiet, and the upper limbs should be immobilized. Second, hypotension from
the sympathetic block after spinal anesthesia can occur if fasting is prolonged. [40]
In older children, there are few indications for spinal block because of the short duration of postoperative analgesia.
Nonetheless, a child with a full stomach who is scheduled for a testicular torsion is a good candidate for a spinal
block without sedation. The usual dosage of tetracaine, 1%, plus glucose, 10%, is 1 mg per year of age (for children
younger than 3 years: 0.2 mg/kg). Hyperbaric bupivacaine, 0.5%, can also be used in older children.
SPECIFIC TECHNIQUES AND PROBLEMS OF CENTRAL REGIONAL BLOCK
Application of Regional Blocks in Outpatients
Outpatient surgery for infants and children is rapidly gaining in popularity, as is the use of regional anesthesia to
obtain prolonged postoperative analgesia. Indeed, it seems that there may be a real advantage for pediatric
outpatients in the combination of light general anesthesia with application of a regional block. Good [17] [45]
postoperative pain relief for the outpatient may be expected to lead to a more rapid return to full activity, less
requirement for analgesics, and a more rapid return to a normal appetite with less nausea and vomiting.
The criteria for participation and discharge are the same as those for general and regional anesthesia. Indeed, I use a
combination of both. Furthermore, if the child has had an upper extremity limb block, it is not necessary that sensory
or motor function return before discharge. The involved extremity is immobilized in a splint or sling, and the parents
are informed that the child is unable to feel pain in the blocked arm for the duration of the block. Children who have
had caudal anesthesia are also eligible for discharge before regression of sensory blockade. In fact, prolonged
analgesia is the advantage of a caudal block. However, children must be able to walk with minimal assistance and be
free from postural hypotension. No residual sympathetic block has been found 2 hours after a caudal block. To [46]
reduce the duration of motor blockade, it is possible to use ropivacaine administered caudally at the end of surgery [38]
instead of bupivacaine. Parents of any child with a residual sensory blockade are told that the child must avoid
contact with sharp or warm objects until sensation returns. Furthermore, the use of an appropriate block for
outpatient surgery is required (e.g., penile block is better than caudal block for a circumcision ). [47]
Intrathecal and Epidural Opioid Analgesia
The use of morphine by the epidural route—caudal or lumbar —gives prolonged analgesia (more than 12 hours
[48] [49] [9]
with a single injection of morphine) after abdominal, thoracic, or cardiac surgery, and allows respiratory
physiotherapy without pain. In addition, intrathecal morphine injection has been used to obtain postoperative
analgesia after cardiac or spinal fusion surgery. Caudal morphine analgesia should be regarded as feasible for
[49] [50] [51]
relief of cancer pain in children of all ages. [52]
The presence of high concentrations of opioid receptors in the spinal cord makes it possible to achieve analgesia
with small doses of morphine administered in either of the intrathecal or epidural spaces. Intrathecal and epidural
injections of morphine produce more profound and prolonged analgesia than comparable morphine doses
administered parenterally and are capable of relieving both visceral and somatic pain.
473
SIDE EFFECTS
Potential side effects of intrathecal and epidural morphine are pruritus, nausea, urinary retention, and early and late
respiratory depression.
Pruritus.Intense itching has been reported in approximately 20% of pediatric patients after the epidural
[9] [53]
administration of morphine in the postoperative period. The occurrence of pruritus was delayed, and itching began 3
hours after morphine administration, at a time when the cutaneous analgesia was beginning to spread cephalad at its
fastest rate. Although the analgesia appeared to be segmental, the pruritus did not appear to be limited to the
[54]
dermatomal segments affected by epidural morphine. The intense itching frequently occurred initially in the facial
region, and then spread to other areas of the body. However, the incidence of severe pruritus that was troublesome to
the patient appeared to be only about 1%. The parenteral administration of naloxone reverses this intense itching. [55]
Nalbuphine, 0.1 mg/kg, may also be very useful. [56]
Nausea and Vomiting. Nausea and vomiting have also been reported in approximately 20% of patients receiving
epidural morphine,[ ] [ ] usually within 60 minutes, although the onset may be delayed up to 10 hours. The early
9 54
stage of nausea and vomiting is probably related to the absorption of the morphine from the epidural space, which is
similar to the reaction observed after the intramuscular administration of morphine. The delayed onset of nausea and
vomiting probably reflects the time required for diffusion of epidural morphine into the CSF.[ ] It is believed that
55
both early and delayed occurrence of nausea and vomiting is due to the stimulation of the vomiting and
chemoreceptor trigger zone in the area postrema on the floor of the fourth ventricle. Fortunately, the incidence of
nausea and vomiting seems to be much less with repeated epidural dosing. Various antiemetic agents have proven
useful in the treatment of the nausea and vomiting. In addition, intravenous naloxone has been effective without
diminishing analgesia.[ ] 55
Urinary Retention. This side effect has been observed in 50% of patients receiving epidural morphine. Urinary [9] [57]
retention can persist for 10 to 20 hours and is more frequent in males. Parenteral naloxone has been reported to be
useful in treating urinary retention. Continuous intravenous naloxone infusion has been proposed for use in
[58]
children who are receiving epidural morphine. The mechanism is not clear, but it is possible that the epidural opioid
interferes with parasympathetic activity in the sacral roots.
Respiratory Depression. The most serious side effect reported after the use of epidural morphine is respiratory
depression, which may be life threatening in certain patients. As with nausea and vomiting, respiratory
[59] [60]
depression may occur as an early phenomenon or it may be delayed. There is a progressive increase in sedation
[54]
and a decrease in respiratory rate, leading ultimately to apnea coupled with a decreased respiratory response to
elevated PaCO2 levels.
The early onset of respiratory depression occurs approximately 1 hour after the administration of epidural morphine
and is believed to be related to the vascular absorption via epidural veins and the subsequent migration of the agent
to the respiratory center in the region of the fourth ventricle. [61]
The late phase of respiratory depression has been reported to occur approximately 6 to 12 hours after the
administration of these agents into the epidural space. Again, this delay is probably related to the migration of the
[9]
morphine from the epidural space into the CSF and subsequent diffusion to the fourth ventricle, where direct
depression of the respiratory center occurs. In addition, the onset of delayed respiratory depression is similar after
intrathecal morphine, confirming the role of rostral spread of morphine in CSF. The following factors may
contribute to delayed respiratory depression: (1) residual effects of parenteral morphine given before epidural
[62]
morphine or after epidural opioid, at a time when it is known that significant respiratory effects of epidural
morphine are still present; (2) residual effects of other CNS depressant drugs used in anesthesia; (3) lack of [9]
tolerance to opioids, because most operative patients have not received opioids for prolonged periods before surgery;
(4) raised intrathoracic pressure with “grunting” respiration in response to the pain; (5) raised intraabdominal
pressure and obstruction of inferior vena cava by a tumor, with increased blood flow through the azygos system; (6)
inadvertent dural puncture. Doses of epidural morphine greater than 50 µg/kg in a child may be associated with a
higher incidence of respiratory depression. In addition, lipid-soluble opioids such as fentanyl or sufentanil induce an
early, short respiratory depression despite their high affinity for spinal cord opioid receptors in adults and [63]
children. This ventilatory depression is associated with spread of epidural analgesia in a rostral direction, which
[64] [54]
suggests a rostral spread of lipophilic opioid in the neuraxis, as previously reported, after epidural morphine. This
spread may have occurred either in the CSF or, more probably, via direct perimedullary vascular channels.
Fortunately, respiratory depression appears to be less frequent than the other side effects, such as pruritus, nausea
and vomiting, and urinary retention (about 1 case in 1000 administrations). Respiratory depression has rarely been
[62]
474
observed when epidural opioids have been employed for the treatment of chronic pain. It is believed that patients
with chronic pain who have been exposed to parenteral opioids for a long period of time develop a tolerance to
opioids administered epidurally.
Low-dose naloxone (i.e., 5 µg/kg) has been shown to be effective in rapidly reversing the respiratory depression
associated with epidural morphine while not reversing the analgesic effects. In addition, a high dose of naloxone
[65]
(i.e., 10 µg/kg) reverses the respiratory depression associated with epidural fentanyl administration. [66]
CLINICAL USE OF EPIDURAL OPIOIDS
The three factors that can change the analgesia obtained with epidural opioids are drug structure and lipid solubility,
dose, and mode of delivery. Physicochemical factors related to the individual agents are shown in ( Table 21–3 ).
Doses. The efficacy and duration of analgesia are correlated with the dose up to a plateau. The usual doses of
morphine range from 30 to 50 µg/kg. The doses for epidural use of fentanyl and sufentanil are respectively, 1 to 2
µg/kg and 0.75 µg/kg. The dose for intrathecal morphine is between 0.01 and 0.02 µg/kg.
Mode of Delivery. In comparing bolus versus infusion, the infusion results in lower dose requirements, more
effective analgesia, and fewer side effects in adults.
TABLE 21-3 -- PHYSICOCHEMICAL CHARACTERISTICS AND CLINICAL IMPLICATIONS OF DRUGS

Parameter Onset Duration
High hydrophilicity (morphine) Slow Long
High lipid solubility Rapid Only slightly longer than i.m.
Moderate receptor affinity (fentanyl)
High lipid solubility Rapid Medium to long
High receptor affinity (sufentanil)
However, no comparative studies have been performed in children. A combination of single-shot morphine via
epidural administration and postoperative patient-controlled analgesia using morphine is also an efficient technique
for very painful surgery when the patient awakes from general anesthesia. [67]
MONITORING OF PATIENTS RECEIVING EPIDURAL OPIOIDS
The potential for respiratory depression is so grave a complication that we recommend admission to a specialized
monitored intensive care unit location. The patient should be clinically monitored as follows: sedation and
respiratory rate checked every 2 hours, a capnogram recording of end-tidal CO2 tension should be maintained by
nasal prong, or transcutaneous PCO2 may be used. The duration of monitoring should be between 18 and 24 hours for
a single dose of morphine and 3 hours for a single dose of fentanyl or sufentanil.
Headaches After Spinal Puncture in Children
In adults, the incidence of post–lumbar puncture headache depends on age, with the greatest number occurring in the
youngest adults. Therefore, the risk of this complication could be expected to be especially high in children.
Unfortunately, few studies have focused on this point. Surprisingly, pediatricians claim that children rarely develop
post–lumbar puncture headache despite routine use of larger needles. In oncologic patients, the incidence of post–
[68]
lumbar headache is low in patients younger than the age of 13 years. Thus, a heightened awareness of the risk of
[69]
post–lumbar puncture headache may be required if spinal anesthesia is used in adolescents. This difference can be
explained by the hormonal changes that take place with aging. Nonetheless, an early report of spinal anesthesia in
children mentions a negligible risk of post–lumbar puncture headache. If spinal block is used in older children, the
[70]
risk of headache should be explained to the child and parents. If a headache occurs, therapy includes placing the
patient in the supine position, increasing oral or intravenous fluids, and giving analgesics for 12 to 24 hours. If
headache is still present, a blood patch is strongly recommended, as in adults. [71]
Techniques for Performing Peripheral Regional Anesthesia
ANATOMIC AND PHYSIOLOGIC CONSIDERATIONS
475
Myelination begins during the fetal period and continues to the age of 3 years. In an infant, the nerve fiber diameter
is smaller, the myelin sheath thinner, and the internodal distance smaller, so a lower concentration of local anesthetic
is needed, leading to fewer toxic effects. The local distribution is excellent because of several factors: volume,
concentration, and presence and thickness of the aponeuroses and sheaths around the nerves.
GENERAL TECHNICAL CONSIDERATIONS
Because most regional anesthetic techniques were developed in adult patients, we have considerable experience in
their use. The application of these techniques to children requires an awareness of certain anatomic differences that
exist between children and adults. The details of the segmental innervation of various plexuses and larger nerves
need not be repeated in this chapter as they are explained and reviewed elsewhere in the text.
After defining the anatomic landmarks, the anesthesiologist, wearing gloves, prepares the material in an aseptic
manner. The site of puncture is cleaned thoroughly with an antiseptic solution. Before injection, a count of muscular
contractions should be obtained for a minimal intensity (less than 1 mA). An aspiration test should be done before
each injection. The test dose (1 mL) should stop the muscular contraction and no abnormalities should be seen on
the electrocardiogram monitor for 30 to 40 seconds after the test dose. The local anesthetic solution should be
administered slowly over a period of at least 60 to 120 seconds irrespective of the type of block, with repeated
aspirations after every 5 mL of injected solution.
BRACHIAL PLEXUS AND BRANCHES
Fractures of the upper extremity, especially at the elbow and wrist, are common injuries during the summer months
when children are outside playing on jungle gyms and riding skateboards. These patients are often brought for
treatment in the late afternoon or early evening, having eaten just before the traumatic event. Surgery focuses on
reduction and realignment procedures with hardware insertion and casting. Use of a sedative may complicate the
anesthetic considerations of a full stomach. In these cases, brachial plexus blockade may be established with a
variety of effective techniques ( Fig. 21–7 ).
476
Figure 21-7 Diagram of the brachial plexus, with needle placements highlighted for axillary, interscalene, parascalene, and perivascular approaches.
Axillary Approach
The indication of the axillary approach is elective or emergency surgery on the forearm and the hand. The
[72] [73]
specific contraindications are axillary lymphadenopathy or the requirement that the limb be immobilized as in
patients with intense pain or unstable fractures.
The positioning chosen is determined by the patient’s ability to cooperate, which may be limited by pain or
enhanced by a light plane of general anesthesia. The arm should be abducted between 45 and 90 degrees and
externally rotated. The correct position is determined by the operator’s ability to identify the axillary arterial
pulsation and to trace it beneath the major pectoral muscle toward the apex of the axilla. The anatomic landmarks
are the axillary artery, the major pectoral muscle, and the coracobrachial muscle. The point of puncture is situated at
the intersection where the major pectoral muscle crosses the coracobrachial muscle, at the upper border of the
axillary artery. The needle is introduced at an angle of 45 degrees at the upper margin of the axillary artery, with the
needle pointing toward the midpoint of the clavicle. A characteristic pop is felt as the needle enters the periplexus
sheath and the axillary artery pulsations are transmitted to the needle. If a nerve stimulator is used, muscle twitches
are seen in the forearm and the hand. Once the correct position of the needle is confirmed, the injection can begin.
Only one nerve should be assessed because of the excellent diffusion in the periplexus sheath. One of several [74]
variations that have been described is Dalens’ technique, in which the needle is introduced perpendicular to the
[75]
skin surface of the arm in the direction of the upper border of the axillary artery and the humerus until the periplexus
sheath is penetrated. If a tourniquet is necessary for the surgical procedure and to provide good tolerance for the
patient, a subcutaneous infiltration of local anesthetic solution at the puncture point may be needed to block the
medial cutaneous nerve. Catheters can be tunneled away from the insertion site if a long implantation is expected or
they can simply be sutured in place and the site covered with a clear plastic dressing to facilitate daily inspections
for disconnection, erythema, drainage, or other signs of infection. The particular pediatric advantages are a success
rate close to 100% and a high benefit to risk ratio.
477
Parascalene Block
The parascalene approach to the brachial plexus has been described by Dalens and colleagues and is recommended
[76]
for elective or emergency surgery of the upper limb when lesions are located above the elbow or when the limb
cannot be moved, either because of severe pain or because of the nature of the lesion itself. This block provides
excellent intra- and postoperative analgesia. The lower branches of the cervical plexus are affected in more than
50% of reported block procedures. Specific contraindications are acute or chronic respiratory insufficiency
(mucoviscidosis) or the requirement of bilateral supraclavicular block for the surgery, because of the risk of phrenic
block. Side effects can occur such as stellate ganglion block with a Horner syndrome (ptosis of the eye, miosis,
anaphthalmos, hyperemia of the conjunctiva, hyperthermia, and anhidrosis of the face), risk of damage to the
vertebral artery or the large blood vessels of the neck, or pneumothorax. An epidural or intrathecal injection is not
used with this approach.
The patient is placed in the supine position with the head turned away from the side to be blocked, the arms
extended along the sides of the body, and the shoulders raised with a rolled sheet. The anatomic landmarks are the
midpoint of the clavicle and Chassaignac’s tubercle (the anterior tubercle of the transverse process of the sixth
cervical vertebra), which is projected onto the skin at the intersection of the sternocleidomastoid, with the transverse
plane passing through the cricoid cartilage. The point of puncture is situated at the junction of the upper two thirds
and lower one third of the line joining the midpoint of the clavicle and Chassaignac’s tubercle. The needle is
inserted perpendicular to the skin in anteroposterior plane until muscle twitches are elicited. If the needle is too
lateral, muscle contractions of the shoulder are seen when the supraclavicular nerve, which lies outside the plexus, is
stimulated. If the needle is too medial or too deep, the phrenic nerve may be stimulated, leading to contractions of
the diaphragm. In either case, the needle should be withdrawn up to the subcutaneous tissue and redirected correctly.
It is noteworthy that in pediatric patients the brachial plexus is located at a depth of 7 mm to 30 mm from the skin,
depending on age. Parascalene block provides excellent analgesia to the upper extremity, and use of this technique
in children is safer and has an much lower incidence of complications than the other blocks (interscalene block,
perisubclavian block).
Interscalene Block
Blockade of the brachial plexus high in the neck by an interscalene approach is relatively simple in children
[77]
because of their lack of fat and the ease with which the anterior scalene and middle scalene muscles can be palpated
with the index and middle fingers. The groove between these muscles runs parallel to the posterior border of the
sternocleidomastoid muscle and is identified when the palpating fingers fall off the posterior portion of the
sternocleidomastoid at the level of the cricoid cartilage. The groove may also be identified at the point where the
external jugular vein crosses the sternocleidomastoid muscle. The sheathed needle is inserted between the palpating
fingers, with the tip directed toward the sternal notch and angled posteriorly toward the transverse process of the
vertebral body and not the vertebral artery. Once again loss of resistance to injection and the experience of a fascial
click when a blunt needle is used identifies the brachial sheath. The use of a nerve stimulator may be of assistance in
the performance of this block.
Subclavian Perivascular Block
In contrast to the parascalene and interscalene techniques described earlier, Winnie’s subclavian perivascular
approach to the brachial plexus relies on a single palpating digit, moved to the inferior limit of the interscalene
[78]
groove from C6. The inferior limits of this palpation are reached with pulsation of the subclavian artery, which
passes between the insertions of the anterior and middle scalene muscles on the first rib or the belly of the omohyoid
muscle. Through the skin nick made above the palpating finger, a short-bevel, sheathed needle is inserted in a caudal
direction parallel to the long axis of the body. A fascial pop identifies the correct needle placement in the sheath.
The use of a nerve stimulator may be of assistance in the performance of this block.
LUMBAR PLEXUS AND BRANCHES
Innervation of the skin, muscles, periosteum, and joints of the hip, thigh, and knee make the blockade of the lumbar
plexus particularly useful in pediatric patients. Analgesia for lower extremity procedures in children frequently
involves areas innervated by branches of the lumbar plexus. Procedures involving joint or bone realignment,
especially with insertion of hardware, are common, particularly in a disabled child whose ability to sit upright in a
wheelchair or to manage transfers from chair to bed and vice versa is vital for reducing dependence on family or
nursing staff. In children with cerebral palsy, lengthening of muscles and tendons is equally important.
Unfortunately, these children may suffer from long periods of muscle spasm and pain after surgery. Because of their
478
disabilities, communication regarding the efficacy of pain relief may be very difficult. Regional techniques, which
effectively block the development of muscle spasm, eliminate the need for benzodiazepines and their supposed
muscle relaxant effect. A patient with clearer sensorium is more responsive and is able to assess the quality of pain
relief. Congenital hip dislocation, which does not respond to immobilization in plaster, may require open reduction.
In this setting, unilateral blockade of the lumbar plexus or bilateral blockade from a central approach makes life
easier for all concerned.
Femoral Block
The area anesthetized by a femoral block is the quadriceps group of muscles, the periostium of the shaft of the femur,
the skin on the anterior aspect of the thigh, the medial part of the leg, and a small portion of the foot. The indications
are analgesia in patients with fracture of the femur and surgery on the thigh and analgesia combined with a sciatic
[79]
block for knee and leg surgery. The “3-in-1” block as described by Winnie and colleagues is an excellent technique
[80]
for the combined approach to the femoral nerve, the obturator nerve, and the lateral femoral cutaneous nerve.
The anatomic landmark in a patient who is supine with the lower limb abducted, the knee slightly flexed, and the
lateral border of the feet in contact with the bed is the inguinal ligament, which extends from the anterosuperior iliac
spine to the pubic tubercle and the femoral artery, which can be palpated just below the inguinal ligament. The
femoral nerve compartment lies under two layers of fascia below the skin, inferior to the inguinal ligament and
lateral to the femoral artery pulse ( Fig. 21–8 ). The site of puncture is between 0.5 and 1.0 cm below the inguinal
ligament and lateral to the femoral artery. The needle (length of 25 mm for weight under 25 kg; 50 mm over 25 kg)
is inserted perpendicular to the skin surface or with a slight upward tilt until muscle twitches of the rectus femoris
muscle are seen. Sometimes, the correct insertion of ashort-bevel needle yields two fascial pops as it penetrates the
fascia iliaca and fascia lata to enter the nerve compartment. A volume of 0.3 to 0.5 mL/kg is used (but no more than
35 mL should be used). [81]
Using a two-injection technique in 50 children undergoing lower limb procedures, McNicol showed that excellent
[82]
analgesia could be achieved by using combined lateral femoral cutaneous and femoral nerve blocks. His alternate
technique relies on using a fan-type injection for the lateral femoral cutaneous nerve inferior to the inguinal ligament
and medial to the anterosuperior iliac spine. The femoral nerve block was performed lateral to the femoral pulsation
and inferior to the inguinal ligament. Wendel demonstrated the safe effective use of combined femoral cutaneous
[83]
nerve blocks for muscle biopsy in 73 children.
Fascia Iliaca Compartment Block
The fascia iliaca compartment block anesthetizes the femoral nerve in all cases and the lateral cutaneous nerve of
[84]
the thigh and the obturator nerve in 75% of cases.
The anatomic landmarks in a patient in the supine position with a slight abduction of the thigh is the inguinal
ligament, which extends from the anterosuperior iliac spine to the pubic tubercle and the femoral artery. The site of
puncture is between 0.5 and 1.0 cm below the junction of the lateral third and the medial two thirds of the inguinal
ligament, lateral to the femoral artery. The needle is introduced at a right angle to the skin. A first loss of resistance
is felt when the needle pierces the fascia lata, and the second is felt as it penetrates the fascia iliaca. For this block,
the use of a nerve stimulator is not needed. In addition, a catheter for continuous infusion of local anesthetic can be
used as with the femoral block. [85]
479
Figure 21-8 Diagram of the major nerves of the groin— femoral, lateral femoral cutaneous, ilioinguinal and iliohypogastric—and their relation to palpable landmarks.
Sciatic Nerve
With contributions from the lumbar roots (L4 and L5) and the sacral roots (S1 to S3), the sciatic nerve is the largest
in the body. Although relatively well hidden by various large muscle groups, it can be approached in children both
posteriorly by the classical Labat technique or anteriorly. [86] [87]
The indications for sciatic nerve block analgesia are trauma of the leg and foot. In elective surgery, a sciatic nerve
block can be performed for surgery on the foot, and if combined with a femoral nerve block, all operations on the
lower limb can be performed. In addition, pediatric orthopedic procedures below the knee are primarily associated
with congenital deformities such as talipes equinovarus and structural imbalances caused by cerebral palsy. Leg
length discrepancy may also require prolonged treatment with an external fixator. In this setting, if bone length can
be gained early, which is possible because of excellent analgesia from regional blockade, it will shorten the
hospitalization and reduce the associated expenses.
ANTERIOR APPROACH TO THE SCIATIC NERVE
The anterior approach to the sciatic nerve relies on the path of the sciatic nerve between the ischial tuberosity and
the greater trochanter of the femur ( Fig. 21–9 ). The patient lies supine with the leg in a neutral position. After a
sterile preparation and drape, two parallel lines are drawn with a perpendicular dropped between them. The first line
follows the inguinal ligament from the anterosuperior iliac spine to the pubic tubercle. A perpendicular line is drawn
from the intersection of the medial third and the lateral two thirds of the first line. The second line is drawn from the
greater trochanter parallel to the inguinal ligament until it intersects the perpendicular. At this point, a short-bevel
needle is inserted until the surface of the femur is reached. The needle is then withdrawn and redirected to pass
behind the lesser trochanter until it enters the neurovascular sheath containing the sciatic nerve, the sciatic artery,
and the inferior gluteal veins. The use of a nerve stimulator is mandated to access dorsal flexion of the foot and
eversion (tibial nerve) or plantar flexion and inversion of the foot (common peroneal nerve).
POSTERIOR APPROACH TO THE SCIATIC NERVE
The posterior approach to the sciatic nerve identifies the sciatic nerve at the same level as the anterior approach
described earlier. In this setting, the patient is placed in the lateral position, with the upper leg flexed at the hip. At
the midpoint of a line drawn from the ischial tuberosity to the greater trochanter, a short bevel needle is inserted
with a nerve stimulator attached (length 25 mm under 10 kg, 50 mm until 25 kg, 100 mm over 25 kg). The depth at
which twitches are seen depends on the patient’s age (between 16 and 60 mm). When the chosen end point is found,
the injection of 1 mL of local anesthetic abolishes the stimulation of muscle activity (i.e., dorsal flexion of the foot
and eversion
480
Figure 21-9 Cross-sectional diagram of the sciatic nerve and its relation to the lesser trochanter of the femur for anterior and posterior approaches.
[tibial nerve] or plantar flexion and inversion of the foot [common peroneal nerve]). The volume is 0.5 mL/kg. No
more than 35 mL should be used.
When a femoral nerve block is combined with a sciatic nerve block, the total dose is reduced by one third for each
block.
LATERAL APPROACH TO THE SCIATIC NERVE
The patient position is supine and if possible, the leg is slightly rotated externally. The point of puncture is located
on the lateral aspect of the thigh, 1 to 2 cm, below the greater trochanter, depending on the patient’s age. The needle
is inserted perpendicular to the long axis of the limb in the horizontal plane and directed toward the position
bordering the femur and the ischial tuberosity. If the needle touches bone, it is withdrawn and reinserted more
dorsally under the femur. The depth at which the sciatic nerve is found depends on the patient’s age. Lateral sciatic
nerve block is simple and there is no need to immobilize the child.
MEDIAL POPLITEAL NERVE BLOCK
The indication for medial popliteal nerve block is foot surgery. The anatomic landmarks are between the tendons
[88]
of the biceps femoris and the semitendinous muscles, the intercondylar line, and the bisector of the angle created
with the summit of the popliteal fossa. The point of puncture is located 1 cm lateral to the bisector, at the junction of
the upper third and the lower two thirds of the segment extending from the summit of the popliteal fossa and the
intercondylar line.
The needle is inserted at a right angle to the posterior aspect of the popliteal fossa until muscle twitches are elicited
in the flexor muscles of the foot. The volume (0.5 mL/kg) injected should be less than 35 mL and reduced by one
third if combined with a femoral block.
OTHER BLOCKS
Intravenous Regional Anesthesia for Children
Pediatric patients are good candidates for intravenous regional anesthesia when procedures on the upper
[89] [90]
extremity are of short duration and involve minimal surgical stimulation. Because of the quality of the analgesia,
this technique is ideal for patients with a potentially full stomach because little or no sedation is needed. Use of this
technique in lower extremity surgery is complicated by the volume of local anesthetic required, the difficulty of
481
venous access in the limb, and the fact that combined sciatic and femoral anesthesia, a 3-in-1 block, or an epidural
approach may be easier to perform.
Double tourniquets in a variety of sizes are available for use in children. Older children can cooperate with the
insertion of intravenous catheters without supplemental sedation if they are approached with gentleness and care. As
in adults, tourniquet pain may require blockade of the intercostobrachial nerve for relief. The choice of agent (i.e.,
0.5% lidocaine, 3mg/kg) is a function of anticipated toxicity in the event of a sudden tourniquet failure.
PENILE BLOCK
The indication for penile block is surgery on the foreskin (phimosis, paraphimosis, circumcision). The anatomic
[47] [91]
landmark is the pubic symphysis. The puncture is performed with a 22-G needle, which is 30 mm long. After gently
pulling the penis downward and repered the pubic symphysis, the two points are marked just below each of the
pubic rami, about 0.5 to 1.0 cm on either side of the pubic symphysis. The needle is introduced at the puncture site,
perpendicular to the skin. The penetration is stopped in the subpubic space after a distinct elastic recoil is felt,
corresponding to the crossing of the deep membranous layer of the superficial fascia. The depth of insertion depends
on the patient’s age (8 mm for a newborn; 30 mm for a young adult). The same procedure is repeated on the
opposite side. A volume of 0.1 mL/kg is used for each side with 0.5% bupivacaine and no epinephrine. Epinephrine
is absolutely contraindicated because it can lead to spasm of the dorsal arteries of the penis, with subsequent
ischemia and necrosis of the glands. Ropivacaine should also be avoided with this block. In addition, the midline
[92]
puncture, which is the old technique, can injure the dorsal artery of the penis, leading to a compressive hematoma
and possibly resulting in gland necrosis.
ILIOINGUINAL BLOCK
The main indication for ilioinguinal block is hernia repair. The anatomic landmark is the anterosuperior iliac spine.
[93]
A short-bevel 22-G needle is inserted just below and medial to the anterosuperior iliac spine. The medial distance
depends on the size of the child; it is 0.5 cm in the infant and 2 cm in the adolescent. The needle is slowly advanced
until there is a loss of resistance, which occurs as the aponeurosis of the external oblique muscle is pierced. The
needle is then immobilized in this position. A volume of 0.4 mL/kg bupivacaine, 0.5%, without epinephrine (or 0.6
mL/kg of ropivacaine, 0.5% ) is used.
[94]
INTRAPLEURAL ANALGESIA
Intrapleural analgesia has been used to provide postoperative pain relief for adults and children in a variety of
settings since its first description by Reiestad and Stromskag. Satisfactory pain relief has been demonstrated
[95]
TABLE 21-4 -- MAXIMAL RECOMMENDED DOSES OF LOCAL ANESTHETICS FOR PERIPHERAL BLOCKS
Maximal Recommended Doses without Maximal Recommended Doses without Onset Duration
Concentration (%) Agent Epinephrine (mg/kg) Epinephrine (mg/kg) (min) (hr)
0.5–2 Lidocaine 7.5 10 10–15 1–2
0.25–0.5 Bupivacaine 2 2.5 20–30 2–6
1 Mepivacaine 8 — 10–15 2–3
0.2–1 Ropivacaine 3 — 20–30 2–6
in patients who have had for unilateral chest wall procedures, thoracotomies, subcostal incisions, and flank surgery.
The insertion of the pleural catheter during thoracotomy is best performed by the surgeon at the end of the procedure
and before chest closure; in the closed chest, a percutaneous insertion can also be performed with equipment found
in most epidural trays. The patient is placed in the lateral decubitus position with the superior shoulder flexed to
make the axilla accessible for the puncture. However, the high plasma levels of local anesthetics after 24 hours of
infusion can expose the patient to neurologic or cardiac toxic effects. Therefore, this technique is now rarely used
[96]
in children.
PARAVERTEBRAL BLOCK
Paravertebral block has been used to provide postoperative pain relief for adults and children in a variety of settings.
Satisfactory pain relief has been demonstrated in patients who have had unilateral thoracotomies and urologic
surgery. The percutaneous insertion can be performed with equipment found in most epidural trays. The patient
[97] [98]
is placed in the lateral decubitus position. Because of the variation of size in children, the use of a loss-of-resistance
482
technique to find the space is better than judging the location by depth alone. Potential complications are
pneumothorax and vascular puncture; hypotension is rare because of the lack of sympathectomy. [99]
Conclusion
The goal of regional anesthesia in the pediatric population must always be the provision of effective, safe analgesia
with the least morbidity and the lowest risk of adverse effects. Indeed, safety concerns are prominent because most
children who undergo surgery and anesthesia are healthy and tolerate systemic opoids with a good safety margin
( Table 21–4 ).
Few large studies have reported any incidence of complications. Among a total of 24,409 cases involving
[13] [100]
regional anesthesia, the French-Language Society of Pediatric Anesthesiologists (ADARPEF) study reported only
23 critical incidents (see Table 21–2 ) and none resulted in death or neurologic sequelae, despite the fact that 95% of
these blocks were performed with general anesthesia. Nonetheless, peripheral blocks seem safer than central
[17] [45]
blocks and should be chosen when surgery can be performed with a peripheral block. On the other hand, [101]
prospective sensory and motor examinations were not conducted after regional anesthesia in pediatric patients;
therefore, mild peripheral nerve injury could have been missed. Indeed, neural injuries may resolve more
[102] [103]
rapidly and completely in children, resulting in a lower incidence of neurologic complications after anesthetic
techniques. Futhermore, the theory that children are at lower risk for neural injury is supported by a striking paucity
of claims for pediatric nerve injury (1% of all claims) in comparison with claims for nerve injury in adults (16% of
all claims).
In conclusion, the efficiency of analgesia and the low incidence of complications of different regional anesthesia
techniques are probably the best arguments for using regional anesthesia in pediatric patients.
REFERENCES
1. Kay B: Caudal blockade for postoperative pain relief in children. Anaesthesia 29:610, 1974.
2. Arthur DS: Postoperative thoracic epidural analgesia in children. Anaesthesia 35:1131, 1980.
3. Blaise
G, Roy WL: Postoperative pain relief after hypospadias repair in pediatric patients: Regional vs systemic analgesics. Anesthesiology
65:84, 1986.
4. Dalens
B, Tanguy A, Haberer JP: Lumbar epidural anesthesia for operative and postoperative pain relief in infants and young children. Anesth
Analg 65:1069, 1986.
5. Desparmet J, Saint-Maurice C: Continuous epidural anesthesia in children under 10 years old. Reg Anesth 11:168, 1986.
6. Ecoffey
C, Dubousset AM, Samii K: Lumbar and thoracic epidural anesthesia for urologic and upper abdominal surgery in infants and children.
7. Meignier M, Souron R, Le Neel JC: Postoperative dorsal epidural analgesia in the child with respiratory disabilities. Anesthesiology 59:473,
1983.
8. HatchDJ, Hulse MG, Lindahl SGF: Caudal analgesia in children: Influence on ventilatory efficiency during halothane anesthesia. Anaesthesia
39:873, 1986.
9. Attia J, Ecoffey C, Sandouk P, et al: Epidural morphine in children: Pharmacokinetics and CO2 sensitivity. Anesthesiology 65:590, 1986.
10. Abajian JC, Melish RWP, Browne AF, et al: Spinal anesthesia for surgery in the high risk infant. Anesth Analg 63:359, 1983.
11. Alexander C, Wolf S, Ghia J: Caudal anesthesia for early onset myotonic dystrophy. Anesthesiology 55:597, 1981.
12. Murat
I, Esteve C, Montay C, et al: Pharmacokinetics and cardiovascular effects of bupivacaine during epidural anesthesia in children with
Duchenne muscular dystrophy. Anesthesiology 67:249, 1987.
13. Giaufré
E, Dalens B, Gambert A: Epidemiology and morbidity of regional anesthesia in children: A one year prospective survey of the French-
Language Society of Pediatric Anesthesiologists. Anesth Analg 83:904, 1996.
14. Armitage EN: Regional anesthesia in pediatrics. Clin Anaesthesiol 3:353, 1985.
15. Arthur DS, McNicol LR: Local anesthetic techniques in paediatric surgery. Br J Anaesth 58:760, 1986.
16. Yaster M, Maxwell LG: Pediatric regional anesthesia. Anesthesiology 70:324, 1989.
483
17. Murat I: Anesthésie locorégionale chez l’enfant. Conférence d’experts. Ann Fr Anesth Reanim 16:985, 1997.
18. Soliman IE, Broadman LM, Hannallah RS, McGill WA: Comparison of the analgesic effects of EMLA (eutectic mixture of local anesthetics)
to intradermal lidocaine infiltration prior to venous cannulation in unpremedicated children. Anesthesiology 68:804, 1988.
19. Dohi S, Naito H, Takahashi T: Age related changes in blood pressure and duration of motor block in spinal anesthesia. Anesthesiology 50:319,
1979.
20. Payen D, Ecoffey C, Carli P, Dubousset A: Pulsed Doppler ascending aortic, carotid, brachial, and femoral artery blood flows during caudal
anesthesia in infants. Anesthesiology 67:681, 1987.
21. Touloukian RJ, Wugmeister M, Pickett LK, Hehre FW: Caudal anesthesia for neonatal anoperineal and rectal operations. Anesth Analg 50:565,
1971.
22. Desparmet J, Mateo J, Ecoffey C, Mazoit X: Efficacy of an epidural test dose in children anesthetized with halothane. Anesthesiology 72:249,
1990.
23. Freid
EB, Bailey AG, Valley RD: Electrocardiographic and hemodynamic changes associated with unintentional intravascular injection of
bupivacaine with epinephrine in infants? Anesthesiology 79:394, 1993.
24. Kosek-Longenecker SA, Marhofer P, Jonas K, et al: Cardiovascular criteria for epidural test dosing in sevoflurane- and halothane-anesthetized
children. Anesth Analg 90:579, 2000.
25. Busoni P, Sarti A: Sacral intervertebral regional anesthesia for childhood fractures. J Trauma 11:301, 1971.
26. McGown RG: Caudal analgesia in children: 500 cases for procedures below the diaphragm. Anaesthesia 37:806, 1982.
27. Warner MA, Kunkel SE, Offord KO, et al: The effects of age, epinephrine and operative site on duration of caudal anesthesia in pediatric
patients. Anesth Analg 66:995, 1987.
28. Ecoffey C, Desparmet J, Maury M, et al: Bupivacaine in children: Pharmacokinetics following caudal analgesia. Anesthesiology 63:447, 1985.
29. Mazoit JX, Denson DD, Samii K: Pharmacokinetics of bupivacaine following caudal anesthesia in infants. Anesthesiology 68:387, 1988.
30. Morray
JP, Geiduschek JM, Ramamoorthy C, et al: Anesthesia-related cardiac arrest in children: Initial findings of the Pediatric Perioperative
Cardiac Anest (POCA) Registry. Anesthesiology 93:6, 2000.
31. Morton NS: Ropivacaine in children [editorial]. Br J Anaesth 85:344, 2000.
32. BroadmanLM, Hannallah RH, Norden RS, McGill WA: “Kiddie caudals”: Experience with 1154 consecutive cases without complications.
Anesth Analg 66:S18, 1987.
33. DalensB, Hasnaoui A: Caudal anesthesia in pediatric surgery: Success rate and adverse effects in 750 consecutive patients. Anesth Analg
66:83, 1989.
34. Jamali S, Monin S, Begon C, et al: Clonidine in pediatric anesthesia. Anesth Analg, 78:667, 1994.
35. Kosaka Y, Sato I, Kawaguchi R: Distance from skin to epidural space in children. Jpn J Anesthesiol 23:874, 1974.
36. Dalens B, Bazin JE, Haberer JP: Epidural bubbles as a cause of incomplete analgesia during epidural anesthesia. Anesth Analg 66:679, 1987.
37. Berde CB: Convulsions associated with pediatric regional anesthesia. Anesth Analg 75:164, 1992.
38. Da Conceicao MJ, Coelho L: Caudal anaesthesia with 0.375% ropivacaine or 0.375% bupivacaine in paediatric patients. Br J Anaesth 80:507,
1998.
39. Gregory GA, Steward DJ: Life threatening perioperative apnea in the ex-“preemie” [editorial]. Anesthesiology 59:495, 1983.
40. Mahe V, Ecoffey C: Spinal anesthesia with isobaric bupivacaine in infants. Anesthesiology 68:601, 1988.
41. Harnik
EV, Hoy GR, Potolicchio S, et al: Spinal anesthesia in premature infants recovering from respiratory distress syndrome.
42. Krane
EJ, Haberkern CM, Jacobson LE: Postoperative apnea, bradycardia, and oxygen desaturation in formerly preterm infants: Prospective
comparison of spinal and general anesthesia. Anesth Analg 80:7, 1995.
43. Gleason CA, Martin RJ, Anderson JV, et al: Optimal position for a spinal tap in preterm infants. Pediatrics 71:31, 1983.
44. Batnitzky S, Keucher TR, Mealey J, Campbell RL: Iatrogenic intraspinal epidermoid tumors. JAMA 237:148, 1977.
45. Krane EJ, Dalens BJ, Murat I, Murrell D: The safety of epidural placed during general anesthesia. Reg Anesth Pain Med 23:433, 1998.
484
46. Saint-Raymond S, O’Donovan F, Ecoffey C: Criteria for safe ambulation following caudal block in children. Anesthesiology 69:A769, 1988.
47. Yeoman PM, Cooke R, Hain WR: Penile block for circumcision? Anaesthesia 38:862, 1983.
48. Jensen BH: Caudal block for postoperative pain relief in children after genital operations. A comparison between bupivacaine and morphine.
Acta Anesthesiol Scand 25:373, 1986.
49. Rosen KR, Rosen DA: Caudal epidural morphine for control of pain following open heart surgery in children. Anesthesiology 70:418, 1989.
50. Dalens B, Tanguy A: Intrathecal morphine for spinal fusion in children. Spine 13:494, 1988.
51. Gall O, Aubineau JF, Bernière J, et al: Analgesic effect of low-dose intrathecal morphine after spinal fusion in children. Anesthesiology 94:447,
2001.
52. BerdeCB, Fischel N, Filardi JP, et al: Caudal epidural morphine analgesia for an infant with advanced neuroblastoma: Report of a case. Pain
36, 210, 1989.
53. GlenskiJA, Warner MA, Dawson B, Kaufman B: Postoperative use of epidurally administered morphine in children and in adolescents. Mayo
Clin Proc 59:530, 1984.
54. Bromage PR, Camporesi EM, Durant PA, Nielsen CH: Rostral spread of epidural morphine. Anesthesiology 56:431, 1982.
55. Korbon
GA, James DJ, Verlander JM, et al: Intramuscular naloxone reverses the side effects of epidural morphine while preserving analgesia.
Reg Anesth 10:16, 1985.
56. Kendrick
WD, Woods AM, Daly MY, et al: Naloxone versus nalbuphine infusion for prophylaxis of epidural morphine-induced pruritus.
Anesth Analg 82:641, 1996.
57. Bromage PR, Camporesi EM, Durant PAC, Nielsen CH: Non respiratory side effects of epidural morphine. Anesth Analg 59:473, 1980.
58. Rawal N, Mollefors K, Axelsson K, et al: An experimental study of urodynamic effects of epidural morphine and of naloxone reversal. Anesth
Analg 62:641, 1983.
59. Krane EJ: Delayed respiratory depression in a child after caudal epidural morphine. Anesth Analg 67:79, 1988.
60. Gustafsson LL, Feychting B, Klingstedt C: Late respiratory depression after concomitant use of morphine epidurally and parenterally. Lancet
1:892, 1981.
61. Yaksh TL: Spinal opiate analgesia: Characteristics and principles of action. Pain 11:293, 1981.
62. Gustafsson
LL, Schildt B, Jacobsen K: Adverse effects of extradural and intrathecal opiates: Report of a nationwide survey in Sweden. Br J
Anaesth 54:479, 1982.
63. Negre I, Gueneron JP, Ecoffey C, et al: Ventilatory response to carbon dioxide after intramuscular and epidural fentanyl. Anesth Analg 66:707,
1987.
64. Benlabed M, Ecoffey C, Levron J, et al: Analgesia and ventilatory response to CO2 following sufentanil in children. Anesthesiology 67:948,
1987.
Rawal N, Schott U, Dahlstrom B, et al: Influence of naloxone infusion on analgesia and respiratory depression
65.
following epidural morphine. Anesthesiology 64:194, 1986.
Gueneron JP, Ecoffey C, Carli P, et al: Effect of naloxone infusion on analgesia and respiratory depression after
66.
epidural fentanyl. Anesth Analg 67:35, 1988.
Kiffer F, Joly A, Wodey E, et al: Effect of preoperative epidural morphine on postoperative analgesia in children.
67.
68. Plaut TF: Lumbar puncture in children: Its value and risk. Clin Pediatr 7:130, 1968.
69. Bolder PM: Postlumbar puncture headache in pediatric oncology patients. Anesthesiology 65:696, 1986.
Berkowitz S, Greene BA: Spinal anesthesia in children: Report based on 350 patients under 13 years of age.
70.
71. Purtock RV, Buhl JL, Abram SE: Epidural blood patch in a nine year old boy. Reg Anesth 9:154, 1984.
72. Eriksson E: Axillary brachial plexus anesthesia in children with Citanest. Acta Anesthesiol Scand 16:291, 1965.
485
Fisher WJ, Bingham RM, Hall R: Axillary brachial plexus block for perioperative analgesia in 250 children.
73.
Paediatr Anaesth 9:435, 1999.
Carre P, Joly A, Cluzel Field B, et al: Axillary block in children: Single or multiple injection? Paediatr Anaesth
74.
10:35, 2000.
75. Dalens B: Regional anesthesia in children. Anesth Analg 68:654, 1989.
Dalens B, Vanneuville G, Tanguy A: A new parascalene approach to the brachial plexus in children: Comparison
76.
with supraclavicular approach. Anesth Analg 66:1264, 1987.
77. Winnie AP: Interscalene brachial plexus block. Anesth Analg 49:455, 1970.
Pande R, Pande M, Bhadani U, et al: Supraclavicular brachial plexus block as a sole anaesthestic technique in
78.
children: An analysis of 200 cases. Anaesthesia 55:798, 2000.
Ronchi L, Rosenbaum D, Athouel A, et al: Femoral nerve block in children using bupivacaine. Anesthesiology
79.
70:622, 1989.
Winnie AP, Ramamurty S, Durrani Z: The inguinal paravascular technic of lumbar plexus anesthesia. The “3-in-1
80.
block.” Anesth Analg 52:989, 1973.
Khoo ST, Brown TCK: Femoral nerve block—the anatomical basis for a single injection technique. Anaesth
81.
Intensive Care 11:40, 1983.
82. McNicol LR: Lower limb blocks in children. Anaesthesia 41:27, 1986.
Wedel DJ: Femoral and lateral femoral cutaneous nerve block for muscle biopsies in children. Reg Anesth 14:S63,
83.
1989.
Dalens B, Vanneuville G, Tanguy A: Comparison of the fascia iliaca compartment block with the 3-in-1 block in
84.
children. Anesth Analg 69:705, 1989.
Paut O, Sallabery M, Schreiber-Deturmeny, et al: Continuous fascia iliaca compartment block in children: A
85.
prospective evaluation of plasma bupivacaine concentrations, pain scores, and side effects. Anesth Analg 92:1159,
2001.
86. McNicol LR: Sciatic nerve block for children. Anaesthesia 40:410, 1985.
87. Chelly JE, Delaunay L: A new approach to the sciatic nerve block. Anesthesiology 91:1655, 1999.
Konrad C, Johr M: Blockade of the sciatic nerve in the popliteal fossa: A system for standardization in children.
88.
89. Carrell ED, Eyring EJ: Intravenous regional anesthesia for childhood fractures. J Trauma 11:301, 1971.
90. Fitzgerald B: Intravenous regional anesthesia in children. Br J Anaesth 48:485, 1976.
Circumcision policy statement. American Academy of Pediatrics. Task force on Circumcision. Pediatrics 103:686,
91.
1999.
Burke D, Joypaul V, Thomson MF: Circumcision supplemented by dorsal penile nerve block with 0.75%
92.
ropivacaine: A complication. Reg Anesth Pain Med 25:424, 2000.
Hannallah RS, Broadman LM, Belman AB, et al: Comparison of caudal and ilioinguinal/iliohypogastric nerve
93.
blocks for control of post-orchidopexy pain in pediatric ambulatory surgery. Anesthesiology 66:832, 1987.
Dalens B, Ecoffey C, Joly A, et al: Pharmacokinetics and analgesic effect of ropivacaine following
94.
ilioinguinal/iliohypogastric nerve block in children. Paediatr Anaesth 11:415, 2001.
95. Reiestad F, Stromskag KE: Intrapleural catheter in the management of postoperative pain. Reg Anesth 11:89, 1986.
McIlvaine WB, Knox RF, Fennessey PV, Goldstein M: Continuous infusion of bupivacaine via intrapleural
96.
catheter for analgesia after thoracotomy in children. Anesthesiology 69:261, 1988.
Lonnqvist PA, Olsson GL: Paravertebral vs epidural block in children: Effects on postoperative morphine
97.
requirement after renal surgery. Acta Anaesthesiol Scand 38:346, 1994.
486
Eng J, Sabanathan S: Continuous paravertebral block for post-thoracotomy analgesia in children. J Pediatr Surg
98.
26:556, 1992.
Lonnqvist PA, MacKenzie J, Soni AK, Conacher ID: Paravertebral blockade: Failure rate and complications.
99.
Anaesthesia 50:813, 1995.
100. Gunter J: Caudal anesthesia in children: A survey. Anesthesiology 75:A936, 1991.
101. Ross AK, Eck JB, Tobias JD: Pediatric regional anesthesia: Beyond the caudal. Anesth Analg 91:16, 2000.
Ecoffey C, Samii K: Complication neurologique après anesthésie péridurale chez un enfant. Ann Fr Anesth
102.
Reanim 9:398, 1990.
Bourlon-Figuet S, Dubousset AM, Benhamou D, Mazoit JX: Transient neurologic symptoms after epidural
103.
analgesia in a five-year-old child. Anesth Analg 91:856, 2000.
487
Section IV - Chapter 22 - Efficacy of Regional versus General Anesthesia
Chapter 22 - Efficacy of Regional versus General Anesthesia
DONALD H. LAMBERT
P. PRITHVI RAJ
General anesthesia is the most common anesthetic for surgical procedures. Inhalation and balanced general
anesthesia have many advantages. They are easy to perform, can be employed for any type of surgical procedure,
and their onset and reversal are rapid.
Nonetheless, recent clinical studies demonstrate that regional anesthesia is better than general anesthesia for certain
operations, and the use of regional anesthesia is increasing. However, regional anesthesia is limited. It is not
appropriate for all surgical procedures, it requires skill, and its onset and recovery are sometimes slower than with
general anesthesia. On the other hand, in selected patients, regional anesthesia is associated with fewer perioperative
complications.
This chapter reviews the clinical studies that compare the efficacy and safety of general and regional anesthesia
during the intraoperative and postoperative periods.
Intraoperative Period
EFFICACY OF GENERAL VERSUS REGIONAL ANESTHESIA
Both general and regional anesthesia provide effective pain relief intraoperativly if the anesthesiologist is skilled in
the performance of either type of anesthesia.
TOURNIQUET PAIN
Several studies have compared the effects of general, epidural, and spinal anesthesia on tourniquet pain during lower
extremity orthopedic operations. Valli and Rosenberg reported an increase in systolic or diastolic arterial pressure
[1]
greater than 30% of the control value in 8 of 15 patients given enflurane inhalation anesthesia. In contrast, no patient
given bupivacaine spinal anesthesia, and only 1 patient of 15 given bupivacaine epidural anesthesia, showed this
increase in blood pressure. However, 11 patients in the epidural group and 1 patient in the spinal group experienced
some pain in response to the tourniquet or to surgery and required additional parenteral analgesia.
Rocco and colleagues reported a similar result in patients who received enflurane or halothane general anesthesia.
[2]
In this study, there was no correlation between the tourniquet-induced blood pressure elevation and plasma levels of
epinephrine, norepinephrine, or glucose.
Tourniquet pain is believed to result from activation of small unmyelinated nociceptive C fibers. Presumably, the
increase in blood pressure seen with general anesthesia indicates pain perception in the unconscious patient. The
reason for the absence of a rise in blood pressure in patients under epidural anesthesia who do complain of pain may
be that a decrease in peripheral vascular resistance occurs as a result of epidurally induced sympathetic blockade.
Kohro and associates used the thromboelastogram to determine hypercoagulability in patients receiving
[3]
sevoflurane and N2 O or epidural anesthesia during orthopedic operations in which tourniquets were used.
Hypercoagulation increased significantly after tourniquet inflation in the sevoflurane group but did not change in the
epidural anesthesia group. After tourniquet deflation, thromboelastograph values increased significantly in both
groups but significantly less so in the epidural group. These authors concluded that the hypercoagulability seen with
general anesthesia could be caused by surgical or tourniquet pain, or both, and that epidural anesthesia is a useful
technique for preventing it.
EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY
Several studies have compared the efficacy of general anesthesia with epidural and spinal anesthesia for immersion
extracorporeal shock wave lithotripsy. There was essentially no difference among the three forms of anesthesia in
[4] [5]
488
terms of the degree of stone movement, which might have affected the success rate during the lithotripsy therapy.
Epidural and spinal anesthesia had the advantage of awake patients who could cooperate in the transfer from bed to
bath. The regional anesthetic techniques also diminished the dangers associated with maintaining general anesthesia
in a relatively inaccessible area. On the other hand, epidural anesthesia required longer preparation than either
general or spinal anesthesia. The changes in blood pressure during bath immersion were similar in the various
groups, although the blood pressure response varied more in the general anesthesia group. [6]
Nonimmersion lithotripsy has now come into vogue. Unlike the earlier immersion lithotripsy devices, the newer
machines are less painful and many patients undergo lithotripsy with intravenous sedation alone. Unfortunately,
randomized, blinded trials have shown that topical EMLA cream, a eutectic mixture of prilocaine and lidocaine, did
not decrease nonimmersion lithotripsy pain. [7]
OBSTETRIC ANESTHESIA
Regional anesthesia is preferable to general anesthesia during labor and delivery. The use of continuous epidural
analgesia for labor has significantly improved patient comfort, and, moreover, it is inappropriate to use general
anesthesia for the control of pain associated with labor. Both epidural and spinal anesthesia have proved to be
advantageous for both vaginal and cesarean section deliveries. Although general anesthesia can be employed in
these situations, patients usually prefer to be awake for the delivery, and there are considerable psychological
advantages for them to participate in the birth.
Management of the airway and respiratory system during general obstetric anesthesia is a major cause of morbidity
and mortality. Thus, regional anesthesia, without excessive sedation, eliminates a major source of morbidity and
mortality. Data concerning maternal mortality have been available for many years. Maternal deaths directly [8] [9] [10]
attributable to anesthesia are shown in Figure 22–1 . Sixty-three percent of these deaths were caused by inhalation of
gastric contents or from esophageal intubation, owing to general anesthesia.
On the other hand, a complication of obstetric epidural anesthesia is the accidental intravascular injection of highly
lipid-soluble local anesthetics (bupivacaine and etidocaine). A number of maternal deaths, attributed to pregnancy-
enhanced cardiotoxic effect of these local anesthetics, were reported in the late 1970s and early 1980s. After these [11]
reports, the United States (US) Food and Drug Administration recommended that anesthesiologists avoid 0.75%
bupivacaine in pregnant
Figure 22-1 Categories of maternal deaths in England and Wales directly attributable to anesthesia between 1973 and 1981. Miscellaneous causes included allergic
reaction, inadequate reversal of muscle relaxants, intravenous overload, and postoperative asphyxial episodes.(Data from Tomkinson J, Turnbull A, Robson G, et al:
Report on confidential enquiries into maternal deaths in England and Wales [1973–1975]. London, Her Majesty’s Stationery Office, 1979; Tomkinson J, Turnbull A,
Robson G, et al: Report on confidential enquiries into maternal deaths in England and Wales [1976–1978]. London, Her Majesty’s Stationery Office, 1982; Turnbull
A, Tindall V, Robson G, et al: Report on confidential enquiries into maternal deaths in England and Wales (1979–1981). London, Her Majesty’s Stationery Office,
1986.)
women. Careful titration of lower concentrations of bupivacaine during induction of epidural anesthesia has nearly
eliminated these accidents.
In obstetric anesthesia, the number of regional anesthetic procedures exceeds that of general anesthesia. This is
partly the result of our understanding that the parturient has an increased risk for aspiration of gastric contents
during general anesthesia. However, it is also because of the patient’s desire to participate in the birthing process. As
489
a result, approximately 70% to 80% of anesthetic procedures for childbirth use regional anesthetics. Despite this,
there are fewer fatalities associated with spinal anesthesia, whereas deaths related to general and epidural anesthesia
have shown relative increases. [12]
In a US report published in 1997, Hawkins and coworkers found that anesthesia-related maternal mortality rate
[13]
decreased from 4.3 per million between 1979 and 1981 triennium to 1.7 per million from 1988 to 1990. For the
periods from 1979 to 1984 and 1985 to 1990, the number of US deaths involving general anesthesia remained stable
at 33 per million and 32 per million, respectively, but the number of regional anesthesia-related deaths decreased
from 19 per million to 9 per million, respectively. More importantly, during these time periods, the estimated rate of
death during cesarean section with general anesthesia increased from 20 per million to 32.3 per million. In contrast,
the rate of death during cesarean section with regional anesthesia decreased from 8.6 per million to 1.9 per million.
Between 1979 and 1984, the risk of death during cesarean delivery with general anesthesia was 2.3 times higher
than that for regional anesthesia. From 1985 to 1990, the death rate with regional anesthesia decreased, whereas the
use of regional anesthesia for cesarean section delivery increased. Therefore, the risk of death with general
anesthesia was then 16.7 times greater than that for regional anesthesia. [13]
This analysis of maternal mortality statistics shows that the major cause of anesthesia morbidity and mortality is
difficulty in managing the airway and respiratory system. The data suggest that regional anesthetics, although not
devoid of problems, may decrease morbidity and mortality by eliminating the need to secure the airway and manage
ventilation.
Cardiovascular Effects of General versus Regional Anesthesia
NORMOVOLEMIC PATIENTS
The cardiovascular effects of regional anesthesia are well documented. Peripheral nerve blocks rarely cause
[14] [15] [16]
significant hemodynamic changes, whereas the hemodynamic alterations caused by spinal and epidural anesthesia
depend on the sensory level of anesthesia. For example, spinal anesthesia to the T5 dermatome level decreases mean
arterial blood pressure by 21.3%, although the decline in total peripheral resistance is only 5%. The hypotension
seen with spinal anesthesia is, therefore, caused by a decrease in cardiac output, which averages 17.7%. This fall in
cardiac output is apparently the result of a 25.4% decrease in stroke volume owing to venodilatation. All of these
[16]
cardiovascular effects associated with spinal anesthesia are direct results of preganglionic sympathetic blockade, and
the degree of cardiovascular depression is directly proportional to the level of sympathetic blockade.
Sympathetic blockade occurs also with epidural anesthesia. In most patients, the cardiovascular changes are minimal.
However, profound hypotension may be observed in some individuals. The changes in blood pressure, heart rate,
and cardiac output relate to the level of blockade, the amount of drug administered, the local anesthetic agent used,
the inclusion of epinephrine in the anesthetic solution, and the cardiovascular status of the patient.
As is the case with spinal anesthesia, the level of sympathetic blockade with epidural anesthesia determines the
amount of hypotension. Blockade below the T5 dermatome seldom produces hypotension because of compensatory
vasoconstriction in unblocked segments. Higher blocks not only prevent compensatory vasoconstriction but also
block the cardiac sympathetic nerves that arise in the T1 to T4 segments. Blocks at these dermatomes may decrease
heart rate and cardiac output. The blockade of sympathetic fibers to the heart without block of the vagus nerves can
cause vasovagal reactions that result in profound bradycardia and transient cardiac arrest in some patients. This so-
called vasovagal reaction may be the most common cause of profound hypotension after high levels of epidural or
spinal anesthesia. The venous capacitance vessels are also affected by sympathetic blockade. Pooling can occur if
the head-up position or an enlarged uterus obstructs venous return. Thus, patients are very sensitive to head-up
posture during spinal or epidural anesthesia because this causes expansion of the capacitance vessels and a marked
decrease in venous return and cardiac output.
Relatively large amounts of local anesthetic drugs are required to achieve satisfactory epidural anesthesia. Local
anesthetic agents that are rapidly absorbed from the epidural space may produce systemic effects involving the
cardiovascular system. For example, blood levels of lidocaine greater than 4 µg/mL can cause hypotension in part
because of negative inotropic action and peripheral vasodilatation.
Variation in the onset of epidural anesthesia is a function of the agent employed. Rapidly acting chloroprocaine and
etidocaine cause more hypotension because of rapid blockade of sympathetic fibers.
490
Severe hypotension may occur with epidural anesthesia if the local anesthetic contains epinephrine. The systemic
absorption of epinephrine stimulates β-adrenergic receptors in peripheral vascular beds, leading to vasodilatation
and hypotension. Epinephrine’s β-adrenergic receptor effect produces an increase in heart rate and cardiac output
that counteracts the peripheral vasodilatation. Although absorbed epinephrine may be responsible for the early
cardiovascular changes of epidural block; prolonged hypotension seen with local anesthetics containing epinephrine
is probably caused by sympathetic blockade.
HYPOVOLEMIC PATIENTS
Cardiovascular depression is more severe and more dangerous when epidural anesthesia is given to hypovolemic
subjects. Epidural anesthesia in mildly hypovolemic volunteers causes profound hypotension and bradycardia. [17]
Compensatory vasoconstriction caused by hypovolemia is stopped by sympathetic blockade, and cardiovascular

collapse may ensue. In hypovolemic subjects, the addition of epinephrine to the anesthetic solution results in less
severe hypotension. However, the positive inotropic action of absorbed epinephrine does not completely counteract
the hypotensive effect of epidural blockade caused by the reduced circulating blood volume in these patients.
GYNECOLOGIC SURGERY
The cardiovascular effects of halothane anesthesia and epidural anesthesia with 1.5% lidocaine were evaluated in
healthy females during elective gynecologic surgery. After the induction of general anesthesia, there was a 9%
[18]
decrease in mean arterial pressure owing to a 12% fall in cardiac output, and minimal change in systemic vascular
resistance. Epidural anesthesia extending to the T6 dermatome caused a 20% decrease in mean arterial pressure
resulting from a 24% decrease in systemic vascular resistance with no change in cardiac output. The decline in
blood pressure associated with general inhalation anesthesia was, therefore, due to depression of myocardial
contractility rather than to a decrease in peripheral vascular resistance. On the other hand, hypotension during
epidural anesthesia is caused by sympathetic blockade, resulting in a decrease in peripheral vascular resistance
without myocardial depression.
This study assessed also the effect of combining general and regional anesthesia. The combination of halothane
anesthesia plus epidural blockade produced a 28% decrease in mean arterial pressure owing to a 15% fall in cardiac
output and a 17% decrease in systemic vascular resistance.
AORTIC BYPASS SURGERY
A comparison of neuroleptic anesthesia and thoracic epidural anesthesia with bupivacaine was carried out in patients
who were undergoing aortic bypass surgery. Neither anesthetic was associated with severe hemodynamic
[19]
alterations. Another comparative study of lumbar epidural anesthesia and neuroleptic anesthesia in geriatric patients
failed to show significant changes in hemodynamic parameters with use of either anesthetic. The results of these
[20]
investigations indicate that in uncomplicated surgical patients, inhalation general anesthesia, neuroleptic anesthesia,
and epidural anesthesia are not associated with any clinically significant cardiovascular changes.
On the other hand, a study comparing the cardiovascular effects of neuroleptic anesthesia with those of thoracic
epidural anesthesia combined with light general anesthesia in patients with a recent history of myocardial infarction,
who were undergoing major abdominal vascular surgery, disclosed significant intraoperative hemodynamic
differences. Mean pulmonary artery occlusion pressures of greater than 18 torr were observed in 73% of the
[21]
neuroleptic anesthesia patients compared with 17% in the epidural group. Decreases in coronary vascular resistance
greater than 25% occurred in 59% of the neuroleptic anesthesia patients compared with 13% of the epidural patients.
All of the neuroleptic anesthesia patients demonstrated an increase in myocardial oxygen consumption of greater
than 25% compared with only one patient in the epidural group. Fifty percent of the neuroleptic anesthesia patients
showed ST-T segment depression greater than 1 mm compared with 13% in the epidural group. Ventricular
arrhythmias developed intraoperatively in 36% of the neuroleptic anesthesia patients compared with only 8% of the
epidural patients. These results suggest that patients with cardiac disease who undergo major noncardiac surgery
may develop more serious hemodynamic alterations and may be at greater risk of myocardial ischemia and
ventricular arrhythmias with general anesthesia than when epidural with light general anesthesia is employed.
INTRAOPERATIVE BLOOD LOSS
Many studies have evaluated blood loss during various operations performed with general or regional anesthesia. In
1977, Keith reported 50% less blood loss during total hip replacement with epidural anesthesia than with inhalation
[22]
491
anesthesia. However, this was an uncontrolled and retrospective study. Since then, many controlled studies have
evaluated intraoperative blood loss during total hip replacement. In one study, the average intraoperative blood loss
was 20% to 40% less with epidural or spinal anesthesia than with general anesthesia. [23]
Other studies have compared blood loss during nonorthopedic operations with general or regional anesthesia. Blood
loss was reduced by 37% during retropubic prostatectomy and by 18% during transurethral prostatectomy performed
under regional anesthesia compared with general anesthesia. In another study of retropubic prostatectomy, the
[24] [25]
blood loss with epidural anesthesia was 1490 mL compared to 1940 mL with general anesthesia and 1810 mL with
combined epidural-general anesthesia. Because there was no difference in the amount of blood loss between the
[26]
epidural and the epidural–general anesthesia groups, the authors concluded that epidural anesthesia did not reduce
bleeding but that general anesthesia increased blood loss. Spinal anesthesia reduced intraoperative blood loss 45%
during abdominal hysterectomy. Studies of other abdominal operations have not shown any difference in the
[9]
amount of blood loss with general or regional anesthesia. [28]
The diminished bleeding observed with regional anesthesia may relate to hypotension caused by sympathetic
blockade. For example, Modig and colleagues reported that lumbar epidural anesthesia resulted in a 13% decrease
[29]
in mean arterial pressure, a 21% decrease in mean pulmonary artery pressure, and a 44% decrease in mean right
atrial pressure. In addition, peripheral venous pressure was also significantly reduced in patients who received
lumbar epidural anesthesia compared with those who received general anesthesia.
It is postulated that reduced mean arterial blood pressure causes less surgical arterial bleeding. Furthermore, the
decrease in central venous pressure and lower peripheral venous pressure reduces venous bleeding. Hypotensive
general anesthesia reduces intraoperative blood loss during total hip replacement as well. Although the decreased
blood loss with epidural or spinal anesthesia may be related to decreased mean arterial and venous pressure, another
study found that decreased blood loss with epidural anesthesia was not associated with a significant reduction in
blood pressure. Therefore, the reduction in blood loss during epidural or spinal anesthesia could be the result of a
[29]
redistribution of blood away from the operative site. [22]
Several studies have documented significantly fewer transfusions during certain operations performed with regional
rather than general anesthesia. However, other studies have not confirmed this finding.
[23] [26]
Any reduction in [30] [31]
intraoperative transfusions owing to use of regional anesthesia would clearly be helpful because of the critical
shortage of banked blood and because many patients fear the possibility of contracting AIDS or hepatitis as a result
of blood transfusion.
Postoperative Period
CARDIOVASCULAR COMPLICATIONS
One of the greatest challenges facing anesthesiologists is the anesthetic management of patients with cardiac disease
who require major surgery. Despite the challenge, there are a few prospective, randomized studies in these patients
that have examined the efficacy of regional versus general anesthesia.
Reiz and associates were the first to study postmyocardial infarction patients requiring emergent major abdominal
[21]
surgery. This study compared neuroleptic anesthesia with epidural anesthesia combined with light general anesthesia.
As mentioned earlier, they found significant intraoperative differences in the two groups with regard to various
hemodynamic parameters ( Table 22–1 ). There was no difference in frequency of perioperative myocardial
infarction or 1-month postoperative mortality between the two groups. Two patients in the neuroleptic anesthesia
group and one patient in the epidural group suffered myocardial infarction intraoperatively, whereas three patients in
the neuroleptic anesthesia group developed myocardial infarction in the first postoperative week. Two patients in the
neuroleptic anesthesia group and one patient in the epidural group died in the first postoperative month. The results
suggest a higher incidence of perioperative reinfarction in the general anesthesia group.
In a study of high-risk patients having major surgery, the patients were randomized to receive either general or
epidural–general anesthesia. Postoperatively, pain was relieved with systemic narcotics in the general anesthesia
[82]
group and with epidural narcotics in the epidural–general anesthesia group. Patients who
492
TABLE 22-1 -- INTRAOPERATIVE CARDIOVASCULAR ALTERATIONS IN PATIENTS WITH CARDIAC DISEASE
Neuroleptic (%) TEA * (%)

Authors (yr) Parameter (No.= 22) (No.= 23)
Reiz et al (1982) Mean pulmonary wedge >18 mm Hg 73 17
Decrease in coronary vascular resistance > 25% 59 13
Increase in myocardial oxygen consumption > 25% 100 4
ST-T depression > 1 mm 50 13
Ventricular dysrhythmias 36 8
(No.= 25) (No.= 28)

Yeager et al (1987) Myocardial infarction 12 0
Congestive heart failure 40 4
Modified from Reiz S, Balfors E, Sorenson M, et al: Coronary hemody namic effects of general anesthesia and surgery: Modification by epidural analgesia in
patients with ischemic heart disease. Reg Anesth 7S:S8–S18, 1982; and from Yeager MP, Glass DD, Neff RK, et al: Epidural anesthesia and analgesia in high-risk
surgical patients. Anesthesiology 66:729, 1987.
*Thoracic epidural anesthesia (TEA) combined with light general anes thesia.
received epidural–general anesthesia suffered fewer postoperative episodes of congestive heart failure (see Table
22–1 ).
Damask and coworkers, using hemodynamic monitoring, randomized patients to receive either general or
[33]
epidural anesthesia during peripheral vascular operations. There was a significant reduction in the determinants of
myocardial oxygen consumption in the group that received epidural anesthesia, and these effects persisted into the
early postoperative period.
In a retrospective study, Manolio and colleagues found a higher incidence of myocardial ischemia and infarction in
[34]
patients having lower extremity vascular operations with regional rather than general anesthesia. However, Tuman
and associates prospectively studied 80 patients undergoing lower extremity vascular operations. They randomized
[35]
the patients to receive general anesthesia combined with postoperative epidural analgesia or general anesthesia with
on-demand narcotic analgesia. Compared with controls, the vascular surgical patients were hypercoagulable before
operation and on the first postoperative day. Postoperatively, the hypercoagulability was attenuated in the general–
epidural group and was associated with fewer thrombotic events; moreover, there were fewer thromboses in
peripheral arterial grafts, coronary arteries, or deep veins. The rates of cardiovascular, infectious, and overall
postoperative complications, as well as duration of intensive care unit stay, were significantly reduced in the
general–epidural group. Stepwise logistic regression demonstrated that the only significant predictors of
postoperative cardiovascular complications were preoperative congestive heart failure and general anesthesia
without epidural analgesia. These results are very similar to those observed by Yeager and colleagues. Both studies [32]
continued regional analgesia into the postoperative period.
Baron and associates investigated high-risk patients but failed to find fewer cardiovascular complications with
[36]
epidural anesthesia or analgesia. However, postoperative analgesia techniques were not controlled or randomized.
Hjortso and coworkers studied patient populations at lower risk and Christopherson and colleagues studied a
[31] [37]
high-risk population undergoing less invasive infrainguinal revascularizations. The incidence of myocardial
morbidity in both studies was low and neither identified significant effects on cardiac morbidity related to the type
of anesthesia used. Intraoperative and postoperative epidural analgesia appears to reduce perioperative cardiac
morbidity only in high-risk patients undergoing major operations. [38]
In a study of 423 patients having lower extremity vascular operations, Bode and associates prospectively studied [39]
the effects of general, spinal, and epidural anesthesia. Cardiovascular morbidity and overall mortality were not
significantly different between groups when analyzed by either intention to treat or type of anesthesia received. The
instances of cardiac event or death for the general, spinal, and epidural groups were 16.7%, 21.3%, and 15.4%,
respectively. The authors concluded that the choice of anesthesia did not significantly influence cardiac morbidity
and overall mortality. Unfortunately, these patients underwent peripheral infrainguinal femoral-distal bypass
operations, and regional analgesia was not continued into the postoperative period.
These data indicate the potential benefits of regional anesthesia for patients with cardiovascular disease, especially
those undergoing major operations for whom analgesia continues postoperatively. Nevertheless, the number of
493
prospectively randomized studies and the number of patients in these studies are small, and additional studies are
required to substantiate this beneficial aspect of regional anesthesia. Furthermore, continuing regional analgesia into
the postoperative period may well be the most important treatment for improving outcome in critically ill patients.
THROMBOEMBOLIC COMPLICATIONS
Several studies have indicated that lumbar epidural and spinal anesthesia may decrease the incidence of
TABLE 22-2 -- INCIDENCE OF POSTOPERATIVE THROMBOEMBOLIC DISEASE

Specialty Deep Vein Thrombosis (%) Pulmonary Embolism (%)
General surgery 19–25 2
Orthopedics 20–70 4–18
Gynecology/Obstetrics 7–45 2
Neurosurgery 9–50 1–3
Urology 10–40 1
Modified from Modig J, Burg T, Karlstrom G, et al: Thromboembolism after total hip replacement. Role of epidural and general anesthesia. Anesth Analg 62:174–
180, 1983.
deep vein thrombosis (DVT) and pulmonary embolism, particularly after total hip replacement. [24] [29] [31] [40] [41] [42] [43] [45]
Three recent meta-analyses confirm the usefulness of epidural anesthesia in preventing DVT in patients having
surgery for hip fracture or replacement. The reduced incidence of thromboembolism is believed to result from
[46] [47] [48]
increased blood flow in the lower extremities, a reduction in coagulation tendency, and improved fibrinolytic
function. Local anesthetics have been shown to interact with leukocytes, platelets, erythrocytes, plasma proteins, and
endothelial cells, thus decreasing the risk of thromboembolism.
Table 22–2 shows the incidence of postoperative thromboembolic disease associated with various operations, and
Table 22–3 shows the incidence of thromboembolic complications in orthopedic operations. Thromboembolic [22]
complications represent major morbidity for surgical patients in general and orthopedic patients in particular.
Thromboembolic complications, verified by phlebography or 125-I-fibrinogen/scan are reduced by 50% to 60%

when hip surgery is performed with lumbar epidural anesthesia ( Table 22–4 ). A similar reduction occurs during
prostatectomy. On the other hand, abdominal operations show no significant reduction in thromboembolic
[24]
complications when regional anesthesia is compared with general anesthesia. This discrepancy [28] [41]
TABLE 22-3 -- INCIDENCE OF THROMBOEMBOLIC COMPLICATIONS IN ORTHOPEDIC SURGERY

Fatal Pulmonary Embolism
Deep Vein Thrombosis (%) Pulmonary Embolism (%) (%)
Trauma ?20 ?10 ?1
Hip fracture 11–74 4 4–10
Total hip replacement 40–58 34–75 2–3
Total knee replacement 50–70 18 1
Modified from Modig J, Borg T, Karlstrom G, et al: Thromboembolism after total hip replacement. Role of epidural and general anesthesia. Anesth Analg 62:174–
180, 1983
TABLE 22-4 -- INCIDENCE OF POSTOPERATIVE THROMBOEMBOLIC COMPLICATIONS
Incidence of Thromboembolism (%)

Authors Surgical Procedure Regional General Significance
Davis et al (1981) Acute hip surgery 46 77 S
Modig et al (1981) Hip replacement 20 73 S
Hendolin et al (1981) Prostatectomy 12 52 S
Hendolin et al (1982) Cholecystectomy 17 13 NS
Modig et al (1983) Hip replacement 40 77 S
Mellbring et al (1983) Abdominal 38 38 NS
Hjortso et al (1984) Abdominal 34 32 NS
Data from references [40] [44] [24] [41] [29] [28] and [31]
494
may be due to the use of thoracic epidural anesthesia in two of the abdominal studies. Thoracic epidural anesthesia
does not increase lower limb flow to the same degree as lumbar anesthesia. Furthermore, in one abdominal
operation study, the control group received low-dose heparin treatment, whereas the regional anesthesia group did
not. Because there was no difference in thromboembolic complications in this study, this information suggests that
[31]
regional anesthesia may be as effective as low-dose heparin in preventing thromboembolism.
PULMONARY COMPLICATIONS
Because of a lack of well-controlled studies, the role of regional anesthesia in preventing postoperative pulmonary
complications is unclear. Nevertheless, extending the use of continuous epidural analgesia into the postoperative
period may increase functional residual capacity and improve postoperative pulmonary function. Increased
functional residual capacity improves the relationship between lung closing volume and tidal volume and lessens the
likelihood of atelectasis.
Table 22–5 lists studies showing that epidural or spinal anesthesia decreases pulmonary complications after
cholecystectomy, peripheral vascular surgery, or major thoracoabdominal/vascular surgery in high-risk patients. [32] [49]
Several studies that examined high-risk patients found decreased postoperative pneumonia and respiratory
[50] [51]
failure with intraoperative and postoperative epidural analgesia. On the other hand, studies finding no
[32] [35] [50] [52]
improvement in postoperative pulmonary function from regional anesthesia did not study high-risk [31] [36] [53] [54] [55]
operations or did not control postoperative analgesia. These data suggest that regional anesthesia may improve
postoperative pulmonary function. [56]
GASTROINTESTINAL EFFECTS
Gastrointestinal motility is normally inhibited after abdominal surgery, and postoperative pain relief may itself
affect gastrointestinal function. Volunteer studies indicate that epidural anesthesia with local anesthetics does not
alter gastrointestinal motility, whereas parenteral and epidural opioids slow gastric emptying and intestinal transit
time. Postoperative pain relief with epidural local anesthetics may improve gastric emptying and intestinal motility
[57]
after abdominal operations. [58]
TABLE 22-5 -- PULMONARY COMPLICATIONS

Frequency of Frequency of Total No. of
Frequency of Pulmonary Prolonged Pulmonary
Authors Type of Anesthesia Atelectasis (%) Infection (%) Ventilation (%) Complications (%)
Pflug et al (1974) General 60 60
Epidural 35 35
Cuschieri et al (1985) IM morphine 40 24 64
IV morphine 28 20 48
Cook et al (1986) General 33 33
Spinal 16 16
Yeager et al (1987) General 24 24
Epidural 4 4
Tuman et al (1991) General 10 12.5 22.5
Epidural 33 0 2.5 2.5
IM, intramuscular; IV, intravenous.
Data from references [49] [50] [51] [32] and [35]
Three retrospective studies from St. Vincent’s Hospital in Melbourne, Australia, evaluated the effect of anesthetic
technique on the outcomes of gastrointestinal operations. These studies show that colorectal anastomotic leak and
[59]
death rates were lower with combined epidural and general anesthesia than with general anesthesia alone.
Intraoperative epidural anesthesia and continuous postoperative epidural bupivacaine analgesia achieved the lowest
leak rates, whereas the highest wound dehiscence rate was observed with postoperative epidural morphine analgesia.
495
In another retrospective study of large bowel anastomoses, the incidence of anastomotic dehiscence was 7% with
spinal anesthesia and 8% with epidural anesthesia compared with 23% for general anesthesia. The marked [60]
differences in these retrospective studies suggest a need for additional prospective studies to evaluate the role of
anesthesia in the postoperative complications associated with gastrointestinal operations.
Carpenter reviewed the role of regional anesthesia on gastrointestinal functioning in 1996. He concluded that
[61]
compared with postsurgical systemic narcotic analgesia, there is a more rapid recovery from postoperative ileus
when analgesia is provided with epidural local anesthetic or with local anesthetic–opioid combinations. Furthermore,
Carpenter suggested that the lack of benefit in many studies is likely due to the fact that the postoperative
convalescence protocols were not modified to take advantage of the earlier recovery of bowel motility. Unless there
is a determination to remove nasogastric tubes and feed patients sooner, the benefits of earlier bowel motility and,
possibly, shorter hospital stay will not be realized. In this regard, Basse and colleagues published the results
[38] [62] [63] [64]
of their investigation into the feasibility of a 48-hour postoperative stay program after colon resection. Crucial to this
treatment pathway was the elimination of the pain and stress response with continuous thoracic epidural analgesia.
Other factors included enforced early mobilization and enteral nutrition and a planned 48-hour postoperative
hospital stay. Normal gastrointestinal function (defecation) occurred within 48 hours in 57 of the 60 patients studied,
and the median hospital stay was 2 days, with 32 patients staying 2 days after surgery.
MENTAL FUNCTIONING
There were a few reports in the early to mid-1980s that indicated less mental dysfunction in elderly patients given
regional rather than general anesthesia. However, the data on this topic are conflicting. Some investigators found
[22] [62]
that patients who had limb operations with spinal or epidural anesthesia recovered more quickly than patients who
received general anesthesia. Furthermore, other investigators indicated that after general anesthesia patients tended
to be more drowsy, more sedated, and, on occasion, found to suffer greater mental changes compared with patients
who received regional anesthesia. Overall, they found that both regional and general anesthesia caused modest
postoperative mental dysfunction. [66]
In a study of major noncardiac surgery in 1218 patients 60 years of age or older, which was published in 1998,
Moller and associates detected postoperative cognitive dysfunction in 266 patients (25.8%) at 1 week and in 94
[67]
patients (9.9%) at 3 months. This compared with 3.4% and 2.8%, respectively, in controls. Increasing age, duration
of anesthesia, limited education, a second operation, postoperative infections, and respiratory complications were
risk factors for early postoperative cognitive dysfunction, but only age was a risk factor for early postoperative
cognitive dysfunction. Unfortunately, patients in this study were not randomized to receive regional or general
anesthesia. Decrements in postoperative cognition appeared to be due more to the magnitude and duration of the
operation and resulting complications than to anesthesia per se. On the other hand, cognitive function reaches its
nadir in the postoperative period, and effects of postoperative use of epidural analgesia have not been evaluated.
CONVALESCENCE AND HOSPITAL STAY
Scott and Kehlet reviewed the effect of anesthetic technique on postoperative ambulation and hospital stay. Table
[83]
22–6 shows the results of a number of studies on postoperative ambulation and length of hospitalization. [25] [32] [49] [68] [69] [70]
All of these studies found a small, finite decrease in hospital stay with regional anesthesia. Unfortunately, the
[71]
operation and the type of regional anesthesia varied, and only one study showed a significant decrease in hospital
stay. However, the combined mean 1.6 day decrease in hospital stay (16%) suggests the value of regional
[32]
anesthesia in minimizing convalescence. Partial block of the stress response may have only limited effects on
[23]
convalescence and hospital stay, whereas totally inhibiting the stress response may prove more effective.
The current impact of managed care has underlined the value of limiting hospitalization in terms of patient
satisfaction and insurance costs. This trend has led to so-called fast tracking of patients with certain diagnoses, and
regional anesthesia has played a role in hastening discharges. For example, the use of thoracic epidural anesthesia
and analgesia decreases the length of hospitalization for colon resection. Likewise, performance of carotid
[64]
endarterectomy and thyroidectomy with use of regional anesthesia decreases the length of hospitalization
[72] [73]
associated with these operations.
496
TABLE 22-6 -- LENGTH OF HOSPITAL STAY

Authors No. of Patients Type of Anesthesia Hospital Stay (days) General vs. Regional
Pflug et al (1974) 40 General vs. epidural 7.8 * vs. 4.8 *
Miller et al (1976) 20 General vs. epidural 11.1 vs. 89.2
McGowan et al (1980) 150 General vs. epidural 7.7 vs. 6.2
Crawford et al (1982) 90 Placebo vs. intercostal block 8.4 vs. 8.2
Patel et al (1983) 40 Placebo vs. infiltration 6.6 vs. 5.9
Valentin et al (1986) 508 General vs. spinal 11.0 vs. 10.9
Yeager et al (1987) 53 General vs. epidural 15.8 vs. 11.4
TOTAL (MEAN) 9.8 vs. 8.2
Data from references [49] [68] [25] [69] [70] [71] and [32]
*Not hospital stay, precisely. Day of operation subtracted from the day patient was mobile, capable of independent ambulation, and not in need of
parenteral fluids or analgesics.
STRESS RESPONSE
The stress associated with surgery causes pathophysiologic responses that peak in the postoperative period, when
postoperative morbidity is most likely to occur. Therefore, minimizing the stress response may improve the outcome.
For example, the stress reaction may adversely affect myocardial balance, promote hypercoagulability and
thrombosis, and predispose the patient to infection because of immune suppression.
Few studies have examined the roll of stress markers on postoperative morbidity. Yeager and associates measured [32]
urinary cortisol excretion as an identifier of the stress response. They found significantly less urinary cortisol and
less morbidity with regional than with general anesthesia. Christopherson and coworkers found that regional [37]
anesthesia decreased plasma catecholamines and increased patency of vascular grafts. Hjortso and colleagues [31]
observed similar morbidity and no differences in serum albumin and transferrin levels in patients given epidural or
general anesthesia. Although these few observations hint at a relationship between the stress response and
postoperative morbidity, more studies are clearly indicated.
MORBIDITY AND MORTALITY
Using prospective data of 100,000 anesthetic procedures, Cohen and associates found that 7-day mortality was [74]
associated more with patient and surgical risk factors than with anesthesia per se. The highest mortality was seen
with monitored anesthesia care and narcotic-only anesthesia. Intermediate rates were seen with intravenous and
epidural anesthesia, whereas the lowest rates were with volatile anesthesia, nerve block, and spinal anesthesia. These
data emphasize the important role of patient and surgical risk factors in mortality. In this study, factors controlled by
the anesthesiologist played a lesser role in mortality. Nevertheless, there is evidence that regional anesthesia
decreases the catabolic response elicited by surgery, injury, or trauma, which may reduce morbidity and mortality.
Emergency surgery causes greater morbidity and mortality in elderly patients than elective procedures. These
patients are often malnourished and have multiple system disease that increases morbidity and mortality. Twelve [75]
controlled studies have compared mortality after emergency hip surgery under general, spinal, or epidural anesthesia.
The data are shown in Table 22–7 . Only two of these studies demonstrated improved survival with regional
anesthesia. Pooling the results of all 12 studies shows that the early mortality rate after regional anesthesia was
[83]
6.9% versus 10.3% after general anesthesia. It should be noted that this decrease in mortality after regional
anesthesia occurred only in the short term (< 3 mo). When patients were followed for longer periods, this difference
in mortality was no longer apparent. Meta-analyses, published in 1991 and 2000, and one evidenced based report,
[23] [48]
published in 2000, confirm the reduction in early morbidity for patients with DVT and in mortality for patients
497
TABLE 22-7 -- MORTALITY STUDIES INVOLVING EMERGENCY HIP SURGERY
% Mortality
Investigator Significance No. of Patients General Spinal Observation Period
Couderc et al (1977) 100 24 14 3 mo
McKenzie et al NS (1980) 100 16 10 1 mo
White et al NS (1980) 40 0 0 1 mo
Davis NS (1981) 132 13 5 1 mo
McLaren S (1982) 84 28 7 1 mo
Wickstrom et al NS (1982) 169 6 6 1 mo
McKenzie et al S (1984) 148 16 4 2 wk
McKenzie et al NS (1984) 148 18 19 1 yr
Bigler NS (1985) 40 5 5 3 mo
Valentin et al (1986) 578 8 6 1 mo
Valentin et al NS (1986) 578 25 25 2 yr
Davis et al NS (1987) 538 6 7 1 mo
NS, not significant; S, significant.
having emergency hip operations with regional rather than general anesthesia.
Even though the reduction in morbidity and mortality with regional anesthesia lasts only a few months, that should
be reason enough to choose regional over general anesthesia in certain patients. Any short-term benefits obtained
only with regional anesthesia open the door to making them long-term reductions in morbidity and mortality via
improvements in postoperative surgical and medical care.
As mentioned earlier, Yeager and associates and Tuman and coworkers performed prospective, randomized
[32] [35]
comparisons of epidural and general anesthesia in critically ill patients. Unlike prior studies, they continued the
epidural anesthesia into the recovery period, and the regional anesthesia patients received epidural narcotics for pain
management, whereas the patients who received general anesthesia were given parenteral narcotics. Yeager found
that patients in the general anesthesia group were ventilated for longer periods and incurred more morbidity (cardiac,
pulmonary, renal) and greater cost for hospitalization. In fact, they discontinued their study because of the greater
morbidity in the general anesthesia group. Likewise, Tuman found significantly fewer cardiovascular, infectious,
thrombotic, and overall postoperative complications, as well as a shorter intensive care unit stay, with epidural
anesthesia.
The morbidity and mortality after surgery are mainly due to patient and surgical risk factors, and most studies have
not conclusively showed the effects of the type of anesthesia used. This lack may relate to the fact that anesthesia
[74]
represents only a small fraction of the patient’s illness and hospitalization. However, when the anesthetic is
continued into the recovery period, an effect on morbidity is apparent. Thus, factors such as decreased stress
response and improved pulmonary mechanics persist for longer periods and may improve morbidity and mortality.
More randomized, blinded, prospective studies are needed to substantiate this.
The meta-analysis of randomized trials reported by Rodgers and coworkers in 2000 is timely and provides a useful
[84]
ending for this topic of efficacy of regional versus general anesthesia. Rodgers’ group obtained estimates of the
effects of epidural or spinal anesthesia on postoperative morbidity and mortality by systematically reviewing all
trials, whether they included randomization to intraoperative neuraxial blockade or not. They found that overall
mortality was reduced by about a third in patients allocated to regional anesthesia (103 deaths among 4871 patients
vs. 144 deaths among 4688 patients; P = 0.006). Furthermore, regional anesthesia reduced the odds of DVT vein
thrombosis by 44%, pulmonary embolism by 55%, transfusion requirements by 50%, of pneumonia by 39%, and of
respiratory depression by 59% (all P < 0.001). The magnitude of some of these benefits is uncertain, and further
research is required to determine whether these effects are due solely to benefits of neuraxial blockade or partly to
avoidance of general anesthesia. Nevertheless, these findings support the value of regional anesthesia in preventing
complications.
498
Summary
The comparative effects of general and regional anesthesia during the intraoperative and postoperative periods have
been reviewed. There is a paucity of large, well-designed, randomized, blinded, prospective studies that compare
outcomes after general and regional anesthesia. Nevertheless, the studies that have been completed and the meta-
analyses that have been done show an advantage of regional over general anesthesia in limiting cardiovascular,
thromboembolic, pulmonary, and gastrointestinal complications. Furthermore, convalescence and hospital stay in
critically ill and even noncritically ill patients may be decreased. However, additional studies need to be done,
particularly in the area of continuing regional anesthesia into the postoperative recovery period. Any beneficial
effects of regional anesthesia are more likely to be appreciated if the regional anesthetic duration is extended.
REFERENCES
1. Valli H, Rosenberg PH: Effects of three anesthesia methods on haemodynamic responses connected with the use of thigh tourniquet in
orthopaedic patients. Acta Anaesthesiol Scand 29:142–147, 1985.
2. Rocco A, Concepcion M, Desai S, et al: The effect of general and regional anesthesia on tourniquet induced blood pressure elevation. Reg
Anesth 12:174–180, 1987.
3. Kohro S, Yamakage M, Arakawa J, et al: Surgical/tourniquet pain accelerates blood coagulability but not fibrinolysis. Br J Anaesth 80:460–463,
1998.
4. Rickford
J, Tytler J, Speedy H, et al: Comparative evaluation of general, epidural and spinal anesthesia for extracorporeal shockwave lithotripsy.
Ann R Coll Surg Engl 70:69–73, 1988.
5. Zeitlin GL, Roth RA: Effect of three anesthetic techniques on the success of extracorporeal shock wave lithotripsy in nephrolithiasis.
6. Richardson MG, Dooley JW: The effects of general versus epidural anesthesia for outpatient extracorporeal shock wave lithotripsy. Anesth
Analg 86:1214–1218, 1998.
7. GanapathyS, Razvi H, Moote C, et al: Eutectic mixture of local anesthetics is not effective for extracorporeal shock wave lithotripsy. Can J
Anaesth 43:1030–1034, 1996.
8. TomkinsonJ, Turnbull A, Robson G, et al: Report on confidential inquiries into maternal deaths in England and Wales (1973–1975). London,
Her Majesty’s Stationery Office, 1979.
9. TomkinsonJ, Turnbull A, Robson G, et al: Report on confidential enquiries into maternal deaths in England and Wales (1976–1978). London,
10. Turnbull
A, Tindall V, Robson G, et al: Report on confidential enquiries into maternal deaths in England and Wales (1979–1981). London,
11. Albright G: Cardiac arrests following regional anesthesia with etidocaine or bupivacaine. Anesthesiology 51:285–286, 1979.
12. Bassell
G, Marx G: Anesthesia-related maternal mortality. In Shnider S, Levinson G (eds): Anesthesia for Obstetrics, 2nd ed. Baltimore,
Williams & Wilkins, 1987, p 326.
13. HawkinsJL, Koonin LM, Palmer SK, et al: Anesthesia-related deaths during obstetric delivery in the United States, 1979–1990.
14. Bonica JJ, Akamatsu TJ, Berges PU, et al: Circulatory effects of peridural block. II. Effects of epinephrine. Anesthesiology 34:514–522, 1971.
15. Bonica
JJ, Berges PU, Morikawa K: Circulatory effects of peridural block. I. Effects of level of analgesia and dose of lidocaine.
16. Ward RJ, Bonica JJ, Freund FG, et al: Epidural and subarachnoid anesthesia: Cardiovascular and respiratory effects. JAMA 191:275–278,
1965.
17. Bonica
JJ, Kennedy WF, Akamatsu TJ, et al: Circulatory effects of peridural block. III. Effects of acute blood loss. Anesthesiology 36:219–
227, 1972.
18. Germann
PA, Roberts JG, Prys-Roberts C: The combination of general anesthesia and epidural block. I. The effects of sequence of induction
on haemodynamic variables and blood gas measurements in healthy patients. Anaesth Intensive Care 7(3):229–238, 1979.
19. SeelingW, Ahnefeld FW, Rosenberg G, et al: Aortofemoral bifurcation bypass—effect of anesthesia procedure (NLA, thoracic continuous
catheter, peridural anesthesia) on circulation, respiration and metabolism. Hemodynamic changes caused by peridural anesthesia and anesthesia
499
induction. Anaesthesist 34:217–228, 1985.
20. Stefansson T, Wickstrom I, Haljamae H: Effects of neurolept and epidural analgesia on cardiovascular function and tissue metabolism in the
geriatric patient. Acta Anaesthesiol Scand 26:386–392, 1982.
21. ReizS, Balfors E, Sorenson M, et al: Coronary hemodynamic effects of general anesthesia and surgery: Modification by epidural analgesia in
patients with ischemic heart disease. Reg Anesth 7S:S8–S18, 1982.
22. Keith I: Anaesthesia and blood loss in total hip replacement. Anaesthesia 32:444–450, 1977.
23. Sorensen RM, Pace NL: Mortality and morbidity of regional vs. general anesthesia: A meta-analysis [abstract]. Anesthesiology 75:a1053, 1991.
24. HendolinH, Mattila MA, Poikolainen E: The effect of lumbar epidural analgesia on the development of deep vein thrombosis of the legs after
open prostatectomy. Acta Chir Scand 147:425–429, 1981.
25. McGowan SW, Smith GFN. Anaesthesia for transurethral prostatectomy: A comparison of spinal intradural analgesia with two methods of
general anesthesia. Anaesthesia 35:847–853, 1980.
26. Shir
Y, Raja SN, Frank SM, et al: Intraoperative blood loss during radical retropubic prostatectomy: Epidural versus general anesthesia.
Urology 45:993–999, 1995.
27. Blunnie WP, McIlroy PD, Merrett JD, et al: Cardiovascular and biochemical evidence of stress during major surgery associated with different
techniques of anaesthesia. Br J Anaesth 55:611–618, 1983.
28. Mellbring
G, Dahlgren S, Reiz S, et al: Thromboembolic complications after major abdominal surgery: Effect of thoracic epidural analgesia.
Acta Chir Scand 149:263–268, 1983.
29. Modig J, Borg T, Karlstrom G, et al: Thromboembolism after total hip replacement. Role of epidural and general anesthesia. Anesth Analg
62:174–180, 1983.
30. AndrewsWW, Ramin SM, Maberry MC, et al: Effect of type of anesthesia on blood loss at elective repeat cesarean section. Am J Perinatol
9:197–200, 1992.
31. Hjortso
NC, Neumann P, Frosig F, et al: A controlled study on the effect of epidural analgesia with local anaesthetics and morphine on
morbidity after abdominal surgery. Acta Anaesthesiol Scand 29:790–796, 1985.
32. Yeager MP, Glass DD, Neff RK, et al: Epidural anesthesia and analgesia in high-risk surgical patients. Anesthesiology 66:729, 1987.
33. DamaskM, Weissman C, Barth A, et al: General vs epidural—which is the better anesthetic technique for femoral popliteal bypass surgery?
Anesth Analg 65:S39, 1986.
34. ManolioTA, Beattie C, Christopherson R, et al: Regional versus general anesthesia in high-risk surgical patients: The need for a clinical trial. J
Clin Anesth 1:414–421, 1989.
36. Baron
JF, Bertrand M, Barre E, et al: Combined epidural and general anesthesia versus general anesthesia for abdominal aortic surgery.
37. ChristophersonR, Beattie C, Frank SM, et al: Perioperative morbidity in patients randomized to epidural or general anesthesia for lower
extremity vascular surgery. Perioperative Ischemia Randomized Anesthesia Trial Study Group. Anesthesiology 79:422–434, 1993.
38. Liu S, Carpenter RL, Neal JM: Epidural anesthesia and analgesia. Their role in postoperative outcome. Anesthesiology 82:1474–1506, 1995.
39. Bode RH, Jr., Lewis KP, Zarich SW, et al. Cardiac outcome after peripheral vascular surgery. Comparison of general and regional anesthesia.
40. Davis
FM, Laurenson VG: Spinal anaesthesia or general anaesthesia for emergency hip surgery in elderly patients. Anaesth Intensive Care
9:352–358, 1981.
41. HendolinH, Mattila MA, Poikolainen E: The effect of lumbar epidural analgesia on the development of deep vein thrombosis of the legs after
open prostatectomy. Acta Chir Scand 147:425–429, 1981.
42. McKenzie PJ, Wishart HY, Gray I, et al: Effects of anaesthetic technique on deep vein thrombosis: A comparison of subarachnoid and general
anaesthesia. Br J Anaesth 57:853–857, 1985.
43. McKenzie PJ, Wishart HY, Smith G: Long term outcome after repair of fractured neck of femur. Br J Anaesth 56:581–585, 1984.
44. Modig J, Hjelmstedt E, Sahlstedt B, et al: Comparative influences of epidural and general anaesthesia on deep vein thrombosis and pulmonary
embolism after total hip replacement. Acta Chir Scand 147:125, 1981.
500
45. Modig J, Maripuu E, Sahlstedt B: Thromboembolism following total hip replacement. A prospective investigation of 94 patients with emphasis
on efficacy of lumbar epidural anesthesia in prophylaxis. Reg Anesth 11:72–79, 1986.
46. Parker
MJ, Urwin SC, Handoll HH, et al: General versus spinal/epidural anaesthesia for surgery for hip fractures in adults. Cochrane Database
Syst Rev 2:2000.
47. Sorenson RM, Pace NL: Anesthetic techniques during surgical repair of femoral neck fractures. A meta-analysis. Anesthesiology 77:1095–
1104, 1992.
48. UrwinSC, Parker MJ, Griffiths R: General versus regional anaesthesia for hip fracture surgery: A meta-analysis of randomized trials. Br J
Anaesth 84:450–455, 2000.
49. Pflug
AE, Murphy TM, Butler SH, et al: The effects of postoperative peridural analgesia on pulmonary therapy and pulmonary complications.
50. Cuschieri
RJ, Morran CG, Howie JC, et al: Postoperative pain and pulmonary complications: Comparison of three analgesic regimens. Br J
Surg 72:495–498, 1985.
51. Cook PT, Davies MJ, Cronin KD, et al: A prospective randomized trial comparing spinal anesthesia using hyperbaric cinchocaine with general
anesthesia for lower limb vascular surgery. Anaesth Intensive Care 14:373–380, 1986.
52. Rawal N, Sjostrand U, Christoffersson E, et al: Comparison of intramuscular and epidural morphine for postoperative analgesia in the grossly
obese: Influence on postoperative ambulation and pulmonary function. Anesth Analg 63:583–592, 1984.
53. Jayr
C, Mollie A, Bourgain JL, et al: Postoperative pulmonary complications: General anesthesia with postoperative parenteral morphine
compared with epidural analgesia. Surgery 104:57–63, 1988.
54. Jayr C, Thomas H, Rey A, et al: Postoperative pulmonary complications. Epidural analgesia using bupivacaine and opioids versus parenteral
55. SchulzeS, Roikjaer O, Hasselstrom L, et al: Epidural bupivacaine and morphine plus systemic indomethacin eliminates pain but not systemic
response and convalescence after cholecystectomy. Surgery 103:321–327, 1988.
56. Covino BG: Reasons to select regional anesthesia. Curr Rev Clin Anesth 7:42–47, 1986.
57. Wattwil M: Postoperative pain relief and gastrointestinal motility. Acta Chir Scand (Suppl)550:140–145, 1989.
58. Wattwil
M, Thoren T, Hennerdal S, et al: Epidural analgesia with bupivacaine reduces postoperative paralytic ileus after hysterectomy. Anesth
Analg 68:353–358, 1989.
59. Ryan P, Schweitzer S, Collopy B, et al: Combined epidural and general anesthesia versus general anesthesia in patients having colon and rectal
anastomoses. Acta Chir Scand 550 (Suppl): 146–149, 1989.
60. Aitkenhead AR, Wishart HY, Brown DAP: High spinal nerve block for large bowel anastomosis: A retrospective study. Br J Anaesth 50:177–
183, 1978.
61. Carpenter R: Gastrointestinal benefits of regional anesthesia/analgesia. Reg Anesth 21:13–17, 1996.
62. Liu
SS, Carpenter RL, Mackey DC, et al: Effects of perioperative analgesic technique on rate of recovery after colon surgery. Anesthesiology
83:757–765, 1995.
63. MoinicheS, Bulow S, Hesselfeldt P, et al: Convalescence and hospital stay after colonic surgery with balanced analgesia, early oral feeding,
and enforced mobilisation. Eur J Surg 161:283–288, 1995.
64. Basse L, Hjort Jakobsen D, Billesbolle P, et al: A clinical pathway to accelerate recovery after colonic resection. Ann Surg 232:51–57, 2000.
65. Hole
A, Terjesen T, Breivik H: Epidural versus general anesthesia for total hip arthroplasty in elderly patients. Acta Anaesthesiol Scand
24:279–287, 1980.
66. Jones MJ: The influence of anesthetic methods on mental function. Acta Chir Scand 550 (Suppl):169–175, 1989.
67. MollerJT, Cluitmans P, Rasmussen LS, et al: Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD
investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet 351:857–861, 1998.
68. Miller L, Gertel M, Fox GS, et al: Comparison of effect of narcotic and epidural analgesia on postoperative respiratory function. Am J Surg
131:291–294, 1976.
69. Crawford ED, Skinner DG: Intercostal nerve block with thoracoabdominal and flank incisions. Urology 19:25–28, 1982.
501
70. PatelJM, Lanzafame RJ, Williams JS, et al: The effect of incisional infiltration of bupivacaine hydrochloride upon pulmonary functions,
atelectasis and narcotic need following elective cholecystectomy. Surg Gynecol Obset 157:338–340, 1983.
71. ValentinN, Lomholt B, Jensen JS, et al: Spinal or general anaesthesia for surgery of the fractured hip: A prospective study of mortality in 578
patients. Br J Anesth 58:284–291, 1986.
72. Back MR, Harward TR, Huber TS, et al: Improving the cost-effectiveness of carotid endarterectomy. J Vasc Surg 26:456–462, 1997.
73. Lo Gerfo P: Local/regional anesthesia for thyroidectomy: Evaluation as an outpatient procedure. Surgery 124:975–978, 1998.
74. Cohen MM, Duncan PG, Tate RB: Does anesthesia contribute to operative mortality. JAMA 260:2859–2863, 1988.
75. Daley J, Khuri SF, Henderson W, et al: Risk adjustment of the postoperative morbidity rate for the comparative assessment of the quality of
surgical care: Results of the National Veterans Affairs Surgical Risk Study. J Am Coll Surg 185:328–340, 1997.
76. Couderc E, Mauge F, Duvaldestin P, et al: Comparative results of general and peridural anesthesia for hip surgery in the very old patient.
Anesth Analg 34:987–997, 1977.
77. McKenzie PJ, Wishart HY, Dewar MS, et al: Comparison of the effects of spinal anesthesia and general anesthesia on postoperative
oxygenation and perioperative mortality. Br J Anaesth 52:49–53, 1980.
78. White
IW, Chappell WA: Anaesthesia for surgical correction of fractured femoral neck. A comparison of three techniques. Anaesthesia
35:1107–1110, 1980.
79. McLaren AD: Mortality studies. A review. Reg Anesth 7:172S–174S, 1982.
80. WickstromI, Holmberg I, Stefansson T: Survival of female geriatric patients after hip fracture surgery. A comparison of 5 anesthetic methods.
81. Bigler
D, Adelhoj B, Petring OU, et al: Mental function and morbidity after acute hip surgery during spinal and general anaesthesia.
Anaesthesia 40:672–676, 1985.
82. DavisFM, Woolner DF, Frampton C, et al: Prospective, multi-centre trial of mortality following general or spinal anesthesia for hip fracture
surgery in the elderly. Br J Anaesth 59:1080–1088, 1987.
83. Scott NB, Kehlet H: Regional anesthesia and surgical morbidity. Br J Surg 75:299–304, 1988.
84. Rodgers
A, Walker N, Schug S, et al: Reduction of postoperative mortality and morbidity with epidural or spinal anesthesia: Results from
overview of randomized trials. B M J 321:1493, 2000.
502
Section IV - Chapter 23 - Endocrine-Metabolic Effects
Chapter 23 - Endocrine-Metabolic Effects
Henrik Kehlet
P. Prithvi Raj
Physical injury is followed by a coordinated set of responses characterized by increased fuel production and an
increased rate of metabolism, fuel utilization, and catabolism.
Although the secondary end-organ responses to injury have been well characterized in years, the biochemical basis
of the stress response is still poorly understood, in part because of the complexity of events triggered by the various
stimuli. In surgical patients, injury, pain, hemorrhage, infection, and anxiety are common stimuli that may elicit the
response, additional factors are fluid loss and tissue damage. The mediators involved in setting the injury response
in train to these stimuli are primarily neural and humoral stimuli ( Fig. 23–1 ). Afferent or efferent neural blockade
or both by various techniques of regional anesthesia, may, therefore, alter the response to surgical injury.
Figure 23-1 Release mechanisms of the injury response. The primary mediators are afferent neural stimuli, humoral mediators (monokines [e.g., interleukin, TNF]),
arachidonic cascade metabolites, and plasma protease. Secondary factors are anxiety, pain, hemorrhage, fluid loss, and infection (endotoxin)(From Kehlet H:
Endocrine-metabolic effects. In Raj PP [ed]: Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, p 188.)
The injury response is generally considered a defensive maneuver, although if continued or amplified, it may have
detrimental effects because of increased demands on various organs, catabolism, and muscle wasting, and impaired
immunofunction, among other factors. [1]
This chapter updates current information regarding the modifying effect of regional anesthetic techniques on the
surgical stress response, with an emphasis on the differential effect of anesthetic techniques during various surgical
procedures. However, clinical implications of regional anesthesia in modifying the stress response are only briefly
addressed in this chapter. No attempt is made to review the general aspects of surgical injury, for which the reader is
referred to recent reviews. Furthermore, specific references are only given in some areas of current interest,
[2] [3] [4] [5]
because the topic has been reviewed in detail. [1] [6] [7]
The modifying effect of regional anesthesia on the endocrine-metabolic response to surgery is variable and depends
on the technique of regional anesthesia ( Fig. 23–2 ). Each technique is described.
503
Peripheral Local Anesthetics
INTRAVENOUS LOCAL ANESTHETICS
The effect of intravenously administrated local anesthetics on postoperative pain and endocrine metabolic responses
is minimal. [6]
PERIPHERAL INFILTRATION/INSTILLATION OF LOCAL ANESTHETICS IN THE WOUND
Application of local anesthetics at the wound site may modify the injury response by a dual mechanism: inhibition
of an afferent neural stimulus and a reduction in afferent firing because of the anti-inflammatory effects of local
anesthetics. Although instillation or infiltration of the wound with local anesthetics may provide a variable degree
[6]
of pain relief, only a few studies
Figure 23-2 Neural blockade techniques that may influence the response to surgical injury.(From Kehlet H: Endocrine-metabolic effects. In Raj PP [ed]: Clinical
Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, p 188.)
have looked at the effect on the stress response. Incisional application of lidocaine with an aerosol provides long-
lasting pain relief as well as inhibition of the β-endorphin response. Incisional infiltration with bupivacaine may
[6]
prevent the cortisol and glucose response to herniotomy but may not modify the leukocytic or acute phase response,
even in patients whose wounds are cooled to about 15°C. No studies are available concerning the use of local
[6]
anesthetic creams on the wound postoperatively. In summary, the limited data suggest modification of some aspects
of the stress response by application of local anesthetics to the wound. However, the effect is small and short-lasting
comparable to the short-lasting pain duration.
PERIPHERAL NERVE BLOCKADES
Except for the demonstration of an inhibition of the small stress response to dental extraction, no conclusive data are
available on the modifying effect of peripheral nerve blockades on the stress response.
INTRAPERITONEAL LOCAL ANESTHETICS
In keeping with the idea that pain should be treated at the peripheral site, efforts have been made to elucidate the
effect of intraperitoneal local anesthetics, but the results have been fairly negative with regard to both pain relief and
modification of the surgical stress response. [6]
INTRAPLEURAL LOCAL ANESTHETICS

504
Intrapleural administration of bupivacaine or other local anesthetics may provide some pain relief after such
procedures as cholecystectomy and kidney surgery, but modifying the effect of the stress response and pulmonary
function is negligible.[6]
INTERCOSTAL BLOCKADE
Pain relief by pure somatic blockade with intercostal local anesthetics is well documented, but the effect on the
stress response that occurs after upper laparotomy is small or nonexistent after thoracotomy. [6]
SPLANCHNIC BLOCKADE
Although the pain-relieving effect of a pure visceral afferent blockade after abdominal surgery has not been
addressed, some reduction of intraoperative changes in cortisol, glucose, free fatty acids, and urinary epinephrine
has been demonstrated. [6]
PARAVERTEBRAL BLOCKADE
Paravertebral local anesthetic administration may provide postoperative pain relief by simultaneous somatic and
visceral neural blockade and may provide a small reduction in the catecholamine, glucose, and cortisol response to
cholecystectomy. [6]
Epidural Local Anesthetics
The majority of data that demonstrate that regional anesthesia with local anesthetics may modify the surgical stress
response come from studies in which epidural local anesthetics were used. These studies also document that most
[6] [7]
of the classic endocrine metabolic response is mediated by neural stimuli, whereas other responses (i.e.,
inflammatory responses) are generally mediated by humoral factors. [1] [6]
The effect of epidural local anesthetics on endocrine function without surgery is slight. [7]
The effect of intra- and postoperative neural blockade with epidural local anesthetic on the surgical stress response
is summarized in Figures 23–3 and 23–4 . It should be emphasized that the results shown in Figures 23–3 and 23–4
predominantly come from surgical procedures such as hysterectomy, vaginal surgery, inguinal herniotomy, minor
orthopedic procedures, prostatectomy, and hip replacement. In contrast to these studies involving surgery of the
lower half of the body, more than 25 studies on epidural local anesthetics and the stress response during procedures
in the upper abdomen and thorax have failed to show a similarly pronounced inhibitory effect. [1] [6]
Most of the studies contributing to Figures 23–3 and 23–4 have used bupivacaine, and, therefore, the question as to
the differential modulatory effect of various local anesthetic agents cannot be answered.
PITUITARY HORMONES
The well-known surgically induced increases in plasma growth hormone, arginine, vasopressin, adrenocorticotropic
hormone, pituitary α- and β-endorphin, prolactin, and thyroid-stimulating hormone are blocked or blunted by
epidural local anesthetics (see Fig. 23–3 ). In contrast, the limited data on follicle-stimulating hormone and
luteinizing hormone suggest an accelerated minor postoperative decrease in plasma concentrations.
ADRENAL AND RENAL HORMONES AND CATECHOLAMINES
In studies using rather large volumes of bupivacaine (0.5%) and a well-described neural blockade, the intra- and
postoperative increases in plasma cortisol, aldosterone, and renin, as well as catecholamines, have been inhibited.
Although no systematic studies are available, rather large doses of bupivacaine seem to be necessary to achieve
eradication of these stress parameters.
505
Figure 23-3 Effect of neural blockade on the endocrine response to surgical injury.(From Kehlet H: Endocrine-metabolic effects. In Raj PP [ed]: Clinical Practice of
Figure 23-4 Effect of neural blockade on metabolic responses to surgical injury.(From Kehlet H: Endocrine-metabolic effects. In Raj PP [ed]: Clinical Practice of
506
THYROID HORMONES
Despite inhibition of several hormonal responses, epidural local anesthetics have no effect on the surgically induced
changes in serum thyroxin (T4 ) and triiodothyronine (T3 ) levels, because these are mostly the result of decreased
binding to plasma proteins.
PANCREATIC HORMONES, SEX HORMONES, GASTROINTESTINAL HORMONES, AND

NEURAL TRANSMITTERS
Epidural bupivacaine may lead to an initial slight decrease in plasma insulin and C-peptide concentrations because
of inhibition of resting adrenergic tone to pancreatic islets. Otherwise, no important effect is seen in these hormones,
which are relatively unaffected by surgery in the initial postoperative phase if glucose is not administered. Glucose
tolerance and insulin release are improved by epidural analgesia. The postoperative increase in insulin resistance
also seems to be improved by epidural bupivacaine because postoperative glucose production and oxidation are
reduced. The effect of epidural local anesthetics on plasma glucagon is debatable. No data are available on the
[6] [8]
effect of epidural analgesia and postoperative changes in sex hormones, gastrointestinal hormones, and neural
transmitters.
GLUCOSE, LIPID, AND NITROGEN METABOLISM
Epidural local anesthetics inhibit the conventional hyperglycemic response to surgery. The underlying mechanisms
are complex and involve inhibition of the catabolic hormones, reduce hepatic glycogenolysis and effect the usual
increase in gluconeogenesis. In addition, insulin resistance and glucose tolerance are improved, and isotope turnover
studies have demonstrated reduced glucose production and oxidation. Epidural blockade facilitates whole body
[6]
glucose uptake after a glucose load. [8]
Epidural analgesia, because of inhibition of the catabolic hormone response, also inhibits the usual increase in
lipolysis, because reduced levels of plasma, free fatty acids, and glycerol concentrations have been demonstrated.
However, no data are available that directly assess lipid turnover and oxidation rates.
The postoperative change in nitrogen metabolism leading to muscle wasting is one of the classic metabolic
responses to injury, which is resistant to therapeutic manipulation by any technique (e.g., nutrition, anabolic
hormones). It is, therefore, of interest that epidural analgesia in several studies has been demonstrated to improve
postoperative nitrogen balance. Furthermore, epidural analgesia inhibits the trauma-induced profound changes in
[1] [7]
free amino acid concentrations in skeletal muscle, and studies with isotopes also suggest reduction of postoperative
urea production and new protein catabolism. However, most studies from major abdominal procedures have
[1] [6] [9]
shown a smaller modification of protein catabolism ; the reason for this is discussed in the next section.
[1] [6]
RENAL FUNCTION AND WATER, ELECTROLYTE, AND MINERAL BALANCE
As mentioned, epidural analgesia inhibits various hormones that are supposed to have an effect on water and
electrolyte balance (cortisol, aldosterone, arginine, vasopressin, renin, catecholamines), and, therefore, an important
effect may be expected on postoperative renal function and mineral balance. In addition, neural blockade from T10
to L1 may influence kidney function by inhibition of innervation.
Unfortunately, only a few studies have examined this important area, and, furthermore, differences in study design,
surgical procedures, fluid administration, and techniques of regional anesthesia impede final interpretation. However,
most studies agree that postoperative potassium balance is less negative after epidural bupivacaine, whereas the data
on sodium and water balance are discordant. Some data suggest that interstitial fluid accumulation and pressure are
[7]
reduced. The effect on calcium, magnesium, and zinc balance is unknown.
OXYGEN CONSUMPTION AND THE HYPERTHERMIC RESPONSE
As expected, because of inhibition of the catabolic endocrine response and reduction in intermediary metabolism,
epidural local anesthetics reduce postoperative oxygen consumption. Although, the hyperthermic response has been
reduced in some studies, it is not blocked even when the cortisol and glucose responses are blocked. The effect of
neural blockade on postoperative thermoregulation deserves further study; the effect on postoperative shivering is
also debatable. [6]
507
HEPATIC FUNCTION
Besides the profound effect on glucose, lipid, and nitrogen metabolism, other parameters of hepatic function (e.g.,
microsomatic enzyme activity, acute phase protein synthesis) are accelerated after surgical injury. Thus, a single
dose of epidural analgesia has no effect on hepatic microsomatic enzyme activity or origin. Epidural analgesia, even
if continued for 24 hours, also has no important effect on the acute phase protein response (transferrin, orosomucoid,
haptoglobin, fibronectin), suggesting that factors other than neural stimuli are important in mediating these
responses. The most obvious candidates at present seem to be tumor necrosis factor and interleukins.
COAGULATION AND FIBRINOLYSIS
The well-known postoperative increase in coagulability and the biphasic responses of initial increase and later
reduction in fibrinolysis are mostly uninfluenced by epidural analgesia, suggesting that mediators of humoral orgin
are effective. However, a few studies have demonstrated that the postoperative increase in fibrinolysis inhibition
activity may be blunted by epidural analgesia, and that the increase in thrombocyte aggregation may be reduced. [6]
IMMUNOCOMPETENCE
The complex postoperative changes in immunofunction are generally not modified to any significant degree by
epidural analgesia, although some studies have shown less postoperative lymphopenia as well as improved function
[6]
of T cells, natural killer cells, and monocytes. The effect on postoperative changes in complement activation as
[6]
well as neutrophil function is contradictory and probably insignificant.
LOWER VERSUS UPPER BODY OPERATIONS
The effect of epidural analgesia on the surgical stress response as summarized in Figures 23–3 and 23–4 is largely
based on studies of lower body procedures. However, a similar effective degree of inhibition of the injury response
has not been demonstrated in a large number of studies during abdominal or thoracic procedures. This discrepancy
[7]
has been attributed to unblocked vagal afferents, unblocked phrenic afferents, insufficient afferent blockade,
unblocked pelvic afferents, and other mechanisms. At present, the most plausible explanation is insufficient
[6] [10]
afferent somatic and sympathetic blockade. [6] [10]
Although the degree of sympathetic compared with somatic blockade is debatable, studies using evoked potentials to
peripheral electrical stimulation of somatic afferents suggest a variable intensity of the afferent blockade. Thus,
despite pinprick analgesia, epidural 0.25% bupivacaine (about 20–25 mL) has no important effect on evoked
potentials, in contrast to a total inhibition of fast conducting neural pathways in about 50% of patients receiving a
similar volume of epidural 0.5% bupivacaine. This is in accordance with pronounced inhibition of the surgical stress
response in lower body operations using a lumbar epidural regimen. In contrast, little inhibition of these neural
[7]
pathways could be demonstrated using a conventional thoracic epidural bupivacaine regimen with 9 mL of 0.5%
bupivacaine. Thus, because no effective epidural regimen has been described to block afferent neural stimuli in the
thoracic region, it is easy to understand why the studies available have not demonstrated any major reduction in the
surgical stress response by conventional thoracic epidural regimens. Future studies should consider higher
concentrations of local anesthetics to improve afferent blockade.
INFLUENCE OF DURATION OF EPIDURAL ANALGESIA
Single-dose neural blockade has only a short-lasting (2–5 hr) inhibitory effect on the stress response ( Fig. 23–5 ).
Data are lacking on the effect of an intermediate (6–12 hr) blockade on later postoperative responses, whereas
studies using continuous epidural analgesia for 24 hours have demonstrated a reduction of nitrogen loss during the
following 4 postoperative days, a reduction in plasma creatinine phosphokinase in the later postoperative period, and
a reduction in surgically induced changes in free concentrations of amino acids in skeletal muscles during the first
72 postoperative hours. A block of 48 hours is more effective than a 24-hour block.
[1] [6] [1] [6] [9]
508
THE MODULATORY EFFECT OF COMBINED EPIDURAL AND GENERAL ANESTHESIA
Although epidural analgesia alone has been used in most of the aforementioned studies, addition of general
anesthesia, which usually is endocrine and metabolically inert, does not change the modifying effect of regional
anesthesia on the stress response. [6]
Intrathecal Local Anesthetics
Although systematic comparative studies have not been performed, the available data suggest that the modulatory
effects of intrathecal and epidural anesthesia on the stress response are similar. However, future studies should
[6]
consider the modulatory effect of intrathecal anesthesia on the stress of upper abdominal procedures and the effect
of continuous intrathecal anesthesia.
Figure 23-5 Influence of duration of neural blockade on the stress response to surgery.(From Kehlet H: Endocrine-metabolic effects. In Raj PP [ed]: Clinical
Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, p 193.)
Epidural Intrathecal Opioids and α2 -Adrenergic Agonists
Knowledge of the modulatory mechanisms of nociceptive transmission in the spinal cord has increased
tremendously, but it is still far from complete. Of the many transmitters known to be involved in nociceptive
modulation, only various opioids and α2 agonists have been used in surgical patients.
Several studies have been published on the effects of epidural and intrathecal opioid administration on the surgical
stress response. The main conclusion has been that, despite acceptable postoperative pain relief, these techniques
have no major effect on the overall postoperative stress response. Thus, the modifying effect is not comparable
[1] [6]
with that observed during epidural local anesthesia. However, long-term intrathecal opioids may lead to
hypogonadism, hypocorticism, and growth hormone deficiency. [11]
Systematic studies comparing the differential effects of different opioids on the injury response have not been
performed, but no important differences are anticipated. Comparative studies of the effect of intrathecal versus
epidural opioid administration on the stress response are not available either.
Although clinical studies have shown that intrathecal and epidural α2 -adrenergic agonists have antinociceptive
effects, the effects on the stress response are relatively small and transient. [6]
Effect of Pain Relief Per Se on the Surgical Stress Response
The clinician using regional anesthetic techniques often considers postoperative pain relief as an indication of
afferent neural blockade. However, it must be emphasized that pain-conducting stimuli represent only a part of the
509
total afferent barrage after a surgical stimulus. Although most of the studies investigating the effect of regional
anesthesia on the surgical stress response have not at the same time looked at the degree of pain relief, there are
studies that have simultaneously assessed pain and measured stress responses, which have demonstrated that relief
of postoperative pain may not necessarily be followed by a reduction in metabolic demands. Thus, even combined [6]
analgesic techniques using epidural bupivacaine and morphine to achieve total pain relief after upper abdominal
surgery did not significantly reduce the stress response to any important degree; neither did total pain relief with
combined analgesia using epidural local anesthetics and morphine reduce metabolic responses to upper abdominal
surgery. [6]
These findings emphasize that although pain may release a stress response, pain relief per se may not necessarily
lead to a blockade of the stress response to surgery. Therefore, although a combination of analgesic regimens
(balanced analgesia) undoubtedly will have a major place in the future treatment of postoperative pain, measures to
provide more efficient neural blockade should be explored to evaluate the role of the nervous system in mediating
the injury response as well as to improve measures to suppress these responses.
Regional Anesthesia and Modification of the Surgical Stress Response: Clinical

Implications
Neural stimuli have a major role in releasing the endocrine metabolic response to surgical injury; therefore, the
important question is whether inhibition of the stress response is beneficial to postoperative outcome. Although [6] [7]
this question is still debatable, modern treatment of the surgical patient aims at reducing the catabolic drive by better
anesthetic and surgical techniques, by more efficient control of infection and fluid balance, and by removal of other
stimuli to thermogenesis, such as a cool environment. This approach aims to minimize the potential detrimental
[7]
effects of the injury-induced demands of the organs. However, the implications of removing homeostatic controls by
regional anesthesia are complicated and should be further explored with regard to safety. Nevertheless, a summary
of data from controlled studies comparing postoperative morbidity in patients receiving different techniques of
regional anesthesia versus general anesthesia suggests that reduction of surgically induced neural activity may be
beneficial (see Chapter 9 ). The most beneficial effects on morbidity were seen in the same procedures for which
[12]
regional anesthesia with local anesthetics was found to be most effective in reducing the stress response [6] [12]
suggesting that reduction in at least some parameters of the stress response may be beneficial. However, it remains
to be determined whether a causal relationship exists between reduction in morbidity and stress after regional
anesthesia or whether this is just a coincidental event. Nevertheless, use of regional anesthesia with local anesthetics
provides a rational basis for modern patient care, and this approach should be integrated into fast-track programs to
shorten hospital stay and improve outcome. [7] [13] [14] [15]
In conclusion, evidence from clinical research during the last decades demonstrates that regional anesthesia may
inhibit various reflex responses as well as endocrine metabolic changes, thereby reducing demands on the body and
probably improving postoperative outcome. These data support the original hypothesis of anociassociation
developed by George Crile at the beginning of this century, and there is growing evidence that these physiologic
effects of neural blockade also translate to an improved postoperative outcome.
REFERENCES
1. Kehlet H: Multimodal approach to control postoperative pathophysiology and rehabilitation. Br J Anaesth 78:606, 1997.
2. Desborough JP: The stress response to trauma and surgery. Br J Anaesth 85:109, 2000.
3. Hasselgren P-O. Catabolic response to stress and injury: Implications for regulation. World J Surg 24:1452, 2000.
4. Hill AG: Initiators and propagators of the metabolic response to injury. World J Surg 24:624, 2000.
5. Wilmore DW: Metabolic response to severe surgical illness: Overview. World J Surg 24:705, 2000.
6. Kehlet H: Modification of responses to surgery by neural blockade: Clinical implications. In Cousins MJ, Bridenbaugh PO (eds): Neural
Blockade in Clinical Anesthesia and Management of Pain. Philadelphia, Lippincott-Raven, 1998, pp 129–175.
7. Kehlet H: Manipulation of the metabolic response in clinical practice. World J Surg 24:690, 2000.
8. Schricker T, Wykes L, Carli F: Epidural blockade improves substrate utilization after surgery. Am J Physiol Endocrinol Metab 279:E646, 2000.
510
9. Carli F, Phil M, Halliday D: Continuous epidural blockade arrests the postoperative decrease in muscle protein fractional synthetic rate in
surgical patients. Anesthesiology 86:1033, 1997.
10. Segawa H, Mori K, Kasai K: The role of the phrenic nerves in stress response in upper abdominal surgery. Anesth Analg 82:1215, 1996.
11. Abs
R, Verhelst J, Maeyaert J, et al: Endocrine consequences of long-term intrathecal administration of opioids. J Clin Endocrinol Metab
85:2215, 2000.
12. Rodgers
A, Walker N, Schug S, et al: Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: Results from
overview of randomised trials. BMJ 321:1, 2000.
13. Holte K, Kehlet H: Postoperative ileus: A preventable event. Br J Surg 87:1480, 2000.
14. Wilmore DW: Metabolic response to severe surgical illness: Overview. World J Surg 24:705, 2000.
15. Wilmore DW, Kehlet H. Management of patients in fast track surgery. BMJ 322:473, 2001.
511
Section IV - Chapter 24 - Regional Anesthesia Options in Surgical Specialties
Chapter 24 - Regional Anesthesia Options in Surgical Specialties
P. PRITHVI RAJ
Different surgical specialties require different regional anesthesia procedures. This chapter selectively outlines some
of those regional anesthesia options for a number of surgical specialties.
Neurosurgery
Although the large majority of neurosurgical procedures are performed with a general anesthetic, it is possible to
handle quite a number of operations with a local or regional block. The purpose of this chapter is not to suggest that
regional anesthesia is in any way superior for neurosurgery compared with well-conceived and well-executed
general anesthesia, but that in circumstances in which general anesthesia would be difficult or undesirable, a
regional technique can often present an acceptable alternative.
INTRACRANIAL OPERATIONS
A local anesthetic for intracranial operations should ideally have a duration of 3 to 5 hours, because the procedure
usually lasts that long. Lidocaine or ropivacaine without epinephrine produces anesthesia for about 1 hour; however,
when administered with 1:200,000 epinephrine, it may last 3 or more hours. Epinephrine also helps to control
bleeding in this highly vascular area and slows the absorption of local anesthetic. The blood level rises more slowly,
lessening the likelihood of systemic toxicity. Indeed, Hunter stated that 0.25% lidocaine with epinephrine
[1]
1:400,000 induced effective anesthetic of the scalp. Lidocaine, bupivacaine, or ropivacaine may be regarded as the
agents of choice for local anesthetic in neurosurgery, depending on the duration.
The sensory innervation of the scalp and cranium is via the trigeminal and cervical nerves. The forehead is supplied
by the supraorbital and supratrochlear branches of the frontal nerve and by the zygomaticotemporal nerve, which
originates in the second division of the trigeminal nerve. The temporal region receives its innervation from the
zygomaticotemporal nerve and the auriculotemporal nerve, a branch of the third division of the trigeminal nerve.
The parietal and occipital regions take their innervation from the greater and lesser occipital nerves derived from the
cervical nerves. Because these nerves converge toward the vertex and become subfascial on a line encircling the
head just above the ear and passing through the occiput and glabella, it is possible to anesthetize the scalp of the
operative field by making subcutaneous and subfascial injections of 0.5% to 1.0% lidocaine along this line. Where [2]
the skull is covered by muscle, these layers must be infiltrated to obtain complete anesthesia. The dura is pain-
sensitive only at the base of the skull. The brain and cerebellum are insensitive. Sensory innervation of the dura at
the base of the skull is supplied by several means ( Figs. 24–1 and 24–2 ):
1. The meningeal branch of the vagus serves the dura of the posterior fossa, especially the region of the lateral
and occipital sinuses.
2. The recurrent branch of the ophthalmic nerve supplies the tentorium cerebelli.
3. A recurrent branch of the maxillary nerve separates before it leaves the skull and supplies the middle fossa.
4. A recurrent branch of the mandibular nerve accompanies the middle meningeal artery through the foramen
spinosum and divides into an anterior branch, which supplies the greater wing of the sphenoid and adjacent
dura, and a posterior branch, which supplies the mucous membrane of the mastoid air cells.
512
It is often difficult to cut a bone flap without pulling on or tearing across a branch of the middle meningeal artery,
which results in the stretching of nerve fibers accompanying this structure. The brain is tethered within the skull by
arteries and nerves that traverse the subarachnoid space. Retraction of the brain
Figure 24-1 Innervation of the scalp and cranium.(From Labat G: Regional Anesthesia, Its Technique and Clinical Application. Philadelphia, WB Saunders, 1923.)
for surgical exposure may produce pain from tension on these structures. This effect is especially true for the
posterior fossa, wherein lie the cranial nerves carrying sensory impulses from the head and neck. [2]
The foregoing considerations make gasserian ganglion block helpful for operations involving the base of the skull
and adjacent dura mater. The ganglion lies in Meckel’s cave, which is an invaginated fold of dura in continuity with
cerebrospinal fluid situated at the apex of the petrous temporal bone at the junction of the middle and posterior
cranial fossas. It is bounded medially by the cavernous sinus containing the carotid artery and the third, fourth, and
sixth cranial nerves. Superiorly is the inferior surface of the temporal lobe, and posteriorly the brainstem. Any of
these structures could be damaged by the anesthetic needle entering the middle cranial fossa via the foramen ovale.
Because
Figure 24-2 Area of analgesia after blocking of the nerves of the scalp. A subcutaneous and subfascial injection of local
anesthetic on line A-A[1] produces analgesia in the frontal, parietal, and occipital regions. (From Labat G: Regional
Anesthesia, Its Technique and Clinical Application. Philadelphia, WB Saunders, 1923.)
the ganglion is partially bathed in cerebrospinal fluid, local anesthetic injected into the area might spread to produce
an effect on remote parts of the central nervous system. [2]
POSTERIOR FOSSA SURGERY
The tissues overlying the upper neck and occipital region are innervated by branches of the first three cervical
nerves, which include the greater occipital, lesser occipital, and posterior auricular nerves. Figure 24–3 shows the
most convenient points for injection. At points 1 and 2, deep injections are made at the bases of the mastoid
513
processes. At points 4 and 5, deep injections are performed close to the base of the skull and the posterior aspect of
the transverse processes. At point 3, the soft tissues of the back of the neck are infiltrated as far as the spine. The
needle is first introduced perpendicular to the skin, then withdrawn to the subcutaneous tissue and redirected
laterally several
Figure 24-3 Technique of field block for posterior fossa surgery.(From Labat G: Regional Anesthesia, Its Technique and Clinical Application. Philadelphia, WB
Saunders, 1923.)
times, each time more obliquely until the needle shaft finally lies just subcutaneously and a plane of anesthesia has
been created passing through points 4, 3, and 5. The potential complications include subarachnoid or intravascular
injections into either the vertebral arteries or the large veins of the muscles of the neck. The danger of subarachnoid
injection is minimized by directing the needle slightly caudally so that overlap of the laminae can protect against
inadvertent dural puncture. Intravascular injection is avoided by keeping the needle point constantly moving through
the superficial tissues and by aspirating blood or cerebrospinal fluid before the injection is made in the deeper
portions of the needle track.
Finally, subfascial and subcutaneous injections are carried out to link points 4 and 5 to 1 and 2, and thence to 6, 7, 8,
9, and 10. The total amount of local anesthetic solution required is usually about 100 mL of 0.25% or 0.5% lidocaine
with epinephrine. Painful areas of the dura, especially near the sinuses, may be anesthetized by applying cotton
strips moistened with 2% solution of lidocaine to the region for 1 to 2 minutes.
OTHER NEUROSURGICAL PROCEDURES
Regional anesthesia may also be used in certain neurosurgical operations remote from the head. Rosenberg reviewed
a series of 200 cases of spinal anesthesia for removal of ruptured lumbar intervertebral discs and concluded that it
was safe and effective, although patients with major preoperative neurologic symptoms such as foot drop or severe
paresthesias received general anesthesia. Despite the possibility of medicolegal implications that might dissuade
[3]
many practitioners from using this technique routinely, it could be very advantageous in situations in which general
anesthesia would be difficult or hazardous.
Median nerve decompression is commonly performed with an intravenous regional technique. One can also do this
procedure with brachial plexus block. Other surgical procedures, such as removal of neuromas or repair of nerve
transection, can be done with a variety of extremity blocks.
POSTOPERATIVE PAIN RELIEF
Adequate postoperative pain relief is expected in current anesthesia practice. Conventional parenteral narcotic
administration has, for the most part, been adequate for neurosurgical procedures around the head and cervical
regions. However, postoperative pain after lumbar spine surgery has not been adequately treated by conventional
techniques. Spinal analgesic techniques have been used to provide adequate pain relief for such patients. [1] [4] [5]
Blacklock and colleagues investigated parenteral analgesic requirements and bladder function in patients receiving
intrathecal morphine (1 mg). They found in their five patients that parenteral analgesia was not necessary in the
[4]
first 24 hours. However all patients developed urinary retention for 24 to 36 hours. Rechtine and Love and Ibrahim [5]
and coworkers investigated the effectiveness of epidural bupivacaine and narcotics for postlaminectomy pain. In a
[6]
prospective randomized trial, Ibrahim and coworkers found significantly better pain relief in patients receiving 2
[6]
514
mg morphine epidurally and on demand than in patients receiving 10 mg of intramuscular morphine on demand.
Side effects in both groups were insignificant. Rechtine and Love did not find that paravertebral administration of
[5]
bupivacaine improved the analgesic efficacy of epidural morphine. At the author’s institution, for patients
undergoing spinal surgery, a mixture of 0.03% bupivacaine with 0.5 mg of morphine or 35 µg of fentanyl is infused
continuously per hour in a 70-kg healthy patient. This dosage has provided effective postoperative pain relief
without side effects. However, surgeons are uncomfortable if numbness occurs postoperatively in such patients
because they are not able to diagnose whether that numbness is due to the use of bupivacaine, nerve injury, or edema
caused by surgery. Our experience shows that a mixture of local anesthetic and a narcotic has a synergistic effect,
reducing the bupivacaine concentration to 0.03% has not caused numbness and yet has produced effective analgesia.
In the future, other agents, such as clonidine, will probably be tried in mixtures for severe postoperative pain after
spinal surgery.
Ophthalmic Surgery
The majority of patients who need ophthalmic surgery are frequently at the extremes of age. Aged patients often
suffer from multiple systemic diseases. In fact, the eye problem may be a reflection of ongoing systemic disease
with multiple end-organ involvement. For example, if diabetic patients need surgery for diabetically caused
advanced retinopathy, they may have coronary artery disease, peripheral vascular disease, cardiovascular disease,
kidney disease, peripheral neuropathy, or autonomic neuropathy as well. The extent and degree of end-organ
involvement varies from one patient to another.
The scope of regional anesthesia in ophthalmic surgery is expanding. Elderly patients who are in poor general health
and who, for financial reasons, need ophthalmic operations done on an outpatient basis are increasing in number.
For these patients, regional anesthesia may be preferred. Regional ophthalmic anesthesia has several advantages.
Anesthesia is adequate, and there is a smooth postoperative period. Rapid recovery, early ambulation, prolonged
analgesia with no side effects, and early discharge from the hospital with reduction of cost are additional advantages.
More anesthesiologists are now involved in ophthalmic regional anesthesia, providing safe sedation to the patients
and establishing the blocks themselves.
Anesthesiologists are the best personnel to handle any possible systemic complications that may arise after the
administration of ophthalmic blocks. Additionally, the availability of long-acting local anesthetics, which provide
adequate surgical anesthesia as well as prolonged, postoperative analgesia, has eliminated the need for postoperative
narcotics and their associated potential for respiratory depression, nausea, and vomiting.
SURGICAL PROCEDURES
The vast majority of ophthalmic operations, whether involving the anterior segment of the eye (e.g., cataract
extraction and corneal transplantation), the posterior segment of the eye (e.g., retinal detachment, vitrectomy, scleral
buckling), or the ocular adnexa (e.g., strabismus, ptosis surgery), as well as evisceration of the eye, can all be done
under regional anesthesia. Very lengthy procedures, however, may constitute a relative contraindication to regional
anesthesia because the patient may become tired or restless.
Most ophthalmologists prefer to perform enucleation of the eye with the patient under general anesthesia, although
this procedure can be done under regional anesthesia.
In the presence of globe infection, a local anesthetic may not be effective. Previous eye operations may lead to
formation of adhesions and fibrous tissue, which do not allow an even spread of the local anesthetic, resulting in
incomplete block.
Techniques of regional anesthesia available for ophthalmic operations include retrobulbar block, peribulbar block,
and local infiltration.
PREANESTHESIA EVALUATION
Preoperative evaluation of the patient is extremely important because many ophthalmic patients are elderly and in
poor health. They may have advanced coronary artery disease, hypertension, peripheral vascular disease, diabetes,
renal insufficiency, arthritis, or chronic obstructive lung disease, and they may be receiving multiple medications.
Many anesthesiologists are reluctant to administer general anesthetics to ophthalmic patients who are in poor
general health, which may encourage the use of regional anesthesia.
515
To conduct safe regional anesthesia, preoperative evaluation of the patient’s mental status is extremely important.
The patient should be alert, cooperative, and comfortable and must accept the idea of being awake during surgery.
In addition to the mental status, the ability of the patient to lie supine without dyspnea, persistent cough, discomfort,
or pain should also be carefully evaluated.
A preoperative electrocardiogram (ECG) is indicated in the elderly patient and in the young patient who has
cardiovascular disease. Checking the patient’s oxygen saturation on room air preoperatively helps in the
perioperative management of the patient.
To achieve adequate conditions for ophthalmic surgery, anesthesia of the globe, together with akinesia of the
extraocular and orbicularis muscles, is needed. There are six extraocular muscles, four recti and two obliques ( Fig.
24–4 ), which move the eye in different directions. The four rectus muscles originate from a fibrous annulus at the
apex of the orbit and are inserted into the sclera, forming a space, the muscle cone. The cone transmits and contains
nerves, arteries, and veins.
Figure 24-4 The extraocular muscles, which can move the eye in all directions. The extraocular muscles include four rectus muscles (superior, inferior, medial, and
lateral) and two oblique muscles (superior and inferior).
The eye has a rich and complex supply of sensory, motor, parasympathetic and sympathetic nerves ( Fig. 24–5 ).
Anesthesia and akinesia of the globe can be established by a retrobulbar or peribulbar block. If paralysis of the
orbicularis muscle is needed, a facial nerve block may be employed.
PREPARATION OF THE PATIENT
While these injections are being performed, systemic complications such as generalized convulsions or respiratory
or cardiovascular depression may occur. These complications are rare but, if not handled promptly and
[7]
appropriately, can result in a fatal outcome. Thus, before performing a block, adequate intravenous access should be
obtained. Placing an intravenous catheter in an elderly patient may be difficult because the veins
516
Figure 24-5 The rich nerve supply of the eye, including the optic nerve and the oculomotor nerve, which has a superior division, a branch to the inferior oblique
muscle, and a short root to the ciliary ganglion. The ciliary ganglion has several branches: the short ciliary nerve, the long ciliary nerve, and the nasociliary nerve.
are tortuous, small, and fragile and the catheter placement may lead to excessive ecchymosis, but it can be lifesaving.
The patient should be properly monitored by an apical stethoscope, blood pressure cuff, ECG, and pulse oximeter.
Proper equipment to ventilate the patient, to establish an upper airway, to provide oxygen, and to perform suctioning,
as well as necessary medications to resuscitate a patient and control convulsions, should all be at hand. Medical
personnel who are skilled in establishing an upper airway and resuscitating a patient should be present during the
blocks. Anesthesia personnel are best equipped to handle the possible systemic complications associated with these
blocks. [7]
The anxiety and pain a patient may experience during a block may be associated with an endogenous
sympathoadrenal stress response, causing increased cardiac stress. To reduce this anxiety and pain, the
[8]
anesthesiologist usually administers sedatives, hypnotics, narcotics, or antiemetic drugs to the patient. Each patient
may receive one or more of these drugs. Sedatives administered to elderly patients may cause them to become
restless and uncooperative. The administration of narcotics may lead to chest rigidity, respiratory depression, nausea,
and vomiting. The most commonly used antiemetic drug (droperidol) may lead to dysphoria. For these reasons, I
prefer to administer a short-acting general anesthetic, using a sleeping dose of intravenous sodium methohexital (1–
2 mg/kg) briefly preceded by a small intravenous dose (2–5 µg/kg) of the ultra–short-acting narcotic alfentanil. The
brief period of general anesthesia provides amnesia, analgesia, cardiovascular stability, and an immobile eye in the
most desirable position (i.e., the primary position). If sodium methohexital is used alone to induce brief general
anesthesia, it may lead to cough, hiccough, or abnormal jerky muscle movements and may not attenuate the
cardiovascular responses associated with establishing the block, a response that is expected because sodium
methohexital does not provide analgesia. The intravenous administration of lidocaine (0.5–1 mg/kg) shortly before
the sodium methohexital can partially reduce these side effects. The patient recovers shortly after the methohexital-
alfentanil anesthesia, with a clear sensorium, feeling relaxed, and with minimal or no side effects. The two side
effects we have seen are short-lived nasal itch and bradycardia. None of the patients developed chest wall rigidity,
nausea, or vomiting. During the operation, the need for any additional sedative is rare; if required, it should be given
carefully in low doses while the patient is closely monitored.
A brief general anesthetic can be also provided by the intravenous administration of propofol (1–2.5 mg/kg), but it
may lead to undesirable hypotension. The patient usually experiences severe pain when propofol is intravenously
[9]
injected. The pain can be reduced or abolished by the intravenous injection of 1 to 2 mL of lidocaine immediately
before the propofol injection. The patient regains consciousness after a brief time.
Eye blocks can also be performed under monitored anesthesia care (MAC). Midazolam is a commonly used sedative.
It has the advantages of being short-acting and provides amnesia. Some of the elderly patients react in an adverse
manner to sedatives. Short-acting narcotics such as fentanyl or alfentanil are used. Narcotic administration may lead
to chest wall rigidity, respiratory depression, nausea, and vomiting. A combination of a small dose of short-acting
sedative and a short-acting narcotic is also used. The combination can lead to severe respiratory depression. Proper
monitoring of the patient and titration of the drugs are essential.
If a patient develops a slight cough, the intravenous administration of lidocaine (0.5–1 mg/kg) or intravenous
administration of codeine (15–30 mg) can depress the cough reflex. Persistent cough is a contraindication for
regional anesthesia. If a patient complains of post nasal discharge or of a stuffy nose, the administration of a drying
agent (glycopyrrolate 0.1–0.2 mg intravenously) or a nasal decongestant may comfort the patient.
517
The use of 10% phenylephrine hydrochloride as a mydriatic can lead to severe hypertension with potential
complications when topically applied. The use of 2.5% phenylephrine topically is safer. Overdose of
[10]
cyclopentolate hydrochloride (Cyclogyl) may lead to grand mal seizure, occurring most commonly with the 2%
solution or repeated applications of weaker strengths. The usual toxic reactions of cyclopentolate hydrochloride are
disturbances of behavior or of cerebellar functions. The topical application of the β-adrenergic receptor blocking
[11]
agent, timolol, to reduce intraocular pressure in patients with open angle glaucoma can induce bradycardia. [12]
RETROBULBAR BLOCK
To achieve anesthesia of the globe and akinesia of the ocular muscles, a retrobulbar block is commonly adopted. It
involves placing the local anesthetic behind the eye into the muscle cone ( Fig. 24–6 ). If a short-acting general
anesthetic is administered to the patient while the block is being established, the eye will be in the primary position,
which places the optic nerve away from the tip of the needle, thus reducing the chances of injuring the optic nerve or
injecting the local anesthetic underneath the optic nerve sheath. To achieve the optimal position of the eye, an awake
patient should be instructed to look straight ahead. Traditionally, patients were instructed to look upward and nasally,
aiming to rotate the globe to reduce the chances of injuring it, but this position brings the optic nerve close to the
needle tip, which may increase the chances of injuring the optic nerve or of injecting the local anesthetic
[13]
underneath the optic nerve sheath.
I prefer to use a 23-gauge (G), nondisposable (Atkinson) needle ( Fig. 24–7 ), 3.5 cm long, with a blunt, short bevel
that enables the operator to feel and identify the orbital structures well. Thus, the chances of injuring a vessel may be
less than with a sharp needle. Because I administer a short-acting general anesthetic to the majority of my patients,
[13]
they do not experience the pain associated with the use of a blunt needle.
The needle is passed through the lower lid at the junction of the middle and outer thirds of the lower rim of the orbit
and directed posteriorly along the orbital floor until a pop is felt, indicating that the
Figure 24-6 The position of the needle for placement of a retrobulbar block. The needle is first directed straight backward until a loss of resistance is experienced,
indicating that the point of the needle is at the cone. The needle is then pointed upward toward the apex of the eye and the local anesthetic is placed into the muscle
cone.(From Raj P: Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, pp 197–269.)
518
Figure 24-7 Comparison of the Atkinson needle (A) with the sharp needle (B). The Atkinson needle is blunt and has a rounded point and a short bevel.
septum has been pierced and that the tip of the needle has passed the equator of the eye. The needle is then directed
toward the apex of the orbit into the muscle cone, where the local anesthetic is to be placed. Aspirating before
injecting the local anesthetic may help to avoid intravascular injection. If an unusual resistance is encountered on
injecting the local anesthetic, the injection should be stopped, because the resistance may indicate that the tip of the
needle is inside the globe or in the optic nerve or underneath the optic nerve sheath. The needle should be withdrawn
until the resistance disappears before trying to reinject.
In 1859, Carl Keller discovered the anesthetic properties of cocaine hydrochloride, which resulted in the
[14]
introduction of regional anesthesia into ophthalmic surgery in 1884. In the same year, Knapp, using cocaine,
reported his simple and effective method of retrobulbar injection to produce anesthesia and akinesia of the globe for
enucleation. The fear of cocaine toxic reaction deterred ophthalmologists from making injections to produce local
anesthesia and akinesia for another 20 to 30 years. [15]
An ideal local anesthetic for retrobulbar blocks would be one with rapid onset, which provides profound anesthesia
and akinesia and has prolonged action. A long-acting local anesthetic provides adequate anesthesia for long surgical
procedures, together with prolonged postoperative analgesia that eliminates the need for systemic analgesics or
narcotics. The prolonged paralysis of the orbicularis muscle prevents its squeezing action on the globe, which may
be beneficial from the surgical point of view.
Mepivacaine, prilocaine, etidocaine, and lidocaine are used for retrobulbar blocks. They have a short onset and[16] [17]
provide adequate anesthesia and akinesia, but their duration of action is not long. Lidocaine, for example, has a
limited duration of 60 to 90 minutes. Epinephrine had been added to lidocaine to prolong its duration of action, but
the added epinephrine may lead to retinal vascular spasm and may be contraindicated in elderly patients with
[18]
cardiovascular disease.
The use of bupivacaine in retrobulbar anesthesia first appeared in Scandinavian literature in 1966. In 1973, the Food
and Drug Administration approved its use in the United States, and since then, it has gained wide acceptance as a
safe prolonged-acting local anesthetic. For retrobulbar blocks, bupivacaine 0.75% is recommended because the
[19]
0.5% concentration proved to be insufficiently potent. Bupivacaine used in small volume leads to highly variable
[20]
and often prolonged onset of ocular akinesia. For these reasons, many ophthalmologists use a mixture of equal
[21]
volumes of bupivacaine and either lidocaine or mepivacaine to enhance the onset of the block. Chin believed
[22] [19] [22]
that bupivacaine plus lidocaine might reduce the effectiveness of both anesthetics. He also demonstrated that the
addition of hyaluronidase to bupivacaine appears to quicken the onset of action and that the addition of epinephrine
to bupivacaine solutions did not significantly extend the already prolonged anesthesia and akinesia induced by
bupivacaine. [22]
Several articles in the ophthalmology literature warn about an increased incidence of respiratory arrest with the use
of 0.75% bupivacaine. I believe that any of the local anesthetics used to establish retrobulbar blocks injected
[23] [24]
underneath the optic nerve sheath can cause midbrain anesthesia and respiratory depression.
The addition of the enzyme hyaluronidase (Wydase) to the local anesthetic used to induce retrobulbar block helps
the spread of the local anesthetic into the orbit, speeds the onset of the block, and increases the success rate.
[27]
[22] [24] [25] [26]
An open globe with a large wound is a contraindication for a retrobulbar or peribulbar block. If the wound is small,
a block can be placed safely with a small volume of local anesthetic.
519
LOCAL INFILTRATION
Akinesia of the orbicularis muscle is achieved by blocking the facial nerve. The nerve can be blocked at different
sites proximal to its exit from the skull.
1. The Van Lint technique involves infiltration of the local anesthetic into the orbicularis muscle of the lids. It
may cause extensive ecchymosis around the eye.
2. In the Nadbeth technique, the trunk of the facial nerve is blocked at its exit from the skull. The block is
quite painful and leads to unnecessary paralysis of the total side of the face. It may lead to dysphagia
because the glossopharyngeal nerve can be blocked owing to its proximity to the facial nerve trunk.
3. In the O’Brien technique, the local anesthetic is injected vertically to the tragus of the ear to block all the
facial nerves.
4. In the Atkinson technique, the local anesthetic is injected midway between the areas injected in the Van
Lint and O’Brien techniques. The Atkinson technique blocks the facial nerve branches to the orbicularis
muscle but does not affect the branches to the lip and lower face.
If a large volume of the local anesthetic is used to establish a retrobulbar block and outside pressure is applied to the
globe, the local anesthetic spreads outward. The orbicularis muscle is then paralyzed, eliminating the need for a
separate facial nerve block. For an alternative, as the retrobulbar needle is being withdrawn from the orbit, another
[28]
injection of 2 to 3 mL of the local anesthetic is given into the subcutaneous space as the surgeon’s finger is pressed
into the lid just medial to the needle tip. The local anesthetic spreads laterally and blocks the terminal branches of
[29]
the facial nerve without causing ecchymosis.
Lid surgery is commonly done under MAC, with local anesthesia infiltration in the lid. Epinephrine (1:100,000) is
usually added to reduce the bleeding, prolong the action of the local anesthetic, or both.
When a small volume (1 to 2 mL) of 0.75% bupivacaine is used as the sole anesthetic for the retrobulbar block, its
onset is slow. In our practice, we use a large volume (5 to 7 mL) of 0.75% bupivacaine with hyaluronidase (15
[15]
units mL). In the majority of cases, complete anesthesia and akinesia of the globe are established in less than 5
minutes. The use of a large volume of local anesthetic is associated with rapid onset and a higher success rate,
reducing the need for supplementation. With each injection, there is a risk of systemic complications. The
disadvantage of using a large volume is the associated rise in intraocular pressure. This increase can be counteracted
by applying pressure to the globe with a ball or Honan apparatus for 20 minutes or by using rotary massage with
[30]
pressure on the eye.
COMPLICATIONS
Monitoring of Efficiency of the Block. Akinesia of the extraocular muscles is tested by observing whether the
patient can move the eye in the four opposite directions (up, down, right, and left). The patient is asked to squeeze
the eye to check the orbicularis oculi paralysis. Because the superior oblique muscle is anatomically located outside
the muscle cone, it may not be completely paralyzed after a retrobulbar block. If the patient is asked to look
downward, an intorsion movement of the eye is observed. Persistent minimal ability to move the eye does not, in the
vast majority of cases, interfere with the surgery.
Loss of sensation of the ophthalmic division of the fifth cranial nerve can be tested by touching the conjunctiva with
a sterile cotton swab at the upper or lower fornices.Failure to achieve anesthesia and akinesia 10 minutes after
placement of the retrobulbar block may necessitate repetition of the block.
Monitoring during the Operation. The patient should be carefully monitored by anesthesia personnel. Routine
monitors include a precordial stethoscope, blood pressure, ECG, and pulse oximeter. End-tidal CO2 can be
monitored by placing a special nasal cannula connected to a mass spectrometer, which can reflect the relative
changes in ventilation.
Intraoperative sedatives, if administered at all, should be used with extreme care and titrated to individual needs.
During ophthalmic operations, the anesthesiologist does not have immediate access to the patient’s upper airway. If
the patient’s breathing becomes obstructed due to oversedation, this can create an undesirable or even dangerous
situation. If sedatives are administered to aged patients, some may become restless, uncooperative, or incoherent.
During the operation, they may fall asleep, awaken unexpectedly, and then move in a jerky manner, a situation that
is most undesirable, particularly if the globe is open.
520
Also, during surgery, the face of the patient is commonly covered with sterile plastic drapes. A high flow of air (10
to 15 L/minute) should be blown underneath the drapes. This prevents rebreathing and the possible fall of the drapes
over the patient’s face, with resultant obstruction of the nose or mouth.
The possible complications associated with the administration of a retrobulbar block can be either systemic or ocular.
Systemic complications are inadvertent intravascular injection of the local anesthetic, brainstem anesthesia,
oculocardiac reflex, and allergic reactions.
Systemic Complications
Intravascular Injection. The main arterial blood supply to the eye is from the ophthalmic artery, which is a branch
of the internal carotid artery ( Fig. 24–8 ).
The venous drainage of the eye is mainly via the central retinal vein, which empties directly into the cavernous sinus.
An inadvertent intravascular injection can be secondary to either injecting the local anesthetic into a vein or into an
artery with reversed arterial blood flow, which may lead to an immediate and sudden onset of generalized
[31]
convulsions. Impairment of the mental status of the patient may precede the convulsions, followed by loss of
[32]
consciousness and cardiorespiratory depression of variable degree. As the ophthalmic vessels are quite close to the
brain, the inadvertent injection of even a small volume of local anesthetic into these vessels may lead to systemic
complications. It is wise to aspirate with the syringe before injecting local anesthetic; however, negative aspiration
does not guarantee that the tip of the needle is not in a vessel.
Figure 24-8 The rich arterial blood supply of the eye and the origin of the arterial vessels and branches that supply the globe, other intraocular structures, and the
extraocular adnexa.(From Raj P: Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, pp 197–269.)
The convulsions are usually short-lived and can be controlled by the intravenous administration of a small dose of a
barbiturate or a benzodiazepine. Manual support of the upper airway and administration of oxygen for the increased
oxygen demand associated with the convulsions are indicated. If there is associated respiratory or cardiovascular
depression, artificial ventilation and administration of vasopressors and inotropes are indicated.
Brainstem Anesthesia. If local anesthetic is inadvertently injected into the optic nerve sheath, it may spread along
the optic nerve and the chiasma to the midbrain. The cranial nerves at the midbrain and the respiratory
[7] [33] [34] [35] [36] [37] [38]
centers become anesthetized. Patients may manifest dysphagia, contralateral loss of vision, contralateral ocular
muscle paresis, or apnea. They may become drowsy and lose consciousness but do not develop convulsions. These
521
symptoms occur 2 to 10 minutes after the administration of the retrobulbar block and clear in 60 to 90 minutes, but
residual effects may last for hours. Close observation and monitoring of the patient for at least 10 minutes after the
administration of the blocks is essential.
One patient experienced a self-limited respiratory arrest following a retrobulbar injection. The injection was a
mixture of bupivacaine and lidocaine. Forty-five minutes after the injection, quantities of both drugs were recovered
from the patient’s cerebrospinal fluid obtained via a lumbar puncture. [39]
Drysdale was able to demonstrate the anatomic continuity between the potential space underneath the optic nerve
[40]
sheath and the brain. He injected contrast material in cadaver eyes, and the contrast material was seen tracking along
the optic nerve to the midbrain. He also demonstrated that it was easy to pierce the optic nerve sheath with a sharp,
25-G, 1.5-inch needle used to establish a retrobulbar block, particularly with the eye elevated and adducted.
Unsold used computed tomographic (CT) scanning of a cadaver orbit and showed that with the eye in the elevated
[41]
and adducted position, the optic nerve, the ophthalmic artery and its branches, the superior orbital vein, and the
posterior pole of the globe are all brought into close proximity to the tip of the needle. In addition, because the nerve
is stretched, it may be more susceptible to puncture by the needle because it cannot move out of the way easily. [41]
Close observation of the patient for 10 minutes or more after the time of placement of the retro- or peribulbar block
is recommended. [42]
Oculocardiac Reflex. Traction on the extraocular muscles (particularly the medial rectus), pressure on the globe,
traction on the conjunctiva, or orbital hematoma can lead to the oculocardiac reflex. The afferent limb of the reflex
is the ophthalmic division of the trigeminal nerve, and the efferent limb is the vagus nerve ( Fig. 24–9 ). Bradycardia
is the most common manifestation of the trigeminal vagal reflex, but other dysrhythmias, including junction rhythm,
atrioventricular (AV) block, ventricular bigeminy, and cardiac standstill, have been reported. Hypercapnia,
[43]
hypoxia, and light levels of anesthesia may increase the incidence and severity of the reflex.
Placing a retrobulbar block, particularly if the patient is awake and apprehensive, can lead to the oculocardic reflex.
If the retrobulbar block is complete, further manipulation of the globe or the extraocular adnexa does not elicit the
oculocardiac reflex, but if the block is inadequate, the reflex can occur.
In patients with coronary artery disease, we do not recommend the prophylactic administration of anticholinergic
drugs. Proper and continuous monitoring of the patients to detect early occurrence of the reflex is essential. The
surgeon must release the traction on the tissue that is eliciting the reflex. The intravenous administration of
glycopyrrolate is then justified. In young patients, the prophylactic intravenous administration of atropine to prevent
the occurrence of the reflex is quite effective and safe.
[44]
Ocular Complications
The ocular complications of retrobulbar blocks are retrobulbar hemorrhage, optic nerve injury, perforation of the
globe, central retinal artery occlusion, bilateral amaurosis, and contralateral ophthalmoplegia.
Retrobulbar Hemorrhage. Retrobulbar hemorrhage is the most common ocular complication, occurring in
approximately 1% to 2% of cases. Gifford, using a sharp 5-cm needle designed for deep orbital injection, noted an
[44A]
incidence of 5%. Atkinson reported no retrobulbar hemorrhage in 20 years of practice, using a blunted 3.5-cm
[15]
needle. Retrobulbar hemorrhage is associated with pain, decreased visual acuity, proptosis, increased intraocular
pressure, ecchymosis, subconjunctival hemorrhage, and pallor of the optic nerve. The diagnosis can be confirmed by
CT or ultrasound scan of the orbit. Permanent blindness is rare and is probably due to a neuropathy of the optic
nerve secondary to compression or ischemia. Treatment is conservative,
522
Figure 24-9 The oculocardiac reflex. Afferent impulses from the short ciliary nerve (SCN) and long ciliary nerve (LCN) travel to the ciliary ganglion (CG), to the
gasserian ganglion (GG), and finally to the midbrain nuclei (1, 2, 3): The efferent impulses then travel via the vagus nerve (X) to the sinoauricular node of the heart. O,
ophthalmic nerve; V, trigeminal tract.(From Raj P: Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, pp 197–269.)
but surgical decompression is indicated when proptosis is progressive or if there is deterioration of visual acuity.
Optic Nerve Injury. Injection of the local anesthetic into the optic nerve leads to disastrous visual consequences
( Fig. 24–10 ). It is associated with severe visual loss, optic nerve edema, retinal edema, and vitreous hemorrhage.
The complication results from either direct injury to the nerve or hemorrhage within the optic nerve sheath. Both can
lead to vascular compromise. The reported cases of optic nerve injury were associated with the common, but not
recommended, use of sharp needles. The eyes were looking upward and nasally. [45]
Perforation of the Globe. A rare complication of retrobulbar blocks is perforation of the globe. Myopic eyes are
more susceptible to perforation because of their increased anteroposterior diameter and thinner sclera, compared
with emmetropic or hyperopic eyes ( Fig. 24–11 ). Globe perforation can also result from peribulbar injection of
[46] [47]
local anesthetics. It has also occurred during injection of local anesthetic into the eyelids. The use of a blunt
[48] [47]
needle has been suggested to lessen the risk of globe perforation in peribulbar and retrobulbar injections. Perforation
of the globe leads to marked hypotonia of the globe. The prognosis is good if the perforation is recognized and
treated immediately.
Central Retinal Artery Occlusion. Retrobulbar hemorrhage, direct trauma to the artery, and compression effect of
the injected local anesthetic solution can lead to central artery occlusion. If epinephrine is added to the local
[49] [50]
anesthetic solution, it can cause central retinal artery spasm owing to its vasoactive
523
Figure 24-10 The position of the eye when the patient is instructed to look upward and nasally. Looking upward and nasally stretches the optic nerve and brings it
closer to the tip of the needle, which increases the chance of optic nerve injury and subdural injection of the local anesthetic.(From Raj P: Clinical Practice of
Regional Anesthesia. New York, Churchill Livingstone, 1991, pp 197–269.)
Figure 24-11 Double perforation of the globe during placement of a retrobulbar block. One perforation occurred through a detached part of the retina and the second
perforation occurred through the intact retina.(From Raj P: Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, pp 197–269.)
properties. Combined obstruction of the central retinal artery and vein results from intraneural sheath hematoma. [51]
Contralateral Amaurosis and Contralateral Extraocular Akinesia. When a small amount of local anesthetic is
injected underneath the optic nerve sheath, it tracks back and affects the chiasma, leading to contralateral optic nerve
dysfunction and partial contralateral akinesia. [33] [34] [35]
OCULAR MYELOTOXIC EFFECTS OF LOCAL ANESTHETICS
Postoperative ptosis, horizontal rectus muscle palsy, and lagophthalmos have been reported after retrobulbar
injections using 2% lidocaine hydrochloride plus 1:100,000 epinephrine. The cause of the complications may have
[52]
been inadvertent direct infiltration of the anesthetic into the ocular or extraocular muscles. All the patients recovered
in 8 to 12 weeks. The clinical course was compatible with that observed in patients with myotonic effects of the
local anesthetics. Also, Rainin and Carlson reported similar cases of ptosis and diplopia after individual infiltration
[53]
of rectus muscles with 0.75% bupivacaine.
PERIBULBAR ANESTHESIA
Peribulbar anesthesia is an alternative to retrobulbar anesthesia in ophthalmic surgery. The local anesthetic is
deposited outside the muscle cone ( Fig. 24–12 ). A large volume of the local anesthetic is needed and a longer
[54]
time is required for the block to be effective. Repeated injections of the local anesthetic may also be
524
Figure 24-12 The position of the needle during placement of a peribulbar block via superior and inferior injections.(From Raj P: Clinical Practice of Regional
Anesthesia. New York, Churchill Livingstone, 1991, pp 197–269.)
required. Because the local anesthetic is injected outside the muscle cone, the chances of direct injury to the optic
nerve or of placing the local anesthetic underneath the optic nerve sheath are greatly minimized.
MORTALITY RATES
Several retrospective studies reviewed the mortality rates associated with ophthalmic surgery. They
[55] [56] [57] [58] [59] [60]
showed that death after ophthalmic surgery was much less common than after general surgery. The studies did not
show differences in the mortality rates among the ophthalmic patients who received general, regional, or local
anesthesia. Although the mortality rate per procedure among patients who had local, regional, or general anesthesia
was nearly equal, the comparison was heavily dependent on patient selection.
As reported by Kaplan and Reba, the preexisting medical condition of the patient is the most important factor
[61]
contributing to the death of patients undergoing ocular surgery. Death after general anesthesia is rare among young,
healthy patients, but the rate increases with age. pulmonary embolism was the chief cause of postoperative
ophthalmic surgery death. Heart disease associated with congestive heart failure and immobilization are the most
common predisposing factors to pulmonary embolism. Active ambulation is the most important prophylactic
measure.
Local anesthesia seems to be a safe procedure in elderly patients. It is currently held that for cardiac patients
requiring surgery, local anesthesia is safer than major regional or general anesthesia, provided the patient is
adequately prepared pharmacologically and psychologically. Becker and colleagues found that local anesthesia
[62] [63] [64]
or retrobulbar block for ophthalmic surgery did not pose special risks for reinfarction in the patient with a
perioperative myocardial infarction.
A combination of general anesthesia and retrobulbar block has been used in prolonged ophthalmic surgery. The
combination may be superior to general anesthesia alone in terms of pain relief and speed of recovery from the
anesthesia. [65]
Head and Neck Surgery
Anesthesia for head and neck surgery presents unique problems owing to the proximity of surgery to the mouth and
oropharynx, resulting in a “shared airway.” Judiciously used, regional anesthesia can provide a solution to the
problem of the shared airway, especially in situations in which the oral or nasal endotracheal tube can restrict
surgical access or distort the anatomy.
Regional anesthetic techniques have a well-established place in ophthalmic surgery, plastic surgery of the face,
operations on the nose and ear, major maxillofacial surgery, dental extractions, and reduction of uncomplicated
facial fractures. Many operations of the head and neck involve staged procedures secondary to cancer,
[66]
reconstruction, or burns. These patients require multiple anesthetics over a very short period. In this situation, some
of the intermediate-stage surgery can be under regional anesthesia. Sometimes, severe contractures after facial and
525
neck burns may make induction of general anesthesia unsafe. Under these circumstances, bilateral superficial
cervical plexus block provides adequate analgesia with minimal discomfort to the patient.
Dental extraction under general anesthesia is associated with a significant incidence of arrhythmias. Maxillary or
mandibular nerve blocks have been shown to reduce the incidence of arrhythmias. Regional nerve block combined [67]
with light general anesthesia has proved to be a successful alternative to induced hypotension in providing good
surgical operating conditions, reducing blood loss, and minimizing postoperative complications. [68] [69]
SURGERY ON THE UPPER THIRD OF THE FACE

The Trigeminal Nerve
The trigeminal nerve is the largest of the cranial nerves. It contains both sensory and motor fibers ( Fig. 24–13 ).
General somatic afferent fibers convey both exteroceptive and proprioceptive impluses ( Fig. 24–14 ). Somatic
exteroceptive impulses carried by the trigeminal nerve include touch, pain, and thermal senses. These impulses are
transmitted from the skin of the face and forehead, the mucous membranes of the nasal surfaces and oral cavity, the
teeth, the anterior two thirds of the tongue, and the anterior portions of the cranial dura. Proprioceptive impulses are
conveyed from the teeth, the periodontium, the hard palate, and the temporomandibular joint. The trigeminal nerve
is involved in carrying afferent impulses from stretch receptors in the muscles of mastication. Additionally, visceral
efferent fibers innervate the muscles of mastication, the tensor tympani and tensor veli palatini muscles, the muscles
of the eye, and the facial muscles.
Block of Supratrochlear and Supraorbital Nerves
This block is used for relief of neuralgias and headaches limited to the distribution of the ophthalmic nerve.
Anesthesia is provided over the forehead and scalp as far back as the lambdoidal suture.
Figure 24-13 Anatomy of the trigeminal nerve.(From Raj P: Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, pp 197–269.)
526
Figure 24-14 Superficial sensory nerves of head and neck regions.(Redrawn from Bononi SR: The trigeminal nerve. In Bennett CR [ed]: Monheim’s Local Anesthesia
and Pain Control in Dental Practice, 7th ed. St. Louis, CV Mosby, 1984.)
Anatomy. The supratrochlear and supraorbital nerves are the end branches of the ophthalmic nerve. The
supraorbital nerve traverses the supraorbital foramen, which lies approximately 2 to 3 cm from the midline of the
face at the inferior edge of the supraorbital ridge. The supratrochlear nerve leaves the orbit between the trochlea and
the supraorbital foramen to innervate the lower part of the forehead.
Technique. The supraorbital notch in the supraorbital ridge of the frontal bone is palpated. The needle is advanced
perpendicular to the skin toward the supraorbital notch for the supraorbital block, or medial to the supraorbital notch
for the supratrochlear block, until paresthesias are elicited or the needle reaches bone. No more than 5 mL of local
anesthetic solution should be injected into this region because excess solution can migrate to the eyelids and cause
them to swell.
SURGERY ON THE MIDDLE THIRD OF THE FACE

Block of the Maxillary Nerve
Anesthesia of the maxillary nerve and its subdivisions is indicated for dental pain management and surgical
procedures. By using techniques of local infiltration, nerve blocks, and field blocks, these areas can quite easily be
anesthetized. The following blocks can be performed on the maxillary nerve and its following branches: (1)
supraperiosteal, (2) infraorbital, (3) nasopalatine, (4) greater palatine, and (5) posterosuperior alveolar.
Anatomy. The maxillary (second) division of the trigeminal nerve is entirely sensory. It leaves the skull through the
foramen rotundum and enters the pterygopalatine fossa. It then travels forward, entering the inferior orbital fissure to
pass into the oral cavity. The nerve then transverses the infraorbital groove on the orbital surface of the maxilla and
passes through the infraorbital canal. The nerve emerges on the front of the maxilla by the infraorbital foramen. The
posterosuperior alveolar nerves and the zygomatic nerve originate in the pterygopalatine fossa. The maxillary nerve
branches to become the infraorbital nerve at the infraorbital fissure. The anterior and middle superior alveolar nerves
branch off at the infraorbital groove.
Supraperiosteal Block
Supraperiosteal injection (local infiltration) is one of the most common techniques to anesthetize the maxillary teeth.
However, multiple injections are necessary to anesthetize more than two teeth, requiring an increase in volume of
the local anesthetic administered and increasing the risk of complications, both local and systemic. The large
527
terminal nerve branches are blocked, resulting in anesthesia of the pulp of the tooth, the buccal periosteum, the
connective tissue, and the mucous membrane.
Indications. This technique is useful for anesthesia of one or two maxillary teeth for limited procedures. It is usually
limited to the anterosuperior alveolar area.
Technique. The needle is inserted through the mucosa while the lip is held outward and taut. Squeezing the lip
slightly while talking to the patient during the needle puncture can help to distract the patient’s anticipation and
concentration so that the entrance is painless. Slow injection of the local anesthetic decreases the pain while the
tissues are being distended. The syringe is held parallel to the bony landmark with the bevel toward the bone and is
inserted to the approximate height of the root tip. The amount of solution injected should be approximately 1 mL.
Infraorbital Nerve Block
Anatomy. The infraorbital nerve is the terminal part of the maxillary nerve. The infraorbital foramen lies
approximately 2 to 3 cm from the midline of the face or 2 cm lateral to the frontal process of the maxillary bone. It
emerges from the infraorbital foramen and divides into four branches: the inferior palpebral, the external nasal, the
internal nasal, and the superior labial. These branches innervate the lower eyelid, the lateral inferior portion of the
nose and its vestibule, and the upper lid and its mucosa. The anterosuperior alveolar nerve branches from the
infraorbital nerve in the anterior part of the infraorbital canal and innervates the maxillary incisor and cuspid teeth.
Infraorbital injection is used for the removal of impacted crowns or cysts, or in inflamed or infected areas, where
supraperiosteal injection is prohibited. If the cortical bone overlying the maxillary anterior teeth is extremely thick,
the supraperiosteal block is ineffective. In this case, the infraorbital technique can be employed. This technique uses
a smaller volume of anesthetic than the multiple injections used in the supraperiosteal approach.
Indications. The infraorbital block is useful for procedures involving more than two maxillary teeth, in the presence
of infection that contraindicates the supraperiosteal technique, and when the supraperiosteal approach has been
ineffective.
Intraoral Technique. The area involved in the injection site is cleaned with sterile gauze and a topical antiseptic is
applied. The infraorbital foramen is located by palpation of the infraorbital notch. Applying pressure in this area
causes the patient to experience a dull ache when the foramen is found. The injection site is parallel to the maxillary
second premolar at the height of the mucobuccal fold. The average penetration of the needle is approximately 2 to 3
cm, depending on the height of the mucobuccal fold and the height of the foramen from the maxillary teeth. The
position of the needle tip should be at the opening to the foramen, with the bevel facing the opening. This block
requires approximately 1 mL of anesthetic solution. Finger pressure over the foramen during the injection should not
detect ballooning of the tissue. Continuous pressure after the injection for up to a minute allows the solution to be
deposited in the foramen, anesthetizing the anterior and middle superior alveolar nerves.
Extraoral Technique. After the infraorbital ridge of the maxillary bone is located, the infraorbital foramen is
palpated approximately 2 cm from the lateral surface of the nose. The infraorbital canal lies at a 45-degree angle
backward and upward at its exit from the maxillary bone. The anterior portion of the canal in the orbit is usually
covered with a thin bone plate. Because of this, the needle should start 0.5 cm below and slightly medial to the
foramen to allow for the slant of the infraorbital canal. The needle should not be advanced more than 0.5 cm past the
infraorbital foramen, and no more than 3 mL of anesthetic solution should be deposited in the infraorbital canal;
otherwise, the contents of the orbit can be involved and damaged. If the needle is not advanced past the opening of
the infraorbital canal, the anterior superior alveolar nerve cannot be blocked and, consequently, analgesia of the
gums, teeth, and inside of the upper lip is absent or inadequate.
Nasopalatine Nerve Block
This injection can be very painful because the palatal tissues are not as distensible as the labial structures. Therefore,
preinjection procedures should be performed to try to eliminate as much discomfort as possible, for example, by
applying topical anesthetic or pressure anesthesia. Digital pressure over the foramen for a minute results in a
pressure anesthesia. Additionally, slow injection prevents distention of the tissue, reducing the pain in the area. An
initial injection to the labial plate between the central incisors using a small amount of anesthetic helps to decrease
the pain of injection.
Indications. This injection provides palatal anesthesia when soft tissues are involved by augmenting anesthesia of
the six maxillary incisors, and by supplementing anesthesia of the nasal passages.
528
Technique. After the preparatory techniques as described earlier, the needle is inserted into the area of the incisor
canal over the crest of the papilla. The needle is advanced only 0.5 cm into the canal, and 0.25 to 0.5 mL of solution
is deposited.
Greater Palatine Nerve Block
The junction of the maxillary alveolar process and palatal bone is another area where distention of the tissues can
occur. Pain on injection here can also be avoided by preparatory techniques, such as using a topical anesthetic or
digital pressure.
Indications. This injection anesthetizes the posterior portion of the hard palate and the overlying structures up to the
first bicuspid on the injected side.
Technique. The greater palatine foramen is located between the second and third maxillary molars about 1 cm from
the palatal gingival margin toward the midline. The needle is directed to this foramen from the opposite side of the
mouth. The point of bisection of the palatal bone with the maxillary alveolar process is found, and the needle is
inserted very slowly until palatal bone is contacted; 0.25 to 0.5 mL of anesthetic is injected very slowly. It is
important to note that the greater palatine nerve can be blocked at any point anterior to the foramen. Additionally,
anesthesia of the mucoperiosteum of the palate will result.
Posterior Superior Alveolar Nerve Block
This block is commonly employed in dentistry. However, there is a potential for hematoma formation. The reason
for this is the presence of the pterygoid plexus of veins and the posterior superior alveolar artery (maxillary artery).
Indications. This nerve block is used for unilateral anesthesia of the maxillary posterior teeth, the alveolus, and the
gingiva.
Technique. The height of the mucobuccal fold above the maxillary second molar is located. Movement of the
patient’s lower jaw toward the site of injection allows more space for the area between the coronoid process and
maxilla. The operator’s forefinger is pressed against the area of the coronoid process and the needle is inserted at a
right angle to the occlusal surface of the maxillary teeth and at a 45-degree angle to the patient’s sagittal plane. The
index finger should be pointing in the direction of the path of the needle. The needle is inserted 2 to 4 cm and the
syringe is aspirated to verify that the artery is not entered; approximately 1 to 2 mL of local anesthetic is injected.
Maxillary Nerve Block
Indications. This injection is useful for diagnostic block for neuralgias or facial pains from the maxillary nerve, for
extensive surgical procedures on the upper jaw and teeth, and when inflammation prevents the use of alternative
techniques.
Intraoral Approach. In the intraoral approach, the needle is inserted into the greater palatine foramen until it
reaches the pterygopalatine fossa, where the maxillary nerve passes. In about 15% of cases, obstructions in the
greater palatine foramen prevent this approach.
Extraoral Approach. The needle enters the skin at the point of intersection of the lower border of the zygoma and
the anterior border of the mandibular ramus. The needle is directed slightly upward and back. When the convex
portion of the maxillary tuberosity is reached, the needle is advanced until it contacts the greater wing of the
sphenoid ( Fig. 24–15 ). Approximately 4 mL of solution is required for this block. This injection provides
anesthesia unilaterally to the skin of the nose, the lower eyelid, the upper lip, the maxillary
529
Figure 24-15 Extraoral posterior approach for nerve block of the maxillary division of the trigeminal nerve.(Redrawn from Bononi SR: The trigeminal nerve. In
Bennett CR [ed]: Monheim’s Local Anesthesia and Pain Control in Dental Practice, 7th ed. St. Louis, CV Mosby, 1984.)
sinus, the maxillary alveolar process, the maxillary teeth, the mucoperiosteum of the palate, and the maxillary buccal
fold.
SURGERY ON THE LOWER THIRD OF THE FACE
Surgery of the lower third of the face requires a block of the mandibular nerve. Mandibular nerve block can be done
anywhere from the foramen ovale to the mental foramen for surgery of the mandible, lower teeth, or superficial
operations of the mandibular region. This block is useful for minor reduction of mandibular fractures or extraction
of teeth. Dentists prefer intraoral routes, whereas anesthesiologists commonly use the extraoral route at the coronoid
notch.
Anatomy
The first two divisions of the trigeminal nerve have no motor components. The mandibular division is both sensory
and motor. The motor division does not emerge from the gasserian ganglion but joins the sensory branch after it
leaves the anteroinferior part of the gasserian ganglion. These pass together through the foramen ovale. From this
trunk, a motor branch passes to the internal pterygoid and the two tensor muscles. The trunk then separates into the
anterior and posterior divisions.
The anterior division comprises the external pterygoid, the masseter, and the temporal motor nerves. The long
buccal nerve, which is the sensory nerve of the anterior division, passes between the two heads of the external
pterygoid muscle to cross the anterior border of the ramus at the occlusal plane level of the mandibular second and
third molars. In the mandible, it supplies the mucous membrane of the cheek, the skin of the cheek, the molar buccal
gingiva, and the mucous membrane in the lower part of the buccal vestibule.
The posterior division comprises the auriculotemporal nerve, the lingual nerve, and the inferior alveolar nerve. The
auriculotemporal nerve is a sensory nerve to the zygomatic, buccal, and mandibular areas over the skin, which are
also supplied by branches of the facial (seventh cranial) nerve; the parotid gland by means of the parotid branch;
temporomandibular joint; skin and scalp over the upper part of the external ear; and side of the head up to the vertex
of the skull. The lingual nerve carries sensory input from the mucous membrane covering the anterior two thirds of
the tongue and the floor of the mouth, the lingual side of the mandibular gingivae, and the submandibular and
sublingual glands. The inferior alveolar nerve carries sensory input from all the lower molar and bicuspid
mandibular teeth and their periodontal membranes. The anterior portions of this nerve are called the mental and
530
incisive nerves. The mental nerve is sensory from the skin of the lower lip and chin plus the mucous membrane
lining the lower lip region. The incisive nerve is sensory for the incisors and cuspid teeth plus the associated
periodontal membranes.
Intraoral Block of the Inferior Alveolar Nerve
The anterior border of the ramus of the mandible is located. The needle is inserted at a point medial to this location
and approximately 1 cm above the occlusal surface of the third molar. The needle is advanced along the medial side
of the ramus, with the syringe remaining parallel to the occlusal surfaces of the mandibular teeth to a depth of
approximately 2 to 3 cm. If paresthesia is not elicited, the practitioner should advance the needle until the
periosteum is contacted, then move back 1 mm and inject approximately 1 to 2 mL of anesthetic. For complete
unilateral anesthesia of the mandible, the practitioner should block the lingual nerve by injecting 0.5 mL of
anesthetic solution as the needle passes the oblique line for the inferior alveolar block.
In addition, the long buccal nerve should be blocked by a separate injection of 0.5 mL of anesthetic solution into the
buccal mucosa just distal to the third molar.
Extraoral Block of the Mandibular Nerve
The needle is inserted into the space below the midpoint of the zygomatic process. This technique is essentially the
same as that used for the extraoral block of the maxillary nerve, except that after the needle contacts the lateral
pterygoid plate, it is withdrawn and reinserted with the needle directed upward and slightly posterior. The needle
should then pass posterior to the lateral pterygoid plate while the practitioner watches for paresthesia ( Fig. 24–16 ).
If no paresthesia is encountered, the needle should be stopped at a depth of 5 cm. A total of 3 to 4 mL of local
anesthetic is required for anesthesia.
Todorovic and colleagues evaluated the differences of three techniques that produce inferior dental anesthesia: the
[69]
direct intraoral approach, extraoral approach (Gow-Gates technique), and intraoral mandibular conduction
anesthesia (Akinosi technique). They studied 90 patients undergoing simple tooth extraction, who were randomly
selected into three groups. Each patient received 2 mL of 2% lidocaine with 1:80,000 epinephrine. There were no
differences between groups in providing painlessness or duration of anesthesia. The Gow-Gates technique was
slower in onset for blocking the external branch of the buccal nerve, the fastest onset obtained by direct intraoral
approach.
SURGERY OF THE NOSE AND NASAL SEPTUM
Surgery of the nose requires blocking the sensory nerves derived from the frontal, nasociliary, and infraorbital
Figure 24-16 The technique for the extraoral block of the mandibular nerve is essentially the same as that for the maxillary block, except that the needle is directed
upward and posteriorly, so that the mandibular nerve is contacted as it exits the foramen ovale.(Redrawn from Bononi SR: The trigeminal nerve. In Bennett CR [ed]:
Monheim’s Local Anesthesia and Pain Control in Dental Practice, 7th ed. St. Louis, CV Mosby, 1984.)
531
nerves. In addition, if nasal tip reconstruction is scheduled, the local anesthetic solution must be infiltrated from the
angle of the mouth to the mandibular rim. Sphenopalatine block is useful in providing unilateral anesthesia of the
nose and the upper lip. Full nasal anesthesia is required for rhinoplasty. Topical application of cocaine in the nasal
passages or submucosal infiltration is used for bloodless surgery of the nose, such as nasal septoplasty.
Pfleiderer and Brockbank evaluated the safety and necessity of using epinephrine with topical cocaine for nasal
[70]
surgery. Serial serum cocaine levels were estimated in 30 patients during routine nasal surgery, with half the patients
receiving preoperative nasal preparation with cocaine alone and the other half receiving a cocaine and adrenaline
combination. The serum cocaine values and the incidence of toxic effects of cocaine were compared between the
two groups. Results showed that the addition of adrenaline significantly reduced the systemic absorption of cocaine
during surgery but caused no significant increase in toxic cardiovascular effects compared with the use of cocaine
alone. No evidence of cocaine toxicity was seen in either group. Preparations including adrenaline were also
observed to intensify local nasal vasoconstriction, resulting in a better operative field. It was concluded that
adrenaline can still be a valuable as well as safe addition to topical cocaine used in the nose.
Technique. The outer nose is anesthetized by subcutaneous injection beginning at the glabella and going over the
lateral aspects of the nose ( Fig. 24–17 ). Several anesthetic tracks are required along each side. The bases of the alae
nasi, the back of the nostrils, and the piriform aperture must also be injected for complete anesthesia of the outer
nose.
The mucoperichondrium of the nasal septum and the mucosa of the lateral walls of the nose can be anesthetized by
topical application of local anesthesia. The nasal septum may also be injected with local anesthesia
submucoperichondrially ( Fig. 24–18 ). Taylor and colleagues studied the effects of local anesthetic infiltration
[71]
with vasoconstrictors during nasal operations. Plasma catecholamine concentrations were measured in 19 patients
allocated randomly to receive submucous infiltration with 4 mL of either 0.5% lidocaine with epinephrine 1:200,000
or prilocaine 0.5% with octapressin 0.03 IU/mL. Venous blood samples were obtained before and at 2, 5, and 10
minutes after infiltration. Plasma epinephrine increased from 0.35 to 1.72 mol/mL at 2 minutes infiltration with the
former solution whereas there was little change in plasma noradrenaline concentration. No similar peak in
adrenaline concentration occurred after infiltration with prilocaine/octapressin solutions, but with both solutions,
there was a small increase in plasma noradrenaline and adrenaline concentrations 10 minutes after infiltration, at the
time of surgical stimulation.
EAR SURGERY
Radical Mastoidectomy Anesthesia
The great auricular nerve is blocked by infiltration of local anesthesia along the mastoid process. The
auriculotemporal nerve is anesthetized by injection into the junction between the bony and cartilaginous parts of the
anterior wall of the auditory canal and by infiltration of the skin and periosteum around the auditory canal in front of
the ear.
Tympanotomy Anesthesia
Anesthesia of the auriculotemporal nerve, including the tympanic branch, can best be accomplished by injection into
the junction between the bony and cartilaginous parts of the anterior wall of the auditory canal.
Lancer and Fisch evaluated the efficacy of local anesthesia for middle ear surgery in 32 consecutive patients. Both
[72]
surgeons and patients expressed that anesthesia was satisfactory without any adverse effects. The use of EMLA
cream (2.5% lidocaine, 2.5% prilocaine) for minor ear surgery is now practiced. Its efficacy remains to be
[73]
determined.
532
Figure 24-17 The nerves of the right lateral nasal wall.(Redrawn from Bononi SR: The trigeminal nerve. In Bennett CR [ed]: Monheim’s Local Anesthesia and Pain
Control in Dental Practice, 7th ed. St. Louis, CV Mosby, 1984.)
Figure 24-18 Nerves of the nasal septum. Anatomy of the nasopalatine nerve and the anterior ethmoidal nerve.(Redrawn from Bononi SR: The trigeminal nerve. In
Bennett CR [ed]: Monheim’s Local Anesthesia and Pain Control in Dental Practice, 7th ed. St. Louis, CV Mosby, 1984.)
533
TONSILLECTOMY
There is always a controversy as to whether local or general anesthesia is preferable or safer for tonsillectomy. This
chapter is not the place for answering that question. Only the technique of providing regional anesthesia is described
here. Agren and colleagues evaluated 38 patients randomly assigned for tonsillectomy with either local or general
anesthesia. The parameters compared were time in the operating room, duration of the operation, perioperative
[74]
hemorrhage, number of ligatures required for hemostasis, postoperative hemorrhage, infection, and weight loss.
Postoperative discomfort was assessed with a visual analogue scale and a water drinking test. The total consumption
of analgesic drugs in the postoperative period was recorded. The authors showed that tonsillectomy under local
anesthesia, in suitable patients, is a safe alternative to tonsillectomy under general anesthesia, and that considerable
resources can be saved if the operation is performed with local anesthesia.
Anatomy. The area of the tonsils is innervated by the tonsillar branches of the glossopharyngeal nerve, the trunk of
which runs along the stylopharyngeal muscle.
Technique. Infiltration anesthesia is required in the mucous membrane of the posterior palatal arch, anterior palatal
arch, superficial peritonsillar tissue, base of tongue, floor of mouth, and tonsillar plexus. In addition, topical
anesthesia of the throat and palatal arches can provide additional comfort for the patient.
GLOSSOPHARYNGEAL NERVE BLOCK
Anatomy. The glossopharyngeal nerve supplies the posterior third of the tongue and the oropharynx from its
junction with the nasopharynx at the level of the hard palate. It also supplies the pharyngeal surfaces of the soft
palate and epiglottis, the fauces, and the pharyngeal wall as far as the pharyngoesophageal junction at the level of
the cricoid cartilage. As the ninth cranial nerve emerges through the jugular foramen, it is in close relationship to the
vagus and accessory nerves and the internal jugular vein. The glossopharyngeal nerve is medial to the styloid
process. The styloid process is the calcified rostral end of the stylohyoid ligament. The tip of the styloid process lies
halfway between the angle of the mandible and the mastoid process.
Technique. The styloid process provides a bony landmark for block of the glossopharyngeal nerve. The practitioner
can “walk” the needle across the styloid process until it slips off the posterior aspect of the process. Block of the
glossopharyngeal nerve may result in block of the vagus and accessory nerves. A volume of 1 to 2 mL of solution is
adequate for this block ( Fig. 24–19 ).
NECK DISSECTION AND RECONSTRUCTION
The trigeminal nerve and cervical plexus cover the greater part of the skin and mucosal surface that are involved in
major surgery for excision of carcinoma
Figure 24-19 Field block for neck surgery involving cervical plexus
block, superior laryngeal nerve block, and extended laryngeal nerve
block, along with subcutaneous infiltration of the field of
surgery.(Redrawn from Labat G: Regional Anesthesia: Its Technique
and Clinical Application. Philadelphia, WB Saunders, 1923.)
534
and reconstruction flaps from temporal, deltopectoral, and trapezius muscles. It is essential to have an accurate plan
of the proposed surgery for the appropriate block(s) to be performed (see Fig. 24–19 ). Yerzingatsian describes the
[75]
anatomic compartments of the neck and their innervation, with details of superficial, deep, and modified cervical
blocks that can be performed during thyroidectomy. Advantages and disadvantages of each technique are discussed.
Superficial and deep cervical blocks leave some structures unaffected. A modified cervical block is described and
can be used to overcome these difficulties.
TRACHEOSTOMY
In certain circumstances, emergency tracheostomy must be performed. General anesthesia may not be possible or
indicated in these patients. If intubation before the tracheostomy is to be done, a topical local anesthetic is applied to
the oro- and laryngopharynx for intubation. If intubation cannot be done, the region of tracheostomy can be
infiltrated with the local anesthetic.
THE THYROID REGION
This region derives its primary nerve supply from superficial branches of the cervical plexus. Injection of local
anesthesia at the midpoint of the posterior margin of the sternocleidomastoid muscle provides anesthesia in this area.
Infiltration subcutaneously and under the superficial fascia is necessary. Additionally, somatic nerves accompany
the superior thyroid artery to the superior pole of the thyroid gland, requiring injection above the superior pole of the
thyroid.
Cardiothoracic Surgery
In the anesthetic literature, more study and effort has been devoted to the effects of anesthesia and surgery on the
respiratory complications of upper abdominal and thoracic surgery than on any other topic. In thoracic surgery, the
importance of being able to use high oxygen concentrations with regional anesthesia, without the concomitant use of
potent cardiovascular and respiratory depressants, is a decided advantage. Postoperatively, such techniques allow
patients to emerge responsive and pain-free. This enables them to perform adequate deep breathing and coughing
maneuvers in the recovery room, thus reducing pulmonary morbidity rates.
Local or regional anesthetic techniques are indicated in patients with chronic pulmonary disease, congestive
cardiomyopathies, and other severe, debilitating diseases that necessitate the avoidance of heavy narcotic
supplementation or potent inhalation anesthetics. Certainly these techniques should not necessarily be reserved only
for severely and chronically ill patients. They can be used in a truly balanced anesthetic program in which the local
or regional technique is used to supplement a light general anesthesia. This combination provides adequate sedation,
control of ventilation, and comfort to the patient. This concept is not new. The regional technique serves here only
as an adjunct to the general anesthetic, which is controlled with an endotracheal tube to protect the patient’s airway
and to maintain adequate ventilation.
INNERVATION OF THE THORAX
The nerve supply to the thorax and upper abdomen runs along the intercostal spaces via the corresponding
intercostal nerves and branches. The lateral cutaneous branch of the intercostal nerve supplies the thoracic wall from
the midaxillary line. In addition, the anterior and posterior portions of the chest wall are innervated by brachial
plexus. There is overlapping innervation anteriorly from the lateral edge of the sternum bilaterally, from the anterior
cutaneous branch of the intercostal nerve. There is also overlapping innervation posteriorly from the spinous
processes of the vertebrae to the lateral edge of the paravertebral muscles, from the posterior primary rami of the
thoracic nerve roots.
Field block is difficult in the thoracic region because of the overlapping cutaneous distribution and protection of the
intercostal nerve, deep within the intercostal muscles under the rib.
535
SURGICAL PROCEDURES
Types of surgical procedures that are amenable to local infiltration and field block of the thoracic region are
summarized in Table 24–1 . By far the most common
TABLE 24-1 -- PROCEDURES THAT CAN BE DONE WITH REGIONAL ANESTHESIA

Anesthetic of Choice
Tube thoracostomy
Repair of skin laceration
Incision and drainage of skin abscess
Removal of skin lesions, biopsy
Insertion of a pacemaker
Pericardial effusion or drainage
Anesthetic Alternate *
Breast biopsy, mammoplasty
Rib resection
Drainage of empyema
Lung biopsy in debilitated patient
Thoracotomy in debilitated patient
Plastic procedures, skin flap, etc.
*Often requires supplementation with sedatives, narcotics, and, occasion ally, light general anesthesia.
surgical procedure performed with local infiltration is the tube thoracostomy for pneumothorax or pleural effusion
drainage. Another notable procedure (although not in the class of a thoracostomy) that is performed with regular
frequency under local anesthesia is the simple breast biopsy. Combined with adequate sedation, a small amount of
narcotic analgesia, or light general anesthesia, this procedure is extremely satisfactory as an outpatient procedure.
INTERCOSTAL BLOCKS
Of the local and regional anesthetic techniques, the most useful for thoracic and upper abdominal surgery is the
intercostal block. It is technically easier to perform than paravertebral or epidural blockade and provides adequate
somatosensory block. It does not provide visceral pain blockade for intra-abdominal procedures, but if combined
with celiac plexus block, it can be adequate when supplemented with a light general anesthetic. The intercostal
nerves can basically be blocked at three points. For most thoracic procedures, including thoracostomy, the
intercostal nerves are blocked at the angle of the rib posteriorly, just lateral to the sacrospinalis. The ribs here are
superficial and the block is proximal to the anterior and the lateral cutaneous branches. This approach provides
adequate anesthesia from the angle of the rib anteriorly to the midsternum in the dermatome served by the
corresponding nerve root. Blockade should encompass at least two dermatomes above and below the level of the
incision and should include the level of chest tube insertion.
The second approach is the posterior axillary line, used mostly for incisions anterior to the anterior axillary line and
for upper abdominal incisions. The advantage of this approach is that the patient can be kept supine. It provides
more rapid access for blockade in the unstable or less cooperative patient.
The third approach is parasternally, for surgical procedures on the sternum or for analgesia of sternal fracture. This
is the least useful of the three blocks. However, it may have a place in cardiac surgery with midline, sternum-
splitting incisions.
The technique of blockade is easily learned and is described in Chapter 20 . Some special points for thoracic surgery
are noted here. T1 has branches contributing to the brachial plexus, arising at the neck of the rib and passing over
the first rib to join the nerves from C8 to form the inferior trunk of the brachial plexus. Occasionally, in surgical
exploration of the apex of the lung, pain is transmitted via the brachial plexus, and a brachial plexus block needs to
be performed along with the intercostal blockade. T12 unites with branches from L1 to form the iliohypogastric and
ilioinguinal nerves and is, therefore, not a true intercostal nerve. Blockade of T12 is rarely ever performed.
536
It is preferable to perform the intercostal blocks before the surgical procedure and induction of general anesthesia to
provide anesthesia and analgesia supplemented by light general anesthesia and airway control. This approach
ensures controlled ventilation. An arterial line normally is inserted to monitor arterial blood gases and blood
pressure. The intercostal blocks provide adequate muscle relaxation for intercostal incision and exposure, but muscle
relaxants may be required to produce a quiet diaphragm and motionless field for the surgeon.
Long-acting local anesthetics have improved the efficacy of intercostal blocks as a technique to provide effective
operative and postoperative analgesia. The major goal still is to find a nontoxic, long-acting local anesthetic that can
provide 24 to 48 hours of analgesia with a single injection.
De la Rocha and Chambers studied 20 patients undergoing a posterolateral thoracotomy for lung resection or a
[76]
nonpulmonary procedure. They were divided into four groups. Group 1 was the control group. Patients in group 2
had an intercostal nerve block at the time of closure. Those in group 3 underwent a continuous intercostal nerve
block for 5 days. Electronic pain control was used in group 4. An additional group of patients (group 5) underwent
operation through an anterolateral thoracotomy and was compared with the control group. Breathing performance
was evaluated daily for 5 days with bedside spirometry, and intergroup comparison was done with the unpaired t test
and analysis of variance. Forced expiratory volume in 1 second (FEV1 ), expressed as a percentage of preoperative
values, was significantly better in group 3 (continuous intercostal nerve block) at 52.4 ± 9.2% (standard deviation; P
< .05) and in group 5 (anterolateral thoracotomy) at 52.0 ± 7.5% (P < .05) than in the control group (38.4 ± 8.8%) 5
days postoperatively. They concluded that the pain that follows posterolateral thoracotomy can be substantially
decreased with a continuous intercostal nerve block. Anterolateral thoracotomy is notably less painful than
posterolateral thoracotomy and should be considered the approach of choice for patients with decreased pulmonary
reserve who undergo uncomplicated pulmonary resection.
INTERPLEURAL BLOCK
Interpleural analgesia was first described by Kvalheim and Reiestad in 1984. The authors subsequently reported [77]
their results in 81 patients who had undergone renal surgery, unilateral breast surgery, and cholecystectomy with
subcostal incision. Postoperatively, 78 of these 81 patients were completely pain-free for a mean duration of 10
hours after a single injection of 20 mL 0.5% bupivacaine with epinephrine. In a study comparing interpleural
[78]
bupivacaine with placebo for postcholecystectomy pain, the interpleural technique was shown to decrease
postoperative patient-controlled morphine requirements and to improve forced vital capacity and FEV1 . The [79]
technique involves the percutaneous introduction of a catheter between the parietal and visceral pleura. The
introduction of an interpleural catheter using a lubricated glass syringe or the hanging-drop technique is generally
considered a relatively simple procedure ( Fig. 24–20 ). The apparently high degree of satisfactory postoperative
analgesia and the lack of adverse effects generated widespread interest in the technique. However, doubt was cast [80]
on the efficacy of the technique for post-thoracotomy pain by Rosenberg and colleagues, who demonstrated that [81]
interpleural bupivacaine was ineffective in reducing the need for intramuscular opioid after thoracotomy. Similarly,
in a double-blind study comparing intrapleural block with epidural fentanyl for post-thoracotomy pain, 7 of 8
patients dropped out of the study owing to inadequate pain relief by intrapleural block. [82]
Figure 24-20 Positioning of the patient for interpleural nerve block.(From Raj P: Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991,
pp 197–269.)
537
The mechanism of analgesia is unclear. Currently, it is believed that the local anesthetic solution diffuses from the
pleural space through the parietal pleura and the innermost intercostal muscles to provide multiple, unilateral,
intercostal blocks. However, there are differences between interpleural block and conventional intercostal block.
The interpleural technique provides analgesia but not anesthesia to allow the performance of surgery. Local
[80] [83]
anesthetic solution in the pleural space may also involve phrenic and splanchnic nerves. Indeed, in a case report,
interpleural block with 8 mL 0.5% bupivacaine provided impressive analgesia in a patient with pancreatic carcinoma.
The clinical report by Rosenberg and coworkers evaluating the use of a continuous intrapleural infusion of
[81]
bupivacaine for analgesia after thoracic surgery suggests that intrapleural bupivacaine, either as a bolus injection of
0.5% (15 to 20 mL) or as a continuous infusion of 0.25% (5 to 10 mL/hr), was unsatisfactory in the management of
postoperative pain after thoracic surgery. This report contradicts the initial reports of excellent analgesia achieved
with the intrapleural administration of bupivacaine and lidocaine after abdominal and thoracic surgery. [77] [78] [84] [85] [86] [87]
El-Baz and coworkers designed a study to compare the effects of intrapleural analgesia to continuous epidural
analgesia. A pilot study was conducted, and three patients received continuous intrapleural infusions of lidocaine
[88]
2% with epinephrine 1:200,000 at 15 to 20 mL/hr. Intrapleural lidocaine produced unfavorable results, and the study
was terminated because of the following problems:
1. Pain relief after thoracic surgery was inadequate. Two patients complained of severe pain (analogue pain
score 8 to 10), and one patient complained of moderate pain (pain score 6 to 8). Pain relief was achieved in
these patients by the additional uses of large doses of systemic narcotics (morphine intravenously, at 34 to
48 mg/24 hr).
2. The dose of lidocaine (300 to 400 mg/hr) caused systemic side effects in all patients. Somnolence,
disorientation, and muscle twitches were frequent. Somnolence impaired nursing care and the patients’
communications with their families. Serum lidocaine after 12 to 16 hours was between 2.4 and 4.7 µg/mL;
none of the patients had seizures. Seltzer and colleagues reported a 9% incidence of convulsions during
[87]
their evaluation of intrapleural bupivacaine.

3. Tachycardia and hypertension occurred in all patients. Epinephrine is usually added to intrapleural local
anesthetics to slow the absorption, prolong the effect on the intercostal nerves, and reduce the systemic side
effects of local anesthetics. The large dose of epinephrine infused (75 to 100 µg/hr) in their patients was the
probable cause of postoperative hypertension. High blood pressure was adequately controlled with
intravenous narcotics in two patients and was treated with a sodium nitroprusside infusion in one patient.
The side effects of intrapleural infusion of epinephrine are not desirable in patients with history of
hypertension and coronary artery disease.
EPIDURAL ANESTHESIA
Of all the regional techniques available for cardiothoracic surgery, none offers more versatility and reliability than
epidural catheter techniques.
Lumbar epidural anesthesia with a catheter is useful for upper abdominal and lower thoracic procedures, but the
volume and dose of local anesthetic required to provide adequate anesthesia for an upper thoracic procedure by this
technique may lead to toxicity or an inappropriately large blocked area (i.e., bladder and lower extremity). The usual
volume of anesthetic and dose requirements have been calculated by Bromage. He recommends between 1 and 1.6
[89]
mL of the local anesthetic per dermatomal segment. Greater spread is achieved with higher volume, and lesser
quality of block is seen with lower concentration. For instance, 30 mL of a 1% concentration of lidocaine produces a
higher sensory level than 10 mL of a 3% concentration of lidocaine in a study by Erdmeir and colleagues. [90]
However, low concentrations of anesthetic (i.e., 0.25% bupivacaine) may produce minimal motor block. Usual
thoracic surgical procedures require some degree of segmental motor blockade. The concentrations of currently used
anesthetic agents should be chosen with this in mind (e.g., 2% lidocaine or mepivacaine, 0.75% bupivacaine, 1%
etidocaine). Postoperative analgesia could be maintained with minimal motor block using 0.25% bupivacaine.
Addition of epinephrine reduces vascular absorption and enhances the efficacy of epidural block for the medium-
duration agents such as lidocaine, mepivacaine, or prilocaine. Epinephrine does not seem to improve duration and
quality of block with the longer acting agents such as bupivacaine and etidocaine.
Segmental anesthesia and analgesia can best be provided by insertion of the catheter close to the nerve root exit
from the spinal canal innervating those segments involved in the operative site. Therefore, thoracotomy incision in
the fifth intercostal space should have the catheter placed at T6–T7 interspace and passed cephalad 2 to 3 cm in the
epidural space. The spread of anesthesia would be approximately three to six segments with 10 mL of the local
anesthetic solution. This spares motor function of the bladder and lower extremities. In patient older than 60 years of
538
age or those with severe arteriosclerosis, the dosage of local anesthetic should be reduced by 50% in order to avoid
side effects because of increased spread of segmental block.
Although the technique of placement of epidural catheters is covered in Chapter 16 , an important feature about the
anatomy of the vertebrae in the upper and middle thoracic region should be stressed here. The spinous processes in
this region are directed sharply caudad, so that the top of the spinous process lies at the level of the lamina of the
vertebral body below, thus obscuring the interlaminar space. This necessitates a paramedian approach for needle
placement. The needle is directed cephalad at 130 degrees and 15 degrees medially, using the spinous process as a
guide. The negative pressure from the thoracic cavity is transmitted to the epidural space, but this is not reliable and
is not present in all patients. In chronic obstructive lung disease, it may actually be positive. Therefore, we
recommend the use of the loss-of-resistance technique.
Serious consideration should be given to the physiologic changes associated with thoracic epidural anesthesia before
using the technique as a major part of the anesthetic management. Epidural block is associated with inhibition of the
sympathetic nervous system. Because the sympathetic nervous system controls the vascular tone, the vasodilatation
caused by epidural block may produce significant hypotension if cardiac output is also decreased by inhibition of the
cardioaccelerator fibers. In these situations, the response to major volume changes is not normal. Significant
hypotension and bradycardia develop in a hypovolemic patient, whereas the normal responses would be tachycardia
and peripheral vasoconstriction. Therefore, it is unwise to use a thoracic epidural in a hypovolemic patient or to
allow a patient with a thoracic epidural to become hypovolemic during surgery. Matthews and Govenden [91]
compared paravertebral and extradural infusion of bupivacaine for pain relief after thoracotomy. Pain was controlled
in 20 post-thoracotomy patients by a continuous infusion of 0.25% bupivacaine through an extradural or
paravertebral catheter. Both techniques provided good analgesia. Hypotension and urine retention occurred
significantly less frequently in the paravertebral than in the extradural group.
The effects of epidural blockade on neuroendocrine response to thoracic surgery are variable. As mentioned earlier
in this chapter, adequate epidural block produces reduced catecholamine levels and metabolic response. Pituitary
and hypothalamic reflexes that result in increased ADH and ACTH responses may influence renal and adrenal
responses.
Respiratory effects of epidural anesthesia and analgesia are poorly studied. Concern over motor weakness of chest
wall resulting in decreased vital capacity (VC) and functional residual capacity (FRC) has not proved to be valid. In
sensory blockade to T1, motor blockade rarely exceeds to T3. In normal subjects, this blockade does not result in
significant reduction in either VC or FRC or ability to generate an effective cough. On the other hand, analgesia
produced by epidural blockade actually improves VC, FRC, and PaO2 , as well as the ability to cough effectively in
patients with severe pain.[92] [93] [94]
Epidural blockade for anything more extensive than the most superficial surgical procedures in the thoracic region
requires the addition of general anesthesia with an endotracheal tube, because protection of the airway and provision
for adequate alveolar ventilation is of equal concern with general anesthesia. The use of low concentrations of potent
inhalation anesthetic agents such as halothane, enflurane, or isoflurane allows high concentrations of oxygen to be
used in the inspired mixture. Postoperatively, the epidural catheter can be maintained to provide analgesia with a
continuous infusion of long-acting local anesthetic solution, usually bupivacaine. A lesser concentration of
bupivacaine (0.125%) has been mixed with meperidine (1%) to produce adequate analgesia without motor block.
Experience at some centers indicates that an infusion of 6 to 8 mL per hour of 0.25% bupivacaine maintains
adequate analgesia. This is a safe dose for avoiding systemic toxicity. The availability of assays for plasma
concentration of local anesthetics in most major hospital laboratories is not far from reality and should be done to
follow these patients.
The technique of intermittent administration of narcotic via an epidural catheter is also available. Currently, the
recommended narcotics for intermittent epidural administration are morphine sulfate 5 mg, fentanyl 75 to 100 µg,
and meperidine 50 to 75 mg. Fentanyl and meperidine have a much faster onset and shorter duration, probably
owing to their greater lipid solubility. Side effects are urinary retention, itching, and, occasionally, respiratory
[95]
depression, which may be delayed in onset. Patients with epidural catheters for continuous infusion or after epidural
narcotics should be monitored closely for the first 12 to 24 hours, preferably in an intensive care unit. [92]
Patients who have undergone major thoracic or abdominal surgery are prone to pulmonary complications because
pain prevents them from breathing deeply and coughing effectively. The eradication of pain by epidural block might
be expected to improve pulmonary function. However, the effects of epidural analgesia are not as dramatic as might
be expected. Some improvement in FRC and VC may be seen, but the results are not consistent, and improvement
[96]
is limited to reduction of deterioration rather than restoration of preoperative values. In contrast, there is a
[94] [97]
539
marked improvement in peak expiratory flow rate values in patients who receive epidural analgesia after gallbladder
surgery. [98]
Despite the above-mentioned advantages, the epidural block has not been widely practiced, mainly because the
epidural catheter must be placed in the midthoracic region for reliable analgesia after thoracic and upper abdominal
surgery. This placement is considerably more exacting than lumbar placement. Close surveillance of the patient is
necessary because of the risk of hypotension after every top-up with local anesthetic. The use of a continuous
infusion technique with low-dose local anesthetics, opioids, or combinations of very low doses of both to exploit the
synergistic effects of both groups of drugs has created renewed interest in epidural analgesia for management of
postoperative pain. For some patients, the additional analgesia with epidural opioids may be of critical importance.
This is particularly true when severe pain may compromise pulmonary function, leading to atelectasis and
pneumonia. Examples include patients with rib fractures or pain resulting from abdominal or thoracic incisions.
Those with underlying medical conditions such as respiratory insufficiency or obesity may also derive particular
benefit from the best available analgesia. In such situations, the need for profound analgesia is of major importance
and may make epidural opioids the preferred choice. (Epidural opioids and the combination of epidural opioids and
[99]
local anesthetics are discussed in Chapters 13 and 14 .)
Intermittent doses of epidural analgesics (narcotics or local anesthetics) can provide pain control after many types of
operations. However, their effectiveness is often accompanied by a high incidence of side effects.
[100] [101] [102] [103] [104] [105] [106] [107]
In an attempt to decrease the side effects associated with the intermittent bolus administration of epidural
[108]
analgesics while still preserving their effectiveness, many clinicians have started using continuous epidural analgesia.
El-Baz and colleagues designed a study to determine whether continuous administration of epidural analgesics
[109]
could provide good postoperative pain relief with an acceptably low level of associated side effects. This appears to
be true for the continuous administration of epidural morphine and for the epidural combination of morphine and
bupivacaine. This finding gains even more significance given the fact that the study (with the allowance of
supplemental narcotics given as needed) was designed so that all patients might have good postoperative pain relief.
The traditional method of on-demand intramuscular narcotics, long recognized by patients as an incomplete method
of pain relief, was clearly inferior to the continuous administration of bupivacaine.
[95] [110] [111]
The difference in postoperative pain relief afforded by the epidural infusion of morphine and bupivacaine together,
compared with the epidural infusion of morphine alone, was not significant. Others have suggested that bupivacaine
may not only be the local anesthetic of choice for combination with morphine but also may afford more pain relief
than epidural morphine can provide when administered alone. [106] [112]
The group receiving the epidural combination of morphine and bupivacaine tended to have more complete pain
relief than the epidural bupivacaine group. Epidural bupivacaine has been shown to provide excellent analgesia, [99] [113]
although the use of this agent appears to be associated with an increased likelihood of complications, especially
hypotension. [106] [107]
CARDIAC SURGERY
The use of epidural anesthesia for cardiac surgery is limited because of the unstable volume status of these patients.
However, the possible use of epidural and subarachnoid narcotics for postoperative pain management has recently
been explored. There has been a concern in cardiac surgery and other forms of vascular surgery that the use of
[114]
heparin precludes the placement of an epidural catheter owing to the potential for bleeding and hematoma formation
in the epidural space. In vascular surgery, this has remained only as a potential risk. Not enough data are available to
evaluate this bleeding risk with spinal techniques in cardiac bypass surgery.
Baxter and coworkers compared continuous bilateral intercostal block with conventional intravenous narcotics for
[115]
the first 48 hours after cardiac surgery. The subjective quality of analgesia was significantly superior with the
regional technique. However, pulmonary function tests, gas exchange, lung volume, and radiologic and clinical
evidence of pulmonary complications were not improved. The failure to reduce morbidity and the potential for
complications, such as pneumothorax, make it difficult to recommend the regional analgesia technique in this
situation.
Postoperative pain relief and stress hormones were examined by El-Baz and Goldin during the use of continuous
[114]
epidural infusion of morphine at a rate of 0.1 mg per hour in 30 patients (group B) after coronary artery bypass
grafting. They compared the epidural morphine routine to postoperative analgesia of IV morphine 2 mg over 2 hours
and on demand in another 30 patients (group A). Continuous epidural morphine infusion required occasional
supplementation with IV morphine and achieved effective analgesia in 80% of the patients. Pain relief was adequate
540
in 50% of the patients with the conventional method. The mean dose of morphine used with continuous epidural
infusion during the first 3 postoperative days was 5 mg per patient per day and was significantly lower than that
used systemically (mean of 18 mg per patient per day). Serum morphine was undetectable (below 2.5 ng/mL) in
group B and was significantly lower than that in group A (17 ng/mL). Epidural analgesia was associated with
adequate postoperative pulmonary and cardiovascular functions; nausea and vomiting occurred in two patients.
Levels of postoperative stress, serum cortisol, and β-endorphin were significantly lower in group B than in group A.
This study shows that continuous epidural infusion of morphine at a rate of 0.1 mg per hour provides selective and
effective pain relief and reduces postoperative stress after cardiac operations. This method of analgesia is associated
with minimal side effects and provides an alternative approach for treatment of pain after cardiac operations.
It is clear that the epidural delivery of narcotics can be highly efficacious, presumably working by selective binding
of the narcotic to opiate receptors in the posterior spinal gray matter. In this study, epidural morphine administered
by continuous infusion was found superior in essentially every way in a population of postoperative cardiac surgical
patients. Epidural morphine per se is associated with numerous side effects, but the continuous provision of the drug
is associated with a much lower incidence of problems. This technique of analgesia will probably become a more
routine procedure in the future.
Urologic Surgery
Genitourinary surgery includes procedures of the kidney, ureters, bladder, prostate, genitalia, and urethra. Patients
scheduled for such surgery are often at the extremes of age, may take multiple drugs, and may have borderline
cardiac and respiratory function (e.g., transurethral surgery). They may require multiple procedures, especially
cystoscopies or extraction of calculi. During surgery, the patients can be put in uncompromising positions (e.g.,
Trendelenburg, exaggerated lithotomy, or flank position), with elevated kidney rest.
The choice of regional anesthesia depends on the patient’s physical status, age, fluid and electrolyte balance,
previous drug therapy, and position during surgery. Most of the procedures, except kidney surgery, can be well
managed under regional anesthesia alone. Some require regional anesthesia combined with light general anesthesia
because of either exaggerated position or prolonged surgery. Although regional anesthesia has minimal effects on
glomerular filtration rate and renal perfusion with maintenance of normal blood pressure, general anesthesia
decreases renal perfusion, which is significant with mechanical ventilation.
RENAL AND PERIRENAL SURGERY
The kidney can be approached through lumbar, thoracoabdominal, or transabdominal incisions. For the lumbar
approach, the patient is in the lateral position with the operative side up and the kidney elevator beneath the 12th rib.
Flexion of the table causes the muscles of the loin to be taut, and elevation of the kidney bridge makes more space
available between the 12th rib and the ilium when the incision is made ( Fig. 24–21 ). This position may be
uncomfortable for a conscious patient but may also cause serious cardiovascular and respiratory embarrassment.
This is one of the most serious
Figure 24-21 The flexed lateral decubitus. Note that the kidney rest rises against the 11th and 12th ribs.(Redrawn from Martin JT [ed]:
Positioning in Anesthesia and Surgery. Philadelphia, WB Saunders, 1978.)
541
considerations for determining choice of anesthesia for renal and pelvicalyceal surgery. Besides, injury to the pleura
and lung is a potential problem with a subcostal incision. Endotracheal intubation and intermittent positive pressure
breathing (IPPB) may be indicated to avoid respiratory embarrassment and insufficient ventilation.
Spinal anesthesia, if chosen for renal surgery, should be selected only for patients in good physical condition. When
spinal anesthesia is used, careful consideration should be given to turning the patient gently to the lateral position
and watching closely for the effect of the elevation of the kidney bridge on the patient’s blood pressure and
respiration. Any preexistent hypovolemia only exaggerates the drop in blood pressure from the change in position
and hence is to be avoided. A good infusion line and ready availability of some vasopressor drug is mandatory for
this surgery, as is good rapport with the surgeon so that “break” and “lift” are used only to the degree necessary.
Both in the conscious and unconscious patient, pressure points should be adequately padded and the arms and
shoulders arranged to avoid stretching of the brachial plexus in order to avoid nerve palsies and pressure injuries.
The size and age of the patient also influence the surgical approach to the kidney. Osteoarthritis of the spine or
kyphosis may negate the usefulness of a lumbar approach, and an abdominal approach would be more logical.
Similarly, a patient with severe cardiorespiratory limitation is more suitable for an abdominal approach. In a
retrospective study of patients who underwent urologic surgery in the flank position under general anesthesia,
hypotension and postoperative pulmonary complications occurred in 33.3% and 19%, respectively. Atelectasis [116]
was by far the most common postoperative pulmonary complication. Early detection and treatment of pulmonary
complications usually lead to early resolution of the lesion. Residual effects of high spinal or epidural anesthesia
may reduce the effectiveness of cough in the postoperative period.
A continuous epidural anesthesia technique with a long-acting local anesthetic drug, (e.g., bupivacaine 0.5% or
0.75% or etidocaine 1%) combined with endotracheal light general anesthesia is a good alternative. Blood loss can
vary from 500 to 1500 mL, and adequate replacement with fluids or blood is needed to maintain blood pressure in
view of decreased peripheral resistance resulting from sympathetic block to T6 or T4.
In patients who cannot tolerate such sympathetic block, bilateral intercostal nerve blocks from T5 to T12 with 0.5%
bupivacaine combined with lumbar somatic blocks of L1 through L3 can be performed, and, again, light general
anesthesia is instituted to keep the patient comfortable with good control of respiration and cardiovascular status.
However, a close watch on the quantity of local anesthetic injected is mandatory, because with this technique, there
is a fast vascular uptake that can lead to systemic toxicity.
Intraoperatively, intercostal nerve block with 0.5% bupivacaine may also be performed by direct vision to provide
postoperative pain relief. In a study by Noller and colleagues, the patients with intercostal nerve blocks required
[117]
less postoperative systemic analgesics, ambulated sooner, and were on a regular diet earlier than the control patients.
Patients with renal artery stenosis may undergo either nephrectomy or a vascular reconstructive procedure. Patients
with atherosclerotic renovascular disease and known coronary artery disease have a higher mortality rate (22.4%)
compared with patients who have fibromuscular hyperplasia (3.4%). Similarly, preoperative impairment in renal
function causes an increased surgical mortality rate (22.5% versus 5.3%). [118]
Epidural anesthesia with or without supplementation can be done for arterial reconstructive procedures, but
sympathetic blockade in the presence of preoperative drug therapy, such as propranol or vasodilators, can cause a
precipitous fall in blood pressure and further reduction in regional blood flow.
Kidney biopsy as an open procedure also presents a problem in that patients may have collagen disorders, are
frequently hypertensive, and do not tolerate inhalational anesthetics or postural changes. The anesthesia of choice is
intercostal block supplemented with local anesthesia.
PROSTATIC SURGERY
Open prostatectomy can be either perineal or retropubic in nature. For the retropubic approach, spinal or epidural
anesthesia is ideal because the patients are generally older than 50 years of age, and to have them awake and pain-
free in the recovery period lessens postoperative agitation and restlessness from the presence of packs or urinary
catheter. Because the patient is supine in a retropubic prostatectomy, spinal or epidural anesthesia with light sedation
is adequate. There is also evidence to show that intraoperative blood loss is reduced as a result of regional anesthesia.
542
In perineal prostatectomy, because of the exaggerated lithotomy position combined with slight flexion of the trunk
and the Trendelenburg tilt, both regional and general anesthesia frequently can cause marked impairment in
cardiovascular and respiratory status. In this situation, patient comfort is of utmost importance. A combination of
spinal or epidural anesthesia with light general anesthesia is preferred ( Fig. 24–22 ).
Paraplegics are a special group of patients who may undergo repeated cystoscopies and stone manipulations, and
care must be taken to avoid autonomic hyperreflexia if the cord level is T6 or above. Either
Figure 24-22 The exaggerated lithotomy position. Note that

the lumbosacral area is in the Trendelenburg position, but the
thoracic area is horizontal. The perineum projects over the
end of the operating table to provide the surgical team
maximum accessibility to the area. Shoulder braces (A) are
placed over the acromion rather than medial to it. Additional
padding over the proximal fibula (B) protects the peroneal
nerve.(Redrawn from Martin JT: Positioning in Anesthesia
and Surgery. Philadelphia, WB Saunders, 1978.)
general anesthesia with mask or spinal anesthesia are effective means of preventing this phenomenon.
Transurethral Prostatectomy
Several major problems in these patients are of concern to the anesthesiologist as follows:
• Patients are generally in the older age group and can have other major systemic problems that should be
controlled preoperatively (e.g., hypertension, angina, congestive heart failure, presence of cardiac
pacemaker, diabetes mellitus, neurologic problems, renal failure).
• Absorption of irrigating fluid can cause fluid overload, hyponatremia and water intoxication, and
hypothermia.
• Blood loss (usually > 500 mL) is difficult to determine because blood is returned with some urine and
large amounts of irrigating fluid.
• Continuous postoperative bleeding tendency can be due to coagulation problems caused by urokinase, or
other drugs.
Regional anesthesia is considered the anesthesia of choice for transurethral resection of the prostate (TURP) because
the patient can exhibit early signs of fluid overload and water intoxication. Because bladder sensation from
[119]
overfilling can be uncomfortable, a T9 to T10 level is desirable, but even a level of S3 is adequate in approximately
25% of patients. If the level is greater than T10, the capsular sign (pain on perforation of the capsule of the prostate)
may not be preserved.
543
Spinal anesthesia using 5% lidocaine (Xylocaine) or hyperbaric tetracaine is ideal for TURP. Sacral segments can be
missed with lumbar epidural block, and caudal anesthesia may be more suitable if the patient has had previous spine
surgery or has an osteoarthritic spine.
Blood loss during TURP is related to vascularity of the particular prostate, the surgical technique, the size of the
gland, and the length of the operation. In a study by Abrams and colleagues, a significant reduction in blood loss
[119A]
was noticed in the regional anesthesia group when compared with groups having general anesthesia. The blood loss
is usually less in patients with carcinoma of the prostate.
Hypothermia can occur from absorption of large amounts of irrigating fluid and cause shivering with increased
oxygen consumption and cardiac irritability. Nasal oxygen or mask oxygen supplementation can be used along with
regional anesthesia to provide more oxygen for these elderly patients.
BLADDER SURGERY
Cystoscopic procedures done for diagnosis or surgical manipulation are relatively minor procedures and may even
be performed on an outpatient basis. Spinal, lumbar epidural, caudal, or transsacral block provide entirely
satisfactory analgesia. Urethral instrumentation, especially in females, can be performed with topical anesthesia with
2% lidocaine jelly without much discomfort to the patient. Conduction anesthesia to achieve a level of T9 is equally
satisfactory, and the choice of drug depends on the predicted duration of analgesia.
Suprapubic Cystostomy
Regional anesthesia in the form of spinal, epidural, or caudal anesthesia, or field block can be performed. However,
with field block or local infiltration anesthesia, owing to the limited areas of muscular relaxation, surgical exposure
may cause some discomfort to the patient. In the presence of a scar from a previous operation, abdominal field block
may be difficult, and then intercostal blocks of T8 to T12 with paravertebral lumbar somatic block of L1 to L3 have
to be used to provide analgesia of the lower abdomen, and an infiltration of analgesic solution into the retropubic
space of Retzius must be administered to provide good analgesia for the bladder.
Field Block for Suprapubic Cystostomy. Bilateral rectus sheath block is performed through wheals at the lateral
margins of the rectus between the umbilicus and the pubis. The wheals are joined by lines of subcutaneous
infiltration and a similar linear wheal, subcutaneous and intradermal, from the umbilicus to the pubis. From a wheal
3 cm above the symphysis, a needle is inserted backward and downward, keeping its point near the bone; about 30
mL of local anesthetic is injected into the retropubic space of Retzius. Intravenous sedation can be supplemented to
provide comfort for the patient.
Total Radical Cystectomy and Ileal Loop. Regional anesthesia alone is unsuitable because of the long duration
and extent of this surgery. Blood loss can be considerable, and hypotensive anesthesia has been advocated to
minimize blood loss. By producing sympathetic blockade, continuous epidural anesthesia has been shown to reduce
intraoperative blood loss, but the length of surgery demands a light general anesthesia supplementation. Early
extubation and continued postoperative analgesia can be achieved by continuous epidural block. [117]
Patients scheduled for ileal conduits may be dehydrated owing to extensive bowel cleansing preoperatively with
enemas, and particular care should be taken to hydrate these patients before instituting sympathetic block. Also,
manipulation of the bowel during surgery can cause significant third space losses, and these losses, combined with
the inability to measure urine output, necessitate use of a central venous pressure catheter or similar invasive
procedures to monitor volume status in these patients.
URETHRAL PROCEDURES
Simple procedures such as external urethrotomy or dilation of the urethra can sometimes be performed with topical
anesthesia using 2% lidocaine jelly, especially in older patients and in paraplegics who are not prone to autonomic
hyperreflexia. With good premedication or intravenous sedation, topical anesthesia can be widely employed in
[120]
elderly patients with poor risk status. Penile block also offers good analgesia for the distal urethra and is very simple
to perform in an outpatient setting. The complications from block of the penis are minimal, and this procedure can
be performed by any physician in a clinic setting.
Internal urethrotomies and urethroplasties use the lithotomy position, which requires good sacral block with some
lumbar block for muscle relaxation in the legs to keep the legs in the stirrups. Caudal or spinal anesthesia is ideal for
544
these procedures, and with intravenous supplemental sedation, patients can be kept comfortable. Urethroplasties are
done in the exaggerated lithotomy position, and the duration of surgery (3 to 4 hr) and the required positioning
warrant good patient selection for regional anesthetic techniques. Subarachnoid block using hyperbaric tetracaine
with epinephrine or continuous lumbar epidural block with 0.5% bupivacaine have been employed with good
success. Supplemental sedation is usually necessary. The Level of block needed is T8 to cover the innervation of the
bladder.
OPERATIONS ON THE EXTERNAL GENITALIA
These procedures are done in patients of various age groups. Because high reflexogenic sensitivity is present in the
genital and perineal areas, when general anesthesia is employed, deep planes of anesthesia are generally required to
prevent undesirable autonomic reflexes such as laryngospasm. Neural blockade in the form of penile, caudal, saddle,
or epidural block suppresses these responses completely and is definitely advantageous. Moreover, surgery to the
penis, scrotum, and testes is frequently done on an outpatient basis, and deep general anesthesia prolongs the stay in
the recovery room. The other major reasons for use of regional techniques are the provision of postoperative pain
relief and removal of the need for analgesics in the immediate postoperative period.
Surgical procedures on the penis, such as circumcision and hypospadias correction, lead to moderate pain in the
postoperative period. In children, agitation, restlessness, pain, and (sometimes) manipulation of the operated site
may lead to postoperative hemorrhage. Caudal and penile block both have been employed in children under basal
anesthesia or light general anesthesia with mask. These techniques have proved valuable in providing postoperative
analgesia.
For caudal block, the child is placed in a lateral or semiprone position after induction of general anesthesia or basal
anesthesia with ketamine or a barbiturate. Bupivacaine 0.25% (0.15 mg/kg) can be injected through the
sacrococcygeal membrane with a 1 ½-inch 20-gauge (G) needle. The usual complications associated with a caudal
block are dural puncture, intravascular injection, intraosseous injection, intrapelvic injection, and rapid intravascular
absorption, which cause local anesthetic toxicity. These complications need to be anticipated and avoided. In a study
comparing caudal analgesia (1.5 mg/kg bupivacaine) with IM morphine (0.15 mg/kg) in 40 male children, caudal
analgesia was found to be better than morphine for postoperative pain relief.
In the series of Soliman and Tremblay, a block of the dorsal nerves of the penis resulted in good postoperative
[121]
analgesia in 96% of the children and proved a good alternative to narcotic analgesics. Penile block is a simple and
safe method to perform in adult and pediatric patients, with fewer associated complications than caudal block. Block
of just the dorsal nerves of the penis leaves an area on the ventral aspect of the distal penile shaft sensitive, and a
more complete block of the penis would eliminate this. In a study by Goulding in both adult and pediatric patients
[122]
with this block, none of the patients required postoperative analgesics within the first 12 hours and none of the 25
patients had hematoma formation. In a prospective trial comparing the analgesia and adverse effects produced by
caudal block with penile block in 38 boys undergoing elective circumcision, it was found that the degree and
duration of analgesia appeared similar after the immediate recovery stage. However, the caudal block group had a
higher incidence of motor blockade. There were no significant differences between the groups with regard to delay
before first administration of analgesics. [123]
Penile block can be performed in a supine position with no discomfort to the adult patient; this block has a high rate
of success and is especially useful in the outpatient population.
Penile prosthesis surgery requires 3 to 4 hours of analgesia and can be performed under spinal anesthesia using
hyperbaric tetracaine with epinephrine, or with lumbar or caudal extradural blockade using 15 to 20 mL of 0.5%
bupivacaine.
Surgical procedures on the scrotum, testicles, epididymis, and vas deferens can be done under spinal anesthesia or
extradural block, depending on the duration and extent of surgery. Varicocelectomy may require analgesia to the
level T10 or T8, and both spinal and lumbar epidural block are applicable.
In clinics vasectomies are usually done under local infiltration anesthesia with 1% lidocaine or mepivacaine.
However, reconstructive operations on the vas require several hours of surgical time, and continuous lumbar
epidural block with 0.5% bupivacaine is a good choice.
545
RENAL TRANSPLANT SURGERY
Chronic renal failure progresses toward a multiorgan system imbalance and failure. The patient with end-stage renal
disease who requires surgery has a continuum of problems affecting homeostasis in spite of hemodialysis used for
correction of underlying electrolyte and metabolic disturbances.
Understanding the characteristics of the renal failure patient helps the anesthesiologist to design a rational approach
to management. The following disturbances may be observed. [124] [125] [126]
Anemia. Anemia with hemoglobin between 5 and 8 g/dL is frequently seen. The body attempts to compensate for
this via a hyperdynamic cardiovascular state with an increase in cardiac output up to three times the normal rate.
Metabolic acidosis and increased levels of 2, 3-diphosphoglycerate shift the oxygen dissociation curve to the right
and facilitate tissue oxygenation. [126] [127]
Coagulopathies. The most frequently seen coagulation defect is platelet adhesive abnormality, which can be largely
corrected by hemodialysis. Other causes include systemic heparinization used during hemodialysis or chronically for
patency of vascular shunts. [128] [129]
Acidosis. The acidosis resulting from the inability to excrete hydrogen ion (H+ ) is usually rather severe, with
bicarbonate levels between 18 and 24 mEq/dL. The acidosis persists despite hemodialysis. [130]
Hydration. The volume status of the patient may be difficult to determine without central venous monitoring. If the
patient is chronically hemodialyzed and has been dialyzed within the last 24 hours, the intravascular volume may be
decreased while the total body water may be increased. Patients having symptoms of congestive heart failure are
most likely to have a significant increase in intravascular volume. [128] [130] [131]
Hypotension. Hypotension after induction of anesthesia is frequently seen. Attenuation of the reflex
vasoconstrictive mechanism from chronic antihypertensive medications, cardiac depressant effects of uremia, and
impaired sympathetic nervous system from other causes such as diabetes mellitus, uremia, and shunting from
arteriovenous formation are thought to contribute to the hypotension. [127] [128]
Electrolyte Imbalance. Hyperkalemia is the most serious and frequently seen problem. Elective surgery is not
recommended if the serum potassium concentration is greater than 5.5 mEq/L. Treatment consists of either
intravenous calcium infusion, glucose and insulin infusion, or sodium bicarbonate to acutely lower the serum
potassium level. Potassium exchange resin can alternatively be used for long-term therapy. [124] [128] [130]
Hypocalcemia from alteration in calcium and phosphate metabolism of vitamin D formation results in an increase in
bone resorption, leading to fractures, bone pain, pruritus, and depressed reflexes. [132] [133]
Hypermagnesemia, which can be iatrogenically magnified with magnesium-containing antacid medication, causes
potentiation of neuromuscular block (depolarizing and nondepolarizing). This imbalance can be partially treated
with calcium administration. [124] [133]
Neurologic Problem. Neuropathy of uremia consists of sensory loss, twitching, and dysesthesia. This process can
partially be reversed with dialysis and, in some cases, totally with transplantation. [132]
Hypertension. Systemic hypertension from fluid overload or underlying vascular disease is a frequent complication.
In severe cases, the patient may be refractory to therapy despite a multipharmacologic regimen and dialysis.
Additional vascular problems, such as congestive heart failure and atherosclerosis may be present.
Infection. The leading cause of death in the postoperative period is sepsis, which is most often of pulmonary origin.
Immunosuppression from underlying disease states, such as diabetes and immunosuppressive drugs, contribute to
the patient’s susceptibility to infection. Viral hepatitis from chronic dialysis and blood products also has a high
incidence. Strict aseptic technique is advisable. Judicious use of hemodynamic monitoring is essential to prevent
additional portals of infection. [132] [134]
Full Stomach. A patient may undergo emergency transplantation with a full stomach. Nausea and vomiting are
common in this patient population.
Advantages of Regional Technique
546
Regional block does provide the patient with several advantages. First, the use of skeletal muscle relaxants can be
avoided with spinal and epidural anesthesia. Muscle relaxants such as gallamine, dimethyltubocurarine, and
pancuronium can be harmful because they depend primarily on renal excretion for their elimination. Only d-
tubocurarine is eliminated by the biliary system to a significant degree in the absence of renal function. This may
become a less important consideration with the availability of neuromuscular blocking agents, such as atracurium,
which are not excreted by the kidney. Additionally, hypermagnesemia often accompanies chronic renal
insufficiency, and magnesium ions decrease acetylcholine release at the motor end plate. Therefore, more receptors
are vacant for occupation by nondepolarizing muscle relaxants and may be partly responsible for the prolonged
neuromuscular blockade seen in patients who have general anesthesia. This problem is avoided if a regional
anesthetic is administered. Another advantage of regional anesthesia when intra- or retroperitoneal dissection is
required is that the sympathetic blockade associated with spinal and epidural anesthesia enhances surgical exposure
by constricting the bowel, thus avoiding the dilatation associated with nitrous oxide anesthesia. [130]
A third advantage of regional anesthesia is the avoidance of significant cardiac depression. Cardiac stability is
especially desirable in patients (e.g., diabetics) who may have cardiomyopathy or coronary angiopathy. Maintenance
of cardiac sympathetic tone is possible in procedures, such as nephrectomy and transplantation, that require
anesthesia below the T7 level, because the lowest cardioaccelerator fibers generally exit from the spinal cord at the
T5 level. Other patients may have significant acid-base and electrolyte abnormalities. Although carbonic acid can be
eliminated by the lungs, other acid by-products of metabolism require renal excretion. Furthermore, many patients
with renal failure, especially those with chronic renal insufficiency, suffer from a metabolic acidosis that alone
depresses cardiac function. The acidosis also promotes calcium ion excretion in these patients, who are often already
hypocalcemic due to secondary hyperparathyroidism. Hypocalcemia may further depress cardiac function.
Maintenance of a normal extracellular potassium concentration is dependent on intact renal function; therefore,
these patients are frequently hyperkalemic. Hyperkalemia alone, like hypocalcemia and acidosis, can cause
significant cardiac depression and arrhythmia. These abnormalities frequently occur together, especially in patients
who receive emergency transplantation after not having undergone dialysis for 36 to 48 hours. Combined with the
cardiovascular depression caused by potent inhalation anesthetics, these electrolyte abnormalities can result in life-
threatening hypotension, bradycardia, and dysrhythmias.
A fourth advantage is that airway protective reflexes are maintained intact. This protective mechanism is particularly
important for a renal transplantation recipient who undergoes surgery on short notice because a kidney becomes
available; such a patient may have a full stomach. This factor is becoming increasingly important in all types of
organ transplantation as cadaveric donation becomes more widely accepted by the public. In addition to lowering
the risk of aspiration, the maintenance of intact airway reflexes avoids endotracheal intubation and the concomitant
risk of infecting the lower respiratory tract in patients who are frequently immunosuppressed.
A fifth advantage of regional anesthesia is that postoperative pain relief can be provided without the use of narcotics,
which may be poorly excreted and cause significant sedation and respiratory depression. The duration of analgesia
[135]
can be extended beyond the immediate postoperative period with the use of sterile plastic catheters, which can be
safely placed in the epidural or caudal space and in the axillary sheath. An additional advantage of regional
anesthesia is its greater safety in diabetic patients in whom the signs and symptoms of hypoglycemia may be more
readily observed ( Table 24–2 ).
Techniques and drugs recommended for regional anesthesia in patients with chronic renal failure are summarized in
Table 24–3 . Commonly used drugs and recommended dosages are listed in Table 24–4 .
Among the regional anesthetic techniques, spinal anesthesia offers the advantage of exposing the patient to the least
amount of drug. Drugs administered during spinal anesthesia act on nerve roots in the subarachnoid space, where
they are surrounded by less protein-rich covering than they are in the epidural space or in the periphery. Therefore,
spinal anesthesia generally requires only a fourth or a fifth of the amount of drug needed for caudal, epidural, or
peripheral nerve block. This consideration is particularly important in patients who suffer from both renal and
hepatic insufficiency.[136]
Continuous epidural anesthesia is recommended for both peritoneal and extraperitoneal abdominal procedures.
547
TABLE 24-2 -- ADVANTAGES OF REGIONAL ANESTHESIA FOR THE RENAL PATIENT

Avoids skeletal muscle relaxants
Avoids cardiac depression
Decreases risk of aspiration with maintenance of intact airway reflexes
Reduces risk of infection by avoiding endotracheal intubation
Provides postoperative pain relief
Improves operative field with constricted bowel
Avoids volatile anesthetic agent and potential metabolic and electrolytic problems
TABLE 24-3 -- SUGGESTED TECHNIQUES OF REGIONAL ANESTHESIA ACCORDING TO SURGICAL PROCEDURE

Surgery Level Block
Splenectomy T4–T6 Continuous subarachnoid block
Continuous epidural 1.5–2 mL/dermatome or single-shot epidural
Nephrectomy T4–T6 Continuous epidural
Single-shot epidural
Subarachnoid block
Retroperitoneal iliac renal implant T8 Continuous epidural
Single-shot epidural
Subarachnoid block
Parathyroid C1–C4 Deep cervical plexus block
Block of superficial branches of cervical plexus or local infiltration
Vascular access C5–T1 Interscalene
Scribner shunt Supraclavicular
Brescia-Cimino arteriovenous fistula Infraclavicular
Axillary
Nerve block at elbow
Local infiltration
Although technically more difficult, it affords almost unlimited duration for surgery. Caudal anesthesia is not
recommended because of the risk of infection, increased incidence of block failure compared with epidural
technique, and the large amount of drug needed to achieve a minimum T6 level. Some authors have reported that the
onset of epidural and subarachnoid block is prolonged in the uremic patient. [135]
Supplementation
Regional anesthesia occasionally requires supplementation, which may range from light sedation for patients with a
high level of anxiety or inability to tolerate a prolonged procedure to general anesthesia for inadequate, incomplete
block, or surgical procedures outlasting a single dose of regional anesthetic. Other reasons for supplementation
include difficulty in maintaining an airway if a high block is obtained and persistent intractable nausea and
vomiting. [130]
If the block works well, then N2 O-O2 and narcotic usually suffice. Halothane or isoflurane is recommended if a
volatile agent is needed. Caution should be exercised with use of halothane in a patient with concomitant liver or
heart disease. Succinylcholine can be used if the potassium level is less than 5.5 mEq/L. Repeated dosing is not
recommended. [130] [137]
Rarely is further relaxation needed. Agents of choice are atracurium or pancuronium bromide, except in the patient
[138]
who may not be able to tolerate a significant increase in heart rate. One may not want to use d-tubocurarine if the
patient is hypotensive. The use of gallamine and metocurine are not advised because both drugs undergo renal
excretion. The initial doses should be administered in small increments while monitoring with a peripheral nerve
stimulator. [130] [133]
548
TABLE 24-4 -- LOCAL ANESTHETIC AGENTS COMMONLY USED FOR CONDUCTION BLOCK IN PATIENTS WITH RENAL FAILURE
1.5- to 2- Time Maximal
mL/ Between Dose
Dermatome Top-up (Single-
Abdominal Procedures Initial Dose T8 Top-up Dose Doses (min) Length of Anesthesia (hr) Shot) (mg)
Epidural
Bupivacaine 0.75% 18–24 mL ½ original dose 1 3.5–5 225
100–120
Bupivacaine 0.50% 18–24 mL 45
2-Chlorprocaine 3.0% 18–24 mL 75 4–6 300
Etidocaine 1% 18–24 mL 60 1.5 500
Lidocaine 18–24 mL 60 1.5 500
Mepivacaine 2.0% 18–24 mL 60 1.5 500
Subarachnoid block up to 2.5 mL 0.75–1.5
Lidocaine 5% with epinephrine 100–150 mg 75

*
Tetracaine 1% with = vol. 10% d/L 10–14 mg 1.5–2
Carbocaine 4% 150 mg 1–2 150
Procaine 10% 100 mg 1 150

*10% dextrose in water.
Narcotics are sometimes needed, and fentanyl is the narcotic of choice. Respiratory depression and cardiovascular
depression are common features of all narcotics. Narcotics also decrease glomerular filtration rate and increase
antidiuretic hormone secretion. All narcotics have a prolonged effect in the anuretic patient, and doses should be
titrated. Reversal with naloxone is possible, but renarcotization may occur. [139] [140]
Fifty percent of intravenously administered atropine and hyoscyamine are excreted unchanged by the kidneys, and it
has been recommended that dosages of these drugs be reduced in patients with renal insufficiency. However,
scopolamine is almost entirely metabolized before renal excretion and is preferable if an anticholinergic agent is
indicated. These drugs are useful in patients undergoing spinal or epidural anesthesia because these patients may
[141]
become nauseated if the block is higher than T4 to T6.
Phenothiazines and benzodiazepines are metabolized by the liver, but they do rely on renal excretion of their
metabolites. This is particularly important for diazepam, which has three active metabolites. Seventy percent of the
metabolites appear in the urine; therefore, one may expect a prolonged effect from this drug, particularly when used
in larger doses. [125]
The longer acting barbiturates, barbital and phenobarbital, are best avoided in patients with renal failure because
they are excreted essentially unchanged in the urine. The shorter acting agents, such as pentobarbital, secobarbital,
methohexital, and thiopental, are more satisfactory because they are metabolized by the liver. It is important to note,
however, that the apparently short duration of action of thiopental is the result of redistribution among body tissues
and that it may have a more prolonged effect if large amounts are used. In addition, thiopental may have an
exaggerated effect in uremic patients because of the reduced protein binding and the reduced effectiveness of the
blood-brain barrier that have been demonstrated in these patients. [127]
Contraindications to Regional Anesthesia
The contraindications to regional anesthesia in patients undergoing renal transplantation are the same that apply to
all patients ( Table 24–5 ). Regional blockade should not be attempted in patients who are anticoagulated,
hypotensive, or septic, or who have localized infection in the region selected for needle insertion. At one time,
caudal catheters were associated with a high incidence of infection, but this incidence has decreased. The [142]
decreased incidence of catheter infections today has been attributed to improvements in catheter design, greater use
of the lumbar over the caudal route, use of single-dose ampules of local anesthetics, better sterilization techniques,
use of bacterial filters, and more frequent use of sterile disposable catheter trays. These improvements are
particularly important in immunocompromised recipients of transplantedorgans.
549
TABLE 24-5 -- CONTRAINDICATIONS TO REGIONAL ANESTHESIA IN THE RENAL PATIENT

Preexisting hypotension
Sepsis or local infection
Anticoagulation
Patient refusal
TABLE 24-6 -- COMPLICATIONS WITH REGIONAL ANESTHESIA IN THE RENAL PATIENT

Perineural hematoma or abscess
Hypotension
Infection
Neurotoxic reaction
Complications
The complications arising from regional blockade in patients with renal failure are similar to those that can occur in
other patients. These complications include hemorrhage, hypotension, infection, failure of technique, intravascular
injection, headache, local anesthetic toxicity, and pneumothorax in patients with supraclavicular brachial plexus
block ( Table 24–6 ).
The possibility of neurologic sequelae of spinal anesthesia in the transplantation recipient is a complex consideration.
In patients with uremic or diabetic neuropathy, neurologic symptoms may appear or progress at virtually any time.
The choice of an alternative anesthetic technique avoids confusion regarding the etiology of this complication.
Although uremic neuropathy is associated with demyelination, and the possibility of increased susceptibility of
nerve tissues to local anesthetics has been raised, investigators have shown that the effects of lidocaine and
bupivacaine are, in fact, of shorter duration in uremic patients undergoing brachial plexus block for arteriovenous
shunt placement. This effect was attributed to the hyperdynamic circulatory state of these patients. Superficial [130]
infection, epidural abscess, bacterial meningitis, and chronic arachnoiditis have been reported after spinal and
epidural anesthesia. Epidural abscess occurs primarily in patients who are septic at the time of catheter introduction.
The organisms most commonly implicated in iatrogenic purulent meningitis are Staphylococcus aureus, coliform
bacteria, and Pseudomonas species. However, none of the infectious complications of regional anesthesia has been
[142]
shown to have a higher incidence in patients with renal failure. [142]
The risk of hemorrhage in patients who are fully anticoagulated for dialysis contraindicates the use of regional block.
This is less common today because the heparin anticoagulation is generally reversed as the dialyzed blood is
returned to the patient. Furthermore, it has been shown that there is no increased risk of hematoma formation in
patients who are anticoagulated after an epidural catheter is already in place. Platelet function is decreased in
[143]
uremia but improved by dialysis; decreased function alone generally does not result in significant coagulopathy and
does not contraindicate regional block. Postoperative urinary retention of unusually long duration has been reported
after spinal anesthesia. The urinary retention resolved spontaneously after 1 month in one patient. The significance
of this occurrence is difficult to establish because there are many other factors that may contribute to urinary
retention in renal failure patients, and urinary retention has also been reported after donor nephrectomy in patients
who were under general anesthesia. [156]
Orthopedic Surgery
Many of the surgical procedures in orthopedics can be performed with regional anesthesia. Because of discomfort in
the nonanesthetized areas and long duration of some procedures, a combination of regional with light general
anesthesia may be better than regional anesthesia alone. The regional anesthesia techniques indicated for orthopedic
surgery can be classified according to the regions of operation: (1) upper extremity, (2) lower extremity, and (3)
trunk.
UPPER EXTREMITY SURGERY
Basically, the upper extremity can be divided into four regions: (1) the shoulder, (2) the elbow, (3) the forearm, and
(4) the wrist and hand.
550
The shoulder region ( Fig. 24–23 ) is innervated by C3 to C6 nerve roots. The C3 and C4 nerves are derived from
the cervical plexus and innervate the skin on top of the shoulder. The rest of the skin and deeper tissues
Figure 24-23 Dermatomal innervation, block required for shoulder anesthesia.(From Raj PP: Ancillary measures to assure success. Reg Anesth 5:9, 1980.)
are supplied by C5 and C6 nerve roots via the axillary nerve (C5, C6), deep scapular nerve (C5), and suprascapular
nerves (C5, C6) of the brachial plexus. Thus, analgesia for surgery of the shoulder requires blocking branches of C5
to C6 nerve roots. This is certainly true for superficial operations such as skin grafts, suturing of lacerated skin, or
reduction of a dislocated shoulder. It is, therefore, necessary to block the lower portion of the cervical plexus and the
upper portion of the brachial plexus in what can be called a “cervicobrachial plexus block.”
Because cervical and brachial plexuses are in the same plane and continuous, choice of needle entry is at the
interscalene groove, where the injected volume of local anesthetic is allowed to spread above and below the C6
vertebral level. Alternative choices are the supraclavicular and infraclavicular approaches. Because C3 and C4
[145] [146]
nerve roots are spared when either of those sites is chosen, additional subcutaneous block is necessary to block the
supraclavicular nerves. If the deeper tissues, including the shoulder joint, are to be operated on, the surgical incision
and exposure demand that T1 and T2 nerves also be blocked. This is best done by additionally blocking the second
intercostal nerve at the posterior axillary line ( Table 24–7 ).
Operations at the elbow (e.g., skin grafts, ulnar transposition, and closed and open reduction of the elbow joint)
require blocking of C5 to C8 and T1 to T2 nerve roots or their branches ( Fig. 24–24 ). Of these, C5 to C8 are more
critical if surgery is to be performed on the lateral or posterolateral aspect of the elbow. Block of C8 and T1 to T2
nerves are important for operations on the medial aspect of the elbow. In either case, tourniquet use requires
blocking of superficial branches of C5 to C8 and T1 to T2 nerve roots. The best approach to the brachial plexus for
elbow surgery is at the infraclavicular or supraclavicular region. The interscalene approach may not block C8 and
T1 nerve roots consistently. The axillary approach is not predictable in blocking the musculocutaneous nerve and
muscular
551
Figure 24-24 Dermatomal innervation, block required for elbow anesthesia.(From Raj PP: Ancillary measures to assure success. Reg Anesth 5:9, 1980.)
branches to the upper arm and is, therefore, a poor choice ( Table 24–8 ).
Surgery of the forearm region ( Fig. 24–25 ) requires blocking of the musculocutaneous nerve (C5–C7) on the
lateral aspect, the median nerve (C6–C8, T1), the ulnar nerve (C8, T1) on the anteromedial aspect, the posterior
nerve (C5–C8), and the medial cutaneous nerves (C8, T1) of the forearm derived from the radial nerve and medial
cord, respectively. They are all branches of the brachial plexus formed by the C5 to C8 and T1 nerve roots. The
infraclavicular approach is the technique of choice, because it blocks all of these
TABLE 24-7 -- EFFICACY OF TECHNIQUES: SHOULDER ANESTHESIA
Nerve Roots
Cervical Thoracic
Approach 3 4 5 6 1 2
Interscalene ± ± Separate intercostal block required
Supraclavicular ± ± Separate intercostal block required
Infraclavicular – –
Axillary – – – – – –
Choice of technique
Interscalene
Supraclavicular
Infraclavicular
From Raj PP: Ancillary measures to ensure success. Reg Anesth 5:9, 1980.
TABLE 24-8 -- EFFICACY OF TECHNIQUES: ELBOW ANESTHESIA
Nerve Roots
Cervical Thoracic
Interscalene ± –
Supraclavicular –
Infraclavicular
Axillary ± ± –
552
TABLE 24-8 -- EFFICACY OF TECHNIQUES: ELBOW ANESTHESIA
Nerve Roots
Cervical Thoracic
Choice of technique
Infraclavicular
Supraclavicular
Interscalene
Axillary
From Raj PP: Ancillary measures to assure success. Reg Anesth 5:9, 1980.
nerves at cord level. In addition, the intercostobrachial nerve in the axilla can be blocked easily, which helps to
relieve tourniquet pain (an important factor to consider for upper arm surgery). Supraclavicular, interscalene, and
axillary approaches are also possible but rate in descending order of superiority, as outlined in Table 24–9 .
Wrist and hand surgery ( Fig. 24–26 ) is common in everyday surgical practice. Median nerve decompression,
excision of the ganglion on the dorsum of the hand, and digital tendon and nerve repair are all amenable to brachial
plexus block. Anesthesia around the
Figure 24-25 Dermatomal innervation, block required for forearm anesthesia.(From Raj PP: Ancillary measures to assure success. Reg Anesth 5:9, 1980.)
553
Figure 24-26 Dermatomal innervation, block required for hand anesthesia.(From Raj PP: Ancillary measures to assure success. Reg Anesth 5:9, 1980.)
wrist is a difficult problem because of the richness of nerve supply, as well as cross-innervation, which occurs in
that area. One of the common failures of the axillary approach to the brachial plexus is the lack of good anesthesia at
the base of the thumb in the “snuff box” region. This is because three major nerves compete to innervate that area:
the median nerve from the anterolateral aspect, the radial nerve from the posterolateral aspect, and the
musculocutaneous nerve from the superolateral aspect. All three nerves must be blocked before good surgical
anesthesia can be obtained.
TABLE 24-9 -- EFFICACY OF TECHNIQUES: FOREARM ANESTHESIA
Nerve Roots
Cervical Thoracic
Approach 5 6 7 8 1
Interscalene ± ±
Supraclavicular
Infraclavicular
Axillary ± ±
Choice of technique
Infraclavicular
Supraclavicular
Interscalene or axillary
TABLE 24-10 -- EFFICACY OF TECHNIQUES: WRIST AND HAND ANESTHESIA
Nerve Roots
Cervical Thoracic
Interscalene ± –
Supraclavicular –
Infraclavicular
Axillary ± ± –
Choice of technique
Radial aspect
554
TABLE 24-10 -- EFFICACY OF TECHNIQUES: WRIST AND HAND ANESTHESIA
Nerve Roots
Cervical Thoracic
Supraclavicular
Interscalene
Infraclavicular
Ulnar aspect
Axillary
Supraclavicular
Infraclavicular
For this reason, supraclavicular and interscalene approaches are the primary techniques for surgery at the base of the
thumb. For median nerve decompression, surgery on the ulnar aspect of the wrist, and surgery of the hand and digits,
the axillary approach is very satisfactory ( Table 24–10 ).
LOWER EXTREMITY SURGERY
Basically, the lower extremity can be divided into four regions: (1) the hip, (2) the knee, (3) the leg, and (4) the
ankle and foot.
The hip region is innervated by T12 to S2 nerve roots. The iliohypogastric nerve provides cutaneous innervation to
the skin of the buttock and muscles of the abdominal wall. The ilioinguinal nerve supplies the skin at the base of the
perineum and adjoining portions of the inner thigh. The genitofemoral nerve arises from the L1 to L2 nerve roots. It
supplies innervation to the genital area and the adjacent parts of the thigh. Its lumboinguinal branch supplies the skin
over the area of the femoral artery and femoral triangle. The two major procedures in the hip region are total hip
arthroplasty and various surgical procedures for fracture of the neck of the femur.
Analgesia of the hip requires blocking T10 to S2 nerve roots or the peripheral branches proximal to the hip. To
accomplish so extensive a block, a major conduction anesthesia, such as spinal or epidural technique, is necessary.
There is controversy about the advantages and disadvantages of conduction anesthesia over general anesthesia in the
group of patients undergoing hip surgery ( Table 24–11 ). Hypobaric spinal anesthesia has the advantage that the
patient can be placed in the lateral position without the need for repositioning after the block ( Fig. 24–27 , Table
24–12 ).
TABLE 24-11 -- EFFICACY OF REGIONAL VERSUS GENERAL ANESTHESIA FOR HIP SURGERY
Regional Anesthesia General Anesthesia
Ease of administration Requires more skill Routine skill required
Induction of anesthesia Time-consuming Fast
Maintenance of anesthesia Adequate with catheter (may cause discomfort in a Routine

long procedure)
Intraoperative blood loss Less More
Deep-vein thrombosis Less More
Morbidity and mortality Less More

[23] [64] [73] [89] [128] [150]
Data from references and .
Total Hip Arthroplasty
555
Degeneration of the hip joint can result from general systemic diseases that involve bones and joints or local insults.
Some of the most common precipitating factors are osteoarthritis, rheumatoid arthritis, ankylosing spondylitis,
previous failed hip surgeries, neoplasms of the head and neck of the femur, congenital hip dislocations, and aseptic
necrosis of the hip. Most of
Figure 24-27 For surgery of the hip, dermatomes T10 through S2 need to be
anesthetized.
TABLE 24-12 -- HIP ANESTHESIA

Block T10 T11 T12 L1 L2 L3 L4 L5 S1 S2
Spinal
Hyperbaric
Isobaric
Hypobaric ? ?
Epidural
Lumbar
Caudal ? ? ? ? ?
Peripheral nerve *
Sciatic nerve
Femoral
Obturator − − − ?
Lateral femoral cutaneous nerve −
Efficacy
1. Hyperbaric and isobaric spinal
2. Lumbar epidural
3. Hypobaric spinal
4. Caudal epidural
*Peripheral nerve blocks not indicated.
these procedures are done in the lateral position. There is significant blood loss, and most patients require blood
transfusions. The use of methylmethacrylate to glue the components can cause acute cardiovascular changes, such as
hypotension, especially if the patient is hypovolemic.
Airway management and intubation may be difficult in patients with ankylosing spondylitis and rheumatoid arthritis,
both of which can involve the cervical spine, limiting the mobility of the neck. Forceful movement of the neck can
result in subluxation of the vertebrae causing spinal cord compression. Difficulty in opening the mouth may be
present because of the involvement of the temporomandibular joint. Rheumatoid changes of the cricoarytenoid
cartilages may cause narrowing of the larynx, making damage to larynx more common on intubation. However, [147]
spinal or lumbar epidural anesthetic may be technically difficult to perform in some of these patients. Caudal
anesthesia can be used successfully in these situations.[148]
556
Fractured Neck of Femur
This injury commonly occurs in older people. This population tends to have a high incidence of hypertension,
coronary artery disease, cerebrovascular disease, chronic obstructive pulmonary disease (COPD), diabetes mellitus,
and so forth. Because of the immobilization secondary to fractured neck of femur, there is a tendency for
development of hypostatic pneumonia, paralytic ileus, and decubitus ulcers. Early surgery and mobilization prevent
these complications.
Knee
The common procedures around the knee joint are arthroscopy, meniscectomy, ligament repair, patellar shaving, and
total knee replacement. For knee surgery, analgesia is required in the dermatomes innervated by L2 and S2 nerve
roots. Most knee procedures require a tourniquet around the thigh, which requires anesthesia up to the L1 nerve root.
The regional anesthesia techniques commonly used in the area of the knee are subarachnoid block and epidural and
lower extremity peripheral nerve blocks. Of these, spinal blocks—unilateral or bilateral, hyperbaric or isobaric—
tend to be more reliable. Successful lumbar epidural block gives excellent anesthesia of the knee and can be used for
prolonged pain relief with a catheter technique. If peripheral nerve blocks have to be used, all four major nerves
around the hip—sciatic, femoral, obturator, and lateral femoral cutaneous— should be blocked.
The sciatic nerve (L4 to L5, S1 to S3) is the largest nerve to the leg. It innervates the posterior part of the thigh and
all the areas below the knee joint except the medial aspect up to the medial malleolus. It can be used alone in
operations of these areas but often is used in combination with other nerve blocks.
The femoral nerve (L2 to L4) supplies the skin over the anterior surface of the thigh, the quadriceps muscle, and the
knee joint. The saphenous nerve, which is the terminal branch of the femoral nerve, supplies the medial side of the
calf up to the medial malleolus. Occasionally, it supplies the medial side of the foot. The saphenous nerve has been
used for pain relief for patients with fracture of the shaft of the femur.
The lateral femoral cutaneous nerve (L2 to L3) supplies the anterolateral and lateral aspect up to the middle of the
thigh. It also gives a branch to the patella.
The obturator nerve (L2 to L4) innervates the adductor muscles and skin over the medial aspect of the thigh. It also
sends an articular branch to the knee.
Figure 24-28 For surgery of the knee region, dermatomes L1 through S2 need to be anesthetized.(From Raj P: Clinical Practice of Regional Anesthesia. New York,
Churchill Livingstone, 1991, pp 197–269.)
557
Femoral, lateral femoral cutaneous, and obturator nerves can be blocked by the 3-in-1 block for lumbar plexus block
described by Winnie and colleagues. The sciatic nerve can be blocked by Labat’s approach with the patient in the
[149]
Sims position or by the supine approach described by Beck and Raj.

[2]
A continuous block using a catheter in the
[150] [151]
femoral canal was employed by Rosenblatt for postoperative pain relief after knee surgery in a child with cystic
fibrosis. [151]
Arthroscopy and transcutaneous meniscectomy have been done by local skin infiltration and controlled pressure
irrigation of the knee with local anesthetic solution ( Fig. 24–28 , Table 24–13 ).
[152]
Leg
For surgical procedures in this region, nerves L3 to L5 and S1 to S2 need to be anesthetized. If a tourniquet is used
over the thigh, nerves L1 to O4 also need to be blocked. Conduction blocks (e.g., spinal and epidural) are
satisfactory for this region. A combined sciatic and femoral block at the groin is also adequate. Saphenous nerve—
terminal branch of the femoral—and tibial and common peroneal nerves—branches of the sciatic—can be blocked
around the knee. Neuropathy and intravascular injection are more likely at this level ( Fig. 24–29 , Table 24–14 ).
TABLE 24-13 -- KNEE SURGERY

Block L1 L2 L3 L4 L5 S1 S2
Spinal
Hyperbaric
Isobaric
Epidural
Lumbar
Caudal
Peripheral nerve
Sciatic nerve
Femoral nerve
Obturator nerve
Lateral femoral cutaneous nerve
Efficacy
1. Hyperbaric spinal
2. Isobaric spinal
3. Lumbar epidural
4. Sciatic-femoral-obturator nerve block
5. Caudal epidural
Note: Supine position precludes hypobaric spinal.
Ankle and Foot
The procedures around the foot and ankle are plastic surgery of the toes, correction of hallux valgus and rigidus,
excision of Morton’s neuroma, transmetatarsal osteotomy, screwing of the malleoli, ligament repairs, and ankle
fusion. This region is innervated by the nerve roots of L3 to L5 and S1 to S2. If a tourniquet is needed, L1 to O4 also
must be blocked. As mentioned before, spinal and epidural blocks can be used satisfactorily. Sciatic and femoral
nerve blocks are useful for ankle surgery. For surgery of the forefoot, only sciatic block is necessary. Nerve blocks
around the ankle can be quite satisfactory for surgery of the foot if a tourniquet is not needed.
558
Figure 24-29 For surgery of the leg, dermatomes L1 through S2 need to be anesthetized.(From Raj P:
Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, pp 197–269.)
TABLE 24-14 -- LEG SURGERY

Block L1 L2 L3 L4 L5 S1 S2
Spinal
Hyperbaric
Isobaric
Epidural
Lumbar
Caudal − −
Peripheral nerve
Sciatic nerve
Femoral nerve
Obturator nerve
Lateral femoral cutaneous nerve
Efficacy
1. Hyperbaric spinal
2. Isobaric spinal
3. Lumbar epidural
4. Sciatic-femoral-obturator nerve block
5. Caudal epidural
Alternatives such as intravenous regional anesthesia of the leg have been used in clinical practice. The reliability of
regional anesthesia is not as good as in the upper extremity and patients are prone to toxic reaction if a large volume
is used ( Fig. 24–30 ).
TRUNK SURGERY
Lumbar laminectomies and fusions are the two common orthopedic procedures amenable to regional anesthesia.
These procedures are done with the patient in the prone or lateral position. Spinal anesthesia has been used
successfully with or without a light general anesthesia. The area to be anesthetized should cover T6 to S1
dermatomes. Epidural anesthesia has been used for induced hypotension in scoliosis surgery. A disadvantage of this
technique is that neurologic evaluation and monitoring of the lower extremities are not possible during surgery [153]
( Fig. 24–31 , Table 24–15 ).
General Surgery
Although its scope has become gradually narrower as many surgical specialties have developed, general
559
Figure 24-30 For ankle and foot surgery, dermatomes L3 through S2 need to be
anesthetized.(From Raj P: Clinical Practice of Regional Anesthesia. New York, Churchill
Livingstone, 1991, pp 197–269.)
surgery still encompasses widely differing operations on many parts of the body.
The general surgery procedures are performed on the gastrointestinal system. Thus, surgery of the esophagus,
stomach, duodenum, small and large bowel, appendix, rectum, and anus, together with the associated
TABLE 24-15 -- ADVANTAGES AND DISADVANTAGES OF SPINAL OR EPIDURAL ANESTHESIA VERSUS PERIPHERAL NERVE BLOCK FOR THE
LOWER EXTREMITY
Spinal/Epidural Peripheral Nerve Block
Can be accomplished by one needle prick Multiple needle pricks are necessary unless surgery is limited to one nerve distribution
Amount of drugs used is much less than for A large volume of drugs is used, especially if all the major nerves have to be blocked
peripheral nerve block
Easier to master and taught routinely More difficult to master and not taught frequently
Bladder and bowel dysfunction until the block wears No bladder or bowel dysfunction
off
More hemodynamic changes because of the more Fewer hemodynamic changes because the block is more limited
extensive block
Figure 24-31 For laminectomy, dermatomes T6 through S1 need to be anesthetized.(From Raj P:

Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, pp 197–269.)
560
organs such as the salivary glands, pancreas, biliary tract and gallbladder, liver and spleen, and also the associated
structures that compose the peritoneum, mesentery and omentum, all come into the field of general surgery.
The endocrine organs, namely, the thyroid, parathyroid, and adrenal glands, also fall within the scope of general
surgery, as do operations of the breast and hernias of the abdominal cavity. Minor surgical procedures include
surgery of the lymph nodes and lymphatics, sebaceous cysts, abscesses, and carbuncles.
GENERAL CONSIDERATIONS
Choice of Blocking Agent
The local anesthetic drug and dosage must be selected on the basis of expected duration of surgery and degree of
motor blockade required. Superficial procedures such as removal of a subcutaneous tumor or repair of an
uncomplicated inguinal hernia do not require intense, prolonged motor blockade, whereas the more extensive and
lengthy procedures involving the deep muscle layers of the abdominal wall and the intra-abdominal structures must
be accompanied by muscle relaxation. Information concerning precise dosage, concentration, and volumes of
anesthetic that are required to achieve the desired effects are covered in Chapter 18 , as is discussion of
complications and side effects of individual procedures.
Supplementation During Surgery
Small, short procedures can be carried out readily under regional anesthesia without sedation. For inpatients
requiring light sedation, the premedication given is likely to be adequate for the procedure. If further sedation is
required, small intravenous doses of diazepam, fentanyl, or thiopentone can be given at intervals throughout the
procedure. Heavy sedation may be required because the patient requests it, because pain or discomfort occur or are
expected to occur during the surgery, or because the operation will last longer than 2 hours. The sedation can be
provided intravenously in the form of fentanyl, diazepam, or thiopentone, or by light inhalation anesthesia consisting
of nitrous oxide and oxygen given by mask, nasal airway, or endotracheal tube. Any patient who receives heavy
sedation or whose head is covered with drapes during surgery should receive supplemental oxygen, and respiration
should be carefully and continuously monitored by precordial stethoscope throughout surgery.
If the patient is likely to need heavy sedation, and if, in the judgment of the anesthesiologist, management of the
airway and respiration is likely to prove difficult, such as may occur in the presence of obesity, a full stomach, or
certain positions such as the prone or jackknife position, it may be advisable to insert an endotracheal tube
immediately after completion of the block. The patient will then require light general anesthesia throughout the case.
Care must be taken to assure adequate ventilation and oxygenation when using this technique, especially when the
patient is in the prone position.
HEAD AND NECK SURGERY
Common general surgical operations around the head and neck include thyroid and parathyroid surgery, operations
on the lymphatic system, and surgery for lesions of the scalp and neck, including drainage of abscesses and removal
of cutaneous and subcutaneous tumors.
Nerve Supply
The scalp is supplied anteriorly by branches of the ophthalmic section of the trigeminal nerve: the supraorbital nerve,
the supratrochlea nerve, and the auriculotemporal nerve. Posteriorly, the scalp is supplied by branches of the
cervical plexus: the posterior auricular nerve and the greater and lesser occipital nerves. The somatic structures of
the neck and the skin overlying upper parts of the shoulders are supplied by the cervical plexus, which is formed
from the anterior rami of the first four cervical nerves. The superior pole of the thyroid gland is supplied by the
superior laryngeal nerve. The platysma muscle, which lies subcutaneously in the anterior neck, is supplied by the
facial nerve.
Applicable Regional Techniques
Block of the cervical plexus produces skin anesthesia of the occipital scalp, the neck, and the upper surface of the
shoulders, and relaxation of the deep and superficial neck muscles. It is suitable for soft tissue surgery of the area
described. If the surgical site is well localized, blockade of only some of the branches of the plexus is adequate in
some cases. Thus, removal of the subcutaneous lesion in the occipital region may be performed under block of the
561
posterior auricular nerves and the greater and lesser occipital nerves. The anterior scalp can be anesthetized with
similar procedures by supraorbital, supratrochlear, and preauricular nerve blocks.
Structures of the neck that are not innervated by the cervical plexus must be anesthetized separately if they are
involved in surgery. The pharynx, larynx, trachea, and upper esophagus, which are innervated by cranial nerves, are
not anesthetized to maintain the airway and therefore must be treated gently throughout surgery.
Special Considerations
Toxic Reations. When regional blocks of the head and neck are performed, the risk of toxic reactions to local
anesthetics is greater than when blocks are performed in other parts of the body. The reason is that the drug is
absorbed more rapidly, causing risk of small intra-arterial injections traveling directly to the brain without dilution
in the general circulation.
High Spinal Block. High spinal block is a possibility for cervical plexus block because of its closeness to the
subarachnoid space.
Phrenic Nerve Block. Blockade of the phrenic nerve frequently occurs in cervical plexus block. The phrenic nerve
is supplied by the third to the fifth cervical roots, and the branch from the fifth root may maintain some diaphragm
function. However, if the patient is likely to have difficulty in maintaining respiration with the intercostal muscles
(e.g., in patients with heart or lung disease, or in those with chest deformity or obesity), bilateral cervical plexus
block should be avoided.
Recurrent Laryngeal Nerve Block. Recurrent laryngeal nerve block occurs occasionally in cervical plexus block
and causes hoarseness or stridor. If the patient experiences respiratory embarrassment, endotracheal intubation may
be indicated.
Trachael Compression. If compression of the trachea is liable to occur because of extensive surgery adjacent to the
trachea, endotracheal intubation should be performed and the tube kept in place until danger of compression has
passed.
Thyroid Surgery. For thyroid surgery, anesthesia can be satisfactorily provided with bilateral cervical plexus
[154]
block, and block of the branches of the superior laryngeal nerves supplying the upper pole of the thyroid ( Fig. 24–
32 ). It is considered an advantage of this technique that phonation can be tested throughout surgery to ensure that
no nerve damage has occurred. Blocks of the superior laryngeal nerve, and the recurrent laryngeal nerve are
therefore undesirable. To avoid block of the superior laryngeal nerve, only those branches that supply the superior
pole of the thyroid are blocked, and this is best done under direct vision during surgery.
This technique should be used only in calm, cooperative patients. Moderate to heavy premedication is used,
avoiding drugs that impair cooperation. A suitable local anesthetic solution is 100 mL of 0.5% lidocaine with 0.25
mg epinephrine added, which provides 1½ to 2 hours of anesthesia. For anesthesia lasting up to 6 hours, 100 mL of
0.25% bupivacaine with 0.25 mg epinephrine added is used.
The patient lies supine with the head turned away from the side being blocked. Bilateral deep and superficial
cervical plexus blocks are performed with 40 mL of solution on each side. The line of incision is infiltrated
intradermally and subcutaneously with 15 mL more of solution to reduce bleeding and block the branches of the
facial nerve supplying the platysma muscle. During surgery 2 mL is injected over each superior pole of the thyroid
to intercept the branches of the superior laryngeal nerve.
Throughout surgery, oxygen is administered by nasal cannula, and intravenous sedation is given as required.
Thyrotoxicosis. Thyrotoxic patients are usually rendered euthyroid before surgery. They are excessively sensitive to
endogenous and exogenous catecholamines, and therefore, this technique is best avoided in patients with
thyrotoxicosis.
THE THORAX
General surgical procedures of the thorax are now generally restricted to the chest wall. Thus, the general surgeon
performs operations for pathologic conditions
562
Figure 24-32 Technique of regional anesthesia

for thyroid surgery. Note that bilateral deep
cervical plexus block is essential to anesthetize
the structures that will be stretched by
retractors. In addition, skin infiltration in the
area of the incision helps to minimize
bleeding.(From Raj P: Clinical Practice of
Regional Anesthesia. New York, Churchill
Livingstone, 1991, pp 197–269.)
of the breast, drainage of superficial abscesses, removal of cutaneous and subcutaneous tumors, and repair of
superficial trauma.
Nerve Supply
The chest wall extends from the clavicles and first ribs above to the costal margin below. In its upper part, it is
cloaked by the pectoral girdle. It is innervated at its upper margins by the cervical plexus and over the remainder of
its length by the first through twelfth intercostal nerves. The muscles connecting the upper limb to the trunk are
either supplied by branches of the brachial plexus (pectoralis major, pectoralis minor, and latissimus dorsi muscles)
or by branches of the cervical nerve roots (serratus anterior, lower trapezius, levator scapulae, and rhomboids).
Regional anesthesia of the chest wall can be provided by thoracic epidural block or peripheral nerve block. Thoracic
epidural block has the advantage of being a single injection technique with a low dose of local anesthetic and the
potential for augmentation if necessary. However, in addition to the disadvantages and hazards of lumbar epidural
anesthesia, which are described in Chapter 18 , there is a risk of spinal cord injury. Blockade is bilateral, and,
depending on the level of the block, there is likely to be involvement of both upper limbs and total block of the
cardiac accelerator fibers, causing the risk of bradycardia and hypotension. In addition, the cervical cord may be
involved, and this may result in phrenic nerve block and respiratory embarrassment. Despite these disadvantages, a
carefully and skillfully performed thoracic epidural block provides excellent anesthesia in selected patients. The
contraindications to this form of anesthesia are the same as for high spinal or high epidural anesthesia.
Peripheral nerve block avoids the disadvantages of thoracic epidural anesthesia and is preferable. When surgery is
confined to the lower part of the thorax (below T5), intercostal block alone is adequate. Two segments on each side
of the surgical site should be blocked. If the upper thorax is to be involved, superficial fibers from the cervical
plexus must be blocked by subcutaneous infiltration along the length of the clavicle. If the muscles of the pectoral
girdle are to be involved in surgery, their innervation must be blocked separately either by brachial plexus block or
cervical plexus block, depending on the nerve supply of the muscle. If, as is often the case above the fifth thoracic
segment, the ribs cannot be palpated and, therefore, intercostal blocks cannot be performed safely, the paravertebral
approach may be used. However, use of the paravertebral block reintroduces a risk of sympathetic blockade by
diffusion to the rami communicantes and transmission of solution to the epidural space.
Practical application of these techniques is illustrated by their use for mastectomy. Intercostal nerve blocks must be
performed on the operative side from the second up to and including the sixth intercostal nerve. In addition, the
brachial plexus should be blocked above the clavicle along with the sensory nerves from the cervical plexus and the
opposite side. This method has the advantage of avoiding sympathetic blockade, but large volumes of local
563
anesthetic solution are required, which, even in experienced hands, may cause the patient to approach toxic levels.
There is also the risk of pneumothorax. It should be noted that if this method is used, premedication initially should
be light, because patient cooperation and awareness are required during the performance of the brachial plexus block
when paresthesias are being sought. Heavy sedation can then be administered. This method is more difficult to use
in an obese patient.
ABDOMINAL AND PELVIC SURGERY
Abdominal procedures constitute the bulk of general surgery. These procedures include operations on the abdominal
wall for hernias, infections, tumors, and trauma, as well as intra-abdominal operations including gastric, intestinal,
liver, pancreas, spleen, and adrenal gland surgery. General surgical procedures involving the perineum include
operations for fissure, hemorrhoidectomy, anal fistula, abdominoperineal proctectomy, ischiorectal abscess, and
pilonidal sinus and abscess drainage.
Nerve Supply
The innervation of the abdominal mass is via the lower seven intercostal nerves, the first and second lumbar somatic
nerves, and the corresponding sympathetic ganglia. The perineum is supplied by the lower three sacral somatic
nerves and by the lumbar sympathetic trunk. All the intra-abdominal viscera, including the gonads and the colon
down to the splenic flexure, are innervated by the celiac plexus and the vagus nerve. The pelvic viscera and the
colon from the splenic flexure to the rectum are innervated by the hypogastric plexus and the parasympathetic
outflow from the second to the fourth sacral roots.
Thus, if a spinal block is complete to the fourth thoracic dermatome, the patient undergoing an ovary or appendix
surgery through a lower abdominal incision may still experience upper abdominal pain. This is mediated by pain
fibers passing through the celiac plexus and the splanchnic nerves and thence to the lower eight thoracic sympathetic
ganglia via communicating fibers in the sympathetic chain to the higher unblocked thoracic segments.
Spinal Blockade [155]
Spinal anesthesia for abdominal surgery has the advantages of being easy to perform and requiring a small dose of
drug, making systemic absorption unimportant. Protective airway reflexes are maintained, and cerebral and
myocardial depression are avoided. Abdominal muscle relaxation is good, and the gut is contracted, making
operating conditions easier. Most noxious reflexes are blocked, with the exception of those mediated by the vagus
nerve. The disadvantages of spinal anesthesia include the intense sympathetic blockade, which, if high, may produce
hypotension that is difficult to control. True motor block of the phrenic nerve is very unusual because of high spinal
block, but a respiratory arrest resulting from hypotension and a brainstem hypoperfusion may occur. Furthermore,
even if the blood pressure is satisfactory and the airway reflexes and phrenic nerve are intact, the patient who is
paralyzed up to the neck may have difficulty in protecting the airway. The spinal block may wear off too soon and
require supplementary general anesthesia. However, this difficulty may be avoided by using a Tuohy needle for the
block and inserting the catheter in the subarachnoid space for repeat injections of local anesthetic. Spinal anesthesia
may cause a postoperative headache, but this rarely occurs in patients older than 60 years of age and can usually be
avoided in younger people by using a 26-G needle. Contraindications to spinal anesthesia include lack of patient
consent, infection of the site of injection, hypovolemia, anticoagulant therapy or pathologic coagulopathy, raised
intracranial pressure, septicemia, and progressive neurologic disease. High spinal anesthesia (above the thoracic
dermatomes) is undesirable in patients with severe cerebral and coronary artery disease and in those with severe
hypertension.
Epidural Block[156]
Epidural block has many of the disadvantages, advantages, and complications of spinal anesthesia. If a segmental
block is required, it can be achieved by epidural block if the injection is made at the level corresponding to the
middle of the operative field. This approach reduces the number of unnecessarily blocked segments and lessens the
chance of postoperative urine retention. By carefully choosing the local anesthetic, its concentration, and volume,
the anesthesiologist can select the degree of motor blockade needed to suit the operation and the patient’s general
condition. There is no dural puncture in epidural anesthesia, and so there is no postoperative “spinal headache”;
however, if a dural puncture is made with an epidural needle, the risk of headache is increased, because the needle is
usually longer than that used in the spinal block. The dose of local anesthetic used in epidural anesthesia is four to
five times greater than that used in the spinal block, and the chance of systemic toxicity is therefore increased.
Chance of toxicity is further increased by the presence of many large veins in the epidural space, into which a large
dose of local anesthetic may be accidentally injected, resulting in a systemic toxic reaction. Finally, epidural
564
anesthesia is sometimes patchy because the solution is traveling through a tissue plane in contrast to a fluid-filled
compartment. All these features of spinal and epidural blocks must be taken into account when the choice of
regional technique is being made.
Peripheral Nerve Blocks
Peripheral nerve blocks avoid the complication of hypotension from sympathetic nerve blockade. However, these
blocks take longer to perform, and more training and skill are required to perform successful blockade. Any part of
the abdominal wall can be anesthetized by intercostal or paravertebral blocks. Intercostal nerve block is preferable to
thoracic paravertebral block because the former technique carries a lower risk of pneumothorax when properly
performed, is more reliable, and has a longer duration. Furthermore, paravertebral block sometimes causes a
localized sympathetic block by diffusion to the rami communicantes or a localized epidural block by passage of the
solution through the intervertebral foramen into the epidural space.
UPPER INTRA-ABDOMINAL PROCEDURES

Satisfactory anesthesia for upper intra-abdominal surgery requires anesthesia and relaxation of the abdominal wall,
which is supplied by the 5th through the 12th intercostal nerves and blockade of the pain fibers that pass through the
celiac plexus and are derived from the 5th through the 12th thoracic sympathetic ganglia. These conditions can be
fulfilled by central blockade using spinal or epidural anesthesia, or by peripheral nerve block, which is the
intercostal or paravertebral block combined with the celiac plexus block. It is not feasible to block the diaphragm,
because it maintains respiration. Thus, even in the presence of complete anesthesia of the abdominal wall and
contents, manipulation of the stomach, spleen, or liver causes pain in the shoulder because of referred pain from the
diaphragm.
SPINAL ANESTHESIA
Spinal anesthesia is effective and ensures good muscle relaxation for upper abdominal surgery. This procedure
requires an analgesic block to the T4 level, which frequently causes total sympathetic blockade; hypotension and
bradycardia often result from this and require careful management with intravenous fluids and, possibly,
vasopressors and inotropes. This degree of cardiovascular instability is undesirable in patients with cardiovascular
disease and, therefore, in this group of patients, high spinal anesthesia should be avoided.
LUMBAR EPIDURAL BLOCK
Lumbar epidural block for upper abdominal surgery provides similar anesthesia to that obtained with spinal block.
The intensity and speed of onset of sympathetic blockade are less, thus rendering the cardiovascular manifestations
easier to regulate. Muscle relaxation, however, is less complete than with spinal anesthesia.
THORACIC EPIDURAL BLOCK
Thoracic epidural anesthesia with a catheter placed at the level of the eighth thoracic segment has the advantage of
segmental blockade, which permits adequate anesthesia at the operative site while maintaining at least partial
sympathetic function above and below the block levels. Compared with lumbar epidural or spinal injection, the
thoracic epidural has a lower incidence of loss of bladder or bowel control. It requires a small dose of drug and is
ideal for maintaining continuous postoperative pain relief by means of a bupivacaine infusion.
INTERCOSTAL BLOCK
Intercostal block can be used to provide anesthesia for upper abdominal surgery and is not contraindicated by
coagulopathy as are epidural techniques. This block also has the advantage of lasting 8 to 12 hours without causing
sympathetic blockade. In addition, there is no significant motor or sensory blockade other than that required for
surgery. Intercostal block carries the risk of pneumothorax and toxic reaction and does not anesthetize the viscera.
Thus, light general anesthesia is needed as a supplement for all but small procedures, such as feeding gastrostomy,
cholecystostomy, or drainage of a pericardial effusion through a diaphragmatic window. However, even in these
procedures, a considerable dosage of analgesic is often required along with further infiltration of the viscera with
local anesthetic to keep the patient comfortable. For large procedures such as cholecystectomy or gastric surgery,
endotracheal intubation is advisable to protect the airway from gastric regurgitation. Intubation facilitates
administration of light general anesthesia such as nitrous oxide with oxygen mixture, which may be supplemented
with low doses of intravenous fentanyl or a low concentration of a volatile inhalation agent to obliterate visceral
565
pain. Intercostal block lasts several hours and can, if necessary, be repeated once or twice to give pain relief up to 24
or 36 hours. Thus, long operations can be performed with this regional technique and additional postoperative
analgesia can be given.
CELIAC PLEXUS BLOCK[157]
In the absence of severe debilitation, severe cardiovascular disease, or hypovolemia, the celiac plexus block can be
added to intercostal block to make upper abdominal anesthesia more complete. The main side effect is hypotension
caused by vasodilatation of the splanchnic bed. In the presence of intercostal block and celiac plexus block,
significant manipulation near the stomach may still cause pain through stimulation of the diaphragm and traction on
the esophagus. The patient, therefore, still needs inhalation anesthesia in the form of nitrous oxide to maintain
comfort throughout surgery.
SPECIAL CONSIDERATIONS
Abdominal Relaxation. The component of muscle tension resulting from surgical stimulation is substantially
reduced or obliterated in regional anesthesia. The motor blockade necessary to ensure complete muscle relaxation
can be achieved by intercostal, paravertebral, epidural, or spinal block. Of these, the longest acting is the intercostal
block, with analgesia lasting from 8 to 12 hours. However, motor blockade is not always complete for the whole
operation, especially if the procedure lasts more than 2 hours. Lack of relaxation is most noticeable when there is
surgical stimulation of unblocked areas, such as the diaphragm or upper abdominal viscera in the absence of celiac
plexus block. If an endotracheal tube is in place, loss of muscle relaxation may be overcome by intermittent positive
pressure ventilation and administration of a low concentration of a potent inhalation anesthetic such as enfurane
0.25%, with or without a low dose of a nondepolarizing relaxant.
Diaphragmatic Movement. Diaphragmatic movement may be an inconvenience in upper abdominal surgery,

especially if the patient is obese. This can be overcome by positive pressure ventilation.
Hiccoughs. Hiccoughs is a very embarrassing development during regional anesthesia for upper abdominal surgery,
and, often, can only be arrested by administering a short-acting neuromuscular blocker and employing artificial
ventilation. Occasionally, stimulation of the nasopharynx may suppress an attack of hiccoughs.
Esophageal Surgery: Abdominal Approach. Traction on the esophagus causes stimulation of the esophageal
sympathetic plexus, resulting in central chest pain; therefore, full general anesthesia is required.
Cholecystectomy. Controlled ventilation and apnea are required during intraoperative cholangiography. This
control can be achieved by manual ventilation, which causes depression of the respiratory drive by hypocapnia or by
neuromuscular blockade.
Gastric and Bowel Surgery. Nasogastric tubes should, if possible, be inserted at the same time as the endotracheal
tube. If insertion is performed later, anesthesia must be deepened for the patient to tolerate this procedure.
Emergency Situations. If the diagnosis is uncertain or if the gut is considerably distended, a general anesthetic or
continuous epidural injection is preferable to intercostal block. Epidural route permits extension of the block and
maintenance of complete abdominal motor block.
Hepatic Disease. Patients with severe liver disease may be slow to metabolize local anesthetics of the amino-amide
group. For this reason, repeated doses of local anesthetic after the initial maximal doses should be avoided.
Abnormal coagulation studies (prothrombin time >50% above control, platelets <100,000/mm3 ) contraindicate
epidural or spinal anesthesia, but peripheral nerve blocks are acceptable unless the nerves are involved in a confined
space and potentially subject to compression by hematoma (e.g., brachial plexus block).
Pheochromocytoma. Although the high production of catecholamines by the chromaffin tumor cells during surgical
manipulation cannot be prevented by regional anesthesia, the overall level of catecholamines released can be
reduced by the sympathetic blockade of epidural anesthesia.
Hypersplenism. Patients with hypersplenism often have thrombocytopenia, and in this situation, epidural or spinal
block is contraindicated because of the risk of epidural hematoma.
LOWER ABDOMINAL INTRAPERITONEAL PROCEDURES AND PELVIC SURGERY
566
Nerve Supply
The lower abdomen is innervated by somatic and visceral nerves. The wall is supplied by the 10th to 12th thoracic
nerves and the first and second lumbar somatic nerves. All the abdominal viscera, including the gonads, and except
the distal colon, are supplied by the celiac plexus. The pelvic viscera and the colon distal to the splenic flexure are
supplied by the hypogastric plexus. Pelvic viscera and bones are innervated by the first lumbar to the fifth sacral
nerves.
Lower abdominal surgery can be performed under spinal or lumbar epidural block. If the abdominal viscera are to
be manipulated or incised, blockade of the outflow from the 5th to the 12th thoracic sympathetic
ganglia are necessary to prevent pain, and the upper analgesic limit must be close to this level. Occasionally,
manipulation of the appendix or ovary may result in pain being felt in the upper abdomen or precordium, even when
analgesic block has been extended well above the incision.
SPINAL ANESTHESIA
For lower abdominal surgery, spinal anesthesia to between the fourth and sixth thoracic dermatomes provides good
muscle relaxation and block of noxious reflexes. The high sympathetic block frequently causes hypotension and
sometimes bradycardia. However, in the absence of severe cardiovascular disease, this can usually be managed
without difficulty. For abdominoperineal surgery, spinal block provides unsurpassed anesthesia throughout the
operative field. For perineal surgery limited to the anal margin, perineum, and surrounding skin and soft tissues,
low-dose hyperbaric spinal injection administered with the patient in the sitting position permits limiting of the
block to the sacral segments, the so-called saddle block. If the surgery is to involve the rectum and pelvic viscera
also, the hypogastric plexus must be blocked, which requires an analgesic level to the 10th thoracic dermatome. The
selection of dose and drug to achieve these levels of anesthesia is discussed elsewhere in the book.
LUMBAR EPIDURAL BLOCK
Lumbar epidural block can be used in a manner similar to spinal block for lower abdominal and perineal surgery.
Penetration of the sacral segments, however, is less reliable than in spinal anesthesia. This block can be achieved by
careful selection of the local anesthetic, its concentration and volume, and by performing the block with the patient
in the sitting position. For further information regarding drugs and doses, the reader is referred to the chapter on
epidural anesthesia.
CAUDAL BLOCK
When surgery is restricted to the perineum and its surrounding tissues, as in hemorrhoidectomy and fissurectomy,
caudal block is a very good technique. The sacral segments can be anesthetized with little or no sympathetic block,
thus avoiding cardiovascular instability even in very ill patients. If the rectum is to be operated on, as in
polypectomy, the analgesic level must be raised to the 10th thoracic dematome to include the sympathetic nerve
supply of the hypogastric plexus; because this is sometimes difficult to achieve, it is advisable to insert a catheter
high in the caudal canal and to titrate local anesthetic until the desired block is achieved. It is difficult to raise the
analgesic level above the 10th thoracic dermatome, although this can sometimes be done by using large volumes of
local anesthetic. If the surgery requires the Trendelenburg or jackknife position, use of caudal block avoids the risk
of an unduly high block from spinal anesthesia, which sometimes results from these maneuvers.
ABDOMINAL WALL SURGERY

Nerve Supply
The abdominal wall is supplied by the lower seven intercostal nerves and the upper two lumbar somatic nerves.
When selecting the block to be performed, one must remember that at least two segments above and two segments
below the operative site must be anesthetized.
Spinal and Epidural Anesthesia
567
Abdominal wall anesthesia is readily provided by spinal or epidural anesthesia in a manner similar to that used for
intra-abdominal surgery. However, if the viscera are not to be stimulated, the higher level of anesthesia required for
intra-abdominal surgery is not necessary. Thus, for a simple inguinal hernia repair, which is located at the level of
the 12th thoracic and 1st lumbar dermatomes, an upper analgesic level of the 8th to the 10th thoracic dermatomes is
satisfactory, whereas for intra-abdominal surgery at the same site (e.g., an appendectomy) a fourth thoracic
dermatome analgesic level is needed. Similar principles apply to upper abdominal wall procedures. Superficial
operations do not require intense muscle relaxation nor is postoperative pain severe; therefore, the local anesthetic
solution used in epidural anesthesia should be selected accordingly.
Peripheral Nerve Block
If peripheral nerve block is selected for abdominal wall anesthesia, the block must extend two segments above and
two segments below the incision. Intercostal nerve block is preferable to paravertebral block because there is less
risk of accompanying sympathetic block, and a smaller dose of anesthetic produces a more prolonged intense block.
The most commonly performed abdominal wall operation is the inguinal hernia repair. Innervation of this area is by
the 11th and 12th thoracic nerves and the 1st and 2nd lumbar somatic nerves. These give rise to the ilioinguinal (L1),
iliohypogastric (T12, L1), and genitofemoral (L1, L2) nerves. There is also some innervation from fibers of the 11th
thoracic nerve above and fibers crossing the midline. The spermatic cord carries its own nerve supply, which is
predominantly from the thoracic sympathetic outflow. Regional anesthesia of the inguinal area can be provided by a
combination of peripheral nerve blocks, field blocks, and local infiltration, or, alternatively, by paravertebral, spinal,
or epidural anesthesia.
If the peripheral nerve block method is selected, it is performed as follows. The ilioinguinal, iliohypogastric, and
genitofemoral nerves are blocked before they reach the operative site. Branches from the 11th thoracic nerve and
nerves from the opposite side are intercepted by field block, and local infiltration of the spermatic cord is performed
during surgery. This method of anesthesia is especially suitable for high-risk patients and for those undergoing
surgery on an outpatient basis. However, it is unsatisfactory for the obese, in whom obtaining blockade is more
difficult and who require larger volumes of anesthetic. This method of anesthesia is unsatisfactory for patients with
large or irreducible hernias or for those with femoral hernias in whom much manipulation may cause pain. In these
cases, epidural, spinal, or general anesthesia should be employed, if possible. In the obese patient, if spinal or
epidural anesthesia is deemed undesirable, an alternative is to use paravertebral block of the upper three lumbar
somatic nerves and block of the lower three intercostal nerves.
THE EXTREMITIES
General surgical procedures of the extremities are restricted to removal of superficial tumors and drainage of
infections and varicose veins. Anesthesia for the majority of these procedures is readily provided by regional block.
Upper Limbs
For the upper limbs, a brachial plexus block is the most versatile and reliable method. The approach most suitable
for the operation must be carefully selected. The axillary approach is suitable for operations below the elbow; the
supra- or infraclavicular approach is appropriate for the whole upper arm, and the interscalene approach is best for
the shoulder. If a tourniquet is used, care must be taken to provide anesthesia of the upper limb, including the
intercostal brachial nerve as well as the musculocutaneous, radial, ulnar, and median nerves. For short procedures
below the elbow, intravenous block is usually adequate. For isolated lesions, a single nerve block or digital blocks
may be sufficient.
Lower Limbs
Regional anesthesia for lower limb procedures is most adequately provided by blocking the peripheral nerves to the
area involved. Blocking the peripheral nerves means that the uninvolved lower limb is completely unaffected by
anesthesia and that there is no loss of sphincter control. There is no sympathetic effect outside the limb to be
operated on, and prolonged postoperative analgesia can be provided without top-up doses or sophisticated
monitoring.
For operations below the knee, sciatic and femoral blocks are adequate. If a tourniquet is to be applied, the lateral
femorocutaneous nerve must also be blocked. For knee surgery, the obturator nerve must be blocked as well.
Superficial procedures above the knee, particularly those in the distribution of the femoral and lateral
femorocutaneous nerves may also be performed under peripheral nerve block, but deep procedures require spinal,
caudal, or epidural block.
568
Spinal, epidural, or caudal block can all be used for lower limb surgery. The disadvantages are that the block is
bilateral, causing sympathetic anesthesia that must extend to the 10th thoracic dermatome. This level of blockade
may be difficult to achieve if a tourniquet is to be used on the thigh or if caudal block is wanted. The advantages are
that these blocks are easy and quick to perform; moreover, if a catheter is inserted, the use of a continuous technique
enables the block to be tailored to the duration of the surgery.
If the patient is to be operated on in the lateral or prone position and the spinal technique is selected, the density of
the solution and the positioning of the patient immediately after the block procedure must be carefully chosen to
ensure that the correct limb is blocked and that an unduly high level of block is avoided.
Vascular Surgery
When a patient is scheduled for vascular surgery, the following points should be considered before anesthesia is
selected: (1) arterial disease is a systemic disease, and only its localized manifestations bring patients to the
operating room; (2) manifestations of arterial disease should be sought in other organ systems. [158]
PREOPERATIVE VISIT AND EVALUATION
The majority of patients who undergo vascular surgery have organ function changes secondary to aging and are on
numerous medications. During the preoperative visit, specific answers should be obtained from the patient regarding
events such as a history of transient ischemic attacks, myocardial infarction, congestive heart failure, renal failure, or
angina. A brief examination may reveal an absent or diminished carotid or radial pulse. Absent or widely different
pulse volumes and blood pressures in the two arms occur in about 70% of patients with Takayasu’s disease. This is
obviously important in arterial monitoring of blood pressure.
Patients with vascular disease often take the following types of medication: anticoagulants, cardiotonics,
antiarrhythmics, diuretics, and hypoglycemics, as well as sedatives and tranquilizers. Any of these may affect the
conduct and choice of anesthesia.
Particular attention should be focused on the patient’s range of motion in the cervical spine. Some patients give a
definite history of transient ischemic attacks with certain positions of the head, particularly with extreme cervical
extension. This is probably due to the vascular dependence of the brain on the vertebrobasilar vascular system.
Patients with known pulmonary problems may need a more extensive pulmonary evaluation.
CHOICE OF ANESTHESIA
In some centers, regional anesthesia is the prime choice for patients undergoing vascular surgery. This is because the
sympathetic tone of the blood vessels is blocked by regional anesthesia, which maintains good perfusion at the site
of operation as well as in distal tissues.
Surgical procedures that can be performed with regional anesthesia alone are carotid endarterectomy, vascular
surgery of the upper extremities (e.g., arterial surgery, Gore-Tex graft), aortogram, aortoiliac bypass graft,
iliofemoral bypass graft, and vein stripping. Patients undergoing surgical procedures under regional anesthesia can
receive supplemental light general anesthesia. This is provided for the following reasons:
1. Oxygenation is improved if the level of regional anesthesia is high (e.g., T4 and above).
2. The patient is spared the discomfort and pain of lying in one position during long procedures.
3. The risk of oversedation is reduced during long procedures.
4. Relaxation is provided for very anxious and nervous patients who cannot stay still or remain calm during
the procedure.
The combined technique is indicated for patients with aortic aneurysms, splenorenal shunts, portocaval shunts (in
patients with splenorenal or portocaval shunts, however, liver failure may be so marked that coagulation
abnormalities constitute a relative contraindication to regional anesthesia), vascular tumor of the hepatic artery, or
any prolonged abdominal procedure for vascular surgery.
SURGERY FOR EXTRACRANIAL VASCULAR OCCLUSIVE DISEASE
569
The group of vascular occlusive diseases is characterized by obstruction of vessels supplying the head, neck, and
upper extremities. The obstruction usually results from arteriosclerosis, but, occasionally, it is caused by trauma or
Takayasu’s disease.
All lesions threaten cerebral circulation through embolism or by limitation of cerebral blood flow. In this section,
the main focus is on the problems of surgery for carotid endarterectomy. It is reasonable to assume that patients with
extracranial obstructive lesions also have various degrees of intracranial vascular disease.
In comparison with healthy young individuals, cerebral blood flow and oxygen uptake are lower and
cerebrovascular resistance higher in patients with cerebrovascular disease. These changes progress with age.
Although opinions differ, regional anesthesia is a good choice for carotid endarterectomy. With general anesthesia,
an indwelling internal carotid artery shunt is used routinely unless the collateral cerebral blood flow has been
assessed as adequate. Techniques that are used for assessing cerebral blood flow are the operative determination of
regional cerebral blood flow by isotopic technique and electroencephalographic monitoring, and internal carotid
artery back pressures. Electroencephalographic monitoring has been shown to correlate well with cerebral blood
flow. [159]
All of these methods require special equipment and extra personnel. Such requirements are unnecessary when
carotid endarterectomy is performed with regional anesthesia. One retrospective study reviewed 314 carotid
[160]
endarterectomies. In patients who were neurologically intact before operation, the perioperative mortality was
[161]
0.88% and the incidence of neurologic complications 3.1%. The incidence of nonneurologic complication under
general anesthesia was 12.9%, whereas under regional anesthesia the incidence was 2.8%. These data strongly
recommend the use of regional anesthesia for carotid endarterectomy.
The incidence of significant arteriosclerotic coronary artery disease in patients undergoing carotid endarterectomy is
in the range of 30% to 49%. With less morbidity under regional anesthesia, the risk of general anesthesia in a patient
group with up to 99% incidence of coronary artery disease does not justify its use in preference to regional
anesthesia.
Advantages of Regional Anesthesia for Carotid Surgery
Change in consciousness, seizure, visual disturbances, slurring of speech, and even inappropriate restlessness all
indicate cerebral ischemia in the awake patient. Cerebral ischemia provides the best available monitor of cerebral
blood flow and collateral circulation when carotid blood flow is occluded on the ipsilateral side. [161]
It is easy to recognize the early signs of transient neurologic deficits from undetectable emboli dislodged during
dissection. If not treated early, the deficits may become permanent. It is possible to avoid routine use of shunts in
patients who tolerate a test occlusion. Additional cardiovascular depression resulting from general anesthesia can be
avoided. A smooth transition from operative to postoperative phase is possible without emergence phenomena.
Disadvantages of Regional Anesthesia for Carotid Surgery
Regional anesthesia is technically rather difficult to perform. Training is needed to administer regional anesthesia
comfortably and successfully.
Complications of deep cervical block include intra-arterial or subarachnoid injections with subsequent deterioration
of patient physical status. A minor complication is block of adjacent nerves (e.g., hypoglossal, phrenic, recurrent
laryngeal nerves).
The patient may not cooperate, and the surgeon may not understand the significance of regional anesthesia in carotid
surgery. Neck massage, if used either to check the landmark or to spread anesthetic solution, may produce cerebral
embolization. Delayed intolerance to carotid occlusion is more difficult to manage in patients with regional
anesthesia than in those under general anesthesia.
570
CHOICE OF REGIONAL ANESTHESIA
Deep cervical plexus block may be used on the side of the surgery and superficial cervical block on the opposite side.
In addition, the accessory nerve can be blocked by injecting 2 to 3 mL of local anesthetic in the upper third of the
sternomastoid muscles.
Cervical epidural block may be used for carotid surgery.
ABDOMINAL AORTIC ANEURYSM
Management of patients undergoing abdominal aortic surgical procedures represents a major challenge to the
anesthesiologist. The typical patient with aortic disorders is advanced in years and has generalized arteriosclerotic
vascular disease with concurrent hypertension, diabetes mellitus, and renal dysfunction.
The surgical procedure may last many hours, with significant blood loss, volume shifts, and electrolyte and
temperature changes. Aortic clamping and unclamping are particularly hazardous events during the course of
abdominal aortic operations.
For vascular reconstructive surgical procedures, the indwelling epidural catheter allows injection of titrated amounts
of local anesthetics that provide surgical analgesia and muscular relaxation. Light general anesthesia can be used as
a supplement to provide control of vital functions and comfort to the patient. This produces minimal physiologic
stress. The combined technique is particularly useful in patients with significant myocardial or pulmonary
insufficiency in whom routine general anesthesia may increase morbidity.
Advantages
In the respiratory system, lumbar epidural anesthesia blocks the lower intercostal nerves and relaxes the abdominal
and lower thoracic muscles. In addition, the continuous epidural technique provides excellent analgesia
postoperatively. This allows the patient to cough effectively. Narcotic administration decreases with this technique,
further improving the respiratory function. [162] [163]
Conduction block up to T6 level maintains cardiovascular stability by compensatory vasoconstriction in the upper
trunk and upper extremity.
Some investigators claim that blocking the sympathetic nerves to the kidney prevents or corrects renocortical reflex
vasoconstriction. Kennedy and colleagues studied the normal human and showed that any reduction in glomerular
[164]
filtration rate was a reflection of systemic hypotension and was not due to any change in venovascular resistance.
Because of the sympathetic block, the bowel is contracted. This provides good exposure for surgery.
Profound metabolic response is decreased by blocking the afferent portion of the visceral reflexes.
Reduction in blood loss occurs as a result of low venous pressure at the operative site.
Regional anesthesia provides peripheral vasodilatation during surgery. This enhances collateral circulation around
occluded major vessels and encourages maximal flow through newly inserted grafts.
Regional anesthesia provides postoperative pain relief. This can be done with epidural local anesthetic or a narcotic.
With epidural narcotic, adequate analgesia can be obtained without sympathetic blockade, thus alleviating the risk of
postural hypotension.
Disadvantages
Perioperative anticoagulant therapy involving the use of heparin during surgery has dissuaded many
anesthesiologists from using regional anesthesia techniques. They fear epidural hematoma or abscess. The data in
the literature do not corroborate these fears. In a study by Rao and coworkers, 100 patients scheduled for
[163]
abdominal vascular surgery had epidural anesthesia. These patients were on a miniheparin regimen. There was no
incidence of epidural hematoma. [165]
Hypotension is a physiologic reaction that occurs immediately after the block. It should be expected and routinely
prevented by fluids and vasopressors.
571
Hypotension secondary to declamping can be prevented. Generous use of Ringer’s lactate solution (1–2 L) to
increase pulmonary capillary wedge pressure by 3 to 4 mm above the preoperative value before declamping has
prevented hypotension and maintained urine output. [166]
VASCULAR PROCEDURES OF LOWER EXTREMITIES
There is probably no other better method of blockade for vascular surgery of the lower extremity than spinal or
epidural anesthesia. It can be used for acute arterial embolus or for elective bypass surgery for arterial insufficiency.
The technique provides vasodilatation during and after surgery. Use of an indwelling catheter in the patient’s
epidural space can make general anesthesia unnecessary and can provide postoperative vasodilatation and pain relief.
For below-knee vascular surgery, regional anesthesia can be provided by sciatic-femoral block. This prevents
hypotension by decreasing the sympathetic block seen with conduction blocks.
The choices of technique are spinal, epidural, and femoral-sciatic nerve blocks.
MINOR VASCULAR PROCEDURES
In arteriography, the pain associated with the injection of intra-arterial contrast material is so intense that patients
with peripheral ischemia have refused to undergo such procedures again. To minimize patient distress and the
hemodynamic alterations of extreme sympathetic discharge, the routine use of epidural analgesia in patients
undergoing aortofemoral arteriography is useful. [167]
Sympathetic blockade offers beneficial effects in the form of significant peripheral vasodilatation. At many centers,
the high number of superior radiographs from patients who are resting comfortably has led to the use of sympathetic
blockade as a routine technique in aortofemoral arteriography.
REFERENCES
1. Hunter AR: Neurosurgical Anaesthesia, 2nd ed. Oxford, Blackwell Scientific Publications, 1975.
2. Labat G: Regional Anesthesia, Its Technique and Clinical Application. Philadelphia, WB Saunders, 1923.
3. Rosenberg MK, Berner G: Spinal anesthesia in lumbar surgery. Anesthesia and Analgesics 44:419, 1956.
4. Blacklock JB, Rea AL, Maxwell RE: Intrathecal morphine during lumbar spine operation for postoperative pain control. Neurosurgery 18:341,
1986.
5. Rechtine GR, Love LC: Postoperative laminectomy pain control using bupivacaine and epidural morphine. Orthopedics 9:1711, 1986.
6. Ibrahim AW, Farag H, Naguib M: Epidural morphine for pain relief after lumbar laminectomy. Spine 11:1024, 1986.
7. Javitt JC, Addiego R, Friedberg HL, et al: Brain stem anesthesia after retrobulbar block. Ophthalmology 94:718, 1987.
8. Donlon JV, Moss J: Plasma catecholamine levels during local anesthesia for cataract operations. Anesthesiology 51:471, 1979.
9. Merin RG: Propofol causes cardiovascular depression. Anesthesiology 72:393, 1990.
10. Fraunfelder FT, Scafidi AF: Possible adverse effects from topical ocular 10% phenylephrine. Am J Ophthalmol 85:447, 1978.
11. Kennerdell OS, Wucher FP: Cylopentolate associated with two cases of grand mal seizure. Arch Ophthalmol 87:634, 1972.
12. Kim JW, Smith PH: Timolol-induced bradycardia. Anesth Analg 59:301, 1980.
13. Pautler SE, Grizzard WS, Thompson LN, et al: Blindness from retrobulbar injection into the optic nerve. Ophthalmic Surg 4:334, 1986.
14. Fink BR: Leaves and needles: The introduction of surgical local anesthesia. Anesthesiology 65:77, 1985.
15. Atkinson WS: The development of ophthalmic anesthesia. Am J Ophthalmol 51:1, 1961.
16. Russell DA, Guyton JS: Retrobulbar injection of lidocaine (xylocaine) for anesthesia and akinesia. Am J Ophthalmol 35:78, 1954.
17. Smith PH, Kim JW: Etidocaine used for retrobulbar block. A comparison with lidocaine. Ophthalmic Surg 11:268, 1980.
18. Horven I: Ophthalmic artery pressure during retrobulbar anesthesia. Acta Ophthalmol 56:574, 1978.
572
19. Gills JP, Rudisill JE: Bupivacaine in cataract surgery. Ophthalmic Surg 4:67, 1974.
20. Smith RB, Linn JG: Retrobulbar injection of bupivacaine for anesthesia and akinesia. Invest Ophthalmol 13:157, 1979.
21. Kennerdell JS, Rydze D, Roberson M: Comparison of retrobulbar marcaine and combined marcaine-carbocaine in ophthalmic surgery. Ann
Ophthalmol 8:1236, 1976.
22. Chin GN, Almquist HT: Bupivacaine and lidocaine retrobulbar anesthesia. Am Acad Ophthalmol 90:369, 1983.
23. Beltranena HP, Vega MJ, Garcia JJ, et al: Complications of retrobulbar marcaine injection. J Clin Neuroophthalmol 2:159, 1982.
24. Smith JL: Retrobulbar bupivacaine can cause respiratory arrest. Ann Ophthalmol 14:1005, 1982.
25. Eckenhoff JE, Kirby CK: The use of hyaluronidase in regional nerve blocks. Anesthesiology 12:27, 1951.
26. Mindel JS: Value of hyaluronidase in ocular surgical akinesia. Am J Ophthalmol 85:643, 1978.
27. Nicoll JMV, Treuren B, Acharya PA, et al: Retrobulbar anesthesia: The role of hyaluronidase. Anesth Analg 65:1324, 1986.
28. Martin SR, Baker SS, Muenzler WS: Retrobulbar anesthesia and orbicularis akinesia. Ophthalmic Surg 17:232, 1986.
29. Kimbrough RL, Stewart RH, Willis PA: Site advantages of modified Gills retrobulbar technique. Ophthalmol Times 15:31, 1984.
30. Jay WM, Carter H, Williams B, et al: Effect of applying the Honan intraocular pressure reducer before cataract surgery. Am J Ophthalmol
100:523, 1985.
31. Aldrete JA, Romo-Salas F, Arora S, et al: Reverse arterial blood flow as a pathway for central nervous system toxic responses following
injection of local anesthetics. Anesth Analg 57:428, 1978.
32. Meyers EF, Ramirez RC, Boniuk I: Grand mal seizures after retrobulbar block. Arch Ophthalmol 96:847, 1978.
33. Antoszyk
AN, Buckley EG: Contralateral decreased visual acuity and extraocular muscle palsies following retrobulbar anesthesia.
Ophthalmology 93:462, 1986.
34. Follette JW, LoCascio A: Bilateral amaurosis following unilateral retrobulbar block. Anesthesiology 63:237, 1985.
35. Friedberg HL, Kline OR: Contralateral amaurosis after retrobulbar injection. Am J Ophthalmol 101:688, 1986.
36. Hamilton RC: Brain stem anesthesia following retrobulbar blockade. Anesthesiology 63:688, 1985.
37. Kobet KA: Cerebral spinal fluid recovery of lidocaine and bupivacaine following respiratory arrest subsequent to retrobulbar block.
Ophthalmic Surg 18:11, 1987.
38. Wittpenn JR, Rapoza P. Sternberg P et al: Respiratory arrest following retrobulbar anesthesia. Ophthalmology 93:867, 1986.
39. Wang BC, Bogart BI, Hillman DE, et al: Subarachnoid injection—A potential complication of retrobulbar block. Anesthesiology 71:845, 1989.
40. Drysdale DB: Experimental subdural retrobulbar injection of anesthetic. Ann Ophthalmol 16:716, 1984.
41. Unsold R, Standy JA, DeGroot J: The CT-topography of retrobulbar anesthesia. Graefes Arch Clin Exp Ophthalmol 217:125, 1981.
42. HamiltonRC, Gimbel HV, Strumin L: Regional anesthesia for 12,000 cataract extraction and intraocular lens implantation procedures. Can J
Anaesth 35:615, 1988.
43. McGoldrick KE: Current concepts in anesthesia for ophthalmic surgery, Anesthesiol Rev December 1:297, 1980.
44. MirakhurRK, Jones CJ, Dundee JW, et al: I.M. or I.V. atropine or glycopyrrolate for the prevention of oculocardiac reflex in children
undergoing squint surgery. Br J Anaesth 54:1059, 1982.
44A. Truhlsen SM: Harold Gifford, Sr., M.D. Omaha’s premier turn of the century ophthalmologist. Doc Opthalmol 99:237, 1999.
45. Callahan A: Ultrasharp disposable needles. Am J Ophthalmol 62:173, 1966.
46. Ramsay RC, Knobloch WH: Ocular perforation following retrobulbar anesthesia for retinal detachment surgery. Am J Ophthalmol 86:61, 1978.
47. Zaturansky B, Hyams S: Perforation of the globe during the injection of local anesthesia. Ophthalmic Surg 18:585, 1987.
48. Kimble JA, Morris RE, Witherspoon CD, et al: Globe perforation from peribulbar injection. Arch Ophthalmol 105:749, 1987.
573
49. Klein
ML, Jampol LM, Condon PI, et al: Central retinal artery occlusion without retrobulbar hemorrhage after retrobulbar anesthesia. Am J
Ophthalmol 93:573, 1982.
50. Krausher MF, Seelenfreund MH, Freilich DB: Central retinal artery closure during orbital hemorrhage from retrobulbar injection. Trans Am
Acad Ophthalmol Otol 78:65, 1974.
51. Sullivan KL, Brown GC, Forman AR, et al: Retrobulbar anesthesia and retinal vascular obstruction. Am Acad Ophthalmol 90:373, 1983.
52. Ras VA, Kawatva UK: Ocular myotoxic effects of local anesthetics. Can J Ophthalmol 23:171, 1988.
53. Carlson
BM, Rainin EA: Postoperative diplopia and ptosis: A clinical hypothesis on the myotoxicity of local anesthetics. Arch Ophthalmol
103:1377, 1985.
54. Davis DB, Mandel MR: Posterior peribulbar anesthesia: An alternative to retrobulbar anesthesia. J Cataract Refract Surg 12:182, 1986.
55. Breslin P: Mortality in ophthalmic surgery. Int Ophthalmol Clin 13:215, 1973.
56. Duncalf D, Gartner S, Carol B: Mortality in association with ophthalmic surgery. Am J Ophthalmol 69:610, 1970.
57. LynchS, Wolf GL, Berlin I: General anesthesia for cataract surgery: A comparative review of 2217 consecutive cases. Anesth Analg Curr Res
53:909, 1974.
58. Marx GF, Mateo CV, Orkin LR: Computer analysis of postanesthetic deaths. Anesthesiology 39:54, 1973.
59. Petruscak J, Smith RB, Breslin P: Mortality related to ophthalmological surgery. Arch Ophthalmol 89:106, 1973.
60. Quigley HA: Mortality associated with ophthalmic surgery. Am J Ophthalmol 77:517, 1974.
61. Kaplan MR, Reba RC: Pulmonary embolism as the leading cause of ophthalmic mortality. Am J Ophthalmol 73:159, 1972.
62. Donlon JV: Arrythmias during cataract surgery. Anesthesiol Rev 12:21, 1979.
63. Sapala JA: Operative and nonoperative risks in cardiac patients. J Am Geriatr Soc 23:529, 1975.
64. Becker CL, Tinker JH, Robertson DM, et al: Myocardial reinfarction following local anesthesia for ophthalmic surgery. Anesth Analg 59:257,
1980.
65. Chung F, Westerling D, Chisholm LDJ, Squires GW: Postoperative recovery after general anaesthesia with and without retrobulbar block in
retinal detachment surgery. Anaesthesia 43:943, 1988.
66. Allen ED, Elkington AR: Local anesthesia and the eye. Br J Anaesth 52:689, 1980.
67. Plowman PC, Thomas WJW, Thurlow AC: Cardiac arrhythmias during anesthesia for oral surgery. Anaesthesia 29:571, 1974.
68. Neill RS: Regional anesthesia for major eyelid surgery. Anaesthesia 29:571, 1974.
69. TodorovicL, Stajcic Z, Pefrovic V: Mandibular versus inferior dental anesthesia: Clinical assessment of 3 different techniques. Int J Oral
Maxillofac Surg 15:733, 1986.
70. Pfleiderer AG, Brockbank M: Cocaine and adrenaline: A safe or necessary combination in the nose? A study to determine the effect of
adrenaline on the absorption and adverse side effects of cocaine. Clin Otolaryngol 13:421, 1988.
71. Taylor
S, Achola K, Smith G: Plasma catecholamine concentrations. The effects of infiltration with local analgesics and vasoconstrictors
during nasal operations. Anaesthesia 39:520, 1984.
72. Lancer JM, Fisch U: Local anaesthesia for middle ear surgery. Clin Otolaryngol 13:367, 1988.
73. Bingham B, Hawthorne M: The use of anaesthetic EMLA cream in minor otological surgery. J Laryngol Otol 102:517, 1988.
74. Agren K, Engquist S, Danneman A, et al: Local versus general anaesthesia in tonsillectomy. Clin Otolaryngol 14:97, 1989.
75. Yerzingatsian KL: Thyroidectomy under local analgesia: The anatomical basis of cervical blocks. Ann R Coll Surg Engl 71:207, 1989.
76. De la Rocha AG, Chambers K: Pain amelioration after thoracotomy: A prospective, randomized study. Ann Thorac Surg 37:239, 1984.
77. Kvalheim L, Reiestad F: Intrapleural catheter in the management of postoperative pain. Anesthesiology 61:A231, 1984.
78. Reiestad F, Stromskåg KE, Holmquist E: Intrapleural administration of bupivacaine in postoperative management of pain. Anesthesiology
65:A204, 1986.
79. VadeBoncouer TR, Riegler FX, Gautt RS, et al: A randomized, double-blind comparison of the effects of interpleural bupivacaine and saline
574
on morphine requirements and pulmonary function after cholecystectomy. Anesthesiology 71:339, 1989.
80. Covino BJ: Interpleural regional analgesia. Anesth Analg 67:427, 1988.
81. RosenbergPH, Scheinin BMA, Lepantalo MJA, et al: Continuous intrapleural infusion of bupivacaine for analgesia after thoracotomy.
82. Seltzer
JL, Bell SD, Moritz H, et al: A double-blind comparison of intrapleural bupivacaine and epidural fentanyl for post-thoracotomy pain.
83. Lewis GW: Interpleural block. Can J Anaesth 36:103, 1989.
84. El-Naggar MA, Read C, Yogaratnam G, et al: Intrapleural intercostal nerve block using 0.75 percent bupivacaine. Anesthesiology 67:A258,
1987.
85. Reiestad F, Stromskåg KE: Interpleural catheter in the management of postoperative pain. A preliminary report. Reg Anesth 11:89, 1986.
86. RoccoA, Reiestad F, Gudman J, et al: Intrapleural administration of local anesthetics for pain relief in patients with multiple rib fractures.
Preliminary report. Reg Anesth 12:10, 1987.
87. Seltzer JL, Larijani GE, Goldberg ME, et al: Intrapleural bupivacaine—A kinetic and dynamic evaluation. Anesthesiology 67:798, 1987.
88. El-Baz N, Faber LP, Ivankovich AD: Intrapleural infusion of local anesthetics: A word of caution. Anesthesiology 68:809, 1988.
89. Bromage PR: Epidural Analgesia. Philadelphia, WB Saunders, 1978.
90. Erdmeir HA, Loper LE, Sweet RB: Studies of factors affecting peridural anesthesia. Anesth Analg 44:400, 1965.
91. Matthews PJ, Govenden V: Comparison of continuous paravertebral and extradural infusions of bupivacaine for pain relief after thoracotomy.
Br J Anaesth 62:204, 1989.
92. Christensen V: Respiratory depression after extradural morphine. Br J Anaesth 52:841, 1980.
93. Miller L, Gertel M, Fox GS, et al: Comparison of effect of narcotic and epidural analgesia on postoperative respiratory function. Am J Surg
131:291, 1976.
94. Simpson BR, Parkhouse J, Marshall R, et al: Extradural analgesia and the prevention of postoperative respiratory complications. Br J Anaesth
33:628, 1961.
95. WeisOF, Sriwatanakul K, Alloza JL, et al: Attitudes of patients, housestaff, and nurses toward postoperative analgesic care. Anesth Analg
62:70, 1983.
96. Armitage EN: Local anaesthetic techniques for prevention of postoperative pain. Br J Anaesth 58:790, 1986.
97. Wahba WM, Don HF, Craig DB: Post-operative epidural analgesia: Effects on lung volumes. Can Anaesth Soc J 22:519, 1975.
98. Sjögren S, Wright B: Circulatory changes during continuous epidural blockade. Acta Anaesthesiol Scand 46 (Suppl):5, 1972.
99. James EC, Kolberg HL, Iwen GW, et al: Epidural analgesia for post-thoracotomy patients. J Thorac Cardiovasc Surg 82:898, 1981.
100. Bromage PR, Camporesi E, Chestnut D: Epidural narcotics for postoperative analgesia. Anesth Analg 59:473, 1980.
101. Mehnert JH, Dupont TJ, Rose DH: Intermittent epidural morphine instillation for control of postoperative pain. Am J Surg 146:145, 1983.
102. Modig J, Paalzow L: A comparison of epidural morphine and epidural bupivacaine for postoperative pain relief. Acta Anaesthesiol Scand
25:437, 1981.
104. Rawal N, Sjostrand U, Dahlstrom B: Postoperative pain relief by epidural morphine. Anesth Analg 60:726, 1981.
105. Bromage PR, Camporesi EM, Durant PAC, et al: Nonrespiratory side effects of epidural morphine. Anesth Analg 61:490, 1982.
106. Conacher ID, Paes ML, Jacobson L, et al: Epidural analgesia following thoracic surgery. Anaesthesia 38:546, 1983.
107. Graham JL, King R, McCaughey W: Postoperative pain relief using epidural morphine. Anaesthesia 35:158, 1980.
108. Lanz E, Theiss D, Riess W, et al: Epidural morphine for postoperative analgesia: A double-blind study. Anesth Analg 61:236, 1982.
109. El-Baz NMI, Faber LP, Jensik RJ: Continuous epidural infusion of morphine for treatment of pain after thoracic surgery: A new technique.
575
110. Cohen FL: Postsurgical pain relief: Patients’ status and nurses medication choices. Pain 9:265, 1980.
111. Cullen ML, Staren ED, El-Ganzouri A, et al: Continuous epidural infusion for analgesia after major abdominal operations: A randomized,
prospective, double-blind study. Surgery 98:718, 1985.
112. Writer WDR, Hurtig JB, Evans D, et al: Epidural morphine prophylaxis of postoperative pain: Report of a double blind multicentre study. Can
Anaesth Soc J 32:330, 1985.
113. Ross RA, Clarke JE, Armitage EN: Postoperative pain prevention by continuous epidural infusion. Anaesthesia 35:663, 1980.
114. El-Baz N, Goldin M: Continuous epidural infusion of morphine for pain relief after cardiac operations. J Thorac Cardiovasc Surg 93:878,
1987.
115. Baxter AD, Jennings FO, Harris RS, et al: Continuous intercostal blockade after cardiac surgery. Br J Anaesth 59:162, 1987.
116. Kwik RSH: Complications associated with surgery in the flank position for urological procedures. Middle East J Anesthesiol 7:485, 1980.
117. Noller DW, Gillenwater JY, Howard SS, et al: Intercostal nerve block with flank incision. J Urol 17:59, 1977.
118. Franklin SS, Young JD Jr, Maxwell MH, et al: Operative morbidity and mortality in renovascular disease. JAMA 231:1148, 1975.
119. Melchior J, Valk WL, Foret JD, et al: Transurethral prostatectomy: Computerized analysis of 2,223 consecutive cases. J Urol 112:634, 1974.
119A. Abrams PH, Shah PJ, Bryning K, et al: Blood loss during transurethral resection of the prostate. Anesthesia 37:3, 1982.
120. Tad MS, Bapna BC, Vaidyanathan GCL: Topical or no anesthesia for external urethral sphincterotomy in neurogenic vesical dysfunction due
to spinal injury. Paraplegia 15:226, 1997.
121. Soliman MG, Tremblay NA: Nerve block of the penis for postoperative pain relief in children. Anesth Analg 57:495, 1978.
122. Goulding FJ: Penile block for postoperative pain relief in penile surgery. J Urol 126:337, 1981.
123. Yeoman PM, Cooke R, Hain WR: Penile block for circumcision? A comparison with caudal blockade. Anaesthesia 38:862, 1983.
124. Davie FT: Anesthesia in renal transplantation. In Chatterjee SN (ed): Manual of Renal Transplantation. New York, Springer-Verlag, 1979, pp
87–100.
125. Harvik ME: Drugs used in the treatment of psychiatric disorders. In Goodman LS, Gilman A (eds): The Pharmacological Basis of
Therapeutics. London, MacMillan, 1970, p 179.
126. Smith BH: Anaesthetic problems in renal transplantation. Proc R Soc Med 66:918, 1973.
127. Hilgenberg
JC: Renal disease. In Stoelting RK, Dierdorf SF (eds): Anesthesia and Co-Existing Disease. New York, Churchill Livingstone,
1983, pp 379–406.
128. Bastro RD, Deutsch S: Anesthesia and the Kidney. New York, Grune & Stratton, 1976.
129. Rabiner SF: Uremic bleeding. In Spaet TH (ed): Progress in Hemostasis and Thrombosis. New York, Grune & Stratton, 1972.
130. Linke CL: Anesthesia for renal transplantation. Bull N Y Acad Med 56:458, 1980.
131. Walsh A: Some practical problems in kidney transplantation. Transplantation Proc 1:178, 1969.
132. Farman JV: Anaesthesia for transplant surgery, recent advances in anesthesia and analgesia. Int Anesthesiol Clin 16:92, 1978.
133. Slawson KB: Anesthesia for the patient in renal failure. Br J Anaesth 44:277, 1972.
134. Reenan RL, Boyan CP: Anesthesia for organ transplantation. In Chatterjee SN (ed): Renal Transplantation: A Multidisciplinary Approach.
New York, Raven Press, 1980, pp 127–134.
135. Martin DG: Renal transplantation. Int Anesthesiol Clin 9:151, 1971.
136. Lund PC: Peridural Analgesia and Anesthesia. Springfield, Ill, CC Thomas, 1966.
137. Marx GF: Anesthesia Study Committee of the New York Society of Anesthesiologists: Anesthetic problems in patients on maintenance
dialysis. NY State J Med 69:1084, 1969.
138. Hughes R, Chappel DJ: Pharmacology of atracurium: A new competitive neuromuscular blocking agent. Br J Anaesth 53:31, 1981.
576
139. Don F, Dieppa RA, Taylor P: Narcotic analgesics in anuric patients. Anesthesia 42:745, 1975.
140. Mosterl JW, Evers JL, Hobika GH, et al: Cardiorespiratory effects of anaesthesia with morphine or fentanyl in chronic renal failure and
cerebral toxicity after morphine. Br J Anaesth 43:1053, 1971.
141. Katz J, Kountz SL, Cohn R: Anesthetic considerations for renal transplantation. Anesth Analg Curr Res 46:609, 1967.
142. Raj
PP, Mathieu A, Mathieu D: Local anesthetics, infection, and the perioperative period. In Mathieu A, Burke JF(eds): Infection and the
Perioperative Period. New York, Grune & Stratton, 1982, p 298.
143. Rao
TLK, El-Etr AA: Anticoagulation following placement of epidural and subarachnoid catheters: An evaluation of neurologic sequellae.
Anesthesia 55:618, 1981.
144. Vandam LD, Harrison JH, Murray JE: Anesthetic aspects of renal homotransplantation in man. Anesthesia 23:783, 1962.
145. Raj PP: Ancillary measures to assure success. Reg Anesth 5:9, 1980.
146. Winnie AP: Interscalene brachial plexus block. Anesth Analg 49:455, 1970.
147. Edelist G: Principles of anesthetic management in rheumatoid arthritis. Anesth Analg 43:227, 1964.
148. DeBoard JW, Jawahar N, Ghia WB: Caudal anesthesia in a patient with ankylosing spondylitis for hip surgery. Anesthesiology 54:164, 1981.
149. Winnie AP, Ramamurthy S, Durrari A: The inguinal paravascular technic of lumbar plexus anesthesia: The “3 in 1” block. Anesth Analg
53:989, 1973.
150. Beck GP: Anterior approach to sciatic nerve block. Anesthesiology 24:222, 1963.
151. Raj PP, Parks RJ, Watson TD: A new single-position supine approach to sciatic femoral nerve block. Anesth Analg 54:489, 1975.
152. Wredmark T, Lundh R: Arthroscopy under local anesthesia using controlled pressure-injection with prilocaine. J Bone Joint Surg Br 64:583,
1982.
153. Parnell RG: Scoliosis correction and epidural analgesia. Anesthesia 37:1115, 1982.
154. Bahr VV: Local anesthesia for thyroid surgery. In Eriksson E (ed): Illustrated Handbook in Local Anaesthesia. Philadelphia, WB Saunders,
1969, p 43.
155. Bridenbaugh PO, Kennedy WF Jr: Spinal, subarachnoid neural blockade. In Cousins MJ, Bridenbaugh PO (eds): Neural Blockade.
Philadelphia, JB Lippincott, 1980, p 146.
156. Bromage PR: The Management of Epidural Analgesia for Surgery, Epidural Analgesia. Philadelphia, WB Saunders, 1978, p 466.
157. Thompson GE: Celiac plexus, intercostal and minor peripheral blockade. In Cousins MJ, Bridenbaugh PO (eds): Neural Blockade.
Philadelphia, JB Lippincott, 1980, p 384.
158. Sabawala P, Strong MJ, Keats AS: Surgery of the aorta and its branches. Anesthesiology 30:229, 1970.
159. Sharbrough FW, Nessick J Jr, Sundt T Jr: Correlation of continuous electroencephalograms with cerebral blood flow measurements during
carotid endarterectomy. Stroke 4:674, 1973.
160. Peitzman A, Webster M, Loubeau JM, et al: Carotid endarterectomy under regional anesthesia. Ann Surg 196:59, 1982.
161. Bosiljeval J, Farha SJ: Carotid endarterectomy results using regional anesthesia. Am Surg 46:403, 1980.
162. Cunningham F, Egan JM, Inahara T: Continuous epidural anesthesia in abdominal vascular surgery. Am J Surg 139:624, 1980.
163. Rao T, Adel AE: Anticoagulation following placement of epidural and subarachnoid catheters. Anesthesiology 55:618, 1981.
164. KennedyWF Jr, Sawyer TK, Gerbershagen HW, et al: Systemic cardiovascular and renal hemodynamic alteration during peridural anesthesia
in normal man. Anaesthesiology 32:414, 1969.
165. Odoom JA, Sih IL: Epidural analgesia and anticoagulant therapy. Anaesthesia 38:254, 1983.
166. Lunn JK, Dannemiller FJ, Stanley T: Cardiovascular responses to clamping of aorta during epidural and general anesthesia. Anesth Analg
58:372, 1979.
167. Miller PA, Fagraeus L, Johnsrude I, et al: Epidural anesthesia in aortofemoral arteriography. Ann Surg 192:227, 1980.
577
Section IV - Chapter 25 - Acute Situations: Obstetrics
Chapter 25 - Acute Situations: Obstetrics
CYNTHIA A. WONG
MARK C. NORRIS
Today, the vast majority of procedures performed in the labor and delivery unit employ regional anesthetics.
Maternal safety is the primary reason behind this atypical distribution of anesthetics. Anesthesia-related
complications accounted for 3% of maternal morbidity and death between 1979 and 1990. The majority of deaths [1]
occurred during general anesthesia. Analysis of obstetric cases in the American Society of Anesthesiologists (ASA)
Closed Claims Project found that general anesthesia was more often associated with severe injury and higher
payments than regional anesthesia. [2]
The number of anesthesia-related deaths in both the United States and Great Britain has decreased with each
triennium, beginning in 1979. At the same time, use of neuraxial anesthesia for cesarean delivery increased from
[1] [3]
54% to 65% in 1981, from 78% to 88% in 1992, and from 87% to 92% in 1997. Maternal deaths from regional
[4] [5]
anesthesia decreased in 1985–1990 compared with 1979–1984; during these time frames, deaths increased for
general anesthesia. The increasing use of regional anesthesia for obstetric patients appears to have played a major
[1]
role in decreasing overall anesthesia-related maternal morbidity and mortality rates.
The use of regional analgesia for labor has been steadily increasing. Forty-one percent to 66% of parturients
received regional analgesia in 1997 compared with 21% to 55% in 1992. [5]
Pregnancy-Induced Changes in Physiology and Anatomy: Effects of Regional Analgesia
There are several ways in which use of regional anesthesia and analgesia differ for parturients from their use in
nonpregnant patients. During pregnancy, alterations in physiology bring about further changes in the maternal
anatomy as well as in drug pharmacokinetics and pharmacodynamics. Additionally, regional anesthesia in the
mother may affect the uteroplacental unit and the fetus.
Pregnancy changes the pharmacokinetics of some drugs. Decreased plasma proteins and altered protein binding may
change free drug to total drug ratios of anesthetic agents. For example, protein binding of lidocaine decreases
throughout pregnancy. Increased renal blood flow and glomerular filtration as well as altered hepatic microsomal
[6]
activity change renal and hepatic drug clearance. [7]
Pregnancy-induced neurohumoral changes may alter responses to pain. In rats, the pregnancy-induced increased
concentration of plasma β-endorphin is associated with a naloxone-reversible increased tolerance to visceral
stimulation. Pregnancy is associated with lower plasma substance P concentrations and higher plasma and
[8] [9]
cerebrospinal fluid (CSF) progesterone levels. Both of these compounds have significant roles in pain modulation.
[10]
Nerves from pregnant animals (including humans) appear more susceptible to local anesthetic blockade. In rats [11] [12]
and humans, pregnancy enhances the effect of central and peripheral local anesthetics. However, pregnancy does
[13] [14]
not enhance isolated spinal nerve root axon susceptibility to bupivacaine. Proposed mechanisms of enhanced
[15]
neural blockade during pregnancy include hormone-related changes in the actions of spinal cord neurotransmitters,
potentiation of the analgesic effect of endogenous analgesic systems, increased permeability of the neural sheath, or
other pharmacodynamic or pharmacokinetic differences between pregnant and nonpregnant women. Even during [16]
early pregnancy, the spread of epidural local anesthetic blockade is increased, a phenomenon explained by altered
[13]
sensitivity to local anesthetics as opposed to gross changes in spinal column anatomy.
However, anatomic changes in the mother may affect regional anesthesia techniques. The epidural and vertebral
foraminal veins are enlarged, resulting in an increased risk of intravascular placement of an epidural catheter and
decreased egress of epidural anesthetic agents from the epidural space. Engorged epidural veins are associated with
a decreased lumbosacral CSF volume. An increase in intra-abdominal pressure is also associated with decreased
[17]
CSF volume. In volunteers, decreased lumbosacral CSF volume, as measured by magnetic resonance imaging
[18]
(MRI), was associated with increased sensory blockade after spinal anesthesia. [19]
Hormonal changes affect vertebral ligamentous structures and may make the ligamentum flavum feel “softer.” The [20]
pregnant patient may not flex her lumbar spine optimally, which may narrow the interspinous spaces and move the
578
line between interiliac crests (Tuffier’s line) more cephalad. Pregnancy-induced widening of the pelvis may result
[20]
in a head-down tilt of the spine in the lateral position, potentially affecting the spread of intrathecal drugs.
Parturients may have presacral edema, making landmark identification more difficult. Finally, lumbar lordosis and
thoracic kyphosis are altered during pregnancy, perhaps changing the distribution of spinal anesthetics. [21]
CSF density is decreased in pregnancy. [22] [23]

Hence, the baricity of spinal anesthetic solutions is altered, and their
distribution may change.
Taken together, these changes may contribute to the observation that pregnancy increases the extent of spinal (and
epidural) block produced by a given dose of drug. [13] [24]
Changes in the maternal cardiovascular system can potentially confound the administration of regional anesthesia
and analgesia. In the supine position, aortocaval compression decreases cardiac output by 10% to 20% in the term
parturient. Hemodynamic stability becomes more dependent on the sympathetic nervous system as pregnancy
[25]
progresses. Sympathetic blockade in the term parturient results in a marked decrease in blood pressure compared
[26]
with nonpregnant control subjects. [26]
The central nervous system and cardiac toxicity of lidocaine and ropivacaine are not altered by pregnancy. [27] [28]
Although an earlier study concluded that the plasma bupivacaine concentration necessary for cardiac toxicity was
markedly decreased in pregnant sheep, a subsequent, better controlled, study did not support this conclusion.
[29] [28]
Pregnancy alters the hemodynamic response to endogenous and exogenous sympathomimetics. Arterial
responsiveness to vasopressors is reduced in pregnancy in both in vivo and in vitro animal models. In contrast, [30] [31]
the venous pressor response increases in pregnancy. [32]
UTEROPLACENTAL BLOOD FLOW
Uteroplacental blood flow (UBF) is not autoregulated and is largely dependent on maternal blood pressure. By a
number of mechanisms, neuraxial anesthesia and analgesia may affect UBF in both directions. Pain causes [33]
activation of the sympathetic nervous system. In pregnant ewes, acute stress increased plasma norepinephrine levels
by 25% and decreased UBF by 50%. Labor pain also is associated with a marked increase in plasma epinephrine
[34]
concentration and has been associated with an increased incidence of abnormal fetal heart rate patterns. Labor
[35] [36] [37]
analgesia is associated with a marked reduction in circulating catecholamines. [35] [36]
Pain also causes maternal hyperventilation. Hyperventilation may decrease UBF. [38]
Neuraxial anesthesia-induced sympathetic blockade does not appear to alter UBF in normal parturients in the
absence of hypotension. In the setting of severe preeclampsia, epidural analgesia with local anesthetic may
[39]
increase intervillous blood flow. [40]
Neuraxial anesthesia and analgesia may adversely affect UBF, primarily as a result of sympathetic blockade-induced
maternal hypotension. Maternal hypotension decreases uterine arterial pressure and increases uterine vascular
resistance secondary to reflex release of vasoconstrictors. [33]
Neuraxial analgesia has been associated with uterine hypertonus, resulting in a decrease in UBF and fetal
bradycardia (see later discussion).
Unintentional intravenous injection of local anesthetic may decrease UBF by several mechanisms. In gravid ewes,
intravenous epinephrine (as would be used in the intravenous injection of an epinephrine-containing epidural test
dose) caused a transient decrease in uterine blood flow. The epidural administration of local anesthetic solutions
[41]
containing epinephrine does not appear to affect uterine blood flow in the healthy parturient. However, there is [42]
some concern that the epidural injection of epinephrine-containing local anesthetics may adversely affect UBF in
patients with preeclampsia. [43]
The amount of local anesthetic contained in a normal test dose does not affect uterine perfusion if injected into a
vein, nor does the amount of local anesthetic absorbed from the epidural space after epidural anesthesia. However,
[44]
579
higher concentrations of local anesthetics, achieved after unintentional intravenous injection or after a paracervical
block (see later discussion), may cause uterine hypertonus, decrease in UBF, and subsequent fetal bradycardia. [33]
THE FETUS
Most drugs cross the placenta and can be detected in the fetus. Therefore, the safe administration of anesthetic to the
parturient must take the fetus into account. The extent of placental transfer depends on a number of factors,
including drug concentration and electrochemical gradients across the placenta, molecular weight, lipid solubility,
degree of ionization, membrane surface area and thickness, maternal and fetal blood flow, placental binding and
metabolism, and degree of maternal and fetal protein binding. Anesthetic agents administered to the parturient
[45]
during labor and delivery cross the placenta. Fortunately, most of these drugs, in commonly used doses, have
[45]
minimal immediate fetal effects and no known long-term neonatal effects. [46] [47]
Parturition Pain
Labor pain, a form of acute pain, is perceived by many women as very severe or intolerable. Parturition pain has [48]
both a visceral and somatic component. Visceral stimulation occurs as the cervix and lower uterine segment dilate.
Uterine contractions may result in myometrial ischemia, causing visceral pain. Early labor pain (latent phase and
early active phase) is primarily visceral and occurs during uterine contractions. Afferent impulses are transmitted via
sensory nerves (myelinated A delta and unmyelinated C fibers) that pass through the paracervical nerve plexus (Fig.
25-1 (Figure Not Available) ). These nerves accompany the sympathetic nerves to the inferior, middle, and superior
hypogastric plexus, and then to the celiac plexus. They enter the lumbar sympathetic chain and then pass with T10,
T11, T12, and L1 white rami communicantes to the posterior spinal roots, where they synapse with neurons in the
dorsal horn of the spinal cord. Pain is often referred to other areas, including the skin, the abdominal muscles, and
the back.
The somatic component of labor pain is caused by distention, inflammation, and tissue injury of the pelvic joints,
vagina, pelvic floor, and perineum. Somatic pain
Figure 25-1 (Figure Not Available) The visceral and somatic pain pathways associated with parturition. (From
Chestnut DH (ed): Obstetric Anesthesia: Principles and Practice, 2nd ed. St. Louis, Mosby, 1999, p 323. Modified
from Bonica JJ: The Management of Pain, 2nd ed. Philadelphia, Lea & Febiger, 1990, p 1325.)
TABLE 25-1 -- CENTRAL AND PERIPHERAL BLOCKS FOR LABOR PAIN

Block Visceral Pain Somatic Pain
Lumbar epidural local anesthetics T10, T11, T12, and L1 S2, S3, and S4
Intrathecal local anesthetics T10 level Saddle block (S1–S5)
Intrathecal opioids + −
Paracervical block + −
Lumbar sympathetic block + −
Caudal block (low) − +
Caudal block (high) T10 level +
Pudendal block − +
+ denotes effective block; − denotes block does not block pain pathway.
occurs as the fetus descends in the birth canal during the late first stage and second stage of labor. Afferent impulses
are transmitted via the pudendal nerve through the sacral plexus to the spinal cord at S2, S3, and S4. The pudendal
nerve also supplies motor innervation to the pelvic floor and the perineum.
The visceral and somatic components of labor pain can be blocked at various levels by one or more nerve blocks
( Table 25-1 ). For example, epidural analgesia can block the visceral or somatic components, or both, depending on
the spinal levels blocked. A lumbar sympathetic block stops visceral labor pain and a pudendal block eliminates
somatic pain.
Analgesia requirements increase as labor progresses. The late active phase of labor is the most painful. The
minimum local analgesic concentration (MLAC) increases with advancing cervical dilation, and the same dose of [49]
intrathecal sufentanil and bupivacaine has a longer duration of action in early labor compared with late labor. [50]
580
Regional Analgesia During Labor
The optimal analgesic for labor is one that can provide pain relief for first- and second-stage labor but has otherwise
minimal effects on mother and fetus. The ideal analgesic technique would provide rapid onset of analgesia, effective
analgesia with minimal motor block, minimal risk of maternal toxicity, minimal placental transfer and effects on the
fetus, and long duration. Neuraxial labor analgesia (epidural, spinal, or combined spinal-epidural analgesia) is
currently the most effective method of providing labor and delivery analgesia. The side-effect profiles of these
[51]
techniques are acceptable to most women and obstetricians. Current research aims to decrease the incidence and
severity of side effects while maintaining excellent analgesia.
In addition to being the most effective form of labor analgesia, neuraxial analgesia has other salutary effects on
maternal and fetal well-being. Effective analgesia prevents maternal hyperventilation during labor. Hyperventilation
and hypocarbia may decrease UBF. Also, hypocarbia produces a left shift in the maternal oxyhemoglobin
[38]
dissociation curve, causing oxygen to be more tightly bound and decreasing the transfer of oxygen across the
placenta. Finally, hyperventilation during contractions may be followed by periods of maternal hypoventilation
[52]
between contractions, resulting in maternal and fetal hypoxemia. Neuraxial analgesia results in a decrease in
[53] [54]
maternal oxygen consumption. Compared with meperidine analgesia, epidural analgesia is associated with higher
[55]
maternal oxygen saturation. Most parturients and fetuses are not harmed by this hyper- and hypoventilation cycle
[56]
and increase in oxygen consumption. However, neuraxial analgesia may be advantageous for fetuses with marginal
uteroplacental circulation and function. [57]
EPIDURAL ANALGESIA
For many years, epidural analgesia has been the mainstay of regional analgesia during labor. The advantages of
epidural analgesia include the ability to provide continuous analgesia for an unpredictable period of time and to
convert analgesia to anesthesia should operative intervention become necessary.
A preanesthetic evaluation should be performed, and informed consent must be obtained. This step is best done
early in labor, when the evaluation and consent process can, by circumstances, be less hurried.
Contraindications to epidural analgesia are similar to those in the nonlaboring patient. They include patient refusal
or inability to cooperate, increased intracranial pressure secondary to a mass lesion, skin or soft tissue infection at
the site of insertion, septicemia, coagulopathy, and hypovolemia.
Resuscitation equipment and drugs for the management of minor or serious complications of epidural analgesia or
anesthesia should be immediately available. Monitoring should include frequent maternal blood pressure
determinations and fetal heart rate monitoring until cardiovascular stability is ensured, both during and after
initiation of analgesia. The fetal heart rate should be monitored and documented by a qualified individual. [58] [59]
A large-bore intravenous catheter should be placed, and approximately 500 mL Ringer’s lactate (without dextrose)
should be administered immediately before initiation of neuraxial analgesia to decrease the incidence of maternal
hypotension and subsequent uteroplacental hypoperfusion. In one study, the infusion of crystalloid, 1000 mL,
[60]
provided no additional benefit compared with 500 mL. [61]
Technique
Epidural analgesia for labor is usually administered via a single lumbar epidural catheter. A double-catheter
technique (high lumbar and caudal epidural catheters) is rarely used, although it provides true segmental analgesia.
The epidural catheter can be inserted with the parturient in the lateral or sitting position. The lateral position may be
more comfortable for some women, and fetal monitoring may be easier in this position. However, one study found
cardiac output decreased more in the lateral decubitus position with maximal lumbar flexion compared with the
sitting position. The sitting position may improve respiratory mechanics and may aid the anesthetist in identifying
[62]
anatomic landmarks, particularly in the obese patient. In addition, obese patients may be more comfortable in the
sitting position. Maternal position has minimal effect on the spread of epidural anesthetic solutions.
[63] [64] [65]
Both median and paramedian approaches to the lumbar epidural space are acceptable. One prospective study found
no difference in the success rate between the two techniques. A retrospective study found a higher incidence of
[66]
minor complications (difficulty threading the catheter, paresthesias, and venous cannulation) with the midline
approach compared with the paramedian approach. [67]
581
The loss of resistance technique (to saline or air) is used most commonly to identify the epidural space. One
prospective, randomized study found a higher incidence of unblocked segments using loss of resistance to air
compared with saline after the injection of 8 mL of 0.5% of bupivacaine. However, all patients had satisfactory
[68]
anesthesia after higher volumes were injected. The unintentional subarachnoid injection of air causes an immediate
headache. Postdural puncture headache (PDPH) occurred more commonly in patients who had unintentional dural
puncture as a result of use of the loss of resistance to air technique compared with use of saline. Studies conflict [68] [69]
as to whether the incidence of unintentional dural puncture differs between the two techniques. [68] [70]
Several epidural catheter types are available. Single-orifice catheters restrict the injection of drug to a single site.
Closed-end, multiorifice catheters allow the unintentional injection of drug to more than one site. However,
evidence suggests that there is less likelihood of a patchy or unilateral block with a multiorifice catheter. A wire- [71] [72]
coil, flexible-tip catheter has been associated with fewer catheter-induced paresthesias and venous cannulations. [73]
Short lengths of catheter (2–3 cm) threaded into the epidural space are associated with a higher incidence of
successful epidural analgesia or anesthesia but also with a higher incidence of catheter migration from the epidural
space. D’Angelo concluded that single-orifice catheters should be threaded 2 cm into the epidural space if
[74] [75]
minimal movement or short duration is anticipated, but, otherwise, they should be threaded 6 cm. Beilin suggested [75]
that the optimal length of multiorifice catheter threaded into the epidural space is 4 to 6 cm. Epidural catheters
[74]
move relative to the skin when the patient moves from the sitting-flexed position to the sitting-upright position and
then to the lateral position. It may, therefore, be advisable to secure the catheter after the patient assumes the lateral
[76]
position.
Subarachnoid and Intravascular Test Dose
The unintentional placement of a subarachnoid needle or catheter is tested by aspiration or injection of a small bolus
dose of local anesthetic. Aspiration does not reliably rule out subarachnoid catheter placement with single-orifice
catheters. However, in a study of multiorifice catheters, aspiration was identified in 60 of 62 intravenous
[77]
catheters. Standard subarachnoid test doses (e.g., lidocaine, 45 mg) are likely to result in higher sensory levels and
[78]
significant motor block in pregnant patients compared with nonpregnant patients.
The intravascular placement of a catheter can be detected by aspiration, injection of epinephrine, or local anesthetic.
There are several limitations to an epinephrine-containing test dose in parturients. There is considerable variability
in baseline heart rates in laboring women (mean 27–33 beats/min ). In addition, parturients have an attenuated
[79]
chronotropic response to catecholamines. Leighton and colleagues administered intravenous epinephrine, 15 µg,
[80] [79]
to parturients and noted that only 5 of 10 women had a 25 beat per minute increase over baseline. However, using
the systemic response to lidocaine, 100 mg, as the gold standard, Colonna-Romano and Nagaraj determined that [81]
the sensitivity of a standard epinephrine, 15-µg, test dose was 100% and the specificity 96% when administered
under the following conditions:
1. The epinephrine-containing test dose was injected during uterine diastole.

2. An increase in heart rate of 10 beats/minute was used as a cut-off point.
3. The test dose was repeated if the response was equivocal or uterine systole intervened.
An additional limitation of epinephrine is the possibility of decreased uteroplacental perfusion (demonstrated in

gravid guinea pigs and ewes
[82]
) and consequent fetal distress. Finally, intravenous epinephrine can cause
[41] [83] [79]
dangerous hypertension in preeclamptic parturients. [84]
An unintentional intravascular catheter may be detected with bolus injection of subtoxic doses of local anesthetic,
such as lidocaine, 100 mg (5 mL of 2% lidocaine), with assessment of symptoms of central nervous system
irritability. However, the epidural administration of this amount of drug results in an unnecessary motor block in the
laboring parturient.
Other markers of intravascular injection have been investigated. Leighton and colleagues found that the injection of
1 to 2 mL of air (monitored by placing the external fetal heart rate probe over the parturient’s heart) was a sensitive
and specific indicator of intravascular injection for single-orifice but not for multiorifice catheters. Isoproterenol
[85] [86]
has also been investigated in a small number of patients, as has fentanyl, 100 µg.
[87]
Finally, electrical
[88] [89] [90]
stimulation of a wire-embedded epidural catheter has been suggested as a possible technique. [91] [92]
No matter what test dose is used, or whether one is used at all, incremental dosing of epidural catheters is essential.
No test has a sensitivity of 100%, and catheters may migrate during use. [93]
582
Drugs for Epidural Analgesia
Epidural analgesia has been initiated with many different local anesthetics, local anesthetic concentrations, and
mixtures of local anesthetics and other drugs (e.g., opioids). The general trend for more than a decade has been
toward less concentrated local anesthetic solutions mixed with opioids. Epidural administration of less concentrated
local anesthetic solutions decreases maternal motor block, and results in less fetal malrotation and fewer
instrumental deliveries compared to more concentrated solutions. [94] [95] [96] [97]
Local anesthetics have been the mainstay of epidural analgesia for many years. There are advantages and
disadvantages to using different local anesthetics. Bupivacaine is the most common local anesthetic used for labor
analgesia. Low concentrations (≤ 0.125%) provide excellent analgesia with minimal motor block. Bupivacaine is
highly protein-bound with minimal placental transfer. Duration of analgesia is approximately 2 hours. However,
[98] [99]
it may take 20 minutes to reach peak effect. Lidocaine has a faster onset than bupivacaine, but duration of analgesia
is shorter. It is less protein-bound and, therefore, has a higher umbilical vein-to-maternal vein ratio than
bupivacaine. However, controlled studies have found no differences in neonatal neurobehavioral scores with use
[100]
of epidural lidocaine, bupivacaine, or 2-chloroprocaine. 2-Chloroprocaine has a rapid onset, but the duration of
[101] [102]
the analgesia is less than 45 minutes, limiting its routine use for labor analgesia. It is most useful for rapidly
extending epidural anesthesia for urgent operative delivery. An epidural test dose of 2-chloroprocaine was
associated with a markedly shorter duration of action of subsequent bupivacaine and fentanyl compared with a
lidocaine test dose. [103]
Ropivacaine and levobupivacaine have recently become available in the United States. Equal doses of both drugs
are associated with less cardiac toxicity than bupivacaine. Compared with an equivalent concentration of
[28] [104]
bupivacaine, ropivacaine may be associated with less motor block. A meta-analysis of six randomized and [105]
prospective studies showed that ropivacaine, 0.25%, was associated with a higher incidence of spontaneous vaginal
delivery than bupivacaine, 0.25%. However, because low concentrations of bupivacaine combined with opioid
[106]
minimize both the risk of cardiac toxicity and motor block, the role of these drugs for routine labor analgesia has not
been firmly established.
Both ropivacaine and levobupivacaine have been evaluated for epidural labor analgesia. Most studies [107] [108] [109] [110] [111] [112]
have evaluated local anesthetic concentrations greater than 0.125%. Two recent studies have shown that, when given
by bolus injection at concentrations required to produce effective labor analgesia, ropivacaine is 40% less potent
than bupivacaine. Several recent studies have compared epidural infusion of low-dose (0.08%–0.125%)
[113] [114]
ropivacaine with opioid to bupivacaine with opioid. In this setting, both drugs produce similar analgesia at
[115] [116] [117]
similar doses. Motor block was less in patients who received ropivacaine than in those who received bupivacaine.
The potencies of the local anesthetics commonly used for epidural labor analgesia are listed in Table 25-2 .
Opioids are commonly added to local anesthetics for epidural analgesia. Epidural opioids and local anesthetics
interact synergistically to provide analgesia. Fentanyl decreased the mean effective dose (ED50 ) of bupivacaine
[118] [119]
and 2-chloroprocaine. The addition of opioid allows for a decreased concentration of local anesthetic, thus
[120]
decreasing motor block. Epidural opioids alone can provide moderate analgesia for early labor, but the necessary
dose is accompanied by bothersome side effects (e.g., pruritus, nausea, vomiting, neonatal respiratory depression).
Combining local anesthetics with opioids provides effective analgesia while minimizing the undesirable side
effects. In addition, latency is shorter and duration of analgesia is longer with the addition of opioid to local
[121]
anesthetics. [122]
Although there is significant systemic absorption of epidural opioids, their site of action is primarily
TABLE 25-2 -- EPIDURAL LOCAL ANESTHETIC ED50 AND ED95 FOR LABOR ANALGESIA
Drug ED50 ED95
2-Chloroprocaine[120] 0.43% * 0.83% *
[507] †
Lidocaine 0.37% 0.52% †
Bupivacaine[114] [507] 0.065 † –0.093% * 0.129% †

[113] [114] * *
Ropivacaine 0.111 –0.156%
Levobupivacaine[508] 0.083% †
ED50 , median effective dose; ED95 , dose effective in 95% of parturients. Effective analgesia = pain score less than 10 mm on a scale of 0 to 100 mm.
Data from references , [113] [114] [120] [507] [508] .
583
*Mixed nulliparous and parous parturients, cervical dilation ≤7 cm.

†Mixed nulliparous and parous parturients, cervical dilation ≤5 cm.
**Nulliparous parturients, cervical dilation 2 cm to 5 cm.
TABLE 25-3 -- DRUGS FOR INITIATION AND MAINTENANCE OF LABOR EPIDURAL ANALGESIA
Bupivacaine-Fentanyl Bupivacaine-Sufentanil
LOADING DOSE
Bupivacaine 0.125% 0.125%
Opioid 50–100 µg 10–15 µg
Volume 10–15 mL 10–15 mL
MAINTENANCE INFUSION
Bupivacaine 0.0625%–0.125% 0.0625%–0.125%
Opioid 2 µg/mL 0.2–0.33 µg/mL
Rate 10–20 mL/hr 10–20 mL/hr
Adapted from Riley ET, Rose BK: Epidural and spinal analgesia/anesthe sia. II. Opioid techniques. In Chestnut DH (ed): Obstetric Anesthesia: Principles and
Practice, 2nd ed. St. Louis, Mosby, 1999 pp 386–408; and from Naulty JS: Continuous infusions of local anesthetics and narcotics for epidural analgesia in the
management of labor. Int Anesthesiol Clin 28:17, 1990.
spinal. Bupivacaine requirements are less with epidural than with intravenous fentanyl. [123] [124]
The lipid-soluble opioids, fentanyl and sufentanil, are commonly used for epidural labor analgesia. In the dose
ranges used for epidural analgesia initiation and maintenance, opioids have been shown to be safe for both mother
and neonate. Epidural morphine does not result in satisfactory labor analgesia.
[125] [126] [127]
Epidural labor analgesia can be initiated with a bolus dose of fentanyl, 50–100 µg, or sufentanil, 10–15 µg ( Table
25-3 ). The opioid is usually combined with dilute local anesthetic (e.g., bupivacaine, 0.0625%–0.125%). If given
alone, better analgesia is obtained if opioids are diluted to 10 mL with normal saline. [128]
Epinephrine has been added to local anesthetic solutions for labor analgesia. Although it shortens latency and
potentiates analgesia, epinephrine also increases motor block. Epinephrine, 5 µg/mL, mixed with bupivacaine
[129] [130] [131]
significantly slowed labor compared with a lower epinephrine dose. Therefore, epinephrine appears to offer little [132]
as an adjuvant to epidural analgesia for labor.
Several studies have investigated the role of epidural clonidine in labor analgesia. These initial studies found [133] [134] [135]
no significant adverse effects on mothers or neonates. However, clonidine did cross the placenta. Therefore, more [134]
sophisticated neonatal testing is indicated before the routine use of epidural clonidine can be advocated.
In summary, depending on the stage of labor, epidural analgesia can be initiated with local anesthetics, local
anesthetics with opioid, or opioid alone (only effective for very early labor, usually with a test dose of local
anesthetic). The drug(s) and doses should be individualized for each parturient. For example, early labor pain can be
treated with quite dilute solutions of bupivacaine, 0.0625%, mixed with opioid. More advanced labor, or delivery
that is expected to occur within several hours (e.g., the parous patient in active labor receiving an oxytocin infusion),
requires a more concentrated solution and more volume (to obtain sacral spread). The parturient with a low-lying
fetus requires an earlier sacral block (i.e., larger volume).
Maintenance of Epidural Analgesia
Epidural analgesia may be maintained with intermittent bolus injection or continuous epidural infusion. Patient-
controlled epidural analgesia (PCEA) is a combination of both techniques. Continuous epidural infusions result in
less need for bolus injections and increased patient satisfaction. Continuous infusion is usually
[136] [137] [138] [139] [140] [140] [141]
accompanied by the gradual onset of perineal analgesia, obviating the need for a bolus dose at delivery. In studies
comparing bolus injection with continuous infusion of bupivacaine, continuous infusion results in a higher total
bupivacaine dose. However, the infusion of lower concentration bupivacaine at a higher rate may result in
[136] [140] [141] [142]
similar analgesia with less motor block and no increase in total dose. [138] [141] [143]
Typical maintenance infusions include bupivacaine, 0.0625% to 0.125%, with fentanyl, 2 to 3 µg/mL, or sufentanil,
0.2 to 0.33 µg/mL, at 10 to 20 mL per hour; more dilute solutions usually require higher infusion rates (see Table
25-3 ).
584
PCEA usually provides both a continuous epidural infusion and patient-titrated bolus injections. PCEA may
improve patient satisfaction and decrease the average hourly dose of local anesthetic.
[144] [145]
Most studies [145] [146] [147] [148]
have investigated PCEA using bupivacaine, 0.125%, with opioid. Ferrante and colleagues found comparable [149]
analgesia with PCEA (bupivacaine, 0.0625%, with fentanyl) versus a continuous epidural infusion of bupivacaine,
0.125%, with fentanyl. Few studies have systematically evaluated the effects of manipulating anesthetic
concentration, background infusion, demand dose, and lockout interval. The results of a study published in 2000
suggest that a larger bolus dose and longer lockout interval provided better patient satisfaction than a smaller dose
and shorter lockout interval. [150]
Inadequate Epidural Analgesia
Epidural analgesia may be inadequate because (1) the sensory block is not extensive enough, (2) there are unblocked
segments or the block is unilateral, or (3) the block extent is satisfactory but not dense enough for the degree of pain.
If inadequate analgesia is to be evaluated, the extent of sensory blockade must be determined first. A bilateral T10
through L1 block is adequate for early labor, but sacral blockade is necessary for late first-stage labor and for
second-stage labor. Frequently, the caudad extent of the block is not sufficient, especially if labor proceeds quickly.
A large bolus (10–15 mL) and an increase in maintenance infusion rate may help.
Frequently, there are unblocked segments, or the block is unilateral. In general, this problem is less likely to occur if
large volumes of dilute local anesthetic are used rather than small volumes of more concentrated local anesthetic. [151]
After initiation of analgesia, Beilin and colleagues compared two techniques for treating inadequate analgesia with
[152]
a multiorifice catheter placed 5 cm into the epidural space: (1) withdrawal of the catheter 1 cm followed by
additional local anesthetic, or (2) simply injecting the same dose of local anesthetic without catheter withdrawal.
Both techniques were equally effective for treating inadequate analgesia.
Finally, some patients have pain that breaks through dilute solutions of local anesthetic and opioid. The treatment is
administration of a higher concentration of local anesthetic. Studies have shown that patients with breakthrough pain,
who require frequent top-up doses, are a greater risk for cesarean delivery. Presumably, breakthrough pain is a
[153]
marker for dysfunctional labor, fetal malrotation, or cephalic-pelvic disproportion. Failure to obtain satisfactory
analgesia with a large volume of concentrated local anesthetic should prompt the anesthesiologist to replace the
epidural catheter immediately.
COMBINED SPINAL-EPIDURAL ANALGESIA
Combined spinal-epidural (CSE) analgesia for labor was introduced into the obstetric anesthesiologist’s
armamentarium in the early 1990s after Leighton and colleagues demonstrated that intrathecal fentanyl rapidly
[154]
provided profound analgesia. The technique combines the advantages of spinal and epidural analgesia. Opioid alone,
or opioid in combination with a local anesthetic, is injected intrathecally to initiate neuraxial analgesia. Maintenance
analgesia is provided via the epidural catheter.
CSE analgesia has advantages and disadvantages compared with epidural analgesia ( Table 25-4 ). Onset of
analgesia is rapid, within several minutes. Opioid-only CSE analgesia during latent and early active-phase labor
provides excellent analgesia without sympathectomy or motor block. The lack of sympathectomy is advantageous in
patients in whom a rapid decrease in intravascular volume is undesirable (e.g., patients with preeclampsia or stenotic
valvular heart disease). Lack of motor block is desirable in patients who wish to ambulate. One study found that
CSE analgesia resulted in fewer instrumental vaginal deliveries than epidural analgesia. A significant advantage of[155]
initiating analgesia with a CSE technique (with opioid and a local anesthetic) is the rapid onset of sacral analgesia.
After placement of a lumbar epidural catheter,
TABLE 25-4 -- EPIDURAL VERSUS COMBINED SPINAL- EPIDURAL ANALGESIA FOR LABOR ANALGESIA
Epidural Combined Spinal-Epidural

Onset 10–15 min 2–5 min
Motor block Mild to none None with opioid-only dose
Sacral block Delayed 1–2 hr Immediate
Sympathectomy Present None with opioid-only dose
Epidural catheter Able to determine that catheter is May not know whether catheter is functional for 1–2 hr
functional within 15–30 min
Pruritus Lower incidence, less severe High incidence
585
TABLE 25-4 -- EPIDURAL VERSUS COMBINED SPINAL- EPIDURAL ANALGESIA FOR LABOR ANALGESIA
Epidural Combined Spinal-Epidural
Fetal bradycardia Comparable risk Comparable risk
Postdural puncture headache (PDPH) Slightly increased incidence *
Respiratory depression Increased risk, particularly in presence of systemic opioids
Total drug exposure Greater Less

*Although intentional dural puncture with a small-gauge spinal needle slightly increases the frequency of PDPH, clinical studies report similar
fre quency of headache and epidural blood patch in women receiving either technique.[158]
several hours of continuous epidural infusion or repeat epidural bolus injections are required before adequate sacral
analgesia is achieved. Therefore, CSE analgesia is superior to epidural analgesia in patients who require an
[131]
immediate sacral block (e.g., late first stage or second stage of labor).
Several investigators found that initiation of analgesia with CSE analgesia was less likely to result in failed
[156] [157]
epidural analgesia (i.e., the catheter is more likely to be in the epidural space). The risk of unintentional dural
puncture may be lower with CSE analgesia than with epidural analgesia. Finally, the results of one study suggest [158]
that CSE analgesia is associated with more rapid cervical dilatation than epidural analgesia. [159]
There are several undesirable side effects of CSE analgesia. The incidence of pruritus is higher with intrathecal than
with epidural opioids. Gastric emptying may be delayed more in patients who receive intrathecal opioids than
[155] [158] [160]
in those who receive epidural or systemic opioids. CSE analgesia may be associated with a slightly higher risk of
[161]
PDPH (estimated rate of 3 in 1000). [162]
After analgesia initiation with CSE block, it is not clear for several hours whether the epidural catheter is properly
sited in the epidural space. Therefore, if it is important to have a functioning epidural catheter in place (e.g., in the
presence of a worrisome fetal heart rate pattern or an anticipated difficult airway), CSE analgesia may not be the
technique of choice.
Several potentially serious side effects of CSE analgesia are of concern. Fetal bradycardia not associated with
maternal hypotension occurs after initiation of both epidural and CSE analgesia. Maternal plasma epinephrine
concentration decreases acutely after the initiation of neuraxial analgesia. Epinephrine stimulation of uterine [35] [36]
beta2 -adrenergic receptors results in uterine tocolysis. It has been hypothesized that an acute decrease in maternal
epinephrine results in temporary imbalance of uterine tocolytic and tocodynamic forces, resulting in uterine
hypertonus and a decrease in uterine perfusion. A prospective study comparing CSE with epidural analgesia found
no difference in the incidence of fetal bradycardia (17%). However, Riley suggested that because of patient
[163] [164]
selection, the incidence of fetal bradycardia may be higher after CSE block. CSE analgesia is more likely to be used
in patients with more pain or in more advanced labor, and, therefore, changes in maternal epinephrine concentration
may be more profound. A large retrospective review found no increase in emergency cesarean delivery rate in
patients who received intrathecal sufentanil compared with those who received no or systemic analgesia. [165]
Nitroglycerine has been used successfully to treat uterine hypertonus associated with the initiation of neuraxial
analgesia. [166]
Respiratory depression or arrest has been reported after the intrathecal injection of sufentanil in laboring women. [167]
The risk appears to be increased when intrathecal opioids are administered before or after systemic
[168] [169] [170] [171] [172]
opioids, and the risk is dose-dependent. The current trend toward using lower opioid doses combined with
[167] [170] [172] [173]
local anesthetic (see later discussion) should lessen this risk.
There has been concern that drugs injected into the epidural space after CSE block may traverse the dural hole and
result in higher CSF concentrations than anticipated. Drug transfer across a dural hole is dependent on hole size. It [174]
may also depend on the mode of epidural injection: bolus versus infusion. Bolus injection into the epidural space
results in an acute increase in epidural pressure, which may transiently reverse the normal positive pressure gradient
between the subarachnoid and epidural spaces. Suzuki and colleagues randomized patients to a 26-G dural
[175] [176]
puncture versus no puncture, followed by epidural anesthesia. The cephalad sensory block was not different between
the two groups, although there was increased caudad spread in the group with dural puncture. In contrast, Beaubien
and colleagues found that dural puncture with a 25-G cutting spinal needle did not decrease the need for epidural
[177]
PCEA analgesia. Reassuringly, 3 hours after CSE initiation with a 26-G pencil-point needle, contrast dye injected
through the epidural catheter was not observed in the subarachnoid space. [178]
The clinical effect of the presence of a dural hole may depend on the actual drug injected into the epidural space. In
sheep, epidural morphine injection resulted in cisternal morphine concentrations eight times higher after dural
586
puncture with a 25-G pencil-point needle than occurred in control subjects without dural puncture. In an in vitro [179]
model, meningeal morphine flux increased after dural puncture with a 27-G pencil-point needle, but lidocaine flux
did not. In conclusion, drugs injected into the epidural space after CSE analgesia may have increased flux across
[174]
the dura, and this possibility should be considered when administering drugs into the epidural space.
High sensory levels (facial) associated with dysphagia [180] [181] [182]
and aphasia [183]
have been described after CSE
administration.
Finally, there have been several case reports of meningitis after CSE analgesia in obstetric patients. It is [184] [185] [186]
unclear whether this is a reporting phenomenon of a new technique or whether the risk of meningitis is increased
with CSE.
Technique
Although there are several methods of initiating CSE analgesia, the most popular is the needle-through-needle
technique. After identifying the epidural space with an epidural needle, a small (25-G to 27-G) pencil-point spinal
needle is passed through the epidural needle to puncture the dura. Opioid, or opioid plus local anesthetic, is injected
into the subarachnoid space (spinal dose). The spinal needle is withdrawn, and an epidural catheter is threaded
through the epidural needle. Analgesia is maintained via the epidural catheter, as with traditional epidural analgesia.
The drugs most commonly used for CSE analgesia (bupivacaine, fentanyl, and sufentanil) are hypobaric. [187]
Therefore, patient position during block initiation markedly influences the sensory level (mean sensory level was T3
in the sitting position compared with T6 in the lateral position). The sensory block is more likely to be [188]
asymmetrical when it is performed with the patient in the lateral position. Dextrose added to sufentanil (to make it
hyperbaric) decreases the duration of analgesia. [189] [190]
Blood pressure decreases after CSE analgesia, including opioid-only CSE analgesia. Therefore, hemodynamic
monitoring after the block should mimic the block for epidural analgesia. The drop in blood pressure is not the result
of a sympathectomy and may be due to a decreased level of circulating catecholamines secondary to pain relief.
[164]
Spinal drug(s) and maintenance technique depend on the patient’s stage of labor and desire to ambulate. If a patient
is in early labor and desires ambulation, CSE analgesia can be initiated with opioid only. Epidural analgesia is
initiated via the epidural catheter when the patient requests additional analgesia. This allows the patient freedom to
ambulate without being connected to an infusion pump. Alternatively, the epidural infusion can begin immediately
after initiation of CSE analgesia. This approach obviates the need for an initial epidural bolus. If a patient requires a
somatic block or is expected to require one soon, CSE analgesia can be initiated with opioid and local anesthetic and
the epidural infusion can be started immediately.
Drugs
Lipid-soluble opioids are used alone or in combination with bupivacaine for initiation of CSE analgesia. The ED50 of
intrathecal sufentanil is 1.8 to 2.6 µg, and the ED95 is 8.9 µg (95% CI 7.5–11.5 µg). The ED50 of fentanyl is 14
[191] [192] [191]
to 18.2 µg, and the ED95 is 20 to 30 µg. The duration of both drugs is approximately 90 minutes.
[193] [194]
Campbell and colleagues found that the addition of bupivacaine, 2.5 mg, to sufentanil, 10 µg, improved the quality
[195]
and duration of analgesia. In contrast to Campbell’s study, Sia found an increased incidence of hypotension with
[196]
the addition of bupivacaine. However, results of several studies published within the past few years suggest that
sufentanil, 2.5 to 5 µg, added to bupivacaine, 2.5 mg, provides satisfactory analgesia with a lower incidence of
[197] [198]
side effects compared with sufentanil, 10 µg. Similarly, sufentanil, 2.5 µg, combined with bupivacaine, 1.25 mg,
[197]
and epinephrine, 25 µg, provides analgesia comparable with sufentanil, 5 µg, with less pruritus. [199]
Alternatively, two investigators have manipulated the bupivacaine dose combined with fentanyl, 25 µg. Duration
was significantly longer for bupivacaine, 2.5 mg, than with the lower dosage (1.25 mg). [200] [201]
Initiation of CSE analgesia with bupivacaine alone does not provide satisfactory pain relief for many parturients. [195] [197]
Intrathecal clonidine and neostigmine have been investigated as adjuvants for labor analgesia. Clonidine alone, 200
µg, provided adequate analgesia but was associated with maternal hypotension and sedation. Several investigators [202]
have studied clonidine combined with sufentanil, or sufentanil and bupivacaine mixtures.
[203] [204]
Clonidine, 30 to [205] [206]
50 µg, prolonged the duration of intrathecal sufentanil or sufentanil with bupivacaine. The studies differed as to
587
whether hypotension was exacerbated by the addition of clonidine, although hypotension, when present, was easily
treatable. Clonidine, 30 µg dose, was undetectable in maternal and umbilical cord serum. It did not result in motor [204]
block.
Intrathecal neostigmine decreased the ED50 of sufentanil and prolonged sufentanil/bupivacaine/clonidine

[207]
analgesia. However, neostigmine was associated with an unacceptably high incidence of nausea and vomiting.
[206] [207]
Drug doses for initiating CSE analgesia are listed in Table 25-5 .
Ambulatory (Walking) Epidural Analgesia
Many parturients have questions about walking throughout labor. Although several nonrandomized reports
TABLE 25-5 -- OPIOID DOSES FOR INITIATION OF EPIDURAL OR COMBINED SPINAL-EPIDURAL ANALGESIA
Drug Opioid Alone Opioid with Bupivacaine *
Fentanyl 25 µg 15–25 µg
Sufentanil 5–10 µg 1.25–5 µg

*Bupivacaine, 2.5 mg.
noted faster labor among women who ambulated, several other clinical trials failed to find any positive impact of
ambulation on the duration or outcome of labor. Still, neuraxial analgesia techniques that minimize maternal
[208] [209]
motor blockade may improve patient satisfaction. In addition, parturients like to be able to use the bathroom and to
sit in a chair. When even limited maternal ambulation is contemplated during neuraxial labor analgesia, important
issues to consider include hemodynamic stability, preservation of motor tone, and proprioception.
The addition of small amounts of local anesthetic (i.e., bupivacaine, 2.5 mg) to intrathecal opioids rarely produces
demonstrable motor block. Orthostatic hypotension also is uncommon.
[208] [210]
Gross motor function may be intact, but proprioception and balance may be impaired by intrathecal or epidural local
anesthetics. Buggy and colleagues noted that in patients with intact motor function, 66% had posterior column
[211]
sensory impairment. However, using computed dynamic posturography, Pickering found no functional [212]
impairment in women lacking clinical motor block. Finally, some have argued that intact proprioception is not
necessary for safe ambulation (e.g., diabetic patients walk with altered proprioception). [213]
There has been some debate as to the best test of motor function. Straight leg raise against resistance, the Medical
Research Council scale, and the modified Bromage scale have been used. Some protocols include a partial deep
[214]
knee bend or the ability to step up onto a stool with either leg leading. The best test or tests have not been
determined. There is agreement that women in labor should ambulate with an assistant. [214]
Ambulatory analgesia can be accomplished with any neuraxial analgesic technique that minimizes motor block. This
has been accomplished with CSE analgesia (with and without local anesthetic) and epidural analgesia. A typical
epidural technique includes low-concentration bupivacaine (≤ 0.1% with opioid). Ambulatory CSE analgesia
[208] [215] [216]
has been initiated with bupivacaine, 2.5 mg, and fentanyl, 25 µg. The standard test dose (lidocaine, 1.5%, with
[208]
epinephrine, 1:200,000–3 mL) may interfere with the ability to ambulate after epidural and CSE analgesia. [216] [217]
SPINAL ANALGESIA
In general, single-shot spinal analgesia is not useful for laboring patients because of its limited duration. It may be
used in parturients who require analgesia shortly before anticipated delivery. Continuous spinal analgesia is
currently not practical for most parturients. The available catheters (essentially epidural catheters) require a large-
gauge introducer needle and are therefore associated with an unacceptably high incidence of PDPH. However, the
placement of a continuous spinal catheter is a management option in patients who have suffered an accidental dural
puncture with an epidural needle. Analgesia can be initiated with drugs and doses as for CSE analgesia and
maintained with a continuous subarachnoid infusion (e.g., bupivacaine, 0.0625%, with fentanyl, 2 µg/mL, at 1–3
mL/hour).
Caudal Analgesia
Continuous caudal epidural analgesia is used infrequently in the practice of modern obstetric anesthesia. It is
technically more difficult to place a caudal catheter. Large volumes of local anesthetic are required for first-stage
588
labor analgesia and result in higher maternal plasma drug concentrations and dense sacral motor block early in labor.
There is a risk of needle or catheter misplacement and direct injection into the fetus. Continuous caudal analgesia
may be a management option for patients with fused lumbar vertebrae. [218]
Lumbar Sympathetic Block
A paravertebral lumbar sympathetic block interrupts transmission of visceral afferent nerve impulses from the uterus
and cervix at the level of the L2 to L3 sympathetic chain. Similar to a paracervical block, it provides analgesia for
the first but not the second stage of labor. Disadvantages include the following: (1) the technique is not continuous;
(2) it is technically more difficult to learn and perform; and (3) it requires bilateral injections. There are several
advantages: (1) it is associated with less fetal bradycardia than a paracervical block; (2) it provides first-stage
analgesia without any motor block; (3) it is useful for patients with previous back surgery ; and (4) it does not [219]
adversely affect the progress of labor. In fact, the course of labor appears accelerated compared with that of
[220] [221]
patients who have received epidural analgesia. [221]
ADDITIONAL NERVE BLOCKS
Neuraxial analgesia is the most effective and flexible analgesic technique for labor and delivery. However, some
parturients may not be candidates for neuraxial analgesia, or they may not want it. Other nerve blocks may provide
acceptable, albeit less flexible, analgesia (see Table 25-1 ).
Paracervical Block
A paracervical block halts transmission of visceral afferent nerve impulses from the uterus and cervix through the
paracervical, or Frankenhäuser’s, ganglion. Advantages include adequate analgesia for the first stage of labor, before
fetal descent, without somatic sensory or motor block. However, the block is not continuous, and it does not relieve
somatic pain caused by distention of the pelvic floor, vagina, or perineum.
The block is performed with the patient in the lithotomy position with left uterine displacement. The obstetrician
injects 5 to 10 mL of dilute local anesthetic solution by introducing the needle through the vagina into the left and
right lateral vaginal fornix to a depth of 2 to 3 mm. Aspiration and incremental injection are recommended.
The choice of local anesthetic is controversial. Lidocaine, 1%, is commonly used in the United States. The
manufacturers of bupivacaine state that it is contraindicated for paracervical block because it may be associated with
a higher incidence of adverse neonatal outcome. 2-Chloroprocaine has been advocated for paracervical block
[222]
because its short intravascular half-life may limit adverse maternal and neonatal effects. Studies addressing this
issue have evaluated too few patients to show a statistically significant improvement in outcome with 2-
chloroprocaine. [223] [224]
Serious maternal complications are uncommon. They include systemic local anesthetic toxicity from unintentional
intravascular injection or rapid systemic absorption, postpartum neuropathy secondary to direct sacral plexus trauma
or from hematoma formation, and retropsoas or subgluteal abscesses.
[225] [226]
Serious perinatal complications, including death, may result from paracervical block. Unintentional direct fetal scalp
injection can result in fetal systemic local anesthetic toxicity. This hazard seems more likely with advanced
[227]
cervical dilation (> 8 cm). [228]
Bradycardia is the most common fetal complication. It usually develops within 2 to 10 minutes after injection and
resolves within 5 to 10 minutes. The reported incidence ranges from 0% to 70%. The cause of fetal bradycardia is
[228]
unclear. Most likely, fetal bradycardia results from a decrease in uteroplacental or fetoplacental perfusion secondary
to local anesthetic-induced uterine hypertonus or uterine/umbilical artery vasoconstriction.
[229] [230]
Recommendations to reduce complications include the following: (1) perform the block only in parturients with no
evidence of uteroplacental insufficiency; (2) perform the block when the cervix is dilated less than 8 cm; (3) monitor
uterine activity and fetal heart rate continuously; (4) after injecting local anesthetic on one side, wait 5 to 10 minutes
before injecting anesthetic on the second side; and (5) consider using 2-chloroprocaine. [228]
589
Pudendal Block
The pudendal nerve, which includes somatic fibers from S2, S3, and S4, is the primary source of sensory innervation
of the lower vagina, vulva, and perineum. It also provides motor innervation to the perineal muscles and the external
anal sphincter. Thus, during the second stage of labor, a pudendal block relieves pain resulting from vaginal, vulvar,
and perineal distention. It provides satisfactory analgesia for spontaneous vaginal and low-forceps or outlet-forceps
delivery but not for midforceps delivery or exploration of the upper vagina, cervix, or uterine cavities. The success
rate for bilateral pudendal blocks may be as low as 50%. [231]
The pudendal nerve can be blocked via the transperineal or transvaginal route. Most obstetricians in the United
States employ the transvaginal route immediately before delivery. However, earlier pudendal nerve blocks (just
before or after complete cervical dilation) provide better analgesia and do not increase the incidence of instrumental
delivery. This approach also provides time for a repeat block, should an initial block fail.
[232]
The transvaginal pudendal block is performed through a needle guide. The needle is introduced through the vaginal
mucosa and the sacrospinous ligament, just medial and posterior to the ischial spine. Usually, 7 to 10 mL of local
anesthetic is injected on each side. The pudendal artery lies close to the nerve; therefore, aspiration before and
during injection is imperative. Rapid maternal absorption of local anesthetic occurs, resulting in peak levels in
maternal venous and fetal scalp capillary blood between 10 and 20 minutes after injection. Lidocaine and 2-
[232]
chloroprocaine are commonly used, with the same advantages and disadvantages as for paracervical block. Dilute
concentrations (lidocaine, 1%, or 2-chloroprocaine, 2%) are preferable, thus minimizing the risk of toxic maternal
concentrations of local anesthetic.
Maternal and fetal complications of pudendal nerve blocks are rare. Maternal complications include local anesthetic
toxicity from direct intravascular injection or absorption of an excessive dose of local anesthetic; vaginal,
ischiorectal, or retroperitoneal hematomas ; or subgluteal or retropsoas abscesses. Fetal complications include
[233] [226]
fetal trauma and direct fetal injection of local anesthetic. [234]
Perineal Infiltration
Perineal infiltration is often used immediately before delivery to provide anesthesia for an episiotomy or repair. It
provides no motor relaxation. Several milliliters of local anesthetic are injected into the posterior fourchette. The
complication associated with perineal infiltration is direct injection of local anesthetic into the fetal scalp, resulting
in neonatal local anesthetic toxicity. [235]
Regional Anesthesia for Cesarean Delivery
Anesthesia-related maternal mortality rate is 17 times higher for general anesthesia than for regional anesthesia. [1]
During the past several decades, the use of regional anesthesia has increased, and the anesthesia-related maternal
[5]
morbidity rate has decreased. Most obstetric anesthesiologists recommend using regional anesthesia whenever
[1] [3]
possible. Today, general anesthesia is used for cesarean delivery only when absolutely necessary. [236] [237]
There are other advantages of regional anesthesia for cesarean delivery: (1) the mother is awake and the father may
be present for the delivery; (2) the plasma concentration of markers of maternal stress (e.g., catecholamines, cortisol,
glucose) are significantly lower with regional than with general anesthesia; and (3) postoperative neuraxial analgesia
may be used.
Regional anesthesia provides short-term advantages to the neonate. Although there are no significant differences in
umbilical cord pH and gas measurements between neonates exposed to general versus regional anesthesia for
elective or emergency cesarean delivery, a prolonged incision to delivery time under general anesthesia
[238] [239]
adversely affects neonatal acid-base status and Apgar scores. However, despite a higher incidence of transient
[240] [241]
neonatal depression, there is no difference in ultimate neonatal outcome. [240]
SPINAL ANESTHESIA
Spinal anesthesia is indicated for most elective cesarean deliveries and for urgent cesarean deliveries in patients
without preexisting epidural analgesia. The advantages of spinal over epidural anesthesia include the following
( Table 25-6 ): (1) it is a technically easier block with a higher success rate; (2) onset of anesthesia is faster; (3) the
sensory block is more dense; (4) there is no risk of systemic local anesthetic toxicity; and (5) there is minimal
transfer of drug to the fetus. Disadvantages include the following: (1) it is not a continuous technique; and (2)
[242] [243]
590
acute onset of sympathectomy may not be tolerated in select patients. With the advent of pencil-point spinal needles,
the incidence of PDPH is equal for spinal and epidural anesthesia. [244]
TABLE 25-6 -- EPIDURAL VERSUS SPINAL ANESTHESIA FOR CESAREAN DELIVERY

Feature Epidural Spinal
Ease and speed of insertion Harder and slower Usually easier and faster
Onset 10–30 min 5–10 min
Duration Continuous Single shot
Success rate Higher incidence of patchy, one-sided blocks Higher overall success rate
Block quality: sensory Less dense sensory block More dense sensory block
Block quality: motor Less motor block More motor block
Hypotension Same incidence, slower onset Same incidence, more rapid onset
Risk of postdural puncture headache Approximately 1% Approximately 1%
Risk of systemic local anesthetic Unintentional intravenous injection may cause systemic toxicity Dose too small to cause systemic
toxicity toxicity after intravenous injection
Risk of total spinal Possible with unintentional subarachnoid injection or “overdose” epidural injection Less likely because of small drug dose
Postcesarean delivery analgesia Continuous or single shot Single shot only
Fetal drug exposure Yes Minimal
Preparation
Patient preparation for regional anesthesia for cesarean delivery includes the administration of aspiration
prophylaxis and an intravenous bolus of crystalloid solution. Prevention or timely treatment of hypotension is
particularly important for the parturient because UBF is not autoregulated. Some authors report an increased
incidence of fetal and neonatal acidosis in the presence of hypotension. [245] [246] [247]
Some discussions have called into question whether prehydration prevents regional anesthesia-induced hypotension,
and how much of what intravenous solution should be administered. Administration of crystalloid, 20 mL/kg,
immediately before initiation of spinal anesthesia decreased the incidence of hypotension from 71% to 55%. [248]
Although colloid (500 mL) administration was associated with less hypotension than crystalloid administration, the
incidence was still 40% to 58%. [249] [250] [251]
In conclusion, if time permits, parturients should receive intravenous crystalloid prehydration, 10 to 20 mL/kg,
immediately before the initiation of spinal anesthesia. This dosage will decrease but not eliminate the incidence of
hypotension. Non-glucose-containing solutions should be administered, because glucose may contribute to neonatal
hypoglycemia. [252]
Some anesthesiologists advocate the use of prophylactic ephedrine in an attempt to decrease the incidence of
hypotension. Although several studies have documented a decreased incidence of maternal hypotension after
prophylactic ephedrine, others have found no or minimal change in the incidence of hypotension.
[253] [254]
In [247] [255] [256]
addition, there is an increased incidence of maternal hypertension after prophylactic ephedrine. Two studies [256] [257]
documented lower mean umbilical vein pH values in neonates whose mothers received prophylactic ephedrine
compared with those who did not. Taken together, these studies do not support the routine use of prophylactic
[247] [256]
ephedrine before spinal anesthesia for cesarean delivery.
Preoperative sedation is usually unnecessary before initiation of anesthesia. However, small doses of midazolam
(0.5–2 mg) may be safely administered to the mother to treat severe anxiety. This drug can produce undesirable
maternal amnesia.
Technique
Spinal anesthesia may be initiated in the sitting or the right lateral decubitus position, usually at the L3 to L4 or L2
to L3 interspace. The right lateral decubitus position ensures bilateral spread of hyperbaric local anesthetic solutions
after the patient is placed in left lateral tilt for the operative procedure. A high thoracic (T4) sensory level is
[247]
necessary to block visceral stimulation. In one study comparing the lateral to sitting position, onset of block and
591
hypotension was more rapid in the lateral position, but overall block level was comparable between the two
groups.[258]
The availability of disposable pencil-point spinal needles has revolutionized spinal anesthesia for obstetric patients.
With the possible exception of a 27-G Quincke cutting needle, the use of cutting needles results in an
[244]
unacceptably high incidence of PDPH in the obstetric population. The incidence of PDPH with 25-G Whitacre or
24-G Sprotte needles (pencil-point) ranges from 0.7% to 3% in obstetric patients. [244] [259] [260] [261]
The choice of a local anesthetic depends on the desired duration of action. The most common drugs are lidocaine
(hyperbaric, 70 to 90 mg), bupivacaine (hyper- or isobaric, 12 to 15 mg), and tetracaine (hyperbaric, 8 to 12 mg).
The incidence of transient neurologic symptoms after spinal lidocaine appears to be lower in the obstetric [262]
population than in the general surgery population. [263]
Opioids are often added to local anesthetics for spinal anesthesia. The drugs work synergistically to block
transmission of visceral and somatic pain impulses. Lipid-soluble opioids (e.g., fentanyl, 6.25 to 15 µg, and
[264]
sufentanil, 2.5 to 10 µg) may improve the quality of anesthesia, decrease the incidence of intraoperative nausea and
vomiting, and increase the duration of anesthesia. [265] [266] [267] [268]
However, intraoperative neuraxial administration of lipid-soluble opioids may increase postoperative analgesic
requirements. [269] [270] [271] [272]
Meperidine, 80 to 100 mg, an opioid with local anesthetic properties, has been successfully used as the sole
anesthetic agent for cesarean delivery. [273] [274]
The addition of epinephrine, 200 µg, has been shown to prolong spinal block. However, in circumstances in which
the duration of surgery cannot be predicted with reasonable certainty, CSE anesthesia may provide more control.
Clonidine, 75 µg, improved intraoperative analgesia and duration of postoperative analgesia in combination with
spinal bupivacaine and bupivacaine plus fentanyl. [275]
Morphine is often added to the spinal anesthetic solution for postoperative analgesia. Morphine added to
bupivacaine has also improved intraoperative analgesia. [276]
After induction of spinal anesthesia, the parturient is placed supine with left uterine displacement. Supplemental
oxygen should be delivered and the patient monitored and treated as needed for hypotension. Fetal heart rate
[277]
should be determined before and after block initiation.
Inadequate Anesthesia
Adequate anesthesia should be documented before surgical incision. If anesthesia is inadequate, a second spinal
block (with less local anesthetic if some anesthesia is already present) may be performed. Case reports and [278]
laboratory studies suggest that maldistribution of local anesthetic (pooling around the sacral nerve roots) may be
responsible for cauda equina syndrome after reinjection of spinal microcatheters. It is not clear if this is a
[279] [280]
problem with single-shot spinal anesthesia, but it may be prudent for the anesthesiologist to change the patient’s
[278]
position and insertion site when repeating the block.
If the patient complains of discomfort during the operation, analgesia can be supplemented with nitrous oxide (50%
by face mask), small intravenous doses of ketamine (0.1–0.2 mg/kg), or opioids. Benzodiazepines may cause
undesirable amnesia. Care should be taken not to obtund airway reflexes. Occasionally, the induction of general
anesthesia is necessary. An analysis of the ASA closed claims database showed that inadequate anesthesia was the
cause of a disproportionate number of obstetric claims compared with nonobstetric claims. [281]
Nausea and vomiting may be symptoms of hypotension or visceral traction. Visceral traction stimulation can be
treated with intravenous opioids. Metoclopramide, 10 mg, before surgery decreases the incidence of nausea and
vomiting more than placebo. Occasionally, the induction of general anesthesia is necessary.
[282]
Other causes of intraoperative patient discomfort include the following: (1) a sensation of chest pressure, usually
due to a high thoracic sensory level; (2) shivering; (3) shoulder pain (referred pain, due to blood or amniotic fluid
under the diaphragm ); and (4) precordial pain secondary to venous air emboli.
[283]
The chest-up position, or at
[284] [285]
least avoidance of the Trendelenburg position, may improve shoulder and chest pain.
592
EPIDURAL ANESTHESIA
Epidural anesthesia is frequently used for parturients with indwelling catheters placed for labor analgesia. It may
also be the regional anesthetic technique of choice in parturients for whom the slow onset of sympathetic blockade
may be beneficial (e.g., patients with cardiac disease). Additionally, epidural anesthesia results in a less dense motor
block than spinal anesthesia. This type of block may be advantageous in patients with pulmonary disease who rely
on abdominal and intercostal muscle tone for ventilation and clearing of secretions. However, intraoperative
pulmonary function tests are similar with either anesthetic after the abdomen is opened. Block duration can be [286] [287]
extended by reinjecting the epidural catheter. Finally, postoperative analgesia can be accomplished by continuous or
incremental injection of the epidural catheter.
Preparation for epidural anesthesia is similar to that for spinal anesthesia. Patients in labor [246]
or with preexisting
epidural analgesia are less likely to become hypotensive and require less of a fluid bolus.
Technique
The choice of local anesthetic for epidural anesthesia depends on the desired onset and duration. 2-Chloroprocaine,
lidocaine, and bupivacaine are the local anesthetics used most commonly for cesarean delivery anesthesia. Studies
published in the past few years have evaluated ropivacaine and levobupivacaine. Twenty to 25 mL of local
anesthetic injected into the lumbar epidural space usually provides an adequate thoracic sensory level.
Lidocaine, 2%, with epinephrine is the most commonly used local anesthetic for cesarean delivery. It has an
intermediate onset and duration. Lidocaine without epinephrine may not provide satisfactory anesthesia. [288]
Epinephrine, 2.5 to 5 µg/mL, improves the quality of the sensory and motor block and prolongs block duration. [289] [290]
2-Chloroprocaine, 3%, is often used for urgent cesarean deliveries because its onset is quickest. However, its
duration of action is only 40 to 50 minutes, and it may interfere with subsequent morphine analgesia. [291]
Bupivacaine has a longer onset and greater risk of cardiac toxicity than lidocaine or 2-chloroprocaine. [292]
Concentrations higher than 0.5% are contraindicated for obstetric use. Bupivacaine, 0.5%, may result in inadequate
analgesia for 5% to 10% of parturients. Although bupivacaine has a longer duration, this much time is rarely
[293]
necessary for routine cesarean deliveries. The presence of the epidural catheter allows lidocaine to be reinjected
should the procedure outlast the initial dose. However, in women with an existing labor epidural, titrated doses of
bupivacaine, 0.5%, can provide excellent surgical anesthesia. The prolonged duration can help provide immediate
postoperative analgesia.
Ropivacaine and levobupivacaine have recently been marketed as alternatives to bupivacaine because of decreased
cardiac toxicity compared with equal doses and serum concentrations of bupivacaine. Ropivacaine, 0.5% [28] [104] [294] [295] [296]
and 0.75%,
[297]
provided satisfactory anesthesia and was safe for the neonate. However, the free plasma
[298] [299]
concentration of ropivacaine was nearly twice that of bupivacaine. Ropivacaine, 0.5%, has been approved by
[294] [295]
the Food and Drug Administration for use in obstetric patients.
Levobupivacaine, 0.5%, provided similar anesthesia to bupivacaine, 0.5%. [300]

Maternal and umbilical vein
concentrations were similar for the two drugs.
The addition of epinephrine to local anesthetics other than lidocaine confers little benefit. Studies differ as to
whether plasma bupivacaine concentrations are significantly decreased with the addition of epinephrine to
bupivacaine. Epidural epinephrine may adversely affect uterine artery blood flow in uteroplacental
[293] [301] [302]
circulations with high resistance at baseline. [303]
Commercially prepared local anesthetic solutions that contain epinephrine are buffered to a pH of 3.5 compared
with 5.0 for solutions that do not contain epinephrine. The low pH delays their onset. The addition of sodium
bicarbonate to commercially prepared lidocaine with epinephrine (1 mEq sodium bicarbonate to 10 mL lidocaine)
significantly shortens latency. Sodium bicarbonate also decreased latency when added to 2-chloroprocaine.
[304] [305]
Although epidural local anesthetics cross the placenta, they have no effect on neonatal outcome. [102] [306]
The addition of lipid-soluble opioids to epidural local anesthetic solutions improves intraoperative anesthesia and
may shorten latency. The optimal dose of fentanyl is 75 to 100 µg, and that of sufentanil is 50 µg.
[307] [308] [309] [310] [311] [312] [312] [307]
Neonatal outcome was unchanged with these doses. Maternal side effects included pruritus and sedation.
[307] [311]
593
Epidural morphine may be injected intraoperatively (usually immediately after delivery) for postoperative analgesia.
If prolongation of epidural anesthesia is indicated, the second dose (50% of the first dose) should be injected at
predetermined times, based on the expected duration of action of the local anesthetic. This is particularly important
for 2-chloroprocaine. Awaiting two-segment regression may result in a “window” of inadequate anesthesia.
Inadequate Analgesia
As with spinal anesthesia, patients may experience discomfort under epidural anesthesia for a variety of reasons.
Inadequate spread (cephalad to T4 and caudad to S5), patchy, or one-sided anesthesia can often be corrected by
injecting more volume.
The density of an epidural block may be augmented without increasing the spread of anesthesia by giving 20% of
the initial dose 20 minutes after the first injection. [313]
Finally, spinal anesthesia should be initiated with caution after the patient has failed to respond to epidural
anesthesia. In a retrospective review, the incidence of high spinal anesthesia (sensory level above C8) was 11% after
patients had failed to respond to epidural anesthesia and 0.2% after stand-alone spinal anesthesia. However, [314]
several small series found no complications with this practice. [315] [316]
COMBINED SPINAL-EPIDURAL ANESTHESIA
CSE anesthesia can be used several ways for cesarean delivery anesthesia. CSE anesthesia combines the advantages
of spinal anesthesia (rapid onset of a dense block) with those of epidural anesthesia (ability to prolong the block).
Anesthesia may be initiated with a standard spinal dose followed by placement of the epidural catheter. The [317]
catheter is injected if the block needs to be prolonged. Alternatively, a low spinal dose can be injected, with the
remaining initiation dose injected through the epidural catheter. Proponents of this technique suggest that it is
associated with a lower incidence of hypotension. [318]
Patient position may influence the CSE anesthetic. When using hyperbaric drug, in the sitting position, sacral
pooling may occur if the patient is slow to assume the supine position because of delays in threading the epidural
catheter. Patients randomized to a sitting position for CSE anesthesia had a higher incidence of inadequate spinal
anesthesia compared with those who used the lateral position. However, a low dose of hyperbaric bupivacaine (10
[319]
mg) likely exacerbated this problem. In contrast, a second group found that CSE anesthesia performed in the sitting
position with hyperbaric bupivacaine, 12 mg, resulted in comparable block level with that provided in the lateral
position but a greater incidence of hypotension. [320]
After CSE anesthesia, it may be more difficult to detect the unintentional placement of a subarachnoid catheter. The
epidural injection of a standard test dose of local anesthetic may result in a dangerously high block. A smaller test
dose (e.g., bupivacaine, 2.5 to 5 mg) should be injected, and 5 minutes should elapse before the next injection. [321]
Fifty percent to 75% of a standard epidural dose is sufficient to maintain block level.
After spinal anesthesia, a small epidural dose (of saline or local anesthetic) can significantly extend the sensory
block. Therefore, the epidural top-up dose, particularly if administered soon after the initial subarachnoid
[322] [323] [324]
injection (to extend an inadequate spinal block before initiation of surgery) should be titrated carefully.
POSTCESAREAN DELIVERY ANALGESIA
The optimal postcesarean delivery analgesic regimen would provide profound analgesia and have no maternal or
neonatal side effects. Multiple studies have demonstrated superior analgesia with neuraxial versus systemic
(intramuscular ) or intravenous
[269] [325] [326] [327]
opioid administration. The total opioid dose is
[269] [325] [327] [328] [329] [330] [331]
significantly lower, and mothers are significantly less sedated. In a study of nonobstetric, morbidly
[325] [326] [327] [329] [331]
obese patients undergoing abdominal surgery, epidural morphine analgesia resulted in superior analgesia, less
sedation, fewer pulmonary complications, and earlier return of bowel function than intramuscular morphine. [332]
Neuraxial opioids may be used in multiple ways. Intrathecal morphine is commonly given as single-shot technique
at the induction of spinal anesthesia. A single bolus of epidural morphine may be injected soon after delivery.
Because of its long latency, 30 to 60 minutes, further delaying epidural morphine administration may result in an
[333]
analgesic window as the local anesthetic-induced analgesia wanes. The duration of intrathecal or epidural morphine
is generally 12 to 24 hours and is dose-dependent. Diamorphine has been used outside the United States.
[334] [335] [336]
594
Single-bolus techniques have the advantage of being less cumbersome (the patient is not connected to a continuous
infusion) and cheaper (no infusion pump is necessary). The downside of single-bolus techniques is that the dose is
not titratable to the degree of pain. Administering a higher dose may provide more satisfactory, longer lasting
analgesia to all patients, but at the cost of a higher incidence of undesirable side effects. In addition, the risk of late
respiratory depression is greater with single-bolus injection of hydrophilic opioids (see later discussion). [334]
The results of several studies suggest that the optimal dose of intrathecal morphine when it is administered with
spinal bupivacaine is 0.75 to 1 mg. Higher doses provide no additional analgesia but are associated with an
[337] [338]
increased incidence of pruritus. The optimal dose of epidural morphine appears to be about 4 mg.
[338] [339]
Several drugs may interfere with the analgesia provided by neuraxial morphine. Evidence suggests that epidural 2-
chloroprocaine (even in small doses) significantly impairs subsequent opioid (fentanyl ) and morphine analgesia. [103] [340]
Therefore, epidural morphine analgesia after 2-chloroprocaine anesthesia may be suboptimal compared with
epidural anesthesia using other local anesthetics.
The results of several studies suggest that epidural or intrathecal fentanyl or sufentanil may induce acute
[269] [272] [270] [271]
tolerance to neuraxial or intravenous morphine.

[269] [272]
For example, a prospective, double-blind study found that
[270] [271]
intravenous patient-controlled morphine requirements were increased 65% between 6 and 23 hours after intrathecal
fentanyl administration compared with requirements after placebo. Therefore, if fentanyl or sufentanil is added to
[270]
the local anesthetic and morphine mixture, a higher morphine dose may be necessary.
As an alternative to morphine, short-acting lipophilic opioids (e.g., fentanyl or meperidine) may be administered by
continuous epidural infusion or PCEA.[341]
However, this method requires an infusion pump that is more
[326] [342]
cumbersome and costly.
Side effects of neuraxial opioids include pruritus, nausea and vomiting, sedation, and respiratory depression. Most
studies have found that pruritus occurs more commonly with neuraxial than with systemic opioids. The [269] [325] [327] [331]
incidence of nausea and vomiting is similar for the two techniques. [325] [326] [328] [329] [330] [331]
Respiratory depression occurs after intramuscular, intravenous, and neuraxial opioid administration. Early [343]
respiratory depression (occurring between 30 and 90 minutes after administration) occurs after the neuraxial
administration of all opioids secondary to systemic absorption and transportation of the drug via the circulatory
system to the brainstem respiratory centers. Late respiratory depression (6 to 10 hours after administration) occurs
[344]
after a neuraxial bolus dose of morphine. Risk factors for respiratory depression include advanced age and morbid
[345]
obesity.[334] [346]
Neuraxial opioid analgesia may be supplemented with systemic agents. The current trend is toward using
multimodal analgesic therapy. This choice allows the use of lower doses of neuraxial opioid, resulting in fewer side
effects. Analgesia can be supplemented with nonsteroidal anti-inflammatory agents, acetaminophen, [347] [348] [349] [350] [351] [350]
hydrocodone/acetaminophen, or low-dose intravenous PCA-opioid administration.

[352]
Although several investigators have assessed epidural clonidine for postcesarean delivery analgesia, its role in [353] [354]
this capacity has yet to be established. Clonidine (epidural bolus followed by an infusion) provided excellent
analgesia, but was associated with dose-dependent sedation and a decrease in blood pressure. A lower bolus dose [353]
of clonidine, combined with bupivacaine and epinephrine, markedly prolonged analgesia, but was also associated
with increased maternal sedation. [355]
Finally, intrathecal neostigmine has also been assessed for postcesarean delivery analgesia. Although it [356] [357]
effectively reduced the need for supplemental systemic morphine, its use was associated with a high incidence of
nausea and vomiting.
Anesthesia for Other Obstetric Surgical Procedures
POSTPARTUM TUBAL STERILIZATION
Many anesthesiologists prefer to administer regional anesthesia for immediate postpartum tubal sterilization because
parturients may still be at increased risk for pulmonary aspiration. In particular, parturients who receive opioids for
labor analgesia have delayed gastric emptying compared with parturients who do not receive opioids. Both [161] [358] [359] [360]
systemic and neuroaxial opioids

[359]
delay gastric emptying compared with controls.
[358] [360]
595
Both local and neuraxial anesthesia are alternatives to general anesthesia for postpartum tubal sterilization. A
[361]
sensory level of T4 to T6 is needed to block visceral stimulation. Either epidural or spinal anesthesia is appropriate.
Because the surgical procedure is relatively short, most anesthesiologists use spinal block if anesthesia is started de
novo. However, many parturients have an indwelling epidural catheter placed during labor. This catheter can be
used to increase the extent and density of the block. One study suggested that failure to reactivate epidural
anesthesia successfully increases as the delivery to surgery interval increases. Others report an 87% to 92%
[362]
success rate regardless of time from delivery. [363] [364]
Local anesthetic requirements for both spinal and epidural anesthesia decrease during pregnancy but return to
prepartum levels by 36 hours post partum. Preservative-free intrathecal meperidine, 60 mg, has been used for tubal
[24]
ligation. Compared with lidocaine, meperidine provided longer postoperative analgesia but was associated with a
[365]
higher incidence of pruritus.
CERVICAL CERCLAGE
No prospective studies comparing general with regional anesthesia have assessed obstetric outcome after cervical
cerclage. General anesthesia with halogenated agents has the advantage of providing uterine relaxation and, possibly,
facilitating replacement of bulging membranes into the uterus. However, endotracheal tube-induced coughing, and
vomiting, markedly increase intrauterine pressure. Regional anesthesia with concomitant administration of tocolytic
agents is an excellent alternative. A sensory level from the sacrum to T8 or T10 is necessary to prevent discomfort
during vaginal and uterine manipulation. Additionally, the bladder is often distended with saline. Spinal anesthesia
has the advantage of an immediate, dense sacral block without a high thoracic sensory level. Hyperbaric lidocaine or
bupivacaine may be used. Alternatively, because patients are often maintained in a steep Trendelenburg position,
hypobaric tetracaine or bupivacaine may be used.
EXTERNAL CEPHALIC VERSION
Elective external cephalic version is an uncomfortable procedure. Some obstetricians prefer to perform the
procedure with minimal maternal analgesia. Their rationale is that anesthesia will make the use of excessive force
more likely, increasing the chances of maternal and neonatal morbidity and mortality. Several groups investigated
whether maternal analgesia or anesthesia increases the success rate of external version. Schorr and colleagues [366]
randomized parturients to receive epidural anesthesia with lidocaine, 2%, combined with epinephrine versus no
anesthesia and found a higher success rate in the anesthesia group. Conversely, Dugoff and colleagues randomized [367]
parturients to receive spinal analgesia (sufentanil, 10 µg, and bupivacaine, 2.5 mg) or no analgesia and found no
difference in the success rate between the two groups. Currently, the American College of Obstetricians and
Gynecologists believes that not enough information exists to support or oppose the use of neuraxial analgesia or
anesthesia for external cephalic version.[368]
Regional Analgesia and Anesthesia for Special Circumstances
OPERATIVE VAGINAL DELIVERY
Dense sacral analgesia or anesthesia and perineal muscle relaxation facilitate operative vaginal delivery, particularly
if forceps are applied. This goal can be accomplished by extending segmental lumbar epidural analgesia, or by
spinal or CSE anesthesia, caudal epidural anesthesia, or a pudendal block.
The prolonged epidural administration (more than several hours) of a dilute local anesthetic solution may provide
enough sacral anesthesia for the application of vacuum suction or forceps to the fetal head. Alternatively, a more
concentrated local anesthetic solution (e.g., 2-chloroprocaine, 2% to 3%, or lidocaine, 1% to 2%) may be injected
immediately before the planned operative vaginal delivery.
Alternatively, for a parturient shortly before delivery without an in situ epidural catheter, a single-shot spinal dose of
local anesthetic, with or without the subsequent placement of an epidural catheter, is appropriate. A T10 level is
necessary.
BREECH PRESENTATION
Neuraxial labor analgesia for planned breech vaginal delivery offers several benefits, including inhibition of early
pushing, relaxation of the pelvic floor and perineum, and the option of extending anesthesia for emergency cesarean
delivery. Early pushing may increase the risk of umbilical cord prolapse and delivery of a lower extremity before
596
full cervical dilation. A relaxed pelvic floor facilitates delivery of the after-coming head. The challenge to the
anesthesiologist is to provide enough first-stage analgesia to inhibit early pushing, but minimize second-stage motor
block to facilitate spontaneous delivery of the infant to the umbilicus, and to rapidly extend the perineal block
density at delivery to minimize head entrapment in the perineum and facilitate the application of forceps.
The fetal head may be entrapped in the perineum or, more commonly, in the cervix. Perineal skeletal muscle
relaxation may be achieved with regional anesthesia or the administration of a neuromuscular blocking agent during
the induction of general anesthesia. Cervical smooth muscle relaxation has traditionally been accomplished with the
rapid sequence induction of general anesthesia, followed by the administration of a high concentration of a volatile
anesthetic agent. More recently, intravenous (50 to 500 µg) or sublingual nitroglycerine has been used successfully
for uterine relaxation. [369] [370] [371] [372]
MULTIPLE GESTATION
Regional analgesia has several benefits in multiple gestation. Many physiologic and anatomic changes of pregnancy
are exaggerated in parturients with multiple gestation. For example, weight gain is greater, oxygen consumption is
higher, functional residual capacity (FRC) is smaller, and aortocaval compression and hypotension may be more
profound. Parturients with multiple gestation are at increased risk for cesarean delivery, uterine atony, and
postpartum hemorrhage.
Effective regional analgesia facilitates internal podalic version and total breech extraction of the second twin.
Anesthesia can be extended for an emergency cesarean delivery, thus avoiding the risk of general anesthesia. At the
time of delivery of the first twin, it is helpful to administer a more concentrated local anesthetic solution and extend
the level of epidural blockade (e.g., 3% chloroprocaine, 5 mL). This enhanced block facilitates internal podalic
version and breech extraction of the second twin. The block can be rapidly extended further if emergent cesarean
delivery is necessary.
The epidural dose of local anesthetic for cesarean delivery was unchanged for high-order pregnancies in one
retrospective study. In contrast, the same dose of spinal local anesthetic resulted in significantly higher blockade in
[373]
women with twin versus singleton pregnancies. [374]
Extraction of the second twin may require uterine relaxation. Nitroglycerine has been used for this purpose. [375]
VAGINAL TRIAL OF LABOR AFTER CESAREAN DELIVERY
In the past, there has been concern that regional labor analgesia for vaginal trial of labor after cesarean delivery
would mask the pain of uterine rupture. In addition, it was thought that the sympathectomy associated with neuraxial
analgesia would prevent reflex hemodynamic compensation in the event of uterine rupture and hemorrhage.
However, more recent data support the safety of neuraxial analgesia for vaginal trial of labor.
Several studies have found that abdominal pain, or uterine tenderness, has low sensitivity and specificity as a marker
for uterine rupture or scar dehiscence. There are reports of women with effective continuous epidural analgesia
[376] [377]
who acutely developed breakthrough pain secondary to uterine rupture. Most cases of lower uterine
[378] [379] [380] [381]
segment scar dehiscence do not result in severe maternal hemorrhage. Epidural analgesia did not affect the
[382]
outcome of the trial of labor in several studies. Finally, many women may agree to a trial of labor only if
[383] [384]
guaranteed effective analgesia.
In conclusion, most obstetricians and anesthesiologists and the American College of Obstetricians and
Gynecologists agree that neuraxial analgesia is appropriate for vaginal trial of labor after cesarean delivery. It may
[385]
be prudent to maintain analgesia with dilute solutions of local anesthetic and opioid so that the pain of uterine
rupture is not masked.
PREECLAMPSIA-ECLAMPSIA
Epidural analgesia may be the preferred method of labor analgesia for preeclamptic or eclamptic parturients for
several reasons. First, preeclamptic parturients have higher plasma catecholamine concentrations and an
[386] [387]
exaggerated hypertensive response to catecholamines and pain. These changes are blunted by effective epidural
[84]
analgesia; thus, blood pressure control is facilitated. Second, epidural analgesia may improve intervillous blood
[388] [389]
flow. Finally, preeclamptic parturients are at increased risk for urgent cesarean delivery compared with
[40]
597
normotensive parturients. The early initiation of epidural analgesia allows for epidural anesthesia, should an urgent
or emergent cesarean delivery be necessary.
Preeclampsia-eclampsia is a multiorgan disease. Several aspects of preeclampsia-eclampsia are of particular concern,

including (1) coagulation factor deficits that might preclude neuraxial anesthesia or analgesia, (2) intravascular
volume status, (3) airway edema, and (4) interaction of magnesium with anesthetic techniques and agents.
Approximately 10% of preeclamptic-eclamptic parturients have a platelet count below 100,000/mm3 . Several [390]
investigators have described prolonged bleeding times in both thrombocytopenic and nonthrombocytopenic patients,
presumably secondary to platelet dysfunction. There are no data to support the use of a specific platelet count
[391] [392]
above which neuraxial analgesia or anesthesia is “safe.” Epidural hematoma is a rare complication of neuraxial
anesthesia. A practice survey reported that almost all anesthesiologists indicated they would initiate neuraxial
anesthesia if the platelet count were above 100,000/mm3 but not below 50,000/mm3 . Sixty-six percent of [393]
academic obstetric anesthesiologists place an epidural catheter if the platelet count is above 80,000/mm.3 A review
of systems and a physical examination are necessary to rule out a bleeding diathesis.
Intrapartum, the platelet count may fall rapidly. In this circumstance, an epidural catheter may be placed several
hours before the patient requires analgesia, because at that time the platelet count may be unacceptably low. This
approach also allows an analgesic-free period to observe for symptoms of epidural hematoma. Finally, in parturients
with falling platelet counts, a platelet count should be determined immediately before removal of the epidural
catheter, because epidural hematoma formation has been described at the time of epidural catheter removal. [394]
A small percentage of preeclamptic-eclamptic parturients have coagulation factor deficits. If the platelet count is
greater than 100,000/mm3 , determination of prothrombin time (PT) and activated partial thromboplastin time (aPPT)
is not necessary. [395]
Intravascular volume status should be assessed before the induction of neuraxial analgesia or anesthesia. An
elevated hematocrit or low urine output suggests low intravascular volume. The preeclamptic parturient without
significant volume contraction should receive a 500-mL fluid bolus before induction of analgesia. Severely volume
constricted patients may require a larger fluid bolus and central venous or pulmonary artery pressure monitoring.
The use of epinephrine-containing local anesthetic solutions is controversial. In contrast to healthy parturients,
preeclamptic parturients had an exaggerated response to norepinephrine infusion and lacked the pregnancy-
[84]
induced attenuated chronotropic response to isoproterenol. Epidural bupivacaine-epinephrine anesthesia was

[396]
associated with increased uteroplacental vascular resistance compared with bupivacaine without epinephrine,
although umbilical cord acid-based values were not different. Epinephrine-containing test doses should be used
[43]
with caution in parturients with preeclampsia.
In the United States, most parturients with preeclampsia-eclampsia receive magnesium sulfate therapy. Magnesium
sulfate results in more profound maternal hypotension after the initiation of neuraxial anesthesia to the T10 level in
gravid ewes and may blunt the response to vasoconstrictors. In the same animal model, ephedrine treatment of
[397] [398]
epidural anesthesia-induced hypotension resulted in greater maternal cardiac output and uterine blood flow and
better fetal pH and PO2 than phenylephrine treatment. [399]
General anesthesia for cesarean delivery in the preeclamptic parturient is associated with significant increases in
systemic and pulmonary artery pressures and a decrease in intervillous blood flow. Compared with general
[400] [401]
anesthesia, regional anesthesia is associated with a more stable hemodynamic profile and a decrease in the level of
stress hormones. Finally, epidural anesthesia avoids manipulation of the airway with the increased risk of difficult
airway because of pharyngeal edema. [402]
Controversy exists as to whether spinal anesthesia is appropriate for the severely preeclamptic parturient. Opponents
of spinal anesthesia argue that rapid sympathectomy may result in more profound hypotension in the volume-
constricted, severely preeclamptic patient, and that hypotension is less likely to be tolerated by a fetus with chronic
uteroplacental insufficiency. However, in a retrospective study of 103 severely preeclamptic patients undergoing
cesarean delivery, Hood and Curry demonstrated equal maternal and neonatal outcomes in severely preeclamptic
parturients who had spinal versus epidural anesthesia. In two small randomized and prospective studies addressing
[403]
this issue, there was no difference in outcome for spinal versus epidural anesthesia. [404] [405]
PLACENTA PREVIA
598
The anesthetic implications of placenta previa revolve around the risk of maternal hemorrhage and neuraxial
anesthesia-induced sympathectomy. Hemorrhage was associated with significantly worse maternal hypotension,
uterine blood flow, and fetal oxygenation in pregnant ewes with epidural anesthesia compared with control animals,
unless the anesthetized ewes received prompt fluid resuscitation. Although blood loss is higher compared with
[406]
other elective cesarean deliveries, many obstetric anesthesiologists will consider neuraxial anesthesia for primary
cesarean section in parturients who are not actively bleeding or hypotensive. [407]
However, the risk of placenta accreta increases markedly in patients with placenta previa and a previous uterine
scar. Controversy exists regarding the appropriate type of anesthesia for patients at high risk of placenta accreta
[408]
and cesarean hysterectomy. Arguments supporting the use of neuraxial anesthesia include several series in the
literature that support the safety of this technique. In a series of 25 patients scheduled for elective cesarean
[409] [410] [411] [412]
hysterectomy, 7 patients required the induction of general anesthesia after initial neuraxial anesthesia because of
patient discomfort or inadequate operating conditions. Arguments against the use of neuraxial anesthesia include
[409]
the potential for exacerbated maternal hypotension associated with neuraxial anesthesia, patient discomfort
associated with intraperitoneal manipulation and traction, and patient discomfort associated with a prolonged
surgical procedure. In addition, airway edema markedly worsens during volume resuscitation, thus increasing the
risk of a difficult airway if urgent endotracheal intubation is necessary. [413]
If neuraxial anesthesia is chosen for a repeat procedure, a continuous technique provides anesthesia for prolonged
operations.
PLACENTAL ABRUPTION
The anesthetic considerations in patients with placental abruption include (1) the possibility of disseminated
intravascular coagulation, (2) intravascular volume status, and (3) the potential for continued blood loss. Patients
who are hemodynamically stable, without ongoing hemorrhage and without coagulopathy, are candidates for
neuraxial analgesia or anesthesia.
POSTPARTUM HEMORRHAGE
The anesthetic considerations in postpartum hemorrhage are hemodynamic stability and maternal blood volume. If
the mother is hemodynamically stable and euvolemic, extension of epidural analgesia or initiation of neuraxial
anesthesia is appropriate.
FETAL DISTRESS
Fetal distress or fetal intolerance to labor often necessitates urgent or emergent vaginal or abdominal delivery.
Uncontrolled or retrospective studies suggest that there is no long-term difference in neonatal outcome between
general and regional anesthesia, although early neonatal condition may favor regional anesthesia. However,
[239] [240] [240]
data from the United States and the United Kingdom indicate that regional anesthesia is safer for the mother. [1] [3]
Parturients at risk for urgent or emergent delivery should have epidural analgesia initiated early in labor. Morgan [237]
found that 87% of at-risk parturients were identified as such on routine preanesthetic evaluation. Epidural labor
analgesia allowed 70% of these women to have epidural rather than general anesthesia for their emergent delivery.
Epidural analgesia can be extended with 2-chloroprocaine, 3%, for emergency cesarean delivery. The addition of
sodium bicarbonate slightly decreases latency. [414]
There is some controversy as to whether lidocaine, 2%, with epinephrine 1:200,000 is an appropriate anesthetic
agent for an urgent or emergent cesarean delivery. Ion trapping of lidocaine may occur in the acidotic fetus. [415]
Epidural epinephrine increased uteroplacental vascular resistance in women with preexisting high vascular
resistance. However, several groups of investigators found no difference in outcome after epidural lidocaine
[303]
anesthesia. [416] [417] [418]
INTRAUTERINE FETAL DEMISE
Intrauterine fetal demise may be associated with coagulation deficits for several reasons. Thromboplastin released
by the dead fetus may lead to a consumptive coagulopathy, although this is unusual unless the fetus has been dead
longer than a month. About 15% of fetal deaths can be attributed to placental abruption, and abruption can be
[419]
599
associated with disseminated intravascular coagulation. Therefore, before initiating regional analgesia in women
[420]
with fetal demise, a disseminated coagulation profile may be indicated. [421]
MATERNAL SUBSTANCE ABUSE
Many drugs, both legal and illegal, have the potential to adversely affect the anesthetic care of a parturient.
Cocaine
The risks of regional anesthesia are increased in cocaine-abusing parturients. Cocaine abuse is associated with
thrombocytopenia ; therefore, the platelet count should be determined before initiating neuraxial analgesia or
[422]
anesthesia. After neuraxial blockade, the degree of hypotension is more profound. Because ephedrine is both an
[423]
indirect- and direct-acting vasopressor, it is less effective in treating hypotension in the cocaine-positive parturient. [424]
Finally, cocaine-abusing parturients often experience pain despite apparently adequate regional anesthesia. [425]
Amphetamines
Neuraxial anesthesia in amphetamine-abusing patients may be associated with severe hypotension and unpredictable
response to vasopressors. Cardiac arrest has been reported after regional anesthesia for cesarean delivery. [426]
Opioids
Regional analgesic or anesthetic techniques may be advantageous for the opioid addict because analgesia can be
provided without opioids. Autoimmune thrombocytopenia has been reported in opioid abusers. As with cocaine [427]
abuse, apparently adequate regional anesthesia may not provide acceptable pain relief in some opioid users. [428]
Ethanol
Ethanol abuse is associated with multiorgan disease. Patients with liver involvement should have their coagulation
status evaluated before the initiation of regional analgesia or anesthesia.
PREMATURITY
Although preterm infants may be more vulnerable than term infants to the effects of drugs used for analgesia and
anesthesia, the direct drug effects are far less important than preventing neonatal asphyxia and providing an
atraumatic delivery. Good maternal anesthetic care generally provides the best possible neonatal outcome.
INFECTIOUS DISEASE
Chorioamnionitis
There has been considerable debate about the use of neuraxial analgesia or anesthesia in infected patients. The
classic teaching has been that neuraxial anesthesia is relatively contraindicated in patients at risk for bacteremia.
However, epidural abscess and meningitis associated with neuraxial anesthesia are rare events. Four reviews of
more than 500,000 obstetric patients who received epidural analgesia or anesthesia found two cases of epidural
abscess and no cases of meningitis. Given the frequency of fever and bacteremia (1% of laboring patients
[93] [429] [430] [431]
in one study ), it is likely that some of these patients were bacteremic.

[432]
Several retrospective studies have not found any cases of epidural abscess or meningitis in parturients with
chorioamnionitis. However, given the low incidence of neuraxial infection, these studies are not large enough
[433] [434] [435]
to rule out the possibility that the risk of neuraxial infection after regional anesthesia is increased in parturients with
chorioamnionitis.
An additional issue is the difficulty in identifying which patients with chorioamnionitis are bacteremic. Fever and
leukocytosis do not differentiate patients with positive and negative blood cultures. In an Escherichia coli
[432] [433] [434]
bacteremic rat model, investigators found that administration of antibiotics before dural puncture protected the rat
from meningitis. [436]
600
The current consensus of obstetric anesthesiologists is that neuraxial analgesia or anesthesia may be administered to
parturients with chorioamnionitis after the systemic administration of antibiotics, unless they appear overtly septic. [437]
Human Immunodeficiency Virus
Human immunodeficiency virus (HIV) particles can be isolated from CSF at the time of initial infection. [438]
Therefore, there is no chance that neuraxial analgesia or anesthesia will introduce central nervous system HIV
infection, because this has already occurred. In a small group of 18 HIV-positive patients who received neuraxial
anesthesia, there was no evidence of accelerated disease progression or increased infection or neurologic
complications. [439]
Protease inhibitors (saquinavir, indinavir, nelfinavir, and ritonavir) are metabolized by the CYP3A isoenzyme of the
liver microsomal cytochrome P-450 system. All the protease inhibitors, but particularly ritonavir, competitively
inhibit this enzyme. Many central nervous system depressants are also metabolized by this isoenzyme. Hence,
plasma concentrations are markedly elevated and the clinical effect (and side effects) is markedly pronounced.
Drugs in this category include fentanyl, meperidine, diazepam, midazolam, and methylergonovine. [440]
Herpes Simplex Virus
Patients with symptomatic herpes simplex virus type 2 (HSV-2) often have cesarean delivery. Primary HSV-2
infection is associated with transient viremia, but recurrent infections are not. Retrospective studies have found no
[441]
sequelae after neuraxial anesthesia in patients with symptomatic HSV-2. However, very few patients in
[442] [443] [444] [445]
these studies had primary infections. There is a general consensus among anesthesiologists that neuraxial anesthesia
is safe for parturients with secondary HSV-2 infections. There are not enough data to support the safety of neuraxial
anesthesia in parturients with primary infections. Therefore, the theoretical risk of introducing virus into the central
nervous system must be weighed against the risk of general anesthesia.
Several randomized prospective studies have found an increased incidence of herpes simplex virus type 1 (herpes
simplex labialis or “cold sores”) in cesarean delivery patients who received epidural morphine rather than systemic
morphine. The incidence of recurrent lesions was 15% and 5.2%, respectively. A prospective but
[446] [447] [446] [447]
nonrandomized study found a much lower incidence of 3.5% after epidural or spinal morphine. [448]
CARDIOVASCULAR DISEASE
The diagnosis and treatment of congenital heart disease has improved markedly over the past several decades,
leading to an increased number of pregnant women with congenital heart disease. The sympathectomy associated
with neuraxial techniques acutely decreases systemic vascular resistance and myocardial preload. This sudden
change may not be well tolerated in women with stenotic valvular lesions, asymmetrical septal hypertrophy, or
right-to-left shunts. In contrast, patients with left-to-right shunts and regurgitant valvular lesions often benefit from a
decrease in systemic vascular resistance and preload. Intrathecal opioids (for labor analgesia) or slow injection of
epidural local anesthetic (for labor analgesia or cesarean delivery) are ideal for patients who may not tolerate acute
decreases in systemic vascular resistance or preload. Single-shot spinal anesthesia is contraindicated in these
patients.
Regional labor analgesia is beneficial to patients with ischemic heart disease. Effective analgesia decreases maternal
plasma catecholamine concentrations, thus preventing tachycardia and increased myocardial work.
[35] [36]
Many parturients with cardiovascular disease remain at risk for cardiovascular complications (e.g., congestive heart
failure) in the first 12 to 24 hours after delivery. These patients may benefit from the sympathectomy and analgesia
afforded by the continuous infusion of epidural local anesthetics in the immediate postpartum period.
COAGULOPATHY
Neuraxial anesthesia is contraindicated in the presence of a coagulopathy. Spinal hematoma may result in permanent
neurologic damage if not diagnosed and decompressed within 6 to 12 hours after onset of symptoms. [394]
Unfortunately, it is often difficult to assess whether patients with abnormal laboratory coagulation parameters have a
clinical coagulopathy. In general, an international normalized ratio greater than 1.4 or a prolonged aPTT are
[449]
considered contraindications to neuraxial anesthesia. Platelet count and function are discussed earlier under the
[450]
heading “Preeclampsia-Eclampsia.”
601
The American Society of Regional Anesthesia recently published consensus statements on neuraxial anesthesia and
anticoagulation. In summary, (1) antiplatelet drugs (aspirin and nonsteroidal anti-inflammatory drugs) are not a
[451]
contraindication to neuraxial anesthesia, (2) neuraxial anesthesia should not be initiated for at least 12 hours after the
last prophylactic dose and 24 hours after a therapeutic dose of low-molecular-weight heparin, and (3) neuraxial
anesthesia is not contraindicated after prophylactic subcutaneous standard heparin therapy. These same parameters
apply for removing an epidural catheter, because epidural hematomas can occur immediately after catheter
removal. [394]
MORBID OBESITY
Obesity accentuates many of the physiologic and anatomic changes of pregnancy. For example, there is less
pulmonary reserve because functional residual capacity is smaller and oxygen consumption is higher than in the
nonobese parturient. Similarly, cardiac output and blood volume are increased in obese individuals. There is a
higher incidence of comorbidity (e.g., hypertension and diabetes mellitus), and a higher incidence of difficult
[452]
airway. Obese parturients are more at risk for hypoventilation and oxygen desaturation after opioid administration. [346]
They are at increased risk for cesarean delivery. Obesity increases the risk of anesthesia-related maternal death
[453]
during cesarean section. Finally, associated fetal problems include macrosomia, shoulder dystocia, and birth
[454] [455]
trauma.
Epidural labor analgesia has several advantages for the obese parturient. Excellent analgesia can be provided with
minimal doses of opioid. The block can be extended for cesarean delivery, thus avoiding the increased risk of
general anesthesia. Epidural analgesia did not affect the outcome of labor in obese parturients weighing more than
300 lb. Initiation of successful epidural analgesia is technically more difficult in the obese parturient. In one study,
[453]
42% of obese parturients versus 6% of control subjects required epidural catheter replacement to achieve
satisfactory analgesia. The incidence of unintentional dural puncture is higher, although the incidence of PDPH
[453] [453]
is lower. The sitting position may aid in successful identification of the epidural space because the midline is more
[456]
readily identified and the skin-to-epidural space distance is less in the sitting position. There may be less risk of
[457]
catheter dislodgment if the patient assumes the lateral position before the catheter is secured. Continuous spinal [76]
analgesia or anesthesia is an alternative for patients who have experienced unintended dural puncture and who have
difficult identification of the epidural space.
For the obese parturient, there are several considerations when regional anesthesia is being chosen for cesarean
delivery. Patient positioning may have a profound impact on respiratory and hemodynamic stability, surgical
exposure, and ability to perform emergency intubation. Operative duration is significantly longer in obese patients. [453]
Studies differ as to whether obese patients require less local anesthetic for spinal or epidural anesthesia. In
[458] [459] [460] [461]
any case, the consequences of an undesirably high block are potentially more serious for the obese parturient.
Finally, it may be technically easier to advance a rigid epidural needle rather than a more flexible spinal needle
when initiating neuraxial anesthesia.
Providing satisfactory postoperative analgesia is also a challenge in obese parturients. One study demonstrated
improved outcome in morbidly obese, nonobstetric, abdominal surgery patients who received epidural rather than
intramuscular morphine. However, obese patients are at increased risk for respiratory depression after opioid
[332]
administration by any route, and a titratable analgesic technique (patient-controlled intravenous or epidural analgesia)
may be preferable.
SCOLIOSIS OR SPINAL SURGERY
Parturients with significant scoliosis or previous spinal fusion surgery should be referred to the anesthesiologist for
an antenatal consultation. There may be associated pulmonary, cardiac, or neuromuscular disease. Local anesthetic
requirements for neuraxial analgesia or anesthesia may vary significantly from the norm. Therefore, a continuous
technique allows more precise titration of sensory blockade.
Reports of several small series suggest that parturients with a history of spine surgery and instrumentation may be
offered neuraxial analgesia or anesthesia without risk of long-term adverse outcome. However, there is an
[462] [463] [464]
increased incidence of multiple attempts, unsuccessful placement, inadequate block, and dural puncture.
Complications of Regional Analgesia/Anesthesia
HYPOTENSION
602
Hypotension after neuraxial analgesia or anesthesia (defined as a 20% decrease in baseline blood pressure or a
systolic blood pressure less than 100 mm Hg) results primarily from a decrease in cardiac output secondary to
diminished preload from increased venous capacitance after sympathetic blockade. Because uteroplacental perfusion
is not autoregulated, uncorrected maternal hypotension may decrease uteroplacental perfusion and produce fetal
hypoxia and acidosis. Hypotension is more likely to occur in women who are not in labor at the time of
[245] [246]
induction of regional anesthesia. Measures to decrease the incidence and severity of maternal hypotension include
[246]
left uterine displacement (the lateral position) and prophylactic intravenous fluid administration. Despite these
measures, more than 70% of parturients develop hypotension after the induction of spinal anesthesia for elective
cesarean delivery. Small doses of a vasopressor usually readily correct the hypotension. Although laboratory
[248]
studies of hypotension suggest that ephedrine maintains uterine blood flow better than pure alpha agonists, [465] [466]
clinical studies suggest that small doses of phenylephrine are safe for the mother and fetus. [467]
FETAL BRADYCARDIA
Fetal bradycardia after initiation of neuraxial labor analgesia is discussed earlier in this chapter under “Combined
Spinal-Epidural Analgesia.”
PRURITUS
A bothersome side effect of neuraxial opioids is pruritus. During labor, the incidence of pruritus is higher after CSE
anesthesia with intrathecal opioid analgesia versus epidural analgesia with opioid and local anesthetic. Pruritus [158]
occurs in virtually 100% of parturients who receive solely intrathecal opioids. The incidence of pruritus was [468] [469]
dose-dependent after epidural fentanyl (increased incidence with fentanyl, 4 µg/mL, epidural infusion versus
fentanyl, 2 to 3 µg/mL ) and intrathecal fentanyl. Severity of pruritus was dose-dependent after intrathecal
[119] [470]
sufentanil. In one study, the addition of bupivacaine, 2.5 mg, to intrathecal fentanyl decreased the incidence of
[197]
pruritus from 95% to 36%. However, this was not the case in a study of bupivacaine added to sufentanil. Most
[471] [195]
cases of pruritus associated with lipid-soluble opioids and labor analgesia are self-limiting and need not be treated.
Patients with severe pruritus can be treated with intravenous naloxone, 40 to 80 µg, or nalbuphine, 2.5 to 5 mg.
Pruritus after neuraxial morphine seems to be more bothersome to patients. Studies differ as to whether there is a
dose-response relationship. Suggested treatments include a continuous naloxone infusion, nalbuphine
[337] [338] [472] [473]
infusion, or oral naltrexone.

[474]
Several reports describe the use of ondansetron (approximately 8 mg) to
[475] [476]
successfully treat patients with neuraxial morphine-induced pruritus. In contrast to nonobstetric patients, [477] [478]
obstetric patients with morphine-induced pruritus were not successfully treated with subhypnotic doses of
propofol. [479]
SHIVERING
Shivering is common during labor and is both thermoregulatory and nonthermoregulatory. Thermoregulation is [480]
impaired more by spinal anesthesia than by epidural anesthesia. Therefore, patients tend to shiver less with spinal [481]
anesthesia. The intraoperative incidence of shivering is decreased by the epidural administration of opioids (e.g.,
[482]
meperidine ), sufentanil, and fentanyl. Intravenous meperidine, 25 to 50 mg, is effective for treating shivering
[483] [484] [485]
once it occurs. [486]
MATERNAL FEVER
Several studies have documented low-grade maternal fever in parturients who receive epidural labor analgesia
compared with those who do not. Although Lieberman reported a much higher incidence of neonatal sepsis
[487] [488] [489] [488]
workups in newborns delivered of mothers with epidural analgesia, two thirds of the sepsis workups were performed
on neonates whose mothers were without fever. There is no evidence that epidural analgesia is associated with
maternal or neonatal sepsis. Alteration in heat dissipation is a possible mechanism (e.g., lack of hyperventilation or
inhibition of diaphoresis).
BACKACHE
Back pain is a common complaint, in both the antepartum and postpartum periods. Prospective studies have found
no relationship between the use of regional analgesia and the development of long-term postpartum back pain.
[492]
[490] [491]
POSTDURAL PUNCTURE HEADACHE
603
PDPH is a complication of spinal or epidural anesthesia. It must be differentiated from other causes of postpartum
headache. The incidence of PDPH is approximately 1% after dural puncture with a 25-G pencil-point spinal needle.
The incidence of unintentional dural puncture during induction of epidural analgesia or anesthesia also is
approximately 1%. Of these patients, 75% to 90% develop PDPH.
[493] [494] [495]
Treatment of PDPH depends on the severity of the symptoms. Mild headaches that do not interfere with activities of
daily living can be treated conservatively. Conservative treatment includes lying supine, hydration, and caffeine
(intravenous or oral ). However, conservative treatment is often not effective for the newly delivered mother,
[496] [497]
because the activities of daily living include the care of a newborn.
The standard treatment for moderate to severe headaches is an epidural blood patch. A single epidural blood patch
results in complete cure in 33% to 68% of patients. The patch may be repeated if unsuccessful. The most
[70] [495] [498]
common side effect of an epidural blood patch is backache. [499]
Several reports and studies have suggested that a prophylactic blood patch may decrease the incidence of PDPH. [500] [501]
Autologous blood is injected through the indwelling epidural catheter after delivery and resolution of epidural
[502]
analgesia or anesthesia.
UNINTENTIONAL INTRAVASCULAR INJECTION OF LOCAL ANESTHETICS
In 1979, Albright reported a series of maternal deaths after the unintentional intravascular injection of bupivacaine.
[292]
As a consequence, the Food and Drug Administration banned the use of bupivacaine, 0.75%, inobstetric patients.
Studies differ as to whether bupivacaine cardiovascular toxicity is enhanced during pregnancy. In any case,
[28] [29]
resuscitation from local anesthetic-induced cardiovascular collapse may be particularly difficult in parturients. In [292]
addition to the standard treatment of cardiac arrest (ventricular dysrhythmias should be treated with bretylium), left
uterine displacement is absolutely necessary to ensure adequate maternal circulation. Prompt delivery of the fetus
may be necessary. [503]
RESPIRATORY DEPRESSION AND ARREST
Respiratory depression and arrest are discussed earlier in this chapter under “Combined Spinal-Epidural Analgesia”
and “Postcesarean Delivery Analgesia.”
SUBDURAL INJECTION
Anesthetic agents may be accidentally injected into the subdural space. One case report suggests that subdural
catheter placement may be less easy to recognize when dilute local anesthetic solutions are used. [504]
MENINGITIS
Meningitis has been reported after CSE analgesia for labor. Currently, it is not clear whether the risk of meningitis
[162]
is higher after CSE analgesia or whether the case reports are a reporting phenomenon of a new technique.
NERVE INJURY
Postpartum lower extremity nerve injury may be secondary to intrinsic maternal palsy arising from the birth process
or secondary to neuraxial analgesia. Nerve injury secondary to epidural or spinal anesthesia is rare and is commonly
associated with paresthesia during initiation of the block. One prospective study found a 1% incidence of intrinsic
[505]
maternal palsy after labor and delivery. The most common injuries were to the lateral femoral cutaneous nerve
[506]
(lateral thigh numbness) and the femoral nerve (anterior thigh numbness and weakness of knee extension and hip
flexion). Fortunately, both intrinsic maternal palsy and iatrogenic injuries usually resolve spontaneously.
SPACE-OCCUPYING LESIONS OF THE SPINAL CANAL
Epidural abscesses, spinal abscesses, and hematomas are rare complications of neuraxial anesthesia. If they occur,
timely diagnosis and treatment are essential to prevent permanent neurologic deficits. Signs and symptoms include
[394]
backache, lower extremity sensory and motor deficits, bowel and bladder dysfunction, fever, and malaise.
Separately and combined, these signs and symptoms are not unusual in the postpartum period; therefore, a high
index of suspicion must be maintained.
604
Summary
Childbirth is one of the most painful events a woman is likely to experience. Fortunately, analgesic techniques are
available to reduce or eliminate labor pain. Neuraxial labor analgesia offers the most complete analgesia and is safe
and reliable.
Anesthesia-related maternal morbidity and mortality rates have steadily decreased. This decrease may be a result of
the more widespread use of regional analgesia and anesthesia in obstetric patients.
REFERENCES
1. HawkinsJL, Koonin LM, Palmer SK, et al: Anesthesia-related deaths during obstetric delivery in the United States, 1979-1990. Anesthesiology
86:277, 1997.
2. ChadwickHS: An analysis of obstetric anesthesia cases from the American Society of Anesthesiologists closed claims project database. Int J
Obstet Anesth 5:258, 1996.
3. Why Mothers Die. Report on Confidential Inquiries into Maternal Deaths in the United Kingdom 1994-1996. London, HMSO, 1998.
4. Hawkins JL, Gibbs CP, Orleans M, et al: Obstetric anesthesia work force survey, 1981 versus 1992. Anesthesiology 87:135, 1997.
5. Hawkins JL, Beaty BR, Gibbs CP: Update on U.S. OB anesthesia practices. Anesthesiology 91:A1060, 1999.
6. Fragneto RY, Bader AM, Rosinia F, et al: Measurements of protein binding of lidocaine throughout pregnancy. Anesth Analg 79:295, 1994.
7. Cummings AJ: A survey of pharmacokinetic data from pregnant women. Clin Pharmacokinet 8:344, 1983.
8. Iwasaki H, Collins JG, Saito Y, et al: Naloxone-sensitive, pregnancy-induced changes in behavioral responses to colorectal distention:
Pregnancy-induced analgesia to visceral stimulation. Anesthesiology 74:927, 1991.
9. DalbyPL, Ramanathan S, Rudy TE, et al: Plasma and saliva substance P levels: The effects of acute pain in pregnant and non-pregnant women.
Pain 69:263, 1997.
10. Datta
S, Hurley RJ, Naulty JS, et al: Plasma and cerebrospinal fluid progesterone concentrations in pregnant and nonpregnant women. Anesth
Analg 65:950, 1986.
11. Kaneko M, Kirhara Y, Kosaka Y: Pregnancy enhances the antinociceptive effects of extradural lignocaine in the rat. Br J Anaesth 72:657,
1994.
12. Popitz-BergezFA, Leeson S, Thalhammer JG, et al: Intraneural lidocaine uptake compared with analgesic differences between pregnant and
nonpregnant rats. Reg Anesth 22:363, 1997.
13. Bromage PR: Spread of analgesic solutions in the epidural space and their site of action: A statistical study. Br J Anaesth 34:161, 1962.
14. Butterworth JF, Walker FO, Lysak SZ: Pregnancy increases median nerve susceptibility of lidocaine. Anesthesiology 72:962, 1990.
15. Dietz FB, Jaffe RA: Pregnancy does not increase susceptibility to bupivacaine in spinal root axons. Anesthesiology 87:610, 1997.
16. Lauretti GR: Mechanisms of labor pain. In Norris MC (ed): Obstetric Anesthesia, 2nd ed. Philadelphia, Lippincott, 1999, pp 235.
17. Hirabayashi Y, Shimizu R, Fukada H, et al: Soft tissue anatomy within the vertebral canal in pregnant women. Br J Anaesth 77:153, 1996.
18. Hogan QH, Prost R, Kulier A, et al: Magnetic resonance imaging of cerebrospinal fluid volume and the influence of body habitus and
abdominal pressure. Anesthesiology 84:1341, 1996.
19. CarpenterRL, Hogan QH, Liu SS, et al: Lumbosacral cerebrospinal fluid volume is the primary determinant of sensory block extent and
duration during spinal anesthesia. Anesthesiology 89:24, 1998.
20. Brown DL: Spinal, epidural, and caudal anesthesia: Anatomy, physiology, and technique. In Chestnut DH (ed): Obstetric Anesthesia:
Principles and Practice, 2nd ed. St. Louis, Mosby, 1999, p 187.
21. Hirabayashi
Y, Shimizu R, Fukuda H, et al: Anatomical configuration of the spinal column in the supine position. II. Comparison of pregnant
and non-pregnant women. Br J Anaesth 75:6, 1995.
22. Lui
A, Polis T, Cicutti NJ: Densities of cerebrospinal fluid and spinal anaesthetic solutions in surgical patients at body temperature. Can J
Anaesth 45:297, 1998.
23. Richardson MG, Wissler RN: Density of lumbar cerebrospinal fluid in pregnant and nonpregnant humans. Anesthesiology 85:326, 1996.
605
24. Abouleish EI: Postpartum tubal ligation requires more bupivacaine for spinal anesthesia than does cesarean section. Anesth Analg 65:897,
1986.
25. Clark SL, Cotton DB, Pivarnik JM, et al: Position change and central hemodynamic profile during normal third-trimester pregnancy and
postpartum. Am J Obstet Gynecol 164:883, 1991.
26. Assali
NS, Prystowsky H: Studies on autonomic blockade. I. Comparison between the effects of tetraethylammonium chloride (TEAC) and
high selective spinal anesthesia on blood pressure of normal and toxemic pregnancy. J Clin Invest 29:1354, 1950.
27. Morishima HO, Finster M, Arthur R, et al: Pregnancy does not alter lidocaine toxicity. Am J Obstet Gynecol 162:320, 1990.
28. Santos
AC, Arthur GR, Wlody D: Comparative systemic toxicity of ropivacaine and bupivacaine in nonpregnant and pregnant ewes.
29. Morishima HO, Pedersen H, Finster M, et al: Bupivacaine toxicity in pregnant and nonpregnant ewes. Anesthesiology 63:134, 1985.
30. Annibale DJ, Rosenfeld CR, Kamm KE: Alterations in vascular smooth muscle contractility during ovine pregnancy. Am J Physiol 256:H1282,
1989.
31. Magness
RR, Rosenfeld CR: Systemic and uterine responses to alpha-adrenergic stimulation in pregnant and nonpregnant ewes. Am J Obstet
Gynecol 155:897, 1986.
32. Hohmann M, Keve TM, Osol G, et al: Norepinephrine sensitivity of mesenteric veins in pregnant rats. J Physiol 259:R753, 1990.
33. Eisenach JC: Uteroplacental blood flow. In Chestnut DH (ed): Obstetric Anesthesia, Principles and Practice, 2nd ed. St. Louis, Mosby, 1999, p
43.
34. Shnider
SM, Wright RG, Levinson G, et al: Uterine blood flow and plasma norepinephrine changes during maternal stress in the pregnant ewe.
35. Shnider
SM, Abboud T, Artal R, et al: Maternal catecholamines decrease during labor after lumbar epidural analgesia. Am J Obstet Gynecol
147:13, 1983.
36. Abboud TK, Artal R, Henriksen EH, et al: Effect of spinal anesthesia on maternal circulating catecholamines. Am J Obstet Gynecol 142:252,
1982.
37. Lederman RP, Lederman E, Work B, et al: Anxiety and epinephrine in multiparous labor: Relationship to duration of labor and fetal heart rate
pattern. Am J Obstet Gynecol 153:870, 1985.
38. Motoyama EK, Fuchigami T, Gotto H, et al: Response of fetal placental vascular bed to changes in pCO2 in sheep. In Longo LD, Reneau DR
(eds): Fetal and Newborn Cardiovascular Physiology. New York, Garland STPM Press, 1978, p 33.
39. HollmenA, Jouppila R, Jouppila P, et al: Effect of extradural analgesia using bupivacaine and 2-chloroprocaine on intervillous blood flow
during normal labor. Br J Anaesth 54:837, 1982.
40. Jouppila P, Jouppila R, Hollmen A, et al: Lumbar epidural analgesia to improve intervillous blood flow during labor in severe preeclampsia.
Obstet Gynecol 59:158, 1982.
41. Hood DD, Dewan DM, James FM: Maternal and fetal effects of epinephrine in gravid ewes. Anesthesiology 64:610, 1986.
42. Alahuhta S, Rasanen J, Jouppila R, et al: Effects of extradural bupivacaine with adrenaline for Cesarean section on uteroplacental and fetal
circulation. Br J Anaesth 67:678, 1991.
43. AlahuhtaS, Räsänen J, Jouppila P, et al: Uteroplacental and fetal circulation during extradural bupivacaine-adrenaline and bupivacaine for
cesarean section in hypertensive pregnancies with chronic fetal asphyxia. Br J Anaesth 71:348, 1993.
44. ChestnutDH, Weiner CP, Herrig JE: The effect of intravenously administered 2-chloroprocaine upon uterine artery blood flow velocity in
gravid guinea pigs. Anesthesiology 70:305, 1989.
45. Herman NL: The placenta: Anatomy, physiology, and transfer of drugs. In Chestnut DH (ed): Obstetric Anesthesia: Principles and Practice,
2nd ed. St. Louis, Mosby, 1999, p 57.
46. Ounsted M, Scott A, Moar V: Delivery and development: To what extent can one associate cause and effect? J R Soc Med 73:786, 1980.
47. Ounsted M, Scott A, Moar V: Pain relief during childbirth and development at 4 years. J R Soc Med 74:629, 1981.
48. Melzack R, Taezner P, Feldman P, et al: Labour is still painful after prepared childbirth training. Can Med Assoc J 125:357, 1981.
49. CapognaG, Celleno D, Lyons G, et al: Minimum local analgesia concentration of extradural bupivacaine increases with progression of labor.
Br J Anaesth 80:11, 1998.
606
50. Viscomi CM, Rathmell JP, Pace NL: Duration of intrathecal labor analgesia: Early versus advanced labor. Anesth Analg 84:1108, 1997.
51. Paech MJ: The King Edward Memorial Hospital 1,000 mother survey of methods of pain relief in labour. Anaesth Intensive Care 19:393, 1991.
52. Aarnoudse JG, Oeseburg G, Kwat A, et al: Influence of variations in pH and pCO2 on scalp tissue oxygen tension and carotid arterial oxygen
tension in the fetal lamb. Biol Neonate 40:252, 1981.
53. Peabody JH: Transcutaneous oxygen measurement to evaluate drug effects. Clin Perinatol 6:109, 1979.
54. Huch
A, Huch R, Schneider H, et al: Continuous transcutaneous monitoring of fetal oxygen tension during labour. Br J Obstet Gynaecol
84(Suppl 1):1, 1977.
55. Sangoul
F, Fox GS, Houle GL: Effect of regional analgesia on maternal oxygen consumption during the first stage of labor. Am J Obstet
Gynecol 212:1080, 1975.
56. Griffen
RP, Reynolds F: Maternal hypoxemia during labour and delivery: The influence of analgesia and effect on neonatal outcome.
57. Huch R: Maternal hyperventilation and the fetus. J Perinatol Med 14:3, 1986.
58. Guidelines for Regional Anesthesia in Obstetrics. Park Ridge, IL, American Society of Anesthesiologists, 1991.
59. Guidelines
for Perinatal Care, 4th ed. Washington, DC, American Academy of Pediatrics, American College of Obstetricians and
Gynecologists, 1997.
60. CollinsKM, Bevan DR, Beard RW: Fluid loading to reduce abnormalities of fetal heart rate and maternal hypotension during epidural
analgesia in labour. Br Med J 2:1460, 1978.
61. Zamora JE, Rosaeg OP, Lindsay MP, et al: Haemodynamic consequences and uterine contractions following 0.5 or 1.0 litre crystalloid
infusion before obstetric epidural analgesia. Can J Anaesth 43:347, 1996.
62. Andrews PJD, Ackerman WE, Juneja MM: Aortocaval compression in the sitting and lateral positions during extradural catheter placement in
the parturient. Can J Anaesth 40:320, 1993.
63. Vincent
RD, Chestnut DH: Which position is more comfortable for the parturient during identification of the epidural space? Int J Obstet
Anesth 1:9, 1991.
64. Norris MC, Dewan DM: Effect of gravity on the spread of extradural anaesthesia for caesarean section. Br J Anaesth 59:338, 1987.
65. Norris MC, Leighton BL, DeSimone CA, et al: Lateral position and epidural anesthesia for cesarean section. Anesth Analg 67:788, 1988.
66. Griffin RM, Scott RP: Forum. A comparison between the midline and paramedian approaches to the extradural space. Anaesthesia 39:584,
1984.
67. Jaucot J: Paramedian approach of the peridural space in obstetrics. Acta Anaesthesiol Belg 37:187, 1986.
68. Valentine SJ, Jarvis AP, Shutt LE: Comparative study of the effects of air or saline to identify the extradural space. Br J Anaesth 66:224, 1991.
69. Aida S, Taga K, Yamakura T, et al: Headache after attempted epidural block: The role of intrathecal air. Anesthesiology 88:76, 1998.
70. Stride PC, Cooper PC: Dural taps revisited. A 20-year survey from Birmingham Maternity Hospital. Anaesthesia 48:247, 1993.
71. D’Angelo R, Foss ML, Livesay CH: A comparison of multiport and uniport epidural catheters in laboring patients. Anesth Analg 84:1276,
1997.
72. Dickson MA, Moores C, McClure JH: Comparison of single, end-holed and multi-orifice extradural catheters when used for continuous
infusion of local anaesthetic during labour. Br J Anaesth 79:297, 1997.
73. Banwell BR, Morley-Forster P, Krause R: Decreased incidence of complications in parturients with the Arrow (FlexTip PlusTM ) epidural
catheter. Can J Anaesth 45:370, 1998.
74. Beilin
Y, Bernstein HH, Zucker-Pinchoff B: The optimal distance that a multi-orifice epidural catheter should be threaded into the epidural
space. Anesth Analg 81:301, 1995.
75. D’Angelo R, Berkebile BL, Gerancher JC: Prospective examination of epidural catheter insertion. Anesthesiology 84:88, 1996.
76. Hamilton CL, Riley ET, Cohen SE: Changes in the position of epidural catheters associated with patient movement. Anesthesiology 86:778,
1997.
77. MulroyMF, Norris MC, Liu SS: Safety steps for epidural injection of local anesthetics: Review of the literature and recommend ations. Anesth
Analg 85:1346, 1997.
78. Norris MC, Fogel ST, Dalman H, et al: Labor epidural analgesia without an intravascular “test dose.” Anesthesiology 88:1495, 1998.
607
79. Leighton
BL, Norris MC, Sosis M, et al: Limitations of epinephrine as a marker of intravascular injection in laboring women. Anesthesiology
66:688, 1987.
80. DeSimone CA, Leighton BL, Norris MC, et al: Chronotropic effect of isoproterenol is reduced in term pregnant women. Anesthesiology
69:626, 1988.
81. Colonna-Romano P, Nagaraj L: Tests to evaluate intravenous placement of epidural catheters in laboring women: A prospective clinical study.
82. Chestnut
DH, Weiner CP, Martin JG, et al: Effect of intravenous epinephrine on uterine artery blood flow velocity in the pregnant guinea pig.
83. Marcus MA, Gogarten W, Vertommen JD, et al: Haemodynamic effects of repeated epidural test-doses of adrenaline in the chronic maternal-
fetal sheep preparation. Eur J Anaesthesiol 15:320, 1998.
84. Nisell
H, Hjemdahl P, Linde B: Cardiovascular responses to circulating catecholamines in normal pregnancy and in pregnancy-induced
hypertension. Clin Physiol 5:479, 1985.
85. Leighton
BL, Norris MC, DeSimone CA, et al: The air test as a clinically useful indicator of intravenously placed epidural catheters.
86. Leighton BL, Topkis WG, Gross JB, et al: Multiport epidural catheters. Does the air test work? Anesthesiology 92:1617, 2000.
87. Leighton
BL, DeSimone CA, Norris MC, et al: Isoproterenol is an effective marker of intravenous injection in laboring women.
88. Yoshii WY, Miller M, Rottman RL, et al: Fentanyl for epidural intravascular test dose in obstetrics. Reg Anesth 18:296, 1993.
89. Freeman AB, Hicks L: Epidural fentanyl as a test dose [letter]. Anesth Analg 68:187, 1989.
90. Morris GF, Gore-Hickman W, Lang SA, et al: Can parturients distinguish between intravenous and epidural fentanyl? Can J Anaesth 41:667,
1994.
91. Tsui BC, Gupta S, Finucane B: Determination of epidural catheter placement using nerve stimulation in obstetric patients. Reg Anesth Pain
Med 24:17, 1999.
92. Tsui BC, Gupta S, Finucane B: Detection of subarachnoid and intravascular epidural catheter placement. Can J Anaesth 46:675, 1999.
93. Crawford JS: Some maternal complications of epidural analgesia for labour. Anaesthesia 40:1219, 1985.
94. James
KS, McGrady E, Quasim I, et al: Comparison of epidural bolus administration of 0.25% bupivacaine and 0.1% bupivacaine with
0.0002% fentanyl for analgesia during labour. Br J Anaesth 81:501, 1998.
95. Stoddart
AP, Nicholson KEA, Popham PA: Low dose bupivacaine/fentanyl epidural infusions in labour and mode of delivery. Anaesthesia
49:1087, 1994.
96. Thorburn J, Moir DD: Extradural analgesia: The influence of volume and concentration of bupivacaine on the mode of delivery, analgesic
efficacy and motor block. Br J Anaesth 53:933, 1981.
97. Turner MJ, Silk JM, Alagesan K, et al: Epidural bupivacaine concentration and forceps delivery in primiparae. J Obstet Gynaecol 9:122, 1988.
98. Belfrage P, Berlin A, Raabe N, et al: Lumbar epidural analgesia with bupivacaine in labor. Drug concentration in maternal and neonatal blood
at birth and during the first day of life. Am J Obstet Gynecol 123:839, 1975.
99. Crawford JS: Lumbar epidural block in labour: A clinical analysis. Br J Anaesth 44:66, 1972.
100. Kennedy RL, Bell JU, Miller RP, et al: Uptake and distribution of lidocaine in fetal lambs. Anesthesiology 72:483, 1990.
101. Kuhnert BR, Harrison MJ, Linn PL, et al: Effects of maternal epidural anesthesia on neonatal behavior. Anesth Analg 63:301, 1984.
102. Abboud
TK, Kim KC, Noueihed R: Epidural bupivacaine, chloroprocaine, or lidocaine for cesarean section: Maternal and neonatal effects.
103. Grice
SC, Eisenach JC, Dewan DM: Labor analgesia with epidural bupivacaine plus fentanyl: Enhancement with epinephrine and inhibition
with 2-chloroprocaine. Anesthesiology 72:623, 1990.
104. Huang YF, Proyer ME, Lather LE, et al: Cardiovascular and central nervous system effects of intravenous levobupivacaine and bupivacaine
in sheep. Anesth Analg 86:797, 1998.
105. Zaric D, Nydahl P, Philipson L, et al: The effect of continuous lumbar epidural infusion of ropivacaine (0.1%, 0.2%, and 0.3%) and 0.25%
bupivacaine on sensory and motor block in volunteers. Reg Anesth 21:14, 1996.
608
106. Writer WD, Stienstra R, Eddleston JM, et al: Neonatal outcome and mode of delivery after epidural analgesia for labour with ropivacaine and
bupivacaine: A prospective meta-analysis. Br J Anaesth 81:713, 1998.
107. Beilin
Y, Galea M, Zahn J, et al: Epidural ropivacaine for the initiation of labor epidural analgesia: A dose finding study. Anesth Analg
88:1340, 1999.
108. Cascio MG, Gaiser RR, Camann WR, et al: Comparative evaluation of four different infusion rates of ropivacaine (2 mg/mL) for epidural
labor analgesia. Reg Anesth Pain Med 23:548, 1998.
109. Eddleston JM, Holland JJ, Griffin RP, et al: A double-blind comparison of 0.25% ropivacaine and 0.25% bupivacaine for extradural analgesia
in labour. Br J Anaesth 76:66, 1996.
110. Owen MD, D’Angelo R, Gerancher JC, et al: 0.125% ropivacaine is similar to 0.125% bupivacaine for labor analgesia using patient-
controlled epidural infusion. Anesth Analg 86:527, 1998.
111. Stienstra R, Jonker TA, Bourdrez P, et al: Ropivacaine 0.25% versus bupivacaine 0.25% for continuous epidural analgesia in labor: A double-
blind comparison. Anesth Analg 80:285, 1995.
112. Burke D, Henderson DJ, Simpson AM, et al: Comparison of 0.25% S(-)-bupivacaine with 0.25% RS-bupivacaine for epidural analgesia in
labour. Br J Anaesth 83:750, 1999.
113. Polley
LS, Columb MO, Naughton NN, et al: Relative analgesic potencies of ropivacaine and bupivacaine for epidural analgesia in labor:
Implications for therapeutic indexes. Anesthesiology 90:944, 1999.
114. Capogna G, Celleno D, Fusco P, et al: Relative potencies of bupivacaine and ropivacaine for analgesia in labour. Br J Anaesth 82:371, 1999.
115. Campbell DC, Zwack RM, Crone LL, et al: Ambulatory labor epidural analgesia: Bupivacaine versus ropivacaine. Anesth Analg 90:1384,
2000.
116. Fischer C, Blanié P, Jaouën E, et al: Ropivacaine, 0.1%, plus sufentanil, 0.5 µg/ml, versus bupivacaine, 0.1%, plus sufentanil, 0.5 µg/ml, using
patient-controlled epidural analgesia for labor. Anesthesiology 92:1588, 2000.
117. Meister
GC, D’Angelo R, Owen M, et al: A comparison of epidural analgesia with 0.125% ropivacaine with fentanyl versus 0.125%
bupivacaine with fentanyl during labor. Anesth Analg 90:632, 2000.
118. Vercauteren M, Meert TF: Isobolographic analysis of the interaction between epidural sufentanil and bupivacaine in rats. Pharmacol Biochem
Behav 58:237, 1997.
119. Lyons G, Columb M, Hawthorne L, et al: Extradural pain relief in labour: Bupivacaine sparing by extradural fentanyl is dose dependent. Br J
Anaesth 78:493, 1997.
120. Polley
LS, Columb MO, Lyons G, et al: The effect of epidural fentanyl on the minimum local analgesic concentration of epidural
chloroprocaine in labor. Anesth Analg 83:987, 1996.
121. Vertommen JD, Vandermeulen E, Van Aken H: The effects of the addition of sufentanil to 0.125% bupivacaine on the quality of analgesia
during labor and on the incidence of instrumental deliveries. Anesthesiology 74:809, 1991.
122. Justins DM, Francis D, Houlton PG, et al: A controlled trial of extradural fentanyl in labour. Br J Anaesth 54:409, 1982.
123. D’Angelo R, Gerancher JC, Eisenach JC, et al: Epidural fentanyl produces labor analgesia by a spinal mechanism. Anesthesiology 88:1519,
1998.
124. Polley
LS, Columb MO, Naughton NN, et al: Effect of intravenous versus epidural fentanyl on the minimum local analgesia concentration of
epidural bupivacaine in labor. Anesthesiology 93:122, 2000.
125. Bader
AM, Fragneto R, Terui K, et al: Maternal and neonatal fentanyl and bupivacaine concentration after epidural infusion during labor.
126. Porter JS, Bonello E, Reynolds F: The effect of epidural opioids on maternal oxygenation during labour and delivery. Anaesthesia 51:899,
1996.
127. Nybell-Lindahl
G, Carlsson C, Ingemarsson I, et al: Maternal and fetal concentrations of morphine after epidural administration during labor.
Am J Obstet Gynecol 139:20, 1981.
128. Birnbach DJ, Johnson MD, Arcario T, et al: Effect of diluent volume on analgesia produced by epidural fentanyl. Anesth Analg 68:808, 1989.
129. Abboud TK, Sheik-ol-Eslam A, Yanagi T, et al: Safety and efficacy of epinephrine added to bupivacaine for lumbar epidural analgesia in
obstetrics. Anesth Analg 64:585, 1985.
130. Eisenach JC, Grice SC, Dewan DM: Epinephrine enhances analgesia produced by epidural bupivacaine during labor. Anesth Analg 66:447,
609
1987.
131. Yarnell RW, Ewing DA, Tierney E, et al: Sacralization of epidural block with repeated doses of 0.25% bupivacaine during labor. Reg Anesth
15:275, 1990.
132. Dounas M, O’Kelly BO, Jamali S, et al: Maternal and fetal effects of adrenaline with bupivacaine (0.25%) for epidural analgesia during
labour. Eur J Anaesthesiol 13:594, 1996.
133. O’Meara ME, Gin T: Comparison of 0.125% bupivacaine with 0.125% bupivacaine and clonidine as extradural analgesia in the first stage of
labour. Br J Anaesth 71:651, 1993.
134. Cigarini
I, Kaba A, Bonnet F, et al: Epidural clonidine combined with bupivacaine for analgesia in labor. Effects on mother and neonate. Reg
Anesth 20:113, 1995.
135. BuggyDJ, MacDowell C: Extradural analgesia with clonidine and fentanyl compared with 0.25% bupivacaine in the first stage of labour. Br J
Anaesth 76:319, 1996.
136. Bogod DG, Rosen M, Rees GA: Extradural infusion of 0.125% bupivacaine at 10 mL/hr to women during labor. Br J Anaesth 59:325, 1987.
137. Eddleston JM, Maresh M, Horsman EL, et al: Comparison of the maternal and fetal effects associated with intermittent or continuous infusion
of extradural analgesia. Br J Anaesth 69:154, 1992.
138. Ewen A, McLeod DD, MacLeod DM, et al: Continuous infusion epidural analgesia in obstetrics: A comparison of 0.08% and 0.25%
bupivacaine. Anaesthesia 41:143, 1986.
139. Lamont RF, Pinney D, Rodgers P, et al: Continuous versus intermittent epidural analgesia. Anaesthesia 44:893, 1989.
140. Li DF, Rees GAD, Rosen M: Continuous extradural infusion of 0.0625% or 0.125% bupivacaine for pain relief in primigravid labour. Br J
Anaesth 57:264, 1985.
141. Hicks JA, Jenkins JG, Newton MC, et al: Continuous epidural infusion of 0.075% bupivacaine for pain relief in labour. Anaesthesia 43:289,
1988.
142. Smedstad KG, Morison DH: A comparative study of continuous and intermittent epidural analgesia for labour and delivery. Can J Anaesth
35:234, 1988.
143. Chestnut DH, Owen CL, Bates JN, et al: Continuous infusion epidural analgesia during labor: A randomized, double-blind comparison of
0.0625% bupivacaine/0.0002% fentanyl versus 0.125% bupivacaine. Anesthesiology 68:754, 1988.
144. Gambling DR, McMorland GJ, Yu P, et al: Comparison of patient-controlled epidural analgesia and conventional intermittent “top-up”
injections during labor. Anesth Analg 70:256, 1990.
145. Curry PD, Pacsoo C, Heap DG: Patient-controlled epidural analgesia in obstetric anaesthetic practice. Pain 57:125, 1994.
146. Ferrante FM, Rosinia FA, Gordon C, et al: The role of continuous background infusions in patient-controlled epidural analgesia for labor and
delivery. Anesth Analg 79:80, 1994.
147. Gambling DR, Yu P, Cole C, et al: A comparative study of patient controlled epidural analgesia (PCEA) and continuous infusion epidural
analgesia (CIEA) during labour. Can J Anaesth 35:249, 1988.
148. Viscomi C, Eisenach JC: Patient-controlled epidural analgesia during labor. Obstet Gynecol 77:348, 1991.
149. Ferrante
FM, Barber MJ, Segal M, et al: 0.0625% bupivacaine with 0.0002% fentanyl via patient-controlled epidural analgesia for pain of
labor and delivery. Clin J Pain 11:121, 1995.
150. BernardJM, LeRoux L, Vizquel L, et al: Patient-controlled epidural analgesia during labor: The effects of the increase in bolus and lockout
interval. Anesth Analg 90:328, 2000.
151. Christiaens F, Verborgh C, Dierick A, et al: Effects of diluent volume of a single dose of epidural bupivacaine in parturients during the first
stage of labor. Reg Anesth Pain Med 23:134, 1998.
152. Beilin
Y, Zahn J, Bernstein HH, et al: Treatment of incomplete analgesia after placement of an epidural catheter and administration of local
anesthetic for women in labor. Anesthesiology 88:1502, 1998.
153. Hess PE, Pratt SD, Soni AK, et al: An association between severe labor pain and cesarean delivery. Anesth Analg 90:881, 2000.
154. Leighton BL, DeSimone CA, Norris MC, et al: Intrathecal narcotics for labor revisited: The combination of fentanyl and morphine
intrathecally provides rapid onset of profound, prolonged analgesia. Anesth Analg 69:122, 1989.
155. Nageotte MP, Larson D, Rumney PJ, et al: Epidural analgesia compared with combined spinal-epidural analgesia during labor in nulliparous
women. N Engl J Med 337:1715, 1997.
610
156. Norris MC: Are combined spinal-epidural catheters reliable? Int J Obstet Anesth 9:3, 2000.
157. Eappen S, Blinn A, Segal S: Incidence of epidural catheter replacement in parturients: A retrospective chart review. Int J Obstet Anesth 7:220,
1998.
158. Norris
MC, Grieco WM, Borkowski M, et al: Complications of labor analgesia: Epidural versus combined spinal-epidural techniques. Anesth
Analg 79:529, 1994.
159. Tsen LC, Thue B, Datta S, et al: Is combined spinal-epidural analgesia associated with more rapid cervical dilation in nulliparous patients
when compared with conventional epidural analgesia? Anesthesiology 91:907, 1999.
160. Dunn SM, Connelly NR, Steinberg RB, et al: Intrathecal sufentanil versus epidural lidocaine with epinephrine and sufentanil for early labor
analgesia. Anesth Analg 87:331, 1998.
161. Kelly MC, Carabine UA, Hill DA, et al: A comparison of the effect of intrathecal and extradural fentanyl on gastric emptying in laboring
women. Anesth Analg 85:834, 1997.
162. Cook TM: Combined spinal-epidural techniques. Anaesthesia 55:42, 2000.
163. Nielsen PE, Erickson JR, Abouleish EI, et al: Fetal heart rate changes after intrathecal sufentanil or epidural bupivacaine for labor analgesia:
Incidence and clinical significance. Anesth Analg 83:742, 1996.
164. Riley ET, Vogel TM, El-Sayed YY, et al: Patient selection bias contributes to an increased incidence of fetal bradycardia after combined
spinal-epidural analgesia for labor. Anesthesiology 91:S1054, 1999.
165. Albright
GA, Forster RM: Does combined spinal-epidural analgesia with subarachnoid sufentanil increase the incidence of emergency
cesarean delivery? Reg Anesth 22:400, 1997.
166. Mercier FJ, Dounas M, Bouaziz H, et al: Intravenous nitroglycerine to relieve intrapartum fetal distress related to uterine hyperactivity: A
prospective observational study. Anesth Analg 84:1117, 1997.
167. Ferouz F, Norris MC, Leighton BL: Risk of respiratory arrest after intrathecal sufentanil. Anesth Analg 85:1088, 1997.
168. Katsiris
S, Williams S, Leighton BL, et al: Respiratory arrest following intrathecal injection of sufentanil and bupivacaine in a parturient. Can
J Anaesth 45:880, 1998.
169. Hays RL, Palmer CM: Respiratory depression after intrathecal sufentanil during labor. Anesthesiology 81:511, 1994.
170. Jaffee
JB, Drease GE, Kelly T, et al: Severe respiratory depression in the obstetric patient after intrathecal meperidine or sufentanil. Int J
171. Greenhalgh CA: Respiratory arrest in a parturient following intrathecal injection of sufentanil and bupivacaine. Anaesthesia 51:173, 1996.
172. LuJK, Manullang TR, Staples MH, et al: Maternal respiratory arrests, severe hypotension, and fetal distress after administration of intrathecal
sufentanil, and bupivacaine after intravenous fentanyl. Anesthesiology 87:170, 1997.
173. Herman NL, Choi K, Afflick P, et al: Intrathecal fentanyl induces a dose-dependent change in ventilation when given for analgesia during
labor. Anesthesiology 89:A1034, 1998.
174. Bernards CM, Kopacz DJ, Michel MZ: Effect of needle puncture on morphine and lidocaine flux through the spinal meninges of the monkey
in vitro. Implications for combined spinal-epidural anesthesia. Anesthesiology 80:853, 1994.
175. Okada K, Okada S, Nishitani K: Effect of epidural pressure gradient on buprenorphine flux through the dural hole after combined spinal-
epidural anesthesia—Comparison between bolus injection and continuous infusion. Masui 47:64, 1998.
176. Suzuki N, Koganemaru M, Onizuka S, et al: Dural puncture with a 26-gauge spinal needle affects spread of epidural anesthesia. Anesth Analg
82:1040, 1996.
177. Beaubien
G, Drolet P, Girard M, et al: Patient-controlled epidural analgesia with fentanyl-bupivacaine: Influence of prior dural puncture. Reg
Anesth Pain Med 25:254, 2000.
178. Vartis
A, Collier CB, Gatt SP: Potential intrathecal leakage of solutions injected into the epidural space following combined spinal-epidural
anaesthesia. Anaesth Intensive Care 26:256, 1998.
179. Swenson JD, Wisniewski M, McJames S, et al: The effect of prior dural puncture on cisternal cerebrospinal fluid morphine concentrations in
sheep after administration of lumbar epidural morphine. Anesth Analg 83:523, 1996.
180. Currier DS, Levin KR, Campbell C: Dysphagia with intrathecal fentanyl. Anesthesiology 87:1570, 1997.
181. Hamilton CL, Cohen SE: High sensory block after intrathecal sufentanil for labor analgesia. Anesthesiology 83:1118, 1995.
182. Abu Abdou W, Aveline C, Bonnet F: Two additional cases of excessive extension of sensory blockade after intrathecal sufentanil for labor
611
analgesia. Int J Obstet Anesth 9:48, 2000.
183. Fragneto RY, Fisher A: Mental status change and aphasia after labor analgesia with intrathecal sufentanil/bupivacaine. Anesth Analg 90:1175,
2000.
184. Harding SA, Collis RE, Morgan BM: Meningitis after combined spinal-extradural anaesthesia in obstetrics. Br J Anaesth 73:545, 1994.
185. Cascio M, Heath G: Meningitis following a combined spinal-epidural technique in a labouring term parturient. Can J Anaesth 43:399, 1996.
186. Bouhemad B, Dounas M, Mercier FJ, et al: Bacterial meningitis following combined spinal-epidural analgesia for labour. Anaesthesia 53:292,
1998.
187. Lui AC, Polis TZ, Cicutti NJ: Densities of cerebrospinal fluid and spinal anaesthetic solutions in surgical patients at body temperature. Can J
Anaesth 45:297, 1998.
188. Richardson MG, Thakur R, Abramowicz JS, et al: Maternal posture influences the extent of sensory block produced by intrathecal dextrose-
free bupivacaine with fentanyl for labor analgesia. Anesth Analg 83:1229, 1996.
189. Ferouz F, Norris MC, Arkoosh VA, et al: Baricity, needle direction, and intrathecal sufentanil labor analgesia. Anesthesiology 86:592, 1997.
190. Gage JC, D’Angelo R, Miller R, et al: Does dextrose affect analgesia or the side effects of intrathecal sufentanil? Anesth Analg 85:826, 1997.
191. Herman
NL, Calicott R, Van Decar TK, et al: Determination of the dose-response relationship for intrathecal sufentanil in laboring patients.
192. Arkoosh VA, Cooper M, Norris MC, et al: Intrathecal sufentanil dose response in nulliparous patients. Anesthesiology 89:364, 1998.
193. Palmer CM, Cork RC, Hays R, et al: The dose-response relation of intrathecal fentanyl for labor analgesia. Anesthesiology 88:355, 1998.
194. D’Angelo R, Nelson K, Meister G: Dose response study of spinal fentanyl in early labor [abstract]. Anesthesiology 89:A1069, 1998.
195. Campbell DC, Camann WR, Datta S: The addition of bupivacaine to intrathecal sufentanil for labor analgesia. Anesth Analg 81:305, 1995.
196. Sia AT, Chong JL, Tay DH, et al: Intrathecal sufentanil as the sole agent in combined spinal-epidural analgesia for the ambulatory parturient.
Can J Anaesth 45:620, 1998.
197. Wong CA, Scavone BM, Loffredi M, et al: The dose-response of intrathecal sufentanil added to bupivacaine for labor analgesia.
198. Sia AT, Chong JL, Chiu JW: Combination of intrathecal sufentanil 10 µg plus bupivacaine 2.5 mg for labor analgesia: Is half the dose enough?
199. Mardirosoff
C, Dumont L: Two doses of intrathecal sufentanil (2.5 and 5 µg) combined with bupivacaine and epinephrine for labor analgesia.
200. Palmer CM, Van Maren G, Nogami WM, et al: Bupivacaine augments intrathecal fentanyl for labor analgesia. Anesthesiology 91:84, 1999.
201. Lee BB, Ngan Kee WD, Hung VYS, et al: Combined spinal-epidural analgesia in labour: Comparison of two doses of intrathecal bupivacaine
with fentanyl. Br J Anaesth 83:868, 1999.
202. Chiari A, Lorber C, Eisenach JC, et al: Analgesic and hemodynamic effects of intrathecal clonidine as the sole analgesic agent during first
stage of labor: A dose-response study. Anesthesiology 91:388, 1999.
203. Mercier FJ, Dounas M, Bouaziz H, et al: The effect of adding a minidose of clonidine to intrathecal sufentanil for labor analgesia.
204. Gautier PE, De Kock M, Fanard L, et al: Intrathecal clonidine combined with sufentanil for labor analgesia. Anesthesiology 88:651, 1998.
205. D’Angelo R, Evans E, Dean LA, et al: Spinal clonidine prolongs labor analgesia from spinal sufentanil and bupivacaine. Anesth Analg 88:573,
1999.
206. Owen MD, Özsarac Ö, Sahin S, et al: Low-dose clonidine and neostigmine prolong the duration of intrathecal bupivacaine-fentanyl for labor
analgesia. Anesthesiology 92:361, 2000.
207. Nelson KE, D’Angelo R, Foss ML, et al: Intrathecal neostigmine and sufentanil for early labor analgesia. Anesthesiology 91:1293, 1999.
208. Collis
RE, Harding SA, Morgan BM: Effect of maternal ambulation on labour with low-dose combined spinal-epidural analgesia. Anaesthesia
54:535, 1999.
209. Bloom SL, McIntire DD, Kelly MA, et al: Lack of effect of walking on labor and delivery [see comments]. N Engl J Med 339:76, 1998.
210. Shennan A, Cooke V, Lloyd-Jones F, et al: Blood pressure changes during labour and whilst ambulating with combined spinal-epidural
612
analgesia. Br J Obstet Gynaecol 102:192, 1995.
211. Buggy D, Hughes N, Gardiner J: Posterior column sensory impairment during ambulatory extradural analgesia in labour. Br J Anaesth 73:540,
1994.
212. Pickering AE, Parry MG, Ousta B, et al: Effect of combined spinal-epidural ambulatory labor analgesia on balance. Anesthesiology 91:436,
1999.
213. Fernando R, Price CM: Posterior column sensory impairment during ambulatory extradural analgesia in labour [letter]. Br J Anaesth 74:349,
1995.
214. Elton CD, Ali P, Mushambi MC: “Walking extradurals” in labour: A step forward? [editorial]. Br J Anaesth 79:551, 1997.
215. Abrahams M, Higgins P, Whyte P, et al: Intact proprioception and control of labour pain during epidural analgesia. Acta Anaesthesiol Scand
43:46, 1999.
216. Cohen SE, Yeh JY, Riley ET, et al: Walking with labor epidural analgesia. Anesthesiology 92:387, 2000.
217. WangWY, Wong CA, Scavone BM, et al: Does the epidural test dose increase motor block in walking (CSE) labor analgesia?
Anesthesiology April suppl:A82, 1999.
218. Sudunagunta S, Eckersall SJ, Gowrie-Mohan S: Continuous caudal analgesia in labour for a patient with Harrington rods. Int J Obstet Anesth
7:128, 1998.
219. Suelto MD, Shaw DB: Labor analgesia with paravertebral lumbar sympathetic block. Reg Anesth Pain Med 24:179, 1999.
220. Hunter
CA: Uterine motility studies during labor: Observations on bilateral sympathetic nerve block in the normal and abnormal first stage of
labor. Am J Obstet Gynecol 85:681, 1963.
221. Leighton BL, Halpern SH, Wilson DB: Lumbar sympathetic blocks speed early and second stage induced labor in nulliparous women.
222. Teramo K: Effects of obstetrical paracervical blockade on the fetus. Acta Obstet Gynecol Scand 16(suppl):1, 1971.
223. Weiss RR, Halevy S, Almonte RO, et al: Comparison of lidocaine and 2-chloroprocaine in paracervical block: Clinical effects and drug
concentrations in mother and child. Anesth Analg 62:168, 1983.
224. LeFevre ML: Fetal heart rate pattern and postparacervical fetal bradycardia. Obstet Gynecol 64:343, 1984.
225. Gaylord TG, Pearson JW: Neuropathy following paracervical block in the obstetric patient. Obstet Gynecol 60:521, 1982.
226. Svancarek
W, Chirino O, Schaefer G, et al: Retropsoas and subgluteal abscesses following paracervical and pudendal anesthesia. JAMA
237:892, 1977.
227. O’Meara OP, Brazie JV: Neonatal intoxication after paracervical block [letter]. N Engl J Med 278:1127, 1968.
228. Chestnut DH: Alternative regional anesthetic techniques: Paracervical block, lumbar sympathetic block, pudendal block, and perineal
infiltration. In Chestnut DH (ed): Obstetric Anesthesia: Principles and Practice, 2nd ed. St. Louis, Mosby, 1999, p 427.
229. MorishimaHO, Covino BG, Yeh MN, et al: Bradycardia in the fetal baboon following paracervical block anesthesia. Am J Obstet Gynecol
140:775, 1981.
230. Fishburne
JI, Greiss FC, Hopkinson R, et al: Responses of the gravid uterine vasculature to arterial levels of local anesthetic agents. Am J
231. Scudamore JH, Yates MJ: Pudendal block—A misnomer? Lancet 1:23, 1966.
232. Zador G, Lindmark G, Nilsson BA: Pudendal block in normal vaginal deliveries. Acta Obstet Gynecol Suppl 34:51, 1974.
233. Kurzel RB, Au AH, Rooholamini SA: Retroperitoneal hematoma as a complication of pudendal block: Diagnosis made by computed
tomography. West J Med 164:523, 1996.
234. Chase D, Brady JP: Ventricular tachycardia in a neonate with mepivacaine toxicity. J Pediatr 90:127, 1977.
235. DePraeter C, Vanhaesebrouch P, DePraeter N, et al: Episiotomy and neonatal lidocaine intoxication [letter]. Eur J Pediatr 150:685, 1991.
236. Conklin KA: Can anesthetic-related maternal mortality be reduced? Am J Obstet Gynecol 163:253, 1990.
237. Morgan BM, Magni V, Goroszenuik T: Anaesthesia for emergency Cesarean section. Br J Obstet Gynaecol 97:420, 1990.
238. Evans CM, Murphy JF, Gray OP, et al: Epidural versus general anaesthesia for elective caesarean section: Effect on Apgar score and acid-
base status of the newborn. Anaesthesia 44:778, 1989.
613
239. Marx GF, Luykx WM, Cohen S: Fetal-neonatal status following caesarean section for fetal distress. Br J Anaesth 56:1009, 1984.
240. Ong BY, Cohen MM, Palahniuk RJ: Anesthesia for cesarean section—Effects on neonates. Anesth Analg 68:270, 1989.
241. Datta S, Ostheimer GW, Weiss JB, et al: Neonatal effect of prolonged anesthetic induction for cesarean section. Obstet Gynecol 58:331, 1981.
242. Kuhnert
BR, Zuspan KJ, Kuhnert PM, et al: Bupivacaine disposition in mother, fetus, and neonate after spinal anesthesia for cesarean section.
243. Kuhnert BR, Philipson EH, Pimental R, et al: Lidocaine disposition in mother, fetus, and neonate after spinal anesthesia. Anesth Analg 65:139,
1986.
244. Lambert DH, Hurley RJ, Hertwig L, et al: Role of needle gauge and tip configuration in the production of lumbar puncture headache. Reg
Anesth 22:66, 1997.
245. Corke
BC, Datta S, Ostheimer GW, et al: Spinal anaesthesia for caesarean section. The influence of hypotension on neonatal outcome.
246. Brizgys RV, Dailey PA, Shnider SM, et al: The incidence and neonatal effects of maternal hypotension during epidural anesthesia for
cesarean section. Anesthesiology 67:782, 1987.
247. Shearer VE, Ramin SM, Wallace DH, et al: Fetal effects of prophylactic ephedrine and maternal hypotension during regional anesthesia for
cesarean section. J Matern Fetal Med 5:79, 1996.
248. Rout CC, Rocke DA, Levin J, et al: A reevaluation of the role of crystalloid preload in the prevention of hypotension associated with spinal
anesthesia for elective cesarean section. Anesthesiology 79:262, 1993.
249. RileyET, Cohen SE, Rubenstein AJ, et al: Prevention of hypotension after spinal anesthesia for cesarean section: Six percent hetastarch
versus lactated Ringer’s solution. Anesth Analg 81:838, 1995.
250. Siddik SM, Aouad MT, Kai GE, et al: Hydroxyethylstarch 10% is superior to Ringer’s solution for preloading before spinal anesthesia for
Cesarean section. Can J Anaesth 47:616, 2000.
251. Ueyama H, He Y-L, Tanigami H, et al: Effects of crystalloid and colloid preload on blood volume in the parturient undergoing spinal
anesthesia for elective cesarean section. Anesthesiology 91:1571, 1999.
252. Philipson
EH, Kalhan SC, Riha MM, et al: Effects of maternal glucose infusion on fetal acid-base status in human pregnancy. Am J Obstet
Gynecol 157:866, 1987.
253. Gutsche BB: Prophylactic ephedrine preceding spinal analgesia for cesarean section. Anesthesiology 45:462, 1976.
254. Vercauteren MP, Coppijans HC, Hoffman VH, et al: Prevention of hypotension by a single 5-mg dose of ephedrine during small-dose spinal
anesthesia in prehydrated cesarean delivery patients. Anesth Analg 90:324, 2000.
255. King SW, Rosen MA: Prophylactic ephedrine and hypotension associated with spinal anesthesia for cesarean delivery. Int J Obstet Anesth
7:18, 1998.
256. Webb AA, Shipton EA: Re-evaluation of i.m. ephedrine as prophylaxis against hypotension associated with spinal anaesthesia for caesarean
section. Can J Anaesth 45:367, 1998.
257. NganKee WD, Khaw KS, Lee BB, et al: A dose-response study of prophylactic intravenous ephedrine for the prevention of hypotension
during spinal anesthesia for cesarean delivery. Anesth Analg 90:1390, 2000.
258. Inglis
A, Daniel M, McGrady E: Maternal position during induction of spinal anaesthesia for caesarean section. A comparison of right lateral
and sitting positions. Anaesthesia 50:363, 1995.
259. Buettner J, Wresch KP, Klose R: Postdural puncture headache: Comparison of 25-gauge Whitacre and Quincke needles. Reg Anesth 18:166,
1993.
260. Ross BK, Chadwick HS, Mancuso JJ, et al: Sprotte needle for obstetric anesthesia: Decreased incidence of postdural puncture headache. Reg
Anesth 17:29, 1992.
261. Mayer DC, Quance D, Weeks SK: Headache after spinal anesthesia for cesarean section: A comparison of the 27-gauge Quincke and 24-
gauge Sprotte needles. Anesth Analg 75:377, 1992.
262. Wong CA, Slavenas P: The incidence of transient radicular irritation after spinal anesthesia in obstetric patients. Reg Anesth Pain Med 24:55,
1999.
263. FreedmanJM, Li DK, Drasner K, et al: Transient neurologic symptoms after spinal anesthesia: An epidemiologic study of 1,863 patients.
614
264. Maves TJ, Gebhart GF: Antinociceptive synergy between intrathecal morphine and lidocaine during visceral and somatic nociception in the
rat. Anesthesiology 76:91, 1992.
265. Dahlgren
G, Hulstrand C, Jakobsson J, et al: Intrathecal sufentanil, fentanyl, or placebo added to bupivacaine for Cesarean section. Anesth
Analg 85:1288, 1997.
266. Courtney MA, Bader AM, Hartwell B, et al: Perioperative analgesia with subarachnoid sufentanil administration. Reg Anesth 17:274, 1992.
267. HuntCO, Naulty JS, Bader AM, et al: Perioperative analgesia with subarachnoid fentanyl-bupivacaine for cesarean delivery. Anesthesiology
71:535, 1989.
268. Shende
D, Cooper GM, Bowden MI: The influence of intrathecal fentanyl on the characteristics of subarachnoid block for caesarean section.
269. Cohen SE, Subak LL, Brose WG, et al: Analgesia after cesarean delivery: Patient evaluations and costs of five opioid techniques. Reg Anesth
16:141, 1991.
270. Cooper DW, Lindsay SL, Ryall DM, et al: Does intrathecal fentanyl produce acute cross-tolerance to i.v. morphine? Br J Anaesth 78:311,
1997.
271. Manullang TR, Viscomi CM, Pace NL: Intrathecal fentanyl is superior to intravenous ondansetron for the prevention of perioperative nausea
during cesarean delivery with spinal anesthesia. Anesth Analg 90:1162, 2000.
272. Sinatra RS, Sevarino FB, Chung JH, et al: Comparison of epidurally administered sufentanil, morphine, and sufentanil-morphine combination
for postoperative analgesia. Anesth Analg 72:522, 1991.
273. Camann WR, Bader AM: Spinal anesthesia for cesarean delivery with meperidine as the sole agent. Int J Obstet Anesth 1:156, 1992.
274. Kafle SK: Intrathecal meperidine for elective caesarean section: A comparison with lidocaine. Can J Anaesth 40:718, 1993.
275. Benhamou D, Thorin D, Brichant JF, et al: Intrathecal clonidine and fentanyl with hyperbaric bupivacaine improves analgesia during cesarean
section. Anesth Analg 87:609, 1998.
276. Abouleish E, Rawal N, Fallon K, et al: Combined intrathecal morphine and bupivacaine for cesarean section. Anesth Analg 67:370, 1988.
277. Ramanathan S, Gandhi S, Arismendy J, et al: Oxygen transfer from mother to fetus during cesarean section under epidural anesthesia. Anesth
Analg 61:576, 1982.
278. Abouleish E: Cauda equina syndrome, continuous spinal anesthesia and repeated spinal block. Is there a relationship? [letter]. Reg Anesth
17:356, 1992.
279. Rigler ML, Drasner K, Krejcie TC, et al: Cauda equina syndrome after continuous spinal anesthesia. Anesth Analg 72:275, 1991.
280. RossBK, Coda B, Heath CH: Local anesthetic distribution in a spinal model: A possible mechanism of neurologic injury after continuous
spinal anesthesia. Reg Anesth 17:69, 1992.
281. Chadwick HS, Posner K, Caplan RA, et al: A comparison of obstetric and nonobstetric anesthesia malpractice claims. Anesthesiology 74:242,
1991.
282. Lussos SA, Bader AM, Thornhill ML, et al: The antiemetic efficacy and safety of prophylactic metoclopramide for elective cesarean delivery
during spinal anesthesia. Reg Anesth 17:126, 1992.
283. Capogna G, Celleno D: Improving epidural anesthesia during cesarean section: Causes of maternal discomfort or pain during surgery. Int J
284. Fong J, Gadalla F, Pierri MK, et al: Are Doppler-detected venous emboli during cesarean section air emboli? Anesth Analg 71:254, 1990.
285. Handler JS, Bromage PR: Venous air embolism during cesarean delivery. Reg Anesth 15:170, 1990.
286. Kelly MC, Fitzpatrick KT, Hill DA: Respiratory effects of spinal anaesthesia for caesarean section. Anaesthesia 51:1120, 1996.
287. Yun E, Topulos GP, Body SC, et al: Pulmonary function changes during epidural anesthesia for cesarean delivery. Anesth Analg 82:750,
1996.
288. Brose WG, Cohen SE: Epidural lidocaine for cesarean section: Effect of varying epinephrine concentration. Anesthesiology 69:936, 1988.
289. Murphy TM, Mather LE, Stanton-Hicks M, et al: The effects of adding adrenaline to etidocaine and lignocaine in extradural anaesthesia. I:
Block characteristics and cardiovascular effects. Br J Anaesth 48:893, 1976.
290. Bromage PR: Comparison of the hydrochloride salt of lignocaine and prilocaine for epidural analgesia. Br J Anaesth 37:753, 1965.
291. Camann WR, Hartigan PM, Gilbertson LI, et al: Chloroprocaine antagonism of epidural opioid analgesia: A receptor-specific phenomenon?
615
292. Albright GA: Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology 51:285, 1979.
293. Laishley RS, Morgan BM, Reynolds F: Effect of adrenaline on extradural anaesthesia and plasma bupivacaine concentrations during
caesarean section. Br J Anaesth 60:180, 1988.
294. Datta S, Camann W, Bader A, et al: Clinical effects and maternal and fetal plasma concentrations of epidural ropivacaine versus bupivacaine
for cesarean section. Anesthesiology 82:1346, 1995.
295. Ala-Kokko TL, Alahuhta S, Jouppila P, et al: Feto-maternal distribution of ropivacaine and bupivacaine after epidural administration for
cesarean section. Int J Obstet Anesth 6:147, 1997.
296. Griffin RP, Reynolds F: Extradural anaesthesia for caesarean section: A double-blind comparison of 0.5% ropivacaine with 0.5% bupivacaine.
Br J Anaesth 74:512, 1995.
297. Alahuhta S, Rasanen J, Jouppila P, et al: The effects of epidural ropivacaine and bupivacaine for cesarean section on uteroplacental and fetal
circulation. Anesthesiology 83:23, 1995.
298. Morton CP, Bloomfield S, Magnusson A, et al: Ropivacaine 0.75% for extradural anaesthesia in elective caesarean section: An open clinical
and pharmacokinetic study in mother and neonate. Br J Anaesth 79:3, 1997.
299. Irestedt
L, Emanuelsson BM, Ekblom A, et al: Ropivacaine 7.5 mg/ml for elective caesarean section. A clinical and pharmacokinetic
comparison of 150 mg and 187.5 mg. Acta Anaesthesiol Scand 41:1149, 1997.
300. Bader AM, Tsen LC, Camann WR, et al: Clinical effects and maternal and fetal plasma concentrations of 0.5% epidural levobupivacaine
versus bupivacaine for cesarean delivery. Anesthesiology 90:1596, 1999.
301. Burm AG, van Kleef JW, Gladines MP, et al: Epidural anesthesia with lidocaine and bupivacaine: Effects of epinephrine on the plasma
concentration profiles. Anesth Analg 65:1281, 1986.
302. Wilson CM, Moore J, Ghaly RG, et al: Plasma concentrations of bupivacaine during extradural anaesthesia for caesarean section. The effect
of adrenaline. Anaesthesia 43:12, 1988.
303. Marx GF, Elstein ID, Schuss M, et al: Effects of epidural block with lignocaine and lignocaine-adrenaline on umbilical artery velocity wave
ratios. Br J Obstet Gynaecol 97:517, 1990.
304. DiFazio CA, Carron H, Grosslight KR, et al: Comparison of pH-adjusted lidocaine solutions for epidural anesthesia. Anesth Analg 65:760,
1986.
305. AckermanWE, Juneja MM, Kaczorowski DM, et al: The pH adjustment of 2-chloroprocaine hastens the onset of epidural analgesia [letter].
306. Kangas-Saarela
T, Jouppila R, Alahuhta S: The effect of lumbar epidural analgesia on neurobehavioral responses of newborn infants. Acta
Anaesthesiol Scand 33:320, 1989.
307. Capogna G, Celleno D, Tomassetti M: Maternal analgesia and neonatal effects of epidural sufentanil for cesarean section. Reg Anesth 14:282,
1989.
308. Celleno
D, Capogna G, Sebastiani M, et al: Epidural analgesia during and after cesarean delivery. Comparison of five opioids. Reg Anesth
16:79, 1991.
309. Paech
MJ, Westmore MD, Speirs HM: A double-blind comparison of epidural bupivacaine and bupivacaine-fentanyl for caesarean section.
Anaesth Intensive Care 18:22, 1990.
310. Gaffud MP, Bansal P, Lawton C, et al: Surgical analgesia for Cesarean delivery with epidural bupivacaine and fentanyl. Anesthesiology
65:331, 1986.
311. Preston
PG, Rosen MA, Hughes SC, et al: Epidural anesthesia with fentanyl and lidocaine for Cesarean section: Maternal effects and neonatal
outcome. Anesthesiology 68:938, 1988.
312. Helbo-Hansen HS, Bang U, Lindholm P, et al: Maternal effects of adding fentanyl to 0.5% bupivacaine for cesarean section. Int J Obstet
Anesth 2:21, 1993.
313. Cousins MJ, Veering BT: Epidural neural blockade. In Cousins MJ, Bridenbaugh PO (eds): Neural Blockade in Clinical Anesthesia and
Management of Pain, 3rd ed. Philadelphia, Lippincott-Raven, 1998, p 243.
314. Furst SR, Reisner LS: Risk of high spinal anesthesia following failed epidural block for cesarean delivery. J Clin Anesth 7:71, 1995.
315. Stoneham M, Souter A: Spinal anaesthesia for Caesarean section in women with incomplete extradural analgesia [letter]. Br J Anaesth 76:476,
1996.
616
316. Vickers R, Wilkey A: Spinal anaesthesia for caesarean section [letter]. Br J Anaesth 77:301, 1996.
317. DaviesSJ, Paech MJ, Welch H, et al: Maternal experience during epidural or combined spinal-epidural anesthesia for cesarean section: A
prospective, randomized trial. Anesth Analg 85:607, 1997.
318. Fan SZ, Susetio L, Wang YP, et al: Low dose of intrathecal hyperbaric bupivacaine combined with epidural lidocaine for cesarean section—A
balance block technique. Anesth Analg 78:474, 1994.
319. Patel M, Samsoon G, Swami A, et al: Posture and the spread of hyperbaric bupivacaine in parturients using the combined spinal-epidural
technique. Can J Anaesth 40:943, 1993.
320. Yun EM, Marx GF, Santos AC: The effects of maternal position during induction of combined spinal-epidural anesthesia for cesarean
321. Norris MC: Spinal anesthesia for cesarean delivery. In Norris MC (ed): Obstetric Anesthesia, 2nd ed. Philadelphia, Lippincott, 1999, p 415.
322. Blumgart CH, Ryall D, Dennison B, et al: Mechanism of extension of spinal anaesthesia by extradural injection of local anaesthetic. Br J
Anaesth 69:457, 1992.
323. Stienstra R, Dilrosun-Alhadi BZ, Dahan A, et al: The epidural “top-up” in combined spinal-epidural anesthesia: The effect of volume versus
dose. Anesth Analg 88:810, 1999.
324. TakiguchiT, Okano T, Egawa H, et al: The effect of epidural saline injection on analgesic level during combined spinal and epidural
anesthesia assessed clinically and myelographically. Anesth Analg 85:1097, 1997.
325. EisenachJC, Grice SC, Dewan DM: Patient-controlled analgesia following cesarean section: A comparison with epidural and intramuscular
narcotics. Anesthesiology 68:444, 1988.
326. Yarnell RW, Polis T, Reid GN, et al: Patient-controlled analgesia with epidural meperidine after elective cesarean section. Reg Anesth 17:329,
1992.
327. Harrison
DM, Sinatra R, Morgese L, et al: Epidural narcotic and patient-controlled analgesia for post-cesarean section pain relief.
328. Smith CV, Rayburn WF, Karaiskakis PT, et al: Comparison of patient-controlled analgesia and epidural morphine for post-cesarean pain and
recovery. J Reprod Med 36:430, 1991.
329. Paech MJ, Moore JS, Evans SF: Meperidine for patient-controlled analgesia after cesarean section. Intravenous versus epidural administration.
330. Cade L, Ashley J: Towards optimal analgesia after caesarean section: Comparison of epidural and intravenous patient-controlled opioid
analgesia. Anaesth Intensive Care 21:416, 1993.
331. Parker RK, White PF: Epidural patient-controlled analgesia: An alternative to intravenous patient-controlled analgesia for pain relief after
cesarean delivery. Anesth Analg 75:245, 1992.
332. Rawal N, Sjostrand U, Christoffersson E: Comparison of intramuscular and epidural morphine for postoperative analgesia in the grossly obese:
Influence on postoperative ambulation and pulmonary function. Anesth Analg 63:583, 1984.
333. Dottrens
M, Rifat K, Morel DR: Comparison of extradural administration of sufentanil, morphine and sufentanil-morphine combination after
caesarean section. Br J Anaesth 69:9, 1992.
334. Cousins MJ, Mather LE: Intrathecal and epidural administration of opioids. Anesthesiology 61:276, 1984.
335. Husaini SW, Russel IF: Intrathecal diamorphine compared with morphine for postoperative analgesia after Caesarean section under spinal
anaesthesia. Br J Anaesth 81:135, 1998.
336. KellyMC, Carabine UA, Mirakhur RK: Intrathecal diamorphine for analgesia after caesarean section: A dose finding study and assessment of
side-effects. Anaesthesia 53:231, 1998.
337. Jiang CJ, Liu CC, Wu TJ, et al: Mini-dose intrathecal morphine for post-cesarean section analgesia. Ma Tsui Hsueh Tsa Chi 29:683, 1991.
338. Palmer
CM, Emerson S, Volgoropoulos D, et al: Dose-response relationship of intrathecal morphine for post-cesarean analgesia.
339. Palmer CM, Nogami WM, Van Maren G, et al: Post-cesarean epidural morphine: A dose-response study. Anesth Analg 90:887, 2000.
340. Eisenach JC, Schlairet TJ, Dobson CE, et al: Effect of prior anesthetic solution on epidural morphine analgesia. Anesth Analg 73:119, 1991.
341. YoungstromP, Hoyt M, Herman M: Dose-response study of continuous infusion epidural fentanyl-epinephrine for post-cesarean analgesia.
617
342. Cohen S, Amar D, Pantuck CB: Post-cesarean delivery epidural patient-controlled analgesia, fentanyl or sufentanil. Anesthesiology 78:486,
1993.
343. Brose
WG, Cohen SE: Oxyhemoglobin saturation following cesarean section in patients receiving epidural morphine, PCA, or i.m.
meperidine analgesia. Anesthesiology 70:948, 1989.
344. Sinatra RS, Ayoub CM: Postoperative analgesia: Epidural and spinal techniques. In Chestnut DH (ed): Obstetric Anesthesia: Principles and
Practice, 2nd ed. St. Louis, Mosby, 1999, p 521.
345. Kafer ER, Brown JT, Scott DD: Biphasic depression of ventilatory responses to CO2 following epidural morphine. Anesthesiology 58:418,
1987.
346. Abouleish E, Rashad MN, Rawal N: The addition of 0.2 mg subarachnoid morphine to hyperbaric bupivacaine for cesarean delivery: A
prospective study of 856 cases. Reg Anesth 16:137, 1991.
347. Cardoso MMSC, Carvalho JCA, Amaro AR: Small doses of intrathecal morphine combined with systemic diclofenac for postoperative pain
control after cesarean delivery. Anesth Analg 86:538, 1998.
348. Dennis AR, Leeso-Payne CG, Hobbs GJ: Analgesia after caesarean section. The use of rectal diclofenac as an adjunct to spinal morphine.
349. Pavy TJG, Gambling DR, Merrick PM, et al: Rectal indomethacin potentiates spinal morphine analgesia after caesarean delivery. Anaesth
350. Roseag OP, Lui ACP, Cicutti NJ, et al: Peri-operative multimodal pain therapy for caesarean section: Analgesia and fitness for discharge. Can
J Anaesth 44:803, 1997.
351. SunHL, Wu CC, Lin MS, et al: Effects of epidural morphine and intramuscular diclofenac combination in post-cesarean analgesia: A dose-
range study. Anesth Analg 76:284, 1993.
352. Gerancher JC, Floyd H, Eisenach J: Determination of an effective dose of intrathecal morphine for pain relief after cesarean delivery. Anesth
Analg 88:346, 1999.
353. Huntoon M, Eisenach JC, Boese P: Epidural clonidine after cesarean section. Appropriate dose and effect of prior local anesthetic.
354. Mendez R, Eisenach JC, Kashtan K: Epidural clonidine analgesia after cesarean section. Anesthesiology 73:848, 1990.
355. Capogna G, Celleno D, Zangrillo A, et al: Addition of clonidine to epidural morphine enhances postoperative analgesia after cesarean
delivery. Reg Anesth 20:57, 1995.
356. Chung CJ, Kim JS, Park HS, et al: The efficacy of intrathecal neostigmine, intrathecal morphine, and their combination for post-cesarean
section analgesia. Anesth Analg 87:341, 1998.
357. Krukowski JA, Hood DD, Eisenach JC, et al: Intrathecal neostigmine for post-cesarean section analgesia: Dose response. Anesth Analg
84:1269, 1997.
358. Ewah B, Yau K, King M, et al: Effect of epidural opioids on gastric emptying in labour. Int J Obstet Anesth 2:125, 1993.
359. O’Sullivan GM, Sutton AJ, Thompson SA, et al: Noninvasive measurement of gastric emptying in obstetric patients. Anesth Analg 66:505,
1987.
360. WrightPMC, Allen RW, Moore J, et al: Gastric emptying during lumbar extradural analgesia in labor: Effect of fentanyl supplementation. Br
J Anaesth 68:248, 1992.
361. Cruikshank DP, Laube DW, DeBacker LJ: Intraperitoneal lidocaine anesthesia for postpartum tubal sterilization. Obstet Gynecol 42:127,
1973.
362. Vincent RD, Reid RW: Epidural anesthesia for postpartum tubal ligation using epidural catheters placed during labor. J Clin Anesth 5:289,
1993.
363. Lawlor M, Weinter M, Fantauzzi M, et al: Efficacy of epidural anesthesia for postpartum tubal ligation utilizing indwelling labor epidural
catheters. Reg Anesth 19:54, 1994.
364. GoodmanEJ, Dumas SD: The rate of successful reactivation of labor epidural catheters for postpartum tubal ligation surgery. Reg Anesth
Pain Med 23:258, 1998.
365. Norris MC, Honet JE, Leighton BL, et al: A comparison of meperidine and lidocaine for spinal anesthesia for postpartum tubal ligation. Reg
Anesth 21:84, 1996.
618
366. Schorr SJ, Speights SE, Ross EL, et al: A randomized trial of epidural anesthesia to improve external cephalic version success. Am J Obstet
Gynecol 177:1133, 1997.
367. Dugoff L, Stamm CA, Jones OW, et al: The effect of spinal anesthesia on the success rate of external cephalic version: A randomized trial.
368. External cephalic version. Practice Patterns No. 4: 2000 Compendium of Selected Publications. Washington, DC, American College of
Obstetricians and Gynecologists, 2000, p 1035.
369. Dufour
P, Vinatier D, Orazi G, et al: The use of intravenous nitroglycerin for emergency cervico-uterine relaxation. Acta Obstet Gynecol
Scand 76:287, 1997.
370. Greenspoon JS, Kovacic A: Breech extraction facilitated by glyceryl trinitrate sublingual spray. Lancet 13:124, 1991.
371. Rolbin S, Hew E, Bernstein A: Uterine relaxation can be life saving. Can J Anaesth 38:939, 1991.
372. WessenA, Elowsson P, Axemo P, et al: The use of intravenous nitroglycerin for emergency cervico-uterine relaxation. Acta Anaesthesiol
Scand 39:847, 1995.
373. Behforouz N, Dounas M, Benhamou D: Epidural anaesthesia for caesarean delivery in triple and quadruple pregnancies. Acta Anaesthesiol
Scand 42:1088, 1998.
374. Jawan B, Lee JH, Chong ZK, et al: Spread of spinal anaesthesia for caesarean section in singleton and twin pregnancies. Br J Anaesth 70:639,
1993.
375. Vinatier D, Dufour P, Berard J: Utilization of intravenous nitroglycerin for obstetrical emergencies. Int J Obstet Gynaecol 55:129, 1996.
376. Johnson C, Oriol N: The role of epidural anesthesia in trial of labor. Reg Anesth 15:304, 1990.
377. Case BD, Corcoran R, Jeffcoate N, et al: Caesarean section and its place in modern obstetric practice. J Obstet Gynaecol Br Commonw
78:203, 1971.
378. Carlsson C, Nybell-Lindahl G: Extradural block in patients who have previously undergone caesarean section. Br J Anaesth 52:827, 1980.
379. Kelly MC, Hill DA, Wilson DB: Low dose epidural bupivacaine/fentanyl infusion does not mask uterine rupture. Int J Obstet Anesth 6:52,
1997.
380. Rowbottom SJ, Tabrizian I: Epidural analgesia and uterine rupture during labour. Anaesth Intensive Care 22:79, 1994.
381. Rowbottom SJ, Critchley LAH, Gin T: Uterine rupture and epidural analgesia during trial of labour. Anaesthesia 52:483, 1997.
382. Uppington J: Epidural analgesia and previous caesarean section. Anaesthesia 38:336, 1983.
383. Flamm BL, Lim OW, Jones C, et al: Vaginal birth after cesarean section: Results of a multicenter study. Am J Obstet Gynecol 158:1079,
1988.
384. Phelan JP, Clark SL, Diaz F, et al: Vaginal birth after cesarean. Am J Obstet Gynecol 157:1510, 1987.
385. Vaginal birth after previous cesarean delivery. Practice Bulletin No. 5: 2000 Compendium of Selected Publications. Washington, DC,
American College of Obstetricians and Gynecologists, 2000, p 1017.
386. Gambling
DR, Writer D: Hypertensive disorders. In Chestnut DH (ed): Obstetric Anesthesia: Principles and Practice, 2nd ed. St. Louis,
Mosby, 1999, p 875.
387. Abboud T, Artal R, Sarkis F, et al: Sympathoadrenal activity: maternal, fetal, and neonatal responses after epidural anesthesia in the
preeclamptic patient. Am J Obstet Gynecol 144:915, 1982.
388. Ramos-Santos E, Devoe LD, Wakefield ML, et al: The effects of epidural anesthesia on the Doppler velocimetry of umbilical and uterine
arteries in normal and hypertensive patients during active term labor. Obstet Gynecol 77:20, 1991.
389. Newsome LR, Bramwell RS, Curling PE: Severe preeclampsia: Hemodynamic effects of lumbar epidural anesthesia. Anesth Analg 65:31,
1986.
390. Weiner CP: The clinical spectrum of preeclampsia. Am J Kidney Dis 9:312, 1987.
391. Kelton JG, Hunter DJ, Neame PB: A platelet function defect in pre-eclampsia. Obstet Gynecol 65:107, 1985.
392. Ramanathan J, Sibai BM, Vu T, et al: Correlation between bleeding times and platelet counts in women with pre-eclampsia undergoing
393. Beilin Y, Bodian CA, Haddad EM, et al: Practice patterns of anesthesiologists regarding situations in obstetric anesthesia where clinical
619
management is controversial. Anesth Analg 83:735, 1996.
394. Vandermeulen EP, Van Aken H, Vermylen J: Anticoagulants and spinal-epidural anesthesia. Anesth Analg 79:1165, 1994.
395. Leduc L, Wheeler JM, Kirshon B: Coagulation profile in severe preeclampsia. Obstet Gynecol 79:14, 1992.
396. LeightonBL, Norris MC, DeSimone CA, et al: Pre-eclamptic and healthy term pregnant patients have different chronotropic responses to
isoproterenol [letter]. Anesthesiology 72:392, 1990.
397. Vincent RD, Chestnut DH, Sipes SL, et al: Magnesium sulfate decreases maternal blood pressure but not uterine blood flow during epidural
anesthesia in gravid ewes. Anesthesiology 74:77, 1991.
398. Sipes
SL, Chestnut DH, Vincent RD Jr, et al: Does magnesium sulfate alter the maternal cardiovascular response to vasopressor agents in
gravid ewes? Anesthesiology 75:1010, 1991.
399. Sipes SL, Chestnut DH, Vincent RD Jr, et al: Which vasopressor should be used to treat hypotension during magnesium sulfate infusion and
epidural anesthesia? Anesthesiology 77:101, 1992.
400. Ramanathan J, Coleman P, Sibai B: Anesthetic modification of hemodynamic and neuroendocrine stress responses to cesarean delivery in
women with severe pre-eclampsia. Anesth Analg 73:772, 1991.
401. Jouppila P, Kuikka J, Jouppila R, et al: Effect of induction of general anesthesia for cesarean section on intervillous blood flow. Acta Obstet
Gynecol Scand 58:249, 1979.
402. Brimacombe J: Acute pharyngolaryngeal oedema and pre-eclamptic toxaemia. Anaesth Intensive Care 20:97, 1992.
403. HoodDD, Curry R: Spinal versus epidural anesthesia for cesarean section in severely preeclamptic patients: A retrospective survey.
404. WallaceDH, Leveno KJ, Cunningham FG, et al: Randomized comparison of general and regional anesthesia for cesarean delivery in
pregnancies complicated by severe preeclampsia. Obstet Gynecol 86:193, 1995.
405. Sharwood-Smith G, Clark V, Watson E: Regional anaesthesia for caesarean section in severe preeclampsia: Spinal anaesthesia is the preferred
choice. Int J Obstet Anesth 8:85, 1999.
406. Vincent
RD, Chestnut DH, Sipes SL, et al: Epidural anesthesia worsens uterine blood flow and fetal oxygenation during hemorrhage in gravid
ewes. Anesthesiology 76:799, 1992.
407. BonnerSM, Haynes SR, Ryall D: The anaesthetic management of cesarean section for placenta previa: A questionnaire survey. Anaesthesia
50:992, 1995.
408. Chattopadhyay SK, Kharif H, Sherbeeni MM: Placenta praevia and accreta after previous caesarean section. Eur J Obstet Gynecol Reprod
Biol 52:151, 1993.
409. Chestnut DH, Redick LF: Continuous epidural anesthesia for elective cesarean hysterectomy. South Med J 78:1168, 1985.
410. Chestnut
DH, Dwarn DM, Redick LF, et al: Anesthetic management for obstetric hysterectomy: A multi-institutional study. Anesthesiology
70:607, 1989.
411. Frederiksen MC, Glassenberg R, Stika CS: Placenta previa: A 22-year analysis. Am J Obstet Gynecol 180:1432, 1999.
412. Parekh N, Hussaini SWU, Russell IF: Caesarean section for placenta praevia: A retrospective study of anaesthetic management. Br J Anesth
84:725, 2000.
413. Bhavani-Shankar K, Lynch EP, Datta S: Airway changes during Cesarean hysterectomy. Can J Anaesth 47:338, 2000.
414. Ackerman WE, Juneja MM, Denson DD, et al: The effect of pH and PCO2 on epidural analgesia with 2% 2-chloroprocaine. Anesth Analg
68:593, 1989.
415. Morishima HO, Covino BG: Toxicity and distribution of lidocaine in nonasphyxiated and asphyxiated baboon fetuses. Anesthesiology 54:182,
1981.
416. Price ML, Reynolds F, Morgan BM: Extending epidural blockade for emergency caesarean section. Int J Obstet Anesth 1:13, 1991.
417. Gaiser RR, Cheek TG, Gutsche BB: Epidural lidocaine versus 2-chloroprocaine for fetal distress requiring urgent Cesarean section. Int J
418. Gaiser RR, Cheek TG, Adams HK, et al: Epidural lidocaine for cesarean delivery. Int J Obstet Anesth 7:27, 1998.
419. Pritchard JA: Haematological problems associated with delivery, placental abruption, retained dead fetus, and amniotic fluid embolism. Clin
Haematol 2:563, 1973.
620
420. Fretts RC, Boyd ME, Usher RH, et al: The changing pattern of fetal death, 1961-1988. Obstet Gynecol 79:25, 1992.
421. Hartwell
BL, Reisner DP: Intrauterine fetal death. In Datta S (ed): Anesthetic and Obstetric Management of High-Risk Pregnancy, 2nd ed. St.
Louis, Mosby, 1996, p 589.
422. Orser B: Thrombocytopenia and cocaine abuse. Anesthesiology 74:195, 1991.
423. Birnbach D, Grunebaum A, Collins E, et al: The effect of cocaine on epidural anesthesia [abstract]. Am J Obstet Gynecol 164:400S, 1991.
424. Birnbach DJ, Stein DJ, Danzer BI, et al: Ephedrine resistance in the cocaine-positive parturient [abstract]. Anesthesiology 85:A892, 1996.
425. Birnbach DJ: Substance abuse. In Chestnut DH (ed): Obstetric Anesthesia: Principles and Practice, 2nd ed. St. Louis, Mosby, 1999, p 1027.
426. Samuels SI, Maze A, Albright A: Cardiac arrest during cesarean section in a chronic amphetamine abuser. Anesth Analg 58:528, 1979.
427. Savona S, Nardi MA, Lennette ET, et al: Thrombocytopenic purpura in narcotics addicts. Ann Intern Med 102:737, 1985.
428. Scheutz F: Drug addicts and local anesthesia: Completeness of anesthesia and general side effects. Scand J Dent Res 90:99, 1982.
429. Hellmann K: Epidural anesthesia in obstetrics: A second look at 26,127 cases. Can Anaesth Soc J 12:398, 1965.
430. Paech MJ, Godkin R, Webster GS: Complications of obstetric epidural analgesia and anaesthesia: A prospective analysis of 10,995 cases. Int
J Obstet Anesth 7:5, 1998.
431. Scott DB, Hibbard BM: Serious non-fatal complications associated with extradural block in obstetric practice. Br J Anaesth 64:537, 1990.
432. Blanco JD, Gibbs RS, Casteneda YS: Bacteremia in obstetrics: Clinical course. Obstet Gynecol 58:621, 1981.
433. Bader AM, Gilbertson L, Kirz L, et al: Regional anesthesia in women with chorioamnionitis. Reg Anesth 17:84, 1992.
434. Goodman EJ, DeHorta E, Taguiam JM: Safety of spinal and epidural anesthesia in parturients with chorioamnionitis. Reg Anesth 21:436,
1996.
435. Ramanathan J, Vaddadi A, Mercer BM, et al: Epidural anesthesia in women with chorioamnionitis. Anesthesiol Rev 19:35, 1992.
436. Carp H, Bailey S: The association between meningitis and dural puncture in bacteremic rats. Anesthesiology 76:739, 1992.
437. Segal S, Carp H, Chestnut DH: Fever and infection. In Chestnut DH (ed): Obstetric Anesthesia: Principles and Practice, 2nd ed. St. Louis,
Mosby, 1999, p 711.
438. Denning DW, Anderson J, Rudge P, et al: Acute myelopathy associated with primary infection with human immunodeficiency virus. Br Med
J 294:143, 1987.
439. Hughes
SC, Dailey PA, Landers D, et al: Parturients infected with human immunodeficiency virus and regional anesthesia. Clinical and
immunologic response. Anesthesiology 82:32, 1995.
440. Norvir: Physicians’ Desk Reference, 54th ed. Montvale, NJ, Medical Economics Company, 2000, p 465.
441. Corey L, Adams HG, Brown ZA, et al: Genital herpes simplex virus infections: Clinical manifestations, course, and complications. Ann Intern
Med 98:958, 1983.
442. Bader AM, Camann WR, Datta S: Anesthesia for cesarean delivery in patients with herpes simplex virus type-2 infections. Reg Anesth
15:261, 1990.
443. Crosby ET, Halpern SH, Rolbin SH: Epidural anaesthesia for caesarean section in patients with active recurrent genital herpes simplex
infections: A retrospective review. Can J Anaesth 36:701, 1989.
444. RamanathanS, Sheth R, Turndorf H: Anesthesia for cesarean section in patients with genital herpes infections: A retrospective study.
445. Ravindran RS, Gupta CD, Stoops CA: Epidural analgesia in the presence of herpes simplex virus (type 2) infection. Anesth Analg 61:714,
1982.
446. CroneLA, Conly JM, Storgard C, et al: Herpes labialis in parturients receiving epidural morphine following cesarean section. Anesthesiology
73:208, 1990.
447. Boyle
RK: Herpes simplex labialis after epidural or parenteral morphine: A randomized prospective trial in an Australian obstetric population.
Anaesth Intensive Care 23:433, 1995.
448. Norris MC, Weiss J, Carney M, et al: The incidence of herpes simplex virus labialis after cesarean delivery. Int J Obstet Anesth 3:127, 1994.
621
449. Enneking FK, Benzon HT: Oral anticoagulants and regional anesthesia: A perspective. Reg Anesth Pain Med 23(suppl 2):140, 1998.
450. Sharma SK, Lechner RB: Hematologic and coagulation disorders. In Chestnut DH (ed): Obstetric Anesthesia: Principles and Practice, 2nd ed.
St. Louis, Mosby, 1999, p 842.
451. Neuraxial Anesthesia and Anticoagulation: Consensus Statements. American Society of Regional Anesthesia, Chicago, May 2–3, 1998.
452. Perlow
JH, Morgan MA, Montgomery D, et al: Perinatal outcome in pregnancy complicated by massive obesity. Am J Obstet Gynecol
167:958, 1992.
453. Hood DD, Dewan DM: Anesthesia and obstetric outcome in morbidly obese parturients. Anesthesiology 79:1210, 1993.
454. Endler GC, Mariona FG, Solol RJ, et al: Anesthesia-related mortality in Michigan 1972-1984. Am J Obstet Gynecol 159:187, 1988.
455. May WJ, Greiss FC: Maternal mortality in North Carolina: A four year experience. Am J Obstet Gynecol 161:555, 1989.
456. Faure E, Moreno R, Thisted R: Incidence of postdural puncture headache in morbidly obese parturients [letter]. Reg Anesth 19:361, 1994.
457. HamzaJ, Smida M, Benhamou D, et al: Parturient’s posture during epidural puncture affects the distance from skin to epidural space. J Clin
Anesth 7:1, 1995.
458. McCulloch WJ, Littlewood DG: Influence of obesity on spinal analgesia with isobaric 0.5% bupivacaine. Br J Anaesth 58:610, 1986.
459. Norris MC: Height, weight, and the spread of subarachnoid hyperbaric bupivacaine in the term parturient. Anesth Analg 67:555, 1988.
460. Pitkanen MT: Body mass and spread of spinal anesthesia with bupivacaine. Anesth Analg 66:127, 1987.
461. Hodgkinson R, Husain FJ: Obesity and the cephalad spread of analgesia following epidural administration of bupivacaine for Cesarean
section. Anesth Analg 59:89, 1980.
462. Daley MD, Rolbin SH, Hew EM, et al: Epidural anesthesia for obstetrics after spinal surgery. Reg Anesth 15:280, 1990.
463. Crosby ET, Halpern SH: Obstetric epidural anaesthesia in patients with Harrington instrumentation. Can J Anaesth 36:693, 1989.
464. Hubbert CH: Epidural anesthesia in patients with spinal fusion [letter]. Anesth Analg 64:843, 1985.
465. RalstonDH, Shnider SM, DeLorimier AA: Effects of equipotent ephedrine, metaraminol, mephentermine, and methoxamine on uterine blood
flow in the pregnant ewe. Anesthesiology 40:354, 1974.
466. Tong C, Eisenach JC: The vascular mechanism of ephedrine’sbeneficial effect on uterine perfusion during pregnancy. Anesthesiology 76:792,
1992.
467. LaPortaRF, Arthur GR, Datta S: Phenylephrine in treating maternal hypotension due to spinal anesthesia for caesarean delivery: Effects on
neonatal catecholamine concentrations, acid base status and Apgar scores. Acta Anaesthesiol Scand 39:901, 1995.
468. Cohen SE, Cherry CM, Holbrook RH Jr, et al: Intrathecal sufentanil for labor analgesia—Sensory changes, side effects, and fetal heart rate
changes. Anesth Analg 77:1155, 1993.
469. Norris
MC, Fogel ST, Holtmann B: Intrathecal sufentanil (5 vs. 10 µg) for labor analgesia: Efficacy and side effects. Reg Anesth Pain Med
23:252, 1998.
470. Herman NL, Choi KC, Affleck PJ, et al: Analgesia, pruritus, and ventilation exhibit a dose-response relationship in parturients receiving
intrathecal fentanyl during labor. Anesth Analg 89:378, 1999.
471. Asokumar B, Newman LM, McCarthy RJ, et al: Intrathecal bupivacaine reduces pruritus and prolongs duration of fentanyl analgesia during
labor: A prospective, randomized controlled trial. Anesth Analg 87:1309, 1998.
472. Uchiyama A, Ueyama H, Nakano S, et al: Low dose intrathecal morphine and pain relief following caesarean section. Int J Obstet Anesth
3:87, 1994.
473. Luthman JA, Kay NH, White JB: Intrathecal morphine for post-caesarean section analgesia: Does naloxone reduce the incidence of pruritus?
Int J Obstet Anesth 1:191, 1992.
474. CohenSE, Ratner EF, Kreitzman TR, et al: Nalbuphine is better than naloxone for treatment of side effects after epidural morphine. Anesth
Analg 75:747, 1992.
475. Abboud TK: Preparation of oral naltrexone solution [letter]. Anesthesiology 73:190, 1990.
476. Abboud TK, Afrasiabi A, Davidson J, et al: Prophylactic oral naltrexone with epidural morphine: Effect on adverse reactions and ventilatory
responses to carbon dioxide. Anesthesiology 72:233, 1990.
622
477. Yeh HM, Chen LK, Lin CJ, et al: Prophylactic intravenous ondansetron reduces the incidence of intrathecal morphine-induced pruritus in
patients undergoing cesarean delivery. Anesth Analg 91:172, 2000.
478. Borgeat A, Stirnemann HR: Ondansetron is effective to treat spinal or epidural morphine-induced pruritus. Anesthesiology 90:432, 1999.
479. Beilin
Y, Bernstein HH, Zucker-Pinchoff B, et al: Subhypnotic doses of propofol do not relieve pruritus induced by intrathecal morphine after
cesarean section. Anesth Analg 86:310, 1998.
480. Panzer O, Ghazanfari N, Sessler DI, et al: Shivering and shivering-like tremor during labor with and without epidural analgesia.
481. Saito T, Sessler DI, Fujita K, et al: Thermoregulatory effects of spinal and epidural anesthesia during cesarean delivery. Reg Anesth Pain Med
23:418, 1998.
482. Helbo-Hansen S, Bang U, Garcia RS, et al: Subarachnoid versus epidural bupivacaine 0.5% for caesarean section. Acta Anaesthesiol Scand
32:473, 1988.
483. Sutherland J, Seaton H, Lowry C: The influence of epidural pethidine on shivering during lower segment caesarean section under epidural
484. Sevarino FB, Johnson MD, Lema MJ, et al: The effect of epidural sufentanil on shivering and body temperature in the parturient. Anesth
Analg 68:530, 1989.
485. Liu WH, Luxton MC: The effect of prophylactic fentanyl on shivering in elective caesarean section under epidural analgesia. Anaesthesia
46:344, 1991.
486. Casey WF, Smith CE, Katz JM, et al: Intravenous meperidine for control of shivering during caesarean section under epidural anaesthesia.
487. Camann WR, Hortvet LA, Hughes N, et al: Maternal temperature regulation during extradural analgesia for labour. Br J Anaesth 67:565, 1991.
488. Lieberman E, Lang JM, Frigoletto F Jr, et al: Epidural analgesia, intrapartum fever, and neonatal sepsis evaluation. Pediatrics 99:415, 1997.
489. Philip J, Alexander JM, Sharma SK, et al: Epidural analgesia during labor and maternal fever. Anesthesiology 90:1271, 1999.
490. Breen TW, Ransil BJ, Groves PA, et al: Factors associated with back pain after childbirth. Anesthesiology 81:29, 1994.
491. MacArthur A, MacArthur C, Weeks S: Epidural anesthesia and low back pain after delivery: A prospective cohort study. Br Med J 311:1336,
1995.
492. MacArthurAJ, MacArthur C, Weeks SK: Is epidural anesthesia in labor associated with chronic low back pain? A prospective cohort study.
493. Hurley RJ, Lambert D, Hertwig L, et al: Postdural puncture headache in the obstetric patient: Spinal vs. epidural anesthesia [abstract].
494. Morewood GH: A rational approach to the cause, prevention and treatment of postdural puncture headache. Can Med Assoc J 149:1087, 1993.
495. Williams EJ, Beaulieu P, Fawcett WJ, et al: Efficacy of epidural blood patch in the obstetric population. Int J Obstet Anesth 8:105, 1999.
496. Sechzer PH, Abel L: Post-spinal anesthesia headache treated with caffeine. Evaluation with demand method. Curr Ther Res 24:307, 1978.
497. CamannWR, Murray RS, Mushlin PS, et al: Effects of oral caffeine on postdural puncture headache: A double-blind, placebo-controlled trial.
498. Taivainen T, Pitkanen M, Tuominen M, et al: Efficacy of epidural blood patch for postdural puncture headache. Acta Anaesthesiol Scand
37:702, 1993.
499. Abouleish E, de la Vega S, Blendinger TO: Long term follow-up of epidural blood patch. Anesth Analg 54:459, 1975.
500. Colonna-Romano P, Shapiro BE: Unintentional dural puncture and prophylactic epidural blood patch in obstetrics. Anesth Analg 69:522,
1989.
501. Cheek TG, Banner R, Sauter J, et al: Prophylactic extradural blood patch is effective. A preliminary communication. Br J Anaesth 61:340,
1988.
502. Ackerman WE, Juneja MM, Kaczorowski DM: Prophylactic epidural blood patch for the prevention of postdural puncture headache in the
parturient. Anesthesiol Rev 17:45, 1990.
503. Marx GF: Cardiopulmonary resuscitation of late-pregnant women. Anesthesiology 56:156, 1982.
504. Forrester DJ, Mukherji SK, Mayer DC, et al: Dilute infusion for labor, obscure subdural catheter, and life-threatening block at cesarean
623
505. Auroy Y, Narchi P, Messiah A, et al: Serious complications related to regional anesthesia. Anesthesiology 87:479, 1997.
506. Wong CA, Scavone BM, Dugan S, et al: The incidence of postpartum nerve injuries [abstract]. Anesthesiology 91:A1061, 1999.
507. Columb MO, Lyons G: Determination of the minimum local analgesic concentrations of epidural bupivacaine and lidocaine in labor. Anesth
Analg 81:833, 1995.
508. Lyons G, Columb M, Wilson RC, et al: Epidural pain relief in labour: Potencies of levobupivacaine and racemic bupivacaine. Br J Anaesth
81:899, 1998.
624
Section IV - Chapter 26 - Acute Situations: Trauma
Chapter 26 - Acute Situations: Trauma
HONORIO T. BENZON
ADRIENNE E. KNIGHT
Trauma is tissue damage caused by an extrinsic force. The stress response to trauma and the accompanying pain
[1]
activate neurohumoral and physiologic processes ( Table 26–1 ). These responses result in hyperglycemia, lipolysis,
protein catabolism, increased catecholamine and antidiuretic hormone levels, a hypercoagulable state, and
immunosuppression. Trauma has direct and reflex-related effects on the cardiovascular, pulmonary,
[2] [3] [4] [5]
gastrointestinal, renal, musculoskeletal, and immunologic systems. Clinically, there is tachycardia and hypertension.
Thoracic and abdominal injuries cause chest splinting, reflex-activated diaphragmatic dysfunction, hypoventilation,
atelectasis, ventilation perfusion mismatch, and hypoxia. Vital capacity and the functional residual capacity decrease,
coughing is impaired, secretions are retained, and secondary pneumonia develops. Immobility may result in deep
venous thrombosis and possible pulmonary embolism. There is increased sympathetic tone, decreased
gastrointestinal motility, and ileus. These consequences result in prolonged hospitalization, high morbidity, and
significant expense.
Neuralgia, complex regional pain syndromes, and neuroma formation may accompany traumatic events. Patients
may develop chronic neuropathic pain syndrome, one of the more difficult chronic pain syndromes to treat.
Studies that have evaluated the management of
TABLE 26-1 -- NEUROHUMORAL AND PHYSIOLOGIC RESPONSES TO TRAUMA

Release of inflammatory mediators
Activation of the cytokine and complement cascades
Activation of the coagulation cascade, hypercoagulable state
Activation of neutrophils and stimulation of lymphocytes
Increased catecholamines and sympathetic activity
Increased cortisol, growth hormone, ACTH, and prolactin
Increased renin, angiotensin, aldosterone, and vasopressin
Increased oxygen consumption
Increased minute ventilation
Altered immune response
Adapted from Patel N, Smith CE: Pain management in trauma. Anesthe siol Clin North Am 17:295;1999. Hedderich R, Ness TJ: Analgesia for trauma and burns.
Crit Care Clin 15:167;1999.
pain in trauma and burn victims indicated that these patients have a high incidence of moderate to severe pain. In [6]
reports of these studies, there was an inordinate concern for the hemodynamic changes and respiratory depression
caused by analgesics. The results of these studies are surprising, because analgesic interventions have been shown
[6] [7]
to modify the stress response and to aid in early rehabilitation of the patient. The application of the ideal
[3] [4]
analgesic/anesthetic regimen also reduces the incidence of chronic pain syndromes. [8]
Continuum of Pain Management of Patients with Trauma
The management of pain in trauma victims starts in the prehospital environment, at the site of the injury, and during
transport of the patient to the hospital. Pain management continues in the emergency room, the operating room, the
intensive care unit, and during the rehabilitation period. Relief of pain on location or during transport to the hospital
is usually inadequate. This is because no medical personnel accompany the paramedics, emergency medical
[9]
technicians, or ambulance personnel. The emergency medical service (EMS) providers are mainly concerned with
assessing the patient's injury, monitoring the vital signs, and reporting the vital signs to the emergency room medical
personnel.
Pain relief has a low priority in the emergency room. It is justifiable that the attention is directed toward initial
[10]
resuscitation and stabilization, establishment of cardiovascular and ventilatory stability, control of visible
625
hemorrhage, and restoration of the patient's fluid and blood volume. The dilemma is confounded by the difficulty of
assessing pain in the emergency room. Patients may have neurologic injuries that could alter behavior or they may
be intoxicated with alcohol or drugs. After the initial therapeutic interventions, attention is focused on diagnosing
the problem. Physicians worry that the administration of analgesics may interfere with diagnosis by decreasing
patients' responses to their injuries.
The administration of an analgesic does not necessarily interfere with the diagnosis. In fact, a prospective double-
blind study showed that the administration of analgesics in the emergency department may actually facilitate
diagnosis. In spite of this study, pain is not treated immediately in the emergency room; moreover, an
[11]
inappropriate drug may be given or the analgesic may be given intramuscularly rather than intravenously. [12]
Pain is usually assessed by the patient's vital signs, verbal complaints, or nonverbal behaviors. Often, there is no
direct correlation between the perception of the patient's degree of pain by the nurse or physician and the patient's
report of pain. A better assessment tool should probably be instituted, such as the visual analogue scale scoring
[13]
(VAS) system or another pain scale. Most adults and children older than 7 years of age can score their pain intensity
on a visual analogue scale (e.g., a 10-cm line with one end labelled no pain and the other end labeled worst possible
pain), on a numerical scale (e.g., 0 = no pain and 10 = the worst pain imaginable), or on a category scale (e.g. none,
little, moderate, or severe). Children younger than 7 years of age and adults who are unable to use the scales can rate
their pain based on a series of several facial expressions that represent emotions ranging from crying to smiling. [14]
Also, there are behaviors that convey the presence of pain. These include grimacing, crying or wincing with
movement, irritability, decrease in activity, inability to move an extremity, and apathy. In infants, a characteristic
facial expression of pain includes a brow bulge, eye squeeze, deepened nasolabial furrow, open lips with mouth
stretched both vertically and horizontally, pursed lips, taut tongue, tongue protrusion, and chin quiver. [15]
The management of pain in the operating room is discussed in the section on regional anesthesia for trauma. In the
intensive care setting, the goals are to improve comfort, facilitate sleep, reduce anxiety, and reduce undesired
responses to the injury. Critically injured patients cannot communicate their discomfort. They may have an altered
[16]
level of consciousness from their injuries or from their medications, or they may be intubated or paralyzed. The
level of sedation can be assessed by a sedation scale, wherein the degree of wakefulness or response to stimulation is
graded. Other scale scores for sedation include the observers' assessment of alertness/sedation scale and the facial
[17]
pain scale that is applicable to children.

[14]
The management of trauma patients during their period of rehabilitation involves treatment of contractures,
spasticity, and pressure sores. Chronic pain may develop in the form of neuropathic pain, myofascial syndrome,
complex regional pain syndromes, and phantom limb pain. The specific treatment of these syndromes is beyond the
scope of this chapter.
Pharmacologic Management of Pain
NONOPIOIDS
Analgesics include nonopioid drugs and opioid medications for acute pain. Tranquilizers are used as adjuvants
during the acute period, whereas sedatives are added to the opioids during intensive care. Antidepressants and
anticonvulsants are used in addition to opioids for management of chronic pain.
Nonopioid analgesics include aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen. These
agents differ from opioids in several ways. Their primary mechanism of action, excluding that of acetaminophen, is
inhibition of the enzyme cyclooxygenase, which prevents the formation of prostaglandins; they are antipyretics; they
have a ceiling analgesic effect; and, finally, they do not produce tolerance or addiction.
[18]
NSAIDs inhibit the cyclooxygenase enzyme (also called prostaglandin synthetase), and some inhibit the
lipooxygenase enzyme. The metabolites of the lipooxygenase system are the leukotrienes, some of which are
involved in pain transmission (e.g., leukotriene B4 produces thermal hyperalgesia). The cyclooxygenase system, on
the other hand, produces prostaglandins, which sensitize peripheral nerves and central sensory neurons to painful
stimuli.
In the past, NSAIDs were thought to produce analgesia through actions outside the central nervous system (CNS),
but studies have revealed that NSAIDs may partially produce analgesia through a CNS mechanism that may
[19] [20] [21] [22]
involve facilitation of the descending inhibitory pain pathways or possible inhibition of peripheral inflammation
through nonprostaglandin mechanisms in the CNS. [21] [23]
626
The different nonopioid drugs are shown in Table 26–2 . Aspirin is the oldest, the most studied, and the most
commonly used of these drugs. Gastric disturbances and bleeding are common side effects. Its use is contraindicated
in children younger than 12 years of age who have a viral illness because of the possible development of Reye
syndrome.
Acetaminophen is a para-aminophenol derivative, which has analgesic and antipyretic properties similar to those of
aspirin. Although acetaminophen has an insignificant anti-inflammatory effect it has no antiplatelet effects and does
not damage the gastric mucosa. However, although it has no antiplatelet effects, the combination of acetaminophen
and warfarin can result in overanticoagulation. Acetaminophen is almost entirely metabolized in the liver; its
[24]
metabolites are responsible for the hepatotoxicity seen in cases of overdose. For adults and for children whose
weight is
TABLE 26-2 -- SELECTED NONOPIOID DRUGS FOR PAIN MANAGEMENT

Pediatric Dose
Drug Average Analgesic Dose (mg) Dose Interval (hr) Maximal Daily Dose (mg/kg)
Aspirin 500–1000 4–6 4000 10–15 q 4–6 hr
Acetaminophen 500–1000 4–6 4000 15 q 4–6 hr
Ibuprofen 200–400 4–6 2400 10 q 6–8 hr
Naproxen 500 initial; 250 subsequent 6–8 1250 5 bid
Diclofenac 50 8 150 —
Ketorolac 30 mg IM or IV initial, 15 or 30 mg subsequent 6 150 first day, 120 —

subsequent
Celecoxib 100–200 12 200 —
Rofecoxib 25–50 24 50–100 —
Adapted from American Pain Society: Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain, 4th ed. Glenview, Illinois, 1999.
greater than 45 kg, the maximum recommended daily dose is 4000 mg/day. For children who weigh less than 45 kg,
the maximum dose is 90 mg/kg per day. Patients with alcoholism and chronic liver disease or patients who are
fasting can develop hepatotoxicity with therapeutic doses of acetaminophen. In fact, there have been reported cases
[25]
of hepatic injury in patients who drank moderate amounts of alcohol and ingested therapeutic doses of
acetaminophen. To prevent acetaminophen toxicity, the physician should be aware of the concentrations of
[26]
acetaminophen in the commercially available combinations of hydrocodone and acetaminophen ( Table 26–3 ).
Individual responses to NSAIDs can be highly variable. Some patients respond very well to some NSAIDs and not
to others. Because of interpatient variability, the use of other NSAIDs is necessary to provide alternative therapy.
[27] [28]
There are two isoforms of the enzyme cyclooxygenase (COX-1 and COX-2) that are selectively inhibited by
NSAIDs. The COX-1 isoenzyme is found in the blood vessels, stomach, and kidneys, whereas COX-2 is induced in
peripheral tissues by inflammation. The inhibition of COX-1 is associated with gastric, renal, and platelet side
effects. The NSAIDs described earlier
TABLE 26-3 -- SELECTED COMMERCIALLY AVAILABLE HYDROCODONE/ACETAMINOPHEN COMBINATIONS
Hydrocodone (mg) Acetaminophen (mg)

Vicodin 5 500
Vicodin ES 7.5 750
Vicodin HP 10 660
Lorcet HD 5 500
Lorcet plus 7.5 650
Lorcet 10/650 10 650
Lortab 5, 7.5, 10 500
Zydone 5, 7.5, 10 500
Norco 10 320
Note: Maximum dose of acetaminophen is 4000 mg per day.
are both COX-1 and COX-2 inhibitors. Two new, specific COX-2 inhibitors, rofecoxib (Vioxx) and celecoxib
(Celebrex), have been introduced. Celecoxib should not be prescribed for patients with known allergy to
627
sulfonamides. Neither drug affects the platelets, and neuraxial blocks can be safely performed in patients taking
these drugs.
OPIOID MANAGEMENT OF PAIN
Opioids are the mainstay in treatment of pain secondary to trauma. Opioids act in the CNS by binding to specific
opioid receptors, specifically the µ, κ, and δ receptors. Opioids also have a peripheral site of action, especially in the
presence of inflammation ; in such cases, opioid receptors have been identified in the immunocompetent cells that
[29]
migrate to the inflamed tissue. Clinically, the intra-articular injection of morphine has been used in the
[30]
management of pain after knee arthroscopy. [31]
Opioids are classified as follows:2
1. Naturally occurring opium derivatives (morphine and codeine)

2. Semisynthetic derivatives of morphine (hydromorphone, oxymorphone, and heroin)
3. Synthetic compounds (fentanyl, sufentanil, alfentanil, meperidine, methadone, and propoxyphene)
4. Mixed agonist–antagonists (pentazocine, nalbuphine, and butorphanol)
5. Partial agonists (buprenorphine and dezocine)
Some of the opioids are listed in Table 26–4 .
All opioids have similar clinical effects that vary in degree from one drug to another. Analgesia, sedation, euphoria,
dysphoria, respiratory depression, cough suppression, nausea and vomiting, and constipation are dose-dependent
effects of the opioid agonists. Respiratory depression is due to the opioid effects on the µ2 receptors in the brainstem.
The depression is mainly
TABLE 26-4 -- OPIOID ANALGESICS FOR PAIN MANAGEMENT
Equianalgesic Dose (mg) Oral Dose

Drug Oral Parenteral Adults (mg) Children (mg/kg)
Morphine 30 10 15–30 0.30
Hydromorphone 7.5 1.5 4–8 0.06
Methadone 20 10 5–10 0.20
Oxycodone 20 — 15–30 0.30
Meperidine 300 75 Not recommended
Fentanyl — 0.1 — —
Nalbuphine — 10 — —
Butorphanol — 2 — —
Adapted from American Pain Society: Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain, 4th ed. Glenview, Illinois, 1999.
in the respiratory rate, and to a lesser extent in the tidal volume. Nausea and vomiting are due to the stimulation of
the emetic chemoreceptor trigger zone (ECTZ) in the medulla. There is increased tone in the smooth muscle
sphincters, specifically in the sphincter of Oddi.
Opioids reduce sympathetic tone, which may lead to hypotension, especially in hypovolemic patients. Morphine
also causes histamine release, resulting in hypotension. Histamine release is less frequent with fentanyl, sufentanil,
[32]
and meperidine. Most opioids cause bradycardia via vagal stimulation. Meperidine, on the other hand, often
[32] [33] [34]
causes tachycardia. This may be due to meperidine's atropine-like structure or to a reflex response to the
hypotension after its injection. Intramuscular injections are not recommended for acute pain, especially in patients
[35]
with trauma, because these injections are painful, there is a 30- to 60- minute lag time before the opioid's analgesic
effect, and because there is a rapid falloff in the drug's action. Most important, there is unpredictable absorption
from the site of injection; the result is that times to reach peak blood concentrations are variable. The erratic [36] [37]
absorption is exaggerated in trauma patients because of the presence of hypotension, hypothermia, and peripheral
vasoconstriction. Intravenous injection is the ideal route. For morphine, the intravenous loading dose is 0.08 to 0.12
mg/kg. Onset of action is between 15 and 30 minutes and duration is 2 to 3 hours. Fentanyl's effect, on the other
hand, is seen in 1 to 5 minutes and lasts 30 minutes. The loading dose of fentanyl is 0.5 to 1 µg/kg. Fifty to a
hundred percent of the initial dose of morphine or fentanyl can be repeated after 2 to 5 minutes.
628
In patients with severe pain, intravenous boluses may be repeated until there is pain relief, followed by a
maintenance intravenous infusion. Edwards and Breed recommended initial intravenous injections of 0.03 mg/kg
[38]
of morphine, or the equivalent dose of another opioid, every 10 minutes until there was 50% reduction of the
patient's pain. They also recommended an initial maintenance dose based on the elimination half-life of the opioid,
which is approximately 3 hours for morphine and hydromorphone. For practical purposes, the hourly maintenance
dose of the opioid is approximately one sixth of the loading dose.
Patient-controlled analgesia (PCA) is a technique whereby the patient regulates the amount of analgesic delivered. [39]
PCA allows patients to titrate their analgesic needs, bypassing the unavoidable delays that occur when analgesics
[40]
are provided upon request, and giving patients a feeling of control over their analgesic requirements. With PCA,
[41]
patients maintain a narrower range of plasma drug concentrations compared with that of intramuscular injections.
Several studies have shown that the opioid requirements of patients using PCA are fewer than those of patients on
conventional intramuscular dosing.
As stated, the patient controls the amount of analgesic delivered. The demand button should not be pushed by
anyone other than the patient. The patient must be cooperative and able to understand the use of PCA. This
requirement restricts the use of PCA in patients younger than 3 to 5 years and in patients with mental or physical
handicaps.
The attributes of an ideal analgesic for PCA use include a rapid onset of analgesic action, a high level of analgesic
efficacy, and an intermediate duration of effect for better controllability. Morphine and hydromorphone satisfy
[42]
most of these characteristics and are, therefore, the most widely used drugs in PCA. Fentanyl is too short acting,
whereas methadone and buprenorphine have very long durations of action. The agonist–antagonist drugs have
ceiling effects that limit their effectiveness. Recommended bolus doses and lockout intervals for the various
analgesics are shown in Table 26–5 .
The use of a basal infusion for PCA, which was recommended to eliminate the trough in morphine plasma
concentrations, was found not to decrease resting pain but to reduce movement-associated pain scores. There [43]
seems to be a higher incidence of nausea and vomiting with the addition of basal infusion to the PCA. Also, the [43]
addition of a nighttime basal infusion does not necessarily improve the patient's ability to sleep or rest comfortably. [44]
Therefore, basal infusions in intravenous PCA are not routinely recommended.
TABLE 26-5 -- PATIENT-CONTROLLED ANALGESIA: BOLUS DOSES, LOCKOUT INTERVALS, AND CONTINUOUS INFUSIONS FOR PARENTERAL
ANALGESICS
Drug Bolus (mg) Lockout Interval (min) Continuous Infusion (mg/hr)
Morphine 0.5–3 5–20 1–10
Hydromorphone 0.1–0.5 5–15 0.2–0.5
Meperidine 5–15 5–15 5–40
Methadone 0.5–3 10–20 —
Oxymorphone 0.2–0.8 5–15 0.1–1
Fentanyl 0.015–0.05 3–10 0.02–0.1
Sufentanil 0.003–0.015 3–10 0.004–0.03
Buprenorphine 0.03–0.2 10–20 —
Nalbuphine 1–5 5–15 1–8
Pentazocine 5–30 5–15 6–40
The addition of a basal infusion is controversial (see text). The use of meperidine is generally not recommended.
Adapted from Sherwood ER, Benzon HT: Patient-controlled analgesia. In Benzon HT, Raja SN, Borsook D, et al (eds): Essentials of Pain Medicine and Regional
Anesthesia. New York, Churchill Livingstone, 1999, p 147.
The oral route is recommended if the patient can tolerate oral intake. This route is convenient and flexible and
produces steady systemic levels. Except for the sustained-release preparations, the peak effect of oral opioids
usually occurs between 60 and 90 minutes after intake. When switching from the parenteral to the oral route, the
physician should be familiar with the equivalent doses between these routes of administration. For example, 30 mg
of oral morphine is equivalent to 10 mg of parenteral morphine (see Table 26–4 ). The introduction of sustained-
release preparations of opioids has allowed less frequent intake, resulting in fewer interruptions of sleep. MS Contin,
Oramorph-SR, and Oxycontin provide up to 12 hours of analgesia. A 24-hour oral preparation of morphine and
hydromorphone is also available. For these long-acting drugs, provisions should be made for the addition of an
immediate-release opioid preparation for breakthrough pain. Methadone, although it is not available in a sustained-
629
release preparation, has a long duration of action. Its plasma half-life is 12 to 60 hours; the dosing interval varies
from 6 to 12 hours.
Meperidine is not recommended for prolonged use. In fact, some hospitals have removed meperidine from their
formularies. Normeperidine, a metabolite of meperidine, accumulates with repetitive dosing. Normeperidine [45]
causes CNS excitation, resulting in anxiety, tremors, myoclonus, and generalized seizures. Patients with renal
insufficiency are at increased risk. Naloxone cannot reverse these symptoms. Patients with sickle cell disease are at
risk for normeperidine toxicity ; they may have compromised renal function and a low seizure threshold. The
[46]
American Pain Society has recommended that meperidine should not be used for more than 48 hours in patients
without renal or CNS disease, that it should not be prescribed for doses greater than 600 mg over 24 hours, and that
it should not be used for the treatment of chronic pain. Finally, a hyperpyrexic syndrome has been described when
meperidine is given to patients on monoamine oxidase inhibitors. [47]
Fentanyl is available in a transdermal preparation. This delivery system is ideal in patients with colostomies or short
gut syndrome, or in those who have difficulty swallowing. The patches come in doses of 25, 50, 75, and 100
µg/hour. The 25 µg per hour dose is roughly equivalent to 45 to 80 mg per day of oral morphine. The preparation is [48]
designed to release fentanyl for 72 hours, although in some patients the patch may have to be changed after 48 hours.
Although approved for the management of chronic pain, fentanyl should not be used in patients with acute pain.
Between 12 and 16 hours for a therapeutic effect and 48 hours are required for a steady state concentration. [49]
Moreover, significant blood levels are still present 17 hours after its removal. [50]
Tramadol hydrochloride (Ultram) exerts its analgesic effect via opioid and nonopioid mechanisms. It binds weakly
with the µ receptor and it inhibits the uptake of serotonin and norepinephrine. This drug usually is taken every 4 to 6
hours. Its analgesic efficacy is comparable with that of acetaminophen with codeine. Tramadol is useful in patients
[51]
who are not receiving adequate relief from acetaminophen, in those at risk for adverse side effects of NSAIDs, and
in those who cannot tolerate opioid analgesics. Side effects of tramadol include nausea, constipation, dizziness, and
somnolence. Doses greater than 400 mg a day are associated with increased risk of seizures. Patients older than 75
years should not take more than 300 mg per day. The use of tramadol has not been associated with clinically
[52]
significant side effects such as sedation, respiratory depression, or constipation. In addition, tolerance and physical
and abuse potential seem to be minimal with this drug. [52] [53]
ANTIDEPRESSANTS
Antidepressants are used during rehabilitation of the trauma patient. They have very little use in acute pain situations.
Of all the antidepressants, the tricyclic antidepressants (TCAs) have undergone the most scientific scrutiny. TCAs
block the reuptake of norepinephrine, serotonin, and dopamine. The different TCAs have varying abilities to block
the biogenic amines affecting their antidepressant efficacy and selectivity. These drugs also have inhibitory effects
in the cholinergic, histaminergic, and adrenergic systems, resulting in undesirable side effects. They have been used
mostly with regard to neuropathic pain syndromes.
Antidepressants have been used successfully in patients with postherpetic neuralgia. Initially, antidepressants were
used in case series for the treatment of patients with depression associated with postherpetic neuralgia. The [54]
effectiveness of antidepressants was proved in a double-blind, placebo-controlled, crossover trial of amitriptyline. [55]
Good results were achieved in 67% of the patients. The patients reported pain relief without an adverse change in
their depression scores, and analgesia occurred at dosages lower than those used in treating depression. Another
randomized clinical trial showed the efficacy of amitriptyline over lorazepam in the treatment of patients with
postherpetic neuralgia. [56]
Noradrenergic agents are also effective in patients with postherpetic neuralgia. Desipramine, a selective
norepinephrine reuptake inhibitor, is more effective than placebo. Nortriptyline is equal to amitriptyline and has
[57]
fewer side effects, whereas the serotonergic agents appear not to be effective in patients with postherpetic
[58]
neuralgia. Based on all the studies done so far, Watson recommended that amitriptyline or nortriptyline be the
[59]
initial antidepressant of choice in patients with postherpetic neuralgia. [60]
The tricyclic antidepressants (TCAs), especially the older drugs, are effective in relieving the pain of diabetic
neuropathy. Amitriptyline and imipramine
[61]
are superior to placebo, and both drugs are superior to diazepam.
[62] [63] [64]
Amitriptyline appears to be as effective as gabapentin. The noradrenergic desipramine and the serotonergic
[65]
paroxetine have also been found to be effective. From these studies, it appears that antidepressants with
[66] [67]
serotonergic and noradrenergic effects (e.g., imipramine) are most effective in cases of painful diabetic neuropathy.
630
TCAs should be selected based on their efficacy in treatment of patients with a particular pain syndrome as well as
their side-effect profiles and the patient's age. Side effects include somnolence, cardiovascular effects resulting from
anti–alpha-adrenergic and local quinidine-like antiarrhythmic properties, anticholinergic effects, and antihistaminic
effects. The side effects may be used to benefit the patient (e.g., use of the sedative property to improve a patient's
sleep. Table 26–6 lists some of the useful TCAs and their side-effect profiles. These drugs should be started at low
[68]
doses (i.e., 10–50 mg) and slowly increased to patient's tolerance. Signs and symptoms of TCA overdose include
electrocardiographic changes (widening of the QRS and of the PR and QT intervals), hypotension, tachycardia,
delirium, and respiratory depression.
MEMBRANE STABILIZERS
The use of membrane stabilizers is appropriate in neuropathic pain syndrome—especially in patients with nerve
injuries and during the rehabilitation of trauma patients. Carbamazepine, an iminostilbene derivative chemically
related to the antidepressants, blocks ionic conductance and suppresses spontaneously active A-delta and C fibers
[69]
without interfering with normal conduction. Carbamazepine is the drug of choice for patients with trigeminal
[69] [70]
neuralgia. Several double-blind, crossover trials showed that carbamazepine was better than placebo,
[71]
with [72] [73]
response rates of 70% to 80% after 5 to 14 days of treatment. It has also been shown to have a beneficial effect in
patients with peripheral diabetic neuropathy. The initial dose is 100 mg twice a day, increased at weekly intervals
[74]
until the desired effect is obtained. Side effects of carbamazepine include nausea, vomiting, dizziness, and
drowsiness. Because aplastic anemia and agranulocytosis can occur, a complete blood count is recommended at the
start of treatment and at 3 and 6 months of follow-up.
TABLE 26-6 -- USEFUL TRICYCLIC ANTIDEPRESSANTS AND MEMBRANE STABILIZERS IN PAIN MANAGEMENT
Side-effect Profile
Drug Trade Name Starting Dose, mg (range) Sedative Anticholinergic Orthostatic
Amitriptyline Elavil 25–75 (75–300) ++++ +++ ++++
Doxepin Sinequan 10–50 (75–300) +++ +++ ++
Imipramine Tofranil 25–50 (75–300) ++ ++ ++++
Desipramine Norpramin 50–100 (75–100) + + ++++
Nortriptyline Pamelor 10–50 (30–150) + + ++
Gabapentin Neurontin 100–300 (up to 3600 mg/d) Sedation
Mexiletine Mexitil 150 mg bid (up to 1200 mg/d) CNS effects, GI distress
CNS, central nervous system; GI, gastrointestinal.
Adapted from Borsook D, Fishman SM: Psychotropic drugs useful in pain treatment. Vu TH, Borsook D: Membrane stabilizers. In Benzon HT, Raja SN, Borsook D,
et al (eds): Essentials of Pain Medicine and Regional Anesthesia. New York: Churchill Livingstone, 1999, p 63.
Gabapentin is structurally similar to the gamma-aminobutyric acid (GABA) analogue, but it does not have GABA-
ergic activity. Neither does it affect GABA uptake or metabolism. Its binding site is located at the alpha-2-delta
subunit at the L-type calcium channel. Two large clinical trials showed the efficacy of gabapentin in patients with
postherpetic neuralgia and peripheral diabetic neuropathy. The doses used in these studies ranged from 900 to
[75] [76]
3600 mg per day given in three doses. It is recommended, however, that doses start at 100 to 300 mg, initially taken
at bedtime, and increased every 3 days to a maximal dose of 2400 to 3600 mg a day. Side effects include [77]
somnolence, fatigue, dizziness, and ataxia.
Other membrane stabilizers used in pain management include phenytoin (Dilantin), lamotrigine (Lamictal),
topiramate (Topamax), and mexiletine (Mexitil). The mechanism of neuropathic pain relief of mexiletine may be
due to its suppressive effects on spontaneous ectopic discharges from the injured nerve without blocking normal
nerve conduction. [78]
Regional Anesthesia for Trauma
ADVANTAGES OF NEURAXIAL AND REGIONAL ANESTHESIA
Neuraxial and regional anesthesia are suitable for patients whose traumatic injuries are limited. This type of
anesthesia is not recommended in patients with multiple trauma who are clinically unstable and require emergent
treatment. There are several advantages to using regional anesthesia, including the suppression of the surgical stress
response, improved or maintained mental status of the patient, improved peripheral circulation, decreased incidence
of venous thromboembolism, decreased blood loss, and reduced pulmonary complications ( Table 26–7 ). The [79]
631
trauma patient usually has a full stomach, and the use of a regional anesthesia technique avoids intubation and the
possibility of aspiration. This is especially important in
TABLE 26-7 -- ADVANTAGES OF NEURAXIAL AND REGIONAL ANESTHESIA

Avoid risks of intubation
Decreased incidence of thromboembolism
Decreased stress response
Decreased blood loss
Increased limb blood flow
Less impairment of cognitive function
Earlier mobilization
Provision of postoperative analgesia
Decreased length of hospital stay
From Gajraj NM, Giesecke AH: Pain management in the operating room: Regional anesthesia for operative intervention and to augment general anes thesia. In
Rosenberg AD, Grande CM, Bernstein RL (eds): Pain Management and Regional Anesthesia in Trauma. New York, WB Saunders, 2000, p 131.
trauma patients, because up to 3% of patients with major trauma have cervical spine injury, and the majority of these
patients are unstable.
Patients who received regional anesthesia were shown to have better mental function scores than those who received
general anesthesia. This advantage persisted up to the fifth postoperative day. The preservation of mental function
[80]
is important, especially in head-injured patients.
The sympathetic nervous system is activated during surgery and anesthesia. This produces tachycardia, hypertension,
and increased myocardial contractility, resulting in increased myocardial oxygen demand. There is also decreased [81]
myocardial oxygen supply because of constriction of the coronary arteries. In the postoperative period, increased
sympathetic nervous system activity due to uncontrolled postoperative pain may lead to dysrhythmias, angina, and
increased areas of myocardial infarction. Attenuation of sympathetic activity in the perioperative period
[82] [83]
decreases morbidity and mortality after surgery. The use of neuraxial and regional anesthesia during surgery and
[84]
improved management of postoperative pain obtund this sympathetic hyperactivity; the result is a more stable
cardiovascular state. [85]
Trauma and major surgery are associated with a hypercoagulable state that persists into the postoperative period. [86] [87]
This state is induced primarily by activation of the stress response and the sympathetic nervous system in response
[88]
to surgery and pain. There is vascular injury, with activation of the coagulation cascade, increased coagulation
factors, decreased coagulation inhibitor concentrations, enhanced platelet activity, and impaired fibrinolytic
[86] [89] [90]
activity. Vasoocclusive and thromboembolic events are consequences. Epidural anesthesia increases limb blood
[91]
flow and reduces postoperative hypercoagulabity, decreasing the incidence of thromboembolic events. Improved
[92] [93]
management of postoperative pain with epidural opioids or continuous peripheral nerve blocks reduces the stress
response decreasing vaso-oclusive and thromboembolic morbidity.
Thoracic and upper abdominal incisions decrease intercostal muscle tone and cause postoperative diaphragmatic
dysfunction. The epidural administration of local anesthetic has been shown to prevent inhibitory neural reflex
[94] [95]
and to restore postoperative diaphragmatic function. Improved pain control in the postoperative period with use
[95] [96]
of neuraxial opioid and local anesthetic infusions can reduce postoperative pulmonary complications such as
atelectasis, hypoxemia, and infection.
The use of epidural anesthesia and postoperative epidural analgesia reduces the incidence of postoperative ileus. The
reason for this reduction is the blockade of the sympathetic innervation of the bowel as well as improved analgesia,
which reduces the sympathetic nervous system–mediated stress response and lowers parenteral opioid
requirements. [97]
CONTRAINDICATIONS
There are absolute and relative contraindications to neuraxial anesthesia. Patient refusal or lack of cooperation,
hemodynamic instability with hypovolemia, infection at the site of the injection, presence of sepsis, or coagulopathy
are some of the contraindications to neuraxial anesthesia.
632
A history of intake of aspirin or of NSAID is not a contraindication to use of neuraxial anesthesia. In the rare [98] [99] [100]
case reports of spinal hematoma involving antiplatelet drugs, some complicating factors were present, such as
concomitant heparin intake, epidural venous angioma, repeated epidural injections, or technical difficulties in
[101] [101] [102]
performing the injection. It should be noted that bleeding time is not a reliable prediction of bleeding in
[103] [104] [105]
patients on aspirin or NSAIDs. Caution should be observed in performing neuraxial block in patients taking the
[106]
newer antiplatelet drugs such as ticlopidine and clopidogrel. Although aspirin and NSAIDs inhibit the
cyclooxygenase enzyme, these thienopyridine derivatives inhibit platelet aggregation by altering platelet membrane
and blocking the interaction between fibrinogen and the membrane glycoprotein receptor GPIIb-IIIa. [107] [108]
Clopidogrel is 40 to 100 times more potent than ticlopidine. Case reports of epidural hematoma after neuraxial
injection have been described with both ticlopidine and clopidogrel. [105] [109]
The American Society of Regional Anesthesia has established guidelines for the performance of neuraxial blocks in
patients who are taking anticoagulants. If a local anesthetic is added to the epidural opioid, a minimal concentration
of the local anesthetic is recommended so that signs and symptoms of spinal hematoma may be noted early. For
patients on chronic oral anticoagulation, warfarin must be stopped and the INR measured. An INR value of 1.5 or
less is acceptable for the performance of neuraxial blocks. In patients who have received an initial dose of
[110]
coumadin, neuraxial blocks are probably safe if performed within 24 hours of the coumadin intake. This is [110]
because it takes 2 to 3 days before the INR is greater than 1.5, and it takes 3 to 4 days for coumadin to take full
[111]
effect. If the coumadin has been taken more than 24 hours earlier, or a second dose was administered, the
prothrombin time and INR should be checked before performance of the block.
The use of subcutaneous heparin does not appear to contraindicate the performance of a neuraxial block. Most [112]
surveys have shown that anesthesiologists do not consider low-dose subcutaneous heparin as a contraindication to
neuraxial anesthesia. These beliefs are supported by the performance of neuraxial blocks without complications
[113] [114]
in more than 9000 patients who were taking subcutaneous heparin. There were complicating factors in the [112]
reported cases of spinal hematoma in patients who were taking subcutaneous heparin. These include a prolonged
thrombin time, a bloody tap, and a difficult placement of the block. Neuraxial block and intraoperative heparin
[115] [116]
administration are acceptable if the following recommendations are followed: [112]
1. Heparin administration should be delayed for 1 hour after needle placement.

2. The catheter should be removed 1 hour before heparin administration or 2 to 4 hours after the last heparin
dose.
3. Neuraxial block should be avoided in patients with other coagulopathies.
4. The patient should be monitored postoperatively for early detection of motor blockade.
The occurrence of bleeding at epidural needle placement increases the risk of hematoma. However, there are no [117]
data to support cancellation of the surgery, and any decision to proceed should involve the surgeon, the
anesthesiologist, and the patient. Prolonged anticoagulation with heparin appears to increase the risk of spinal
hematoma, especially in the presence of other anticoagulants. Neuraxial block is best avoided in this scenario.
[112]
With regard to low molecular weight heparin (LMWH), the monitoring of the anti-Xa level is not recommended,
because these levels are not predictive of the risk of bleeding in patients taking LMWH. Patients taking LMWH [118]
are simply assumed to have altered coagulation. The concomitant administration of other anticoagulants, such as
NSAIDs, heparin, or dextran, increases the risk of bleeding. For patients who have been given a prophylactic dose of
LMWH (i.e., 30 mg bid), the neuraxial block should be performed 12 hours after the LMWH dose. There should be
a waiting period of 24 hours if a therapeutic dose of 1 mg/kg has been given. If LMWH is to be started [119]
postoperatively, it should not be given until at least 24 hours after surgery. The same guidelines apply to catheter
removal. The epidural catheter should not be removed for at least 12 hours after the last dose of LMWH, or 24
[120]
hours if a full anticoagulant dose was administered. The subsequent dose of the LMWH should not be given until 2
hours after the catheter is removed. [119]
NEURAXIAL BLOCKS
Patients with pain originating from below the thorax are amenable to spinal or epidural anesthesia, whereas those
with pain in or below are responsive to epidural analgesia. The use of epidural catheter techniques allows the
administration of opioids for postoperative pain. A patient scheduled for a leg amputation is a particularly good
candidate for an epidural catheter placement. A previous study showed that the use of epidural morphine before the
amputation decreased the incidence of phantom limb pain. This study, however, was not confirmed by a subsequent
[8]
study. Epidural catheter placement can also be used for a patient who has a leg amputated and who undergoes
[121]
daily dressing changes; the catheter can be dosed before each dressing change.
633
The decision on whether spinal or epidural anesthesia is to be employed depends on several issues. Spinal anesthesia
causes a more precipitous drop in blood pressure. Because unsuspected hypovolemia is frequent in trauma patients,
an epidural anesthetic may be preferable. A one-shot spinal or epidural procedure, rather than a catheter placement,
is recommended if anticoagulation with LMWH is planned in the postoperative period. If postoperative pain
management is planned, a continuous epidural technique is indicated.
INTRASPINAL OPIOIDS
The use of intraspinal opioids has revolutionized the management of postoperative and cancer pain. Increasingly, it
is being used for chronic pain secondary to noncancer conditions. The epidural technique is employed for
postoperative pain and trauma (i.e., fractured ribs), whereas the intrathecal approach is used for cancer via an
implanted pump.
Although almost all the opioids can be used for intraspinal injections, the most commonly used drugs are morphine,
hydromorphone, and fentanyl. The latency and duration of postoperative analgesia with the different epidural
opioids are summarized in Table 26–8 . Morphine can be given in intermittent injections, a technique
[122] [123] [124]
popularized by Ready and colleagues. In their 2-year experience with 11089 individual morphine injections in 1106
patients, they had no deaths, neurologic injuries, or infections. Nurses on the floor, however, are very reluctant to
[125]
inject drugs into an intraspinal catheter. The use of continuous morphine epidural infusions eliminates this problem.
They are as effective as intermittent injections and have minimal side effects. The epidural opioid infusion can be [126]
administered with or without patient-controlled epidural analgesia (PCEA). In PCEA, a basal continuous infusion of
the drug is given and the patient is allowed a demand dose of 2 to 5 mL of the drug every 15 to 30 minutes.
The selection of a particular opioid depends on several factors. Morphine is the least lipophilic opioid, and its use
has been advocated by several investigators. Its onset requires 20 to 30 minutes and it has an average duration of
[127]
18 hours. For the management of postoperative pain, morphine is recommended when the level of catheter insertion
is located at a distance from the vertebral level of surgery. Its use is ideal for cancer pain because of its prolonged
duration of action. Morphine recipients have a higher incidence of respiratory depression, urinary retention, and
pruritus. Hydromorphone has an onset of 10 to 15 minutes and a duration of 11 hours. The potency ratio of
hydromorphone to morphine is between 3:1 and 5:1. The continuous infusion of hydromorphone was found to be
associated with a lower incidence of side effects than morphine. [128]
Fentanyl is a highly lipophilic drug with an onset of 4 to 5 minutes and a duration of 3 to 5 hours. Its rapid onset
makes it ideal for the patient-controlled epidural anesthesia (PCEA) technique. Fentanyl undergoes rapid vascular [129]
absorption from the epidural space. Because of this and because of its high lipid solubility, it has low cerebrospinal
fluid (CSF) levels and limited cephalad migration. This results in a lower incidence of side effects. Rapid vascular [130]
and tissue uptake limit its anatomic spread, requiring that injection of the drug be close to the spinal level where the
pain originates for it to be effective. The high systemic levels of epidural fentanyl contribute to its analgesic effect.
In fact, some investigators have theorized that the predominant mechanism of the analgesic effect of
TABLE 26-8 -- DOSE RANGE FOR EPIDURAL OPIOID INFUSIONS

Solution
Drug (%) Bolus Dose Infusion Rate (hr) Breakthrough Bolus
Morphine 0.01 4–6 mg 0.1–0.8 mg 0.2–0.3 mg q 15 min
Hydromorphone
0.001 0.8–1 mg 0.15–0.3 mg 0.15–0.3 mg q 15 min
Meperidine 0.25 20–100 mg 5–20 mg
Fentanyl 0.001 0.5–1.5 µg/kg 0.5–1 µg/kg 10–15 µg q 15 min
Sufentanil 0.0001 0.3–0.7 µg/kg 0.15–0.3 µg/kg 5–7 µg q 15 min
Alfentanil 0.25 10–15 µg/kg 10–18 µg/kg 250 µg q 10 min
Reprinted from Wong HY, Benzon HT: Epidural opioid infusion. In Benzon HT, Raja SN, Borsook D, et al (eds): Essentials of Pain Medicine and Regional
epidural fentanyl is systemic in nature. This impression is supported by studies that showed that the epidural and
intravenous routes of opioid infusion produced the same levels of analgesia and similar plasma opioid
concentrations. Other studies, however, were more supportive of the epidural route.
[131] [132] [133]
One reason for the [134] [135] [136]
conflicting results is the placement of the epidural catheter. When the catheter is placed near the vertebral level of
surgery, it is more effective than an intravenous infusion. If placed at a distance from the vertebral level of surgery,
[135]
i.e., lumbar placement for a thoracotomy, then it is no more effective than an intravenous infusion. [133]
634
The addition of a local anesthetic to the opioid is generally recommended; laboratory studies have shown a
synergistic effect when both types of drugs were administered intrathecally. Clinical studies, however, were not
[137] [138]
uniform in their findings. Studies that compared the epidural opioid–local anesthetic combination with epidural local
anesthetic showed that this combination was significantly more effective. The advantages included
[139] [140] [141] [142] [143] [144]
better pain relief, increased duration of analgesia, and comparable analgesia with lower concentration of the local
anesthetic. Studies that compared the combination of epidural opioid–local anesthetic with epidural opioid alone
were not uniform in their results. Some studies showed some advantage with the combination, whereas other [145] [146] [147]
studies did not. In our practice, we usually add a local anesthetic. The analgesia is improved, and the
[148] [149] [150] [151] [152]
recovery of gastrointestinal motility is enhanced. We usually place epidural catheters at the low to midthoracic
levels to decrease the incidence of lower extremity numbness. The local anesthetic is removed from the infusion if
the patient has hypotension or numbness of the lower extremity.
The use of intraspinal opioids has been shown to decrease the hospital stay of patients having a gastroplasty, to [153]
lower the incidence of infection and major cardiorespiratory complications in high-risk patients, to decrease the [154]
stay in the intensive care unit, and to decrease the hospital stay of patients having thoracotomy. A study on
[87] [135]
patients who had abdominal surgery showed improved analgesia, but the length of hospital stay was the same. The
[155]
American Society of Regional Anesthesia issued a consensus statement on acute pain management in 1996. They
considered the benefits of improved perioperative analgesia to include improvement of pain control, reduction of
opioid requirements with diminished side effects, provision of preemptive analgesia, reduction in thromboembolic
complications, recovery of gastrointestinal function after intraabdominal surgery, preservation of immune function,
reduction in cardiovascular complications, inhibition of endocrine metabolic stress response, rehabilitation and
return of function, reduction in hospital costs, preservation of cognitive function, and prevention of chronic pain. [156]
REGIONAL ANESTHETIC TECHNIQUES
Both peripheral and neuraxial blocks avoid the systemic effects of opioids. In contradistinction to neuraxial blocks,
hypotension and interference with bowel and bowel functions are not consequences of peripheral nerve blocks. Also,
the sensory and motor blockades are unilateral. Ambulation, early mobilization, and assessment of limb function are
easier to achieve with peripheral nerve blocks.
Several regional anesthesia techniques can be done in the emergency room. These techniques can decrease the
amount of analgesics required by the patient. Infiltration of an intermediate or long-acting local anesthetic into a
wound can give pain relief that lasts several hours. Suturing of lacerations can be performed under infiltration local
anesthesia. A field block extends the area of anesthesia to a wider area; the addition of epinephrine to the local
anesthetic prolongs the duration of anesthesia. The irrigation of wounds with local anesthetic solutions can be
performed with a catheter left in place under the skin. Digital nerve blocks of the toes and fingers are easy to
[157]
perform. The addition of epinephrine to the local anesthetic in digital blocks is not recommended because the injury
is close to the terminal capillary system. Other blocks that can be performed in the emergency room if expert help is
available include ankle blocks and similar simple peripheral nerve blocks.
UPPER EXTREMITY BLOCKS
The typical use of regional anesthesia for trauma patients is in surgery on the extremities. [158]
Techniques for these
blocks are not described in this section. They have been described in several textbooks [159] [160] [161]
and in separate
chapters of this book.
The different techniques of brachial plexus blockade have their own indications, advantages and disadvantages
( Table 26–9 ). The choice of technique depends on the site of surgery. Operations on the elbow, such as closed
[162] [163]
or open reduction of the joint, skin graft, or ulnar transposition, are best done via the infraclavicular or
supraclavicular approach. Surgery on the forearm region requires blockade of the musculocutaneous nerve on the
[163]
lateral aspect, the median nerve, the ulnar nerve on the anteromedial aspect, the posterior nerve, and the medial
cutaneous nerve of the forearm. All of these nerves are branches of the brachial plexus formed by the C5–T1 nerve
roots, and the infraclavicular approach is the technique of choice. The interscalene, supraclavicular, or
[163]
infraclavicular approaches
635
TABLE 26-9 -- TECHNIQUES OF BRACHIAL PLEXUS BLOCKADE

Technique Areas of Anesthesia Advantages Disadvantages
Axillary Hand, forearm, elbow Simple, easy landmarks, minimal May miss musculocutaneous nerve;
complications arm needs to be abducted
Interscalene Shoulder, arm, elbow, forearm and Blocks upper brachial plexus (shoulder) May miss ulnar nerve
hand
Subclavian perivascular Entire arm except shoulder Blocks entire brachial plexus Pneumothorax risk
Infraclavicular Entire arm except shoulder Ideal for catheter technique Painful (classic technique)
From Molloy RE: Axillary brachial plexus block. In Benzon HT, Raja SN, Borsook D, et al (eds): Essentials of Pain Medicine and Regional Anesthesia. New York,
Churchill Livingstone, 1999, p 399.
can be used for surgery on the lateral aspect of the forearm, whereas the axillary approach can be employed for
surgery on the medial aspect of the forearm. For surgery of the wrist and hand, the interscalene and supraclavicular
approaches are recommended when the site of surgery is at the base of the thumb. The axillary approach is ideal for
median nerve decompression, surgery of the ulnar aspect of the wrist, or surgery of the hand and digits. The [163]
musculocutaneous nerve may have to be separately blocked if the axillary approach is used.
For trauma patients, it is recommended that one of the long-acting agents—bupivacaine, ropivacaine, or
levobupivacaine—be used so that the residual analgesia is used for the control of postoperative pain. Volumes for
the different approaches to brachial plexus blockade range from 25 to 40 mL of local anesthetic. The dose of the
local anesthetic can be decreased and the success rate of the axillary block improved with multiple injection
techniques. [164] [165] [166] [167]
The classic technique of supraclavicular block is associated with a small incidence of pneumothorax, which is
significantly lower with the plumb-bob technique. Interscalene block is associated with blockade of the phrenic
[168]
nerve. Its use is contraindicated in the trauma patient with pneumothorax, rib fractures or when there is
[169]
accompanying respiratory difficulty. Spinal or epidural block and block of the recurrent laryngeal nerve or the
stellate ganglion are possible consequences of the interscalene approach. These consequences are not seen with the
infraclavicular or axillary approaches. The classic infraclavicular technique is painful, because the needle has to [170]
penetrate the pectoral muscles. The Sims approach to infraclavicular block is less painful because the site of needle
insertion bypasses the pectoralis muscles. The needle is inserted into the groove between the coracoid process of the
scapula and the inferior border of the clavicle. This insertion site is closer to the brachial plexus than the one used
[171]
with the classic infraclavicular approach.
Upper extremity blocks offer some advantages over general anesthesia. The use of interscalene blocks for shoulder
surgery has been shown to reduce blood loss, to minimize patient's stay in the recovery room, and to decrease the
number of admissions for pain and nausea and vomiting. Suprascapular nerve blocks reduce morphine[172] [173]
consumption, decrease the incidence of nausea, and reduce the duration of hospital stay after arthroscopic shoulder
surgery. [174]
LOWER EXTREMITY BLOCKS
Peripheral nerve blocks are employed to provide analgesia in patients with lower extremity trauma. Blockade of the
femoral nerve is performed to provide pain relief and abolish muscle spasm in patients with fracture of the shaft of
the femur. A lumbar plexus block or a combination of femoral, lateral femoral cutaneous, and obturator nerve
[175]
blocks can be useful for surgery on the proximal femur and the femoral neck. A combined lumbar plexus block [176]
and sciatic nerve block provide anesthesia for surgery in the knee and for amputations.
[177]
A sciatic–femoral [177] [178]
nerve block or a popliteal saphenous nerve block provides anesthesia to the foot. It is important to keep in mind the
total dose of the local anesthetic when a combination of peripheral nerve blocks is performed.
The combination of several blocks for lower extremity surgery may result in high plasma levels of the local
anesthetic. In two studies, 680 mg lidocaine were used for combined lumbosacral and sciatic nerve blocks, and [179]
650 mg of lidocaine were used for combined “3-in-1” and sciatic blocks. All but one patient had plasma levels that [180]
were considered safe in one study, whereas no patient approached toxic levels in the other study. None of the
[179] [180]
patients showed signs of systemic toxicity. In spite of the results of these studies, the total dose administered should
be kept in mind and signs of systemic toxicity should be checked.
Multiple injection techniques have been used to improve the success rate, to shorten the latency of the block, and to
decrease the dose of the local anesthetic. A faster onset and a more complete sensory blockade of the sciatic nerve
have been noted when the tibial and common peroneal nerves were separately blocked. The same findings were [181]
noted after a popliteal nerve block. Multiple injections of the femoral nerve (i.e., injection after elicitation of
[182]
636
contraction of the vastus medialis, vastus intermedius, and vastus lateralis) shortened the onset time and improved
the quality of the block with smaller amounts of the local anesthetic. [183]
The combination of a lumbar plexus block and general anesthesia for total hip arthroplasty resulted in lower
intraoperative analgesic use and decreased blood loss. Sciatic–femoral nerve block, in addition to general
[184]
anesthesia, was found to be more effective than spinal/general anesthesia for total knee arthroplasty. Patients who [185]
had the block had lower postoperative pain scores and lower morphine intake for the first 24 hours. In addition,
these patients had no bowel or bladder problems. Increasingly, lower extremity blocks are being used not only for
surgical anesthesia but also to provide postoperative pain relief. Lateral femoral cutaneous nerve blocks have been
employed to provide analgesia after surgery of the femoral neck. Femoral or femoral–sciatic nerve blocks improve
[186]
analgesia with lower opioid usage after total knee arthroplasty. [187]
PCA techniques that employ a basal infusion of the local anesthetic plus PCA doses or PCA boluses only are as
effective as continuous infusion of the local anesthetic. In addition, the amount of local anesthetic consumed is
[188]
less. Continuous sciatic nerve blocks after amputations provide effective postoperative analgesia and no incidence of
phantom limb pain. Finally, the popliteal sciatic nerve blocks after foot or ankle surgery have reduced
[189]
postoperative pain, with patients requiring only hydrocodone after surgery. [190]
USE OF A NERVE STIMULATOR
The use of a nerve stimulator is recommended, especially in situations in which the surrounding anatomy is not
consistent relative to the target nerve location or when patient cooperation may not be present. A nerve stimulator [191]
is useful in trauma patients who cannot cooperate because of head injury or because of the effects of alcohol or
drugs, because the use of a nerve stimulator requires little or no patient cooperation. Because painless muscle
contraction is the end point, there is less pain when a nerve stimulator is used compared with paresthesia. Finally,
the possibility of nerve damage is less because the needle does not contact the nerve. Although sedation is generally
recommended, sedation of the trauma patient with a full stomach should be light or omitted.
The negative (cathode) electrode is connected to the exploring needle, and the positive (anode) electrode is
connected to the ground lead. The stimulating current is set between 1 and 2 mA and the needle is advanced until the
maximal motor response is elicited. The stimulating current is then decreased to elicit a motor response with the
smallest possible amount of current. The needle is considered to be close to the nerve when the stimulating current is
greater than 1 mA. The proximity of the tip of the needle to the nerve is confirmed when an injection of 1 to 2 mL
[190]
of local anesthetic causes an immediate cessation of the elicited motor response.
The smallest stimulating current that is acceptable before injection of the local anesthetic was the subject of
discussion. Although Vloka and associates recommended injection of the local anesthetic only when the
[192] [193]
stimulating current that elicits the motor response is less than 0.4 mA or 0.5 mA, other investigators accepted
[192] [194] [195]
higher stimulating currents. Benzon et al used 0.3 to 0.8 mA, Bridenbaugh and Crews used 0.5 mA, Magora and
[193] [196]
associates use 0.5 mA, Shannon and colleagues used 0.6 mA, Rigler 0.2 to 1.5 mA, and Rongstad and
[197] [198] [199]
coworkers used between 0.5 and 1 mA. An intraneural injection may occur with stimulating currents less than 0.5
[190]
mA. In fact, paresthesias have been noted with stimulating currents less than 1 mA.
[190] [193] [200]
CONTINUOUS TECHNIQUES
Continuous peripheral nerve blocks allow the maintenance of analgesia either by repeated injections or by
continuous infusion of local anesthetics. Most of the studies on the use of this technique are in the postoperative
setting rather than in the setting of trauma. The advantages of this technique in trauma, however, are quite obvious.
With a catheter in place, the duration of the analgesia or anesthesia can be extended, and the concentration of the
local anesthetic can be changed to provide sympathetic block, sensory block, or motor block with muscle relaxation,
as desired.
Winnie popularized the concept of a fascial covering of the brachial plexus from its roots emerging from the
intervertebral foramina to the level of nerves at the axilla. He equated a continuous axillary brachial block to a
continuous caudal block, a continuous subclavian perivascular block to a continuous lumbar epidural block, and a
continuous interscalene block to a continuous thoracic or cervical epidural block. As previously stated, this [201]
chapter does not go into the details of the techniques but rather provides only general comments.
Placement of a catheter in the axilla is easy and free of serious complications. However, axillary catheters have the
highest rate of accidental displacement secondary to movement of the upper extremity, and suturing may be required.
The presence of moisture and hair in the axilla makes it difficult to maintain a sterile environment, and infections are
637
possible. In one study, however, axillary catheters were left in place for a mean of 11.5 days, and cultures of the
catheter tips were positive only in those that were left in place longer than 4 days. None had signs or symptoms of
[202]
local or systemic infection.
An infraclavicular catheter is less likely to be dislodged, and catheters have been left in place for 3 weeks. The [203]
infraclavicular technique is ideal for patients who cannot abduct the upper arm. A subclavian perivascular catheter
also moves very little with movements of the head and neck because it lies flat against the patient's neck. Blockade
of the brachial plexus at this level involves the trunks and can be achieved with a smaller volume of local anesthetic.
Possible complications of the subclavian perivascular technique include pneumothorax and injection into the
vertebral artery. Interscalene catheters are difficult to immobilize and easily dislodged by movements of the head
and neck because the catheter emerges from the skin at a right angle to the head and neck. Suturing the catheter
[201]
has been recommended. Hemidiaphragmatic paralysis is common with this technique.

[204]
The local anesthetic can be administered continuously, or injections may be given intermittently. There appears to
be no difference in the sensory or motor blockade characteristics between these two techniques, although higher
plasma concentrations were noted with continuous infusion. Bupivacaine is the most commonly used local
[205]
anesthetic, and the 0.25% concentration is the most commonly used concentration. The use of 0.125% concentration
is recommended when assessment of motor function is required. Winnie discouraged the use of adjuvants such as
bicarbonate or alpha-agonists because these adjuncts only complicate the pharmacologic management of the trauma
patient.
[201]
Continuous plexus blocks of the lower extremity can be achieved with the inguinal paravascular lumbar plexus
block, “3-in-1” block, lumbosacral plexus block, psoas compartment block, and continuous sciatic nerve block.
With the 3-in-1 block, the “intracath technique” is recommended. With this technique, a catheter can be inserted
[201]
through the initial catheter and inserted as far as desired. Contraction of the quadriceps muscles from the nerve
stimulator is seen with the 3-in-1 block. In patients with fracture of the femur, this painful muscle contraction should
be minimized during the nerve stimulation. Studies have shown that the efficacy of the continuous lumbar plexus
block via the 3-in-1 technique is as effective as continuous epidural morphine, with less incidence of pruritus,
[206] [207]
nausea, vomiting, and urinary retention. The use of 0.125% bupivacaine appears to be as effective as 0.25%
[207]
bupivacaine. Blockade of the lumbar plexus, however, does not provide analgesia to areas innervated by the
[208]
sciatic nerve.
Continuous lumbosacral plexus block has been achieved with the use of a Tuohy needle and an epidural catheter. [209]
A continuous sciatic nerve block has been described, whereby the catheter is placed near the sciatic nerve after its
exit from the greater sciatic foramen. A combination of the continuous parasacral sciatic nerve block and the
[210]
lumbar plexus block has also been described. There is less experience with these techniques compared with the “3-
[211]
in-1” approach to the lumbar plexus.
PEDIATRIC REGIONAL ANESTHESIA
As is the case of regional anesthesia for adults, most of the publications on pediatric regional anesthesia have dealt
with surgery and management of postoperative pain. This chapter deals with general principles and not the details of
the technique. Nerve blocks for pediatric trauma should be performed on awake, unsedated patients. They should be
limited to blocks of the extremities and should be performed on children who can communicate. A paresthesia [212]
should not be sought; rather, a nerve stimulator should be used. Broadman and Glass recommended the application
[212]
of EMLA cream 1 hour before the block or before the insertion of the intravenous catheter for Bier block. To avoid
overdose, the weight of the child should be known before the block is performed, and the appropriate dose of the
local anesthetic in milligram per kilogram should be calculated. If the block is used for surgery, some sort of
diversion is advocated during the operation. These diversions may include the use of headphones or conversation
about topics of interest to the child. If the block is not completely effective, heavy sedation is contraindicated.
Instead, general anesthesia with rapid sequence induction should be performed.
The use of Bier blocks is confined to the extremity and employed for the management of simple operations,
fractures, and dislocations. Exsanguination can be achieved by the use of an Esmarch bandage or by elevation
[213] [214] [215]
of the patient's arm for 3 minutes. Lidocaine 0.5% is the local anesthetic of choice; the dose is 3 mg/kg. The cuff is
not deflated until after 20 minutes have elapsed.
Upper extremity blocks are used for repair of lacerations, reduction of fractures, or other surgeries of the upper
extremity. The approach selected to block the brachial plexus depends on the site of surgery, as outlined in the
section of regional nerve blocks for adults. The performance of an axillary block has been shown to decrease the
incidence of postoperative nausea and vomiting and to reduce opioid usage after the surgery. For the performance [216]
638
of axillary block in children, Dalens recommended perpendicular insertion of the needle at the point where the
[217]
pectoralis muscle crosses the coracobrachialis muscle. The parascalene approach, as described by Dalens and
colleagues, appears to offer some advantages over the interscalene approach. It is easier to perform, blocks the
[218]
lower branches of the cervical plexus, and produces less incidence of Horner's syndrome. Doses for brachial plexus
block are 0.33 mL of local anesthetic per kg of weight, 0.7 to 1 mg/kg for prilocaine, and 0.6 mg/kg for
bupivacaine. [212]
Lower extremity nerve blocks include the sciatic nerve block, the 3-in-1 block, the lumbar plexus block, and the
fascia iliaca block. There are several approaches to sciatic nerve block in children. Of these, the posterior approach[219]
is not ideal for trauma patients because of the positioning required for performance of the block. Regardless of the
approach used, a nerve stimulator is recommended.
As in adults, the femoral nerve block is ideal for patients with fractures of the shaft of the femur. A continuous [220]
catheter technique has been described in children. The dose is 0.25 to 0.3 mL/kg of local anesthetic. To achieve a
[221]
3-in-1 block, a dose of 0.5 mg/kg of local anesthetic is recommended. The fascia iliaca technique blocks the femoral,
lateral femoral cutaneous, and obturator nerves with one injection. Paresthesia or nerve stimulation is not required in
the fascia iliaca block.
The approaches to lumbar plexus blockade include the techniques of Chayen and Winnie. The dose is 0.75 mL of
local anesthetic/kg, with a maximum volume of 25 mL. There is a fairly high incidence of epidural blockade with
the techniques of Chayen and associates. The technique of Winnie and colleagues is easier to perform, and there is
[222]
ipsilateral blockade of the lumbar and sacral plexuses without epidural spread. [223]
Caudal and epidural blocks can be used to provide anesthesia and analgesia of the lower abdomen and the lower
extremities. Broadman and Glass advised against the use of these blocks in trauma patients with injuries in the
[212]
lower back, skin damage over the sacral hiatus, or hemodynamic instability. Most anesthesiologists place the caudal
block after the child is asleep and before the start of the surgery. A 22-G or 23-G B-bevel needle is recommended
[224]
by Broadman and Glass. The dose is 0.75 to 1.0 mL/kg of local anesthetic or a volume of 0.75 mL/kg. The
[212] [225]
addition of epinephrine to bupivacaine is not recommended because of reports of cardiac dysrhythmias. The [226] [227]
addition of fentanyl, 1 to 2 µg/kg, or morphine, 70 to 100µg/kg, allows the use of more dilute concentrations of the
local anesthetic and prolongs the duration of analgesia. As in adults, a continuous catheter technique can be
[228]
employed. The catheter can be threaded from the sacral hiatus to the thoracic vertebral level. [229] [230]
THORACIC TRAUMA
Trauma to the chest is a significant cause of morbidity and mortality. The pathophysiologic sequelae of multiple rib
fractures, especially with flail chest, are pain and hypoxia. Hypoxia results from the ventilation and perfusion
mismatch in the underlying contused lung. Uncontrolled pain can result in splinting and muscle spasms, which lead
to decreased ventilation and atelectasis. The compromise in pulmonary function causes hypoxemia, an increase in
shunt fraction, or infection.
The treatment of flail chest has changed from the initial technique of external traction and stabilization. Avery and
associates demonstrated decreased incidence of morbidity and mortality with hyperventilation and intermittent
[231]
positive pressure ventilation. Mechanical ventilation was associated with a high incidence of infection and
mortality. In 1975, Trinkle and coworkers managed flail chest with spontaneous ventilation and treated the
[232] [233]
underlying pulmonary contusion. Analgesia was provided by intravenous morphine and intercostal nerve blocks.
These analgesic techniques are not without side effects and risks. Systemic narcotics may cause respiratory
depression or diminished consciousness, resulting in the patient's inability to cough or cooperate with physiotherapy.
There is a risk of pneumothorax when intercostal nerve blocks are repeated frequently.
The use of epidural local anesthetics has been advocated by other investigators. Dittmann and associates
[234] [235] [236] [236]
showed the effectiveness of thoracic epidural local anesthetics in the management of multiple fractured ribs. They
reserved the epidural anesthetic infusion, without mechanical ventilation, for patients who were conscious and
cooperative, whose vital capacities were greater than 15 mL/kg, and for those whose alveolar oxygen pressures were
greater than 60 mm Hg breathing room air. The disadvantage of epidural local anesthetic infusions is that the patient
may develop tachyphylaxis after 24 to 48 hours of use, resulting in its abandonment. [237]
In 1979, Behar and associates used morphine to treat pain after surgery, trauma, and chronic conditions. This was
[238]
followed by numerous reports of the efficacy of epidural opioids for postoperative analgesia, including [87] [153] [154]
procedures after thoracic surgery. In 1980, Johnston and McCaughey reported the use of epidural morphine
[135] [136] [239] [240]
639
as a method of management of multiple rib fractures. Four years later, Rankin and Comber [237]
reported on combined
epidural morphine and bupivacaine.
Two studies showed the effectiveness of epidural opioids in patients with multiple rib fractures. In a prospective
study, Ullman and colleagues showed the superiority of thoracic epidural morphine infusion over intravenous
[241]
injections of morphine. The epidural infusion consisted of 70 µg/mL morphine at 8 to 10 mL/hour, whereas the
intravenous morphine was given at 1 to 1.5 mg doses every 3 to 4 hours as necessary. The patients who had the
epidural morphine infusion had less ventilator-dependent time (3.07±1.35 d vs. 18.23±8.12 d), less time in the
intensive care unit (5.93±1.44 d vs. 18.69±5.25 d) and a shorter hospital stay (14.85±2.21 d vs. 47.69±14.67 d) than
the patients who were given intravenous morphine. Also, the patients who had the epidural morphine infusion had a
lower incidence of tracheostomy (6.7%±6.7% vs. 38.5%±14%).
Another study compared intravenous patient-controlled analgesia (PCA) with thoracic epidural analgesia in thoracic
trauma. The patients on intravenous PCA had a loading dose of 0.1 mg/kg before the PCA was established. The
[242]
PCA regimen consisted of a demand dose of 2 mg and a lockout interval of 10 minutes. There was no background
infusion. In the epidural group, fentanyl 50 µg and morphine 3 mg were injected after a negative test dose. This was
followed by a continuous infusion of bupivacaine 0.25% and morphine 0.005% at a rate of 4 to 6 mg per hour. The
use of epidural analgesia resulted in significantly lower verbal rating scores on days 1 and 3, significantly greater
maximal inspiratory force and tidal volumes on day 3, and lower plasma levels of interleukin (IL)-8 on days 2 and 3.
IL-8 or neutrophil-activating peptide-1 is a neutrophil and lymphocyte chemoattractant and activator implicated in
acute lung injury. The authors theorized that reduced levels of IL-8 might decrease infectious or inflammatory
complications in the trauma patient. [242]
Summary
Trauma activates neurohumoral and physiologic processes, resulting in increased catecholamine and antidiuretic
hormone levels, a hypercoagulable state, and activation of the sympathetic nervous system. The management of pain
in trauma starts on site in the emergency room and continues in the operating room, in the intensive care unit, and
during the postoperative period. Regional anesthesia offers several advantages in the management of pain in trauma
patients. It avoids the risks associated with general anesthesia and confines the anesthesia to the affected extremity
or extremities. Regional anesthesia can be used in the management of postoperative pain. In trauma patients who do
not need surgery, regional anesthesia can be used as an adjunct for pain management to reduce the dose of opioids.
In patients with thoracic trauma, the use of epidural analgesia improves pain management, decreases hypoxemia,
and facilitates recovery.
REFERENCES
1. Hedderich R, Ness TJ: Analgesia for trauma and burns. Crit Care Clin 15:167, 1999.
2. Patel N, Smith CE: Pain management in trauma. Anesthesiol Clin North Am 17:295, 1999.
3. Kehlet H: Surgical stress: The role of pain and analgesia. Br J Anaesth 63:189, 1989.
4. Kehlet H: The surgical stress response: Should it be prevented? Can J Surg 34:565, 1991.
5. Calixto JB, Cabrini DA, Ferreira J, Campos MM: Kinins in pain and inflammation. Pain 87:1, 2000.
6. Whipple J, Lewis K, Quebbeman E, et al: Analysis of pain management in critically ill patients. Pharmacotherapy 15:592, 1995.
7. Choiniere M, Melzack R, Girard N, et al: Comparisons between patients' and nurses' assessment of pain and medication efficacy in severe burn
injuries. Pain 40:143, 1990.
8. BachS, Noreng M, Tjellden N: Phantom limb pain in amputees during the first 12 months following limb amputation, after preoperative lumbar
epidural blockade. Pain 33:297, 1988.
9. Chambers JA, Guly HR: The need for better prehospital analgesia. Arch Emerg Med 10:187, 1993.
10. Reichl M, Bodiwala GG: Use of analgesia in severe pain in the accident and emergency department. Arch Emerg Med 4:25, 1987.
11. Zolitie N, Cust MP: Analgesia in the acute abdomen. Ann R Coll Surg Engl 68:209, 1986.
12. Dempster E: Pain relief in accident and emergency? Accid Emerg Nurs 3:3, 1995.
13. Teske K, Daut R, Cleeland C: Relationships between nurses' observations and patient's self reports of pain. Pain 16:289, 1983.
640
14. BieriD, Reeve RA, Champion GD, et al: The facies pain scale for the self-assessment of pain experienced by children: Development, initial
validation, and preliminary investigation for ratio scale properties. Pain 41:139, 1990.
15. Grunau RVE, Craig KD: Facial activity as a measure of neonatal expression. In Tyler DC, Krane EJ (eds): Advances in Pain Research and
Therapy, vol. 15. New York, Raven Press, 1990, p 147.
16. Hill
LL, Pearl RG: Pain management and sedation in the intensive care unit. In Rosenberg AD, Grande CM, Bernstein RL (eds): Pain
Management and Regional Anesthesia in Trauma. WB Saunders, 1999, p 137.
17. Chernick
D, Gillings D, Laine H, et al: Validity and reliability of the observer's assessment of alertness/sedation scale: Study with intravenous
midazolam. J Clin Psychophamacol 10:244, 1990.
18. American Pain Society: Principles of analgesic use in the treatment of acute pain and cancer pain, 4th ed. Glenview, Ill, American Pain Society,
1999.
19. Willer
J, De Boucker T, Bussel B: Central analgesic effects of ketoprofen in humans: Electrophysiological evidence for a supraspinal
mechanism in a double-blind and cross-over study. Pain 8:1346, 1989.
20. Carlsson K, Monzel W, Juma I: Depression by morphine and the nonopioid analgesic agents metamizol (dipyrone), lysine acetylsalicylate and
paracetamol, of activity in rat thalamus neurons evoked by electrical stimulation of nociceptive afferents. Pain 32:313, 1988.
21. Taiwo Y, Levine J: Prostaglandins inhibit endogenous pain control mechanisms by blocking transmission at spinal noradrenergic synapses. J
Neurosci 8:1346, 1988.
22. Fabri
A, Cruccu G, Sperti P, et al: Piroxicam-induced analgesia: Evidence for a central component which is not opioid mediated. Experientia
48:1139, 1992.
23. Catania
A, Arnold J, Macaluso A, et al: Inhibition of acute inflammation in the periphery by central action of salicylates. Proc Natl Acad Sci U
S A 88:8544, 1991.
24. Hylek EM, Heiman H, Skates SJ, et al. Acetaminophen and other risk factors for excessive warfarin anticoagulation. JAMA 279:657, 1998.
25. Whitcomb DC, Block GD: Association of acetaminophen hepatoxicity with fasting and ethanol use. JAMA 272:1845, 1994.
26. Zimmerman HJ, Maddrey WC: Acetaminophen (paracetamol) hepatoxicity with regular intake of ethanol: Analysis of instances of therapeutic
misadventure. Hepatology 22:767, 1995.
27. Day RO, Graham GG, Williams KM, et al: Clinical pharmacology of nonsteroidal antiinflammatory drugs. Pharmacol Ther 33:384, 1987.
28. Dukes
M, Lunde I: The regulatory control of nonsteroidal antiinflammatorydrug preparations within individual rheumatology practices. J
Rheumatol 16:1253, 1989.
29. Stein C: The control of pain in peripheral tissues by opioids. N Engl J Med 332;1685, 1995.
30. Sibinga NES, Goldstein A: Opioid peptides and opioid receptors in cells of the immune system. Ann Rev Immunol 6:219, 1988.
31. Stein C, Comise K, Haimerl E, et al: Analgesic effect of intra-articular morphine after arthroscopic knee surgery. N Engl J Med 325:1123,
1991.
32. Rosow CE, Moss J, Philbin DM, Savarese JJ: Histamine release during morphine and fentanyl anesthesia. Anesthesiology 56:93, 1982.
33. Bovil
J, Sebel P, Stanley T: Opioid analgesics in anesthesia: With special reference to their use in cardiovascular anesthesia. Anesthesiology
61:731, 1984.
34. Reitan
JA, Stengert KB, Wymore ML, et al: Central vagal control of fentanyl induced bradycardia during halothane anesthesia. Anesth Analg
57:31, 1978.
35. Freye RE: Cardiovascular effects of high dosages of fentanyl, meperidine, and naloxone in dogs. Anesth Analg 53:40, 1974.
36. Austin
KI, Stapleton JV, Mather LE: Multiple intramuscular injections: A major source of variability in analgesic response to meperidine. Pain
8:47, 1980.
37. Austin KI, Stapleton JV, Mather LA: Relationship between blood meperidine concentrations and analgesic response. Anesthesiology 53:460,
1980.
38. Edwards WT, Breed RJ: Treatment of postoperative pain in the postanesthesia care unit. Anesthesiol Clin N Am 8:235, 1990.
39. Benzon HT: Postsurgical pain. In Raj PP (ed): Pain Medicine. A Comprehensive Review. St. Louis, Mosby–Year Book, 1996, p 359.
40. Sherwood ER, Benzon HT: Patient-controlled analgesia. In Benzon HT, Raja SN, Borsook D, et al (eds): Essentials of Pain Medicine and
641
Regional Anesthesia. New York, Churchill Livingstone, 1999, p 147.
41. Graves DA, Foster TS, Batenhorst RL, et al. Patient-controlled analgesia. Ann Intern Med 99:360, 1983.
42. White PF: Patient-controlled analgesia: A new approach to the management of postoperative pain. Sem Anesth 4:255, 1985.
43. Sinatra
R, Chung KS, Silverman DG, et al: An evaluation of morphine and oxymorphone administered via patient-controlled analgesia (PCA)
or PCA plus basal infusion in postcesarian-delivery patients. Anesthesiology 71:502, 1989.
44. ParkerRK, Holtmann B, White PF: Effects of a nighttime opioid infusion with PCA therapy on patient comfort and analgesic requirements
after abdominal hysterectomy. Anesthesiology 76:362, 1992.
45. Kaiko RF, Foley KM, Grabinski PY, et al: Central nervous system excitatory effects of meperidine in cancer patients. Ann Neurol 13:180,
1983.
46. Tang R, Shimomura SK, Rotblatt M: Meperidine-induced seizures in sickle cell patients. Hosp Formulary 15:764, 1980.
47. BrowneB, Linter S: Monoamine oxidase inhibitors and narcotic analgesics: A critical review of the implications for treatment. Br J Psychiatr
151:210, 1987.
48. Donner B, Zenz M, Tryba M, et al: Direct conversion from oral morphine to transdermal fentanyl: A multicenter study in patients with cancer
pain. Pain 64:527, 1996.
49. Portenoy RK, Dsoutham MA, Gupta SK, et al: Transdermal fentanyl for cancer pain. Repeated dose pharmacokinetics. Anesthesiology 78:36,
1993.
50. Harrison
P: Transdermal fentanyl. In Benzon HT, Raja SN, Borsook D, et al (eds): Essentials of Pain Medicine and Regional Anesthesia. New
York, Churchill Livingstone, 1999, p 55.
51. Rauck R, Ruoff G, Mcmillen J: Comparison of tramadol and acetaminophen with codeine for long term pain management in elderly patients.
Curr Ther Res 55:1417, 1994.
52. Jensen EM, Ginsberg F: Tramadol versus dextropropoxyphene in the treatment of osteoarthritis. Drug Geriatr Invest 8:211, 1994.
53. Dalgin DH: Use of tramadol in chronic pain. Clin Geriatr 3:17, 1995.
54. Taub A: Relief of postherpetic neuralgia with psychotropic drugs. J Neurosurg 39:235, 1973.
55. Watson CPN, Evans RJ, Reed K, et al: Amitriptyline versus placebo in postherpetic neuralgia. Neurology 32:671, 1982.
56. Max MB, Schafer SC, Culname M, et al: Amitriptyline but not lorazepam relieves postherpetic neuralgia. 38:1427, 1988.
57. Kishore-Kumar R, Max MB, Schafer SC, et al: Desipramine relieves postherpetic neuralgia. Clin Pharmacol Ther 47:305, 1990.
58. Watson CPN, Vernich L, Chipman M, et al: Amitriptyline versus nortriptyline in postherpetic neuralgia. Neurology 51:1166, 1998.
59. Watson CPN, Evans RJ: A comparative trial of amitriptyline and zimelidine in postherpetic neuralgia. Pain 23:671, 1985.
60. Watson CPN: The treatment of neuropathic pain: Antidepressants and opioids. Clin J Pain 16:S49, 2000.
61. MaxMB, Culname M, Schafer S, et al: Amitriptyline relieves diabetic neuropathy in patients with normal or depressed mood. Neurology
37:589, 1987.
62. Kvinesdal B, Molin J, Frolan A, Gram LF: Imipramine treatment of painful diabetic neuropathy. JAMA 251:1727, 1984.
63. Sindrup
SH, Gram LF, Skjold T, et al: Concentration-response relationship in imipramine treatment of diabetic neuropathy symptoms. Clin
Pharmacol Ther 47:509, 1990.
64. Turkington RW: Depression masquerading as diabetic neuropathy. JAMA 243:1147, 1980.
65. Morello CM, Lechband SG, Stoner CP, et al: Randomized double-blind trial of gabapentin with amitriptyline in diabetic peripheral neuropathy
pain. Arch Intern Med 59:1931, 1999.
66. Max MB, Kishore-Kumar R, Schafer SC, et al: Efficacy of desipramine in painful diabetic neuropathy: A placebo-controlled trial. Pain 45:3,
1991.
67. Sindrup
SH, Gram LF, Brosen K, et al: The selective serotonin reuptake inhibitor paroxitine is effective in the treatment of diabetic neuropathy
symptoms. Pain 42:135, 1990.
68. Borsook
D, Fishman SM: Psychotropic drugs used in pain treatment. In Benzon HT, Raja SN, Borsook D, et al (eds): Essentials of Pain
Medicine and Regional Anesthesia. New York, Churchill Livingstone, 1999, p 63.
642
69. Backonja MM: Anticonvulsants (antineuropathics) for neuropathic pain syndromes. Clin J Pain 16:S67, 2000.
70. TanelianDL, Cousins MJ: Combined neurogenic and nociceptive pain in a patient with Pancoast tumor managed by epidural hydromorphone
and oral carbamazepine. Pain 36:85, 1989.
71. Blom S: Trigeminal neuralgia: Its treatment with a new anticonvulsant drug. Lancet 1:839, 1962.
72. Campbell FG, Graham JG, Zikha KJ: Clinical trial of carbamazepine (Tegretol) in trigeminal neuralgia. J Neurol Neurosurg Psychiatry 29:265,
1966.
73. Nicol C: A four-year double-blind randomized study of Tegretol in facial pain. Headache 9:54, 1969.
74. Rull
JA, Quibrera R, Gonzalez-Milan H, et al: Symptomatic treatment of peripheral diabetic neuropathy with carbamazepine: Double-blind
crossover study. Diabetologia 5:215, 1969.
75. Rowbotham M, Harden N, Stacey B, et al: Gabapentin for the treatment of postherpetic neuralgia: A randomized clinical trial JAMA 280:1837,
1998.
76. Backonja M, Beydoun A, Edwards KR, et al. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes
mellitus. A randomized clinical trial. JAMA 280:1831, 1998.
77. To-NhuHV, Borsook D: Membrane stabilizers. In Benzon HT, Raja SN, Borsook D, et al (eds): Essentials of Pain Medicine and Regional
78. Mao J, Chen LL: Systemic lidocaine for neuropathic pain relief. Pain 87:7, 2000.
79. Garaj NM, Giesecke AH: Pain management in the operating room: Regional anesthesia for operative intervention and to augment general
anesthesia. In Rosenberg AD, Grande CM, Bernstein RI (eds): Pain Management and Regional Anesthesia in Trauma, New York, WB Saunders,
1999, p 131.
80. Chung F, Meier R, Lautenschlager E, et al: General or spinal anaesthesia: Which is better in the elderly? Anesthesiology 67:422, 1987.
81. Liu S, Carpenter RL, Neal JM: Epidural anesthesia and analgesia. Their role in postoperative outcome. Anesthesiology 82:1474, 1995.
82. BloombergSG: Long-term home self-treatment with high thoracic epidural anesthesia in patients with severe coronary artery disease. Anesth
Analg 79:413, 1994.
83. Flatley KA, DeFily DV, Thomas JX: Effects of cardiac sympathetic nerve stimulation during adrenergic blockade on infarct size. J Cardiovasc
Pharmacol 7:673, 1985.
84. Mangano DT, Layug EL, Wallace A: Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. N Engl J Med
335:1713, 1996.
85. Liu
SS, Benzon HT: Outcomes and complications of acute pain management. In Raj PP (ed): Practical Management of Pain, 2nd ed. St. Louis,
Mosby, 2000, p 871.
86. Collins GJ, Barber JA, Zajtchuk R, et al: The effects of operative stress on the coagulation profile. Am J Surg 133:612, 1977.
87. TumanKJ, McCarthy RJ, March RJ: Effects of epidural anesthesia and analgesia on coagulation and outcome after major vascular surgery.
88. Rosenfeld BA, Beattie C, Christopherson R: The effects of different anesthetic regimens on fibrinolysis and the development of postoperative
arterial thrombosis. Anesthesiology 79:435, 1993.
89. Anderson TR, Berner NS, Larsen ML: Plasma cofactor II, protein C, and antithrombin in elective surgery. Acta Chir Scand 153:291, 1987.
90. O'Brien
JR, Tulevski VG, Etherington M: Platelet function studies before and after operation and the effect of postoperative thrombosis. J Lab
Clin Med 83:342, 1974.
91. KluftC, Verheijen JH, Jie AFH: The postoperative fibrinolytic shutdown: A rapidly reverting acute phase pattern for the fast-acting inhibitor
of tissue type plasminogen activator after trauma. Scand J Clin Lab Invest 45:605, 1985.
92. Modig J, Malmberg P, Karlstrom G: Effect of epidural versus general anesthesia on calf blood flow. Acta Anaesthesiol Scand 24:305, 1980.
93. McKenzie PJ, Wishart HY, Gray I, et al: Effects of anesthetic technique on deep vein thrombosis: A comparison of subarachnoid and general
anesthesia. Br J Anaesth 57:853, 1985.
94. Duggan J, Drummond G: Activity of lower intercostal and abdominal muscle after upper abdominal surgery. Anesth Analg 66:852, 1987.
95. Pansard
JL, Mankikian B, Bertrand M: Effects of thoracic extradural block on diaphragmatic electrical activity and contractility after upper
abdominal surgery. Anesthesiology 78:63, 1993.
643
96. Mankikian B, Cantineau JP, Bertrand M: Improvement of diaphragmatic function by a thoracic epidural block after upper abdominal surgery.
97. Liu SS, Carpenter RL, Mackey DC: Effects of perioperative analgesic technique on rate of recovery after colon surgery. Anesthesiology
83:757, 1995.
98. Benzon HT, Brunner EA, Vaisrub N: Bleeding time and nerve blocks in patients who had aspirin. Reg Anesth 9:86, 1984.
99. Horlocker TT, Wedel DJ, Schroeder DR, et al: Preoperative antiplatelet therapy does not increase the risk of spinal hematoma associated with
regional anesthesia. Anesth Analg 80:303, 1995.
100. UrmeyWF, Rowlingson J: Do antiplatelet agents contribute to the development of perioperative spinal hematoma? Reg Anesth Pain Med
23S:146, 1998.
101. Eastwood DW: Hematoma after epidural anesthesia: Relationship of skin and spinal angiomas. Anesth Analg 73:352, 1991.
102. Williams KN, Jackowski A, Evans PJD: Epidural haematoma requiring surgical decompression following repeated cervical epidural steroid
injections for chronic pain. Pain 42:197, 1990.
103. Greensite F, Katz J: Spinal subdural hematoma associated with attempted epidural anesthesia and subsequent spinal anesthesia. Anesth Analg
59:72, 1980.
104. Gerancher
JC, Waterer R, Middleton J: Transient paraparesis after postdural puncture spinal hematoma in a patient receiving ketorolac.
105. Mayumi T, Dohi S: Spinal subarachnoid hematoma after lumbar puncture in a patient receiving antiplatelet therapy. Anesth Analg 62:777,
1983.
106. Rodgers RP, Levin J: A critical reappraisal of the bleeding time. Semin Thromb Haemost 16:1, 1990.
107. Herbert JM, Frechel D, Vallee E, et al: Clopidogrel, a novel antiplatelet and antithrombotic agent. Cardiovasc Drug Rev 11:180, 1993.
108. DefreynG, Gachet C, Savi P, et al: Ticlopidine and clopidogrel (SR 25990C) selectively neutralize ADP inhibition of PGE1-activated platelet
adenylate cyclase in rats and rabbits. Thromb Haemost 65:186, 1991.
109. BenzonHT, Wong HY, Siddiqui T, et al: Caution in performing epidural injections in patients on several antiplatelet drugs [letter].
110. Enneking FK, Benzon H: Oral anticoagulants and regional anesthesia: A perspective. Reg Anesth Pain Med 23:5140, 1998.
111. Benzon HT, Esposito P: Timing of removal of epidural catheters in anticoagulated patients. Anesthesiology 87:A798, 1997.
112. Liu SS, Mulroy MF: Neuraxial anesthesia and analgesia in the presence of standard heparin. Reg Anesth Pain Med 23:S157, 1998.
113. Millar
FA, Mackenzie A, Hutchison G, et al: Hemostasis-altering drugs and central neural block. A survey of anesthetic practice in Scotland
and the United Kingdom. Reg Anesth 21:529, 1996.
114. Rodgers A, Sage D, Futter M, et al: Attitudes and practices of New Zealand anaesthetists with regard to epidural and subarachnoid
115. Vandermeulen EP, Van Aken H, Vermylen J: Anticoagulants and spinal-epidural anesthesia. Anesth Analg 79:1165, 1994.
116. Greaves JSD: Serious spinal cord injury due to haematomyelia caused by spinal anaesthesia in a patient treated with low-dose heparin.
117. Rao TL, El-Etr AA: Anticoagulation following placement of epidural and subarachnoid catheters: An evaluation of neurologic sequelae.
118. Horlocker TT, Heit JA: Low molecular weight heparin: Biochemistry, pharmacology, perioperative prophylaxis regimens, and guidelines for
regional anesthetic management. Anesth Analg 85:874, 1997.
119. Horlocker
TT, Wedel DJ: Neuraxial block and low-molecular-weight heparin: Balancing perioperative analgesia and thromboprophylaxis.
Reg Anesth Pain Med 23:S164, 1998.
120. Horlocker TT: When to remove a spinal or epidural catheter in an anticoagulated patient. Reg Anesth 18:264, 1993.
121. Nikolajsen L, Ilkjaer S, Christensen JH, et al: Randomised trial of epidural bupivacaine and morphine in prevention of stump and phantom
pain in lower limb amputation. Lancet 350:1353, 1997.
644
123. de Leon-Casasola OA, Lema MJ: Postoperative epidural opioid analgesia: What are the choices? Anesth Analg 83:867, 1996.
124. Wong HY, Benzon HT: Epidural opioid infusion. In Benzon HT, Raja SN, Borsook D, et al (eds): Essentials of Pain Medicine and Regional
125. Ready LB, Loper KA, Nessly M, et al: Postoperative epidural morphine is safe on surgical wards. Anesthesiology 75:452, 1991.
126. El-Baz
NM, Faber P, Jensik RJ: Continuous epidural infusion of morphine for treatment of pain after thoracic surgery: A new technique.
127. Bernards CM: Pro: Lipid soluble opioids should not be used for postoperative epidural analgesia. ASRA Newsletter 12, May 1999.
128. Chaplan SR, Duncan SR, Brodsky JB, et al: Morphine and hydromorphone epidural analgesia. Anesthesiology 77:1090, 1992.
129. Liu SS, Allen HW, Olsson GL: Patient-controlled epidural analgesia with bupivacaine and fentanyl on hospital wards. Anesthesiology 88:688,
1998.
130. Fisher RL, Lubenow TR, Liceaga A, et al: Comparison of continuous epidural infusion of fentanyl-bupivacaine and morphine-bupivacaine in
the management of postoperative pain. Anesth Analg 67:559, 1988.
131. Loper
KA, Ready LB, Downey M, et al: Epidural and intravenous fentanyl infusions are clinically equivalent after knee surgery. Anesth
Analg 70:72, 1990.
132. Ellis DJ, Millar WA, Reisner LS: A randomized double-blind comparison of epidural versus intravenous fentanyl infusions for analgesia after
133. Sandler AN, Stringer D, Panos L, et al: A randomized, double-blind comparison of lumbar epidural and intravenous fentanyl infusions for
posthoracotomy pain relief. Anesthesiology 77:626, 1992.
134. Salomaki TE, Laitinen JO, Nuutinen LS: A randomized double-blind comparison of epidural versus intravenous fentanyl infusion for
analgesia after thoracotomy. Anesthesiology 75:79, 1991.
135. Guinard JP, Mavrocordatos P, Chiolero R, et al: A randomized comparison of intravenous versus lumbar and thoracic epidural fentanyl for
136. Grant RP, Dolman JF, Harper JA, et al: Patient-controlled lumbar epidural fentanyl compared with patient-controlled intravenous fentanyl for
postthoracotomy pain relief. Can J Anaesth 39:214, 1992.
137. Akerman B, Sarwestrom E, Post C: Local anesthetics potentiate spinal morphine antinociception. Anesth Analg 67:943, 1988.
138. Wang C, Chakrabarti MK, Whitman JG: Specific enhancement by fentanyl of the effects of intrathecal bupivacaine on nociceptive afferent
but not on sympathetic efferent pathways in dogs. Anesthesiology 79:766, 1993.
139. Hjortso
NC, Lund C, Mogensen T, et al: Epidural morphine improves pain relief and maintains sensory analgesia during continuous epidural
bupivacaine after abdominal surgery. Anesth Analg 65:1033, 1986.
140. Niv D, Rudick V, Golan A, et al: Augmentation of bupivacaine analgesia in labor by epidural morphine. Obstet Gynecol 67:206, 1986.
141. Chestnut DH, Owen CL, Bates JN, et al: Continuous infusion epidural analgesia during labor: Randomized double-blind comparison of
0.0625% bupivacaine/0.002% fentanyl versus 0.125% bupivacaine. Anesthesiology 68:754, 1988.
142. Scott
DB, Mogensen T, Bigler D, et al: Continuous thoracic extradural 0.5% bupivacaine with or without morphine: Effect on quality of
blockade, lung function and the surgical stress response. Br J Anaesth 62:253, 1989.
143. Hunt CO, Nulty JS, Malinow AM, et al: Epidural butorphanol-bupivacaine for analgesia during labor and delivery. Anesth Analg 68:323,
1989.
144. King MJ, Bowden MI, Cooper GM: Epidural fentanyl and 0.5% bupivacaine for elective cesarean section. Anaesthesia 45:285, 1990.
145. George
KA, Wright PMC, Chisakuta A: Continuous thoracic epidural fentanyl for postthoracotomy pain relief: With or without bupivacaine?
146. Hanson AL, Hanson B, Matousek M: Epidural anesthesia for cesarean section: The effect of morphine-bupivacaine administered epidurally
for intra and postoperative pain relief. Acta Obstet Gynecol Scand 63:135, 1984.
147. Dahl
JB, Rosenberg J, Hansen BL, et al: Differential analgesic effects of low-dose epidural morphine and morphine-bupivacaine at rest and
during mobilization after major abdominal surgery. Anesth Analg 74:362, 1992.
148. Douglas MJ, McMorland GH, Janzen JA: Influence of bupivacaine as an adjunct to epidural morphine for analgesia after cesarean section.
645
149. ParkerRK, Sawaki Y, White PF: Epidural patient-controlled analgesia: Influence of bupivacaine and hydromorphone basal infusion on pain
control after cesarean delivery. Anesth Analg 75:740, 1992.
150. Badner NH, Reimer EJ, Komar WE: Low-dose bupivacaine does not improve postoperative epidural fentanyl analgesia in orthopedic cases.
151. Badner
NH, Komar WE: Bupivacaine 0.1% does not improve postoperative epidural fentanyl analgesia after abdominal or thoracic surgery.
152. Benzon HT, Wong CA, Wong HY, et al: The effect of low-dose bupivacaine on postoperative epidural analgesia and thrombelastography.
153. Rawal N, Sjostrand U, Christofferson E, et al: Comparison of intramuscular and epidural morphine for postoperative analgesia in the grossly
154. Yeager MP, Glass DD, Neff RK, et al: Epidural anesthesia and analgesia in high-risk surgical patients. Anesthesiology 66:729, 1987.
155. Jayr
C, Thomas H, Rey A, et al: Postoperative pulmonary complications: Epidural analgesia using bupivacaine and opioids versus parenteral
opioids. Anesthesiology 78:666, 1993.
156. Carpenter RL, Abram SE, Bromage PR, Rauck RL: Consensus statement on acute pain management. Reg Anesth 21(suppl 6):152, 1996.
157. Thomas DFM, Lambert WG, Lloyd-Williams K: The direct perfusion of surgical wounds with local anesthetic solutions: An approach to
postoperative pain. Ann R Coll Surg Engl 65:226, 1983.
158. Brown DL: Special situations for regional anesthesia: Trauma. Reg Anesth 21(suppl 6):122, 1996.
159. Cousins MJ, Bridenbaugh PO: Neural Blockade in Clinical Anesthesia and Management of Pain, 3rd ed. Philadelphia, Lippincott-Raven,
1998.
160. Brown DL: Regional Anesthesia and Analgesia, Philadelphia, WB Saunders, 1996.
161. Wedel DJ: Nerve blocks. In Miller R (ed): Anesthesia, 5th ed. Philadelphia, Churchill Livingstone, 2000, p 1520.
162. MolloyRE: Axillary brachial plexus block. In Benzon HT, Raja SN, Borsook D, et al (eds): Essentials of Pain Medicine and Regional
163. Raj PP: Ancillary measures to success. Reg Anesth 5:9, 1980.
164. Koscielnak-Nielsen ZJ, Stens-Pedersen HL, Lippert FK: Readiness for surgery after axillary block: Single or multiple injection techniques.
Eur J Anaesth 14:164, 1997.
165. Fanelli G, Casati A, Garancini P, et al: Nerve stimulator and multiple injections technique for upper and lower limb blockade: Failure rate,
patient acceptance, and neurologic complications. Anesth Analg 88:847, 1999.
166. Lavoie
J, Martin R, Tetrault JP, et al: Axillary brachial plexus block using peripheral nerve stimulator: Single or multiple injections. Can J
Anaesth 39:583, 1992.
167. Baranowski AP, Pither CE: A comparison of three methods of axillary brachial plexus anesthesia. Anaesthesia 45:362, 1990.
168. Brown DL., Cahill DR, Bridenbaugh LD: Supraclavicular nerve block: Anatomic analysis of a method to prevent pneumothorax. Anesth
Analg 76:530, 1993.
169. UrmeyWF, Talts KH, Sharrock NE: One hundred per cent incidence of hemidiaphragmatic paresis associated with interscalene brachial
plexus anesthesia as diagnosed by ultrasonography. Anesth Analg 72:498, 1991.
170. Raj PP, Montgomery SJ, Nettles D, et al: Infraclavicular brachial plexus block: A new approach. Anesth Analg 52:897, 1973.
171. Sims JK: A modification of the landmarks for infraclavicular approach to brachial plexus block. Anesth Analg 56:554, 1977.
172. Tetzlaff JE, Yoon HY, Brems J: Interscalene brachial plexus block for shoulder surgery. Reg Anesth 19:339, 1994.
173. D'Alessio
JG, Rosenblum M, Shea KP, Freitas DG: A retrospective comparison of interscalene block and general anesthesia for ambulatory
surgery shoulder arthroscopy. Reg Anesth 20:62, 1995.
174. Ritchie ED, Tong D, Chung F, et al: Suprascapular nerve block for postoperative pain relief in arthroscopic shoulder surgery: A new modality?
175. Berry FR: Analgesia in patients with fractured shaft of the femur. Anaesthesia 32:576, 1977.
176. Rosenberg AD, Albert DB, Bernstein RL: Regional anesthesia for orthopedic trauma. Problems in Anesthesia 8:426, 1994.
646
177. Farny J, Girard M, Drolet P: Posterior approach to the lumbar plexus combined with a sciatic nerve block using lidocaine. Can J Anaesth
41:486, 1994.
178. Greengrass
RA, Klein SM, D'Ercole J, et al: Lumbar plexus block and sciatic nerve block for knee arthroplasty: A comparison of ropivacaine
and bupivacaine. Can J Anaesth 45:1094, 1998.
179. Farny J, Girard M, Drolet P: Posterior approach to the lumbar plexus combined with a sciatic nerve block using lidocaine. Can J Anaesth
41:486, 1994.
180. Atanassoff PG, Elmas C: Increased dosage of lidocaine 1% in combined sciatic-femoral 3-in-1 block for lower limb surgery. Reg Anesth
17:48, 1992.
181. Bailey SL, Parkinson SK, Little WL, et al: Sciatic nerve block. A comparison of single versus double injection technique. Reg Anesth 19:9,
1994.
182. Benzon HT: Popliteal sciatic nerve block: Posterior approach. Tech Reg Anesth Pain Manag 3:23, 1999.
183. Casati
A, Fanelli G, Beccaria P, et al: The effects of the single or multiple injection technique on the onset time of femoral nerve blocks with
0.75% ropivacaine. Anesth Analg 91:181, 2000.
184. Stevens RD, Van Gessel E, Flory N, et al: Lumbar plexus block reduces pain and blood loss associated with total hip arthroplasty.
185. Allen JG, Denny NM, Oakman N: Postoperative analgesia following total knee arthroplasty. Reg Anesth Pain Med 23:142, 1998.
186. Jones SF, White A: Analgesia following femoral neck surgery. Lateral cutaneous nerve block as an alternative to narcotics in the elderly.
187. Allen HW, Liu SS, Ware PD, et al: Peripheral nerve blocks improve analgesia after total knee replacement surgery. Anesth Analg 87:93, 1998.
188. Singelyn
FJ, Gouverneur JA: Extended “three-in-one” block after total knee arthroplasty: Continuous versus patient-controlled techniques.
189. Fisher A, Meller Y: Continuous postoperative regional analgesia by nerve sheath block for amputation surgery—a pilot study. Anesth Analg
72:300, 1991.
190. Rongstad K, Mann RA, Prieskorn D, et al: Popliteal sciatic nerve block for postoperative analgesia. Foot Ankle Intl 17:378, 1996.
191. Katz
JA: Use of nerve stimulators for peripheral nerve blocks. In Benzon HT, Raja SN, Borsook D (eds): Essentials of Pain Medicine and
Regional Anesthesia. New York, Churchill Livingstone, 1999, p 395.
192. Vloka JD, Hadzic A: The intensity of the current at which sciatic nerve stimulation is achieved is a more important factor in determining the
quality of nerve block than the type of motor response obtained [letter]. Anesthesiology 88: 1408, 1998.
193. Benzon HT: In reply—the intensity of the current at which sciatic nerve stimulation is achieved is a more important factor in determining the
quality of nerve block than the type of motor response obtained. Anesthesiology 88:1410, 1998.
194. Vloka JD, Hadzic A, Mulcare R, et al: Combined blocks of the sciatic nerve at the popliteal fossa and posterior cutaneous nerve of the thigh
for short saphenous vein stripping in outpatients: An alternative to spinal anesthesia. J Clin Anesth 9:618, 1997.
195. Vloka JD, Hadzic A, Koorn R, et al: Supine approach to the sciatic nerve in the popliteal fossa. Can J Anaesth 43:964, 1996.
196. Bridenbaugh PO, Crews JC: Perioperative management of patients for neural blockade. In Cousins MJ, Bridenbaugh PO (eds): Neural
Blockade in Clinical Anesthesia and Management of Pain, 3rd ed. Philadelphia, Lippincott-Raven, 1997, p 179.
197. Magora E, Rosin R, Ben-Menachem Y, et al: Obturator nerve block: An evaluation of technique. Br J Anaesth 41:695, 1969.
198. Shannon J, Lang SA, Yip RW, et al: Lateral femoral cutaneous nerve block revisited: A nerve stimulator technique. Reg Anesth 20:100, 1995.
199. Rigler F: Brachial plexus block with the nerve stimulator: Motor response characteristics at three sites. Reg Anesth 20:100, 1995.
200. Singelyn FJ, Gouverneur JA, Gribomont BF: Popliteal sciatic nerve block aided by nerve stimulator, a reliable technique for foot and ankle
surgery. Reg Anesth 16:278, 1991.
201. Winnie AP, Candido KD, Torres ML: Continuous plexus blocks for the management of trauma to the extremities. In Rosenberg AD, Grande
CM, Bernstein RL (eds): Pain Management and Regional Anesthesia in Trauma. New York, WB Saunders, 2000, p 209.
202. Gauman DM, Lennon RL, Wedel DJ: Continuous axillary block for postoperative pain management. Reg Anesth 13:77, 1988.
203. Raj PP: Infraclavicular approaches to brachial plexus anesthesia techniques. Tech Reg Anesth Pain Manag 1:169, 1997.
647
204. Tuominen MK, Haasia J, Hekali R, et al: Continuous interscalene brachial plexus block: Clinical efficacy, technical problems and
bupivacaine plasma concentrations. Acta Anaesthesiol Scand 33:84, 1989.
205. Mezzatesta JP, Scott DA, Schweitzes SA, et al: Continuous axillary brachial plexus block for postoperative pain relief. Reg Anesth 22:357;
1997.
206. Dahl
JB, Christiansen CL, Daughard JJ, et al: Continuous blockade of the lumbar plexus after knee surgery-postoperative analgesia and
bupivacaine plasma concentration. Anaesthesia 43:1015, 1988.
207. Schultz P, Christensen EF, Anker-Moller E, et al: Postoperative pain treatment after open knee surgery: Continuous lumbar plexus block with
bupivacaine versus epidural morphine. Reg Anesth 16:34, 1991.
208. Anker-MollerE, Spangsberg N, Dahl JB, et al: Continuous blockade of the lumbar plexus after knee surgery: A comparison of the plasma
concentration and analgesic effect of bupivacaine 0.25% and 0.125%. Acta Anaesthesiol Scand 34:468, 1990.
209. Vaghadia H, Kapnoudhis P, Jenkins LC, et al: Continuous lumbosacral block using a Touhy needle and a catheter technique. Can J Anaesth
39:75, 1992.
210. Smith BE, Fisher HBJ, Scott PV: Continuous sciatic nerve block. Anaesthesia 39:155, 1984.
211. Morris GF, Lang SA: Continuous parasacral nerve block: Two case reports. Reg Anesth 22:469, 1997.
212. BroadmanLM, Glass NL: Regional anesthesia for pediatric trauma. In Rosenberg AD, Grande CM, Bernstein RL (eds): Pain Management
and Regional Anesthesia in Trauma. New York, WB Saunders, 2000, p 265.
213. Fitzgerald B: Intravenous regional anesthesia in children. Br J Anaesth 48:485, 1976.
214. Rudzinski JP, Ampel LL: Pediatric applications of intravenous regional anesthesia. Reg Anesth 8:69, 1983.
215. Colizza WA, Said E: Intravenous regional anesthesia in the treatment of forearm and wrist fractures and dislocations in children. Can J Surg
36:225, 1993.
216. Wedel DJ, Krohn JS, Hall JA: Brachial plexus anesthesia in pediatric patients. Mayo Clin Proc 66:583, 1991.
217. Dalens B: Regional Anesthesia in Infants, Children, and Adolescents. Baltimore: Williams & Wilkins, 1995, p 305.
218. Dalens
B, Vanneuville G, Tanguy A: A new approach to the brachial plexus in children: Comparison with the supraclavicular approach.
Anesth Analg 1987; 66:1264, 1987.
219. DalensB, Tanguy A, Vanneuville G: Sciatic nerve blocks in children: Comparisons of the posterior, anterior, and lateral approaches in 180
pediatric patients. Anesth Analg 70:131, 1990.
220. Ronchi L, Rosenbaum D, Althouel A, et al: Femoral nerve block in children using bupivacaine. Anesthesiology 70:622, 1989.
221. Malawar MM, Buch R, Khurana JS, et al: Postoperative infusional continuous regional analgesia. Clin Orthopaed 266:227, 1991.
222. Chayen D, Nathan H, Chayen M: The psoas compartment block. Anesthesiology 45:95, 1976.
223. Dalens B, Tanguy A, Vanneuville G: Lumbar plexus block in children: A comparison of two procedures in 50 patients. Anesth Analg 67:750,
1988.
224. BroadmanLM, Hannallah RS, Norden JM, et al: Kiddie caudals: Experience with 1154 consecutive cases without complications. Anesth
Analg 66:S18, 1987.
225. Dalens B, Hasnaoui A: Caudal anesthesia in pediatric surgery: Success rate and adverse effects in 750 consecutive cases. Anesth Analg 68:83,
1989.
226. Freid
EB, Bailey AG, Valley RD: Electrocardiographic and hemodynamic changes associated with unintentional intravascular injection of
bupivacaine with epinephrine in infants. Anesthesiology 79:394, 1993.
227. Ved
SA, Pinosky M, Nicodemus H: Ventricular tachycardia and brief cardiovascular collapse in two infants after caudal anesthesia using a
bupivacaine-epinephrine solution. Anesthesiology 79:1121, 1993.
228. Valley RD, Bailey AG: Caudal morphine for postoperative analgesia in infants and children. A report of 138 cases. Anesth Analg 72:120,
1991.
229. Bosenberg AT, Bland BAR, Schulte-Steinberg O, et al: Thoracic epidural anesthesia via caudal route in children. Anesthesiology 69:265,
1988.
230. Gunter JB, Eng C: Thoracic epidural anesthesia via the caudal approach in children. Anesthesiology 76:935, 1992.
648
231. AveryEE, Morch ET, Benson DW: Critically crushed chests: A new method of treatment with continuous mechanical hyperventilation to
produce alkalotic apnea and internal pneumatic stabilization. J Thor Surg 32:291, 1956.
232. Relihan M, Litwin MS: Morbidity and mortality associated with flail chest injury: A review of 85 cases. J Trauma 13:663, 1973.
233. Trinkle KJ, Richardson DJ, Franz JL, et al: Management of flail chest without mechanical ventilation. Ann Thor Surg 19:355, 1975.
234. Worthley LIG: Thoracic epidural in the management of chest trauma. Intensive Care Med 11:312, 1985.
235. Abouhatem R, Hendrickx T, Titeca M: Throacic epidural analgesia in the treatment of rib fractures. Acta Anaesth Belg 35(Suppl):271, 1984.
236. Dittman M, Steenblock U, Kranzlin M, et al: Epidural analgesia or mechanical ventilation for multiple rib fractures? Intensive Care Med 8:89,
1982.
237. Rankin APN, Comber REH: Management of fifty cases of chest injury with a regimen of epidural bupivacaine with morphine. Anaesth
238. Behar M, Magora F, Olshwang D, et al: Epidural morphine in treatment of pain. Lancet 10:527, 1979.
239. BenzonHT, Wong HY, Belavic AM, et al: A randomized double-blind comparison of epidural fentanyl infusion versus patient-controlled
analgesia with morphine for postthoracotomy pain. Anesth Analg 76:316, 1993.
240. Johnston JR, McCaughey W: Epidural morphine. A method of management of multiple fractured ribs. Anaesthesia 35:155, 1980.
241. Ullman DA, Fortune JB, Greenhouse BB, et al: The treatment of patients with multiple rib fractures using continuous thoracic epidural
narcotic infusion. Reg Anesth 14:43, 1989.
242. RyanMoon M, Luchette FA, Gibson SW, et al: Prospective, randomized comparison of epidural versus parenteral opioid analgesia in thoracic
trauma. Ann Surg 229:684, 1999.
649
Section IV - Chapter 27 - Nonmalignant Pain
Chapter 27 - Nonmalignant Pain
Craig T. Hartrick
Chronic pain is never benign. Those afflicted with persistent pain suffer both emotional and physiologic harm. The
term chronic benign pain is, therefore, a misnomer; chronic nonmalignant pain is the preferred terminology.
Although it can be successfully argued that any debilitating painful condition is truly “malignant,” for the purpose of
this discussion the term chronic nonmalignant pain is defined as persistent pain not associated with cancer.
Certainly there are severe chronic pain states associated with advanced peripheral vascular disease, demyelinating
diseases of the central nervous system (CNS), and other chronic debilitating conditions that deserve measures as
heroic as those offered patients with malignancies. In these cases, the severity of the pain and resultant dysfunction
may outweigh the potential risk of untoward side effects. Hippocrates asserted, “Extreme remedies are very
appropriate for extreme diseases.” Yet even for these seemingly desperate scenarios, the principle of escalating
[1]
degrees of intervention given in the World Health Organization (WHO) Ladder underlies the structure of therapeutic
intervention. Judicious use of invasive therapies reduces unnecessary risk and conserves valuable healthcare
[2]
resources.
In this chapter, the rationale for neural blockade techniques in the management of chronic nonmalignant pain is
addressed. Identification of patients most likely to benefit from intervention therapies is crucial to cost-effective
management and patient satisfaction. Empirical treatment guided by anecdotal evidence ultimately can be
systematically replaced by prospective clinical study that invites outcome analysis. The approach described here has
evolved from an outcome-based model. Far from a static recipe collection, it continues to undergo constant revision.
However, the general format is meant to provide a template for individualization based on reassessment of results
and subsequent modification of the programs offered patients with chronic nonmalignant pain. Although standard
outcome software is commercially available and allows direct comparison of program results to other like facilities,
it less easily lends itself to individualized interpretation of predictive factors and is open to selective enrollment for
marketing purposes. The following system for outcome measurement offers advantages with respect to research-
oriented data extraction, protocol refinement, and continuous quality improvement to reduce medical errors. [3]
The goal to provide dynamic, cost-effective, outcome-based intervention can be attained when the sufficient
underlying structure permits the recognition of predictive measures as well as the direct comparison of parallel
treatment strategies. Standardization and simplification are also integral to the reduction of medical errors The use
[4]
of simple tools that are easy for both the operator and patient to administer and score is preferred. Dogmatic
insistence upon strict scientific rigor at the expense of compliance helps neither physician nor patient. It is, therefore,
of primary importance that data collection be incorporated into the routine care of patients in such a way as to
require minimal additional effort. A database program is an efficient means of collecting and managing the intake,
treatment, and outcome information necessary to bring to life the pain treatment protocols.
Nerve Block and Chronic Pain
The destruction of peripheral nerves providing afferent information from a painful area for the treatment of chronic
pain, although seemingly logical, has long been recognized to be fraught with pitfalls. Even when functional motor
deficits are not at issue, the plasticity of both the central and peripheral nervous system in response to injury tends to
defeat long-term analgesia, and may eventually give rise to pain and dysesthesias in the denervated territory. [5] [6] [7] [8]
By the 19th century, this failure of neurotomy to effect lasting analgesia led to recommendation of alternatives such
as peripheral injection of morphine directly into the sites of pain and the prescription of electrical current for
[9]
stimulation-induced analgesia. Neural blockade with local anesthetics and other analgesic agents has since found a
[10]
number of diagnostic, prognostic, and therapeutic indications in the management of chronic pain.
Diagnostic and Prognostic Neural Blockade
Neural blockade is an important tool in the evaluation of chronic pain when used as an adjunct to a detailed history
and physical examination. The complexity of neural pathways, especially in chronic pain states, and the
psychosocial impact on self-reporting make the use of nerve block in isolation subject to misinterpretation. However,
when specific endpoints are sought, particularly with respect to predicting the effect of a proposed therapeutic
intervention, considerable utility can be realized.
650
The importance of a detailed history and physical examination cannot be overemphasized. Routine neurologic,
orthopedic, and psychiatric workups should be supplemented as indicated, with additional evaluations to document
physical function, anxiety, depression, and coping mechanisms. Diagnostic injections, like other evaluative
investigations, are a supplement to the history and physical examination and as such can only be interpreted
accurately within that context.
Controversy exists with respect to appropriate diagnostic use of discography, facet joint injection, medial branch
blocks, root blocks, and both differential peripheral and differential neuraxial blockade. Idiosyncratic reactions,
placebo response, psychological factors, and secondary gain may each contribute to subjective response.
Additionally, unconsidered alternative mechanisms of pain relief, altered pain pathways, and other confounding
factors complicate the interpretation of results. Block of a peripheral nerve may relieve pain secondary to
radiculopathy if the lesion is proximal to the site of injection. Peripheral nerve block may fail to relieve pain after
nerve injury, whereas relief might be produced with blockade of an adjacent nerve. Pain that breaks through
apparently solid spinal blockade in the face of complete motor block is yet another example of the difficulties
encountered in using simplistic interpretive paradigms. Further confounding effects due to analgesia secondary to
systemic absorption of local anesthetics add to the uncertainty.
Hogan and Abrams reviewed the use of diagnostic neural blockade. They addressed neurophysiologic, local
[11]
anesthetic, psychosocial, and anatomic issues pertinent to diagnostic blocks. Alterations in the peripheral nervous
system, such as heightened nociceptor sensitivity, abnormal impulse generation, and antidromic conduction, are
well-documented phenomena. The sympathetic nervous system contributes to the sensitization of nociceptors to
catecholamines, perpetuation of sensitization in wide dynamic range (WDR) neurons of the dorsal horn, and the
production of neurogenic inflammation. CNS perturbations also confound interpretive efforts. CNS processing
alterations such as those seen after partial nerve injuries, especially when there has been a relative loss of large fiber
afferents, are common. The convergence of input on WDR neurons in the spinal cord and the presence of referred
pain make it possible to effect significant relief by blocking one limb of the reflex without necessarily addressing the
cause, either mechanistically or anatomically. Frequently, pain arises predominantly from trigger point activity that
is a secondary phenomenon; without aggressive search for the underlying pathology, the cause will remain elusive.
CNS plasticity resulting from sensitization, sprouting, or spreading dysesthesias associated with the loss of
inhibitory surround and resultant stocking or glovelike pain caused by recruitment of surrounding peripheral nerve
distributions and denervation dysesthesia confound interpretive efforts.
Hogan and Abrams also referred to the inability to assure intensity and completeness of blockade, the confusion
[11]
over differential blocks with respect to the blocking concentrations of local anesthetics for different fibers, central
blockade of the spinal tracts themselves, use dependency, and systemic effects. Taken together with the anatomic
uncertainties caused by inconsistent nerve distributions, dermatomal overlap, and differing origins of sensory,
sudomotor, and vasomotor innervation, these conditions dictate caution in the interpretation of diagnostic nerve
block. Visceral receptive fields are particularly large and also overlap extensively. Similar overlap of the afferent
supply characterizes the innervation of vascular structures, bones, joints, muscles, and fascia. Other deep somatic
elements, such as costovertebral joints, posterior and anterior longitudinal ligaments, anulus of the intervetebral disc,
and the dura, have innervation that traverses the sympathetic rami. These sensory afferents travel diffusely with
sympathetic nerves, giving rise to poor somatotopic localization, referred pain, and motor and autonomic reflexes.
Although sympathetic interruption may temporarily eliminate pain arising from these structures, these pains are not
necessarily sympathetically maintained. Finally, although the application of dilute local anesthetics into the spinal
canal has been used in an attempt to block only the smallest, most susceptible nerve fibers, the effects may have
more to do with the anatomic susceptibility of the most superficial tracts within the spinal cord.
In evaluating the efficacy of diagnostic injections North and colleagues found isolated positive blocks to be
[12]
nonspecific. Negative blocks, or a pattern of responses, however, did seem to have some predictive value. [12]
Whenever possible, provocative maneuvers should be utilized and quantitated before and after neural blockade. The
addition of changing examination findings in response to diagnostic block increases the power of the intervention.
Provocative maneuvers also help to determine the completeness of neural blockade. Other objective evidence of the
blockade, such as quantitative sensory testing, should be used when appropriate to strengthen the evidence in
support of both the indications for and the effectiveness of neural blockade.
The placebo response is a complex phenomenon that accompanies diagnostic injections. Expectation and belief in
therapy on the part of both patient and physician contribute. Preexistent patient anxiety and learned responses are
[13]
also important factors. The use of standard patient instructions before a diagnostic test has been suggested to help to
minimize these effects but cannot be expected to eliminate the placebo response. Even acute pain patients can be
[14]
expected to exhibit a placebo response in one third of all interventions. The response in chronic pain patients is
[15]
reported to be twice as prevalent. Personality traits have not predicted placebo response, as most individuals will
[16]
651
eventually respond to placebo when the procedure is repeated, especially if the active treatment precedes the placebo
trial. Further, invasive procedures such as injections and surgery are more likely to evoke the placebo
[17] [18] [19] [20]
response than oral medication. The placebo response should not be used as part of a diagnostic evaluation outside
the bounds of informed consent.
The utility of so-called differential blocks is also limited. For example, postoperative pain may be relieved by
epidural application of local anesthetic concentrations that fail to achieve any demonstrable sensory block, yet
clearly incision pain is not considered visceral or sympathetically mediated. The introduction of spinal opioid does
not improve the reliability of these antiquated examinations. Further, the duration of relief in many instances
[21]
inexplicably outlasts the expected duration of the agent employed. Even comparisons between long- and short-
acting agents become difficult, because they necessarily follow sequentially and, therefore, interact with one another.
This process itself increases the uncertainty as to whether it is the act of observation or the actual procedures that are
responsible for the observed response. Interpretation of the duration of the expected effect with various anesthetic
agents, and especially the use of placebo injection, is, therefore, often questionable. The temptation to oversimplify
the interpretation of diagnostic neural blockade must be rigorously resisted and always tempered by clinical
judgment. Accordingly, this potential for confusion highlights the necessity for specific protocols that are modified
based on objective outcome data as an ongoing process.
Therapeutic Neural Blockade
The development of outcome-based protocols for clinical use within a particular practice requires scientific
compromise. Double-blind, placebo-controlled trials are often impractical within the confines of clinical
nonacademic practice. Further, the limitations of the size of any given practice make meta-analysis of numerous
investigations at multiple sites necessary to meaningfully validate specific interventions. Yet, considerable
information can be derived from individual pain practices that help to guide and shape the treatment process.
Prospective, randomized, crossover designs that strive to quantitate diagnosis and outcome are achievable. Matching
pairs of patients with similar pretreatment profiles for entry into parallel clinical pathways can further reduce the
number of subjects needed to arrive at valid conclusions.
The following arbitrarily subdivides treatment strategies into three categories: pain of spinal origin, neuropathic pain,
and myofascial pain. This division, admittedly artificial, is in large part based on practical numeric constraints.
Experience within even a large interventional pain practice has made it evident that a large number of subcategories
limits statistically meaningful results because the numbers needed to treat rise exponentially. Consequently, patients
often are enrolled in more than one treatment protocol simultaneously, but the designations help to monitor clinical
progress through the schema nonetheless.
GENERAL PRINCIPLES OF MANAGEMENT
The treatment of chronic pain that persists because of deranged patterns of healing, the development of altered pain
pathways, chronic ischemia, or the misuse or disuse of myofascial structures is far more complex than the treatment
of acute pain syndromes. The contribution of psychological factors to the interpretation and outward expression of
pain takes on added importance as resultant behavioral changes often contribute to the perpetuation of pain.
Furthermore, the group of patients suffering from chronic pain is far from homogeneous. Instead, these patients
represent a complex clinical syndrome manifesting varying degrees of psychosocial, physical, and vocational
dysfunction.
Obviously, no one approach can be expected to achieve the desired goals of reducing pain, improving the quality of
life, and reducing dependency on the healthcare system. Successful intervention requires not only accurate medical
diagnosis but also behavioral and functional considerations in concert with medical and physical therapeutic
modalities. Neither can a single mode of treatment be expected to consistently provide satisfactory results.
Consequently, a goal-oriented, multidisciplinary approach to chronic pain continues to be essential to proper and
cost-effective management of chronic pain. The paucity of scientific evidence in support of the multidisciplinary
approach may have much to do with the lack of systematic evaluation and implementation.
Brena and Chapman provided a conceptually useful template for interdisciplinary evaluation and treatment. They
[22]
classified patients into four clusters and recommended different approaches to treatment for each group. Patients
with low pathology and high behavioral scores (cluster I) are directed into structured rehabilitation-oriented tracks.
Those with low behavioral and low pathology scores (cluster II) are offered activities-of-daily-living instruction,
relaxation, and self-control and pacing educational tracks. Patients in clusters III and IV are potential candidates for
medically related intervention. Patients with both high pathology and high behavioral scores (cluster III) require
matched and psychological rehabilitation-directed programs. Patients with low behavioral scores with high
652
pathology scores (cluster IV) require medically oriented intervention structured with restraint so as to preserve
coping skills as much as possible. Although the scoring of these clusters as originally described is outdated, the
concept retains its vitality. The description of structured tracks to accommodate each of these clusters is beyond the
scope of this chapter.
In comparison with patients with acute post-traumatic pain, far fewer chronic pain patients benefit from neural
blockade. The basis for the use of therapeutic neural blockade in chronic post-traumatic pain involves the following:
1. Interruption of ongoing nociceptive input

2. Interruption of abnormal neurogenic reflex mechanisms
3. Interruption of sympathetic overactivity
4. Relief of muscle spasm and abolition of trigger point activity
The medications administered by regional block technique for these purposes include local anesthetics,
antisympathetic agents, α2 -adrenergic agonists, opioids, and depot forms of corticosteroid. It cannot be
overemphasized that neural blockade is rarely sufficient treatment in and of itself in the chronic pain patient
(although in the acute pain patient, neural blockade alone is sufficient). Even when the aforementioned conditions
are present, other methods of treatment should be used concomitantly.
The complexity of chronic pain mechanisms is such that, when compared with the acute pain syndromes previously
described, one generally is forced to accept lesser degrees of therapeutic success. Reasonable goals should be
discussed frankly with the patient at the onset of treatment and frequently reiterated. Chronic pain management
should be directed toward pain control rather than a cure, with specific goals that include the following:
1. Reduction in pain and elevation in pain threshold.

2. Emphasis on improved function, rehabilitation, and education to prevent overuse injury.
3. Finally, and perhaps most important, the acute pain model, which features the passive patient healed by the
active physician, must be abandoned in the chronic pain situation. The patient must become the active
component and accept the challenge of becoming well. The physician should provide guidance and work to
preserve the patient's independent functioning.
General Evaluation for All Protocols
Initial intake data are derived from a detailed or comprehensive initial evaluation including history and physical
examination, review of previous workup, and completion of a pain questionnaire, which includes a pain drawing.
The results in each field within the intake questionnaire are then converted into numerical values for entry into the
database along with other quality assurance, insurance, and demographic data at the time of initial evaluation. A
short-form McGill Pain Questionnaire, visual analogue scale (VAS) for pain, Zung Anxiety Scale, Beck
[23] [24] [25]
Depression Inventory, Pain Stages of Change Questionnaire (PSOCQ), Post-traumatic Chronic Pain Test
[26] [27]
(PCPT), and the Low Back Outcome Score are incorporated into the intake questionnaire. Although a plethora of
[28] [29]
other similar scales exist, these particular tools have several practical characteristics. They were each selected for
their ease of administration and scoring. Patients can routinely complete them without assistance, and they lend
themselves to a repeat application for an outcome comparison via a mailed questionnaire. Additionally, they can be
scored easily in a few moments with a minimum of practice by use of simple addition and are not associated with
additional expense. Most important, instruments such as these enjoy a simplicity of implementation that is essential
to both patient and physician compliance.
Psychological and Behavioral Assessment
PSYCHOLOGICAL FACTORS
Although a number of factors influence the development of chronic pain, psychosocial features are more important
risk factors for chronicity than biomedical symptoms and signs. Premorbid psychological factors have been
[30] [31]
implicated in the subsequent development of chronic low back pain and complex regional pain syndrome type II
[32]
(reflex sympathetic dystrophy, RSD). High levels of anxiety, personality disorder,

[33] [34]
passive coping strategies,
[35] [36] [37]
and job dissatisfaction all predict the progression of acute low back pain to chronic pain and disability. These
[38]
correlations should not be misinterpreted as implying that chronic pain is “psychogenic,” thus lacking a biologic
basis. Hardcastle made the philosophic argument that no pain is due to mental disorder and that attempts to
[39]
distinguish psychological pain from physical pain are illogical and counterproductive. The coexistence of chronic
pain and depression as a reflection of the biochemical imbalance in serotonin levels is a well-described example.
653
Yet psychological factors do play important roles in the outward expression and adjustment to both acute and
chronic pain. Patients with medically unexplained symptoms do exhibit higher psychiatric morbidity, perhaps as a
reflection of the distress induced by the uncertainty of both diagnosis and prognosis. Anxiety states, depression,
[40]
organic brain dysfunction, and post-traumatic stress disorder (PTSD) can all lead to expression of pain seemingly
out of proportion to what would be typically expected based strictly on the overt physical damage. Denial, [41] [42]
anxiety, depression, irritability, family problems, sleep disorders, and increasing narcotic use or dependence on
alcohol or tranquilizers frequently accompany chronic pain.
Bias can easily be introduced when self-reporting measures are used exclusively. Patients have shown great ability
to fake responses on the Coping Strategies Questionnaire, the Multidimensional Pain Inventory, and the Pain Beliefs
and Perceptions Inventory. Objective measures should be included whenever practical.
[43]
PATIENT SELECTION AND OUTCOME PREDICTION
A number of investigators have included psychological data in the selection of patients for invasive therapies such
as nerve block, spinal cord stimulation (SCS)
[44]
and spine surgery. The efficacy of therapy at a 6-month follow-
[45] [46] [47]
up for epidural steroids and a 12-month follow-up for SCS was successfully predicted. The extensive Belgian
[44] [48]
experience also bears out the utility of psychological screening from both patient care and cost-containment
perspectives.[49]
The psychological screening tests are properly used to identify patients at risk for serious underlying
psychopathology, to predict treatment response, and to guide multimodal therapy. They should in no way be taken
as a substitute for the psychological interview. The importance of the personal interview in outcome prediction and
validation of the screening data has been stressed by many investigators. [50] [51]
Psychological selection criteria for SCS have been extensively studied. The intense interest in refinement of the
[52]
screening process for SCS may have been influenced by the frequent requirement for psychological clearance by
insurers. Although these studies considered only SCS, the criteria developed may be applicable generally to invasive
pain interventions. Both absolute and relative exclusionary criteria have been advanced. The most significant
contraindications to intervention include active psychosis, suicidal or homicidal ideation, poorly controlled major
depression, debilitating anxiety and panic disorders, somatization disorder, drug dependency, litigation, poor social
support, and cognitive impairment. Relative concern was also expressed with respect to inconsistencies, abnormal
testing data, and paranoid, schizoid, schizotypal, antisocial, borderline, histrionic, or narcissistic personality
disorders.
DEPRESSION
The Beck Depression Inventory has been widely used for the quantification of degrees of reported depression; it is
ineffective in states of masked depression. Although none of the proposed tools are meant to substitute for the
evaluation of an experienced psychiatrist or psychologist, both the affective portion of the McGill Pain
Questionnaire and the Beck Depression Inventory have demonstrated predictive value. [53]
ANXIETY
Anxiety states are well known to interfere with self-reporting. It may well be true that given sufficient ambient
anxiety, patients are unable to recognize even dramatic improvements in analgesia and function. This effect is not [44]
restricted to patients with chronic nonmalignant pain. The effects of anxiety in both the acute pain setting as well as
in the expression of pain associated with cancer are also impressive but frequently neglected. Further, although [54] [55]
anxiety in chronic pain has long been thought to relate to situational distress, more findings suggest premorbid
personality characteristics are of primary importance, as Zung Anxiety Scale scores failed to improve in patients
who otherwise reported symptomatic and functional improvement after treatment. Anxiety score elevations predict
[44]
treatment failure in response to epidural steriods and SCS. In contrast, Wallis and associates reported resolution
[44] [46] [56]
of generalized psychological distress, as measured more globally by the Symptom Checklist-90-Revised (SCL-90-
R), after effective pain elimination.
COPING
Patients' coping mechanisms, whether passive or active, adaptive or maladaptive, have much to do with their ability
to accept responsibility for getting well and achieving independent functioning. Assessment of results helps to
structure a specific pain-coping skill intervention for each patient. Adaptive coping mechanisms, especially coping
[57]
654
self-statements, are associated with improved pain control. The PSOCQ has validity not only as an intake
[58]
assessment tool but also as an outcome measurement device. The PSOCQ subscales for precontemplation and
contemplation predict treatment compliance, whereas changes in the action and maintenance subscales after
treatment are associated with improved outcome. [59]
POST-TRAUMATIC STRESS DISORDER
Post-traumatic stress disorder is a state characterized by high levels of anxiety after a traumatic incident. Panic
attacks, phobic reactions related to stimuli involving the original traumatic event, and pain symptoms predominate.
Symptoms consistent with PTSD in chronic pain patients are associated with affective distress and depression. [60] [61]
The PCPT has been developed as a screening instrument to aid in early detection of PTSD. Patients who attribute
their pain to a specific traumatic event, even in the absence of PTSD, report higher emotional distress, life
interference, and pain severity and have greater disability. Accident-related high PTSD scores are associated with
[62]
increased pain, increased affective distress, and greater disability. The potential for bizarre and exaggerated
[44] [63]
responses after invasive therapies is increased in the presence of both PTSD and anxiety disorders. Psychological
“clearance” after stabilization is suggested before nerve block, or any invasive procedures, in these patients.
Functional Assessment
The challenge to find shorter questionnaires to satisfy evaluative and outcome needs has led to the comparison of the
Oswestry low back pain disability questionnaire to shorter instruments. The Short-Form-36 (SF-36) was compared
with the Oswestry questionnaire in patients with low back pain. Mental health items had the weakest correlation;
other measures were significantly correlated. Patients with low back pain had only a moderate correlation between
[64]
the Oswestry and the Roland-Morris scales; however, both successfully distinguished between patients with
radicular and nonradicular low back pain. [65]
Although the modified Roland Scale was as good as the Sickness Impact Profile in assessing physical function, it
was less effective in measuring psychosocial function. The Roland Scale consists of 24 questions, whereas the
[66] [67]
Oswestry questionnaire has 60 questions in 10 sections. Another short questionnaire, the Low Back Outcome
[68]
Score, was found to be more comprehensive and discriminating than the Waddell Disability Rating, Waddell
Physical Impairment Rating, or Oswestry disability scores. Although this information was not validated for
[29]
patients with other pain syndromes, the general nature of the questions makes this questionnaire adaptable to a wide
range of conditions.
INCONSISTENCIES
Perhaps the most widely recognized examples of inconsistencies in the examination of low back pain are Waddell's
signs. These findings include superficial nonanatomic tenderness; pain with axial loading or twisting the torso as a
unit; a discrepancy between straight-leg raising (SLR) in the sitting and lying-down positions; nonphysiologic
regional disturbances in sensation, pain distribution, or weakness; and overreaction, excessive verbalization, facial
grimacing, or other pain behaviors out of proportion to test stimulus and physical findings. The presence of three
[69]
or more of Waddell's signs predicts treatment failure and is associated with alterations in Minnesota Multiphasic
Personality Inventory (MMPI) scales for defensiveness (K), lie (L), and hypochondriasis (Hs). Although [70]
Waddell's signs predict poor outcome acutely, they are not necessarily negative predictors in an interdisciplinary
context. An Inconsistency Profile has similarly sought to objectify this effect. This profile specifically includes
[71] [22]
the response to diagnostic injections that do not correspond to recognizable physiologic, pharmacologic, or anatomic
patterns. The inherent danger in strict adherence to this philosophy is that as our understanding of pain mechanisms
improves, previously unrecognizable findings become explicable, which makes the physician component the
inconsistent piece of the puzzle.
Interpretation of inconsistencies and other pain behaviors as malingering does little to benefit the patient. These
findings should instead be viewed as a plea to enlist the practitioner as an advocate. For example, the patient may
feel trapped in a job that has unrealistic activity requirements relative to the patient's age or health status.
Negotiations with an insurer, legal action, or other psychological or socioeconomic pressures may influence this
behavior on a conscious or unconscious level. The overall goal should always be to facilitate the patient's recovery
and to avoid the development of chronic disability.
PHYSICAL FUNCTIONING IN EVERYDAY LIFE AND FUNCTIONAL ASSESSMENT
655
The battery of tests described by the pain group at St. Thomas' Hospital in London is an improvement over standard
self-reporting methods. The measures suggested include the Walk Test: 5 minutes, Stair Climb: 1 minute, Stand-up:
[72]
1 minute (from chair), and Arm Endurance Test (holding both arms horizontally out to the side while describing
small circles). These simple assessments not only offer an advantage in the ease of an application for an initial and
follow-up evaluation but also may be more appropriate for chronic patients than more complex computerized
functional capacity tests.
Functional capacity evaluations reveal less than maximal effort in the presence of anxiety, depression, and self-
reported disability. Functional evaluations emphasizing precise measurement are flawed in that the magnitude of
[73]
improvement in pain is poorly correlated with improvements in movement. Further, specific exercise programs for
[74]
patients with low back pain have not shown a positive effect on physical impairments, functional limitations, or
disability. One exception may be in specific programs designed to strengthen the abdominal and lumbar multifidus
[75]
muscles proximal to the pars defect as a stabilizing maneuver for symptomatic spondylosis or spondylolisthesis. [76]
The finding that multifidus muscle recovery is not necessarily spontaneous after remission of pain may explain a
high level of recurrence of acute back pain and the genesis of chronic problems. This is consistent with the finding
[77]
that mechanical low back pain responds favorably to physical therapy interventions in contrast to the lack of
improvement in patients with radicular pain. These physical therapy interventions, however, for maximal benefit,
[78]
should consist of manual therapy techniques based on motion-provoked symptoms. For most patients, functioning in
everyday life may provide a better objective measure of both disability and improvement.
JOB-SPECIFIC TASKS AND WORK HARDENING
Vocational rehabilitation, disability evaluation, and work hardening are often available through interfacing with
physical medicine and rehabilitation specialists. Although biomechanical and ergonomic approaches have been
traditionally used at first onset of low back pain, there is little evidence that these principles are applicable to the
genesis or treatment of chronic pain. An early return to work rather than restricted activity is recommended
whenever possible. [79]
RETURN TO WORK
Fifty percent of claimants on disability for a given period of time can be expected to remain on disability for six
times that long, resulting in 7% of claims extending beyond 1 year. These protracted periods of disability, extending
for 12 months or longer, account for 75% of the cost of the disability. Patients completing a spine rehabilitation
[80]
program with and without workers' compensation had similar length of treatment, flexibility, strength, lifting ability,
and lower extremity work performance both before and after treatment, but at 12 months, pain scores were only
improved in the noncompensation group. This dichotomy with respect to functional improvement, without
[81]
subjective improvement in pain report, is also seen with neural blockade interventions in patients receiving
[44]
compensation or involved in litigation related to their pain complaints.
Multimodal Treatment
Although multidisciplinary treatment has been presumed to be the gold standard, the effectiveness of multimodal
treatments has been poorly documented. The failure to define a given study population for pretreatment
psychological characteristics makes comparisons of various interventions difficult. One objective measure of
effectiveness previously discussed is the return to work. Yet depression and pain are higher in patients with workers'
compensation. In a rehabilitation model, the presence of compensation significantly impaired the ability of
[81]
treatment to affect both disability and depression. This effect has also been reported with respect to anxiety and pain
in the presence of compensation or litigation. [44]
Coping mechanisms have also been well studied. Catastrophizing, searching for information, and cognitive control
can be measured. Self-evaluation of the potential for return to work, application for pension, length of absence from
work, and subjective sense regarding the extent of the disability correlate well with return to work, whereas coping
strategies per se, or their alterations, failed to predict return to work. Physical variables also poorly predict return to
work as outlined in the preceding section. The patient's outlook regarding the future has repeatedly been identified
[82]
as one, if not the key, indicator for predicting outcome. Patients with an optimistic outlook perceive a greater control
over pain and endorse coping strategies that involve diverting attention, ignoring pain, and making coping self-
statements. [83] [84]
BEHAVIORAL MEDICINE
656
Incorporation of cognitive behavior therapy in the medical care of chronic low back pain patients in a controlled,
randomized study caused patients to experience less pain, better control, more pleasure, less avoidance, and less
disability. Relaxation and imagery were primary components of therapy. Although some contend that cognitive
[85]
behavior programs help regardless of whether the patients are treated individually or as a group, others claim that
inpatient or “full-time” intensive treatments offer advantages. [86] [87]
The suggested behavioral medicine intervention is to engage the individual in dynamic psychotherapy designed to
reduce anxiety and depression and to promote the development of active and adaptive coping styles. Psychiatric
screening for potentially serious underlying mood disturbance and the presence of PTSD is routine. Additionally,
pain-reducing interventions are emphasized. These include relaxation exercises for myofascial pain,
electromyographic (EMG) biofeedback for myofascial and spinal pain, and skin conductance or temperature
biofeedback for neuropathic pain states.
PHYSICAL THERAPY
Despite the lack of evidence supporting the efficacy of physical therapy techniques used in isolation to treat chronic
musculoskeletal pain, the stretching of trigger points after injection and the application of moist heat are
[88]
considered essential components of treatment. Similarly, instruction in home stretching to maintain the gains
achieved should also be considered routine. The ability of patients with myofascial dysfunction to recognize the
early onset of exacerbation and take active measures to control the pain is of immeasurable value. Stretching
programs progressing to a 3-month training and conditioning at home have not only been successful in reducing
both pain and disability but also in increasing optimism and self-control. Exercise in association with cognitive
[89]
retraining, although typically failing to improve the number of patients returning to work, may reduce symptoms and
improve coping in patients with chronic spinal pain. Physical interventions after other nerve blocking techniques
[75]
are less well studied.
The use of neural blockade immediately before manipulation of the spine arguably enhances the efficacy of either
treatment used alone or sequentially. Denervation of receptive fields related to the innervation of the facet joints
may allow improved manipulation efforts because of the prevention of reflex muscle spasm and guarding during
treatment. Yet total sensory blockade may permit dangerous overstretching of the tissues. Precise neural blockade of
the posterior elements of the spine allows optimal therapeutic intervention with improved safety.
The use of neural blockade in concert with physical therapy has long been employed to help patients tolerate a more
aggressive manipulative program. However, careful scientific scrutiny has been applied in a limited subset of these
multimodal treatments. The use of physical manipulation immediately after epidural steroid injection has been
reported, anecdotally and in one small series, to provide superior results compared with the use of both therapies
concomitantly, but not on the same day. The use of manipulation after blockade of the posterior, “mechanical”
[90] [91] [92]
elements of the spine was reported in a series consisting of only four cases of lumbar facet and sacroiliac
dysfunction.[93]
The reason for improvement when these therapies are temporally linked to neural blockade may relate to the degree
of pain relief obtained after injection. The type of block and quality of denervation vary with epidural, sacroiliac
joint, intra-articular facet injection, or medical branch blockade. What influence these neural blockade interventions
have on the quality of subsequent manipulation may depend on the precise mechanisms involved in the generation
of pain and effective resolution of attendant muscle guarding.
Manipulation of the spine has been associated with rare complications. Manipulation under anesthesia may mask
[94]
reflex muscle guarding and permit dangerous overstretching. A case of epidural hematoma was reported as a result
of manipulation after cervical epidural analgesia. In the case report cited, the patient performed the stretching
[95]
exercise without supervision. The authors postulated that the widespread nonspecific blockade that was provided
permitted stretch beyond safe limits. However, hematoma resulting from the epidural anesthesia itself cannot be
excluded. Nevertheless, careful and specific physical interventions within the physiologic range, combined with
blockade limited to specific target elements, should minimize these risks.
The suggested physical therapy intervention is that all patients undergo an initial evaluation that includes a
functional capacity assessment as well as instruction in biomechanics, perpetuating factors, and corrective actions.
Patients being treated for myofascial pain receive instruction in home stretching exercises for the specific muscles
involved. Muscle-specific stretch within 2 hours after injections precedes a gradual transition to strengthening
exercise. Patients in the neuropathic pain protocols typically receive desensitization interventions with mobilization
of the extremity immediately after neural blockade. Spine protocol subjects who receive neural blockade directed
657
toward facet, atlanto-occipital (A-O), or sacroiliac articulations are treated with manual therapy techniques to
facilitate mobilization of the affected segment. Strengthening exercises designed to stabilize the spine (e.g., multifidi
and abdominal muscles) are introduced gradually. For painful upper extremities, a computerized hand evaluation
system to quantitate volumetric and temperature changes during the course of treatment has also been helpful. All
patients undergo repeat functional capacity assessment at discharge, and, when possible, at long-term follow-up.
MEDICATION ADJUSTMENT
Although oral analgesics are beyond the scope of this chapter, it should be noted that specific protocols might
include the introduction and adjustment of antidepressants, anticonvulsants, α2 -adrenergic agonists, nonsteroidal
anti-inflammatory drugs (NSAIDs), muscle relaxants, narcotics, and other medications. These protocols run
concurrently with all other protocols of medical management. Consideration as to concurrent medical conditions and
their associated medications, as well as the contemplated interventional therapy, is necessary to avoid adverse
outcome caused by drug interaction. [96]
REHABILITATIVE MEDICINE
Vocational and disability evaluation should be performed as part of the structured rehabilitative pain services.
Regular progress reports, including functional capacity assessments, direct a gradual transition into a work-
hardening program. Exercises are designed to address specific functional impairments. Behavioral techniques to
promote wellness behavior while extinguishing pain behavior are used. Cognitive retraining in association with
physical therapy, whereby an initial week of home stretching gradually evolves into strengthening and aerobic
exercises, has been effective. Overzealous acceleration of active physical components is a frequent cause of pain
aggravation and failed treatment.
Neural Blockade
The protocols presented in the following paragraphs have been deliberately generalized. Although a number of
clinical guidelines and algorithms for specific nerve blocks have been advanced, these recommendations generally
lack scientific basis. The correct number of interventions, or sequence of trials, cannot be predetermined without
clear outcome-based investigation. Protocols that sequentially offer patients a series of diagnostic and trial
therapeutic procedures may seem unlikely to effect improvement when patients are far out on the tertiary branches
of the algorithmic tree. However, quite to the contrary, at least in the short term, these programs have demonstrated
surprising efficacy. Still, a rational approach based upon clinical findings and patient selection provides further
[97]
refinement.
When nerve blocks are used in the treatment of chronic nonmalignant pain, the documentation should include the
following:
1. Initial assessment and indication before each intervention

2. Measures of pretreatment pain intensity
3. The presence and degree of pain reproduction with provocative maneuvers
4. Sufficient treatment detail to permit comparative analysis between operators
5. Immediate results following an injection with respect to alterations in pain and the response to provocative
maneuvers to assess the effectiveness and completeness of blockade
6. Pain diaries for long-term assessment, because memory for pain lacks sufficient precision to draw
diagnostic conclusions
Specific examples include the following:
• Myofascial trigger point injection: pressure algometry, abolition of the local twitch response, improved
range of motion with stretching
• Sympathetic blockade: quantitative sensory testing, allodynia resolution, and temperature changes
• Medial branch block: reverse straight-leg raising (RSLR) or other provocative testing, improved tolerance
for manual therapy
• Epidural steroid: straight-leg raising (SLR) reduction in radicular symptoms
PROVOCATIVE TESTING
658
Diagnostic medial branch blocks may produce considerable soreness in the area of injection, masking the responses
obtained on a pain diary. Provocative testing performed after the block is critical to the interpretation of the test.
This physical examination of the patient must not be confused with pain provocation on injection (distention) of the
joint itself. This effect (pain on joint distention) has questionable validity as the sole criterion for the diagnosis.
Schwarzer and associates examined more than 200 joints as follows: reproduction of exact or similar pain on
[98]
injection; elimination of the produced pain after block with 2% lidocaine; then, in those with positive responses, a
repeat procedure with 0.5% bupivacaine. They found that reproduction of the patient's typical pain correlated with
definite or complete relief with a single block (P < .0001), but this was not correlated with a long-acting
confirmatory block. Although the authors contended that because pain provocation did not accurately predict which
patients would exhibit a pattern of response to injections, the responders to the first injection were essentially
placebo responders. Whether this conclusion is justified or not, the addition of physical examination findings, before
and after block, is a more reliable monitor than simple self-reporting measures alone.
The false-positive rates of cervical zygapophyseal joint blocks (medial branch blocks) were reported by Barnsley
and colleagues. They considered to be true positive responders only those patients who could correctly distinguish
[99]
the longer duration of relief with bupivacaine as opposed to lidocaine. They found a false-positive rate from the
initial block based on the preceding criterion to be 27%. According to their rigid criteria, individuals who obtained
increased duration of relief with lidocaine on the second injection, experienced this relief simply because it was their
second injection and hence their condition was improving; these patients were eliminated from further consideration.
The clinical pattern of improvement should not be ignored simply because of an apparent incongruity in the
expected duration of relief based on the nature of the agent used. A well-placed lidocaine block may, in fact, outlast
a poorly placed bupivacaine block if only a small amount of bupivacaine were to reach the target nerve.
Referral, Discharge, and Follow-up
Short-term follow-up generally includes analysis of a pain diary completed by the patient, depending on the
treatment given, in the first hours to weeks after injection. Long-term follow-up is generally at least 6 months after
the patient's last treatment and includes a VAS, the Low Back Outcome Score, and a measure of overall patient
satisfaction, the Treatment Helpfulness Questionnaire (THQ). The THQ has been suggested to be a reliable and
valid tool for assessing patient perceptions regarding satisfaction with treatment modalities provided in chronic pain
management programs. [100]
Protocol Adjustments
OUTCOME ASSESSMENT
As previously mentioned, all protocols should evolve with time, staying responsive to new developments globally
and the practical results locally. Intramural introspection plays the pivotal role in continuous quality improvement,
and may well be essential to the continued use of regional blockade for chronic pain in the future. Therapies that fail
to provide evidence-based outcome in a cost-effective manner, especially those with significant risk for causing
harm, will likely be phased out of the medical armamentarium. The use of regional anesthesia techniques for chronic
nonmalignant pain management has historically been of tremendous value. However, continued use of these
powerful tools will only be justified in a setting that allows continuous systematic reexamination of their use.
COMPLIANCE
The importance of capturing a true assessment of a program's performance is crucial to making appropriate protocol
modification. Compliance with mailed questionnaires is historically poor. Outcome questionnaires for patients
receiving epidural steroids over a 4-year period studied were returned by only 26% of patients. Aggressive
telephone contact increased that value to 72% (the residual being essentially lost to follow-up due to change of
address, death, or confinement). Compliance with outcome data collection was further improved with the reduction
[44]
of the mailed evaluation form to a single page. Yet factors other than convenience play significant roles in patient
cooperation with outcome assessment follow-up.
Evaluated patients in the aforementioned study who failed to receive authorization for treatment were followed up as
controls. None of the patients entered in this category returned their questionnaires. Satisfaction with the treatment
received, or not received, certainly plays a major role in outcome data compliance. Additionally, a statement to be
signed by the patient acknowledging the responsibility for returning the outcome questionnaire at 6 months as a
condition of the treatment can also be included with the orientation materials.
659
DATA ANALYSIS
Data collection intramurally can be disappointing unless a limited number of protocols are investigated. The number
of patients needed to achieve statistical significance with a large number of groupings overwhelms even large
centers, especially if a variety of parallel programs are being compared. Functional assessments and rate of return to
work are most useful in determining efficacy of treatment, especially in the presence of active litigation, workers'
compensation, or disability benefits.
PROTOCOL STRUCTURE AND MODIFICATION
Written admission criteria for each protocol help to assure that patients accepted for treatment are likely to benefit
from the service provided. Screening of referral information permits judicious continuation of the evaluation process
by avoiding unnecessary duplication of tests. Discussion of treatment goals, treatment options, and patient
responsibilities are integral to the intake and orientation process.
Entry into various treatment protocols takes place with consideration of the patient's physical, psychological, social,
vocational, and educational status. The individual's program should focus on integration into the community by
maximizing independent functioning. The patient's program and goals must be continually reviewed and modified as
dictated by the response to treatment. Although patients are initially enrolled with the criteria of specific treatment
protocols, sufficient latitude is retained by the practitioners to allow individualization of treatment and treatment
goals. Case managers are assigned to assure implementation and orientation, as well as to monitor the progress of
the patient's treatment program.
Exit criteria, referral, and ongoing treatment patterns are established before treatment. Specific criteria for
movement within each individual protocol, as well as for the program as a whole, are defined prospectively. Follow-
up procedures help to guide further program efforts, to provide ongoing quality improvement, and to shape protocol
modification.
Protocols for Neural Blockade in the Treatment of Chronic Nonmalignant Pain
Defining a limited number of treatment protocols is accomplished most efficiently by using a system based on the
mechanisms of pain generation. Mechanistic taxonomy has been advanced wherein pain is classified as transient
pain, tissue injury pain, or nervous system injury pain. Tissue injury pain and nervous system injury pain are both
[101]
further subdivided into primary afferent and CNS disorders. Unfortunately, for many chronic pain conditions, there
is currently insufficient knowledge as to the underlying mechanisms to permit the practical application of this
approach. Further pragmatic considerations, especially with respect to pains that are amenable to regional anesthesia
intervention, have led to the following arbitrary subdivision into pain of spinal origin, neuropathic pain, and
myofascial pain for the purposes of this discussion. In assigning patients to these categories, it is essential to
recognize that mechanistic, and hence therapeutic, crossover from one protocol to another is often necessary.
PAIN OF SPINAL ORIGIN
Sources of Spinal Pain. The number of pain-sensitive structures now recognized as potential causes of persistent
pain of spinal origin is increasing. The anulus of the intervertebral disc, the facet joint and capsule, the spinal nerve,
the dorsal root ganglion (DRG), the dura, the posterior longitudinal ligament, and the paravertebral musculature, as
well as the articulations at either end of the vertebral column, with the pelvis (sacroiliac joint, SIJ) and the skull (O-
A joint), are common sites of chronic pain generation.
In the cervical region, the sinuvertebral nerve receives contributions from the ramus communicans, the sympathetic
trunk, and the stellate ganglion and provides innervation to the dura, the posterior longitudinal ligament, and dorsal
anulus fibrosus. The sinuvertebral nerve in the lumbar area supplies sensation to the lateral and dorsal intervertebral
disc, the posterior longitudinal ligament, and the dura. Additional fibers to the posterolateral disc from the anterior
root, the lateral and anterolateral disc from the DRG via the ramus communicans, and to the anterior disc from the
sympathetic chain (also via the ramus communicans) provide sensory innervation. Figure 27–1 gives a diagram of
medical protocols regarding pain of spinal origin.
The complex nature of spinal innervation makes it likely that even the most precise diagnostic injections will affect
a number of structures simultaneously. A practical outcome-based analysis is necessary to avoid the previously
mentioned pitfalls due to oversimplification after diagnostic intervention. Additional diagnostic pitfalls described in
the Agency for Health Care Policy and Research report on acute low back pain in 1994 and modified by the Royal
660
College of Surgeons in 1997, are also important considerations in chronic pain situations. Pain of nonspinal origin [102]
mimicking spinal pain, undiagnosed malignancy in the spinal column or epidural space, and evidence of cauda
equina syndrome are conditions requiring urgent medical intervention.
Anterior Spinal Segment
Epidural steroids.Patients with anterior spinal segment dysfunction and radicular irritation typically display
characteristic pain patterns. These patterns may be dermatomal or myotomal depending on whether the dorsal or
ventral root is involved, respectively. Symptoms and signs consistent with radicular irritation are often reproduced
during activity that might be expected to stretch the nerve roots, resulting in limited spinal flexion. Positive SLR
(lumbar) or Spurling's (cervical) tests may result. The use of epidural steroids in this setting is well established.
The therapeutic use of neural blockade for the treatment of pain of spinal origin was comprehensively reviewed by
Stolker and associates. The literature regarding the efficacy of epidural steroids was reviewed by Koes and
[103]
colleagues. Flaws in method

[104]
Figure 27-1 Pain of spinal origin. SCS, Spinal cord stimulation; Sl, sacroiliac.
predominate in the literature because patients are often reluctant to participate as controls and selection criteria are
rarely rigorous. Numerous other reasons for study failures are described in McLain's review. [105]
Reported long-term results after epidural steroid injection for chronic radiculopathies have varied. These [104] [106] [107]
differences may also be partially explained by the multifactoral nature of chronic radicular pain syndromes.
Identification of factors that predict response to epidural steroid treatment aids in the selection of appropriate
candidates, thus reducing unnecessary invasive procedures. Failure of lumbar epidural steroids (LESs) to provide
long-term relief in low back pain patients has been associated with pain that did not limit activity, unemployment
due to pain, pain undiminished by medication, and normal pretreatment SLR. Hopwood and Abram likewise [108] [109]
reported failure of LESs in association with nonradicular pain and lack of employment. Additionally, these authors
also noted that both a history of prolonged duration of symptoms before treatment and a history of smoking were
also predictive of treatment failure.
Harrtick studied patients demonstrating lumbar radicular symptoms with positive SLR on physical examination.
[44]
The presence of workers' compensation claims, disability benefits currently being paid, or pending litigation
correlated significantly with failed LES therapy. The pronounced deleterious effect introduced by these “litigation”
factors overshadowed all other measures. The susceptibility of self-reporting measures to bias under these
661
circumstances has been previously mentioned. These results strongly suggest that predictive measures based on
[81]
self-reporting are of limited value in the presence of litigation or other financial compensation for continued pain
complaints.
Both litigants and nonlitigants reported significant improvements in function after LES treatment. This functional
improvement, however, was not associated with reported improvement in pain in the litigant group. The tendency in
the nonlitigant group toward increased pain with activity before treatment and reduced pain with activity after LES
therapy was consistent with the findings of Jamison and coworkers. Similarly, the significantly reduced efficacy of
[108]
LESs with increasing duration of pain before treatment as reported by Hopwood and Abram was again only seen [109]
in the nonlitigant group. Although litigation factors were associated with higher post-treatment anxiety scores,
pretreatment elevations in the Zung Anxiety Scale were of predictive value only in the nonlitigant group. For
nonlitigants, elevated pretreatment anxiety levels were associated with reduced efficacy as measured by reported
pain reduction. In those patients with significant improvement, however, commensurate reductions in anxiety levels
subsequent to treatment were not observed. This may suggest that the affective measures used are indicative of traits
as opposed to general measures of distress in this setting. For those patients with PCPT scores suggesting the
presence of PTSD, this effect was most apparent.
Improving access to epidural steroid injection may have significant implications with respect to the reduction in
surgical interventions. The so-called fast-tracking of the evaluation process to facilitate this treatment may also be
[110]
justified in selected circumstances. High anxiety, long duration of pain, pain unrelated to activity, and
[111]
nonradicular pain distribution all predict poor response to epidural steroids.
Epidurogram.Persistent pain after laminectory has infrequently resulted from the development of sympathetically
maintained neuropathic pain. Yet chronic postlaminectomy pain is quite common. A frequent radiographic
[112] [113]
finding is the presence of epidural scarring that can be seen to tether the symptomatic nerve roots. Notably, epidural
scarring involving asymptomatic roots is of no clinical importance and should not be manipulated. Further, in the
interpretation of epidurograms it is important to note that fibrous structures appear in the normal subarachnoid and
epidural spaces with some frequency. The linear characteristics are readily distinguished from the irregular
[114]
patterns of epidural fibrosis. Epidural fibrosis observed using magnetic resonance imaging (MRI) is distinguished
from recurrent disc herniation by enhancement with gadolinium.
The presence of extensive epidural fibrosis may limit the spread of epidural steroid injected, thus preventing steroid
delivery to the affected root. When such a condition is suspected, an epidurogram is performed under fluoroscopic
guidance. If adhesions are seen to prevent the appropriate spread of medication to the affected root (clinically
matching the patient's symptoms), epidural lysis of adhesions may be attempted with use of a wire-reinforced
catheter or a myeloscope.
Epidural Adhesiolysis. Lysis of epidural adhesions was described and popularized by Racz and Holubec. A [115]
review of the accumulated experience further defined the role of this technique. Neuroplasty through lysis of thin
[116]
fibrinous adhesions is accomplished by the mechanical action of the catheter and, possibly, by other mechanisms.
Several areas of controversy remain with respect to this technique. The use of hyaluronidase has been associated
with serious neurologic sequelae when inadvertently placed into neural tissue, and the long-term results do not
appear to be affected by the addition of this agent. Secondly, the use of hypertonic saline has been associated with
[117]
a number of transient neurologic consequences and has debatably demonstrated marginally improved long-term
outcome. Finally, the use of a catheter for daily injection may or may not be of long-term benefit.
[117] [118]
Myeloscopy Epiduroscopy.This is a developing technology that permits an alternative approach to lysis of

adhesions. One advantage of direct visualization is that it allows observation of the results of manipulation. Perhaps
more important, direct inspection permits monitoring of any trauma induced by the procedure itself. Further
advances in this technique may allow percutaneous treatment of pathology that heretofore required open
laminectomy. Laser-assisted myeloscopic adhesiolysis has been reported. Patients with preexisting bowel or
[119]
bladder dysfunction may also be at risk for increased incidence of complications. Further, the introduction of
epidural instrumentation may itself produce changes in the epidural space. Repeated epidural injections, especially
when a rigid catheter or myeloscope is employed, may induce adhesions because of direct trauma and hemorrhage. [120]
Selective Root Block. Paravertebral spinal nerve injection (root injection is technically incorrect as both anterior
and posterior contributions are present) has been used as a predictor of surgical intervention Cutaneous evaluation is
unlikely to be helpful as loss of a single root often fails to produce numbness because of overlap from the roots
above and below. Thermographic evaluation may be useful. Paravertebral spread to adjacent levels often occurs
with as little as 2 mL of anesthetic. Spread into the intervertebral foramen may result in block of the sinuvertebral
nerve, which affects innervation of the dura, posterior longitudinal ligament, and anulus of the disc. Anesthetic
662
introduced through this approach may also spread epidurally to other spinal levels. Despite these failings, this
technique is reported to be better than imaging studies or EMG in the prediction of surgical outcome. [121] [122]
Radicular pain secondary to epidural fibrosis that is unresponsive to neuroplasty may be amenable to selective root
block under fluoroscopic control. Transforaminal injection of local anesthetic diluted in 1500 units of hyaluronidase
and 40 mg methylprednisolone has been reported to be effective in this situation. The precise deposition of drug on
the specific nerve root should be documented with contrast injection. [123]
Spinal Cord Stimulation.SCS success depends to a considerable degree on the ability of the electrodes to provide
stimulation over the levels of the cord required to cover the painful areas. Best results are observed in patients with
unilateral lower extremity pains treated with a single electrode. Midline pain, bilateral pain, or pain at multiple sites
requiring more than one electrode is associated with higher rates of technical failure. Surgically implanted electrodes
via limited laminotomy are associated with less long-term migration. The efficacy at 1-year follow-up in a
prospective study of 70 patients was reported with 55% of patients experiencing improvement defined as greater
than 50% pain relief. As previously discussed, screening with a psychological interview and trial stimulation were
used. Improvements were also measured in the VAS, McGill Pain Questionnaire, the Oswestry questionnaire, the
Sickness Impact Profile, and the Beck Depression Inventory. Complications requiring surgical intervention were
seen in 17% of patients in the first year. [47]
Others have attempted to predict success or failure of SCS with screening psychological evaluation. Dumoulin and
coworkers reported a high correlation between outcome with SCS and predictive assessment based on a
[50]
psychological interview. The interviewers assessed 24 items prospectively and six evaluative items at 6 months. The
weighting and scoring methods, however, were not described. Similarly, Meilman and associates lent support to
[51]
the notion that a trained psychologist's interview is more accurate than any specific tests. They found short-term (1-
month follow-up) prediction to be poor. However, when single nerve root injury or mononeuropathy patients were
separated from those exhibiting arachnoiditis or multiply injured roots, or both, those with single-root involvement
not only had much better results, but their improvement was accurately predicted on psychological grounds.
The extensive Belgian experience also bears out the utility of psychological screening. This investigation was
[49]
carried out by Belgian health authorities for the purpose of assessing the rapid expansion in the use of SCS from a
cost containment viewpoint. They found that few patients had returned to work and that 52% of the patients reported
good to very good subjective improvement after 3.5 years (mean follow-up time). They also found that positive
psychiatric advice predicted significantly better therapeutic outcome (64% improved at 6 months) compared with
patients about whom the psychiatrist had reservations (18% improved at 6 months). Long and colleagues also [124]
reported improvement in success rates from 33% to 70% when psychological screening was instituted. Randolph [125]
offered further refinement by combining the exclusionary criteria presented by Nelson and coworkers with the [52]
graduated psychiatric advice of Kupers and associates. [49]
North and colleagues summarized more than 20 years of experience with SCS. Nearly 50 studies were reviewed.
[46]
Long-term response has been inconsistent. Most likely, this reflects in large part an inability to predict which
patients are most likely to benefit. With improved screening, more centers are reporting long-term positive results in
patients with “failed back syndrome.” The indications for implanted devices in the treatment of intractable pain
[126]
include an objective basis for the pain; the failure of alternative therapies; the absence of serious psychopathology;
secondary gain or drug dependency; and, for SCS, the topography of pains must be such that they are amenable to
superimposed stimulation paresthesias. The routine placement of a temporary electrode addresses the last issue.
[127]
SCS is appropriate for arachnoiditis or failed back pain, ischemic pain secondary to peripheral vascular disease,
peripheral nerve injury, and complex regional pain syndrome (CRPS). The less frequently suggested indications of
phantom limb or stump pain and segmental pain due to well-circumscribed lesions in the spinal cord are associated
with higher failure rates.
SCS is associated with vasodilation and improved cutaneous oxygenation that promotes healing of ischemic
ulceration. In a review of SCS for peripheral vascular disease, Claeys suggested improved efficacy when patient
[128]
selection criteria included persistent rest pain or ischemic ulceration of less than 3 cm2 , otherwise inoperable
pathology, and a greater than 6-month life expectancy. SCS has also been used in the treatment of symptomatic
coronary artery disease. Jessurun and associates reviewed the now extensive European experience with SCS for
[129]
angina pectoris unresponsive to medical management and not amenable to angioplasty or surgical intervention. The
effectiveness and safety in this setting appear to be established.
Discography.Pain from the anterior spinal segment that is nonradicular, that is, does not follow dermatomal or
myotomal patterns, may emanate from the intervertebral disc. Scleratomal distribution of pain with referred pain
posteriorly into the buttock is common. Discography is a test to determine the origin of pain generation in the spine
663
and should not be used as a test for disc herniation. Other noninvasive tests (computed tomography [CT], MRI) are
more suitable. It is the disc distention or “stress testing” that yields significant information. This diagnostic testing
[130]
identifies candidates for surgical intervention and disc denervation.
Single-level discogenic pain documented by discography may be expected to predict the need for surgical
intervention. A retrospective, unrandomized study reported that patients without psychiatric disease with discogenic
low back pain had comparable or better outcome without surgery than those who had received surgery. Their
population had 80% workers' compensation. Follow-up was at a minimum of 3 (mean 4.9) years. Older age at onset
of pain and shorter duration of pain predicted better outcome. A properly controlled study would be difficult or
[131]
impossible to perform in a patient population unlikely to consent to withholding treatment for a minimum of 3 years,
but it does raise the issue of whether surgical intervention is an effective long-term treatment.
Positive discograms have also been used to guide anterior lumbar interbody fusion. However, postoperative results
reported by Knox and Chapman were uniformly poor in two-level fusions, whereas only 35% of single-level
[132]
fusions reported good results. They also noted workers' compensation and previous surgery to be predictors of poor
outcome. Cervical discography, however, has been reported to accurately predict outcome for anterior cervical
fusion. When the patient's typical pain was provoked on discogram injection, good to excellent results were reported
in 73% of subjects studied. [133]
Intervertebral Disc Denervation. Radiofrequency lesioning of the ramus communicans has been advocated to
denervate the anterolateral and lateral intervertebral disc. Radiofrequency lesioning also has been performed
[134]
directly into the disc for internal disc disruption. These lesions can be performed when characteristic pain is
reproduced with provocative discography in the presence of a well-hydrated disc.
Intradiscal thermocoagulation represents a further refinement whereby a larger region of disc can be denervated by
passing a heating wire around the inner circumference of the anulus fibrosus. Candidates must have relatively
[135]
well-preserved disc height with no major disc protrusion or free fragments within the spinal canal. Intradiscal
electrothermal therapy heats the anular disc in an effort to destroy nociceptors and reorganize collagen fibrils, thus
sealing fissures within the disc. Because the collagen helices are rearranged, care must be taken to avoid placing any
stress on the treated disc until the structural integrity is reestablished. Physical therapy beginning at 6 weeks after
the procedure must be introduced gradually and designed to enhance lower extremity flexibility and truncal
stabilization.
Partial Rhizotomy. After epidural steroid treatment, a divergence in response, with respect to the radicular and
axial components of the pain, may be observed. When the radicular pain subsides but leaves the axial pain
unresolved, in the absence of posterior segment (facet) pain, other therapeutic options are suggested. Schwarzer and
colleagues. reported the relative infrequency of patients suffering from both discogenic and facet pain
[136]
simultaneously. However, the population studied was relatively young, with pain predominantly arising from work
or motor vehicle accidents. The frequency of these simultaneous maladies increases dramatically when severe
degenerative processes exist. In an older population, diagnostic delineation is often required. Discography may help
to confirm the origin of the pain as discogenic. Because the disc itself behaves as a visceral structure with regard to
the pain pathway (lower intervertebral discs send sympathetic afferents through the sinuvertebral nerves that pass
through the L2 nerve root), selective L2 root block may relieve the axial discogenic pain. If selective root
[137]
blockade relieves the pain, partial L2 dorsal root ganglionotomy (partial rhizotomy) may provide lasting relief. [138]
Rarely, in patients with a single affected root with dense adhesions that have failed adhesiolysis, a selective partial
rhizotomy may be performed at other levels, especially if the patient is not a candidate for spinal stimulation.
Vertebral Body Denervation. Vertebral body compression fractures, often resulting from osteoporosis, may
produce neural foraminal stenosis and radicular pain. However, when axial pain results, the pain may emanate from
the vertebral body, periosteum, or adjacent ligamentous structures, which are innervated in part by afferents from
the rami communicantes. Although vertebroplasty has been used to prevent further collapse by injecting methyl
methacrylate, improvement in pain is infrequent. In initial reports, radiofrequency lesioning of the ramus
[139] [140]
communicans under fluoroscopic control has resulted in dramatic improvement at 6 months. The use of CT
guidance may offer further refinement as the rami communicantes are often visualized with this technique.
Posterior Spinal Segment
Spinal Articulations.Patients with posterior spinal segment dysfunction typically display characteristic pain
patterns that vary on provocative testing depending on the segment involved. Symptoms and signs consistent with
mechanical spinal articulation dysfunction are often reproduced during activity that might be expected to stress or
distract these joints. Pain is usually aggravated after prolonged inactivity and results in limited spinal extension.
664
Greater Occipital Nerve Block. Although pain over the greater occipital nerve distribution, as the peripheral
continuation of the dorsal rami of the C2 root, may be considered radicular pain, it is included here because of its
frequent contribution to the perpetuation of cervicogenic headaches. Cryoneurolysis is effective in providing long-
lasting relief. The location of the nerve as it emerges from the suboccipital musculature allows safe placement of a
cryoprobe inserted cephalad over the occiput and directed caudally.
Cervicogenic headache is another form of spinal pain with multiple pain-producing sites. Precision diagnostic
injections are, again, useful. A-O articulation, atlanto-axial articulation, C2 root, suboccipital muscles, and the
[141]
vasculature all may contribute. The cervical-trigeminal-vascular hypothesis describes a possible interconnection of
neurochemical, vascular, and muscular mechanisms. Trigeminal connections to the vasculature are known. The
trigeminal nucleus extends into the cervical spinal cord. The potential for a common pain pathway for migrainous,
tension, and cervicogenic (facet or cervical root involvement) headaches is, therefore, established.
Atlanto-Occipital Joint Block. Characteristic referred pain patterns from the A-O joint demonstrate considerable
overlap with the distributions of the greater and lesser occipital nerves, as well as the referred pain emanating from
the C2–C3 facet joint. Diagnostic block under fluoroscopic control is essential to the diagnosis. Involvement of the
[142]
A-O joint after whiplash injury is less frequent than involvement of the cervical facets.
Facet Block. Whiplash injury was reviewed by Barnsley and coworkers The zygapophyseal joints, disc, muscles,
[143]
trigger points and myofascial pain, ligaments, atlanto-axial complex, cervical vertebrae, brain, temporomandibular
joints, and other tissues were examined for their contribution to the symptom complex. The treatment necessarily
depends on which structures contribute in a given patient. Before diagnostic injections, neuropsychiatric testing, as
is appropriate in closed head injuries, may be indicated. A prospective, double-blind, placebo-controlled study of
whiplash patients found dramatic long-term relief with radiofrequency lesioning of the medial branches supplying
the cervical facets. [144]
The medial branch of the dorsal primary ramus of the spinal nerve supplies the facet joint, the supraspinous ligament,
and interspinous ligaments. Branches from the adjacent spinal nerve and the spinal nerve one level above supply
each joint. Stimulation of these joints in the lumbar region produces back, buttock, and thigh pain. The pain patterns
are seen to vary depending on the level of involvement and whether the pain generator is intra-articular or
pericapsular. However, the commonality in pain distribution patterns at all spinal levels makes diagnostic
[145] [146]
injection essential to accurate diagnosis. Cervical facet pain is referred to the occiput and neck or the scapular area,
depending on the level. Thoracic facet pain is generally referred to distributions near the posterior division of the
[147]
respective roots Stimulation of the posterior and anterior longitudinal ligaments, anular ligament of the
[148]
intervertebral disc, anterior dura mater, or costovertebral joints produces pain indistinguishable from facet
stimulation pain. Adequacy of facet denervation is difficult to test unless provocative maneuvers are applied
[149] [150] [151]
after injection. Post-traumatic neck pain may frequently test positively for “facet” pain, recognizing that other
structures share innervation.
Pain reproducing the patient's typical pain on needle stimulation does not necessarily guarantee success, in part
because of superimposed referred pain patterns. Although confirmation of adequate denervation is typically
provided on postoperative examination, others have reported poor correlation between pain provocation and relief
with local anesthetic. Technical difficulties as well as differing approaches contribute to the conflicting reports.
[152]
Intra-articular injections exceeding 1 mL are associated with capsular rupture and spilling of anesthetic onto
adjacent structures. Passage of anesthetic into the epidural space or intervertebral foramen occurs routinely with
capsular rupture and can affect other pain-sensitive structures, such as the anterior dura, the posterior longitudinal
ligaments, or generally those structures subserved by adjacent spinal rootlets. Further, in the presence of spondylosis,
intra-articular injection is consistently followed by spread epidurally to adjacent and contralateral facet joints and
along the spinal nerve. Intra-articular steroid injection may give lasting relief, but this is not predicated by degree
[153]
of response to the local anesthetic.
Medial branch blocks denervate the facets and muscle, ligament, and periosteum over the dorsal rami distribution.
Spread to anterior primary rami or medial branches above or below is not usually seen. Inasmuch as complete
denervation of any given facet requires blockade of two levels (each medial branch supplying partial innervation to
the joint below), if relief is obtained after blocking two contiguous levels, it is sometimes difficult to distinguish
which of the three joints affected is responsible for pain generation. Although it may be argued that intra-articular
facet injections provide marginally better results than medial branch blocks with steroid, medial branch blocks are
[154]
preferred over intra-articular injections when used as a predictor of response to radiofrequency ablation. Relief after
repeated injections is not correlated with any known feature on history or physical examination. However,
[155] [156]
others have contended that with experience, the accuracy of physical examination in the diagnosis of facet pathology
can be quite accurate. Still, a great deal depends on the expertise on the examiner, thus making these results difficult
665
to standardize and reproduce. Medial branch blocks have also been used to predict the response to surgical fusion,
[157]
with variable results. Similarly, standardization of facet block and medial branch block technique may further
[158] [159] [160]
reduce confusion relative to their diagnostic, prognostic, and therapeutic value. [161]
Sacroiliac Joint Block. Radiation of pain locally into the gluteal region, and occasionally to the posterior thigh and
knee is seen on stimulation of the SIJ. Gaenslen's maneuver (pain on hyperextension of the hip over the side of the
bed with flexed contralateral hip and knee) or Yeoman's sign (hyperextension in the prone position) may be [162]
positive. Anatomic variability of the joint is considerable. The presence of pain on provocation is associated with
equally variable interrater reliability. Pain relief may not necessarily relate to intra-articular injection but may relate
to sacroiliac ligament or sacrospinous muscle infiltration. Yet, when the joint is distended during fluoroscopically
[163]
confirmed SIJ injection, a characteristic linear band of pain inferior and caudad to the region of the posterior
superior iliac spine is reliably reported. [164]
Neurolytic Medial Branch Blocks. Chemical neurolysis with phenol, cryoneurolysis, and radiofrequency ablation
are all acceptable techniques when indicated by the diagnostic and therapeutic maneuvers previously described.
Chemical neurolysis, however, is rarely used because of the possibility of spread to unwanted structures and
resultant neuritis.
Although somewhat time-consuming to employ when multiple levels are involved, the cryoprobe creates a well-
defined lesion. A simplified approach to cryoneurolysis of the medial branches of the dorsal rami has been described
by Brechner. When the pain is reproduced with minimal electrical stimulation during the procedure, good relief
[165]
can be expected for 2 to 3 months. Percutaneous facet rhizotomy can also be accomplished with electrocoagulation.
In recent years, considerable refinement in both technique and instrumentation
have improved both the efficacy and safety of this treatment. [166]
Radiofrequency ablation offers the technical advantage of permitting precise localization of the target medial
branches using relatively small-caliber probes. Local discomfort in the paraspinal area is therefore minimized,
resulting in the facilitation of accurate postoperative assessment and enhanced patient satisfaction. Prognostic
factors in the treatment of mechanical low back pain treated with percutaneous lumbar facet denervation have been
studied. North and colleagues. reported that nearly 50% of patients treated after diagnostic medial branch blocks
[167]
had greater than 50% relief at a mean follow-up interval of 3.2 years. There was no difference between long-term
results in unilateral pain compared with those treated bilaterally for axial pain, no difference in those having had
previous back surgery and those who did not, and there were no significant complications. Both the diagnostic and
the radiofrequency lesions were always done (either unilaterally or bilaterally, depending on the symptoms) from L4
through S1 inclusively. No attempt to distinguish a particular level at fault was made. Considering the extensive
overlap of distributions and the low likelihood of complications, a multiple-level “shotgun” approach may be
justified.
A similar “shotgun” approach was used by Lord and associates. as previously mentioned for chronic cervical facet
[144]
pain, with excellent long-term results. The median time for the pain to return to 50% of the preoperative level was
263 days compared with 8 days in the controls in a randomized, double-blind, placebo-controlled trial. Blocking
multiple levels bilaterally without regard for the precise levels of involvement has raised concern over unnecessary
segmental instability resulting from loss of innervation to the adjacent mutifidi. Clinically, this effect is not usually
significant, probably in some part owing to the frequent use of physical therapy postoperatively to strengthen the
paraspinal musculature along with the ability of the medical branches to regenerate within months.
NEUROPATHIC PAIN
Neuropathic Pain and the Sympathetic Nervous System
The sympathetic nervous system has been shown to contribute to the evolution and maintenance of certain chronic
pain states through a variety of mechanisms. Numerous studies document sympathetic involvement in protective
reflexes during acute and impending pain as well as reorganization and sensitization of spinal cord neuronal
connections in response to persistent noxious stimulation, through inflammatory induction of hyperalgesia and in
association with visceral pain. Obviously, many pain syndromes are sympathetically mediated, either partially or
primarily, yet are not considered to be sympathetically maintained. The taxonomy is continually evolving. Fig. 27–2
illustrates the medical protocols associated with neuropathic pain.
Complex Regional Pain Syndrome
666
Complex regional pain syndrome is defined as a regional pain with sensory changes after a noxious event that are
associated with vasomotor or sudomotor changes. [168]
The development of CRPS can be expected in 5% of all trauma cases. Burning, aching pain, initially localized and
[169]
then spreading proximally; cold sensitivity; and allodynia characterize the clinical syndrome. When it occurs as the
result of traumatic insult, the onset of such changes is usually relatively rapid, often beginning within days or weeks
of the injury. CRPS has been divided into two types. CRPS type I (reflex sympathetic dystrophy) exists in the
[170]
absence of a definable nerve lesion, whereas type II (causalgia) requires a specific nerve injury. A suggested [168]
taxonomy requires that CRPS I follow an initiating noxious event, exhibit spontaneous pain and allodynia out of
proportion to the inciting event, not necessarily limited to a single peripheral nerve distribution, and be associated
with a history of edema or sudomotor changes, vasomotor changes, and motor or trophic changes in the absence of
other explanatory disease. This definition includes CRPS that is not necessarily sympathetically mediated
[171] [172] [173]
while acknowledging the presence of allodynia as a primary finding.
Figure 27-2 Neuropathic pain. CRPS, Complex regional pain syndrome; SCS, spinal cord stimulation.
CRPS II describes a similar syndrome of burning pain with allodynia and accompanying history of edema and
vasomotor, or sudomotor disturbances occurring after nerve injury. Pain is usually constant, severe, and spontaneous.
Allodynia or hyperpathia is not necessarily limited to the distribution of the injured nerve. Pathologically, ruptured
axons seem to heal with endoneural fibrosis rather than discrete neuromas. Why some partial nerve injuries result in
neuritis and others in causalgia is not known. Whether the nature of the insult affects either the mode of healing or
the subsequent symptoms is also unclear.
Sympathetically Maintained Pain
Sympathetically maintained pain (SMP) is a term that retains clinical utility for its therapeutic implications. It
applies to a multitude of post-traumatic pain conditions characterized by both burning pain and allodynia, which are,
by definition, relieved by sympathetic block. Dystrophic changes, neural injury, and vasomotor or sudomotor
changes are often present but are not required. CRPS I and II may be either SMP or sympathetically independent
pain (SIP).
Alternatively, neural injury can result in alterations in the tonic level of antidromic conduction emanating from the
dorsal root ganglia. This antidromic conduction has been shown to sensitize the nociceptors subserving the
[174]
cutaneous distributions of the affected nerve root. The spread of sensitization to areas surrounding the injury by
667
antidromic conduction appears to be mediated via WDR neurons. WDR neurons also appear to be the mediators of
[175]
SMP. Further, a number of investigations have demonstrated that it is the myelinated low-threshold
[176] [177]
mechanoreceptor afferents, and not the C fiber unmyelinated afferents, that are responsible for ongoing pain in
SMP. [178] [179] [180]
Roberts proposed that SMP occurs after trauma to peripheral tissue, with or without neural injury, which activates
[179]
unmyelinated nociceptors (C fibers). This in turn sensitizes the WDR neurons in the spinal cord in a process termed
wind-up. Once sensitized, any low-threshold myelinated mechanoreceptor afferent activity converging on the same
WDR neurons results in an exaggerated response such as that observed clinically as allodynia. Continuous pain
results from sympathetic efferent sensitization of the peripheral sensory receptors, which in turn produces tonic
firing of the low-threshold myelinated mechanoreceptors projecting onto previously sensitized WDR neurons. Yet
sensory testing reveals widely varying degrees of low-threshold mechanoreceptor involvement in patients with RSD
(reflex sympathetic dystrophy). Price and coworkers. reported heat-induced hyperalgesia (C fiber) in 54.8%, low-
[181]
threshold mechanoreceptor-mediated (A beta fiber) allodynia in 45.2%, and high-threshold mechanoreceptor-

mediated (A delta fiber) allodynia in 54.8% of RSD patients studied. Temporal summation, however, was associated
with significantly greater intensity of spontaneous pain.
CRPS I most often appears in the distal upper or lower extremities, usually after traumatic injury to the limbs.
Traumatic CNS insults may also give rise to RSD-like syndromes. CRPS is frequently seen following
cerebrovascular accidents and spinal cord injuries. [182] [183]
Neuralgias and Neuromas
Partial nerve injuries resulting from mechanical trauma sometimes result in an irritative state with associated
perineuritis, neuritis, or plexalgia. Pain that is burning, lancinating, worse at night, and aggravated by stretching the
affected nerve is typical of neuritis. Other irritative phenomena, such as fascicular muscle twitching or spasm,
hyperesthesia, paresthesia, or dysesthesia may be present. Anatomic disruption often precludes proper realignment
of each proximal axon with its corresponding distal component, which may result in dysesthesias. Abnormal
afferent impulses emanating from the dorsal root ganglion after nerve injury also contribute to production of
abnormal sensation. Additionally, severed ends of neurons may search in vain for the missing nerve trunk,
[174]
eventually curling around themselves in whorl-like fashion or may become embedded in scar or other soft tissue.
These bulbous collections of nonmyelinated neurons are called neuromas.
Neuromas do not behave as normal sensory receptors but instead, when stimulated, generate an exaggerated
response with sharp, lancinating pain in the distribution of the affected nerve. Protracted, often clonic muscular
contractions over the affected stump can result. Neuromas can be quite labile, causing spontaneous discharge,
especially when large and tender, as can be the case when infection complicates the postamputation period. Both
mechanosensitivity and thermosensitivity are observed.
Central Pain Mechanisms: Deafferentation Dysesthesia, Phantom Pain, and CNS Trauma
Many of the aforementioned mechanisms of neuropathic pain involve deafferentation. Deafferentation pain is
generally considered to be primarily a disorder of abnormal central processing, and, therefore, a form of central pain.
Direct traumatic injury to the brain or spinal cord injuries (SCIs) are also important sources of central pain.
Postamputation phantom sensations occur in most amputees; however, it has been reported that only 5% to 10%
report phantom limb pain in association with these phenomena. Still other studies suggest that the incidence may be
much higher (50% to 72%). The pain can be burning, crushing, shooting, throbbing, or related to the impression
[184] [185]
that the missing part is fixed in an abnormal and uncomfortable position in space. This is particularly true if pain or
abnormal posture was present before amputation. Epidural block with bupivacaine and morphine before
[186] [187]
amputation reduces the incidence of postamputation phantom limb pain. Phantom pain is also more frequent when
[188]
the medical condition of the stump is poor. The presence of painful neuromas, infection, painful cicatrix, or
[189]
generally poorly constructed stumps are indications for surgical exploration and revision.
Despite the appearance of vasomotor and sudomotor changes in some patients with phantom limb pain, sympathetic
interruption rarely is of lasting value. Phantom sensations usually correspond to the areas with the greatest
[190]
representation in the sensory cortex, with gradual shortening of the phantom limb until only the hands or feet remain
attached to the stump just before resolution. The presence of pain prevents this usual shrinkage.
Deafferentation dysesthesias occur relatively commonly after intercostal nerve injury, brachial plexus avulsion, and
SCI. Several central mechanisms have been proposed. There is evidence to suggest that reorganization of neural
668
pathways at spinal as well as thalamic and cortical levels takes place after peripheral deafferentation. Melzack
[191] [192]
and Loeser proposed a central biasing mechanism. Sensory loss results in the release of normal tonic inhibition
[193]
from central sites. This presumably predisposes to self-perpetuating neuronal activity at spinal and higher centers in
the CNS. Epileptiform activity and abnormal sensitivity in the medial thalamic nuclei, dorsal columns, and other
central sites after deafferentation appear to contribute to burning pain and hyperpathia. Alternatively, an imbalance
between the spinothalamic and dorsal column systems, as has been observed in SCI victims, may be an important
mechanism. N-methyl-D-aspartate receptors may also play a role in the pathogenesis of central dysesthetic pain
[194]
after SCI as intravenous (IV) ketamine markedly reduces both spontaneous and evoked pain. [195]
Clinically, both traumatic brain injury and traumatic SCI

[196]
can result in pain states that are mixed in character.
[197] [198]
Both myofascial dysfunction and RSD may simultaneously complicate traumatic myelopathy.
[199]
Neurophysiologic Testing
Assessment of sensory nerve function can help to guide interventional therapies in the treatment of neuropathic pain
states. Objective evidence of abnormal C or A delta fiber function at rest or under stressed conditions aids diagnosis
( Fig. 27–3 A), confirms the adequacy of blockade (see Fig. 27–3 B and 3C), and is useful as a monitor of
therapeutic progress (see Fig. 27–3 D). Observations including surface temperature asymmetry, resting or evoked
sudomotor asymmetry (quantitative sudomotor axon reflex, QSART), response to infusion of systemic α-adrenergic
antagonists, tourniquet ischemia testing, measurements of cutaneous blood flow with laser Doppler, and
percutaneous oxygen partial pressure differences have all been advocated.
CRPS I sometimes is associated with increased activity on triphasic bone scanning or, more reliably, as regional
hypothermia on thermographic evaluation. Low and associates studied sudomotor and vasomotor changes in
[200]
CRPS I, whereby abnormalities were detected using the QSART in 75% of patients, with 80% having abnormal
thermograms. When both measures were combined, all patients studied demonstrated significant abnormalities. The
authors subsequently suggested that combining measures of resting sweat output and skin temperature reduction
with asymmetry in the QSART reliably confirms the clinical features of CRPS I. Still, quantitative evaluation
[201]
clinically remains difficult, as patients demonstrate considerable variability in objective neural dysfunction.
Computer-assisted quantitative sensory testing provides systematic objective evaluation of sensory fiber function.
Thermal sensory analysis uses the surface application of both heat and cold to permit discrimination between C fiber
and A delta fiber perception and pain thresholds (see Fig. 27–3 A). Similar discrimination can be observed with
[202]
the application of electrical stimulation at frequencies specific for pain sensation. These tests, applied after
[203]
treatment, can be used to document the effectiveness of sympathetic blockade. A reduction in C fiber–mediated heat
perception and allodynia in the absence of significant alteration in A delta fiber–mediated cold perception confirms
functional
669
Figure 27-3 A, Complex regional pain syndrome I of the left hand. Documentation of marked cold pain (C fiber and A delta fiber) and heat pain (predominatly C fiber)
allodynia, with no loss of discrimination for either cold sensation (A delta fiber) or the sensation of warmth (C fiber). B, A left-sided infraclavicular brachial plexus
catheter was infused with a dilute local anesthetic immediately before testing. The onset of minor A delta fiber (cold sensation) and C fiber (warm sensation) block is
associated with abolition of both cold and heat pain allodynia. C, Twenty minutes after injection, repeat testing demonstrates pronounced C fiber block with no further
progression of the A delta fiber block. Allodynia remains absent. Occupational therapy commences. D, The brachial plexus block was maintained continuously for 5
days with a balloon home infusion device. Daily OT treatments emphasized desensitization and mobilization during the infusion. Home exercise instruction was
provided. Follow-up testing at 30 days documented only minor residual C fiber allodynia.
sympathectomy without clinically significant somatic neural blockade (see Fig. 27–3 B and 3 C).
Although quantitative sensory testing is a useful adjunct, the diagnosis of CRPS must be made on clinical grounds.
Overzealous interpretation of either the diagnostic criteria described above or neurophysiologic testing results leads
to overdiagnosis by including such entities as diabetic neuropathy. Although QSART, systemic phentolamine, and
[204]
other examinations have been reported to predict the response to sympathetic block, their reliability is poor.
Sympathetic block itself remains the standard for prognostic intervention.
Quantitative sensory testing using vibratory modes to evaluate larger A beta fiber function has been helpful in
monitoring patients with painful toxic or metabolic peripheral neuropathy, as is often seen in chronic diabetes
mellitus. In patients with acute herpes zoster infection, the involvement of A beta fibers, documented in this fashion,
has been reported to predict the subsequent development of postherpetic neuralgia. [205]
670
Rationale for Treatment
Sympathetic block, by definition, relieves the pain of SMP. Although repeated sympathetic blockade may reduce or
permanently eliminate clinical findings, most neuropathic pains are not sympathetically maintained. In fact, not
[206] [207]
all RSD (CRPS I) is amenable to sympathectomy. When a positive response from sympathetic blockade is
[208]
obtained, the effect of the block often seems to significantly outlast the action of the local anesthetic, especially
when repeated. Yet, despite resolution of clinical symptoms, even “cured” patients may continue to have abnormal
[207]
pain in response to cutaneous injection of norepinephrine. The significance of this residual is unknown. Certainly
[209]
overwhelming afferent barrage due to severe pain may then lead to central neuroplasticity that persists after the
clinical syndrome resolves. Alternatively, predisposition to some neurologic conditions, including neuropathic pain,
[8]
may have a heritable basis, and thus an underlying susceptibility to nociceptor sensitization.
[210]
Vasomotor and sudomotor changes often seen in patients with CRPS may also result from C fiber overactivity.
Experimental evidence that antidromically acting nociceptive C fibers induce an inflammatory response mediated by
peripheral neuropeptides in neuropathic pain states lends further support to this hypothesis. Clearly, afferent [211]
nociception is required for the development of perivenous edema after hyperosmolar saline injection in humans. [212]
The mechanism for edema formation in neuropathic pain states may also involve venous innervation.
Interestingly, neural blockade distal to the sympathetic chain is also effective in reducing SMP, presumably [213] [214]
because neurogenic block of the affected receptive field effectively reduces the low-threshold mechanoreceptor
activity that is stimulated by sympathetic outflow. Over time, the plasticity of the CNS permits enhanced
transmission over previously quiescent pathways. This contributes to the clinical impression that in the most chronic
cases, peripheral measures are ineffective in the long term. This seems logically to emphasize the need for early
diagnosis and treatment, thus preventing the cascade of events resulting in the reorganization of spinal processing.
Scientific evidence linking early treatment to improved response, however, is scant. [208]
Medications for neuropathic pain are administered by oral, topical, IV regional, and intraspinal routes, and by nerve-
blocking techniques. Sympathetic blockade can be accomplished by introducing antisympathetic agents regionally.
Regional antisympathetic blocks are most frequently performed using bretylium in a Bier block. This agent depletes
norepinephrine in the postganglionic axon, thus blocking the effect of sympathetic stimulation and breaking the
“reflex.” This technique has the added benefit of reducing the chemosensitivity to circulatory norepinephrine seen in
SMP. Clonidine, an α2 -adrenergic agonist, applied to the dorsal horn suppresses the release of the C fiber
neurotransmitter substance P. Baclofen is also used intrathecally, usually for spasticity after SCI. The myofascial
[215]
components of SCI pain is more effectively controlled than the neurogenic pain component with use of spinal
baclofen. These effects are presumably mediated via the GABAB (γ-aminobutyric acid) receptor complex.
[216] [217]
Likewise, the success of SCS in the treatment of neuropathic pains, such as CRPS, may in part be mediated via
GABAB activation because it has been shown to be independent of SCS-induced vasodilation.
[218] [219]
Local anesthetics, such as sodium channel blockers, are also useful in the treatment of pain resulting from nerve
injury. After injury to a peripheral nerve, focal demyelination takes place with subsequent leakage of sodium across
the neural membrane. This raises the resting membrane potential, thus rendering it susceptible to spontaneous
depolarization as well as inducing a mechanosensitivity that is the pathophysiologic basis for Tinel's sign, which is
seen in physical diagnosis. Similarly, neuromas are both mechanically sensitive and spontaneously active in
producing ectopic discharge. Furthermore, an increased rate of spontaneous depolarization from the dorsal root
[220]
ganglion, the spinal cord, and more proximal CNS sites is seen after nerve injury and denervation. [174] [221]
Interruption of peptide transport between the CNS and the periphery because of transection of C fibers is also likely
to play a major role. The rate of ectopic firing and mechanosensitivity is reduced by local anesthetic blockade.
Clinically, the hyperpathic components that follow nerve injury are frequently improved after sympathetic nerve
blocks, whether performed by IV regional or sympathetic ganglion-blocking techniques. Chemosensitivity of
neuromas can also be reduced by depletion of peripheral norepinephrine stores.
The use of corticosteroids for pain relief has long been practiced on empirical grounds. The anti-inflammatory
action reduces perineuritis, perineural edema, and the elaboration of algesic nociceptor-sensitizing substances
produced as a consequence of the inflammatory reaction. However, perhaps equally important is the fact that
corticosteroids, when injected perineurally (but not systemically), reduce the spontaneous rate of ectopic discharge
seen in neural injury and neuromas. [222] [223]
In central pain states, therapies resulting in further peripheral denervation are rarely of value. Although destruction
of the dorsal root entry zone has been used with some success in persistent phantom limb pain, brachial plexus
avulsion, and lumbosacral nerve root avulsion. SCS is preferable in most situations and may more directly address
[224]
671
the pathophysiologic mechanism of deafferentation. Postsympathectomy neuralgia results when visceral and somatic
afferent within the sympathetic chain are severed. Central sensitization and deafferentation hyperexcitability from
peripheral afferent interruption act simultaneously to produce postsympathectomy pain. [225]
Chronic pain complicates traumatic brain injury in approximately 50% of all cases. Cognitive, emotional, and [226]
psychosocial alterations create unique diagnostic and therapeutic challenges. Cognitive retraining and the
[227] [228] [229]
development of adaptive coping strategies should be considered as adjuncts to other pain management protocols.
Cervicothoracic Ganglion Block.Diagnostic cervicothoracic ganglion (stellate ganglion) block requires sufficient
volume of local anesthetic (depending on the approach: intrapleural, anterior to C6 tubercle, or C7 anteromedial
vertebral body) to fully bathe the target. Poor spread into the mediastinum, thus missing the upper thoracic
contributions to the sympathetic innervation of the upper extremity, is the most frequent cause of failed block.
Stevens and associates. reported that development of Horner's sign and a rise in hand temperature of at least 2° C,
[230]
over and above any contralateral increase, were associated with complete sympathectomy in most, but not all, cases.
Lumbar Sympathetic Block.When lumbar paravertebral sympathetic block of the lower extremity is performed
with a single needle at the L3 level, caudad spread to include the lowest fibers serving the foot, especially the heel,
may be missed. Effective lumbar sympathetic blockade in the treatment of sympathetically maintained pain, as
indicated by postprocedural resolution of allodynia, is correlated with warming of the extremity. The temperature [231]
rise, as measured at the great toe, should approach to within 3° C of core body temperature at 35 minutes. A
transpsoas approach can also be employed, whereby the needle tip lies in close approximation to the genitofemoral
nerve. The transpsoas approach is more comfortable for the patients and may be considered if fluoroscopy is not
[232]
available or in pediatric patients, but this approach is not suitable for neurolytic use. For patients receiving
significant relief, repeat injections or continuous infusion techniques are appropriate. When sustained response is
lacking, neurolysis may be considered.
Continuous Perineural Infusion of Local Anesthetics.Although both stellate infusions and lumbar sympathetic
chain infusions have been performed, the catheters tend to become dislodged easily. The use of continuous brachial
plexus infusion for upper extremity pain is suitable for maintaining prolonged sympathetic effect. Axillary catheters
are situated in a potentially contaminated area and are difficult to fix in place for long-term use. The infraclavicular
approach is preferred as it avoids both of these shortcomings. The stability of this location has facilitated the use
[233]
of home infusion devices for outpatient application. The interscalene approach is also possible when a soft
[234]
catheter can be directed caudally to sufficient depth to allow normal head rotation without retraction of the system
out of the interscalene compartment. [235]
Lumbar plexus infusions or epidural infusions are best for lower extremity pain. Lumbar plexus catheters can be
placed anteriorly, adjacent to the femoral nerve as a “3-in-1 block,” or posteriorly, either within the psoas
[236] [237]
compartment or as a single paravertebral catheter in the midlumbar region. A number of studies have
[238]
demonstrated continuous infusion or repeated daily blocks to be most efficacious in the facilitation of physical and
occupational therapy techniques. Modulation of the intensity of the block is more difficult than with the upper
[208]
extremity because the femoral nerve is quite easily blocked with a relatively small amount of local anesthetic.
Lumbar epidural infusion is a simple but effective means of producing continuous analgesia for the lower
extremity. As such, this approach enjoys widespread usage in hemodynamically stable patients. More important,
[239]
the degree of neural blockade is readily modifed by changing the amount of local anesthetic delivered. In a similar
manner, continuous sympathetic blockade can be provided for pain in the trunk by using thoracic, epidural,
intrapleural, extrapleural, paravertebral, or intercostal catheters.
Intravenous Regional Sympathetic Block.The use of bretylium as an IV regional anesthetic agent has been shown
to be effective in the treatment of CRPS I. Hord and associates, in a randomized, double-blind study,
[240] [241]
demonstrated significant pain improvement for a mean of 20 days after treatment with IV regional bretylium.
Although inhibition of norepinephrine release is presumed to provide sympathetic interruption, tourniquet-induced
ischemic block could theoretically play a minor role.
Peripheral Nerve Block.Perineural depot steroid injection has been shown experimentally, as previously discussed,
to reduce spontaneous pain from neuromas and after nerve injury. Although perineural steroid injection for other
peripheral neuropathies has enjoyed long-standing clinical use on empirical grounds, with the notable exceptions of
the greater occipital nerve block, median nerve block for carpal tunnel syndrome, and epidural injection, there are
few controlled studies to document its efficacy. [242]
672
Intraspinal Drug Delivery Systems.When conservative measures fail to provide lasting relief, implantation of a
permanent system for intraspinal drug delivery can be considered. Considerations as to the potential for infection
and the development of tolerance take on added significance in the chronic nonmalignant pain setting compared
with treatment of cancer patients with relatively limited life expectancies. Neuraxial delivery of the medications can
often provide greater efficacy while limiting the overall amount of drug required and the subsequent untoward side
effects. Whether this holds true for any given patient must be ascertained during a trial infusion before permanent
implantation ( Fig. 27–4 ).
Whenever possible, fully implanted systems are preferred over systems that require externalized catheters and
external pumps. Intrathecal narcotic delivery is associated with better analgesia, fewer treatment failures, and
reduced complications compared with epidural administration. Still, implanted pumps are associated with high rates
of technical failures. Although implanted intrathecal catheters can be used with external pumps, the concern over
[243] [244]
the potential for infection should not be minimized. Cost savings are realized after only 3 months of therapy when
implanted intrathecal pump systems are used compared with epidural infusions using external pumps. [245]
Determining patient suitability for intrathecal opioid therapy requires the same considerations as used in screening
for the appropriateness of chronic opioid therapy in general. A psychological clearance to assess the patient's
emotional stability and potential for abuse is advisable and required by many insurers. A detailed drug history, as
well as a history of failed nonopioid therapy, with a record of improved functional capacity during opioid therapy
should be documented. In general, the risks of addiction, respiratory depression, and imparied psychomotor function
have been exaggerated. Tolerance to the sedating and psychomotor-impairing effects usually takes 1 or 2 weeks.
Stable doses, for example, do not usually significantly affect the patient's ability to drive an automobile. [246]
Although the role of opioids in the treatment of chronic nonmalignant pain is continually evolving, extreme
positions at both ends have served patients poorly. The ability to identify patients likely to benefit safely from long-
term opioids remains the key element to success of this therapy. Contractual arrangements with patients as well as a
thorough understanding about who will be prescribing the medication on an ongoing basis must be agreed upon
before the institution of the regimen. Additionally, candidates for this indwelling form of narcotic administration
should meet the same criteria and fulfill the same contractual and long-term management arrangements as those
patients who require oral and transdermal narcotics.
Prescription abuse criteria for patients with chronic nonmalignant pain have been studied. Past opiate or alcohol
[247]
abuse or psychosocial testing was specifically not correlated with opiate abuse in the pain clinic setting. Abusers and
nonabusers had similar pain levels and frequencies, a similar perceived need for opiates, similar confidence in
psychological treatment, no significant difference in function, and similar depression scores. Anxiety levels and
coping mechanisms were not studied. Abusers demonstrated an overwhelming focus on opiate issues, a pattern of
request for early refill or multiple telephone calls for problems associated with the opiate prescription, and the
discovery of supplemental sources of opiates from multiple providers, emergency rooms, or illegal sources. The use
of a pump requiring refill programming provides a degree of control over some of these issues.
Opioids alone may be inadequate to control neuropathic pain, even when given intraspinally. Local anesthetic or
[248]
the α2 -adrenergic agonist, clonidine, or both, have been an effective adjunct in this setting. The addition of
[249]
bupivacaine reliably improves the quality of the epidural technique. Intrathecal bupivacaine produces minimal side
effects when the total daily dose of bupivacaine is less than 30 mg by continuous infusion. Epidural clonidine is
[250]
also a useful adjunct to epidural narcotics in neuropathic pain. Severe hypotension may result in the first days of
[251]
therapy. When discontinuing therapy, the dose should be gradually decreased over 2 to 4 days and not abruptly
terminated. Its relative efficacy when given epidurally for neuropathic conditions, compared with musculoskeletal
pain complaints, is demonstrated in the differential dose conversions from epidural to intrathecal administration. [252]
SCI patients may benefit from intrathecal baclofen to reduce spasticity as an alternative to neurolytic or surgical
intervention. Pain is often also reduced. Again, a differential effect with respect to pain is seen; chronic
[253]
musculoskeletal pain associated with spasticity seems better handled than the neuropathic component. Yet others
[216]
report significant analgesic effect in the absence of spasticity. Adverse effects are more pronounced at higher
[254]
dosages, as might occur with the trial bolus. The typical lightheadedness, double vision, drowsiness, dry mouth,
[255]
and nausea may give way insidiously over the first few hours after injection to seizures (if epileptic) and
incontinence, as well as ascending muscle weakness, respiratory depression, and even coma. Attempting to reach the
upper extremities also predisposes to this respiratory depression and has resulted in mechanical ventilation for up to
2 days. In general, the lower extremities are more effectively treated with this therapy than are the upper extremities.
As with oral baclofen, it should be weaned, not abruptly discontinued. Tolerance may develop in the first 6 to 9
months, but stable doses are the rule thereafter. [256]
673
Neurolysis.Although sympathetic cryoneurolysis can be employed, the relatively bulky cryoprobes are somewhat
cumbersome for many of these blocks. Cryoneurolysis is more commonly applied to mixed peripheral nerves or
neuromas, as the nerves tend to regenerate normally in a few months. Greater occipital nerve block, intercostal block,
block of the anterior intercostal branches in rectus sheath syndrome, facet rhizotomy, sacral foraminal block, and the
treatment of coccygodynia are well-known applications.
Chemical sympathectomy with phenol (6%) or, less commonly, 50% alcohol (due to increased neuritis and extensive
spread) is used for both cervicothoracic and lumbar sympathectomy. The difficulty in controlling unwanted spread
to somatic nerves makes chemical neurolysis less desirable in chronic nonmalignant pain. A transdiscal approach to
the lumbar sympathetic chain is reported to reduce the potential for subsequent genitofemoral neuritis. The[257]
neurolytic stellate technique developed by Racz and Holubec is very effective, but should be undertaken in only
[258]
extreme circumstances when alternative approaches are not possible. Radiofrequency sympathectomy for upper
extremity pain is accomplished by block of the stellate ganglion, or from a posterior approach to the sympathetic
[259]
chain at T2–T3. Radiofrequency stellate ganglion neurolysis is reportedly most successful in CRPS II, ischemic
[260]
pain, degenerative cervicobrachialgia, and post-thoracotomy pain. Permanent sympathectomy has enjoyed
[261]
widespread application in the treatment of pain secondary to vascular insufficiency, especially in the lower
[262]
extremity. For patients with long life expectancies, upper extremity neurolysis accomplished by means of a
thoracoscopic approach offers less opportunity to introduce unwanted side effects such as persistent hoarseness.
674
Figure 27-4 Intraspinal drug delivery systems. IT, Intrathecal; MS, morphine sulfate.
Sympathetic denervation of the viscera can similarly be accomplished by blockade of the celiac plexus, the greater
splanchnic nerves, the superior hypogastric plexus, and the ganglion impar. Celiac plexus block via a posterior
approach commonly takes advantage of the spreading abilities of alcohol, whereas the anterior approach with CT
guidance is suitable for alcohol or phenol with greatly reduced volumes. Hypogastric plexus block likewise may be
suitable for either phenol or alcohol. The anterior approach is easily accomplished with fluoroscopic guidance.
[263]
675
Radiofrequency lumbar sympathectomy allows a discrete lesioning of the sympathetic chain, thus minimizing, but
not eliminating, the unwanted spread associated with chemical neurolysis (genitofemoral neuralgia, ureteral injury,
sexual dysfunction, sphincter dysfunction, and somatic nerve spread). The nerve stimulator, properly used, reduces
the potential for unwanted involvement of mixed somatic nerves. As described by Rocco, the technique can be
[264]
performed at a single level just cephalad to the midbody of L3, much like the single-injection chemical
sympathectomy. Diagnostic confirmation of probe placement is accompanied by reproduction of the patient's pain,
appropriate dye spread, rapid rise in temperature, and an increase in pulse volume in the toes. Postsympathectomy
neuralgia and an excessively hot, swollen foot were reported. However, long-lasting relief was not the rule.
Improved results for radiofrequency lumbar sympathectomy are seen when multiple-level lesioning is performed.
Inclusion of L2, L3, and L4 for forefoot pain and even L5 for the heel are suggested. An anatomic study of the
lumbar sympathetic chain to explain the variation and instances whereby multiple levels were required demonstrated
lumbar ganglia most often present just cephalad to the middle of the body of L3 and at the discs above and below. [265]
Infrequently, ganglia appear as high as L1 and extend caudally to the L5–S1 disc. Although the sympathetic chain is
closest to the vertebral body at L3, it diverges both above and below L3 from this approximation. Further, the
authors noted that the lumbar sympathetic ganglia could be either a single elongated mass or up to six discrete
ganglia. Avoidance of lesioning in the upper lumbar region limits the subsequent potential for development of
genitofemoral neuralgia.
MYOFASCIAL PAIN
Sources of Muscle Pain
Perhaps the most common persistent pain following trauma is that emanating from myofascial (musculoskeletal)
structures (i.e., muscle, bone, tendon, ligament, and other soft tissues of mesodermal origin). Nonmuscular
structures such as tendons, ligaments, and fasciae are common sources of musculoskeletal pain. Yet by far the most
frequent source of musculoskeletal pain is muscle injury ( Fig. 27–5 ).
Muscle pain and deep hyperalgesia are associated with a number of conditions as secondary phenomena, but they
may exist as the primary source of pain. Primary afferent nerve fibers play a significant role in muscle pain
sensation. Nociceptors with slow conducting afferents, A delta fibers (group III), and C fibers (group IV) give rise to
poorly localized pain. Mechanical and chemical stimuli result in cramping pain from skeletal muscle. Polymodal
nociceptors are associated with group III fibers, whereas nociceptors responding to chemical and ischemic stimuli
are subserved by unmyelinated group IV fibers. Temporal summation
676
Figure 27-5 Myofascial pain. IT, Intrathecal; PT, physical therapy; TPI, trigger point injection.
gives rise to diffuse and poorly localized complaints. Mense suggested that acute muscle pain might be mediated
[266] [267]
via group III fibers and chronic muscle pain due to use might be through group IV fibers. Obviously, if the acute
muscle injury involved tissue damage with resultant release of algesic substances, chemosensitive group IV fibers
would contribute. Symptomatically, the cramping pain resulting from either group III or group IV fiber stimulation
is indistinguishable. The referred pain from muscle likely represents the extensive involvement of reflex
mechanisms in the CNS. Hyperalgesia arising from central sensitization may result from NMDA activation or other
mechanisms of modulation of central synaptic processing.
Myofascial pain dysfunction is characterized by specific changes within affected muscles. After trauma, discrete
regions within a muscle may develop lesions called trigger points. These trigger points appear clinically as palpable
taut bands of muscle that elicit tenderness when stimulated by direct pressure and, depending on the severity of the
stimulus, elicit referred pain. These regions of muscle present a limitation to active and passive motion, with
[268]
apparent shortening and weakening of the involved musculature. Pain from deep somatic structures is typically dull
and diffuse. The ability to localize precise trigger areas decreases with increasing tissue depth. Diffusion and
radiation can be indicators of severity, with muscle spasm and tenderness in zones of reference (as distinguished
from trigger points) often appearing at sites distant from the lesion.
Histologic changes have been described and include atrophy of type II muscle fibers, a characteristic “moth-eaten”
appearance of type I fibers, and segmental muscle fiber necrosis. Some investigators have noted elastic projections
constricting affected muscle fibers. Lipid and glycogen deposition, as well as abnormal mitochondrial
accumulations, are seen. Clinically, objective quantification of trigger points can be accomplished with
[269] [270] [271]
thermography or measurement using pressure algometry or tissue compliance meters. Kawakita and [272] [273]
colleagues, using pulse algometry electrodes, found the site of tenderness associated with clinical trigger points to
[274]
be on or near the muscle fascia. They proposed an inflammatory process within the fascia resulting from mechanical
damage to the muscle as the source of pain.
The precise mechanism of trigger point generation and perpetuation after trauma is not known. Simons and Travell [275]
hypothesized a mechanism that is consistent with most of the clinical features observed. They proposed that
transient overload of a muscle may cause damage to the sarcoplasmic reticulum. Stored calcium ions are then
released into the area of injury, and, in the presence of adenosine triphosphate (ATP), may activate the actin-myosin
contractile mechanism focally; a palpable band of muscle results. Inasmuch as the sarcoplasmic reticulum is
disrupted, calcium reuptake is limited, and unabated focal contractile activity persists. High levels of metabolic
activity, documented by ATP depletion, produce the “hot spots” seen on infrared thermography. Further, because
[276]
ATP is required for the calcium pump to retrieve calcium into the sarcoplasmic reticulum, depletion of ATP further
enhances calcium availability and thus perpetuates contractile activity. Accumulation of metabolic byproducts
results in local acidosis, which sensitizes adjacent nociceptors. Likewise, increased calcium may act as a second
messenger to induce nociceptive neuronal hypersensitivity. Increased vascular permeability, local vasoconstriction, [277]
and reduced tissue oxygenation also contribute to the elaboration of algesic substances previously described,
[278] [279]
which sensitize peripheral nociceptors. Additionally, sensitized dorsal horn cells may cause enlargement of the
receptive field, resulting in spreading dysesthesia. [280]
677
According to this hypothesis, perpetuation of trigger point activity can be expected until the integrity of the
sacoplasmic reticulum is reestablished or the band is physically lengthened to prevent further interaction of the
actin-myosin complex. Sensitized nociceptors may evoke sympathetic hyperactivity. Sympathetic activation may
[281]
itself sensitize nociceptors, inducing cyclic reflex mechanisms. Alternatively, increased sensitivity of muscle
[282]
vasculature to sympathetic transmitter substances may contribute. Clinically, persistence of trigger point activity
[283]
can result in sympathetically mediated vasomotor changes. The progression from acute post-traumatic muscular pain
to chronic myofascial pain likely involves peripheral sensitization of high-threshold mechanoreceptors, recruitment
of low-threshold mechanoreceptors, and central sensitization of dorsal horn neurons. [267]
Muscle Injury
The musculotendinous unit can become injured from overuse, with the greatest strain occurring during muscular
contraction. The tendon adapts more slowly than the muscle, and therefore is susceptible to aseptic inflammatory
changes. Chemotactic influences of the inflammatory mediators lead to an exudative infiltration that, if prolonged,
may result in metaplastic changes, leaving calcific deposits within the musculotendinous unit. [284]
The response to connective tissue injury has been divided into stages. The first stage in the healing process is the
[285]
inflammatory response. This phase typically extends through the first 2 days, during which time chemotactic
mechanisms induce cell mobilization and infiltration. The second stage lasts from the third through the fifth day and
is characterized by ground substance proliferation in preparation for collagen deposition. Collagen formation begins
in the third proliferative phase, lasting through the second week following injury. The final stage is termed the
formative stage, as it is from 14 days onward that the cross-linking of collagen organizes into functional fibrils in the
healed tissue.
The timing of therapeutic intervention can affect the quality of the reparative process. Corticosteroid administration
early in the first 2 weeks can inhibit prostaglandin synthesis, thus interfering with the initial proliferative phases of
healing. Equally detrimental is prolonged immobilization after the first weeks. Contraction of adjacent musculature
creates both a piezoelectric effect and necessary stress on the newly formed fibers, helping them to align themselves
along the lines of normal tensile force.[284]
Chronic pain emanating from muscle tissue is also seen in fibromyalgia. Fibromyalgia has a different clinical
presentation from that of post-traumatic myofascial pain, does not respond to the same therapeutic protocols, and
likely has a very different pathophysiology than what has been presented for myofascial pain. Fibromyalgia
manifests with widespread pain. It is associated with migraine, memory loss, word-finding difficulties, irritable
bowel, morning stiffness, and sleep disturbance. Serotonin deficiency, emotional trauma, lymphocyte phenotype
[286]
and IgE alterations, hypervigilance, genetic factors, and abnormal muscle blood flow have been suggested as
etiologic considerations. Treatment emphasizing a rehabilitative process, including sleep restoration; relaxation and
biofeedback training; stress management; attention to depression; and the use of medications for depression,
increasing serotonin levels, and sleep promotion are advanced. Nerve block techniques for fibromyalgia are
generally of no lasting value.
Rationale for Treatment
The importance of maintaining function, as a means of ultimately reducing pain, cannot be overemphasized. Pain-
induced fear and avoidance behaviors are in many cases crucial to the development of chronic myofascial pain. [287]
Physical therapy directed specifically toward stretch of the trigger points back to the normal resting length is key.
This prevents actin-myosin interaction, thereby reducing metabolic activity, and permits improved local blood flow
and tissue oxygenation. Physical therapy and mobilization of affected body parts are often difficult or impossible
without first alleviating attendant pain. Stretch of the already tender regions frequently produces increased pain and
may aggravate the trigger points. Specific techniques are used to distract or relieve pain so as to permit passive
stretching. These modalities include the use of vapocoolant spray, ischemic compression, dry-needling, acupressure,
acupuncture, and most effectively, infiltration with local anesthetic, trigger point injection. This injection provides
pain relief and muscular relaxation (by blocking ongoing reflex activity) while physically flushing away excess
extracellular calcium, hydrogen ions, and algesic agents.
Trigger Point Injection.Afferent pain signals secondary to activation of nociceptors enter the spinal cord through
the dorsal root, where communication via internuncial neurons leads to hyperactivity in the anterior and anterolateral
horn cells. This hyperactivity results in efferent traffic, causing more muscle spasm and vasoconstriction. Neural
blockade interrupts this reflex arc. Referred pain in the trigger point's zone of reference may be produced by
continual afferent barrage of nociceptive input from the trigger region projected onto the dorsal horn of the spinal
cord. Resultant alterations in CNS processing of the input from that receptive field can be responsible for the
spreading tenderness seen following injury. This response is terminated by local anesthetic application. [5]
678
While far more effective in myofascial syndrome than fibromyalgia, the mechanism of action of trigger point
injection may alternatively relate to myotoxicity of local anesthetic, thus encouraging new growth of myocytes.
Diagnostic interpretation of trigger point injections must consider inaccuracies in diagnosis, limited objective
measures, and potential spread to adjacent nerves. Objective documentation of the presence and post-treatment
abolition of trigger point activity is easily accomplished using algometry. Contralateral and normative comparisons
further enhance diagnostic accuracy. [288]
Trigger point injections should always be followed by effective stretch of the treated muscles in an attempt to return
the muscle fibers to their normal length in the resting state. This prevents actin-myosin interaction, thereby reducing
metabolic activity, and permits improved local blood flow and tissue oxygenation. The application of moist heat
immediately following the blocks helps to minimize local soreness and reflex muscle spasm. Best results are
obtained when these injections are reserved for patients exhibiting acute trigger points, which, on physical
examination, reproduce the patient's pain and are ineffectively stretched using physical means alone. Physical
therapy interventions after injection may also include myofascial release techniques and manual therapy as indicated
by the underlying pathology. Manual therapy–based physical therapy treatment is most effective when based on the
motion-provoked symptoms. Relaxation and EMG biofeedback techniques should be considered as adjunctive
[79]
measures. [289]
Patient education after trigger point injections should include discussion of aggravating and alleviating factors as
well as the development of a home stretching program as a means of facilitating ongoing therapeutic exercise. When
several sequential trigger point infiltrations fail to result in sustained progress, despite appropriate physical
interventions, a search for an underlying inciting or initiating process as yet undiscovered or not addressed
therapeutically should ensue. Consideration should then be given to sympathetic blockade or continuous regional
blockade to facilitate therapy. Neurolytic trigger point injections (phenol, alcohol, or cryoneurolysis) may be
employed for the most recalcitrant cases. Alternatively, muscular injection of botulinum toxin often results in long-
lasting effect.
Regional and Sympathetic Block.Somatic regional block can also be used when multiple trigger points in a
contiguous region make individual injection impractical or when a simultaneous antisympathetic effect is required to
promote increased blood flow or reduced sympathetic activity. Regional sympathetic blockade has been proposed
both to block perpetuating sympathetic activity and to improve microcirculation, thus decreasing focal ischemia. [290]
Botulinum Toxin Injection.Botulinum toxin prevents the release of acetylcholine at the neuromuscular junction,
thus causing relaxation of the contracted state. Injection of botulinum toxin type A directly into muscular trigger
points produces a prolonged localized paralysis. This period of quiescence frequently lasts 10 to 12 weeks. During
[291]
this interval, considerable progress with physiotherapy may be realized. Because the clinical effect may take several
days, the addition of a local anesthetic can help to confirm appropriate placement and the expected clinical effect.
An EMG apparatus helps to validate the trigger point location in conditions where repetitive firing may be expected,
such as spasticity after cerebrovascular accident. The same device may also permit prediction of surgical outcome in
thoracic outlet syndrome. [292]
A variety of myofascial and spastic syndromes have been treated successfully in this fashion, including thoracic
outlet syndrome, piriformis syndrome, iliopsoas dysfunction, cervical dystonia, and spasticity after stroke or
demyelinating disease. Botulinum toxin inclusion in both brachial plexus and lumbar plexus blocks has also been
[293]
advanced. The injection of botulinum toxin type A into trigger points in the iliopsoas, anterior scalene, and
[294]
piriformis muscles of patients with chronic myofasical pain was associated with improved efficacy compared with
steroid injection combined with physiotherapy. [293]
Acupuncture.Stimulation-induced analgesia using transcutaneous electrical nerve stimulation (TENS) has been
effective in a variety of conditions. Conventional low-intensity, high-frequency stimulation and acupuncture-like
high-intensity, low-frequency stimulation are both commonly employed. Long-term use of TENS is associated with
reduced use of pain medication and physical and occupational therapy services. Cost reductions for medication and
physical and occupational therapy have been reported to approach 55% and 69%, respectively, when TENS was
used for more than 6 months. Electroacupuncture has been used in myofascial pain conditions, placing needles
[295]
locally along segmental receptive fields, and distally in both myotomal and sclerotomal distributions. Chronic
nociceptive musculoskeletal pain is effectively reduced by low-frequency electrical stimulation. Periosteal
stimulation is anecdotally reported to have the greatest effect upon nociceptive visceral pain, although other modes
of acupuncture and low-frequency TENS also proved helpful. To date there is no convincing evidence for the
efficacy of acupuncture in the treatment of chronic pain, but it remains useful when employed immediately
[296] [297]
before physical therapy interventions as a means of facilitating the stretching of painful trigger points.
679
Epilogue
The fate of neural blockade in the treatment of chronic nonmalignant pain in the near term may well depend on
results of both evidence-based outcome data and cost analyses of the common procedures outlined in this chapter.
Indications for regional anesthesia for pain control will undoubtedly expand as long-acting local anesthetic and [298]
opioid preparations using biodegradable polymers and lipid encapsulation become available for clinical use. Other
[299]
novel applications for existing therapeutic agents are also under investigation. Intraspinal infusions of calcium
channel blockers, NMDA antagonists, acetylcholinesterase inhibitors, adenosine, somatostatin, and cyclooxygenase-
2 inhibitors all exhibit analgesic effect. Among the most innovative intraspinal injectates are adrenal chromaffin
[300] [301]
cells as an ongoing source of analgesic neuropeptides. The refinement of a delivery system to protect the cells
[302]
from the host immune system may make this technique practical for chronic nonmalignant pain. [303]
Recent basic scientific progress may lead to still further novel applications of neural blockade in the future. The
most exciting of these developments is indisputably the sequencing of all 120,000 genes by the collaborative Human
Genome Project. Preemptive intraspinal administration of NMDA antagonists has been demonstrated to interfere
[304]
with the development of neuropathic pain after injury. Identification of patients at risk for neuropathic pain may
[305] [306]
guide judicious post-traumatic intervention aimed at the prevention of chronic pain. For example, a gene or genes
conferring susceptibility on the development of neuropathic pain and the responsiveness to treatment with
sympathetic blocks has been suggested to be associated with the major histocompatibility complex region on the
short arm of chromosome 6. The genes associated with the major histocompatibility complex are now
[210]
sequenced ; the ability to predict CRPS following trauma may soon be possible in some cases. Teleologically, this
[307]
association, if eventually proved, may further the already mounting evidence for an immunologic basis for
neurogenic inflammation. Conversely, because sympathetic blocks are known to affect immune function,
[308] [309]
additional indications for their use may arise quite aside from pain management.
Certainly, the abundance of new intrathecal analgesics designed to preempt or control chronic pain has fueled
tremendous enthusiasm for further research to explore their clinical therapeutic potential. However, there is another
area where advances may lead to actual repair of neural damage in chronic pain states already established: the
injection of neurons themselves. Subarachnoid injection of neurons modified to secrete brain-derived neurotropic
factor have behaved as “biologic minipumps” to reduce neuropathic pain in an animal model. Yet the experimental [310]
finding that spinally injected embryonic stem cells can promote axonal regrowth and recovery of neural function
after injury to the spinal cord may have the most profound implications for pain control. Obviously, improved
[311]
function is quite different from a repair that permits the reestablishment of normal interneuronal architecture and
thus relieves attendant pain. Still, it is conceivable that the introduction of neural progenitor cells may allow some
[312]
reorganization of disrupted pathways, especially when one considers the magnitude of the progress made in recent
decades and the discoveries that surely lie in the future. Thus the lessons learned using neural blockade in the
treatment of chronic nonmalignant pain may prove invaluable.
REFERENCES
1. Hippocrates: Citation 14. In Bartlett J, Kaplan J (eds): Familiar Quotations, 16th ed. Boston, Little, Brown, 1992, p 71.
2. World Health Organization: Cancer Pain Relief, 2nd ed. Geneva, World Health Organization, 1996.
3. Leape LL: Error in medicine. JAMA 272:1851–1857, 1994.
4. Committee on Quality Health Care in America, Institute of Medicine: Creating safety systems in health care organizations. In Kohn LT,
Corrigan J, Donaldson MS (eds): To Err is Human: Building a Safer Health System. Rockville, Md, National Academy Press, 2000, pp 155–202.
5. McMahon SB, Wall PD: Receptive fields of rat lamina I projection cells move to incorporate a nearby region of injury. Pain 19:235–247, 1984.
6. Dostrovsky J, Millar J, Wall PD: The immediate shift of afferent drive of dorsal column nucleus cells following deafferentation: A comparison
of acute and chronic deafferentation in gracile nucleus and spinal cord. Exp Neurol 52:480–495, 1976.
7. Inbal R, Rousso M, Ashur H, et al: Collateral sprouting in skin and sensory recovery after nerve injury in man. Pain 28:141–154, 1987.
8. Coderre TJ, Katz J, Vaccarino AL, et al: Contribution of central neuroplasticity to pathological pain: Review of clinical and experimental
evidence. Pain 52:259–285, 1993.
9. Rey R: The 19th century: The great discoveries. In History of Pain. Paris, Editions La Decouverte, 1993, p 246.
680
10. Chase
AW: Medical recipes: Sciatica cured with electricity—a very cheap, simple battery—how to make and use. In Dr. Chase's Receipt Book
and Household Physician, 3rd ed. Detroit, FB Dickerson, 1892, pp 36–37.
11. Hogan QH, Abrams SE: Neural blockade for diagnosis and prognosis. Anesthesiology 86:216–241, 1997.
12. NorthRB, Kidd DH, Zahurak M, et al: Specificity of diagnostic nerve blocks: A prospective, randomized study of sciatica due to lumbosacral
spine disease. Pain 65:77–85, 1996.
13. Arntz A, Vanden Hout MA, Vanden Berg G, et al: The effects of incorrect pain expectations on acquired fears and pain responses. Behav Res
Ther 29:547–560, 1991.
14. Raja SN: Nerve blocks in the evaluation of chronic pain. Anesthesiology 86:4–6, 1997.
15. Beecher HK: The powerful placebo. JAMA 159:1602–1606, 1955.
16. Traut EF, Passarelli EW: Study on the controlled therapy of degenerative arthritis. Arch Intern Med 98:181–186, 1956.
17. Liberman R: An experimental study of the placebo response under three different situations of pain. J Psychiatr Res 2:233–246, 1964.
18. Houde
RW, Wallenstein MS, Rogers A: Clinical pharmacology of analgesics: A method of assaying analgesic effect. Clin Pharmacol Ther
1:163–174, 1966.
19. Kantor TG, Sunshine A, Laska E, et al: Oral analgesic studies: Pentazocine hydrochloride, codeine, aspirin, and placebo and their influence on
response to placebo. Clin Pharmacol Ther 7:447–454, 1966.
20. Laska E, Sunshine A: Anticipation of analgesia: A placebo effect. Headache 13:1–11, 1973.
21. JacobsonL, Chabal C, Mariano AJ, et al: Persistent low-back pain is real. However, diagnostic spinal injections are not helpful in its
evaluation. Clin J Pain 8:237–241, 1992.
22. Brena
SF, Chapman SL: Chronic pain states and compensable disability: An algorithmic approach. In Benedetti C (ed): Advances in Pain
Research and Therapy, vol 7. New York, Raven Press, 1984, pp 131–145.
23. Melzack R: The McGill Pain Questionnaire: Major properties and scoring methods. Pain 1:277–299, 1975.
24. Myles PS, Troedel S, Boquest M, et al: The pain visual analog scale: Is it linear or nonlinear? Anesth Analg 89:1517–1520, 1999.
25. Zung WWK: A rating instrument for anxiety disorders. Psychosomatics 12:371–379, 1971.
26. Beck AT, Ward CH, Mendelson M, et al.: An inventory for measuring depression. Arch Gen Psychiatry 4:561–571, 1961.
27. Kerns RD, Rosenberg R, Jamison RN, et al: Readiness to adopt a self-management approach to chronic pain: The Pain Stages of Change
Questionnaire (PSOCQ). Pain 72:227–234, 1997.
28. MuseM, Frigola G: Development of a quick screening instrument for detecting post-traumatic stress disorder in the chronic pain patient:
Construction of the Post-traumatic Chronic Pain Test (PCPT). Clin J Pain 2:151–153, 1987.
29. Greenough CG, Fraser RD: Assessment of outcome in patients with low-back pain. Spine 17:36–41, 1992.
30. Deyo RA, Diehl AK: Psychosocial predictors of disability in patients with low back pain. J Rheumatol 15:1557–1564, 1988.
31. Burton AK, Tillotson KM, Main CJ, et al: Psychosocial predictors of outcome in acute and subchronic low back trouble. Spine 20:722–728,
1995.
32. FranceRD, Krishnan KRR, Trainor M: Chronic pain and depression. III: Family history study of depression and alcoholism in chronic low
back pain patients. Pain 24:185–190, 1986.
33. Bruehl S, Carlson CR: Predisposing psychological factors in the development of reflex sympathetic dystrophy: A review of the empirical
evidence. Clin J Pain 8:287–299, 1992.
34. Philips HC, Berkowitz J: The prevention of chronic pain and disability: A preliminary investigation. Behav Res Ther 29:443–450, 1991.
35. GatchelRJ, Polatin PB, Kinney RK: Predicting outcome of chronic back pain using clinical predictors of psychopathology: A prospective
analysis. Health Psychol 14:415–420, 1995.
36. Gatchel RJ, Polatin PB, Mayer TG: The dominant role of psychosocial risk factors in the development of chronic low back pain disability.
Spine 20:2702–2709, 1995.
37. Klenerman L, Slade PD, Stanley IM, et al: The prediction of chronicity in patients with an acute attack of low back pain in a general practice
setting. Spine 20:478–484, 1995.
681
38. Cats-Baril WL, Frymoyer JW: Identifying patients at risk of becoming disabled because of low back pain. Spine 16:605–607, 1991.
39. Hardcastle VG: The Myth of Pain. Cambridge, Mass, MIT Press, 1999, p 34.
40. Kouyanou K, Pither CE, Rabe-Hesketh S, et al: A comparative study of iatrogenesis, medication abuse, and psychiatric morbidity in chronic
pain patients with and without medically explained symptoms. Pain 76:417–426, 1998.
41. Benedikt RA, Kolb LC: Preliminary findings on chronic pain and posttraumatic stress disorder. Am J Psychiatry 143:908–910, 1986.
42. Kelley JT: Chronic pain and trauma. Adv Psychosom Med 16:141–142, 1986.
43. Robinson ME, Myers CD, Sadler IJ, et al.: Bias effects in three common self-report pain assessment measures. Clin J Pain 13:74–81, 1997.
44. Hartrick CT: Screening instruments predict long-term response to epidural steroids. J Contemp Neurol 3(1):1–6, 1998, Available at
http://www.mitpress.mit.edu
45. Burchiel KJ: Prognostic factors of spinal cord stimulation for chronic back and leg pain. Neurosurgery 36:1101–1111, 1995.
46. North
RB, Kidd DH, Zahurak M, et al: Spinal cord stimulation for chronic intractable pain: Experience over two decades. Neurosurgery
32:384–395, 1993.
47. Hagedorn SD, Maruta T, Swanson DW, et al: Premorbid MMPI profiles of low back pain patients: Surgical successes versus surgical failures.
Clin J Pain 1:177–179, 1985.
48. Burchiel KJ, Anderson VC, Brown FD, et al: Prospective, multicenter study of spinal cord stimulation for relief of chronic back and extremity
pain. Spine 21:2786–2794, 1996.
49. KupersRC, Van den Oever R, Van Houdenhove B, et al: Spinal cord stimulation in Belgium: A nation-wide survey on the incidence,
indications, and therapeutic efficacy by the health insurer. Pain 56:211–216, 1994.
50. Dumoulin K, Devulder J, Castille F, et al: A psychoanalytic investigation to improve the success rate of spinal cord stimulation as a treatment
for chronic failed back surgery syndrome. Clin J Pain 12:43–49, 1996.
51. Meilman PW, Leibock LG, Leong FTL, et al: Outcome of implanted spinal cord stimulation in the treatment of chronic pain: Arachnoiditis
versus single root injury and mononeuropathy. Clin J Pain 5:189–193, 1989.
52. Nelson DV, Kennington M, Novy DM, et al: Psychological selection criteria for implantable spinal cord stimulators. Pain Forum 5:93–103,
1996.
53. BedderMD: Spinal cord stimulation and intractable pain: Patient selection. In Waldman S, Winnie A (eds): Interventional Pain Management.
Philadelphia, WB Saunders, 1996, pp 412–418.
54. Parbrook GD, Steel GF, Dacrymple FG: Factors predisposing to postoperative pain and pulmonary complications. Br J Anaesth 45:21–33,
1973.
55. Eysenck SB, Eysenck HJ: The measurement of psychoticism: A study of factor stability and reliability. Br J Soc Psychol 7:286, 1968.
56. Wallis BJ, Lord SM, Bogduk N: Resolution of psychological distress of whiplash patients following treatment by radiofrequency neurotomy:
A randomised, double-blind, placebo-controlled trial. Pain 73:15–22, 1997.
57. Keefe FJ, Crisson J, Urban BJ, et al: Analyzing chronic low back pain: The relative contribution of pain coping strategies. Pain 40:293–301,
1990.
58. Haythornthwaite JA, Menefee LA, Heinberg, et al: Pain coping strategies predict perceived control over pain. Pain 77:33–39, 1998.
59. KernsRD, Rosenberg R: Predicting responses to self-management treatments for chronic pain: Application of the pain stages of change model.
Pain 84:49–55, 2000.
60. Geisser ME, Roth RS, Bachman JE, et al: The relationship between symptoms of post-traumatic stress disorder and pain, affective disturbance
and disability among patients with accident and non-accident related pain. Pain 66:207–214, 1996.
61. Kuch
K, Cox BJ, Evans RJ: Post-traumatic stress disorder and motor vehicle accidents: A multidisciplinary overview. Can J Psychiatry
41:429–434, 1996.
62. Turk DC, Okifuji A: Perception of traumatic onset, compensation status, and physical findings: Impact on pain severity, emotional distress,
and disability in chronic pain patients. J Behav Med 19:435–453, 1996.
63. Geisser ME, Roth RS, Bachman JE, et al: The relationship between symptoms of post-traumatic stress disorder and pain, affective disturbance
and disability among patients with accident and non-accident related pain. Pain 66:207–214, 1996.
64. Grevitt M, Khazim R, Webb J, et al: The short form-36 health survey questionnaire in spine surgery. J Bone Joint Surg Br 79:48–52, 1997.
682
65. Leclaire
R, Blier F, Fortin L, et al: A cross-sectional study comparing the Oswestry and Roland-Morris Functional Disability scales in two
populations of patients with low back pain of different levels of severity. Spine 22:68–71, 1997.
66. DeyoRA: Comparative validity of the Sickness Impact Profile and shorter scales for functional assessment of low back pain. Spine 11:951–
954, 1986.
67. RolandM, Morris R: A study of the natural history of back pain. Part I: Development of a reliable and sensitive measure of disability in low-
back pain. Spine 6:141–144, 1983.
68. Fairbank JCT, Couper J, Davies JB, et al: The Oswestry low back pain disability questionnaire. Physiotherapy 66:271–273, 1980.
69. Waddell G, McCulloch JA, Kummel E, et al: Nonorganic physical signs in low-back pain. Spine 5:117–125, 1980.
70. MarutaT, Goldman S, Chan CW, et al: Waddell's nonorganic signs and Minnesota Multiphasic Personality Inventory profiles in patients with
chronic low back pain. Spine 22:72–75, 1997.
71. Polatin PB, Cox B, Gatchel RJ, et al: A prospective study of Waddell signs in patients with chronic low back pain. Spine 22:1618–1621, 1997.
72. Harding VR, Williams AC, Richardson PH, et al: The development of a battery of measures for assessing physical functioning of chronic pain
patients. Pain 58:367–375, 1994.
73. Kaplan
GM, Wurtele SK, Gillis D: Maximal effort during functional capacity evaluation: An examination of psychological factors. Arch Phys
Med Rehabil 77:161–164, 1996.
74. Taimela S, Harkapaa K: Strength, mobility, their changes, and pain reduction in active functional restoration for chronic low back disorders. J
Spine Disord 9:306–312, 1996.
75. Malkia E, Ljunggren AE: Exercise programs for subjects with low back disorders. Scand J Med Sci Sports 6:73–81, 1996.
76. O'SullivanPB, Twomey LT, Allison GT: Evaluation of specific stabilizing exercise in the treatment of chronic low back pain with radiologic
diagnosis of spondylolysis or spondylolisthesis. Spine 22:2959–2967, 1997.
77. Hides
JA, Richardson CA, Jull GA: Multifidus muscle recovery is not automatic after resolution of acute first-episode low back pain. Spine
21:2763–2769, 1996.
78. DiFabio RP, Mackey G, Holte JB: Physical therapy outcomes for patients receiving worker's compensation following treatment for herniated
disc and mechanical low back pain syndrome. J Orthop Sports Phys Ther 23:180–187, 1996.
79. Burton AK, Erg E: Back injury and work loss: Biomechanical and psychosocial influences. Spine 22:2575–2580, 1997.
80. Hashemi
L, Webster BS, Clancy EA, et al: Length of disability and cost of worker's compensation low back pain claims. J Occup Environ Med
39:937–945, 1997.
81. RainvilleJ, Sobel JB, Hartigan C, et al: The effect of compensation involvement on the reporting of pain and disability by patients referred for
rehabilitation of chronic low back pain. Spine 22:2016–2024, 1997.
82. Pfingsten M, Hildebrandt J, Leibing E, et al: Effectiveness of a multimodal treatment program for chronic low back pain. Pain 73:77–85, 1997.
83. Lynch
RT, Agre J, Powers JM, et al: Long-term follow-up of outpatient interdisciplinary pain management with a no-treatment comparison
group. Am J Phys Med Rehabil 75:213–222, 1996.
84. Hildebrandt J, Pfingsten M, Saur P, et al: Prediction of success from a multidisciplinary treatment program for chronic low back pain. Spine
22:990–1001, 1997.
85. Basler H-D, Jalle C, Kroner-Herwig B: Incorporation of cognitive-behavioral treatment into medical care of chronic low back patients: A
controlled randomized study in German pain treatment centers. Patient Educ Couns 31:113–124, 1997.
86. BendixAF, Bendix T, Lund C, et al: Comparison of three intensive programs for chronic low back pain patients: A prospective randomized,
observer-blinded study with one-year follow-up. Scand J Rehabil Med 29:81–89, 1997.
87. Williams A C deC, Richardson PH, Nicholas MK, et al: Inpatient vs. outpatient pain management: Results of a randomized controlled trial.
Pain 66:13–22, 1996.
88. Feine JS, Lund JP: An assessment of the efficacy of physical therapy and physical modalities for the control of chronic musculoskeletal pain.
Pain 71:5–23, 1997.
89. Kuukkanen T, Malkia E: Muscular performance after a 3 month progressive physical exercise program and 9 month follow-up in subjects with
low back pain: A controlled study. Scand J Med Sci Sports 6:112–121, 1996.
90. Ben-David B, Raboy M: Manipulation under anesthesia combined with epidural steroid injection. J Manipulative Physiol Ther 17:605–609,
1994.
683
91. Aspergren
DD, Wright RE, Henler DE: Manipulation under epidural anesthesia with corticosteroid injection. J Manipulative Physiol Ther
20:618–621, 1997.
92. NelsonL, Aspergren D, Bova C: The use of epidural steroid injection and manipulation on patients with chronic low back pain. J Manipulative
Physiol Ther 20:263–266, 1997.
93. DreyfusP, Michaelsen M, Horn M: MUJA: Manipulation under joint anesthesia/analgesia: A treatment approach for recalcitrant low back pain
of synovial joint origin. J Manipulative Physiol Ther 18:537–546, 1995.
94. Ludwig SC, Vaccaro AR, Balderston RA, et al: Immediate quadriparesis after manipulation for bilateral cervical facet subluxation: a case
report. J Bone Joint Surg (Am) 79:587–590, 1997.
95. Yagi S, Hida K, Iwasaki Y, et al: Cervical epidural hematoma caused by twisting after epidural anesthesia: A case report. No Shinkei Geka
26:627–632, 1998.
96. Virani A, Mailis A, Shapiro LE, et al: Drug interactions in human neuropathic pain pharmacology. Pain 73:3–13, 1997.
97. Davies HTO, Crombie IK, Brown JH, et al: Diminishing returns or appropriate treatment strategy? An analysis of short-term outcomes after
pain clinic treatment. Pain 70:203–208, 1997.
98. Schwarzer AC, Derby R, Aprill CN, et al: The value of provocation response in lumbar zygapophyseal joint injections. Clin J Pain 10:309–313,
1994.
99. Barnsley L, Lord S, Wallis B, et al: False-positive rates of cervical zygapophyseal joint blocks. Clin J Pain 9:124–130, 1993.
100. Chapman SL, Jamison RN, Sanders, SH: Treatment helpfulness questionnaire: A measure of patient satisfaction with treatment modalities
provided in chronic pain management program. Pain 68:349–361, 1996.
101. Woolf CJ, Bennett GJ, Doherty M, et al: Towards a mechanism-based classification of pain? Pain 77:227–229, 1998.
102. Bigos S, Bowyer O, Braen G, et al: Acute Low Back Problems in Adults. Clinical Practice Guideline No. 14 (AHCPR Publication No 95-
0642). Rockville, Md, Agency for Health Care Policy and Research, Public Health Service, U.S. Department of Health and Human Services,
December 1994.
103. Stolker RJ, Vervest ACM, Groen GJ: The management of chronic spinal pain by blockades: A review. Pain 58:1–20, 1994.
104. Koes BW, Scholten RJ, Mens JM, et al: Efficacy of epidural steroid injections for low-back pain and sciatica: A systematic review of
randomized clinical trials. Pain 63:279–288, 1995.
105. McLain RF: Epidural corticosteroid therapy for back and leg pain: Questions of efficacy and action. Pain Digest 6:153–160, 1996.
106. Brown FW: Management of discogenic pain using epidural and intrathecal steroids. Clin Orthop 129:72–78, 1977.
107. Heyse-Moore G: A rational approach to the use of epidural medication in the treatment of sciatic pain. Acta Orthop Scand 49:366–370, 1978.
108. Jamison RN, VadeBoncouer T, Ferrante FM: Low back pain patients unresponsive to an epidural steroid injection: Identifying predictive
factors. Clin J Pain 7:311–317, 1991.
109. Hopwood MB, Abram SE: Factors associated with failure of lumbar epidural steroids. Reg Anesth 18:238–243, 1993.
110. Straus BN, Gould SJ, Demosthenes C: The effect of epidural steroid injections on laminectomy rate [abstract]. Reg Anesth 22:S74, 1997.
111. Hartrick CT, Silvasi D: The influence of screening consultation on the efficacy of epidural steroids for lumbosacral radiculopathy [abstract].
Reg Anesth 22:S108, 1996.
112. Dobritt DW, Hartrick CT: Reflex sympathetic dystrophy associated with multiple lumbar laminectomies. Clin J Pain 2:119–122, 1986.
113. Sachs BL, Zindrick MR, Beasley RD: Reflex sympathetic dystrophy after operative procedures on the lumbar spine. J Bone Joint Surg Am
75:721–725, 1993.
114. Blomberg RG: Fibrous structures in the subarachnoid space: A study with spinaloscopy in autopsy subjects. Anesth Analg 80:875–879, 1995.
115. Racz CB, Holubec JT: Lysis of adhesions in the epidural space. In Racz GB (ed): Techniques of Neurolysis, Boston, Kluwer Academic, 1989,
pp 57–72.
116. Lewandowski E: The efficacy of solutions used in caudal neuroplasty. Pain Digest 7:323–330, 1997.
117. HeavnerJE, Racz GB, Raj P: Percutaneous epidural neuroplasty: Prospective evaluation of 0.9% NaCl versus 10% NaCl with or without
hyaluronidase. Reg Anesth 24:202–207, 1999.
118. Aldrete
JA, Zapata JC, Ghaly R, et al: Arachnoiditis following epidural adhesiolysis with hypertonic saline. Report of 2 cases. Pain Digest
6:368–370, 1996.
684
119. Epstein JM, Adler RA: Laser-assisted percutaneous endoscopic neurolysis. Pain Physician 3:43–45, 2000.
120. Kitamura
A, Sakamoto A, Aoki S, et al: Epiduroscopic changes in patients undergoing single and repeated epidural injection. Anesth Analg
82:88–90, 1996.
121. Haueisen DC, Smith BS, Myers SR, et al: The diagnostic accuracy of spinal nerve injection studies. Clin Orthop 198:179–183, 1985.
122. Stanley D, McLaren MI, Euinton HA, et al: A prospective study of nerve root infiltration in the diagnosis of sciatica. Spine 15:540–543, 1990.
123. Devulder
J: Transforaminal nerve root sleeve injection with corticosteroids, hyaluronidase, and local anesthetic in the failed back surgery
syndrome. J Spinal Disord 11:151–154, 1998.
124. Long DM, Erickson D, Campbell J, et al: Electrical stimulation of the spinal cord and peripheral nerves for pain control. Appl Neurophysiol
44:207–217, 1981.
125. Randolph PD: Psychologically based selection criteria for spinal cord stimulation: Following the lead of gate control theory. Pain Digest
8:286–291, 1998.
126. De La Porte C, Van de Kelft E: Spinal cord stimulation in failed back surgery syndrome. Pain 52:55–61, 1993.
127. North RB: The role of spinal cord stimulation in contemporary pain management. APS Journal 2:91–99, 1993.
128. Claeys LGY: Spinal cord stimulation for peripheral vascular disease: A critical review—European series. Pain Digest 9:337–341, 1999.
129. Jessurun GAJ, DeJongste MJL, Blanksma PK: Current views on neurostimulation in the treatment of cardiac ischemic syndromes. Pain
66:109–116, 1996.
130. Bogduk N: Diskography. APS Journal 3:149–154, 1994.
131. Rhyne AL, Smith SE, Wood KE, et al: Outcome of unoperated discogram-positive low back pain. Spine 20:1997–2000, 1995.
132. Knox BD, Chapman TM: Anterior lumbar interbody fusion for discogram concordant pain. J Spinal Disord 6:242–244, 1993.
133. SiebenrockKA, Aebi M: The value of diskography in disk-related pain syndrome of the cervical spine for evaluation of indications for
spondylodesis. Z Orthop Ihre Grenzgeb 131:220–224, 1993.
134. Sluijter
ME: Radiofrequency lesions of the communicating ramus in the treatment of low back pain. In GB Racz (ed): Techniques of
Neurolysis. Boston, Kluwer Academic, 1989, pp 145–159.
135. Saal
JS, Saal JA: Treatment of chronic discogenic low back pain with a thermal intradiscal catheter: A prospective outcome study. Spine
25:382–388, 2000.
136. Schwarzer AC, Aprill CN, Derby R, et al: The relative contributions of the disc and zygapophyseal joint in chronic low back pain. Spine
19:801–806, 1994.
137. Nakamura SI, Takahashi K, Takahashi Y, et al: The afferent pathways of discogenic low-back pain. Evaluation of L2 spinal nerve infiltration.
J Bone Joint Surg Br 78:606–612, 1996.
138. WengerCC: Radiofrequency lesions for the treatment of spinal pain. Pain Digest 8:1–16, 1998.
139. DeramondH, Depriester C, Galibert P, et al: Percutaneous vertebroplasty with methylmethacrylate: Technique, indication, and results. Radiol
Clin North Am 36:533–546, 1998.
140. ChandlerGS: Osteoporosis and new technique for relief of vertebral compression fractures. ISIS Sci Newslett 1(2):1–5, 1995. Available at
http://www.spinalinjection.com
141. Wilson PR: Cervicogenic headache. APS Journal 1:259–275, 1992.
142. Dreyfuss P, Michaelsen M, Fletcher D: Atlanto-occipital and lateral atlanto-axial joint pain patterns. Spine 19:1125–1131, 1994.
143. Barnsley L, Lord S, Bogduk N: Whiplash injury. Pain 58:283–307, 1994.
144. Lord SM, Barnsley I, Wallis BJ, et al: Percutaneous radiofrequency neurotomy for chronic cervical zygapophyseal-joint pain. N Engl J Med
334:1721–1726, 1996.
145. Fukuri S, Ohseto K, Shiotani M, et al: Distribution of referred pain from the lumbar zygapophyseal joints and dorsal rami. Clin J Pain 13:303–
307, 1997.
146. McCall IW, Park WM, O'Brian JP: Induced pain referral from posterior lumbar elements in normal subjects. Spine 4:441–446, 1979.
147. Dwyer A, Aprill C, Bogduk N: Cervical zygapophyseal joint patterns: A study in normal volunteers. Spine 15:453–457, 1990.
685
148. Fukui S, Ohseto K, Shiotani M: Patterns of pain induced by distending the thoracic zygapophyseal joints. Reg Anesth 22:332–336, 1997.
149. Kellgren JH: On the distribution of pain arising from deep somatic structures with charts of segmental pain areas. Clin Sci 4:35–46, 1939.
150. Murphy F: Sources and patterns of pain in disc disease. Clin Neurosurg 15:343–351, 1968.
151. Kuslich SD, Ulstrom CL: The tissue of origin of low back pain and sciatica: A report of pain response to tissue stimulation during operations
on the lumbar spine using local anesthesia. Orthop Clin North Am 22:181–187, 1991.
152. Schwarzer AC, Derby R, Aprill CN, et al: The value of provocative response in lumbar zygapophyseal joint injections. Clin J Pain 10:309–
313, 1994.
153. Maldague B, Mathurin P, Malghem J: Facet joint arthrography in lumbar spondylosis. Radiology 140:29–36, 1981.
154. Marks RC, Houston T, Thulbourne T: Facet joint injection and facet nerve block: A randomized comparison in 86 patients with chronic low
back pain. Pain 49:325–328, 1992.
155. Schwarzer AC, Aprill CN, Derby R, et al: The false-positive rate of uncontrolled diagnostic blocks of the lumbar zygapophyseal joints. Pain
58:195–200, 1994.
156. Schwarzer AC, Aprill CN, Derby R, et al: Clinical features of patients with pain stemming from the lumbar zygapophyseal joints. Spine
19:1132–1137, 1994.
157. Jull G, Bogduk N, Marsland A: The accuracy of manual diagnosis for cervical zygapophyseal joint pain syndromes. Med J Aust 148:233–236,
1988.
158. Rask B, Dall BE: Use of the pantaloon cast for the selection of fusion candidates in the treatment of chronic low back pain. Clin Orthop
288:148–157, 1993.
159. Bednar DA, Raducan V: External spinal skeletal fixation in the management of back pain. Clin Orthop 322:131–139, 1996.
160. Esses SI, Moro JK: The value of facet blocks in patient selection for lumbar fusion. Spine 18:185–190, 1993.
161. Bogduk N: International Spinal Injection Society guidelines for the performance of spinal injection procedures, part 1: Zygapophyseal joint
blocks. Clin J Pain 13:285–302, 1997.
162. Yeoman, W: The relation of arthritis of the sacro-iliac joint to sciatica, with an analysis of 100 cases. Lancet 2:1119–1122, 1928.
163. Rosenberg
JM, Quint DJ, de Rosayro AM: Computerized tomographic localization of sacroiliac joint injection does not predict clinical
improvement [abstract]. Anesthesiology 87:A760, 1997.
164. Fortin I, Aprill C, Dwyer A, et al: Sacroiliac joint: Pain referral maps. Paper presented at 7th Annual North American Spine Society Meeting
July 8–12, Boston, 1992, A 78, p 83.
165. Brechner T: Percutaneous cryogenic neurolysis of the articular nerve of Luschka. Reg Anesth 6:18–22, 1981.
166. Wenger CC: Radiofrequency lesions for the treatment of spinal pain. Pain Digest 8:1–16, 1998.
167. North RB, Han M, Zahurak M, et al: Radiofrequency lumbar facet denervation: Analysis of prognostic factors. Pain 57:77–83, 1994.
168. Stanton-Hicks M, Jänig W, Hassenbusch S, et al: Reflex sympathetic dystrophy: Changing concepts and taxonomy. Pain 63:127–133, 1995.
169. Bonica
JJ: Causalgia and other reflex sympathetic dystrophies. In Bonica JJ, Liebeskind JC, Albe-Fressard D, et al. (eds): Advances in Pain
Research and Therapy, vol 3. New York, Raven Press, 1979.
170. Wilson
PR: Sympathetically maintained pain: Diagnosis, measurement, and efficacy of treatment. In Stanton-Hicks M (ed): Pain and the
Sympathetic Nervous System. Boston, Kluwer Academic, 1990, pp 91–123.
171. Stanton-Hicks M, Janig W, Hassenbusch S, et al: Reflex sympathetic dystrophy: Changing concepts and taxonomy. Pain 63:127–133, 1995.
172. BruehlS, Harden RN, Galer BS, et al: External validation of IASP diagnostic criteria for complex regional pain syndrome and proposed
research diagnostic criteria. Pain 81:147–154, 1999.
173. Harden
RN, Bruehl S, Galer BS, et al: Complex regional pain syndrome: Are the IASP diagnostic criteria valid and sufficiently
comprehensive? Pain 83:211–219, 1999.
174. Wall PD, Devor M: Sensory afferent impulses originate from dorsal root ganglia as well as from the periphery in normal and nerve injured
rats. Pain 17:321–339, 1983.
175. Fitzgerald M: The spread of sensitization of polymodal nociceptors in the rabbit from nearby injury and antidromic nerve stimulation. J
Physiol (Lond) 297:207–216, 1979.
686
176. Roberts
WJ, Foglesong ME: Spinal recordings suggest that wide-dynamic-range neurons mediate sympathetically maintained pain. Pain
34:289–304, 1988.
177. Roberts WJ, Foglesong ME: Identification of afferents contributing to sympathetically evoked activity in wide-dynamic-range neurons. Pain
34:305–314, 1988.
178. Price DD, Bennett GJ, Rafii A: Psychophysical observations on patients with neuropathic pain relieved by a sympathetic block. Pain 36:273–
288, 1989.
179. Roberts WJ: A hypothesis on the physiological basis for causalgia and related pains. Pain 24:297–311, 1986.
180. Campbell JN, Raja SN, Meyer RA, et al: Myelinated afferents signal hyperalgesia associated with nerve injury. Pain 32:89–94, 1988.
181. Price DD, Long S, Huitt C: Sensory testing of pathophysiological mechanisms of pain patients with reflex sympathetic dystrophy. Pain
49:163–173, 1992.
182. Cremer SA, Maynard F, Davidoff G: The reflex sympathetic dystrophy syndrome associated with traumatic myelopathy: Report of 5 cases.
Pain 37:187–192, 1989.
183. Gellman H, Eckert RR, Botte MJ, et al: Reflex sympathetic dystrophy in cervical spinal cord injury patients. Clin Orthop 233:126–131, 1988.
184. Jensen
TS, Krebs B, Nielsen J, et al: Phantom limb, phantom pain and stump pain in amputees during the first 6 months following amputation.
Pain 17:243–256, 1983.
185. Krebs
B, Jensen TS, Kroner K, et al: Phantom limb phenomena in amputees seven years after limb amputation. In Fields HL, Dubner R,
Cervero F (eds): Advances in Pain Research and Therapy, vol 9. New York, Raven Press, 1985.
186. Melzack R: Phantom limb pain: Implications for treatment of pathologic pain: Anesthesiology 35:409, 1971.
187. Riddock GP: Phantom limbs and body shape. Brain 64:197, 1941.
188. Bach
S, Noreng MF, Tjellden NU: Phantom limb pain in amputees during the first 12 months following limb amputation, after preoperative
lumbar epidural blockade. Pain 33:297–301, 1988.
189. Steinbach
TV, Nadvorna H, Arazi D: A five year follow-up study of phantom limb pain in posttraumatic amputees. Scand J Rehabil Med
14:203–207, 1982.
190. Kallio KE: Permanency of results obtained by sympathetic surgery in the treatment of phantom pain. Acta Orthop Scand 19:391, 1950.
191. Devor M, Wall PD: Reorganization of spinal cord sensory map after peripheral nerve injury. Nature 276:75, 1978.
192. Wall PD, Eggerr MD: Formation of new connections in adult rat brain after partial deafferentation. Nature 232:542, 1971.
193. Melzack R, Loeser JD: Phantom body pain in paraplegics: Evidence for a “central pattern generating mechanism” for pain. Pain 4:195–210,
1978.
194. Benc A, Dimitnjevic MR, Lindblom U: Central dysesthesia syndrome in spinal cord injury patients. Pain 34:109–116, 1988.
195. EidePK, Stubhaug A, Stenehjem AE: Central dysesthetic pain after traumatic spinal cord injury is dependent on N-methyl-D-aspartate
receptor activation. Neurosurgery 37:1080–1087, 1995.
196. Uomoto JM, Esselman PC: Traumatic brain injury and chronic pain: Differential types and rates by head injury severity. Arch Phys Med
Rehabil 74:61–64, 1993.
197. Frisbie JH, Aguilera EJ: Chronic pain after spinal cord injury: An expedient diagnostic approach. Paraplegia 28:460–465, 1990.
198. Siddall PJ, Taylor DA, Cousins MJ: Classification of pain following spinal Cord injury. Spinal Cord 35:69–75, 1997.
199. Wainapel SF: Reflex sympathetic dystrophy following traumatic myelopathy. Pain 18:345–349, 1984.
200. Low PA, Amadio PC, Wilson PR, et al: Laboratory findings in reflex sympathetic dystrophy: A preliminary report. Clin J Pain 10:235–239,
1994.
201. Sandroni P, Low PA, Ferrer T, et al: Complex regional pain syndrome I (CRPS I): Prospective study and laboratory evaluation. Clin J Pain
14:282–289, 1998.
202. Verdugo RJ, Ochoa JL: Use and misuse of conventional electrodiagnosis, quantitative sensory testing, thermography, and nerve blocks in the
evaluation of painful neuropathic syndromes. Muscle Nerve 16:1056–1062, 1993.
203. Katims JJ: Electrodiagnostic functional sensory evaluation of the patient with pain: A review of the neuroselective current perception
687
threshold and pain tolerance theshold. Pain Digest 8:219–230, 1998.
204. Galer
BS, Bruehl S, Harden N: IASP diagnostic criteria for complex regional pain syndrome: A preliminary empirical validation study. Clin J
Pain 14:48–54, 1998.
205. Baron R, Haendler G, Schulte H: Afferent large fiber polyneuropathy predicts the development of postherpetic neuralgia. Pain 73:231–238,
1997.
206. Wang JK, Johnson KA, llstrup DM: Sympathetic blocks for reflex sympathetic dystrophy. Pain 23:13–17, 1985.
207. WangJK, Erickson R, llstrup DM: Repeated stellate ganglion blocks for upper-extremity reflex sympathetic dystrophy. Reg Anesth 10:125–
128, 1985.
208. Tenelian DL: Reflex sympathetic dystrophy: Reevaluation of the literature. Pain Forum 5:247–256, 1996.
209. Torebjork HE, Hallin RG: Recordings of impulses in unmyelinated nerve fibers in man: Afferent C fibre activity. Acta Anaesth Scand
70:S124–129, 1978.
210. Mailis A, Wade J: Profile of Caucasian women with possible genetic predisposition to reflex sympathetic dystrophy: A pilot study. Clin J Pain
10:210–217, 1996.
211. Daemen MA, Kurvers HA, Kitslaar PJ, et al: Neurogenic inflammation in an animal model of neuropathic pain. Neurol Res 20:41–45, 1998.
212. Holthusen H, Arndt JO: The role of pain from veins for the formation of perivenous edema in humans. Pain 68:395–400, 1996.
213. Doupe J, Cullen C, Chance G: Post-traumatic pain and the causalgia syndrome. J Neurol Neurosurg Psychiatry 7:33–44, 1944.
214. Xavier AV, McDanal J, Kissin I: Relief of sciatic radicular pain by sciatic nerve block. Anesth Analg 67:1177–1180, 1988.
215. Ono H, Mishima A, Ono S, et al: Inhibitory effects of clonidine and tizanidine on the release of substance P from slices of rat spinal cord and
antagonism by alpha-adrenergic receptor antagonists. Neuropharmacology 30:585–589, 1991.
216. Loubser PG, Akman NM: Effects of intrathecal baclofen on chronic spinal cord injury pain. J Pain Symptom Manage 12:241–247, 1996.
217. Yaksh TL, Reddy SVR: Studies in the primate on the analgesic effects associated with intrathecal actions of opiate, α-adrenergic agonists and
baclofen. Anesthesiology 54:451–467, 1981.
218. Cui J-G, O'Connor WT, Ungerstedt U, et al: Spinal cord stimulation attenuates augmented dorsal horn release of excitatory amino acids in
mononeuropathy via a GABAergic mechanism. Pain 73:87–95, 1997.
219. Kemler
MA, Berendse GAM, van Kleef M, et al: Pain relief in complex regional pain syndrome due to spinal cord stimulation does not
depend on vasodilation. Anesthesiology 92:1653–1660, 2000.
220. Blumberg H, Janig W: Discharge pattern of afferent fibers from a neuroma. Pain 20:335–353, 1984.
221. NordinM, Mystrom B, Wallin U, et al: Ectopic sensory discharges and paresthesiae in patients with disorders of peripheral nerves, dorsal
roots and dorsal columns. Pain 20:231–245, 1984.
222. Johansson A, Bennett GJ: Effect of local methylprednisolone on pain in a nerve injury model. Reg Anesth 22:59–65, 1997.
223. Devor
M, Govrin-Lippman R, Raber P: Corticosteroids suppress ectopic neural discharge originating in experimental neuromas. Pain 22:127–
137, 1985.
224. Edgar RE, Best LG, Quail PA, et al: Computer-assisted DREZ microcoagulation: Posttraumatic spinal deafferentation pain. J Spinal Disord
6:48–56, 1993.
225. Kramis RC, Roberts WJ, Gillette RG: Post-sympathectomy neuralgia: Hypotheses on peripheral and central neuronal mechanisms. Pain 64:1–
9, 1996.
226. Lahz S, Bryant RA: Incidence of chronic pain following traumatic brain injury: Arch Phys Med Rehabil 77:889–891, 1996.
227. Stambrook
M, Moore AD, Peters LC, et al: Head injury and spinal cord injury: Differential effects on psychosocial functioning. J Clin Exp
Neuropsychol 13:521–530, 1991.
228. Frank RG, Haut AE, Smick M, et al: Coping and family functions after closed head injury. Brain Inj 4:289–295, 1990.
229. Anderson JM, Kaplan MS, Felsenthal G: Brain injury obscured by chronic pain: A preliminary report. Arch Phys Med Rehabil 71:703–708,
1990.
230. Stevens RA, Stotz A, Kao T-C, et al: The relative increase in skin temperature after stellate ganglion block is predictive of complete
sympathectomy of the hand. Reg Anesth 23:266–270, 1998.
688
231. Tran KM, Frank SM, Raja SN, et al: Lumbar sympathetic block for sympathetically maintained pain: Changes in cutaneous temperatures and
pain perception. Anesth Analg 90:1396–1401, 2000.
232. Hartrick CT: Genitofemoral nerve block: A transpsoas approach. Reg Anesth 19:432–433, 1994.
234. Hartrick CT: Pain due to trauma including sports injuries. Pain Digest 8:237–259, 1998.
235. BorgeatA, Perschak H, Bird P, et al: Patient-controlled interscalene analgesia with ropivacaine 0.2% versus patient-controlled intravenous
analgesia after major shoulder surgery. Anesthesiology 92:102–108, 2000.
236. Rosenblatt RM: Continuous femoral anesthesia for lower extremity surgery. Anesth Analg 59:631–633, 1980.
237. Schultz P, Anker-Moller E, Dahl JB, et al: Postoperative pain treatment after open knee surgery: Continuous lumbar plexus block with
bupivacaine versus epidural morphine. Reg Anesth 16:34–37, 1991.
238. Chudinov A, Berkenstadt H, Salai M, et al: Continuous psoas compartment block for anesthesia and perioperative analgesia in patients with
hip fractures. Reg Anesth 24:563–566, 1999.
239. Aldrete JA: Extended epidural catheter infusions with analgesics for patients with noncancer pain at their homes. Reg Anesth 22:35–42, 1997.
240. Kingery WS: A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndromes. Pain 73:123–
139, 1997.
241. Hord AH, Rooks MD, Stephens BO, et al: Intravenous regional bretylium and lidocaine for the treatment of reflex sympathetic dystrophy: A
randomized, double-blind study. Anesth Analg 74:818–821, 1992.
242. Abram SE: Neural blockade for neuropathic pain. Clin J Pain 16:S56–S61, 2000.
243. Dahm P, Nitescu P, Appelgren L, et al: Efficacy and technical complications of long-term continuous intraspinal infusions of opioid and/or
bupivacaine in refractory non-malignant pain: A comparison between the epidural and the intrathecal approach with externalized or implanted
catheters and infusion pumps. Clin J Pain 14:4–16, 1998.
244. Nitescu
P, Dahm P, Appelgren L, et al: Continuous infusion of opioid and bupivacaine by externalized intrathecal catheters in long-term
treatment of “refractory” nonmalignant pain. Clin J Pain 14:17–28, 1998.
245. Bedder MD, Burchiel K, Larson A: Cost analysis of two implantable narcotic delivery systems. J Pain Symptom Manage 6:368–373, 1991.
246. Vainio A, Ollila J, Matikainen E, et al: Driving ability in cancer patients receiving long-term morphine analgesia. Lancet 346:667–670, 1995.
247. Chabal C, Erjavec MK, Jacobson L, et al: Prescription opiate abuse in chronic pain patients: Clinical criteria, incidence, and predictors. Clin J
Pain 13:150–155, 1997.
248. Benedetti F, Vighetti S, Amanzio M, et al: Dose-response relationship of opioids in nociceptive and neuropathic postoperative pain. Pain
74:205–211, 1998.
249. Coombs DW, Maurer LH, Saunders RL, et al: Outcomes and complications of continuous intraspinal narcotic analgesia for cancer pain
control. J Clin Oncol 2:1414–1420, 1984.
250. VanDongen RTM, Crul BJP, DeBock M: Long-term intrathecal infusion of morphine and morphine/bupivacaine mixtures in the treatment of
cancer pain: A retrospective analysis of 51 cases. Pain 55:119–123, 1993.
251. Coombs DW, Saunders RL, LaChance D, et al: Intrathecal morphine tolerance: Use of intrathecal clonidine, DADLE, and intraventricular
morphine. Anesthesiology 62:358–363, 1985.
252. Eisenach JC, Hood DD, Curry R: Relative potency of epidural to intrathecal clonidine differs between acute thermal pain and capsaicin-
induced allodynia. Pain 84:57–64, 2000.
253. Herman RM, D'Luzansky SC, Ippolito R: Intrathecal baclofen suppresses central pain in patients with spinal lesions. Clin J Pain 8:338–345,
1992.
254. Zuniga RE, Schlicht CR, Abram SE: Intrathecal baclofen is analgesic in patients with chronic pain. Anesthesiology 92:876–880, 2000.
255. Ordia JI, Fischer E, Adamski E, et al: Chronic intrathecal delivery of baclofen by a programmable pump for the treatment of severe spasticity.
J Neurosurg 85:452–457, 1996.
256. AzouviP, Mane M, Thiebaut J-B, et al: Intrathecal baclofen administration for control of severe spinal spasticity: Functional improvement
and long-term follow-up. Arch Phys Med Rehabil 77:35–39, 1996.
257. Ohno K, Oshita S: Transdiscal lumbar sympathetic block: A new technique for chemical sympathectomy. Anesth Analg 85:1312–1316, 1997.
689
258. Racz
GB, Holubec JT: Stellate ganglion phenol neurolysis. In Racz G (ed): Techniques of Neurolysis. Boston, Kluwer Academic, 1989, pp
133–144.
259. Geurts JWR, Stolker RJ: Percutaneous radiofrequency lesion of the stellate ganglion in the treatment of pain in the upper extremity: Reflex
sympathetic dystrophy. Pain Clin 6:17–25, 1993.
260. Wilkinson HA: Radiofrequency percutaneous upper-thoracic sympathectomy. N Engl J Med 311:34–36, 1984.
261. Forouzanfar T, van Kleef M, Weber WEJ: Radiofrequency lesions of the stellate ganglion in chronic pain syndromes: Restrospective analysis
of clinical efficacy in 86 patients. Clin J Pain 16:164–168, 2000.
262. Boas RA: Sympathetic blocks: In search of a role. Reg Anesth 23:292–305, 1998.
263. Kanazi GE, Perkins FM, Thakur R, et al: New technique for superior hypogastric plexus block. Reg Anesth 24:473–476, 1999.
264. RoccoAG: Radiofrequency lumbar sympatholysis: The evaluation of a technique for managing sympathetically maintained pain. Reg Anesth
20:3–12, 1995.
265. Rocco AG, Palombi D, Raeke D: Anatomy of the lumbar sympathetic chain. Reg Anesth 20:13–19, 1995.
266. Simone DA, Marchettini P, Ochoa PL: Primary afferent nerve fibers that contribute to muscle pain sensation in humans. Pain Forum 6:207–
212, 1997.
267. Mense S: Activity in nociceptive primary afferent fibers and clinical muscle pain. Pain Forum 6:212–216, 1997.
268. Khing HN, Van der Does E: The occurrence and inter-rater reliability of myofascial trigger points in the quadratus lumborum and gluteus
medius: A prospective study in non-specific low back pain patients and controls in general practice. Pain 58:317–323, 1994.
269. Kalyan-Raman UP, Kalyan-Raman K, Yunus MB, et al: Muscle pathology in primary fibromyalgia syndrome: A light microscopic,
histochemical, and ultrastructural study. J Rheumatol 11:808–813, 1984.
270. Bartels EM, Danneskiold-Samsoe B: Histological abnormalities in muscle from patients with certain types of fibrositis. Lancet 1:755–757,
1986.
271. Bengtsson A, Henriksson KG, Larsson J: Muscle biopsy in primary fibromyalgia, light microscopical and histochemical findings. Scand J
Rheumatol 15:1–6, 1986.
272. Fischer AA, Chang CH: Temperature and pressure threshold measurement in trigger points. Thermology 1:212–215, 1986.
273. Fischer AA: Tissue compliance meter for objective, quantitative documentation of soft tissue consistency and pathology. Arch Phys Med
Rehabil 68:122–125, 1987.
274. Kawakita K, Miura T, Iwase Y: Deep pain measurement at tender points by pulse algometry with insulated needle electrodes. Pain 44:235–
239, 1991.
275. Simons DG, Travell J: Myofascial trigger points, a possible explanation [letter]. Pain 10:106–109, 1981.
276. Bengtsson A, Henriksson KG, Larsson J: Reduced high energy phosphate levels in the painful muscles of patients with primary fibromyalgia.
Arthritis Rheum 29:817–821, 1986.
277. Caro XJ: Immunofluorescent detection of IgG at the dermal-epidermal junction in patients with apparent primary fibrositis syndrome.
278. Bonadede P, Nelson D, Clark S, et al: Exercising blood flow in patients with fibrositis: A 113 Xenon clearance study [abstract]. Arthritis
Rheum 30: S14, 1987.
279. Lund N, Bengtsson A, Thorborg P: Muscle tissue oxygen pressure, in primary fibromyalgia. Scand J Rheumatol 15:165–173, 1986.
280. Dubner R: Hyperalgesia and expanded receptive fields. Pain 48:3–4, 1992.
281. Gunn CC: Prespondylosis and some pain syndromes following denervation supersensitivity. Spine 5:185–192, 1980.
282. Roberts WJ, Elardo SM: Sympathetic activation of A-delta nociceptors. Somatosens Res 3:33–44, 1985.
283. Mense S: Nociception from skeletal muscle in relation to clinical muscle pain: A review. Pain 54:241–289, 1993.
284. Pecina MM, Bojanic I: Overuse Injuries of the Musculoskeletal System. Boca Raton, Fla, CRC Press, 1993, pp 1–26.
285. Curwin S, Stanish WD: Tendinitis: Its Etiology and Treatment. Lexington, MA, Collamore Press, 1984.
690
286. Tuncer T, Butman B, Arman M, et al: Primary fibromyalgia and allergy. Clin Rheumatol 16:9–12, 1997.
287. Vlaeyen JWS, Linton SJ: Fear-avoidance and its consequences in chronic musculoskeletal pain: A state of the art. Pain 85:317–332, 2000.
288. Fischer AA: Pressure algometry over normal muscles. Standard values, validity and reproducibility of pressure threshold. Pain 30:115–126,
1987.
289. WolfSL, Binder-Macleod SA: Electromyographic biofeedback in the physical therapy clinic. In Basmajian JV (ed): Biofeedback: Principles
and Practice for Clinicians, 2nd ed. Baltimore, Williams & Wilkins, 1983, pp 62–72.
290. Bengtsson A, Bengtsson M: Regional sympathetic blockade in primary fibromyalgia. Pain 33:161–167, 1988.
291. Acquardo M, Borodic G: Treatment of myofascial pain with botulinum A toxin. Anesthesiology 80:705–706, 1994.
292. Jordon SE, Machleder HI: Diagnosis of thoracic outlet using electrophysiologically guided anterior scalene blocks. Ann Vasc Surg 12:260–
264, 1998.
293. Porta
M, Perreti A, Gamba M, et al: The rationale and results of treating muscle spasm and myofascial syndromes with botulinum toxin type
A. Pain Digest 8:346–352, 1998.
294. Porta M, Perretti A, Gamba M, et al: Compartment botulinum toxin injection for myofascial pain relief. Dolor 12:S42, 1997.
295. Chabal C, Fishbain DA, Weaver M, et al: Long-term transcutaneous electrical nerve stimulation (TENS) use: Impact on medication utilization
and physical therapy costs. Clin J Pain 14:66–73, 1998.
296. Ezzo J, Berman B, Hadhazy VA, et al: Is acupuncture effective for the treatment of chronic pain? A systematic review. Pain 86:217–225,
2000.
297. Smith LA, Oldman AD, McQuay HJ, et al: Teasing apart quality and validity in systematic reviews: An example from acupuncture trials in
chronic neck and back pain. Pain 86:119–132, 2000.
298. Garry
MG, Jackson DL, Geier HE, et al: Evaluation of the efficacy of a bioerodable bupivacaine polymer system on antinociception and
inflammatory mediator release. Pain 82:49–55, 1999.
299. Kim T, Murdande S, Gruber A, et al: Sustained-release morphine for epidural analgesia in rats. Anesthesiology 85:331–338, 1996.
300. Wallace M, Yaksh TL: Long-term spinal analgesic delivery: A review of preclinical and clinical literature. Reg Anesth 25:117–157, 2000.
301. Dougherty PM, Staats PS: Intrathecal drug therapy for chronic pain: From basic science to clinical practice. Anesthesiology 91:1891–1918,
1999.
302. Winnie AP, Pappas GD, DasGupta TK, et al: Subarachnoid adrenal medullary transplants for terminal cancer pain. Anesthesiology 79:644–
653, 1993.
303. Decosterd
I, Buchser E, Gilliard N, et al: Intrathecal implants of bovine chromaffin cells alleviate mechanical allodynia in a rat model of
neuropathic pain. Pain 76:159–166, 1998.
304. Liang F, Holt I, Pertea G, et al: Gene index analysis of the human genome estimates approximately 120,000 genes. Nat Genet 25:239–240,
2000.
305. Hartrick
CT, Wise JJ, Patterson JS: Preemptive intrathecal ketamine delays the mechanical hyperalgesia in the neuropathic rat. Anesth Analg
86:557–560, 1998.
306. BurtonAW, Lee DH, Saab C, et al: Preemptive intrathecal ketamine injection produces a long-lasting decrease in neuropathic pain behaviors
in a rat model. Reg Anesth 24:208–213, 1999.
307. Beck S, Geraghty D, Inoko H, et al: Complete sequence and map of a human major histocompatibility complex. Nature 401:921–923, 1999.
308. Steinhoff M, Vergnolle N, Young SH, et al: Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nat
Med 6:151–158, 2000.
309. Yokoyama M, Natatsuka H, Itano Y, et al: Stellate ganglion block modifies the distribution of lymphocyte subsets and natural-killer cell
activity. Anesthesiology 92:109–115, 2000.
310. Cejas PJ, Martinez M, Karmally S, et al: Lumbar transplant of neurons genetically modified to secrete brain-derived neurotropic factor
attenuates allodynia and hyperalgesia after sciatic nerve constriction. Pain 86:195–210, 2000.
311. McDonaldJW, Lui X-Z, Qu Y, et al: Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord.
Nat Med 5:1410–1412, 1999.
312. Bjorkulund A, Linvall O: Cell replacement therapies for central nervous system disorders. Nat Neurosci 3:537–544, 2000.
691
692
Section IV - Chapter 28 - Malignant Pain
Chapter 28 - Malignant Pain
Mark S. Wallace
Albert Y. Leung
Michael D. Mcbeth
Pain is one of the most prevalent symptoms among patients with advanced cancer. It is the consequence they fear
most and with good reason. Numerous studies have shown that 30% to 50% of all cancer patients undergoing
chemotherapy or other antitumor treatments and 50% to 80% of those with advanced cancer suffer severe pain. [1]
Exceeded only by heart disease, cancer is the second leading cause of death in the United States, with 1 of every 4
deaths resulting from cancer. In 1999, the American Cancer Society estimated that 563,100 Americans would die of
cancer—more than 1500 people a day. Projections for the diagnosis of new cancer cases reached an all-time high of
1,220,100. These projections, therefore, even applying a conservative estimate of 50%, result in at least 610,050
new cancer cases that will require treatment for pain from cancer. [2]
The consequences of cancer pain influence the functional capability and psychological well-being of the cancer
patient as the disease progresses. Provision of relief from pain is important not only as a humanitarian goal but
[3] [4] [5]
also to improve patients’ prospects for survival. Unrelieved pain can significantly diminish the patient’s quality of
life and, therefore, diminish the patient’s willingness to continue treatment or even to continue living. Nearly
[4] [5] [6]
60% of Americans indicate that they would favor physician-assisted death as a last resort to end suffering from
uncontrolled pain associated with an illness. [7]
Drug therapy remains the foundation of cancer pain management. Numerous studies have demonstrated that the
World Health Organization (WHO) three-step hierarchy for pain management is effective in controlling pain for
70% to 90% of patients with cancer. However, for the 10% to 30% of cancer patients whose pain is not being
[8]
controlled by the WHO three-step ladder, or in patients who are experiencing severe side effects from the treatments,
regional anesthetic techniques can be very valuable.
This chapter discusses the role of regional anesthetic techniques for the treatment of cancer pain, the different pain
syndromes that may affect the cancer patient, and the regional anesthetic management of specific syndromes.
The Role of Regional Anesthetic Techniques for the Treatment of Cancer Pain
There is no clear consensus as to when more invasive therapies should be used in cancer patients, but, as a general
rule of thumb, therapies should start with more conservative, low-risk procedures and progress to more invasive,
high-risk procedures, which are justified by the presence of severe refractory pain. The United States Agency for
Health Care Policy and Research (AHCPR) has published guidelines for the management of cancer pain. [4] [5]
Although the AHCPR report focuses more on the pharmacologic management of cancer pain, the organization
endorses the use of regional anesthetic techniques for the treatment of severe cancer pain. However, AHCPR is
critical of the lack of well-controlled studies on the outcome of interventional techniques for cancer pain. In 1996,
the American Society of Anesthesiologists published guidelines for the treatment of cancer pain that focused more
on regional anesthetic techniques. The take-home message
[9]
TABLE 28-1 -- INDICATIONS FOR REGIONAL ANESTHESTIC TECHNIQUES FOR THE MANAGEMENT OF CANCER PAIN
Pain unrelieved by the World Health Organization three-step hierarchy of pain management
Unacceptable side effects with systemic therapies
Pain crisis
Patient’s desire to avoid systemic therapy
from these published guidelines is “first do no harm.” If more conservative, noninvasive measures have not been
tried in cancer pain patients, do not forge ahead to more invasive, high-risk procedures. As stated in the introduction,
70% to 90% of patients can be successfully treated with the conservative measures outlined in the WHO three-step
ladder. On the other hand, cancer patients who are suffering from severe unrelieved pain or are experiencing
debilitating side effects from systemic therapy should not be denied the benefits of regional anesthetic techniques
692
that can turn a major pain crisis into a manageable one. Table 28–1 summarizes the indications for regional
[10]
anesthetic techniques in cancer pain.
LOCAL ANESTHETIC NEURAL BLOCKADE
Although it is a temporary measure, local anesthetic neural blockade (LANB) is a valuable tool in the management
of cancer pain. Because the effects are temporary, the role of LANB must be clearly outlined to the patient,
[11] [12]
family, and healthcare providers. It can be very distressing to the patient to experience significant pain relief after
LANB only to have the severe pain return after a few hours. LANB is useful for the purposes of diagnosis,
prognosis, and therapy.
Diagnosis
For diagnostic purposes, LANB can be very valuable in determining the pathway or mechanism of the pain. Table
28–2 gives examples of diagnostic blocks.
The anatomic source of the pain can be diagnosed with a variety of LANB techniques. Joint pain resulting from
cancer (e.g., osteonecrosis, sacroiliac joint metastasis) can be diagnosed with intra-articular injections. Muscle
spasms as a result of tumor invasion of bony structures can be diagnosed with trigger point injections, and peripheral
nerve blocks can diagnose the peripheral neural pathway of the pain.
Although thoracoabdominal pain is often described as more localized and sharp compared with thoracic and visceral
pain, which is described as diffuse and dull, it can sometimes be difficult to differentiate visceral pain from
thoracoabdominal wall pain, especially as the pain becomes more severe. For thoracic pain, intercostal blocks can
differentiate between thoracic wall and visceral pain. With the exception of the cardiac structures, most of the
sensory innervation of the thoracic viscera travels through the T1–T4 sympathetic ganglion. Therefore,
cervicothoracic sympathetic blocks can be used to diagnose thoracic visceral pain. For abdominal pain, intercostal,
celiac plexus, and hypogastric plexus blocks can differentiate between abdominal wall and visceral pain.
Sympathetic blocks can be used to diagnose sympathetically mediated pain and to guide treatment. Because somatic
peripheral nerves contain both sympathetic and somatic fibers, it is necessary to block the sympathetic nervous
system at locations that are free of somatic nerves. This can be accomplished at the stellate ganglion for diagnosis of
head, neck, and upper extremity pain, and at the lumbar ganglion for diagnosis of lower extremity pain.
The technique of differential blockade may be useful in cancer pain diagnosis. Since the description of this
technique was reported by Winnie and Collins, it has generated much controversy. Both in vitro and in vivo studies
[13]
have cast doubt on the existence of a differential effect of local anesthetics on varying sizes of nerve fibers.
Although zones of differential sensory block after neuroaxial local anesthetics have been demonstrated in humans, [14]
both in vivo and in vitro studies have produced conflicting results.

[15] [16] [17]
Differential blockade can be achieved
[18] [19]
with different techniques: (1) spinal, (2) epidural, and (3) peripheral somatic blocks. All three techniques commonly
use 2% lidocaine, which results in motor, sensory, and sympathetic block. The block is evaluated as it regresses to
determine whether the pain correlates with the return of somatic sensory function or sympathetic function.
The use of placebo injections (i.e., saline) is controversial and caution should be exercised with this modality
TABLE 28-2 -- DIAGNOSTIC BLOCKS IN CANCER PAIN MANAGEMENT

Anatomic source of pain
Intra-articular injection
Trigger point injection
Peripheral nerve block
Visceral versus somatic pain
Intercostal nerve block
Differentiates thoracoabdominal wall pain from thoracic and abdominal visceral pain
Celiac plexus block
Differentiates abdominal visceral pain from abdominal wall pain
Hypogastric plexus block
Differentiates pelvic visceral pain from pelvic wall pain
Cervicothoracic ganglion (stellate—T4) block
693
Differentiates thoracic visceral pain from thoracic wall pain
Sympathetic versus somatic pain
Stellate ganglion block
Differentiates sympathetically mediated pain from somatic pain of the head, neck, and upper extremity
Lumbar sympathetic block
Differentiates sympathetically mediated pain from somatic pain of the lower extremity
Differential spinal
Differentiates sympathetically mediated pain from somatic pain
in the cancer patient population. As many as one third of the patients respond to placebo, which does not necessarily
mean that they do not have pain. In addition, saline injected into trigger points has been reported to be as effective
[20]
as local anesthetic injections. [21]
Prognosis
Before any permanent neurolytic procedure, it is recommended that a prognostic local anesthetic block be performed
on the nerve to be ablated. An exception is for the terminally ill patient who incurs an extreme inconvenience during
performance of the block. An example is a patient with terminal pancreatic cancer and severe pain who may
experience severe discomfort from positioning during the block. Many practitioners would proceed with the
neurolytic block in this setting. If numbness and motor blockade are unlikely to result from the block (i.e., celiac
plexus block), it is more acceptable to proceed with the permanent neurolytic block without a diagnostic block.
The purpose of prognostic blocks is to allow the patient to experience not only the pain relief that may result from
the block but also the numbness and motor blockade. The numbness and motor blockade that result may be more
distressing to the patient than the pain itself. [22]
Unfortunately, the prognostic value of long-term pain relief from a positive LANB is not guaranteed. However, a [23]
negative LANB almost certainly predicts failure, thus supporting the use of the prognostic LANB before an ablative
procedure. [12]
Therapy
LANB is useful in the management of myofascial pain, sympathetically mediated pain, long-term treatments
employing catheter techniques and continuous delivery, and in crisis management of severe pain.
Reflex muscle spasm caused by tumor invasion of deep tissues can be debilitating. Some patients receive long-term
benefit from trigger point injections of local anesthetics. If long-lasting benefit results, trigger point injections can be
repeated at intervals of 1 to several weeks. [24]
As tumors encroach on the nervous system, neural damage can result. This damage can lead to complex regional
[25]
pain syndromes that may be responsive to sympathetic blockade. It is known that the pain relief from such blockade
can far outlast the duration of the local anesthetic. It is in these cases that the sympathetic blockade can be
[26] [27]
repeated at intervals of 1 to several weeks. Whereas the use of sympathetic blockade in chronic benign pain is
focused more on improving function, the use of this technique in cancer pain is focused more on pain control.
Continuous LANB can be achieved by epidural or intrathecal placement of catheters at peripheral nerve sites. The
brachial and lumbar plexus are the most common sites for placement of peripheral nerve catheters. A case report on
long-term continuous axillary plexus blockade demonstrated no adverse effects for up to 16 days. Other sites that [28]
can be cannulated include the intercostal nerve, celiac plexus, hypogastric plexus, stellate ganglion, and lumbar
sympathetic ganglion. The ease and low complication rate of epidural catheters favor this technique over
[29]
peripheral nerve catheters for long-term pain management of localized pain (e.g., lower extremity, sacrum, upper
extremity). Even the chronic delivery of cervical epidural local anesthetics is safe, and studies have shown that
[30]
high concentrations of local anesthetic do not result in phrenic nerve block. There are several studies on the use of
[31]
intrathecal local anesthetics in combination with opioids for the treatment of cancer pain with bupivacaine
[32] [33] [34] [35] [36]
doses as high as 100 mg/day. It can be concluded from these studies that a sensory motor block does not occur at
doses below 30 to 40 mg per day. There is one case report on severe refractory cancer pain treated with daily
intrathecal bupivacaine doses as high as 800 mg per day. [37]
694
Some cancer patients develop severe pain that is refractory to opioid analgesics, even in high doses. These patients
can benefit from continuous techniques to give them respite from the debilitating pain and to allow a drug holiday
from the opioids. Continuous LANB may also provide pain control until palliative techniques such as chemotherapy,
radiation therapy, or radionucleotide therapy take effect.
STEROID INJECTIONS
Invasion or compression of nerves by growing tumors is a common source of pain. It is thought that inflammation
plays a major role in the production of pain ; however, other pain mechanisms that are responsive to the local
[38] [39]
application of steroids have been postulated, including a weak local anesthetic action, a change in the activity in
[40]
dorsal horn cells, and reduced ectopic discharge from neuromas.

[41]
The local instillation of steroid into the
[42] [43]
compartment of the affected neural structure (e.g., brachial plexus, lumbar plexus, intercostal nerve) can result in
significant and prolonged pain. If the tumor invades the vertebral column and compresses nerve roots, epidural
[12]
steroid injections can be very helpful. A number of steroids may be used locally or epidurally, including
methylprednisolone, triamcinolone, betamethasone, and dexamethasone. Although not performed routinely, the
[44] [45]
intrathecal delivery of steroids has been used for lumbar radiculopathy. There is a concern of inducing arachnoiditis
with this technique, but many reports fail to show any serious adverse events. A comprehensive review by
[45] [46] [47]
Abram and O’Connor concluded that most cases of arachnoiditis after subarachnoid steroid injections occur with
[48]
multiple injections over a prolonged time period.
NEUROLYSIS
Neurolytic procedures are potentially very useful for patients with severe localized pain. Examples are gasserian
ganglion block for facial pain, celiac plexus block for abdominal pain, and intrathecal alcohol for dermatomal pain.
The use of a single procedure for the treatment of pain may reduce cost and is usually viewed favorably by the
patients. However, there is no clear consensus on when to use neurolytic procedures for cancer pain management.
Because of inherent risks associated with neurolysis, one must be reasonably certain that the outcome will be
favorable.
The decision to perform neurolytic procedures for cancer pain control is based on life expectancy, pain description
and location, and pain mechanism. At best, the duration of pain relief from neurolytic procedures averages 3 to 6
[49]
months. In addition, with long life expectancies, there is a risk of developing postneurolysis neuropathic pain.
Exceptions to postneurolysis pain are techniques that use more focused lesions (e.g., cryoanalgesia, and
radiofrequency thermal lesioning); sympatholysis (e.g., celiac plexus, hypogastric plexus, stellate ganglion, lumbar
sympathetic ganglion); and intrathecal neurolysis. Therefore, the decision to use neurolysis in patients with a life
expectancy longer than 12 months should be made with caution. On the other hand, patients with imminent death
who are experiencing severe pain may benefit from neurolytic procedures; however, some neurolytic procedures
require special techniques (e.g., fluoroscopy) or unacceptable recovery periods that may cause an extreme
inconvenience for the patient. Therefore, a careful discussion with the patient, family, and healthcare team should
ensue. If the neurolytic procedure can be done at the bedside, it is more favorable than one requiring transport to
another facility.
Patients who describe their pain poorly or those who have diffuse pain are not good candidates for regional
neurolysis. An exception is a patient who has multiple areas of pain but can clearly define a localized area of
dominant pain. However, all of these patients run the risk of focusing on the lesser pain problem once the dominant
pain is relieved.
Patients with nociceptive pain (e.g., bone pain, soft tissue pain, abdominal pain) usually respond to neurolytic
procedures better than those with neuropathic pain. Because neuropathic pain often results in more central nervous
[50]
system changes, neurolysis of peripheral nerves is often ineffective. In these cases, unequivocal positive results from
a diagnostic block are important before neurolysis is undertaken.
For nerves that have a significant sensory motor function (e.g., cervical and lumbar nerve roots), aggressive
neurolysis may result in debilitating motor dysfunction. Pulsed radiofrequency (RF) lesioning, a technique that
delivers an electromagnetic field without producing neurodestructive heat, leaves sensory motor function intact.
[51]
The pulsed fashion results in a silent period that eliminates the heat produced during the active cycle. This technique
permits delivery of a higher generator output without raising the tip temperature above 42°C. This technique can be
applied to a variety of peripheral nerves without the risk of motor dysfunction. With nerve injury, persistent small
afferent fiber activity originates from the dorsal root ganglion after an interval of days to weeks; therefore, it is
reasonable to use this technique directed at the dorsal root ganglion. Pulsed RF lesioning has been reported to
[52]
provide long-term pain relief from both lumbar and thoracic radicular pain. The advantage of this technique, which
[53]
695
has a lower risk of deafferentation pain, is minimal tissue destruction. The exact mechanism of pulsed RF lesioning
is unknown.
The technique of pulsed RF lesioning for the treatment of postmastectomy pain is as follows. The uninsulated
portion of the insulated RF needle should be bent approximately 45 degrees. Manufactured prebent needles are
recommended because there is less risk of damage to the electrode tip. The tip of the needle is advanced into the
neural foramen; the curvature of the tip serves to guide the needle into place. On lateral view, the tip should be
located in the superoposterior portion of the neural foramen, which is the location of the dorsal root ganglion ( Fig.
28–1 ). The lesion is created with use of a pulsed RF (300 kHz) for 20 milliseconds out of a 1-second cycle. The tip
temperature should not exceed 42°C, and the duration is 120 seconds. A percutaneous sterotactic laminar osteotomy
has been described and may be required to reach to the thoracic dorsal root ganglion.
INTRASPINAL DRUG THERAPY
Determining the efficacy of intraspinal drug therapy for cancer pain remains one of the greatest challenges in pain
management. To date, there are no prospective randomized studies evaluating the efficacy of drug therapy for cancer
pain. All studies rely on retrospective reviews of large numbers of patients with a limited duration of follow-up.
One of the reasons for the lack of controlled trials is that the high cost and invasiveness of such treatment ethically
precludes a double blind, placebo-controlled study design. Therefore, we can only rely on the retrospective reviews
of patients who have received this therapy in our attempts to draw conclusions on the efficacy of this treatment.
There is currently a randomized controlled trial comparing intrathecal drug therapy with conventional medical
management for cancer pain. This data from this trial may allow better conclusions to be made concerning on the
efficacy of this important therapy.
Barriers to intraspinal drug therapy include (1) the requirement of specialized care (e.g., services of a neurosurgeon
or anesthesiologist) for placement and management; (2) the high cost of the implanted device; and (3) limited day-
to-day flexibility of this technique. Therefore, a single pain-relieving procedure, such as neurolysis, is likely to be
viewed more favorably. However, as discussed earlier, neurolysis has limitations that may result in intraspinal drug
therapy being the treatment of choice.
The decision to start intraspinal drug therapy is based on pain location, pain mechanism, and life expectancy. In
contrast to neurolysis, intraspinal drug therapy may be effective in controlling more generalized pain. This is
because the drug diffuses throughout the intrathecal space to reach receptors located at multiple levels of the spinal
cord. As discussed earlier, neurolysis is less effective for neuropathic pain. Therefore, intraspinal drug therapy may
be more effective in these cases. The location of the pain influences the technique of delivery. Pain that is localized
and unilateral is often better managed with the epidural delivery of opioid and local anesthetic combinations.
However, if the life expectancy is longer than 3 months, epidural delivery may be more costly and less effective
over time because of development of epidural fibrosis. Pain that is more diffuse is better managed with intrathecal
[54]
drug delivery. Because neuropathic pain is often less responsive to the opioids, other drugs, such as clonidine,
[55] [56] [57]
or bupivacaine, may be more effective.

[32] [33] [34] [35] [36]
Figure 28-1 Anteroposterior view (A) and lateral view (B) of correct needle location for pulsed radiofrequency lesioning of the intercostal dorsal root ganglion. The
needle tip has a 45-degree curve, which is used to guide the needle into the foramen. The uninsulated portion of the needle should be located in the superoposterior
portion of the neural foramen, where the dorsal root ganglion is found.
696
There is no lower or upper life expectancy limits for intraspinal drug therapy. However, based largely on cost of
therapy, life expectancy influences the choice of which technique is to be used for delivery of the intraspinal drug.
The three basic types of intraspinal delivery techniques are (1) an externalized system, (2) a partially externalized
system, and (3) a totally implanted system. Each technique has different risks and costs that are taken into account
[58]
when deciding which approach to use. Bedder and colleagues compared the cost of epidural morphine delivered
[59]
via an external pump or by intrathecal delivery. They concluded that although the initial costs for an intrathecal
pump implant were higher (1.67 times higher), the break-even point appeared at 3 months, and at 1 year, the total
charges for the epidural group were approximately twice as high as those for the intrathecal group. Therefore, the [59]
following general rule can be applied: with life expectancy of less than 1 month, use a percutaneous catheter and
external pump; with life expectancy of 1 to 6 months, use an implanted port and external pump; and with life
expectancy longer than 6 months, use a totally implanted system.
Cancer Pain Syndromes
BONE METASTASIS
Bone metastasis is the most common cause of cancer-related pain. Many common malignancies (e.g., breast,
[60]
prostate, lung, kidney, thyroid) have a propensity to metastasize to the bone. Although the overall incidence of bone
metastasis is about 66%, the incidence of bony metastasis of breast and prostate cancer may be as high as 90%.
[60] [61]
Although there is a high incidence of bone metastasis, the majority of metastatic lesions are not painful. Bone pain [62]
may also result from cancer treatment (e.g., osteonecrosis secondary to corticosteroid therapy or radiation therapy).
[63]
[39]
Bone pain is often described as constant and exacerbated with movement. Because the bone is a deep structure, it is
often described as a dull, deep ache with referred pain to other areas of the body. There may be spasms of the
muscle that support the affected bone.
A bone scan is more sensitive than a plain roentgenogram, because up to 50% bone decalcification must be present
for plain films to detect a lesion. It has been estimated that up to 50% of bone metastases detected by bone scan are
not detected by plain roentgenograms. However, in certain malignancies (e.g., bone cancers, multiple myeloma,
[64]
thyroid cancers), plain roentgenograms may be more sensitive. In addition, bone scans may be falsely negative in
[65]
areas of previously irradiated bone metastasis as the lesion becomes “burned out”; in lesions that are predominately
osteoclastic; in breast, lung, and prostate cancers; and at certain hidden sites, such as the T1 vertebral body, the base
of the skull, and the sacrum. When bone scans are evaluated, other causes must be ruled out, such as infection,
[60] [66]
trauma, and degenerative changes.
The causes of bone pain are unclear; however, it is known that bone structures are highly innervated, especially the
periosteum. It is likely that the mechanism of bone pain is both mechanical and chemical. Mechanisms of pain
[67] [68]
from bone metastasis include the release of algogenic substances (prostaglandins, bradykinin, substance P, histamine)
from the damaged bone tissue that stimulates free nerve endings, stretching of the periosteum and fascia by
increasing tumor size, and pathologic fracture. [69] [70]
VERTEBRAL METASTASIS
The bony spine is the most common site of bone metastasis, especially from breast, lung, prostate, and kidney
tumors. Vertebral metastases deserve special attention because of their proximity to major neural structures (nerve
[64]
root, spinal cord). Because of this proximity, vertebral metastasis can lead to serious spinal neuropathic syndromes.
Focal back pain is the earliest sign of vertebral metastasis. At this stage, local palpation of the vertebrae increases
[71]
the pain. As the tumor grows, pain can be referred to other areas, such as the sacroiliac joints, iliac crest, abdomen,
or pelvis. If epidural extension occurs, nerve root compression may result in radicular pain in the affected
[72]
dermatome. Radicular pain is often unilateral in lumbar and cervical metastases and bilateral in thoracic
metastases. As the tumor continues to grow, spinal cord compression can result in sensory-motor changes,
[73]
autonomic dysfunction, and severe pain. The pain of spinal cord compression is often described as burning and
dysesthetic below the level of the compression. Intramedullary cord metastasis usually results in a rapid
[39]
progression of neurologic deficit in a matter of days to weeks. [74]
697
NEURAL COMPRESSION AND INVASION
The cervical, brachial, and lumbar plexuses are vulnerable to compression from metastatic tumors. The brachial
plexus is quite vulnerable to metastatic breast cancer, metastatic melanoma, and superior sulcus lung tumors. [39]
Lumbar plexus compression can result from cervical, rectal, or metastatic cancer.
Pain is often an early sign of plexus compression and often precedes any neurologic deficits. The pain is
characterized as a diffuse ache in the distribution of the plexus innervation and progresses to dysesthesia, allodynia,
muscle weakness, and sensory loss as the tumor infiltrates the neural structures. [75]
Plexopathies must be differentiated from spinal metastasis and compression. Radiologic investigation of the spine
and pelvis is the gold standard in differentiating the two.
VISCERAL PAIN
The abdominal viscera are innervated structures that can be painful when diseased. The most common causes of
visceral pain include liver cancer, metastasis to the liver, and pancreatic cancer. Pain is present in approximately
80% of pancreatic patients before death. Visceral pain is often described as dull, diffuse, and poorly localized.
[76]
There is often reflex muscle spasm in the paraspinous muscles or the abdominal wall as well as cutaneous
hyperalgesia in the dermatomes that converge centrally with the innervation of the diseased organ. Liver pain is
often referred to the epigastrum, and if diaphragmatic irritation occurs, the pain is often referred to the shoulder.
Pancreatic pain is often referred to the epigastrum and back.
CANCER TREATMENT–RELATED PAIN

Postmastectomy Pain
Up to a third of women develop pain as a result of treatment of breast cancer. The pain is often described as a
[77]
general burning and aching sensation referred to the axilla, the medial upper arm, the chest, or all of these areas.
There may be paroxysmal episodes of shooting and lancinating pain. In addition, some women report phantom
breast pain, mainly in the nipple. The pain may be exacerbated with arm movement, leading to a frozen shoulder as
the patient attempts to
TABLE 28-3 -- CAUSES OF POSTMASTECTOMY PAIN AND SYMPTOMS

Intercostobrachial nerve injury Axillary and arm pain
Fourth intercostals nerve injury Phantom nipple pain
Multiple intercostal nerve injuries Chest wall pain
Shoulder disuse Shoulder pain
keep the arm in a flexed position close to the chest wall. The intercostobrachial nerve has been reportedly injured in
80% to 100% of mastectomy patients undergoing axillary dissection and has been described as the cause of the
axillary and upper arm pain. Phantom breast pain occurs in 10% to 64% of women, with most of the phantom pain
[78]
and sensations reported in the nipple. This is because the nipple is the most highly innervated breast tissue. It is
supplied by the fourth intercostal nerve. Other causes of postmastectomy pain include damage to the long thoracic
[79]
nerve, leading to denervation of the serratus anterior muscle; winged scapula and musculoskeletal pain in the
shoulder girdle; damage to the thoracodorsal nerve, leading to denervation of the latissmus dorsi and
musculoskeletal pain; and mastectomy scar sensation, which is described as painful and dysesthetic. Table 28–3 [78] [80]
summarizes the causes of postmastectomy pain.
Post-thoracotomy Pain
The incidence of chronic post-thoracotomy pain ranges from 26% to 67%. The pain is often described as a general
burning and aching along the chest wall surrounding the surgical scar. There may be associated scar pain and
myofascial pain involving the chest wall. The etiology of post-thoracotomy pain is thought to be secondary to
surgical trauma to the intercostal nerve. [81]
Post–Radical Neck Dissection Pain
698
Many patients develop pain after radical neck dissection. The pain is described as a sensation of tightness, burning,
and dysesthesia in the shoulder, neck, and jaw. Lancinating-type pains are occasionally reported. The cause of the [82]
pain is likely secondary to damage to the cervical nerves and cervical plexus during surgery. Shoulder pain can
result from loss of normal support to the shoulder secondary to loss of the neck musculature, leading to
musculoskeletal pain. It has been suggested that the cervical plexus provides some innervation to the trapezius. If
[83]
the cervical plexus is damaged, chronic shoulder and arm pain may result. In addition, damage to the spinal
[84]
accessory nerve has been shown to increase the risk of chronic shoulder pain. This can result in loss of innervation
to the trapezius muscle and musculoskeletal pain in the shoulder girdle. Damage to the auriculotemporal nerve
[85]
after cancer surgery has been reported to lead to gustatory sweating, hyperemia, and pain. [86]
Phantom Limb and Stump Pain
Phantom limb pain is a well-described syndrome with an incidence as high as 85% in the first 12 months after
surgery. Sixty percent of patients continue to have pain 1 year after surgery. The incidence increases with more
proximal amputations. It occurs most often in the amputated extremities; however, phantom pain may occur in any
appendage (e.g., tongue, penis, breast, nose). It is more common in patients who have preamputation pain. Phantoms
often assume painful postures, which eventually telescope into the stump. Phantom pain and stump pain are often
described as burning and dyesthetic, with intermittent lancinating sensations. Stump pain is differentiated from
phantom pain in that the cause is often abnormalities at the stump site, such as bone spurs, osteomyelities,
myofascial trigger points, or neuromas. Traumatic neuromas account for approximately 20% of stump pains.
[87]
Postradiation Pain Syndromes
Radiation therapy for the treatment of cancer can result in debilitating pain. Severity and time of onset are
proportional to the total dose. Major plexuses are exceptionally susceptible to radiation neuritis. For example,
[88] [89] [90]
radiation to the axilla essentially encompasses not only the local innervation but also the cords of the brachial plexus.
The mechanism of pain is thought to be secondary to damage to the microvasculature of the nervous system,
resulting in ischemia. Electron microscopy of the sciatic nerve 12 months after radiation showed a significant
decrease in nerve fiber density, primarily in the large fiber population. In addition, an increase in microtubule and
neurofilament density was observed. Another mechanism was fibrosis of the connective tissue, leading to nerve
compression, demyelination, and chronic inflammation of the connective tissue. The pain is often described as
[78]
burning and dysesthetic. Radiation-induced pain can be delayed for years after treatment. [91]
Postchemotherapy Pain Syndromes
Peripheral neuropathy is the most common pain syndrome secondary to chemotherapy. The agents that most
commonly cause peripheral neuropathy include vinca alkaloids, cisplatinum, procarbazine, misoniadazole, and
hexamethylmelamine. The pain is usually described as burning, dysesthetic, and localized to the hands and feet.
[92]
Occasionally, it may progress to a sensory and motor neuropathy.
Regional Techniques for Cancer Pain
HEAD AND NECK

Overview
Pain related to a malignant neoplasm of the head and neck poses one of the most challenging pain management
problems because of the overlapping sensory innervation of the area. Most of the pain can be managed with medical
regimens; however, neural blockade can be a very effective addition. Sensory innervation of the head and
[93] [94] [95] [96]
neck arises from cranial nerves V, VII, IX, and X, and dorsal roots of the second, third, and fourth cervical nerves.
Sympathetic innervation derives from the T1 and T2 spinal cord segments. Preganglionic sympathetic axons exit the
ventral roots of T1 and T2 and travel as white communicating rami before joining the sympathetic chain, and these
axons synapse at the inferior (stellate), middle, or superior cervical ganglion. Postganglionic nerves either follow the
carotid arteries to the head or integrate as the gray communicating rami before joining the cervical plexus or upper
cervical nerves to innervate the structure of the neck. Use of local anesthetic blocks helps to localize the relative
contribution of individual nerves to the painful area, and subsequent neurolytic blockade can be considered to
prolong pain relief.
Deep and Superficial Cervical Plexus Blockade
The dorsal roots of the second, third, and fourth cervical nerves pass posteriorly to the vertebral artery as they exit
the intervertebral foramen. The anterior branches of the cervical nerves join to form the cervical plexus. The
699
superficial branches, including the lesser occipital, the greater auricular, the transverse cervical, and the
supraclavicular nerves, travel posteriorly to the sternocleidomastoid (SCM) muscle through the cervical fascia to
provide cutaneous sensory innervation. The lesser occipital nerve (C2, C3) passes superiorly from the posterior
border of the SCM muscle to innervate the supralateral aspect of the neck, the upper pole of the ear, and the
occipital region of the scalp. The greater auricular nerve (C2, C3) travels anterosuperiorly from the posterior border
of the SCM muscle before dividing into the anterior and posterior branches. The anterior branch supplies cutaneous
innervation to the posteroinferior face, whereas the posterior branches innervate the mastoid process and lower pole
of the ear. The transverse cervical nerve (C2, C3) passes anteriorly from beneath the external jugular vein and
supplies cutaneous innervation over the anterolateral aspect of the neck from the mandible to the sternum. The
supraclavicular nerve (C3, C4) also exits posteriorly to the SCM to innervate the lower neck to the
acromioclavicular junction, as well as to the anterior chest to the level of the second rib. The greater occipital
[97] [98]
nerve is the dorsal branch of the second cervical nerve and is not a part of the cervical plexus. The deep branches of
the cervical plexus supply sensory innervation to the musculature and to the bony and articular structures of the neck.
SUPERFICIAL CERVICAL BLOCKADE
For occipital and posterior auricular neuralgia caused by acute inflammation or tumor compression, a superficial
plexus block, or a greater occipital nerve block, or both, are indicated. The patient is placed in the supine position,
and the neck is flexed and rotated to the contralateral side of the blockade. The posterior borders of the SCM muscle
and external jugular vein are identified. At the location where the external jugular vein passes the posterior border of
the neck, a 25-gauge (G), 4-cm needle is inserted subcutaneously immediately posterior and deep to the SCM.
Along the posterior border of the SCM, 10 to 20 mL of local anesthetic is injected. [99] [100]
DEEP CERVICAL PLEXUS BLOCKADE
A deep cervical plexus block is indicated for pain in the neck and occiput resulting from compression of the cervical
plexus by tumors or metastatic lesions to the deep structures of the neck. With the patient in the supine position and
the head turned to the contralateral side of the block, a line is drawn from the mastoid process to the anterior
tubercle of the C6 transverse process at the level of the cricoid cartilage. Points marked 1.5, 3, and 4.5 cm inferior to
the mastoid process along the line correspond to the location of C2, C3, and C4, respectively. A 25-G, 8- to 9-cm
needle is inserted until either the transverse process is contacted or paresthesia is encountered. After negative
aspiration, 2 to 4 mL of local anesthetic are injected at each of the 3 locations. An alternative approach for the
[98]
cervical plexus block can be performed with a single injection after localization of the cervical plexus with a nerve
stimulator.
The most common complication of the cervical plexus block is blockade of the phrenic nerve, which may lead to
respiratory distress resulting from paralysis of the hemidiaphragm. Therefore, bilateral deep cervical plexus
blockade is not recommended. Intravascular injection and subsequent signs of local toxicity may develop if careful
needle placement and aspiration are not carried out before the injection. Puncture of the dural sleeve and subsequent
subarachnoid injection may occur and lead to total spinal blockade. [3] [97] [100] [101]
CONTINUOUS CERVICAL PLEXUS BLOCK
A continuous cervical plexus block can be readily achieved with the placement of a catheter in the superior portion
of the interscalene groove. A local anesthetic tracks superiorly to reach the nerve roots that supply the cervical
plexus. However, a local anesthetic also reaches the brachial plexus, which may result in upper extremity
[102]
weakness. To determine efficacy, the negative effects of this weakness need to be balanced with the positive effects
of analgesia. In addition, the phrenic nerve is frequently blocked with this technique, but this is seldom of
significance with unilateral blocks. However, prolonged blocks may result in poor ventilation of the ipsilateral lung,
leading to atelectasis. Therefore, it is recommended that intermittent injections rather than continuous infusions be
used.
NEUROLYSIS OF THE CERVICAL PLEXUS
Although neurolysis of the cervical plexus has not been described, intermittent interscalene neurolysis has been
performed for tumors of the upper extremity via the interscalene approach. Case reports by Mullin and Neill [103] [104]
described using 3% phenol and 50% alcohol, respectively, with minimal neurologic sequelae. Therefore,
theoretically, cervical plexus neurolysis is possible with placement of the anesthetic agent in the upper interscalene
groove.
Cervical Epidural Infusions
700
For neck pain that does not respond to intermittent regional anesthetic techniques, a continuous cervical epidural
infusion should be considered. A cervical epidural infusion can be accomplished via a percutaneous temporary
catheter with infusion of low concentrations of bupivacaine (1/33% to 1/10%). The tip of the catheter should be
placed as close as possible to the dermatomes supplying the cervical plexus (C2–4). Cervical epidural anesthesia
(CEA) for head and neck pain has been reported to be an adequate and safe technique. Many avoid this technique
[105]
because of fear of inducing a bilateral phrenic nerve block and respiratory distress. Although this is a theoretical
consideration, studies have shown that a clinically significant phrenic nerve block does not occur even with high
concentrations of local anesthetic. However, actual phrenic nerve activities show a suppression of 72% and 57% of
control value with 1% and 2% lidocaine, respectively. Studies evaluating the effect of CEA on respiratory function
[31]
have failed to show a significant effect on PO2 , although most studies show a significant increase in PCO2 . The [106] [107]
most common effects of CEA are decreases in heart rate and blood pressure. There is also a blunted response to
atropine and atropine-like drugs. Therefore, close hemodynamic monitoring should be done for the first 24 to 48
[108] [109]
hours after the procedure.
Stellate Ganglion Block
The stellate ganglion, which consists of the inferior cervical and first thoracic ganglia, lies just anterior to the
transverse process of the seventh cervical vertebra and lateral to the trachea. A blockade of the stellate ganglion
produces an ipsilateral sympathetic blockade of the head, neck, upper extremity, and chest, as well as sensory block
of the anterolateral cervical vertebrae. The development of Horner’s syndrome, which consists of miosis, ptosis and
enophthalmos, ipsilateral facial anhidrosis, and conjunctival injection, may confirm a sympathetic block of the head
and neck. It does not necessarily confirm a sympathetic block of the upper extremity, because some thoracic
sympathetic preganglionic fibers, which also innervate the upper extremities, lie in the higher thoracic ganglion at
the T1 and T2 levels, bypassing the stellate ganglion. [100] [110]
There are many indications for the use of a stellate ganglion block for the treatment of head and neck cancer pain.
These include pain resulting from herpes zoster, postherpetic neuralgia, cervical vertebral metastasis, neuropathic
[111]
pain secondary to chemotherapy or radiotherapy, pain from central nervous system lesions, and complex regional
pain syndrome type I and type II. Response to stellate blockade with local anesthetic can serve as a diagnostic
[112]
indication that pain transmission is caused by autonomic contribution. In addition, the initial response to the block
also serves as a prognostic indicator for possible repeated local anesthetic blocks, neurolytic block, or surgical
intervention.
ANTERIOR APPROACH AT THE SIXTH CERVICAL VERTEBRAE (C6)
At the beginning of the procedure, the patient is asked to lie supine with the placement of a thin shoulder roll so that
the patient’s neck is extended to facilitate finding the appropriate anatomic landmark for performing the injection.
First, the cricoid cartilage, which is at the C6 level, is identified. The C6 transverse process, which is known as
Chaussaignac’s tubercle, is palpated 1 to 1.5 cm lateral to the cricoid cartilage and medial to the carotid pulse. The
skin is prepared antiseptically. With the index and middle fingers of the nondominant hand, the operator gently
retracts the common carotid artery in a lateral direction. A skin wheal is made with an injection of 1% lidocaine via
a 25-G, 1- to 2-cm needle. After that, a 25-G, 4- to 5-cm needle is advanced perpendicular to the coronal cervical
plane until it comes into contact with bone. The operator then fixes the needle in position with the index and middle
fingers of the nondominant hand. The depth of the needle rarely exceeds 2.0 to 2.5 cm. Before the injection, the
needle is withdrawn 2 to 5 mm and aspirated to ensure no cerebrospinal fluid (CSF) or blood return, thereby
minimizing the risk of intravascular or intrathecal injection. If the aspiration is negative, 0.5 to 1.0 mL of solution is
administered to assess the absence of adverse events. If the patient speaks, the needle may become dislodged,
causing discomfort; therefore, instructing the patient to point the index finger or thumb upward may be a safer
method of communicating during the procedure. After the initial test dose, a total of 8 to 10 mL of solution can be
injected in 2 to 3 mL increments with frequent aspiration. [97] [113]
ANTERIOR APPROACH AT THE SEVENTH CERVICAL VERTEBRAE (C7)
A similar approach can be used at the C7 vertebra. The C7 tubercle is difficult to palpate; therefore, one must find
Chaussaignac’s tubercle first and then move one fingerbreath caudally to locate the C7 tubercle. A pillow can be
placed under the patient’s shoulders, extending the cervical spine to facilitate palpating the cervical spine tubercle.
The risk of pneumothorax increases as the dome of the lung is in close proximity to the entry site of the needle.
Fluoroscopic radiologic guidance provides a more accurate and safer way of performing the block. A linear
cephalad and caudal spread of radiopaque contrast medium is usually indicative of good needle placement for local
anesthetic or neurolytic agent injection ( Fig. 28–2 ).
701
Interruption of the sympathetic outflow to the head and neck by the stellate ganglion block is substantiated by the
presence of Horner’s syndrome, characterized by miosis, ptosis, and enophthalmos. Other findings, such as
conjunctival injection, nasal congestion, and facial anhidrosis, may also be present. [110]
The most common side effect of the stellate ganglion block is Horner’s syndrome. Preprocedural explanation and
postprocedural reassurance are necessary and can ease the patient’s anxiety. Complications such as seizures can
result from intravascular injection. Loss of consciousness, severe hypotension, or respiratory compromise can result
from subarachnoid injection. Skill in airway management is necessary for the operator of the procedure. Other
complications, such as brachial plexus blocks, which result in upper extremity motor or sensory deficit, and
unilateral phrenic nerve blocks, which result in transient hemidiaphragmatic paresis, may also occur. Therefore,
bilateral stellate ganglion block is not recommended. Pneumothorax is another potentially life-threatening
complication associated with the block, especially with the anterior C7 approach. [97] [100] [114]
CONTINUOUS STELLATE GANGLION BLOCK
If consistent pain relief is achieved with intermittent stellate ganglion blocks, a continuous block should be
considered. Catheters can be placed fluoroscopically by using the anterior approach at C7. The catheter should be
placed close to the lateral portion of the anterior surface of the body of C7 on the affected side. A continuous
infusion of 0.1% to 0.25% bupivacaine or intermittent injections of bupivacaine can be used. There is about a 50%
incidence of catheter migration requiring replacement. [115]
NEUROLYSIS OF THE STELLATE GANGLION
Although there exist anecdotal reports of good results and minimal complications with the use of 1 to 2 mL of 6%
aqueous phenol or less than 1.5 mL of absolute
Figure 28-2 Anteroposterior view of a C7 stellate ganglion block. A, The stellate ganglion is the fusion of the inferior cervical and first thoracic
ganglia. It is located between the medial portions of the transverse processes of the seventh cervical (C7) and first thoracic vertebrae (white
structure). The needle should be advanced until contact is made at the junction of the transverse process and the vertebral body of C7. B,
Injection of radiopaque contrast should result in a linear cephalad and caudad spread.
alcohol in stellate gangliolysis, the close proximity of the stellate ganglion to major neurovascular structures makes
the injection of neurolytic agents into the area potentially dangerous. Complications such as erosion, thrombosis, or
spasm of major vessels, cerebral infarction, prolonged hoarseness from recurrent laryngeal nerve injury, and upper
limb motor or sensory deficit resulting from brachial plexus injury may occur. Therefore, the use of the neurolytic
stellate block is reserved for exceptional cases after a thorough trial of local anesthetic blockades. Radiologic
guidance is usually recommended. After evaluating the extent of pain relief with multiple local anesthetic blocks,
Arter and Racz described placement of 5 mL of a 3% phenol solution (1 mL of triamcinolone, 1.5 mL of 0.5%
[116]
bupivacaine, and 2.5 mL of 6% phenol) at the lateral ventral portion of the C7 vertebral body. A series of 150
procedures were performed with no serious complications. Transient Horner’s syndrome did occur, with the longest
lasting up to 6 months.
702
Because of the possibility of diffusion of neurolytic solutions, stellate radiofrequency ablation (RFA) may have a
[117]
significant advantage compared to stellate ganglion chemical neurolysis. Radiofrequency lesioning of the stellate
ganglion and upper thoracic sympathetic chain has been described with few complications. An RF cannula is
[118] [119] [120]
placed under fluoroscopic guidance at the junction of the transverse process and the vertebral body of C7. Three
lesions are made in a triangular pattern after proper negative sensory stimulation to prevent injury to the recurrent
laryngeal nerve.
Gasserian Ganglion Block
The trigeminal nerve consists of both motor and sensory fibers. The gasserian ganglion is formed from two roots
that exit the ventral surface of the brainstem at the midpontine level. At the middle cranial fossa, they form a recess
called Meckel’s cave, which is constructed by an invagination of the surrounding dura mater. The trigeminal cistern,
which lies behind the ganglion, contains CSF. The gasserian ganglion consists of three sensory divisions, namely,
the ophthalmic (V1), maxillary (V2), and mandibular (V3), which exit the anterior convex aspect of the ganglion.
The smaller motor root joins the mandibular division and exits the cranial fossa at the foramen ovale. [98]
The gasserian ganglion block is indicated for the palliation of pain caused by invasive tumors of the orbit, maxillary
sinus, and mandible. Another nonmalignant indication is the management of pain caused by trigeminal neuralgia
[86]
that has not been responsive to conservative medical management. Oncogenic pain limited to the distribution of the
fifth cranial nerve and one of its branches may respond well to RFA or chemical ablation of the involved nerve.
When feasible, RFA may be the treatment of choice, because analgesia can be achieved without possible sensory
loss. The decision of blocking a branch of the fifth cranial nerve versus the gasserian ganglion relies on the area of
pain and the likelihood of further tumor invasion. Blocking the gasserian ganglion may prophylactically extend the
field of analgesia in patients with rapidly growing malignancy. Tew and Keller reported on the use of
[114] [121] [122] [123]
neurolysis of the gasserian ganglion with alcohol in 20 cancer patients. Seventy-five percent obtained initial relief
and 60% had relief at 3 months. Of the patients who survived for 12 and 18 months, 70% and 40%, respectively, had
pain relief.
This procedure is usually performed under the guidance of fluoroscopy, and intravenous access is required for
sedation or management of potential intravascular injections. The patient is placed in the supine position, with a
shoulder roll in place to maximize cervical extension. By using an oblique caudal-to-cephalic fluoroscopic view, the
foramen ovale can usually be identified as an oval-shaped radiolucent area just inferior to the orbit ( Fig. 28–3 ).
Having the patient open the mouth may facilitate visualization of the foramen ovale. The needle entry site is usually
located at the skin just lateral to the second maxillary premolar. Using aseptic technique after the skin is
anesthetized with 1% lidocaine, a 25-G, 9-cm Quincke-type point spinal needle is advanced, aiming toward the
medial edge of the foramen ovale until contact is made with the base of the skull. The needle is then withdrawn
slightly and advanced laterally into the foramen ovale. The patient should be warned of paresthesia as the needle is
advanced into the foramen ovale. The needle should be aspirated for blood. The presence of free flow of CSF may
confirm the needle placement. However, the absence of CSF does not necessarily imply incorrect needle positioning,
because the tip of the needle may reside in Meckel’s cave, which is more anterior than the trigeminal cistern. One [124]
to 2 mL of water-soluble contrast medium may then be injected to confirm the needle placement ( Fig. 28–4 ). For
diagnostic block, 0.1 mL aliquots of preservative-free local anesthetic such as 1% lidocaine or 5% bupivacaine may
then be injected to a total volume of 0.4 to 0.5 mL. For neurolytic blocks, a similar amount of absolute alcohol or
6.5% phenol in glycerin can be used. The destruction of the gasserian ganglion should be reserved for patients who
have failed to respond to conservative medication interventions. Continuous gasserian ganglion block has been
described, whereby a catheter was placed in the foramen ovale under fluoroscopic guidance. [125]
A local anesthetic can track into the subarachnoid space, resulting in brain stem anesthesia. Therefore, the patient
should be carefully monitored and life support should be readily available.
Glossopharyngeal Nerve Block
The glossopharyngeal nerve, which contains both motor and sensory fibers, lies just posterior to the styloid process
of the temporal bone. The motor fibers innervate the stylopharyngeus muscle. The sensory fibers innervate the
posterior third of the tongue, the palatine tonsils, and the mucous membranes of the mouth and pharynx.
Parasympathetic nerves travel along with the glossopharyngeal nerve to innervate the parotid gland.
703
Figure 28-4 Lateral view of a gasserian ganglion Figure 28-3 Oblique caudal-to-cephalic fluoroscopic view of the foramen
block with contrast outlining Meckel’s cave.. ovale (closed arrow). The needle tip is located in the foramen ovale
A glossopharyngeal nerve block is indicated for the palliation of cancer-related pain in the distribution of the
glossopharyngeal nerve. Pain in the distribution of the glossopharyngeal nerve can occur in the ear, throat, tongue,
or back of the nose. Swallowing or chewing may often exacerbate pain. Refractory hiccup may also respond to
glossopharyngeal nerve block. Percutaneous radiofrequency thermocoagulation of the glossopharyngeal nerve
[126] [127]
offers low risk and effective pain control. [94]
EXTRAORAL APPROACH
The glossopharyngeal nerve is blocked by first placing the patient in a supine position. Using aseptic technique, a
25-G, 9-cm Quincke spinal needle is inserted perpendicular to the skin at the midpoint of an imaginary line
connecting the mastoid process and the angle of the mandible. Once the needle is in contact with the styloid process,
it is withdrawn and redirected posteriorly until the bony contact is lost. After aspiration for blood and CSF, 7 to 10
mL of preservative-free local anesthetic is injected in small increments. [128]
Intraoral Approach
With the patient’s mouth open wide, the tongue is retracted inferiorly and contralaterally with a 4×4 gauze. A 25-G,
9-cm long Quincke spinal needle is inserted into the mucosa at the lower lateral portion of the posterior tonsillar
pillar. After aspiration for CSF and blood, 7 to 10 mL of preservative-free local anesthetic, with or without steroid,
are injected in small increments. [129]
Complications associated with glossopharyngeal nerve block are hematoma, local anesthetic toxicity, intravascular
injection, tachycardia, anesthesia dolorosa, dysphagia, infection, and trauma to nerves. Chemical neurolytic blocks
should be avoided or reserved for extreme situations because of potential prolonged paralysis of the pharyngeal and
laryngeal muscles.
UPPER EXTREMITY
Overview
The differential diagnosis of upper extremity pain associated with primary or metastatic tumor is extensive. Pain [130]
of neuropathic origin may occur from invasion of the cervical or thoracic spinal cord, spinal roots, or cervical and
brachial plexuses, and individual peripheral nerves. Regional musculoskeletal pain may arise from invasion into
[131] [132]
the skeletal areas and soft tissues of the shoulder girdle and upper extremity.
Circulatory (arterial, venous, lymphatic) occlusion may cause either ischemic pain or variations of claudication. [133]
Because of the extensive innervation of the upper extremity by motor and sensory fibers, the benefit of
neuroablative procedures for the treatment of pain must be balanced with the potential risks of loss of sensation and
704
motor function. With the generalized neurolysis of agents such as alcohol and phenol, nerves with sensory and
motor fibers should not be subjected to chemical neurolysis unless the involved extremity has significantly limited
function. Although a majority of cancer patients “often gratefully exchange unremitting pain for numbness,” [134]
patients rarely tolerate loss of motor function even in a nondominant extremity. As discussed earlier in relation to
neurolysis in the role of regional anesthetic techniques for the treatment of cancer pain, pulsed RF lesioning is an
option that preserves sensory motor function and should be considered in the treatment of upper extremity pain.
Sensory innervation of the upper extremity arises from the cervical nerves V through VIII and from the first thoracic
nerve. Innervation to the axilla and upper inner arm is from the lateral branch of the second intercostal nerve
(intercostobrachial nerve). Sympathetic innervation derives from the T1 and T2 spinal cord segments. Preganglionic
sympathetic axons exit the ventral roots of T1 and T2 and then travel as white communicating rami before joining
the sympathetic chain as well as to synapse at the inferior (stellate), middle, or superior cervical ganglion.
Postganglionic nerves either follow the axillary artery to the upper extremity or integrate as the gray communicating
rami before joining the brachial plexus to innervate the upper extremity. Use of local anesthetic blocks helps to
localize the relative contribution of individual nerves to the painful area, and subsequent neurolytic blockade can be
considered to prolong pain relief.
Cervical Subarachnoid Neurolysis
Neurolytic procedures in the cervical spinal cord region have been shown to have limited effectiveness compared
with those at more caudad levels. This is certainly because of multifactorial causes of pain, such as anatomic
[135]
factors and multidermatomal involvement of the upper extremity. Combined with a higher risk of complications,
cervical subarachnoid neurolysis may be considered if limited sensory dermatomal coverage is needed (i.e., a few
spinal segments). Because the cervical nerve roots pass horizontally from the cord to their point of exit at the
intervertebral foramen, the injection of the neurolytic agent is made at the spinal segment level to be blocked ( Fig.
28–5 ). [136]
INTRATHECAL ALCOHOL
The patient is placed in the lateral position with the affected extremity upward. The patient should be rolled forward
into a 45-degree oblique position. This maintains the posterior roots in the uppermost position. A spinal needle
should then be placed into the intrathecal space at the vertebral interspace of the dermatome to be blocked. A
volume of up to 0.5 mL of 100% alcohol may be administered at a slow rate. It is recommended that a tuberculin
syringe be used and that increments of 0.1 mL be administered every minute. The patient may experience a transient
burning sensation in the dermatomal segments to be blocked. If 0.5 mL has been reached and the painful
dermatomal segments have not been blocked, a second needle may be placed two spinal segments above or below
the first needle placement, and the same dosing procedures should be followed. On completion of the injection, the
patient should remain in the same position for 15 to 20 minutes, after which the CSF alcohol concentrations are
negligible, precluding any further extension of the block (Fig. 28–6 (Figure Not Available) ). [136]
Figure 28-5 The alignment of spinal nerve roots with the neural foramen. The vertebral bodies and spinous processes are indicated by
Roman numerals, the spinal cord segments and their respective nerves by Arabic numerals. The cervical nerve roots pass horizontally
from the cord to their point of exit at the intervertebral foramen.
705
Bilateral blocks may be achieved with the patient in the prone position, with the posterior roots uppermost. In this
position, the injected alcohol can spread bilaterally to both posterior roots. Alternatively, each side can be done
separately as described in the next paragraph.
INTRATHECAL PHENOL
The patient is placed in the lateral position, with the affected extremity downward. The patient should be rolled
backward into a 45-degree oblique position. This maintains the posterior roots in the lowermost position. A spinal
needle should then be placed into the intrathecal space at the vertebral interspace of the dermatome to be blocked. A
volume of up to 0.5 mL of 5% to 10% phenol may be administered at a slow rate. It is recommended that a
tuberculin syringe be used and that increments of 0.1 mL be administered every minute.
Figure 28-6 (Figure Not Available) Positioning of a patient for administration of intrathecal alcohol. The painful side should be up, with a 45-
degree anterior tilt. This results in the posterior (sensory) roots being the most superior structures. Because alcohol is hypobaric, the sensory roots
are bathed, with sparing of the anterior (motor) roots.(From Swerdlow M: Neurolytic blocks. In Patt RB [ed]: Cancer Pain. Philadelphia, JB
Lippincott, 1993, p 435.)
Because phenol has local anesthetic properties, the patient should experience a feeling of warmth and tingling in the
affected dermatome. If these symptoms do not occur, it has been suggested that higher concentrations should be
used. If 0.5 mL has been reached and the painful dermatomal segments have not been blocked, a second needle
[137]
may be placed two spinal segments above or below the first needle placement, and the same dosing procedures
should be followed. On completion of the injection, the patient should remain in the same position for 15 to 20
minutes, after which the CSF phenol concentrations are negligible, precluding any further extension of the block
(Fig. 28–7 (Figure Not Available) ). [136]
Cervical Epidural Neurolysis
There is limited experience in the use of cervical epidural neurolysis. Racz and associates reported on a series of[138]
18 patients with cancer pain who were treated with cervical epidural phenol. Six patients had pain relief on
discharge, and five patients had pain relief lasting from 1 to 3 months. Korevaar’s experience in upper thoracic
[139]
neurolysis using alcohol through an indwelling catheter showed some promise, but extensive use has not been
realized.
Technique.An epidural catheter is placed at the C7 to T1 interspace and advanced to the desired level under
fluoroscopic guidance. Catheter placement can be verified by either injection of contrast or a local anesthetic. If a
local anesthetic is used, the volume of phenol should be equal to the required volume of local anesthetic required for
pain relief. However, before the phenol is administered, the local anesthetic block should be allowed to fully regress
to avoid spread of the phenol block beyond the initial local anesthetic test block. Phenol concentrations vary from
5% to 10%. [140]
Paravertebral Block and Neurolysis
Because of the extensive sensory overlap of the upper extremity, paravertebral somatic blocks are usually reserved
for well-localized pain. Even with localization, multiple cervical nerve roots must be blocked, usually resulting in
some degree of motor weakness. In a case report by Kaplan and coworkers, residual pain after a phenol neurolytic
[141]
procedure of the brachial plexus was managed with paravertebral phenol blocks. Using
Figure 28-7 (Figure Not Available) A patient positioned for administration of intrathecal phenol. The painful side should be down, with a 45-
degree posterior tilt. This results in the posterior (sensory) roots being the most inferior structures. Because phenol is hyperbaric, the sensory
roots are bathed, with sparing of the anterior (motor) roots.(From Swerdlow M: Neurolytic blocks. In Patt RB [ed]: Cancer Pain. Philadelphia,
706
JB Lippincott, 1993, p 435.)
0.5 to 1.0 mL of 6% aqueous phenol per segment, injections at C5 and C6 and (later, in response to tumor
enlargement) at T1 to T3 provided supplemental relief of upper extremity pain secondary to a sarcoma of the
humeral head. [141]
Radiologic guidance is strongly recommended for neurolytic paravertebral block as well as careful observation of
the effects of local anesthetic test dose(s) used in diagnostic procedures before neurolytic injection. The
administration of small doses of neurolytic solutions is recommended to minimize the risk of subarachnoid or
epidural spread.
Brachial Plexus Block and Neurolysis
Intermittent brachial plexus blockade can result in short-term pain relief and give patients respite from severe pain.
Continuous interscalene infusions of local anesthetic have been shown to be effective in symptomatic treatment of
patients with cancer pain for up to 2 weeks. A supraclavicular approach using nerve stimulation at the level of C6
[142]
in the interscalene groove, described by Haasio and Rosenberg, has an advantage of improved proximal upper
[143]
extremity coverage. The infraclavicular technique reviewed and described by Raj has improved distal upper
[144]
extremity coverage, including the ulnar segment of the medial cord and the intercostobrachial nerve. Although
neither of these techniques was described for use in cancer pain management, their effectiveness may prove
efficacious in the treatment of proximal or distal upper extremity pain secondary to tumor invasion.
Tumor encroachment is one of the most common causes of brachial plexopathy. A significant percentage of these
[145]
tumors arise as breast cancer, lymphoma, and apical tumors of the lung (Pancoast tumor). Pain is ubiquitous in these
patients, with the lower trunk (C7–T1) most often involved. Because of the mixed sensory and motor components of
the brachial plexus, neurolysis should not be performed unless the upper extremity is already weak or useless
secondary to pain or a physiologic derangement. Multiple case reports have described approaches to infiltrate
[141] [146]
neurolytic solutions around the brachial plexus. Bonica and associates described effective pain relief and weakness
[146]
in patients after local anesthetic prognostic blocks using 25 mL of 5% aqueous phenol and effective pain relief and
paralysis in patients after 20 mL of 95% alcohol. Kaplan reported a case of supraclavicular brachial plexus
[141]
injection of 12.5 mL of 6% phenol in water with significant but incomplete relief. Patt described good to excellent
[134]
pain relief from tumor invasion of the brachial plexus using 10 to 20 mL of 10% to 20% aqueous phenol mixed with
20% glycerin injected via an axillary approach. There were no unexpected complications, but increased motor
weakness occurred in all cases. The duration of the pain relief from these case reports ranged from weeks to months,
and patients occasionally required repeat injections.
Intermittent interscalene neurolysis has been performed for tumors of the upper extremity via the interscalene
approach. Case reports by Mullin and Neill discussed using 3% phenol and 50% alcohol, respectively, with
[103] [104]
minimal neurologic sequelae.
Peripheral Nerve Blocks and Neurolysis
A good understanding of the sensory innervation to the upper extremity can be very helpful in guiding neural
blockade for pain control. If the pain distribution is limited to one or two peripheral nerves, neurolytic techniques
may result in long-term pain relief in selected patients. Suprascapular chemical neurolysis has been employed for
shoulder and upper extremity pain. Using localization with nerve stimulation, an injection of 4 to 5 mL of 10%
[134]
phenol and 4 mL of 95% alcohol afforded weeks of pain relief and no loss of motor function.
Cryoneuroablation of the suprascapular nerve is minimally invasive and has been used as an effective treatment for
chronic pain of the shoulder. This procedure also may provide prolonged relief of pain of the upper shoulder
secondary to multiple myeloma, lung cancer, and so forth. For the procedure, the patient is placed in the prone
position, and a 14-G or 12-G intravenous catheter is advanced into the supraspinatus notch, parallel to the direction
of the nerve. Using sensory stimulation, the 1.4- or 2.0-mm cryoprobe is advanced until the nerve is localized.
Usually two or three 3-minute freeze cycles are adequate.
Stellate Ganglion Blockade and Neurolysis
Stellate ganglion block (SGB) may be effective for upper extremity pain associated with visceral involvement,
brachialgia, or certain types of deafferentation processes (secondary to radiotherapy). Local anesthetic SGBs have
been performed and shown to have some long-lasting effects in lung cancer patients. A further discussion on stellate
ganglion blockade and neurolysis may be found in the section on head and neck pain.
707
Cervical Epidural Infusions
For upper extremity pain that does not respond to intermittent regional anesthetic techniques, a continuous cervical
epidural infusion should be considered. This infusion can be accomplished via a percutaneous temporary catheter,
with the infusion of low concentrations of bupivacaine (1/32% to 1/10%). The tip of the catheter should be placed as
close as possible to the dermatomes supplying the brachial plexus (C5–T1). For a discussion on cervical epidural
infusions, refer to the section on head and neck pain.
THORACIC AND ABDOMINAL WALL

Overview
The causes of pain originating in the chest and abdominal wall vary, but they are usually secondary to neoplastic
invasion of the vertebral bodies and rib cage (prostate, breast), spinal cord and peripheral nerves, or parietal
peritoneum (lung). Various therapies for patients with thoracic or abdominal wall pain syndromes are derived in
[147] [148]
part from regional anesthetic procedures such as treatment with intercostal or paravertebral blocks, and the
[149] [150] [151]
quest continues for a longer duration of pain relief with the use of various techniques such as intercostal, epidural,
and subarachnoid neurolysis.
Intercostal Nerve Blocks and Neurolysis
An intercostal nerve block is usually performed posteriorly at the angle of the rib just lateral to the paraspinous
muscles, where the ribs are usually easily palpable. The nerve is still contained within the intercostal groove,
[153]
where drugs tend to be spread more predictably, and failures may be fewer than with anterior approaches because
[151]
the nerve has not yet given off its lateral cutaneous branch near the midaxillary line. Radiologic guidance has been
[140]
cited for intercostal nerve block and should be used especially when neurolysis is attempted. “Walking the needle”
[151]
toward the inferior margin and under the rib (2–4 mm), with a concomitant paresthesia, is a reliable confirmation of
needle placement ( Fig. 28–8 ). The most significant complication of an intercostal nerve block is pneumothorax,
although with proper technique, the incidence of symptomatic pneumothorax may be as low as 0.092%, as was
demonstrated in a series of 50,097 intercostal blocks that were performed. The requirement for chest tube drainage
[150]
is rare and should be considered only if the lung fails to expand after observation or if percutaneous aspiration fails
to relieve the pneumothorax. Previous surgical procedures of the chest (partial or complete lung resection) increase
the risk of complications from intercostal nerve blocks and ablative procedures. A case report by Atkinson and
Shupack highlights a patient with adhesions who experienced acute bronchospasm after a presumed intrabronchial
or intrapulmonary injection of 0.5 mL of 8% phenol in saline.
Reports are sparse on treatment of patients with thoracic and abdominal wall pain syndromes by means of
intercostal neurolysis. Chemical neurolysis was reported by Doyle with a series of 46 hospice patients treated with
[155]
multiple intercostal blocks using 1.0 to 1.5 mL of 5% phenol “in oil” per segment. Total relief of pain for a mean
duration of 3 weeks (range 1–6 wk) was achieved and no complications were reported. Intercostal cryoneurolysis
has been used in the treatment of post-thoracotomy pain, with a variable duration of relief. In patients with
[156]
intercostal neuralgia after thoracotomy (91%) and herpes zoster (9%), Green and associates reported on [157]
percutaneous intercostal cryo-neurolysis with use of a large probe through a 14-G cannula for a single cycle of 4
minutes. All patients experienced initial pain relief, which regressed over 2 to 3 weeks, and, ultimately, one half and
one quarter of patients reported significant pain relief at 3 and 6 months, respectively. RF lesioning of peripheral
nerves is discouraged because patients have developed severe neuritis and deafferentation syndrome. With the
advent of pulsed radiofrequency (PRF) generators, case reports of treatment of some forms of neuropathic pain
syndromes may portend an improved method of RFA for intercostal DRG or peripheral nerves. The reported
advantage of PRF is that there is no clinical evidence of neural damage resulting from the
minimal elevation of probe temperature to 42°C. For a discussion of PRF lesioning, refer to the
[53]
earlier discussion of neurolysis in the section on the role of regional anesthetic techniques for the
treatment of cancer pain.
708
Figure 28-8 Overview of posterior intercostal nerve block. A, The patient is placed in the prone position, with the arms hanging off the table to retract the scapula
laterally. B, The rib is palpated and the needle advanced until the rib is contacted. C, The needle is then “walked off” inferiorly below the rib, with care taken to keep
the angle of the needle in a slight caudad-to-cephalad direction. D, The needle is then advanced a couple of millimeters underneath the inferior edge of the rib, and 3
to 5 mL of local anesthetic are injected. E and F, The needle is removed and the procedure can be repeated at another level. (From Thompson GE: Intercostal nerve
block. In Waldman SD, Winnie AP [eds]: Interventional Pain Management. Philadelphia, WB Saunders, 1996, pp 311–317).
Paravertebral Blocks and Neurolysis
Paravertebral neurolytic blocks of the somatic roots just outside the intervertebral foramina are frequently
undertaken. Bonica mentioned favorable results subsequent to the paravertebral injection of 1 mL of alcohol per
[158] [159]
involved segment in patients with abdominal and chest wall pain secondary to vertebral, paravertebral, and visceral
neoplasms associated with peritoneal invasion. Jain and colleagues mentioned performing 39 paravertebral alcohol
[160]
and phenol injections without serious complication under radiologic guidance. In a brief report, Vernon noted good
relief of back pain of metastatic origin and no untoward effects after paravertebral injection of alcohol in two
patients. The usual technique relies on paresthesias and bony landmarks, such as the transverse process, as well as
[152]
radiologic guidance, careful observation of the effects of preneurolytic test doses of local anesthetic, and
fractionated administration to avoid subarachnoid, epidural, or intrapleural spread, all of which have been
documented. [161]
RF lesioning of thoracic intercostal nerves by percutaneous partial rhizotomy has been well documented. More [162]
recently, RFA of the thoracic dorsal root ganglion was shown to be effective in 52% of patients with limited
segmental nonmalignant thoracic pain. The thoracic dorsal root ganglion is located in the superior dorsal quadrant of
the foramen. In the lower thoracic vertebra, the percutaneous access is approached laterally and directed medially
toward the vertebral body. In the upper thoracic region, a small laminotomy is created directly over the superior
aspect of the foramina. Van Kleef and colleagues treated 43 patients using an RF probe adjacent to the dorsal root
[163]
ganglion for 60 seconds, noting no major complications such as dysesthesia or increased pain. Although three cases
of pneumothorax occurred, no patients experienced post-treatment neuritis. Munglani provided a case report of [53]
PRF ablation of the spinal roots of T2 to T4, which created significant relief, without loss of sensation, of
neuropathic pain of the anterior chest wall secondary to radiation.
Thoracic Sympathectomy
Thoracic sympathetic block has been indicated for intractable cancer pain of the upper two thirds of the esophagus
(T2–T8) and pleuritic chest pain secondary to lung neoplasm. The difficulty of multiple needle placements,
[146] [164]
709
along with potential serious complications and the effectiveness of epidural and subarachnoid neurolysis, have
minimized the usefulness of this procedure. Permanent sympathectomy may be accomplished with RF lesioning [165]
( Fig. 28–9 ).
Interpleural Analgesia and Neurolysis
Placement of an interpleural catheter for treatment of patients with cancer pain has been used sparingly secondary to
the concerns of local anesthetic absorption (especially bupivacaine) and the risk of pneumothorax in patients with [166]
marginal pulmonary function ( Fig. 28–10 ). O’Leary and Myers described the use of interpleural catheters in
[167] [166]
10 patients with metastatic disease to the chest, neck, and upper extremities, using various infusions of bupivacaine
up to 0.5%. Neurolytic interpleural therapy was reported by Lema and coworkers for a patient with metastatic [168]
esophageal cancer. The infusion of 6% phenol provided significant reduction of chest pain and opioid requirements
over a 4-week period, without histiologic pleura or lung damage.
Thoracic Subarachnoid and Epidural Neurolysis
The upper and lower thoracic regions provide relatively safe and simple access for the performance of subarachnoid
chemical neurolysis using either phenol or alcohol. The possible advantages of subarachnoid block in this region
include low morbidity, presence of a reliable end point using CSF, no requirement to localize multiple individual
nerves, and fewer problems related to overlapping distribution. Although the risk of pneumothorax exists, the
probability is limited. Epidural chemical neurolysis has been employed, with single or multiple injections
administered via an epidural catheter (see the section on cervical epidural neurolysis). The upper thoracic nerve [139]
roots pass horizontally from the cord to their point of exit at the intervertebral foramen, whereas in the mid- and
lower thoracic region, the nerve root passes out of the vertebral column one or two segments below the exit from the
spinal cord. Because it is thought that the neurolytic agent exerts its maximal effect on the fine rootlets leaving the
cord, the needle entry site should be one or two segments above the vertebral column exit site of the nerve root (see
Fig. 28–5 ).
Figure 28-9 Overview of cannula placement for radiofrequency lesioning of the sympathetic chain. A, Lateral view, showing correct cannula placement. B, C, and D,
The sympathetic ganglia are located near the middle and posterolateral positions of each vertebral body. The posteroanterior (B), oblique (C), and lateral views (D)
show correct needle placement. (From Kline MT: Radiofrequency techniques in clinical practice. In Waldman SD, Winnie AP [eds]: Interventional Pain Management.
Philadelphia, WB Saunders, 1996, pp 185–217).
710
Figure 28-10 Overview of interpleural catheter placement. A, The entry site is approximately 10 cm lateral to T7 to T10. B, The skin is anesthetized. C and D, An
epidural needle with a loss-of-resistance syringe filled with 2 to 4 cc of air is then advanced over the rib. E, As the tip of the needle enters the interpleural space, the
air in the loss-of-resistance syringe is drawn inward. F and G, The bevel of the needle should be rotated to face medially and the catheter quickly advanced through
the needle into the interpleural space to avoid air being indrawn, after which the needle is removed over the catheter, leaving the catheter in place. (From Myers DP,
O’Leary KA, Lema MJ: Interpleural catheters: Indications and techniques. In Waldman SD, Winnie AP [eds]: Interventional Pain Management. Philadelphia, WB
Saunders, 1996, pp 319–323.)
INTRATHECAL ALCOHOL
The patient is placed in the lateral position, with the affected extremity upward. The patient should be rolled forward
into a 45-degree oblique position. This maintains the posterior roots in the uppermost position. For upper thoracic
pain, a spinal needle is placed into the intrathecal space at the vertebral interspace of the dermatome to be blocked.
For mid- to lower thoracic or abdominal pain, a spinal needle is placed into the intrathecal space one or two
segments above the vertebral interspace of the dermatome to be blocked. A volume of up to 1.0 mL of 100% alcohol
may be administered at a slow rate. It is recommended that a tuberculin syringe be used and that increments of 0.2
mL be administered every minute. The patient may experience a transient burning sensation in the dermatomal
segments to be blocked. If 1.0 mL has been reached and the painful dermatomal segments have not been blocked, a
second needle may be placed two spinal segments above or below the first needle placement, and the same dosing
procedures should be followed. On completion of the injection, the patient should remain in the same position for 15
to 20 minutes, after which the CSF alcohol concentrations are negligible, precluding any further extension of the
block (see Fig. 28–6 (Figure Not Available) ).
INTRATHECAL PHENOL
backward into a 45-degree oblique position. This maintains the posterior roots in the lowermost position. For upper
thoracic pain, a spinal needle is placed into the intrathecal space at the vertebral interspace of the dermatome to be
blocked. For mid to lower thoracic or abdominal pain, a spinal needle is placed into the intrathecal space one or two
segments above the vertebral interspace of the dermatome to be blocked. A volume of up to 1.0 mL of 5% to 10%
phenol may be administered at a slow rate. It is recommended that a tuberculin syringe be used and that increments
of 0.2 mL be administered every minute. Because phenol has local anesthetic properties, the patient should
experience feelings of warmth and tingling in the affected dermatome. If these symptoms do not occur, it has been
711
suggested that higher concentrations should be used. If 1.0 mL has been reached and the painful dermatomal
[137]
segments have not been blocked, a second needle may be placed two spinal segments above or below the first needle
placement, and the same dosing procedures should be followed. On completion of the injection, the patient should
remain in the same position for 15 to 20 minutes, after which the CSF phenol concentrations are negligible,
precluding any further extension of the block (see Fig. 28–7 (Figure Not Available) ).
ABDOMINAL PAIN
Overview
The upper gastrointestinal (GI) tract and surrounding viscera receive sensory innervation from T5 to T12, which
travel through the celiac plexus. Therefore, blockade of the celiac plexus denervates sensation to the upper GI tract
(liver, stomach, pancreas, spleen, kidneys) and is commonly used for patients with painful disease of these
structures. The celiac plexus receives input from the greater (T5–T10), lesser (T10–T11), and least (T12)
[169] [170]
splanchnic nerves. The aorta is just posterior to the plexus on the left.
Local anesthetic block of the celiac plexus results in transient pain relief, and a neurolytic block is usually required
for long-term pain relief. Although somatic neurolytic blocks may result in sensory motor dysfunction, this is a rare
occurrence with a celiac plexus block, making it a very attractive technique that should be used early in patients
unresponsive to conservative measures. Although neurolytic celiac plexus blocks are most often used for the
treatment of pancreatic cancer pain, studies have shown similar results in patients with nonpancreatic cancer pain
(70% to 90% satisfactory pain relief at death).[171] [172] [173]
Celiac Plexus Block and Neurolysis
The celiac plexus can be blocked by either anterior or posterior approaches. The posterior approach includes
retrocrural, anterocrural, transaortic, and splanchnicectomy techniques. A prospective randomized study in 61
pancreatic cancer patients showed no significant differences in outcomes among the retrocrural, transaortic, and
splanchnicectomy techniques. In the retrocrural technique, local anesthetic or neurolytic agent is injected posterior
[174]
and cephalic to the diaphragmatic crura, whereas in the anterocrural approach, the blocking agent is injected anterior
to the diaphragmatic crura behind the aorta, at the level of the L1 vertebra. Both the anterocrural and retrocrural
techniques can be performed with the patient lying prone under fluoroscopic or computed tomography (CT)
guidance. The anterior approach is usually performed with patients in a supine position under the guidance of CT
scan.
RETROCRURAL APPROACH
The patient is positioned in the prone position, with a pillow underneath the abdomen to decrease lumbar lordosis.
The inferior borders of the tip of the 12th ribs are marked as the needle entry site. The skin is prepared with aseptic
technique and sites of needle entry are numbed with local anesthetic. Under an anteroposterior fluoroscopic view, a
22-G, 15-cm long needle is advanced from the needle entry site toward the inferior one third of the L1 vertebral
body. Once the needle is in contact with the vertebral column, 2 to 3 mL of local anesthetic should be given to
facilitate needle manipulation along the vertebral body. The needle is then withdrawn to subcutaneous tissue and
advanced at a steepened angle. The maneuver is repeated until the needle slips off the L1 vertebral body. Under a
lateral fluoroscopic view, the needle is then advanced to the anterior border of the L1 vertebral body. The tip of the
needle is advanced 2 cm on the right and preferably 1 cm on the left until the aortic pulsations are felt. After
removing the stylets of the needles, the operator should inspect the hubs of the needles for blood, CSF, and urine. If
these are present, the needle should be withdrawn and redirected. Then 2 to 3 mL of water-soluble contrast medium
are injected. Ideally, contrast medium should spread along the anterior border of the vertebral column with a smooth
posterior contour that corresponds to the psoas fascia on the lateral fluoroscopic view ( Fig. 28–11 A and B). On the
anteroposterior view, the dye spread should be just slightly off the midline and concentrated near the L1 vertebral
body. After aspiration, 2 mL of local anesthetic are injected as a test dose at each needle to rule out intravascular or
intrathecal injection. Then 10 to 15 mL of local anesthetic are injected at each needle. For diagnostic blocks 2%
lidocaine or 0.25% bupivacaine can be used. Neurolytic agents such as anhydrous alcohol or 6% phenol (total of 30–
40 mL) can be used only after a positive response has been established with the local anesthetic injection. An
injection of alcohol can cause severe pain; therefore, an injection of 10 to 20 mL of local anesthetic such as 0.25%
bupivacaine before the neurolytic agent can minimize discomfort associated with the neurolytic agent. [170]
712
Figure 28-11 Anteroposterior view (A) and lateral view (B) of correct needle locations for the retrocrural approach to the celiac plexus block. This technique requires
bilateral needle placement, with the needle tip located at the anterolateral portion of L1.
ANTEROCRURAL APPROACH
This approach is similar to the retrocrural approach, except the needle entry sites are closer to the midline. The
needle tips are anteroinferior to the diaphragm; thus, smaller volumes of local anesthetic and neurolytic agents are
needed, with an equal or better efficacy than afforded by the retrocrural approach. [175]
TRANSAORTIC APPROACH
This unilateral left-sided needle placement technique was described by Ischia and colleagues. Using a similar [174]
posterior approach as described in the classical posterior retrocrural approach, the needle is walked off the L1
vertebral body and advanced until the tip is in the preaortic connective tissue, which is generally felt as an increase
of resistance and pulsatile sensation. The needle is then advanced through the posterior aortic wall, the lumen, and
the anterior aortic wall. Beyond that point, a new loss of resistance is felt, and the tip of the needle is in the preaortic
area, where the celiac plexus is located. Alternatively, applying constant negative aspiration pressure via a 5-mL
syringe can facilitate needle placement. A sudden loss of aspiration pressure after the needle has passed through the
vessel wall signifies that the tip of the needle is in close proximity to the plexus. The needle placement is further
confirmed with contrast medium. [176]
SPLANCHNICECTOMY
This is a bilateral block similar to the technique described for the retrocrural approach; however, the needle is
directed to the upper border of T12. The lateral view should show the needle tips approximately 0.5 cm anterior to
the middle of the upper body of T12. The anteroposterior view should show the needle tips approximately 0.5–1.0
cm inside the lateral edge of T12. This compartment is bound anteriorly by the major vessels, posteriorly by the
vertebral body, laterally by the parietal pleura, and inferiorly by the crus of the diaphragm. [101]
ANTERIOR APPROACH
This approach is performed under CT guidance, with the patient in the supine position. The greatest advantage of
this technique is that for patients with abdominal pain or colostomies, the supine position is more comfortable than
the prone position. In addition, this approach requires only one needle placement, which further minimizes the
discomfort associated with the injection. The precrural needle placement also decreases the risk of neurologic injury
associated with the retrocrural spread of drugs to the somatic nerves or the epidural or subarachnoid space. However,
the potential risks associated with this approach include infection, abscess, and hemorrhage and fistula formation.
The preparation of the patient is similar to that for the posterior approaches. Prophylactic intravenous antibiotic is
recommended to decrease the risk of infection.
First, the patient is placed on a CT table, and the abdomen is prepared with aseptic technique. The needle entry site
is marked approximately 1 to 1.5 cm below and to the left of the xiphoid process. A 22-G, 15-cm needle is
introduced perpendicular to the skin at the anesthetized area and advanced to the depth of the anterior wall of the
aorta as estimated by the CT scan. Final needle placement is confirmed with CT imaging. Fifteen to 20 mL of local
713
anesthetics such as 2% lidocaine or 0.25% bupivacaine injected in small increments is sufficient for a diagnostic
block. For a neurolytic blockade, 20 mL of anhydrous alcohol has been used with good result.
Complications. Risks of a celiac plexus block, regardless of technique, include hypotension, neurologic injury,
local anesthetic toxicity, hematoma, and diarrhea. Hypotension occurs because of loss of sympathetic tone to the
viscera, resulting in pooling of blood in the viscera. Over 2 to 3 days, the hypotension resolves with fluid shifts.
Neurologic injury can occur because the needle is advanced through the upper lumbar plexus. If the major vessels
are entered, local anesthetic toxicity or a hematoma can develop. Because the sympathetic supply to the abdominal
viscera is removed, there is an unopposed parasympathetic innervation, which can result in diarrhea. However, this
usually resolves over 2 to 3 days. With the splanchnicectomy, a pneumothorax may occur, and it is important to
keep the needle as close as possible to the vertebral body.
PELVIC PAIN
Overview
The superior hypogastric plexus lies in the retroperitoneal space, just below the aortic bifurcation, anterior to the
fifth lumbar vertebra and the first sacral vertebral body. The confluence of branches from the lumbar sympathetic
chain (lumbar splanchnics) and branches of the aortic plexus forms the plexus, which also receives parasympathetic
contribution from the S2 to S4 ventral roots. The superior hypogastric plexus divides into the right and left
hypogastric nerves, which descend lateral to the sigmoid colon and rectosigmoid junction into the inferior
hypogastric plexus. The hypogastric plexus, which contains afferent pain fibers and postganglionic sympathetic
fibers as well as preganglionic parasympathetic fibers, innervates the pelvic viscera. Unlike the celiac plexus, the
[100]
superior hypogastric plexus is in close proximity to the sacral plexus; therefore, there is a greater risk of somatic
block.
The first published study on the superior hypogastric plexus block was by Plancarte and associates, who[177]
performed this procedure on 28 patients with pelvic cancer–related pain (20 cervical cancer, 4 prostatic cancer, 1
testicular cancer, and 3 radiation-induced enteritis). There was an overall 70% reduction in pain and no
complications. In 1993, de Leon-Casasola and coworkers showed similar results in 26 patients with pelvic
[177] [178]
cancer–related pain.
Superior Hypogastric Plexus Block and Neurolysis
The patient is placed in a prone position, with a pillow under the pelvic area to decrease lumbar lordosis. The
lumbosacral area is then cleaned with aseptic technique. Using fluoroscopic imaging, the L4-L5 interspinous space
is identified on the anteroposterior view. The needle entry site is marked 5 to 7 cm lateral to the midpoint of the L4–
L5 interspinous space. A skin wheal is raised with local anesthesia administered at the needle entry site. Under the
guidance of fluoroscopy, a 22-G, 15-cm needle is directed at approximately 30 to 45 degrees medially and caudally
toward the anterolateral surface of the L5 vertebral body. The angle of the needle is adjusted until it has walked off
the vertebral body. If the L5 transverse process is encountered, the needle is withdrawn to the subcutaneous tissue
and redirected caudally at a steeper angle. If the needle still cannot pass the iliac crest and L5 transverse process, a
slight bend of the needle to create a curvature may facilitate the needle placement. Alternatively, either passing the
needle through the L5 to S1 area under biplanar view or using CT has been reported as a safe and successful way of
blocking the superior hypogastric plexus. Once the tip of the needle is at the anterolateral border of the vertebral
body, 2 to 3 mL of water-soluble contrast medium can be injected to confirm the needle placement. A smooth
contour of the contrast medium along the anterovertebral border on the lateral view and paramedian or median dye
spread on the anteroposterior view ensure the needle placement. Because of the presence of the bifurcation of the
common iliac vessels, cautious aspiration using a test dose of injection solution is recommended. For diagnostic
blocks, 8 mL of .25% bupivacaine or 1% lidocaine are injected through each needle, and for neurolysis, 8 mL of 6%
to 10% aqueous phenol or anhydrous alcohol are used. The use of CT has also been described for this
[177] [179]
procedure. [180]
With the close proximity of the sacral plexus, smaller volumes of local anesthetic or neurolytic agents should be
used (5–8 mL) than with the celiac plexus block (20–40 mL). This avoids spillage of the agent onto the sacral plexus
and somatic blockade. Other complications include vascular puncture with local anesthetic toxicity or hematoma
formation.
LOWER EXTREMITY
Overview
714
The differential diagnosis of lower extremity pain associated with primary or metastatic tumor is extensive.[ ] [ ]
181 182
Pain of neuropathic origin may result from invasion of the spinal cord, spinal roots, lumbar and sacral plexus, and
individual peripheral nerves.[ ] [ ] Regional musculoskeletal pain may arise from invasion into the skeletal and soft
25 183
tissues of the pelvic girdle and lower extremity. Circulatory (arterial, venous, lymphatic) occlusion may cause either
ischemic pain or variations of claudication.[ ] Because of the extensive innervation of the lower extremity by motor
133
and sensory fibers, the benefit of neuroablative procedures for the treatment of pain must be balanced with the
potential risks of loss of sensation and motor function. With the generalized neurolysis of agents such as alcohol and
phenol, nerves with sensory and motor fibers should not be subjected to chemical neurolysis unless the involved
extremity has significantly limited function. The negative effects of motor dysfunction of the lower extremity should
be weighed against the positive effects of pain relief. As discussed earlier regarding neurolysis in the section on the
role of regional anesthetic techniques for the treatment of cancer pain, PRF lesioning is an option that preserves
sensory motor function and should be considered in treatment of patients with lower extremity pain.
Sensory innervation of the lower extremity arises from the lumbar plexus (L1–L4) and the sacral plexus (L5–S3).
Sympathetic innervation derives from the L1 and L2 spinal cord segments. Preganglionic sympathetic axons exit the
ventral roots of L1 and L2 and then travel as white communicating rami before joining the sympathetic chain to
synapse at the lumbar ganglion. Postganglionic nerves either follow the femoral artery to the lower extremity or
integrate as the gray communicating rami before joining the lumbosacral plexus to innervate the lower extremity.
Use of local anesthetic blocks helps to localize the relative contribution of individual nerves to the painful area, and
subsequent neurolytic blockade can be considered to prolong pain relief.
Lumbar Subarachnoid Neurolysis
Subarachnoid neurolysis of the lumbar region may be considered if limited sensory dermatomal coverage is needed
(i.e., a few spinal segments). The lumbar nerve roots are located at the T11 to T12 level and the sacral nerve roots
are located at the L1 to L2 level. Therefore, for lumbar and sacral dermatomes, neurolysis should be performed at
the T11 to T12 and L1 to L2 interspaces, respectively (see Fig. 28–5 ).
INTRATHECAL ALCOHOL
should then be placed into the intrathecal space at the T11 to T12 interspace for lumbar dermatomes and at the L1 to
L2 interspace for sacral dermatomes. A volume of up to 1.0 mL of 100% alcohol may be administered at a slow rate.
It is recommended that a tuberculin syringe be used and that increments of 0.2 mL be administered every minute.
The patient may experience a transient burning sensation in the dermatomal segments to be blocked. If 1.0 mL has
been reached and the painful dermatomal segments have not been blocked, a second needle may be placed two
spinal segments above or below the first needle placement, and the same dosing procedures should be followed. On
completion of the injection, the patient should remain in the same position for 15 to 20 minutes, after which the CSF
alcohol concentrations are negligible, precluding any further extension of the block (see Fig. 28–6 (Figure Not
Available) ).
INTRATHECAL PHENOL
needle should then be placed into the intrathecal space at the T11 to T12 interspace for lumbar dermatomes and the
L1 to L2 interspace for sacral dermatomes. A volume of up to 1.0 mL of 5% to 10% phenol may be administered at
a slow rate. It is recommended that a tuberculin syringe be used and that increments of 1.0 mL be administered
every minute. Because phenol has local anesthetic properties, the patient should experience feelings of warmth and
tingling in the affected dermatome. If these symptoms do not occur, it has been suggested that higher concentrations
should be used. If 1.0 mL has been reached and the painful dermatomal segments have not been blocked, a second
[137]
needle may be placed two spinal segments above or below the first needle placement, and the same dosing
procedures should be followed. On completion of the injection, the patient should remain in the same position for 15
to 20 minutes, after which the CSF phenol concentrations are negligible, precluding any further extension of the
block (see Fig. 28–7 (Figure Not Available) ).
Lumbar Epidural Neurolysis
715
There is limited experience in the use of lumbar epidural neurolysis. There are anecdotal reports of satisfactory pain
relief with lumbar and caudal epidural neurolysis with phenol; however, there are no data available. The technique is
similar to the one described earlier for the cervical region. [138]
Paravertebral Block and Neurolysis
Because of the extensive sensory overlap of the lower extremity, paravertebral somatic blocks are usually reserved
for well-localized pain. Even with localization, multiple lumbar nerve roots must be blocked, usually resulting in
some degree of motor weakness. Radiologic guidance is strongly recommended for neurolytic paravertebral block,
along with careful observation of the effects of a local anesthetic test dose (or doses) used in diagnostic procedures
before neurolytic injection. The administration of small doses of neurolytic solutions is recommended to minimize
the risk of subarachnoid or epidural spread.
Technique. The patient should be placed in a prone position, with a pillow under the pelvic area to decrease lumbar
lordosis. The lumbosacral area should be cleaned with aseptic technique. Using fluoroscopic imaging, the transverse
process of the vertebral level to be blocked is identified. The needle entry site is approximately 2 cm below the
lateral edge of the vertebral process. A skin wheal is raised with local anesthesia at the needle entry site. Under the
guidance of fluoroscopy, a 22-G, 3.5-inch needle with a 1-cm, 45-degree angled tip is directed at approximately 30
to 45 degrees medially and cephalad toward the junction of the transverse process with the vertebral body. This
direction avoids contact with the nerve root. Alternatively, an oblique view with fluoroscopy can be used to observe
the neural foramen and guide the angle of needle entry. By twisting the needle, the curved tip can be used to guide
the needle’s advancement. Once the neural foramen is approached, the needle should be rotated so that the curved
tip enters the foramen. Injection of the contrast should spread into the neural foramen along the nerve root. If the
needle is advanced far enough into the foramen, epidural spread results. Alternatively, an 18-G, 3.5-inch Crawford
needle can be used. If injected dye does not enter the neural foramen, a 5-inch, 22-G spinal needle can be advanced
through the Crawford needle into the foramen ( Fig. 28–12 A and B).
Lumbar Plexus Block and Neurolysis
Intermittent lumbar plexus blockade can result in short-term pain relief, giving patients respite from severe pain.
Continuous lumbar plexus infusions of local anesthetic through a catheter placed in the psoas compartment may be
beneficial. There are minimal data on lumbar plexus neurolysis. Calava and associates reported on a 56-year-old
[184]
patient with severe lower extremity pain after amputation. The pain was refractory to epidural local anesthetic and
opioid infusions. Ten mL of 10% phenol injected into the psoas sheath resulted in a significant reduction in pain,
with no evidence of motor blockade.
Peripheral Neurolysis
Tibial phenol neurolysis and cryoablation have been used for lower extremity cancer pain. The techniques [29]
described earlier for the upper extremity can also be applied to the lower extremity.
Lumbar Sympathetic Ganglion Blockade and Neurolysis
There are many indications for the use of a lumbar sympathetic ganglion block (LSB) for the treatment of
Figure 28-12 Anteroposterior view (A) and lateral view (B) of correct needle locations for paravertebral block. Note that the contrast spreads
medially into the epidural space (A). The lateral view shows the contrast in the anterior epidural space (B).lower body cancer pain. These include
716
pain resulting from herpes zoster, postherpetic neuralgia,[111] lumbar vertebral metastasis, neuropathic pain secondary to chemotherapy or
radiation therapy, pain from central nervous system lesions, and complex regional pain syndrome type I and type II.[112] Response to performance
of LSB with use of local anesthetic can serve as a diagnostic indication that pain transmission can be the result of autonomic contribution. In
addition, the initial response to the block also serves as a prognostic indicator for possible repeated local anesthetic blocks, neurolytic block, or
surgical intervention.
Technique.The lumbar sympathetic ganglia are located at the anterolateral edge of the vertebral body just
anteromedial to the psoas muscle. Because ganglia at L3 and below do not receive white rami, the block can be
performed at the L2 ganglion, which adequately blocks the sympathetic supply to the lower extremity. The block is
performed with the patient in the prone position. The needle entry site is approximately 5 to 8 cm lateral to the
spinous process of L2. A 5- to 8-inch, 22-G needle is directed medially at approximately a 45-degree angle until
contact is made on the vertebral body of L2. The needle is then withdrawn and the angle increased until the needle
slides off the anterolateral edge of L2. A loss of resistance technique to air may be used because there is an
appreciable loss of resistance as the needle passes out of the psoas muscle. The tip of the needle should be located
on the anterolateral edge of the L2 vertebral body, and the dye should demonstrate a caudad and cephalad spread. If
the dye outlines the fibers of the psoas muscle, the needle should be advanced further. Fifteen mL of local anesthetic
or 6% to 10% phenol should be enough to block the sympathetic supply to the lower extremity.
Complications of a lumbar sympathetic block include local anesthetic toxicity, spinal nerve root block, subarachnoid
or epidural injection, renal trauma, intervertebral disc trauma, and L1 neuralgia.
CONTINUOUS LUMBAR SYMPATHETIC GANGLION BLOCK
If consistent pain relief is seen with intermittent LSB, a continuous block should be considered. Catheters can be
placed fluoroscopically, using the posterior approach described earlier. The catheter should be placed close to the
lateral portion of the anterior surface of the body of L2 on the affected side. A continuous infusion of 0.1% to 0.25%
bupivacaine or intermittent injections of bupivacaine can be used.
PERINEAL PAIN
Overview
The differential diagnosis of perineal pain associated with primary or metastatic tumor is extensive. Pain of
neuropathic origin may occur from invasion of the lumbar spinal cord, spinal roots, sacral plexus, and individual
peripheral nerves. Phantom rectal pain has also been described. [185] [186]
The perineum consists of the area between the ischial tuberosities, extending from the pubis to the coccyx. The area
is divided into two triangles, which are the urogenital triangle anteriorly and the anal triangle posteriorly. The
somatic nerves (iliohypogastric nerve, ilioinguinal nerve, genitofemoral nerve, and pudendal nerve) derive from L1
to L2, and from S2 to S5. The iliohypogastric nerve (L1–L2) provides sensory innervation to the suprapubic region.
The ilioinguinal nerve (L1–L2) provides sensory innervation to the skin over the inguinal ligament, the base of the
penis, and the base of the scrotum in the male or the labia in the female. The genital branch of the genitofemoral
nerve (L1–L2) innervates the lateral scrotum and vulva, whereas the motor branch innervates the cremaster muscle.
The pudendal nerve (S2–S4) divides into several branches (posterior scrotal/labial nerve, dorsal nerve, inferior rectal
and perineal nerve) as the nerve exits the pudendal canal (Alcock’s canal) just medial to the ischial tuberosity. The
posterior scrotal/labial nerve innervates the posterior two thirds of the scrotum/labia majora and minora. The dorsal
nerve provides sensory innervation to the penis/clitoris. The inferior rectal and perineal nerve innervates the anus
and anal sphincter. Parasympathetic innervation derives from S2 to S4, and sympathetic innervation derives from
T10 to L2. Because of the diverse anatomic structure and mixed sympathetic and somatic innervation, a careful
history-taking and physical examination are required to delineate somatic versus sympathetic- or visceral-mediated
pain. Characteristically, sympathetic or visceral pain usually manifests as vague and poorly localized pain and is
frequently accompanied with a burning sensation and urgency.
SACRAL SUBARACHNOID NEUROLYSIS
Subarachnoid neurolysis of the sacral region for the management of perineal pain may be considered if limited
sensory dermatomal coverage is needed (i.e., a few spinal segments). The sacral nerve roots are located at the L1 to
L2 level. Therefore, for sacral dermatomes, neurolysis should be performed at the L1 to L2 interspace. However, it
is possible to perform the block at the L5 to S1 interspace, where the S1 and S2 nerve roots may be spared, resulting
in an S3 and S4 block (see Fig. 28–5 ).
[187]
Intrathecal Alcohol
717
should then be placed into the intrathecal space at the L1 to L2 interspace. A volume of up to 1.0 mL of 100%
alcohol may be administered at a slow rate. It is recommended that a tuberculin syringe be used and that increments
of 0.2 mL be administered every minute. The patient may experience a transient burning sensation in the
dermatomal segments to be blocked. If 1.0 mL has been reached and the painful dermatomal segments have not
been blocked, a second needle may be placed two spinal segments above or below the first needle placement, and
the same dosing procedures should be followed. On completion of the injection, the patient should remain in the
same position for 15 to 20 minutes, after which the CSF alcohol concentrations are negligible, precluding any
further extension of the block (see Fig. 28–6 (Figure Not Available) ).
Bilateral blocks may be achieved with the patient in the prone position and the posterior roots uppermost. In this
INTRATHECAL PHENOL
needle should then be placed into the intrathecal space at the L1 to L2 interspace. A volume of up to 1.0 mL of 5%
to 10% phenol may be administered at a slow rate. It is recommended that a tuberculin syringe be used and that
increments of 1.0 mL be administered every minute. Because phenol has local anesthetic properties, the patient
should experience a feeling of warmth and tingling in the affected dermatome. If these symptoms do not occur, it
has been suggested that higher concentrations should be used. If 1.0 mL has been reached and the painful
[137]
dermatomal segments have not been blocked, a second needle may be placed two spinal segments above or below
the first needle placement, and the same dosing procedures should be followed. On completion of the injection, the
patient should remain in the same position for 15 to 20 minutes after which the CSF phenol concentrations are
negligible, precluding any further extension of the block (see Fig. 28–7 (Figure Not Available) ).
Because phenol is hyperbaric, it is also possible to perform a saddle block with the patient in the sitting position
using 1 to 2 mL of 6% phenol. Although there is a risk of motor weakness and sphincteric disturbances, these side
effects are minimal and transient. [140]
Sacral Epidural Neurolysis
There is limited experience in the use of sacral epidural neurolysis. There are anecdotal reports of satisfactory pain
relief with lumbar and caudal epidural neurolysis with use of phenol; however, there are no data available. The
technique is similar to the one described earlier for the cervical region. [138]
Peripheral Neurolysis
Pudendal nerve phenol neurolysis and cryoablation may be considered for refractory pain. Transacral cryoablation
of the sacral nerve roots has been described for intractable perineal pain secondary to pelvic cancer or coccidynia. [188]
In addition, CT-guided pudendal nerve block has been described for anoperineal pain (see Fig. 28–13 A and B).
[189]
Ganglion Impar (Ganglion of Walther) Block
The ganglion impar is a solitary retroperitoneal structure located at the level of the sacrococcygeal junction, marking
the termination of the paravertebral sympathetic chains. Indications for a ganglion impar block include perineal
[100] [190]
pain in patients with cancer of the cervix, colon, bladder, rectum, and endometrium. Visceral phantom pain of the
rectum and anus after surgical palliative intervention may also benefit from this block. [191] [192] [193]
Technique.The patient is placed in the lateral decubitus position. Using aseptic technique, a skin wheal is raised
with 1% lidocaine at the tip of coccyx. Under the guidance of fluoroscopic imaging, a 25-G or 22-G, 8-cm spinal
needle, which is curved manually at an angle 25 degrees to 30 degrees approximately 1.5 cm from its hub, is
inserted through the skin wheal. The needle is directed anterior to the coccyx until the tip of the needle is at the
sacrococcygeal junction. A smooth linear spread of contrast dye along the anterior border of the sacrum confirms the
retroperitoneal location of the needle placement. Four to 6 mL of local anesthetic can be used for a diagnostic block.
Similar amounts of 6% to 10% phenol or anhydrous alcohol can be used for neurolytic block once the analgesic
effect of the block is established with the local anesthetic. Occasionally, excessive anterior concave curvature of the
sacrum may increase difficulty of the needle placement.
718
An alternative approach of performing the block is done with the patient in a prone position. Using aseptic technique
and fluoroscopic guidance, a skin wheal is made with 1% lidocaine at the sacrococcygeal ligament. A 22-G, 8-cm
spinal needle is inserted through the skin wheal and the sacrococcygeal ligament. A sudden loss of resistance or a
“popping” sensation indicates that the tip of the needle is passing through the sacrococcygeal
ligament. The needle placement is further confirmed with the injection of contrast medium. [179]
Although rare, perforation of the rectum, periosteal injection, epidural injection, or sacral root injury may occur.
VERTEBRAL METASTASIS
Overview
One of the most challenging pain management problems is pain secondary to spinal metastasis. The central location
of the tumor, along with the complex innervation of the spine, limits the use of regional anesthetic techniques for
pain management. However, improvements in the understanding of the innervation of the spine have led to
developments in which regional anesthetic techniques can be useful in managing pain.
Regional techniques for the management of pain arising from vertebral metastasis include the following:
vertebroplasty; first and/or second thoracic nerve root block, stellate ganglion block, or selective cervical nerve root
block for the cervical region; selective thoracic nerve root block or thoracic sympathetic block for the thoracic
region; first and/or second lumbar nerve root block, lumbar sympathetic block, or selective lumbar nerve root block
for the lumbar region; or epidural neural blockade. Vertebroplasty has been reported to be effective in the
management of vertebral metastasis and is discussed in Chapter 43 . [194] [195]
Anatomy
It is generally agreed that the spinal vertebrae and discs are highly innervated structures in which disease is capable
of causing pain. However, the origin of this innervation is a point of controversy. It is generally accepted that the
posterior portion of the vertebral body and discs are innervated by the sinuvertebral nerve, with one sinuvertebral
nerve innervating two adjacent vertebral segments. However, the exact origin of spinal innervation to the
[196]
anterolateral portion of the vertebral bodies and discs is unclear. It is thought that the sensory innervation of the
anterolateral portion of the vertebral bodies and discs travels with the sympathetic nervous system. In conjunction
[197]
with this theory, it has also been suggested that most of the innervation to the anterolateral portion of the vertebral
bodies and discs below L2 travels through the first or second lumbar nerve root and that the anterolateral portion of
the cervical vertebral bodies and discs travels through the first or second thoracic ganglion. If these theories are true,
bilateral blockade of the first or second lumbar nerve root would result in the relief of pain arising from the
anterolateral vertebral bodies and discs of L2 through L5, and bilateral blockade of the first or second thoracic nerve
root would result in relief of pain arising from the anterolateral vertebral bodies and discs of the cervical spine.
Therefore, based on this discussion, it is important to identify the exact location of the spinal metastasis, because
this will determine what regional techniques, if any, are options for the management of pain.
Cervical Vertebral Pain
STELLATE GANGLION BLOCK
If the pain originates from the anterolateral portion of the cervical vertebrae, a stellate ganglion block may bring
relief. If there is consistent relief of the pain, a continuous technique or a neurolytic technique is indicated. For a
discussion on these techniques, refer to the section on the head and neck.
FIRST AND/OR SECOND THORACIC NERVE ROOT BLOCK
As discussed earlier, the innervation of the anterolateral portion of the cervical vertebral bodies and discs is from the
first or second thoracic nerve. Therefore, a unilateral or bilateral first and/or second thoracic nerve root block may
relieve pain secondary to metastatic disease to the cervical spine. This block is performed under fluoroscopic
guidance, with the patient in the prone position. To interrupt sensory innervation to the anterolateral portion of the
cervical spine, it is necessary to block the nerve root proximal to the rami communicantes. Therefore, the needle tip
should be located inside the neural foramen; this often requires that the needle tip be curved ( Fig. 28–13 A and B).
A volume of one milliliter of local anesthetic is sufficient to block these nerve roots.
719
Complications of a thoracic nerve root block include subarachnoid or epidural injection, which can result in loss of
consciousness, severe hypotension, or respiratory compromise. The operator of the procedure must be skilled in
airway management. A pneumothorax is another potentially life-threatening complication associated with this block.
A block of the first thoracic nerve root may result in motor weakness of the ipsilateral upper extremity.
SELECTIVE CERVICAL NERVE ROOT BLOCK
Pain originating from the posterior cervical vertebral body and posterior spinal segments is innervated by each
segmental cervical nerve. Depending on the extent of the metastatic disease, at least one segment above and below
the lesion are required for pain control. This block is performed under fluoroscopic guidance, with the patient in the
supine position. To block both the sinuvertebral nerve innervating the posterior cervical vertebral body and the
dorsal rami innervating the posterior cervical spinal segments, it is necessary to block the nerve root proximal to the
rami communicantes
Figure 28-13 A, Computed tomography (CT) scan through the pelvis. The dotted line corresponds to the area where the pudendal nerve is
blocked. B, CT-guided pudendal nerve block. The pudendal nerve is located just medial to the apex of the falciform process. The sciatic nerve is
located just lateral to the falciform process. The needle is advanced transgluteally toward the pudendal nerve near the ischium, medial to the
falciform process between the sacrotuberal and sacrospinal ligaments. The final needle position is verified by injecting 0.3 mL of contrast, which
should be distributed in the territory of the pudendal nerve. (From Calvillo O, Skaribas I, Rockett C: Computed tomography–guided pudendal
nerve block. A new diagnostic approach to long-term anoperineal pain: A report of two cases. Reg Anesth Pain Med 25:420–423, 2000.)
720
and dorsal rami; therefore, the needle tip should be located inside the neural foramen. This can be accomplished by
using the lateral approach; however, careful fluoroscopic guidance should be used to avoid entry of the needle tip
into the subarachnoid space. An anterior oblique fluoroscopic view opens the cervical neural foramen. From this
view, the carotid artery should be palpated and identified to avoid passing the needle through the carotid sheath.
Also, the needle should be advanced toward the posterior aspect of the neural foramen to avoid the vertebral artery
in performing blocks at the C6 level and above. A volume of 1 mL of local anesthetic is sufficient to block these
nerve roots.
Complications of a cervical nerve root block include subarachnoid or epidural injection with resulting loss of
consciousness, hypotension and respiratory compromise; vertebral artery injection with local anesthetic toxicity;
ipsilateral upper extremity weakness; phrenic nerve paralysis with upper cervical nerve root blocks; and spinal cord
injection.
Thoracic Spine
THORACIC SYMPATHETIC BLOCK
In the thoracic region, the sympathetic chain lies close to the neck of the ribs; thus, it is very close to the somatic
roots. For pain originating from the anterolateral portion of the thoracic vertebral body and disc, a segmental
thoracic sympathetic block may relieve the pain. At least one segment above and below the lesion are required for
pain relief. The procedure is performed with patient in prone position and under fluoroscopic guidance. The needle
entry site is approximately 3 cm of the midline, and the needle is advanced at approximately a 45-degree angle
under the tranverse process of the desired segment. The needle is advanced until the posterolateral aspect of the
vertebral body is contacted, followed by 2 mL of local anesthetic (see Fig 28–5 ).
Complications of a thoracic sympathetic block include pneumothorax and intrathecal/epidural injection.
SELECTIVE THORACIC NERVE ROOT BLOCK
Pain originating from the posterior thoracic vertebral body and posterior spinal segments is innervated by each
segmental thoracic nerve. Depending on the extent of the metastatic disease, at least one segment above and below
the lesion are required for pain control. The procedure is performed with the patient in a prone position and under
fluoroscopic guidance. To block both the sinuvertebral nerve innervating the posterior thoracic vertebral body and
the dorsal rami innervating the posterior thoracic spinal segments, it is necessary to block the nerve root proximal to
the rami communicantes and dorsal rami. Therefore, the needle tip should be located inside the neural foramen; this
often requires that the needle tip be curved (see Fig. 28–13 A and B). The needle entry site is approximately 3 cm of
the midline, and the needle is advanced at approximately a 45-degree angle under the transverse process of the
desired segment. The needle is then advanced into the neural foramen followed by 1 mL of local anesthetic.
Complications of a thoracic nerve root block include a pneumothorax and intrathecal/epidural injection.
Lumbar Spine
LUMBAR SYMPATHETIC GANGLION BLOCK
If the pain originates from the anterolateral portion of the lumbar vertebrae, a lumbar sympathetic ganglion block
may bring relief. If there is consistent relief from the pain, a continuous technique or neurolytic technique is
indicated. For a discussion on the techniques, refer to the section on the lower extremity.
FIRST AND/OR SECOND LUMBAR NERVE ROOT BLOCK
As discussed earlier, the innervation of the anterolateral portion of the lumbar vertebral bodies and discs is from the
first or second lumbar nerve. Therefore, a unilateral or bilateral first and/or second lumbar nerve root block may
relieve pain secondary to metastatic disease of the lumbar spine. This block is performed under fluoroscopic
guidance with the patient in the prone position. To interrupt sensory innervation to the anterolateral portion of the
lumbar spine, it is necessary to block the nerve root proximal to the rami communicantes. Therefore, the needle tip
should be located inside the neural foramen. This location often requires that the needle tip be curved (see Fig. 28–
11 A and B). A volume of 1 mL of local anesthetic is sufficient to block these nerve roots. See the discussion on
paravertebral block in the lower extremity section for a description of the technique.
721
Complications of a lumbar nerve root block include subarachnoid or epidural injection, which can result in loss of
consciousness, severe hypotension, or respiratory compromise. Skills of airway management are necessary for the
operator of the procedure. A block of the first and second lumbar nerve roots may result in motor weakness of the
ipsilateral lower extremity.
SELECTIVE LUMBAR NERVE ROOT BLOCK
Pain originating from the posterior lumbar vertebral body and posterior spinal segments is innervated by each
segmental lumbar nerve. Depending on the extent of the metastatic disease, at least one segment above and below
the lesion are required for pain control. The procedure is performed in the prone patient under fluoroscopic guidance.
To block both the sinuvertebral nerve innervating the posterior lumbar vertebral body and the dorsal rami
innervating the posterior lumbar spinal segments, it is necessary to block the nerve root proximal to the rami
communicantes and dorsal rami. Therefore, the needle tip should be located inside the neural foramen, which often
requires that the needle tip be curved (see Fig. 28–11 A and B). For a description of the technique, refer to the
paravertebral block discussion in the lower extremity section.
Complications of a lumbar nerve root block include intrathecal/epidural injection and lower extremity numbness and
weakness.
Neurolytic Techniques
If a patient consistently achieves short-term benefits from diagnostic blocks, neurolytic procedures should be
considered. Neurolysis can be achieved with chemical ablation (i.e., alcohol or phenol) or RF lesioning. Because
motor dysfunction is not a problem with the ablation of the thoracic nerve roots and the sympathetic chain, chemical,
cryo-, or RF ablation techniques can be used. However, for the cervical or lumbar nerve roots, debilitating motor
dysfunction can result. For cervical and lumbar nerve root neurolysis, it is recommended that PRF lesioning be used,
which preserves sensory motor function. For a discussion of PRF lesioning, refer to the discussion on neurolysis in
the section on the role of regional anesthetic techniques for the treatment of cancer pain.
CANCER TREATMENT–RELATED PAIN

Postmastectomy Pain
Before treating postmastectomy pain, the area of pain should be identified and therapy directed at the innervating
nerve. For axillary and arm pain, a second intercostal or T2 nerve root block can be performed ( Figs. 28–13 A and
B). For chest wall pain at the mastectomy site, multiple intercostal or thoracic paravertebral nerve blocks (T2–T6)
may be helpful. For phantom nipple pain, a fourth intercostal nerve block can be performed (see Table 28–3 ). If a
prolonged response from these blocks results, repeated blocks are indicated. In addition, this block can be done in
conjunction with physical therapy for patients with shoulder pain and frozen shoulder.
Reflex sympathetic dystrophy (RSD) has been reported to occur after mastectomy. If signs of RSD appear, a
[198]
stellate ganglion block should be considered. If a prolonged response results, repeated blocks should be considered.
RSD may result in a frozen shoulder as the patient attempts to minimize movement secondary to pain. Therefore,
physical therapy in conjunction with the stellate ganglion block should be considered.
Other causes of postmastectomy pain include myofascial pain and scar pain. Myofascial pain of muscles
surrounding the shoulder may be a cause of postmastectomy pain and shoulder dysfunction. Careful examination
may identify trigger points in the muscles of the shoulder girdle. These trigger points may respond to local trigger
point injections followed by physical therapy. Pain within the shoulder joint can result from disuse. Because more
than two thirds of the intra-articular innervation of the shoulder joint is from the suprascapular nerve, blockade of
this nerve performed in conjunction with physical therapy can be very valuable. In addition, a shoulder joint/bursal
[199]
injection of a steroid/local anesthetic mixture may enhance rehabilitation of the shoulder. If scar pain is present,
local infiltration of the scar with a steroid/local anesthetic mixture can result in long-term pain relief.
If significant physical dysfunction persists, a continuous regional technique should be considered. This can be
accomplished with catheters placed in the epidural space, the intrapleural space, or the peripheral nerve. These
infusions should be done together with an aggressive physical therapy program. Infusions prolonged beyond 3 to 4
weeks are probably not beneficial. Clear expectations should be outlined for the patient. If no improvement in
physical function is seen within 2 weeks, the infusion should be discontinued. An epidural infusion can be
accomplished via a percutaneous temporary catheter with an infusion of low concentrations of bupivacaine (1/32 %
to ⅛ %). The tip of the catheter should be placed as close as possible to the dermatomes that supply the axilla and
722
the mastectomy site (T2–T6). Fluoroscopic guidance is useful in guiding the catheter to the site of the pain.
Although less widely used, intrapleural analgesia is conceivably appropriate for postmastectomy pain. This
technique has been described for mammography with needle localization and breast biopsy. The catheter tip
[200]
should be placed more toward the sulcus of the pleural cavity to bathe the intercostal nerves that supply the axilla
and the mastectomy site (T2–T6). Positioning should be with the affected side up for the local anesthetic layer to
reach the costovertebral junction and anesthetize the intercostal nerves. The use of indwelling catheters in the
intercostal space has been described for the treatment of rib fractures and postcholecystectomy pain. Although
[201] [202]
the catheter is placed in one intercostal groove, the local anesthetic may reach multiple intercostal nerves by
spreading vertically into the extrapleural tissue plane. Therefore, this technique can be used to treat chest wall pain
as well as axillary and phantom nipple pain. A continuous suprascapular nerve infusion has been described and may
be used if aggressive physical therapy is required for shoulder pain. [203]
If the patient consistently achieves short-term benefit from the diagnostic blocks, neurolytic procedures should be
considered. It should be kept in mind that these patients are often cured of their disease and that aggressive
neurolysis is not indicated because of the risk of deafferentation pain. For postmastectomy pain, it is recommended
that PRF lesioning be used, which preserves sensory motor function. For a discussion of pulse radiofrequency
lesioning, refer to the discussion of neurolysis in the section on the role of regional anesthetic techniques for the
treatment of cancer pain.
Cryoablation of the second intercostal nerve is also an option for the treatment of postmastectomy pain.
Cryoablation is indicated for pain originating from small, well-localized lesions of peripheral nerves. Because
postmastectomy pain is thought to originate from damage to the second intercostal nerve, this is a reasonable
technique for pain management. The cryolesions should be made at the inferior border of the second rib. Because
[204]
the intercostal nerve runs with a large arterial and venous heat source, two 4-minute cryolesions at each level are
suggested. [204]
Post-thoracotomy Pain
The most common cause of post-thoracotomy pain is surgical damage to the intercostal nerve. Therefore, if regional
techniques are needed, the focus should be on the injured nerve. Initially, an intercostal or thoracic nerve root block
can be performed for diagnostic purposes (see Fig. 28–5 ). If a prolonged response results, repeated blocks are
indicated. In addition, this block can be done in conjunction with physical therapy for patients with chest wall
muscle spasms.
Other causes of thoracotomy pain include myofascial pain and scar pain. Myofascial pain of the chest wall
musculature may be a source of pain. Careful examination may identify trigger points in these muscles. These
trigger points may respond to local trigger point injections followed by physical therapy. If scar pain is present, local
infiltration of the scar with a steroid/local anesthetic mixture can result in long-term pain relief.
If significant physical dysfunction persists the continuous thoracic epidural infusion of local anesthetics should be
considered. This infusion should be done together with an aggressive physical therapy program. This can be
accomplished via a percutaneous temporary catheter with the infusion of low concentrations of bupivacaine (1/32%
to ⅛%). The tip of the catheter should be placed as close to the injured intercostal nerve as possible. Fluoroscopic
guidance is useful in guiding the catheter to the site of the pain. Infusions prolonged beyond 3 to 4 weeks are
probably not beneficial. Clear expectations should be outlined for the patient. If no improvement in physical
function is seen within 2 weeks, the infusion should be discontinued.
If the patient consistently achieves short-term benefit from the diagnostic blocks, neurolytic procedures should be
considered. It should be kept in mind that these patients are often cured of their disease and that aggressive
neurolysis is not indicated because of the risk of deafferentation pain. PRF lesioning and cryoneurolysis of the
intercostal nerve are options (for a discussion of PRF lesioning, refer to the discussion on neurolysis in the section
on the role of regional anesthetic techniques for the treatment of cancer pain).
Postradical Neck Dissection Pain
Causes of postradical neck dissection pain include damage to the cervical plexus leading to neck, arm, and shoulder
pain; and damage to the spinal accessory nerve, leading to shoulder pain and dysfunction. A study reported complete
temporary relief of neuropathic pain symptoms in 17 subjects who underwent a superficial cervical plexus block.
The same study demonstrated a significant reduction in somatic pain of the shoulder area with trigger point
injections. If a prolonged response from these procedures results, repeated blocks are indicated. In addition, these
[82]
procedures can be done in conjunction with physical therapy for patients with shoulder pain and frozen shoulder. If
shoulder pain and stiffness are present, blockade of the suprascapular nerve performed in conjunction with physical
723
therapy can be very valuable. In addition, a shoulder joint/bursal injection of a steroid/local anesthetic mixture
[199]
may enhance rehabilitation of the shoulder.
If significant physical dysfunction persists, a continuous regional technique should be considered. This can be
accomplished via catheters placed in the epidural space or cervical plexus. These infusions should be done together
with an aggressive physical therapy program. Infusions prolonged beyond 3 to 4 weeks are probably not beneficial.
Clear expectations should be outlined for the patient. If no improvement in physical function is seen within 2 weeks,
the infusion should be discontinued (for a discussion of this topic, see the section on the head and neck).
Phantom Limb and Stump Pain
The efficacy of preamputation regional anesthesia in reducing the incidence of phantom limb and stump pain is
controversial. There are few reports in the literature on this issue. Bach and colleagues demonstrated a reduction in
[205]
the incidence of phantom limb pain in the first year after operation by using a lumbar epidural infusion of local
anesthetic and opioid for 72 hours after the surgery. Jahangiri and associates showed similar results with the
[206]
perioperative delivery of epidural diamorphine, clonidine, and bupivacaine on phantom limb pain but no effect on
stump pain. In contrast, Nikolajsen and coworkers showed no effect of perioperative epidural morphine and
[207]
bupivacaine on long-term phantom limb pain or stump pain. In addition, Nikolajsen and colleagues also [208]
demonstrated no long-term effects of perioperative epidural morphine and bupivacaine on stump pain. Using Teflon
catheters placed at the site of the transected sciatic nerve or the posterior tibial nerve, Pinzur and associates [209]
showed no long-term effect on phantom limb pain in a double-blind placebo controlled study.
Patients with stump pain should be closely examined for trigger points, neuromas, and myofascial pain. Local
injections of these areas often result in short-term pain relief. If local treatment is insufficient in managing the pain,
the techniques described earlier, in the discussion of the upper and lower extremities, can be applied for the
management of phantom limb pain.
REFERENCES
1. von Gunten CF (ed): Palliative Care and Rehabilitation of Cancer Patients. Boston, Kluwer Academic, 1999.
2. American Cancer Society Website. Statistics. February 22, 2000.
3. BonicaJJ, Cailliet R: General considerations of pain in the neck and upper limb. In Bonica JJ (ed): The Management of Pain, 2nd ed, vol I.
Philadelphia, Lea and Febiger, 1990, pp 812–847.
4. Jacox
A, Carr DB, Payne R, et al: Management of cancer pain: Clinical practice guidelines number 9. AHCPR publication no. 94-0592.
Rockville, Md, U.S. Department of Health and Human Services, Agency for Health Care Policy and Research, 1994.
5. Jacox A, Carr DB, Payne R: New clinical practice guidelines for the management of pain in patients and with cancer. N Engl J Med 330:651,
1994.
6. Foley KM: Controlling the pain of cancer. Sci Am 275:164, 1996.
7. Blendon RJ, Szalav US, Knox RA: Should physicians aid their patients in dying? The public perspective. JAMA 267:2658, 1992.
8. de Conno F, Ripamonti C, Sbanotto A, et al: The pharmacological management of cancer pain. Ann Oncol 4:267, 1993.
9. Ferrante
FM, Bedder M, Caplan RA, et al: Practice guidelines for cancer pain management. A report by the American Society of
Anesthesiologists Task Force on Pain Management, Cancer Pain Section. Anesthesiology 84:1243, 1996.
10. Lund PC: The role of analgesic blocking in the management of cancer pain: Current trends. A review article. J Med 13:161, 1982.
11. Abrams SE: The role of nonneurolytic nerve blocks in the management of cancer pain. In Abrams SE (ed): Cancer Pain. Boston, Kluwer
Academic, 1989, p 67.
12. Raj PP: Local anesthetic blockade. In Patt RB (ed): Cancer Pain. Philadelphia, JB Lippincott, 1993, pp 329–341.
13. Winnie AP, Collins VJ: Differential neural blockade in pain syndromes of questionable etiology. Med Clin North Am 52:123, 1968.
14. Brull
SJ, Greene NM: Time-courses of zones of differential sensory blockade during spinal anesthesia with hyperbaric tetracaine or
bupivacaine. Anesth Analg 69:342, 1989.
15. Brull SJ, Greene NM: Zones of differential sensory block during extradural anaesthesia. Br J Anaesth 66:651, 1991.
724
16. RoccoAG, Raymond SA, Murray E, et al: Differential spread of blockade of touch, cold, pinprick during spinal anesthesia. Anesth Analg
64:917, 1985.
17. Greene NM: Area of differential block in spinal anesthesia with hyperbaric tetracaine. Anesthesiology 19:45, 1958.
18. Gasser HS, Erlanger J: The role of fiber size in the establishment of nerve block by pressure or cocaine. Am J Physiol 88:581, 1929.
19. Gissen AJ, Covino BG, Gregust J: Differential sensitivities of mammalian nerve fibers to local anesthetic agents. Anesthesiology 53:467, 1980.
20. Turner JA, Deyo RA, Loeser JD, et al: The importance of placebo effects in pain treatment and research. JAMA 271:1609, 1994.
21. Sola AE, Kuitert JH: Myofascial trigger point pain in the neck and shoulder girdle. Northwest Med 54:980, 1955.
22. BonicaJJ: Current role of nerve blocks in the diagnosis and therapy of pain. In Bonica JJ (ed): Advances in Neurology. New York, Raven
Press, 1974, p 445.
23. Loeser JD: Dorsal rhizotomy for the relief of chronic pain. J Neurosurg 36:745, 1972.
24. Travell J, Simons DG: Myofascial Pain and Dysfunction: The Trigger Point Manual. Baltimore, Williams & Wilkins, 1983.
25. Patchell RA, Posner JB: Neurologic complications of systemic cancer. Neurologic Clin 3:729, 1985.
26. Bonica JJ: Causalgia and other reflex sympathetic dystrophies. In Bonica JJ, Liebeskind JC, Albe-Fessard D (eds): Advances in Pain Research
and Therapy, vol 3. New York, Raven Press, 1979, p 141.
27. Bonica JJ: Sympathetic Nerve Blocks for Pain Diagnosis and Therapy. Breon Laboratories, New York, 1984.
28. Sarma VJ: Long-term continuous axillary plexus blockade using 0.25% bupivacaine. Acta Anaesthesiol Scand 34:511, 1990.
29. Ramamurthy S, Winnie AP: Regional anesthetic techniques for pain relief. Semin Anesth IV: 237, 1985.
30. DuPen S, Williams AR: Management of patients receiving combined epidural morphine and bupivacaine for the treatment of cancer pain. J
Pain Symptom Manage 7:125, 1992.
31. KasabaT, Inoue T: The effects of cervical epidural anesthesia on epidural somatosensory evoked potentials and phrenic nerve activities. Masui
46:321, 1997.
32. Nitescu
P, Appelgren L, Linder L-E, et al: Epidural versus intrathecal morphine-bupivacaine: Assessment of consecutive treatments in
advanced cancer pain. J Pain Symptom Manage 5:18, 1990.
33. NitescuP, Sjoberg M, Appelgren L, et al: Complications of intrathecal opioids and bupivacaine in the treatment of “refractory” cancer pain.
Clin J Pain 11:45, 1995.
34. Sjoberg M, Appelgren S, Einarsson E, et al: Long-term intrathecal morphine and bupivacaine in “refractory” cancer pain. I. Results from the
first series of 52 patients. Acta Anaesthesiol Scand 35:30, 1991.
35. Sjoberg
M, Nitescu P, Appelgren L, et al: Long-term intrathecal morphine and bupivacaine in patients with refractory cancer pain.
36. Van Dongen RTM, Crul BJP, De Bock M: Long-term intrathecal infusion of morphine and morphine/bupivacaine mixtures in the treatment of
cancer pain: A retrospective analysis of 51 cases. Pain 55:119, 1993.
37. Berde CB, Sethna NF, Conrad LS, et al: Subarachnoid bupivacaine analgesia of seven months for a patient with a spinal cord tumor.
38. Hanks GW, Trueman T, Twycross RG: Corticosteroids in terminal cancer—a prospective analysis of current practice. Postgrad Med J 59:28,
1983.
39. Elliot
KJ, Portenoy RK: Cancer pain: Pathophysiology and syndromes. In Yaksh TL, Lynch C, Zapol WM, et al (eds): Anesthesia: Biologic
Foundations. Philadelphia, Lippincott-Raven, 1998, pp 803–818.
40. Seeman PM: Membrane stabilization by drugs: tranquilizers, steroids and anaesthetics. Int Rev Neurobiol 9:145, 1966.
41. Hall ED: Acute effects of intravenous glucocorticoids on cat spinal motor neuron electrical properties. Brain Res 240:186, 1982.
42. DevorM, Govin-Lippman R, Raber P: Corticosteroid application blocks transmission in normal nociceptive C-fibers. Acta Anaesthesiol Scand
34:335, 1990.
43. Johansson A, Bennett GJ: Effect of local methylprednisolone on pain in a nerve injury model. Reg Anesth 22:59, 1997.
44. Benzon HT: Epidural steroid injections. Pain Digest 1:271, 1992.
725
45. Langmayr JJ, Obwegeser AA, Schwarz AB, et al: Intrathecal steroids to reduce pain after lumbar disc surgery: A double-blind, placebo-
controlled prospective study. Pain 62:357, 1995.
46. FeldmanS, Behar AJ: Effect of intrathecal hydrocortisone on advanced adhesive arachnoiditis and cerebrospinal fluid pleocystosis: An
experimental study. Neurology 11:251, 1961.
47. Hartmann IT, Winnie AP, Ramamurthy S: Intradural and extradural corticosteroids for sciatic pain. Orthop Rev 3:21, 1974.
48. Abrams SE, O’Connor TC: Complications associated with epidural steroid injections. Reg Anesth 21:149, 1996.
49. Patt
RB: Interventions for intractable cancer pain. In Portenoy RK (ed): Real Patients, Real Problems: Optimal Assessment and Management
of Cancer Pain. Glenview, Illinois, American Pain Society Monograph, 1997, pp 21–30.
50. BrownAS: Current views on the use of nerve blocking in the relief of chronic pain. In Swerdlow M (ed): The Therapy of Pain. Philadelphia,
JB Lippincott, 1981.
51. Sluijter
ME, Cosman ER, Rittman WB, et al: The effects of pulsed radiofrequency fields applied to the dorsal root ganglion—a preliminary
report. Pain Clin 11:109, 1998.
52. Wall PD, Devor M: Sensory afferent impulses originate from dorsal root ganglia as well as from the periphery in normal and nerve injured rats.
Pain 17:321, 1983.
53. Munglani R: The longer term effect of pulsed radiofrequency for neuropathic pain. Pain 80:437, 1999.
54. Arner
S, Rawal N, Gustafsson LL: Clinical experience of long-term treatment with epidural and intrathecal opioids—a nationwide survey.
Acta Anaesthesiol Scand 32:253, 1988.
55. Arner S, Meyerson BA: Lack of analgesic effect of opioids on neuropathic and idiopathic form of pain. Pain 33:1, 1988.
56. Samuelsson H, Malmberg F, Eriksson M, et al: Outcomes of epidural morphine treatment in cancer pain: Nine years of clinical experience. J
57. Eisenach JC, DuPen S, Dubois M, et al: Epidural clonidine analgesia for intractable cancer pain. Pain 61:391, 1995.
58. Wallace MS, Yaksh TL: Long-term intraspinal drug therapy: A review. Reg Anesth Pain Manage 25:117, 2000.
59. Bedder MD, Burchiel K, Larson SA: Cost analysis of two implantable narcotic delivery systems. J Pain Symptom Manage 6:368, 1991.
60. Patt RB: Classification of cancer pain and cancer pain syndromes. In Patt RB (ed): Cancer Pain. Philadelphia, JB Lippincott, 1993, pp 3–22.
61. Rosier RN, Hicks DG, Teot LA, et al: Mechanisms of bone metastasis. APS Bull 7:12, 1997.
62. Pollen JJ, Schmidt JL: Bone pain in metastatic cancer of the prostate. Urology 13:129, 1979.
63. Engel IA, Straus DJ, Lacher M, et al: Osteonecrosis in patients with malignant lymphoma: A review of 25 cases. Cancer 48:1245, 1981.
64. Harrington KD: Orthopedic Management of Metastatic Bone Disease. Washington, DC, CV Mosby, 1988.
65. Edeiken J, Karaskick D: Imaging in cancer. Cancer 37:239, 1987.
66. Thrupkaew AK, Henkin RE, Quin JL: False negative bone scans in disseminated metastatic disease. Radiology 113:383, 1974.
67. Hill EL, Elde R: Distribution of CGRP, VIP, D beta H, SP, and NPY immunoreactive nerves in the periosteum of the rat. Cell Tis Res 264:469,
1991.
68. Hukkanen M, Konttinen YT, Rees RG, et al: Innervation of bone from healthy and arthritic rats by substance P and calcitonin gene related
peptide containing sensory fibers. J Rheumatol 19:1252, 1992.
69. Nielson OS, Munro AJ, Tannock IF: Bone metastases: Pathophysiology and management policy. J Clin Oncol 9:509, 1991.
70. Scher HI, Yagoda A: Bone metastases: Pathogenesis, treatment, and rationale for use of resorption inhibitors. Am J Med 82:6, 1987.
71. Rao S, Badani K, Schildhauer T, et al: Metastatic malignancy of the cervical spine. A nonoperative history. Spine 17(Suppl 10):S407, 1992.
72. StübgenJP: Palliative care rounds: T12 epidural metastasis mimicks pelvic recurrence of cecal adenocarcinoma. J Pain Symptom Manage
11:61, 1996.
73. Ruff RL, Lanska DJ: Epidural metastases in prospectively evaluated veterans with cancer and back pain. Cancer 63:2234, 1989.
74. Grem JL, Burgess J, Trump DL: Clinical features and natural history of intramedullary spinal cord metastasis. Cancer 56:2305, 1985.
726
75. Foley
KM: Overview of cancer pain and brachial and lumbosacral plexopathy. In Foley KM (ed): Management of Cancer Pain. New York,
Memorial Sloan Kettering Cancer Center, 1985, p 25.
76. Horton J: Pain in pancreatic cancer. In Foley KM, Payne RM (eds): Current Therapy of Pain. Philadelphia, Marcel Dekker, 1989, pp 332–341.
77. Wallace MS, Wallace AM, Lee J, et al: Pain after breast surgery: A survey of 282 women. Pain 66:195, 1996.
78. Wallace
AM, Dobke MK, Wallace MS: Breast Pain. In Biebuyck J (ed): Anesthesia: Biologic Foundations. Philadelphia, Lippincott-Williams
& Wilkins, 1997, pp 849–857.
79. Kroner K, Knudsen UB, Lundby L, et al: Long-term phantom breast syndrome after mastectomy. Clin J Pain 8:346, 1992.
80. Scov J, Kroner K, Krebs B, et al: Pain and dysesthesias in the mastectomy scar. Ugeskr Laeger 152:3081, 1990.
81. Wallace MS: Postthoracotomy Pain. In Biebuyck J (ed): Anesthesia: Biologic Foundations. Philadelphia, Lippincott-Williams & Wilkins, 1997,
pp 841–848.
82. Sist T, Miner M, Lema M: Characteristics of postradical neck pain syndrome: A report of 25 cases. J Pain Symptom Manage 18:95, 1999.
83. Swift TR, Nichols FT: The droopy shoulder syndrome. Neurology 34:212, 1984.
84. Krause
HR: Shoulder-arm-syndrome after radical neck dissection: Its relation with the innervation of the trapezius muscle. Int J Oral
Maxillofac Surg 21:276, 1992.
85. Terrell JE, Welsh DE, Bradford CR, et al: Pain, quality of life, and spinal accessory nerve status after neck dissection. Laryngoscope 110:620,
2000.
86. Hanowell S, Lees DE, MacNamara T: Auriculotemporal syndrome after combined modality therapy for cancer. South Med J 72:1116, 1979.
87. Foley KM: Pain syndromes in patients with cancer. Med Clin North Am 71:169, 1987.
88. Johnstone
PA, DeLuca AM, Bacher JD, et al: Clinical toxicity of peripheral nerve to intraoperative radiotherapy in a canine model. Int J Radiat
Oncol Biol Phys 32:1031, 1995.
89. Parsons JT, Bova FJ, Fitzgerald CR, et al: Radiation optic neuropathy after megavoltage external-beam irradiation: Analysis of time-dose
factors. Int J Radiat Oncol Biol Phys 30:755, 1994.
90. VujaskovicZ, Gillette SM, Powers BE, et al: Ultrastructural morphometric analysis of peripheral nerves after intraoperative irradiation. Int J
Radiat Biol 68:71, 1995.
91. Gillette EL, Mahler PA, Powers BE, et al: Late radiation injury to muscle and peripheral nerves. Int J Radiat Oncol Biol Phys 31:1309, 1995.
92. Mollman JE, Glover DJ, Hogan DJ, et al: Cisplatin neuropathy: Risk factors, prognosis, and protection by WR-2721. Cancer 61:2192, 1988.
93. Carron H: Control of pain in the head and neck. Otolaryngol Clin North Am 14:631, 1981.
94. Shapshay SM, Scott RM, McCann CF, et al: Pain control in advanced and recurrent head and neck cancer. Otolaryngol Clin North Am 13:551,
1980.
95. Rizzi R: Nerve block in the treatment of cranio-facial pain. Minerva Stomatol 24:112, 1975.
96. Bonica JJ, Madrid JL: Cancer pain in the head and neck. Role of nerve blocks. In Bonica JJ, Liebeskind JC, Albe-Fessare D (eds): Advances in
Pain Research and Therapy, vol 3. New York, Raven Press, 1979.
97. PappasJL, Kahn CH, Kahn MD, et al: Cervical plexus blockade. In Waldman S, Winnie A (eds): Interventional Pain Management.
98. Brown DL: Cervical plexus block. In Brown DL (ed): Atlas of Regional Anesthesia. Philadelphia, WB Saunders, 1992, pp 165–170.
99. Masters RD, Castresana EJ, Castresana MR: Superficial and deep cervical plexus block: Technical considerations. AANA J 63:235, 1995.
100. Patt
RB, Cousins MJ: Techniques for neurolytic neural blockade. In Cousins MJ, Bridenbaugh PO (eds): Neural Blockade in Clinical
Anesthesia and Management of Pain, 3rd ed. Philadelphia, Lippincott-Raven, 1998, pp 1007–1061.
101. Moore DC: Intercostal nerve block combined with celiac plexus (splanchnic) block. In Moore DC (ed): Regional Block: A Handbook for Use
in Clinical Practice of Medicine and Surgery. 4th ed. Springfield, CC Thomas, 1967, pp 145–162.
102. Winnie AP, Ramamurthy S, Durrani Z, et al: Interscalene cervical plexus block. Anesth Analg 54:370, 1975.
103. Mullin V: Brachial plexus block with phenol for painful arm associated with Pancoast’s syndrome. Anesthesiology 53:431, 1980.
727
104. Neill R: Ablation of the brachial plexus. Anesthesia 34:1024, 1979.
105. Catchlove RF, Braha R: The use of cervical epidural nerve blocks in the management of chronic head and neck pain. Can Anaesth Soc J
31:188, 1984.
106. Huang CH, Hsu JL, Chen WS: Effects of lidocaine cervical epidural blockade on respiratory function. Ma Tsui Hsueh Tsa Chi 28:311, 1990.
107. Santanche G, Goedecke A: Hemodynamic and respiratory changes in cervical peridural anesthesia. Reg Anesth 12:110, 1989.
108. Biboulet P, Deschodt J, Capdevila X, et al: Hemodynamic effects of 0.375% versus 0.25% bupivacaine during cervical epidural anesthesia for
hand surgery. Reg Anesth 20:33, 1995.
109. ArakawaM, Amemiya N, Nagai K, et al: Effects of epidural analgesia combined with general anesthesia on hemodynamics during neck
surgery. Masui 42:1464, 1993.
110. Raj PP, Rauck RL, Racz GB: Autonomic Nerve Blocks in Pain Medicine: A Comprehensive Review. St. Louis, Mosby, 1996, pp 227–255.
111. Currey TA, Dalsania J: Treatment for herpes zoster ophthalmicus: Stellate ganglion block as a treatment for acute pain and prevention of
postherpetic neuralgia. Ann Ophthalmol 23:188, 1991.
112. Arden RL, Bahu SJ, Zuazu MA, et al: Reflex sympathetic dystrophy of the face: Current treatment recommendations. Laryngoscope 108:437,
1998.
113. Hogan Q: Stellate ganglion. In Hahn MB, McQuillan PM, Sheplock GJ (eds): Regional Anesthesia: An Atlas of Anatomy and Techniques. St.
Louis, Mosby-Year Book, 1996, pp 169–174.
114. Jain S: Neurolytic procedures for cancer pain management. In Lefkowitz M, Lebovits SA (eds): A Practical Approach to Pain Management.
Boston, Little, Brown, 1996, pp 107–108.
115. LinsonMA, Leffert R, Todd DP: The treatment of upper extremity reflex sympathetic dystrophy with prolonged continuous stellate ganglion
blockade. J Hand Surg 8:153, 1983.
116. Arter O, Racz G: Pain management in the oncologic patient. Adv Pain Res Ther 4:135, 1990.
117. Christie J, Martinez C: Computerized axial tomography to define the distribution of solution after stellate ganglion nerve block. J Clin Anesth
7:306, 1995.
118. Wilkinson HA: Percutaneous radiofrequency upper-thoracic sympathectomy: A new technique. Neurosurgery 15:811, 1984.
119. Wilkinson HA: Radiofrequency percutaneous upper-thoracic sympathectomy: Technique and review of indications. N Engl J Med 311:34,
1984.
120. Geurts JWM, Stolker RJ: Percutaneous radiofrequency lesion of the stellate ganglion in the treatment of pain in upper extremity reflex
sympathetic dystrophy. Pain Clin 6:17, 1993.
121. Frothingham RE, Atchison JW, Bailey CC: Treatment of facial pain by percutaneous injection of the gasserian ganglion. J South Carolina
Med Assoc 70:1650, 1974.
122. Greenberg C, Papper EM: The indications for gasserian ganglion block for trigeminal neuralgia. Anesthesiology 31:566, 1969.
123. Tew JM, Keller JT: The treatment of trigeminal neuralgia by percutaneous radiofrequency technique. Clin Neurosurg 24:577, 1977.
124. Feldstein G: Percutaneous retrogasserian glycerol rhizotomy. In Racz G (ed): Techniques of Neurolysis. Boston, Kluwer, 1989, pp 126–128.
125. Raj PP: Prognostic and therapeutic local anesthetic blockade. In Cousins MJ, Bridengaugh PO (eds): Neural Blockade. Philadelphia, JB
126. Babacan A, Ozteurk E, Kaya K: Relief of chronic refractory hiccups with glossopharyngeal nerve block [letter comment]. Anesth Analg
87:980, 1998.
127. Gallacher BP, Martin L: Treatment of refractory hiccups with glossopharyngeal nerve block [letter]. Anesth Analg 84:229, 1997.
128. Bajaj P, Gemavat M, Singh DP: Ninth cranial nerve block in the management of malignant pain in its territory. Pain Clin 6:153, 1993.
129. Funasaka S, Kodera K: Intraoral nerve block for glossopharyngeal neuralgia. Arch Otorhinolaryngol 215:311, 1977.
130. Bonica JJ, Ventafridda V, Twycross RG: Cancer pain. In Bonica JJ (ed): The Management of Pain, vol I, 2nd ed. Philadelphia, Lea and
Febiger, 1990, pp 400–460.
131. Jaeckle K: Nerve plexus metastases. Neurol Clin 9:857–866, 1991.
728
132. Marmor L: Solitary peripheral nerve tumors. Clin Orthop 43:183, 1965.
133. Gerard J, Frank N, Moussa Z, et al: Acute ischemic brachial plexus neuropathy following radiation therapy. Neurology 39:450, 1989.
134. Patt RB: Peripheral neurolysis and the management of cancer pain. In Patt RB (ed): Cancer Pain. Philadelphia, JB Lippincott, 1993, pp 359–
376.
135. SwerdlowM: Spinal and peripheral neurolysis for managing Pancoast syndrome. In Bonica JJ, Ventafridda V, Pagni CA (eds): Advances in
Pain Research and Therapy, vol 4. New York, Raven Press, 1982, p 135.
136. Swerdlow M: Neurolytic blocks of the neuraxis. In Patt RB (ed): Cancer Pain. Philadelphia, JB Lippincott, 1993, pp 427–442.
137. Ichiyanagi K, Matsuki M, Kinefuchi S, Kato Y: Progressive changes in the concentrations of pheno and glycerine in the human subarachnoid
space. Anesthesiology 42:622, 1975.
138. Racz GB, Heavner J, Haynsworth P: Repeat epidural phenol injections in chronic pain and spasticity. In Lipton S, Miles J (eds): Persistent
Pain: Modern Methods of Treatment, vol 5. Orlando, FL, Grune and Stratton, 1985, p 157.
139. Korevaar W: Transcatheter thoracic epidural neurolysis using ethyl alcohol. Anesthesiology 73:491, 1990.
140. Cousins
MJ, Dwyer B, Gibb D: Chronic pain and neurolytic neural blockade. In Cousins MJ, Bridenbaugh PO (eds): Neural Blockade in
Clinical Anesthesia and Management of Pain, 2nd ed. Philadelphia, JB Lippincott, 1988, pp 1053–1084.
141. Kaplan R, Aurellano Z, Pfisterer W: Phenol brachial plexus block for upper extremity cancer pain. Reg Anesth 13:58, 1988.
142. Sato S, Yamashita S, Iwai M, et al: Continous interscalene block for cancer pain. Reg Anesth [letter]. 19:73, 1994.
143. Haasio J, Rosenberg PH: Continuous supraclavicular brachial plexus anesthesia. Tech Reg Anesth 1:4, 1997.
144. Raj P: Infraclavicular approach to brachial plexus anesthesia. Tech Reg Anesth 1:4, 1997.
145. Kori S, Foley K, Posner J: Brachial plexus lesions in patients with cancer. Neurology 31:45, 1981.
146. Bonica JJ, Buckley FP, Moricca G, et al: Neurolytic blockade and hypophysectomy. In Bonica JJ (ed): The Management of Pain, vol II, 2nd
ed. Philadelphia, Lea and Febiger, 1990, pp 1980–2039.
147. Colemen R: Skeletal complications of malignancy. Cancer 80(Suppl):8, 1997.
148. Osborn JL, Getzenberg R, Trump D: Spinal cord compression in prostate cancer. J Neurooncol 23:135, 1995.
149. Churcher M: Peripheral nerve blocks in the relief of intractable pain. In Swerdlow M, Charlton J (eds): Relief of Intractable Pain, 4th ed.
Amsterdam, Elsevier, 1989, p 195.
150. Moore D, Bridenbaugh D: Intercostal nerve blocks in 4333 patients: Indications, techniques, complications. Anesth Analg 41:1, 1962.
151. Moore D: Intercostal nerve block and celiac plexus block for pain therapy. Adv Pain Res Ther 7:309, 1984.
152. Vernon S: Paralgesia: Paravertebral block for pain relief. Am J Surg 21:416, 1930.
153. Thompson GE: Intercostal nerve block. In Waldman SD, Winnie AP (eds): Interventional Pain Management. Philadelphia, WB Saunders,
1996, pp 311–317.
154. Atkinson G, Shupack R: Acute bronchospasm complicating intercostal nerve block with phenol. Anesth Analg 68:1, 1989.
155. Doyle D: Nerve blocks in advanced cancer. Practitioner 226:539, 1982.
156. Pastor J, Morales P, Cases E, et al: Evaluation of intercostal cryoanalgesia versus conventional analgesia in postthoracotomy pain. Respiration
63:241, 1996.
157. Green C, deRosayro A, Tait A, et al: Long-term follow-up of cryoanalgesia for chronic thoracic pain. Reg Anesth 18:46, 1993.
158. Thompson G, Moore D: Celiac plexus, intercostal and minor peripheral blockade. In Cousins M, Bridenbaugh P (eds): Neural Blockade, 2nd
ed. Philadelphia, Lippincott, 1988, pp 503.
159. Bonica J: Management of pain of malignant disease with nerve blocks. Anesthesiology 15:134, 1954.
160. Jain S, Kestenbaum A, Khan Y: Ethanol or phenol for peripheral neurolysis? Does it make a difference. Pain (Suppl):S92, 1990.
729
161. Conacher I, Korkri M: Postoperative paravertebral blocks for thoracic surgery: A radiological appraisal. Br J Anesth 59:155, 1987.
162. Stolker R, Verest A, Groen G: The treatment of chronic thoracic segmental pain by radiofrequency percutaneous partial rhizotomy. J
Neurosurg 80:986, 1994.
163. VanKleef M, Gerard A, Barends M, et al: Effects of producing a radiofrequency lesion adjacent to the dorsal root ganglion in patients with
thoracic segmental pain. Clin J Pain 11:325, 1995.
164. Bonica
JJ: Chest pain related to cancer. In Bonica JJ (ed): The Management of Pain, vol II, 2nd ed. Philadelphia, Lea and Febiger, 1990, pp
1083–1113.
165. Kline
MT: Radiofrequency techniques in clinical practice. In Waldman SD, Winnie AP (eds): Interventional Pain Management. Philadelphia,
166. O’Leary K, Myers M: Interpleural analgesia and neurolysis. Tech Reg Anesth Pain Manage 1:11, 1997.
167. Myers DP, O’Leary KA, Lema MJ: Interpleural catheters: Indications and techniques. In Waldman SD, Winnie AP (eds): Interventional Pain
Management. Philadelphia, WB Saunders, 1996, pp 319–323.
168. Lema M, Myers D, deLeon-Casasola O: Pleural phenol for the treatment of chronic esophageal cancer pain. Reg Anesth 17:166, 1992.
169. Patt RB, Reddy SK, Black RG: Neural blockade for abdominal pain of oncologic origin. Int Anesthesiol Clin 36:87, 1998.
170. de Leon-Casasola OA: Critical evaluation of chemical neurolysis of the sympathetic axis for cancer. Cancer Control 7:142, 2000.
171. Brown DL: A retrospective analysis of neurolytic celiac plexus block for nonpancreatic intra-abdominal cancer pain. Reg Anesth 14:63, 1989.
172. Sharfman WH, Walsh TD: Has the analgesic efficacy of neurolytic celiac plexus block been demonstrated in pancreatic cancer pain? Pain
41:267, 1990.
173. Eisenberg E, Carr DB, Chalmers TC: Neurolytic celiac plexus block for treatment of cancer pain: A meta-analysis. Reg Anesth Pain Manag
80:290, 1995.
174. Ischia S, Luzzani A, Ischia A, et al: A new approach to the neurolytic block of the celiac plexus: The transaortic technique. Pain 16:333, 1983.
175. Lopez M: Neurolytic block of the celiac plexus by transcrural and transaortic techniques. Rev Esp Anesthesiol Reanim 34:340, 1987.
176. Feldstein G, Waldman SD: Loss of resistance technique for transaortic celiac plexus block. Anesth Analg 65:1089, 1986.
177. Plancarte R, Amescua C, Patt RB, et al: Superior hypogastric plexus block for pelvic cancer pain. Anesthesiology 73:236, 1990.
178. de Leon Casasola OA, Kent E, Lema MJ: Neurolytic superior hypogastric plexus block for chronic pelvic pain associated with cancer. Pain
54:145, 1993.
179. Plancarte R, de Leon-Casasola OA, El-Helaly M: Neurolytic superior hypogastric plexus block for chronic pelvic pain association with cancer.
Reg Anesth 22:562, 1997.
180. de Leon Casasola OA, Plancarte-Sanchez R, Patt RB, Lema MJ: Superior hypogastric plexus block using a single needle and computed
tomography guidance. Reg Anesth 18:63, 1993.
181. Jaeckle KA, Young DF, Foley KM: The natural history of lumbosacral plexopathy in cancer. Neurology 35:8, 1985.
182. Pettigrew LC, Glass JP, Maur VP, et al: Diagnosis and treatment of lumbosacral plexopathy in patients with cancer. Arch Neurol 41:1282,
1984.
183. Posner JB: Back pain and epidural spinal cord compression. Med Clin North Am 71:185, 1987.
184. CalavaJM, Patt RB, Reddy S, et al: Psoas sheath chemical neurolysis for management of intractable leg pain from metastatic liposarcoma.
Clin J Pain 12:69, 1996.
185. Boas RA, Schug SA, Acland RH: Perineal pain after rectal amputation: A 5-year follow-up. Pain 52:67, 1993.
186. Radbruch L, Zech D, Grond S, et al: Perineal pain and rectal cancer—prevalence in local recurrence. Med Klin 86:180, 228, 1991.
187. Porges P, Zdrahal F: Intrathecal alcohol neurolysis of the lower sacral roots in inoperable rectal cancer. Anaesthesist 34:627, 1985.
188. Evans PJ, Lloyd JW, Jack TM: Cryoanalgesia for intractable perineal pain. J R Soc Med 74:804, 1981.
189. Calvillo O, Skaribas I, Rockett C: Computed tomography–guided pudendal nerve block. A new diagnostic approach to long-term anoperineal
pain: A report of two cases. Reg Anesth Pain Med 25:420, 2000.
730
190. Clemente CD: The perineum and pelvis. In Anatomy: A Regional Atlas of the Human Body, 3rd edition. Baltimore, Urban & Schwarzenberg,
1987, p 290.
191. Irving GA, Wallace MS: Chronic perineal pain. In Pain Management for the Practicing Physician. Philadelphia, Churchill-Livingstone, 1997,
pp 203–208.
192. Uppington
J, Warfield CA: Perineal pain. In Warfield CA (ed): Principle and Practice of Pain Management: Perineal Pain. New York,
McGraw-Hill, 1993, pp 153–166.
193. Wesselmann U, Burnett AL, Heinberg W: The urogenital and rectal pain syndromes. Pain 73:269, 1997.
194. Cotten A, Boutry N, Cortet B, et al: Percutaneous vertebroplasty: State of the art. Radiographics 18:311, 1998.
195. Gangi A, Kastler BA, Dietemann JL: Percutaneous vertebroplasty guided by a combination of CT and fluoroscopy. Am J Neuroradiol 15:83,
1994.
196. Parke WW: Applied anatomy of the spine. In Herkowitz HN, Garfin SR, Balderston RA, et al (eds): The Spine. Philadelphia, WB Saunders,
1992, pp 29–73.
197. Bogduk N: The innervation of the lumbar spine. Spine 8:286, 1983.
198. Saddison DK, Vanek VW: Reflex sympathetic dystrophy after modified radical mastectomy: A case report. Surgery 114:116, 1993.
199. Brown DE, Roy JS: Pain relief by suprascapular nerve block in gleno-humeral arthritis. Scand J Rheumatol 17:411, 1988.
200. Schlesinger
TM, Laurito CE, Carranzo C, et al: Intrapleural anesthesia for mammography with needle localization and breast biopsy.
201. O’Kelly E, Garry B: Continuous pain relief for multiple fractured ribs. Br J Anaesth 53:989, 1981.
202. Murphy DF: Continuous intercostal nerve blockade for pain relief following cholecystectomy. Br J Anaesth 55:521, 1983.
203. Breen TW, Haigh JD: Continuous suprascapular nerve block for analgesia of scapular fracture. Can J Anaesth 37:786, 1990.
204. Saberski
LR: Cryoneurolysis in clinical practice. In Waldman SD, Winnie AP (eds): Interventional Pain Management. Philadelphia, WB
Saunders, 1996, pp 172–184.
205. Bach S, Noreng MF, Tielden NU: Phantom limb pain in amputees during the first 12 months following limb amputation, after preoperative
lumbar epidural blockade. Pain 33:297, 1988.
206. Jahangiri M, Jayatunga AP, Bradley JW, et al: Prevention of phantom pain after bupivacaine. Ann R Coll Surg Engl 76:324, 1994.
207. NikolajsenL, Ilkjaer S, Christensen JH, et al: Randomised trial of epidural bupivacaine and morphine in prevention of stump and phantom
pain in lower-limb amputation. Lancet 350:1353, 1997.
208. Nikolajsen
L, Ilkjaer S, Jensen TS: Effect of preoperative extradural bupivacaine and morphine on stump sensation in lower limb amputees.
Br J Anaesth 81:348, 1998.
209. Pinzur MS, Garla PG, Pluth T, Vrbos L: Continuous postoperative infusion of a regional anesthetic after an amputation of the lower extremity.
A randomized clinical trial. J Bone Joint Surg Am 78:1501, 1996.
731
Section V Chapter 29 - Untreated Pain and Its Cost to Society
Section V - Advanced Interventional Techniques in Regional

Anesthesia
Gabor B. Racz
732
Chapter 29 - Untreated Pain and Its Cost to Society: What Are Our
Options?
ELLIOT S. KRAMES
FRANCIS S. PECORARO
Pain is ubiquitous in any human society and is a natural aspect of the human condition. Writing about pain can be
traced back to the beginnings of recorded history, and they have continued uninterrupted. Because pain can occur in
the absence of visible disease, in the past, more emphasis was placed on stopping pain and less on understanding its
etiology. Theophrastus (372 BC–287 BC), a Greek philosopher, proposed that pain was not experienced externally but
internally. He believed that all humans had the ability to experience pain and that the brain was the main organ for
processing pain. However, it was not until later (300 AD) that it became known that the brain was not only
responsible for processing pain but for sensory input, and motor output as well. Nevertheless, a considerable lack of
understanding regarding pain and its central and peripheral processes remained. [1]
Galen (c. 129 AD–c. 200 AD), a Greek physician who lived in Rome, believed strongly in the link between mind and
body. Through a series of physiologic experiments, he was able to elucidate a connection between the peripheral
nervous system and the central nervous system. The understanding of this connection was helpful in turning the
treatment of pain from external or nonmedical therapy, such as physical manipulation or spiritual remedies, to more
internal medical management. These early internal remedies came mostly in the form of herbal concoctions for the
[2]
relief of pain. Since then, our understanding of pain and the remedies for its relief has developed significantly.
Melzack’s and Wall’s gate control theory led the way for a less empiric and more scientific approach to treating
[3]
pain. In 1965, it was known that large-diameter nerve fibers inhibit nervous transmission and that small-diameter
nerve fibers encourage nervous transmission. Melzack and Wall hypothesized that large-diameter fibers inhibit
nerve transmission of small-diameter nerve fibers and that this control occurs at the spinal cord level. Additionally,
this spinal locus of control, or modulation of noxious information, was influenced by descending input from the
brain. This control from higher central neural centers is now called central control. Thus, central modulatory control
incorporates higher cortical functions, such as those responsible for cognition, motivation, and emotion, on the
modulation of pain. With the elucidation of the gate control theory, innovations in the treatment of chronic pain—
[3]
specifically neuropathic pain—have evolved. Despite all the current advances in the study and understanding of pain,
one successful treatment of all types of chronic pain remains elusive. What exist today are multiple treatment
options. This chapter attempts to place these options in a logical algorithm that apparently makes order out of chaos.
Chronic Pain
EUDYNIA AND MALDYNIA
To discuss the topic of chronic pain (maldynia), one must understand acute pain (eudynia). The International
Association for the Study of Pain (IASP) defines acute pain as an unpleasant sensory and emotional experience
associated with actual and potential tissue damage and also describes pain in terms of tissue damage. The latter
[4]
type of pain has biologic usefulness in that the experience locates body areas that are being “attacked” by external or
internal noxious inputs, while activating “fight or flight mechanisms.” The perception of acute pain, or eudynia, is
preceded by activation of nociceptors. These are discrete functional anatomic entities, ubiquitous in the body, which
transduce the noxious inputs into electrical energy and which in turn are transmitted via the peripheral and central
nervous system to the brain. There is appreciation of cause and effect with this process of nociception. The
foundation of acute pain management is pharmacologic treatment, which generally relies on the use of opioids and
nonsteroidal anti-inflammatory drugs for relatively short periods of time until there is no longer tissue damage and
ongoing nociception. Relief of nociceptive, acute pain is expected by both patients and caregivers alike. In acute
pain, cause and effect, nociception, and the typical animal response to pain can be readily appreciated. However, in
chronic pain, this cause and effect relationship is not always clear.
The IASP defines chronic pain as pain that persists longer than 3 to 6 months, or pain that extends beyond the
[4]
expected period of healing. Verhaak and colleagues referred to chronic pain that has no obvious persistent cause or
[6]
identifiable pathology as chronic benign pain. A cause and effect relationship is not always appreciated with the
experience of chronic pain. Relief of chronic pain is a goal that may not, in fact, be achieved.
733
THE PREVALENCE OF CHRONIC PAIN
The prevalence of chronic benign pain in industrialized countries has been estimated at 25% to 30%. However, [5]
others have found the prevalence of chronic pain in the general population to be from 2% to 40%, with a median
point prevalence of 15%. The most common areas of the body in which pain occur are the low back, neck, and
shoulder. Frølund stated that the most common areas were bone and joint (24%), muscle and ligament (17%), low
[6]
back (13%), and head (headache) (2%). A study by Elliott suggests that the prevalence of chronic pain in the
[7] [8]
present day general population is approximately 46.5%, with one third of this population having a diagnosis of low
back pain or osteoarthritis. The relative variations in prevalence of chronic pain reported in different studies are
probably secondary to the particular research methods and the populations studied. Clearly, the prevalence of
chronic pain in the United States is high, and, undoubtedly, the socioeconomic impact of chronic pain is great.
WHO GETS CHRONIC PAIN?
When incidence and prevalence of chronic pain are studied, there are obvious gender and age variations. For
example, men have a higher prevalence of ankylosing spondylitis and angina related to coronary artery disease,
whereas women have a higher prevalence of fibromyalgia headache and arthritis. [9]
In examining predisposition to chronic pain in 1994, Harkins reported that 80% to 85% of all persons with disease
[10]
have some form of chronic pain after age 65. In addition, individuals in nursing homes have a higher incidence of
pain than age-matched individuals living in the community. Cognitive impairment among older individuals
increases the reporting of pain complaints. Interestingly, in the Iowa 65+ study, a statistically significant lower
[11]
prevalence of pain was reported in individuals older than 85 years of age. This finding was supported by Brattberg
and associates in 1996. It has been suggested that a leveling off of pain complaints occurs at around 65 years of age,
and that the incidence of pain complaints tapers from there. Explanations for these findings have been lacking, but
Harkins has suggested that the decrease in the prevalence of pain in the individuals older than 65 years is perhaps
[12]
secondary to a higher mortality rate. Changes in nociception, such that the intensity of pain experienced by the
[12]
elderly is less than in younger individuals, has also been suggested as a reason for the decrease in pain reporting. [13]
Pain-related disabilities and chronic pain are also seen in the young population. Thirty to forty percent of children
complain of pain at least once per week. The most common pain complaints of children and adolescents are
[14] [15]
various musculoskeletal complaints (32.1%), headache (30.5%), and abdominal pain (10%). Adult manifestations
[16]
of childhood chronic pain may take the form of anxiety and depression. Early diagnosis and treatment of children
[17]
and adolescents with pain is essential for maintaining normal development and a healthy state of well-being. Being
able to participate in peer-related activities is critical to the psychological and social development of a young person.
WHY DO PEOPLE HAVE CHRONIC PAIN?
It is well known that mechanical, chemical, or thermal excitation activation of the nociceptors causes pain. With
tissue damage, algesic substances in the form of prostaglandins, histamine, bradykinin, and various endogenous
chemicals (Na+ , substance p glutamate, aspartate) are released locally and stimulate chemical nociceptors. Certain
algesic substances, such as histamines, actually cause an increase in local blood flow secondary to increased
capillary permeability. This in turn serves to increase pain as more algesic substances are brought into proximity
with these nociceptors. As nociceptors are continually activated, they actually become “sensitized” (peripheral
sensitization of nociceptors) to the point at which previously nonnoxious stimuli become noxious. This pathological
state leads to the abnormal cutaneous dysesthesias of hyperpathia and allodynia. As long as the inflammatory
[18]
response is present, the peripheral pain mechanism is activated.
As nociceptors become sensitized, a positive spinal reflex feedback loop is set up, which further enhances the
abnormal nociceptor response. In addition to increased sympathetic outflow as a response to ongoing nociception,
this exaggerated nociceptor response can result in poor body mechanics, guarding, and, perhaps, exacerbation of the
primary pain complaint. Other peripheral mechanistic theories have been offered, including the idea that increased
[19]
activity of damaged nerve axons leads to collateral sprouting from these axons. Additionally, there is a theory that
tissue damage and nociceptor activation lead to unmasking of silent nociceptors and sympathetic postganglionic
fiber infiltration of the dorsal root ganglia. It is in the above settings that one can understand how an acute pain
process may become chronic.
Although one should look at these peripheral mechanisms to better understand chronic pain, the central theories for
the existence of chronic pain must also be considered. Central pain may be the result of central nervous system
lesions either in the brain or spinal cord. Central pain is characterized most commonly by burning sensations;
however, shooting, numb, and tingling sensations are not uncommon. Collectively, these descriptors constitute what
734
is called the neuropathic pain experience. Neuropathic pain as described by Bonica is further subdivided into
spontaneous, steady, neuropathic pain; neuralgic pain, and evoked neuropathic pain. Evoked pain sensations are
typically allodynia, hyperalgesia, and hyperpathia.
Central sensitization or spinal wind-up is one leading explanation for the phenomenon of chronic pain. In central
sensitization, alterations in the biochemistry of primary afferents lead to the changes in the nociceptive process
discussed earlier. Therapies for this central pain have been varied according to the mechanism impacted as well as
their use and efficacy. Spinal cord stimulation (SCS) and intrathecal analgesic manipulation with opioids and
nonopioids alike have been shown to be effective and have an impact on both peripheral neuropathic pain
mechanisms and some central pain state mechanisms.
COST OF CHRONIC UNRELIEVED PAIN
In the United States, the costs of unrelieved pain and disability arising from chronic pain are and will continue to be
a major problem until appropriate, cost-effective algorithms for the management of chronic pain are created and
implemented. Chronic unrelieved pain is not only a major drain on scarce healthcare resources but is the cause of
untold suffering of millions of people worldwide. The direct, hard costs of unrelieved pain to patients and their
families are loss of job, income, savings (and therefore security), and insurance. More intangible consequences of
unrelieved pain include loss of self-esteem, depression, anger, frustration, and suffering. The end result of these
direct and indirect costs of unrelieved pain is staggering to society and to the individuals who unfortunately suffer
from it. Approximately 30% of the United States population, or approximately 70,000,000 persons, suffer from
chronic pain. Given these alarming data, it is not difficult to imagine the impact of chronic pain on society as a
[20]
whole as well as on the family and the individual.
On a societal level, costs are incurred by lost productivity, ever-increasing insurance premiums, medical care costs,
and the overwork burden inherent in workplace absenteeism. It is well known that chronic pain patients use health
services much more frequently than nonpain patients. In two studies by Von Korff and coworkers, chronic pain
[21] [22]
patients were almost 5 times more likely to visit some form of healthcare setting. Fourteen percent of the adult
population in the United States complains of low back pain, which is the most common cause of workdays missed
and workman’s compensation claims. Labor productivity losses resulting from low back pain claims are estimated
[23]
to be $25 billion per year, and 31 million people per year have lost workdays secondary to low back pain. In
[24] [25] [26]
1991, Frymoyer and Cats-Baril published a study estimating the direct and indirect cost to society of both work-
related and non–work-related low back pain. Their finding was a staggering $27.9 billion for these indirect and
direct costs.
Back injuries sustained at work tend to be more expensive to manage medically and involve more time lost from
work. The cost of low back pain claims to employers in industries such as construction ranges from $10 to $40
[27]
billion per year. Lifetime risk for low back pain in the general population is estimated between 60% and 85%, and
[28]
chronic pain is the most common disability that impairs quality of life. There are 11 million visits per year to
[29]
healthcare professionals for low back pain. [30] [31]
In the Michigan Pain Study, pain was responsible for 400,000 workers, or 12% of the Michigan work force, failing
[32]
to show up for work at some point during 1997. Of those surveyed, 35% missed more than 20 days of work in the
same year. In a 1992 study on the dollar impact on 12 diverse and large United States businesses, disability cost
these businesses an average of $2500 per employee. [32]
The effect of chronic pain on family members can be overwhelming. Ongoing family difficulties and stress,
including overwhelming caretaking burdens, family discord, and loss of financial stability can be devastating. On [33] [34]
an individual basis, chronic pain limits functioning and may lead to the development of lifelong problems. Lost [35] [36]
schooldays and workdays and poor performance compound other complications of chronic pain, including sleep
disturbance, fatigue, poor peer relationships, poor social skills and adjustment, and depression. Chronic pain patients
are more likely to report depression than those who are not in chronic pain. Finally, loss of self-esteem may be the
[37]
most serious ramification of chronic pain.
The Michigan Pain Study surveyed 1,500 Michigan residents 18 years of age and older to determine severity of the
[32]
chronic pain problem, coping strategies, access to treatment, and effectiveness of available pain care. Of the 1.2
million people in Michigan who suffered from chronic pain, 42% stated that the pain affected their relationships
with spouses, family members, and fellow workers. Nearly half (48%) experienced depression, 18% overdosed on
pain medication, and 10% (about 120,000) had contemplated suicide. Five percent of the Michigan chronic-pain
sufferers (representing approximately 60,000 adults) drank alcohol to relieve their pain. Eighteen percent admitted
735
to overdosing on their medication. Twenty-nine percent of the population believed that they were losing sleep from
their chronic pain.
Clearly, the consequences of intractable pain, in respect to both its impact on society and the emotional and physical
price exacted on patients and their families, was staggering. Indeed, the figures stated paint a gloomy and
compelling picture of the true costs of chronic, unrelieved pain. Finding a solution should be a high priority for
government agencies, healthcare intermediaries, and healthcare workers. Abandoning patients when less costly and
less invasive interventions fail to relieve pain and suffering is not acceptable. The purpose of this chapter is to make
a case for interventional pain management, particularly for the implantable technologies that are appropriate and
justifiable for patients suffering from chronic, unrelieved pain, based on efficacy reports in the literature.
Implantable therapies do relieve pain and suffering and, in fact, are cost effective when the alternatives are
examined.
Treatment Options for Chronic Pain
Optimal management of intractable, chronic pain, both of malignant and nonmalignant, begins with thorough
understanding of the complex, biopsychosocial nature of the complaint. Moreover, it comes with the acceptance that
chronic pain is not merely biological or psychological but truly multidimensional. Chronic, intractable pain is
always multidimensional. Chronic pain is not only the end result of activation of neurobiologic mechanisms but also
involves neurophysiologic, emotional, and behavioral systems as well, all of which create a unique and complex
pain presentation. Thus, each chronic pain problem has its own unique set of confounding variables that must be
individually considered in the diagnosis and formulation of an appropriate, individualized treatment plan.
An interdisciplinary approach to treating pain is integrative, and its efficacy in successfully treating intractable pain
is the result of the collective efforts of interdisciplinary team members. Any comprehensive interdisciplinary pain
team should have a physician who is not only trained in pain treatment but who also has knowledge of the fields of
physical therapy, occupational therapy, and recreational therapeutic modalities as they apply to treatment of chronic
pain as well as an understanding of neuropsychology. This pain-trained physician should also know when to refer
patients for appropriate psychological evaluation and treatment. This knowledge is important because the physician,
as interdisciplinary pain team leader, must be able to direct care in a coordinated and cohesive manner.
Other members of the pain team should include psychologists, psychiatrists, or both, who are trained in various
cognitive behavioral therapies, pain-oriented therapies, and perhaps biofeedback and hypnosis. Physical and
occupational therapists have the key responsibility of addressing functional restoration and may employ various
modalities including heat, cold, ultrasonography, and transcutaneous stimulation as well as physical therapy. It is
only through a coordinated interdisciplinary approach that patients with chronic pain may be treated and given the
best chance for lasting and enduring pain benefit.
Before initiating any pain treatment plan, it must be understood that all treatments have some degree of risk of injury
to the patient. It is not difficult to imagine how invasive therapies can be harmful, but even massage and
ultrasonography may be harmful to the patient. Thus, less invasive therapies should, when feasible, be attempted
before more invasive therapies are tried. With this understanding, the World Health Organization (WHO), in the
1970s, set forth guidelines for treating cancer pain ( Fig. 29–1 ). These guidelines, based on the well-recognized
medical management KISS (keep it simple and sweet) principle, were designed to minimize risk to patients and at
the same time provide a treatment algorithm for all those who treat patients with pain. [37] [38]
NONINVASIVE THERAPIES FOR THE TREATMENT OF CHRONIC PAIN
Exercise Programs
The multiple treatment options for patients with chronic pain include noninvasive and less costly therapies as well as
more invasive and more costly therapies. Generally speaking, when treating pain sufferers, the KISS principle
should be invoked—the least invasive therapies should be tried first before more invasive therapies are used.
Exercise and behavior modification should be the first steps along the therapy continuum to pain control ( Fig. 29–
2 ).
Although exercise may be beneficial in the treatment of chronic low back pain secondary to low back disorders, the
same cannot be said for acute low back pain. Exercise is not beneficial in all chronic pain problems. Mannion and
[39]
colleagues looked at three forms of exercise used in the chronic low back pain patient population: modern physical
[40]
therapy, aerobics, and
736
Figure 29-1 The World Health Organization “ladder” is based on pharmacologic tailoring to the needs of the patient. Patients with mild to
moderate pain are given nonopioid analgesics such as aspirin, acetaminophen, or nonsteroidal anti-inflammatory drugs along with adjuvant
medications or medications that have analgesic potential but are not labeled as analgesics. Adjuvant medications include membrane-stabilizing
agents, steroids, and so forth. If pain persists and does not respond to step one of the ladder, patients are continued on nonanalgesics and are
started on weaker opioids plus adjuvant medications. Examples of weak to moderate opioids are codeine and hydrocodone combinations. If pain
continues to be unrelieved, stronger opioids are then tried.
muscle strength training. All three forms of exercise were similar regarding improvement in activities of daily living
and reductions in pain frequency and intensity. With the exception of regression of the physiotherapy group to
[40]
baseline disability, the other two groups were able to maintain relative pain relief at the 6-month follow-up period.
Combination therapies have not been investigated in a controlled manner. It is still difficult to verify which forms of
exercise are superior in relieving chronic pain. Studies have shown that even if pain is not relieved, improvement in
physical functioning can be attained and maintained, providing the exercise program continues. [41] [42] [43]
Adherence to an exercise program is difficult. Even in supervised programs, poor compliance has been reported.
Hartigan and associates suggests that an exercise
Figure 29-2 The pain treatment continuum lists therapies by order of increasing invasiveness and cost. Less invasive therapies should be tried
before more costly or more invasive therapies are started. This figure may suggest that therapies are tried in series, but many of these therapies
should be tried in parallel until adequate pain control is achieved. The continuum emphasizes that spinal cord stimulation and spinally
administered opioids and nonopioid analgesics should be therapies of last resort.
program requiring quantifiable progress improves compliance significantly. Clearly, the role of exercise in the
[44]
treatment of chronic pain states is variable but has been shown to be beneficial. The type, frequency, and duration,
as well as efficacy of the program, are all dependent on type of chronic pain problem. Exercise is not effective in
reducing pain secondary to interstitial cystitis, endometriosis, and migraine headaches, but it is effective in patients
with low back pain and cervical pain. The former pain states are not chronic pain conditions but are relapsing pain
conditions not related to musculoskeletal abnormalities.
Cognitive Behavioral Therapies for the Treatment of Chronic Pain
737
Of the healthcare professionals involved in treating pain, few question the intimate relationship between physical
and psychological pain. Melzack and Wall, in formulating their gate control theory, postulated the influence of
higher cortical centers responsible for emotion and cognition in modulating pain at the spinal cord level. From this
relationship evolved several theories that helped to explain and treat chronic pain sufferers. Cognitive-behavioral
[45]
therapy is designed to assist pain patients to understand their own behavior as it relates to their own environment
and pain. This cognitive-behavioral therapy addresses processes such as problem solving, interpretation of events,
beliefs, and expectations. Successful cognitive therapy should result in replacing maladaptive behavior with
behavior that leads to positive thought processes, decreased stress, increased function, and an improved quality of
life. Examples of cognitive behavioral therapies are relaxation and biofeedback, goal setting, relabeling of perceived
pain, and behavior management. Family involvement is also encouraged in the process and does play a significant
role in changing behavior. Classically, family members are encouraged to support healthy behaviors and ignore pain
behaviors. [46]
Alternative Therapies
Alternative therapies are not typically available in all healthcare settings and are not a normal part of a medical
school curriculum. These therapies are generally holistic in that they attempt to unify body and soul. In 1994, [47]
Borkan and associates noted that 14 billion dollars of the United States’ annual healthcare funds went to some
[48]
form of alternative care (chiropractic, homeopathic, and naturopathic), and that 60% of referrals to alternative
caregivers came from allopathic physicians.
A large proportion of those who seek alternative care possess more education, believe in a holistic approach to
illness, and are more inclined to report a poorer health condition than those who do not use alternative care. A [2]
greater number of physically disabled individuals are more likely to use alternative cures than the general population.
The alternatives to conventional, allopathic pain therapies are many. Biofeedback, acupuncture, massage, and
chiropractic care are the most often used forms of alternative therapies. Other form of alternative care methods
[49] [50]
include but are not limited to Qui Gong, magnet therapy, and acupressure. The use of transcutaneous electrical nerve
stimulation (TENS) in the treatment of low back pain has been shown to be beneficial but further studies are
recommended. Although the data to support the use of alternative therapies for the use of chronic pain states are
lacking, there are studies that clearly demonstrate benefit. The use of alternative medicine is on the rise in the
[51] [52] [53]
United States. Because the experience of pain and pain relief are subjective experiences, any therapy that improves
this subjective experience is successful therapy. As long as patients and physicians maintain an open line of
communication as to what therapies are being used and tried, the use of alternative therapies should not be
discounted.
INVASIVE THERAPIES FOR THE CONTROL OF CHRONIC PAIN
When more conservative, less invasive therapies fail to provide pain relief, the treating physician should offer more
invasive therapies which, if performed correctly by well-trained physicians, may provide pain relief for the patient
suffering from intractable, chronic pain. Interventional strategies used when less invasive therapies fail include
anesthetic blocking techniques, continuous intraspinal analgesia, continuous plexus analgesia, implantable
neuromodulatory techniques, and neurodestructive techniques. [54]
Nerve Blocks in the Management of Pain
Nerve blocks with local anesthetic or neurolytic agents are helpful in managing intractable pain. It is generally
agreed that 50% to 80% of patients receive benefit from single or repetitive blocks. Nerve blocks for pain may be
used diagnostically to determine the pain generator, prognostically as outcome indicators of neurolytic procedures,
or therapeutically for peripheral or central blockade. Blocks used by anesthesiologists for the relief of pain include
blocks of the trigeminal system for relief of head and neck pain; blocks of the cervical, thoracic, lumbar, and pelvic
sympathetic nervous systems; blocks of spinal nerve roots, and nerve plexus blockade.
Anesthetic blockade or chemical rhizolysis with alcohol or phenol of the head can be performed either by blocking
the gasserian (trigeminal) ganglion or by blocking its peripheral branches: the ophthalmic division, the maxillary
division, and the mandibular division. The maxillary nerve forms the second and the mandibular nerve forms the
third division of the trigeminal nervous system. The maxillary nerve divides to form the following end branches:
meningeal, zygomatic, infraorbital, nasal, pterygopalatine, and superior labial branches. The mandibular division
enervates the oral muscles supplied by these nerves, the tympanic membrane, the anterior two thirds of the tongue,
sensation to the lower lip, lower teeth, mandible, and parotid gland. The supraorbital nerve is a branch of the first
738
division—ophthalmic—of the trigeminal nervous system. Blocking the supraorbital nerve can block cancers that
cause pain in the dermatome supplied by the supraorbital nerve; namely, the skin over the frontal region of the skull
including the upper nose. Blocking the supraorbital nerve can block pain confined to the unilateral forehead area.
The infraorbital nerve is a peripheral division of the maxillary nerve. It supplies the skin over the anterior upper lip
and adjacent cheek. Pain in the area inferior to the eye and on the side of the nose can by blocked by infraorbital
nerve block.
Certain painful neuropathic disorders, previously called reflex sympathetic dystrophy (RSD) and causalgia, are now
called complex regional pain syndromes (CRPS) I and II. These painful disorders can be either sympathetically
maintained (SMP) or independent of abnormal activation of the sympathetic nervous system (SIP). Sympathetic [55]
blockade, either in the cervical region as with stellate ganglionic blockade, or at the lumbar region with lumbar
sympathetic blockade, is certainly useful in distinguishing between SMP and SIP and may even be therapeutic if
repeated until symptoms of CRPS disappear. The paravertebral sympathetic chain consists of sympathetic neural
tissue from several sympathetic plexuses that run along the paravertebral region of the body. These axial
sympathetic chains include the cervical, thoracic, and lumbar sympathetic ganglia. The sympathetic system receives
afferent nociceptive impulses from visceral fibers of the head and neck and upper extremities (stellate ganglion),
from the cardiothoracic viscera (thoracic sympathetic ganglia), from the abdominal viscera (celiac plexus), from the
urogenital system and lower extremities (lumbar sympathetic ganglia), and, finally, from the pelvic viscera (superior
hypogastric plexus and ganglion of impar). Pain information from the sympathetic nervous system can be controlled
by either anesthetic nerve blocking or by neurolysis of these ganglia using chemical, surgical, or radiofrequency
thermal lesioning or cryoneurolysis.
The stellate ganglion is formed by fusion of the inferior cervical and first thoracic sympathetic ganglia. The stellate
ganglion, lying over the neck of the first rib, controls sympathetic outflow to the head and neck and upper extremity.
Stellate ganglion block is indicated for the treatment of sympathetically mediated pain of the head and neck and
upper extremities. This block is also used to increase perfusion of the upper extremities, to decrease excessive
perspiration of the head, neck, or upper extremities, as occurs in hyperhydrosis, or for patients suffering from cluster
headache.
Preganglionic neurons from the interomediolateral horn of T5 to T12 exit the spinal cord to join the white rami
communicantes. Instead of synapsing in the sympathetic chain and prevertebral sympathetic ganglia, they pass
through the chain to synapse at the celiac plexus. The celiac plexus lies anterior to the aorta at the level of the L-1
vertebral body and anterior to the crura of the diaphragm. The celiac plexus receives afferent nociceptive impulses
from all abdominal viscera except the transverse colon, the descending colon, the sigmoid colon, and the rectum.
Intractable pain originating from the structures enervated by the celiac plexus can be blocked by local anesthetic
injection or by neurolysis of the celiac plexus with alcohol or phenol.
The lumbar sympathetic ganglia are located anterolateral to and along the L2 and L4 vertebral bodies, bilaterally
between the vertebral bodies, and anteriorly and medially to the psoas major muscle. Indications for lumbar
sympathetic blockade include sympathetically mediated pain relating to radiation lumbosacral plexitis, phantom
limb pain, herpes zoster, neuropathic pain of the lower extremity, vascular insufficiency secondary to malignancy,
spread of tumor to involve sympathetic neural structures, complex regional pain syndromes (RSD or CRPS I and II),
vasospastic disorders of the lower extremities, and peripheral vascular disease.
The superior hypogastric plexus is located bilaterally at the lower third of the fifth lumbar vertebral body and upper
third of the S-1 vertebral body in proximity to the bifurcation of the common iliac vessels. The pelvic splanchnic
nerves arise from the second, third, and fourth sacral nerves. Sympathetic afferents from the distal end of the
transverse colon, left colic flexure, descending colon, sigmoid colon, and, finally, rectum, and parasympathetic
afferents from the sacrum, ascend to the superior hypogastric plexus via the hypogastric nerves. Blocking the
superior hypogastric plexus can alleviate pelvic visceral pain.
Epidural Steroidal Placement
The placement of an epidural steroid around inflamed epidural tissues, although controversial, has been shown to be
efficacious in certain individuals. Much has been written about the efficacy of epidural steroid injection in the low
back pain population. Epidural steroid injections are used as an alternative to surgery because more conservative
treatments should be exhausted before an invasive surgical procedure. However, there is debate as to whether
epidural steroid injections in the low back pain patient, including injections for diagnosis of herniated nucleus
pulposus and spinal stenosis, are helpful in relieving back and leg pain.
Several investigations have been conducted, with conflicting results. Some studies support the use of epidural
steroid injection in decreasing low back pain, whereas others state that no conclusion can as yet be made
[56] [57] [58] [59] [60]
739
regarding the efficacy of epidural steroid injection in low back pain. Explanations for this discrepancy may
[61] [62] [63] [64] [65]
be found in the method of the design by which patients are studied. Patients with low back pain secondary to spinal
stenosis do not appear to respond to epidural steroid injections as well as patients with herniated discs. Additionally,
the long-term benefits of epidural steroid injections appear to be greater in patients with disc herniations. Epidural [66]
steroid injections, however, have been proved to be safe. There are few published reports of consistent
complications resulting from epidural injection procedures. The most common complication is nonpositional
headache (3.1%); incidence of minor complications has been reported at 9.6%. Additionally, randomized case-
[66] [67] [68]
controlled studies are needed to validate the use of epidural steroid injections in treatment of patients with chronic
low back pain. [69]
Continuous Epidural Analgesia
Local anesthetics are commonly used for the relief of pain in both acute and chronic states. However, under certain
circumstances, a single bolus administration of a local anesthetic may not be sufficient to control pain. The use of
continuous epidural infusions for the control of both acute and chronic pain has been well established. Pain [70] [71] [72]
states in which continuous epidural infusions may be indicated include uncontrolled neuropathic pain processes,
failed neck and back surgery syndrome, brachial and lumbosacral plexopathies, and cancer pain. Pain states that
require a sustained sympathetic blockade, such as CRPS I and II and limb ischemia, would benefit because epidural
analgesia does result in a chemical sympathectomy. In addition to continuous analgesia, tighter control of drug
dosages delivered to the epidural space can be achieved. In patients whose pain cannot be controlled with oral or
epidural therapies, the amount of oral medication required for pain relief results in intolerable side effects. In this
setting, epidural analgesia is indicated because lower concentrations of medication can be used to achieve pain relief.
Various medications have been used in continuous epidural analgesia, including local anesthetics, opioids, and
alpha2 agonists. The major complications of epidural anesthesia are infection, dural penetration, spinal cord
[73]
damage, and respiratory depression. One major drawback to the use of continuous epidural analgesia is that it is not
as useful in conditions involving multiple pain states because the epidural catheter is in a fixed position in the
epidural space. Raj and colleagues suggested that medications delivered into the epidural space provided analgesia
[74]
for 5 to 7 continuous dermatomes.
Intrapleural Analgesia
Intrapleural analgesia has been used in a variety of painful conditions, including metastatic bronchogenic
carcinoma, breast surgery, minimally invasive direct coronary artery bypass grafting, open cholecystectomy,
[74] [75] [76] [77]
pancreatic carcinoma, and post-thoracotomy syndrome. Intrapleural analgesia can also be used to produce an
[78] [79]
upper extremity sympathectomy. It also has clear indications in both acute and chronic pain syndromes. However,
actual efficacy depends on the drug used and the condition for which the drug is being administered. In conditions in
which intrapleural analgesia helps to decrease pain, several mechanisms of actions have been postulated. As the
drug or drugs diffuse through the pleura, a block of the thoracic sympathetic chain and the splanchnic nerves may
occur. Additionally, multiple intercostal nerve blocks may occur. Upper extremity analgesia is thought to occur
through diffusion of the medication to the brachial plexis.[80]
An important consideration regarding the use of intrapleural analgesia is that bilateral analgesia should not be
attempted secondary to risks of bilateral pneumothoraxes and because patients who have pleural adhesions would be
at further risk of pneumothorax. Moreover, patients with emphysema, empyema, pleural effusions, or pulmonary
fibrosis should be carefully considered for intrapleural analgesia secondary to differential absorption of local
anesthetic, technical difficulties, and additional risk of pneumothorax.
Neurolytic Techniques
Neurolysis, or destruction of neural tissue, may be performed surgically, chemically, or thermally with use of either
radiofrequency, or cryoneurolysis. A careful selection of patients and a thorough understanding of the
pathophysiology of the specific disease process may help to determine the appropriate modality of neurolysis.
Several chemical neurolytic agents may be used, including commercially available preparations of absolute ethyl
alcohol, phenol, or glycerol.
Absolute, 100% alcohol is available in the United States. It acts by precipitation of the proteins in neural tissue and
extraction of phospholipids and cholesterol; the result is neural degeneration. Alcohol may be used for neurolysis of
the trigeminal, glossopharyngeal, celiac, lumbar, or superior hypogastric sympathetic ganglia. If used intrathecally,
alcohol is relatively hypobaric and, therefore, rises in the cerebrospinal fluid (CSF) after injection. Because alcohol
rises in CSF, correct positioning of a patient undergoing subarachnoid neurolysis via alcohol cannot be
740
overemphasized. Alcohol neurolysis is extremely painful and—except when used in the subarachnoid space—is
usually preceded by injection of local anesthetic to block the area before the injection of the alcohol.
Phenol at lower concentrations acts as a local anesthetic, but at higher concentrations is neurodestructive. Phenol,
therefore, lacks the local algesic properties of alcohol. Commonly used phenol concentrations vary between 6% and
10%. Unlike alcohol, which is hypobaric relative to CSF, phenol is hyperbaric relative to the CSF. Both phenol and
alcohol have been used for neurolysis of peripheral nerves, but both may cause peripheral neuritis. The incidence of
peripheral neuritis is greater when alcohol is used. [81] [82]
Thermal destruction of neural tissue is performed by a radiofrequency generator system. Electrical currents
generated by the radiofrequency (RF) generator heat tissue surrounding the noninsulated RF needle tip, raising the
temperature of the electrode tip and producing a thermal lesion. RF thermocoagulation is required when
neurodestruction of central neural tissues is indicated and when the tissue to be destroyed is accessible to placement
of the RF probe or needle. RF thermocoagulation is used for thermal lesioning of the gasserian trigeminal ganglion. [83]
It is also used for neural enervation of cervical, thoracic and lumbar facet joints
[84]
; sacroiliac joints ; [85] [86] [87] [88] [89]
cervical and thoracic sympathetic chain ; lumbar sympathetic chain

[90]
; and cervical, thoracic, lumbar, and sacral
[91] [92]
dorsal root ganglia. [93]
Cryoneurolysis, unlike RF thermal neurolysis, may be used for neurolysis of peripheral nerves. To perform
cryoneurolysis, a cryoprobe consisting of an inner and an outer cannula is placed on or in very close proximity to the
nerve being frozen. High pressure N2 O or CO2 is passed via the outer cannula to a cooling chamber and returned via
the inner cannula. This process expands the gas and rapidly cools the tip of the probe to −70° centigrade. Like RF
thermal neuroablation, cryoneurolysis is used for temporary cryodestruction of several spinal pain generators such
as those arising from the spinal facet joints, neuromas of the ilioinguinal and iliohypogastric nerves, and the
coccygeal nerve for coccydynia. Pain emanating from the branches of the trigeminal nerve can be relieved with
cryoneurolysis of these branches. Patients may experience pain relief for 3 to 6 months after undergoing
[11]
cryotherapy, but actual pain relief may vary in individual cases. [94] [95] [96]
Implantable Devices for the Control of Chronic Pain
In the preceding paragraphs, we have attempted to lay the foundation for the appropriate use of implantable devices
Because relief of acute pain is usually attained pharmacologically, it should be obvious that implantable devices are
not appropriate for the treatment of acute pain syndromes. Chronic pain, on the other hand, if unrelieved, is costly to
society as well as to patients suffering from the pain and to their families. There are multiple therapies for the
treatment of chronic pain, and, clearly, implantable devices should be used for intractable pain when less invasive
and less costly therapies, including the noninvasive therapies and invasive therapies discussed, fail to work. In
subsequent chapters of this book, implantable devices for the control of pain are discussed in more detail.97 These
therapies should be the treatment of last resort before neurodestructive therapies are performed.
Summary
The history of treatment of pain has provided many challenges during its evolution. The prevalence of intractable
pain is considerable, and its impact on multiple segments of our society is enormous. Melzack and Wall’s gate
control theory has been instrumental in advancing the understanding of pain neurophysiology. Central modulatory
[3]
control theories have helped to validate a biopsychosocial approach to the practice of pain medicine. It is clear that
young and old alike are susceptible to various chronic pain states. Several mechanisms have been proposed to
explain chronic pain. One facet is clear: The biological and psychological aspects of chronic pain are closely related.
Thus, treatment options are variable, and a comprehensive approach to treating pain should be interdisciplinary. The
World Health Organization has provided guidelines that provide a logical approach for addressing pain problems,
and the KISS principle assists in minimizing costs and risks for patients.
REFERENCES
1. Bonica J, Loeser JD: History of pain concepts and therapies. In Bonica J (ed): Bonica’s Management of Pain. New York, Lippincott Williams
& Wilkins, 2001, pp 4–7.
2. Galen C: De Usu Portium. Ithaca, NY, Cornell University Press, 1968.
3. Fields
HL, Basbaum AI: Central nervous system mechanisms of pain modulation. In: Wall PD, Melzack R (eds): Textbook of Pain, 4th ed.
New York, Churchill Livingstone, 2000, pp 309–323.
4. Mersky H, Bogduk M: Classification of chronic pain: Definitions of pain terms, 2nd ed. Seattle, IASP Press, 1996.
741
5. Seers K: Chronic non-malignant pain. Br J Gen Pract 42:452–453, 1992.
6. Verhaak PF, Kerssens JJ, Dekkers J, et al: Prevalence of chronic benign pain disorder among adults: A review of the literature. Pain 77:231–
339, 1998.
7. Frølund F: Pain in general practice. Scand J Primary Health Care 4:97–100, 1986.
8. Elliott T: The epidemiology of chronic pain in the community. Lancet 354:1248–1252, 1999.
9. Gallagher RM, Verma S, Mossey J: Sources of late-life pain and risk factors for disability. Geriatrics 55:40–47, 2000.
10. Williams ME: The American Geriatric Society’s Complete Guide to Aging and Health. New York, Harmony Books, 1995, pp 453–460.
11. Mobily PR, et al: An epidemiological analysis of pain in the elderly: The Iowa 65 + study. J Aging Health 6:139–154, 1994.
12. HarkinsSW: Pain in the elderly. In Dubner R, Gehart FG, Bond HR (eds): Proceedings of the 5th World Congress on Pain. Amsterdam,
Elsevier, 1988, pp 355–357.
13. Gibson SJ, Helme RD: Age differences in pain perception and report: A review of psychological, physiological, laboratory and clinical studies.
Pain Rev 2:111–137, 1995.
14. Kristjansdottir
G: Prevalence of pain combinations and overall pain: A study of headache, stomach pain, and back pain among school children.
Scand J Soc Med 25:59–63, 1997.
15. McGrath PA: Pain in children: Nature, assessment and treatment. New York, Guilford Press, 1990.
16. Goodman JE, McGrath PJ: The epidemiology of pain in children and adolescents: A review. Pain 46:247–264, 1991.
17. Hotopf
M, Carr S, Mayor R, et al: Why do children have chronic abdominal pain, and what happens to them when they grow up? Population-
based cohort study. BMJ 316:1196–1200, 1998.
18. Fitzgerald
M: Developmental neurobiology of pain, In Wall PD, Melzack R (eds): Textbook of Pain, 4th ed. New York, Churchill Livingstone,
2000, pp 235–251.
19. Jacobson L, Mariano A: General considerations of chronic pain. In Bonica J (ed): 3rd ed. New York, Lippincott Williams & Wilkins, 2001, pp
241–254.
20. Bonica JJ: Chronic non-cancer pain. In Anderson S, Bond M, Mehta M, Swerdlow M (eds): Lancaster, England, Museum Tusculanum Press,
1987, p 13.
21. Von Korff M, Dworkin SF, Le Resche L: Graded chronic pain status: An epidemiologic evaluation. Pain 279:91, 1990.
22. Von Korff M, Wagner EH, Dworkin SF, et al: Chronic pain and use of ambulatory health care. Psychosom Med 53:61–79, 1991.
23. Cheadle
A, Franklin G, Wolfhagen C, et al: Factors influencing the duration of work-related disability: A population-based study of
Washington State worker’s compensation. Am J Public Health 84:190–196, 1994.
24. Frymoyer JW, Cats-Baril WL: An overview of the incidences and costs of low back pain. Orthop Clin North Am 22:263–271, 1991.
25. Carey TS, Evans A, Hadler M, et al: Care seeking among individuals with chronic low back pain. Spine 20:312, 1995.
26. Grazier
KL, Holbrook TL, Kelsey JL, et al: The frequency of occurrence, impact and cost of musculoskeletal conditions in the United States.
Proceedings of the American Academy of Orthopaedic Surgeons Conference, Rosemont, Ill, 1984.
27. National Safety Council (US): Accident Facts. Chicago, Ill, 1993.
28. Meridian Research (US): Worker Protection Programs in Construction (OSHA Contract J-9-F-1-0019). Silver Spring, Md, 1994.
29. Spengler D, Bigos S, Martin NA, et al: Back injuries in industry: A retrospective study. I. Overview and cost analysis. Spine 11:241–245, 1996.
30. Hart
LG, Deyo R, Cherkin DC: Physician office visits for low back pain: Frequency clinical evaluation and treatment patters from a U.S.
national survey. Spine 20:11–19, 1995.
31. Bonica JJ: General considerations of chronic pain. In: Bonica JJ (ed): The Management of Pain. Philadelphia, Lea and Febiger, 1990. pp 180–
196.
32. The Michigan Pain Study: EPIC/MRA. Lansing, Mich, 1997.
33. Midence K, Fuggle P, Davies S: Psychosocial aspects of sickle cell disease in childhood and adolescence: A review. Br J Clin Psychol 32:271–
280, 1993.
742
34. Aaslund A, Flato B, Vandvik IH: Psychosocial outcome in juvenile chronic arthritis: A nine-year follow-up. Clin Exp Rheumatol 15:561–568,
1997.
35. Walker
LS, Guite JW: Recurrent abdominal pain: A potential precursor of irritable bowel syndrome in adolescents and young adults. J Pediatr
132:1010–1015, 1998.
36. Walker LS, Green JW: The functional disability inventory: Measuring a neglected dimension of child health status. J Pediatr Psychol 16:39–58,
1991.
37. World Health Organization (WHO): Cancer Pain Relief. Geneva, WHO, 1986.
38. World Health Organization (WHO): Cancer Pain Relief and Palliative Care: Report of a WHO Expert Committee. Geneva, WHO, 1990.
39. KoesBW, Bouter LM, van der Heijden GJMG: Methodologic quality of randomized clinical trials on treatment of efficacy in low back pain.
Spine 20:228–35, 1995.
40. Mannion AF, Müntener M, Simo T, et al: A randomized clinical trial of three active therapies for chronic low back pain. Spine 24:2435–2448,
1994.
41. Mayer
TG, Gatchel RJ, Kishjino N, et al: Objective assessment of spine function following industrial injury: A prospective study with
comparison group and 1-year follow-up. Spine 10:482–493, 1985.
42. HazardRG, Fenwick JW, Kalisch SM, et al: Functional restoration with behavioral support: A 1-year prospective study of patients with
chronic low back pain. Spine 14:157–161, 1989.
43. Rainville JD, Athern DK, Phalen L: Altering beliefs about pain and impairment in a functionally oriented treatment program for chronic low
back pain. Clin J Pain 9:196–201, 1993.
44. Hartigan C, Rainville J, Sobel J, et al: Long-term exercise adherence after intensive rehabilitation for chronic low back pain. Med Sci Sports
Exerc January:551–557, 1999.
45. Gamsa A: The role of psychological factor in chronic pain. I. A half century of study. Pain 57:5–15, 1994.
46. Keefe
FJ, Dunsmore J, Burnett R: Behavioral and cognitive behavioral approaches to chronic pain: Recent advances in future directions. J
Consult Clin Psychol 60:528–536, 1992.
47. Eisenberg
DM, Kessler RC, Foster C, et al: Unconventional medicine in the United States: Prevalence, costs and patterns of use. N Engl J Med
329:246–252, 1993.
48. Borkan J, Neher JD, Anson O, et al: Referrals for alternative therapies. J Fam Prac 6:545–550, 1994.
49. MacLennan AH, Wilson DH, Taylor AW: Prevalence and cost of alternative medicine in Australia. Lancet 347:569–573, 1996.
50. Perkin
MR, Pearcy RM, Fraser JS: A comparison of the attitudes shown by general practitioners, hospital doctors and medical students
towards alternative medicine. J R Soc Med 84:523–525, 1994.
51. BoveG, Nilsson N: Spinal manipulation in the treatment of episodic tension-type headache: A randomized controlled trial. JAMA 280:1576–
1579, 1998.
52. ShlayJ, Chaloner K, Max MB, et al: Acupuncture and amitriptyline for pain due to HIV-related peripheral neuropathy: A randomized
controlled trial. Terry Beirn Community Programs for Clinical Research on AIDS. JAMA 280:1590–1595, 1998.
53. Eisenberg
D, Davis R, Ettner S, et al: Trends in alternative medicine use in the United States, 1990–1997: Results of a follow-up national
survey. JAMA 280:1569–1575, 1998.
54. Krames
E: Interventional pain management. Appropriate when less invasive therapies fail to provide adequate analgesia. Med Clin North Am
83:787–808, 1999.
55. Boas
R: Complex regional pain syndromes: Symptoms, signs, and differential diagnosis in reflex sympathetic dystrophy: A reappraisal. In:
Janig W, Stanton-Hicks M (eds): Progress in Pain Research and Management, vol 6, Seattle, IASP Press, 1996, pp 79–92.
56. Benzon HT: Epidural steroid injections for low back pain and lumbrosacral radiculopathy. Pain 24:277–295, 1986.
57. Bogduk N: Epidural steroids. Spine 20:845–888, 1995.
58. Lutz
GE, Vad VB, Wisneski RJ: Fluoroscopic transforaminal lumbar epidural steroids: An outcome study. Arch Phys Med Rehabil 79:1362–
1366, 1998.
59. Weinstein SM, Herring SA, Derby R: Contemporary concepts in spine care: Epidural steroid injections. Spine 20:1842–1846, 1995.
60. Watts RW, Silagy CA: A meta-analysis on the efficacy of epidural corticosteroids in the treatment of sciatica. Anaesth Invasive Care 23:564–
743
569, 1995.
61. National Health and Medical Research Council of Australia: Epidural use of steroids in the management of back pain. Canberra, Australia,
1994, p 13.
62. Rydevik BL, Cohen DB, Kostuik JP: Spine epidural steroids for patients with lumbar spinal stenosis. Spine 22:2313–2317, 1997.
63. Rozenberg S, Dubourg G, Khalifa P, et al: Efficacy of epidural steroids in low back pain and sciatica. A critical appraisal by a French task
force of randomized trials. Critical Analysis Group of the French Society for Rheumatology. Rev Rhum Engl Ed 66:79–85, 1999.
64. Koes
BW, Schulten RJ, Mens JIM, et al: Efficacy of epidural steroid injections for low back pain and sciatica: A systemic review of
randomized clinical trials. Pain 63:279–288, 1995.
65. Nelemans
PJ, de Bie RA, de Vet HCW, Sturmans E: Injection therapy for subacute and chronic benign low back pain. Cochrane Database Syst
Rev (2):CD0001824, 2000.
66. Schmid G, Vetter S, Gottman D, et al: CT-guided epidural/perineural injections in painful disorders of the lumbar spine: Short and extended-
term results. Cardiovasc Interv Radiol 22:493–498, 1999.
67. Botwin KP, Gruber RD, Bouchlas CG, et al: Complications of fluoroscopically guided transforaminal lumbar epidural injections. Arch Phys
Med Rehabil 81:1045–1050, 2000.
68. Abram SE, O’Connor TC: Complications associated with epidural steroid injections. Reg Anesth 21:149–162, 1996.
69. FredmanB, Nun MB, Zohar E, et al: Epidural steroids for treating “failed back surgery syndrome”: Is fluoroscopy really necessary? Anesth
Analg 88:367–372, 1999.
70. JohnsonBA, Schellhas KP, Pollei SR: Epidurography and therapeutic epidural injections: Technical considerations and experience with 5,334
cases. Am J Neuroradiol 20:697–705, 1999.
71. Rosenblatt RM, Raj PP: Experience with volumetric infusion pumps for continuous epidural analgesia. Reg Anaesth 4:21–23, 1979.
72. Green R, Dawkins CJM: Post-operative analgesia: The use of continuous hip epidural block. Anaesthesia 21:372, 1966.
73. Stoerel WE, Thomas A, Gerula GR: Continuous drip analgesia: Experience with mechanical devices. Can Anaesth Soc J 17:37, 1970.
74. Raj
PP, Denson D, Finnason R: Prolonged epidural analgesia: Intermittent or continuous. In Meyer J, Wolte H (eds): Die Kontineurliche
Peridural Anesthesia. VII International Symposium Uber Die Regional An-Aesthesia Am, Jan 7, 1982, Minden, Germany. Stuttgart, Germany,
George Themaverlag, 1983 pp 26–38.
75. Fineman S: Long-term post-thoracotomy cancer pain management with interpleural bupivacaine. Anesth Analg 68:694–697, 1989.
76. Reiestad F, Stromskag K: Interpleural catheter in the management of postoperative pain. Reg Anesth 11:89–91, 1986.
77. Mehta Y, Swaminathan M, Mishra Y, et al: A comparative evaluation of intrapleural and thoracic epidural analgesia for postoperative pain
relief after minimally invasive direct coronary artery bypass surgery. J Cardiothorac Vasc Anesth 12:162–165, 1998.
78. Clarke K: Effective pain relief with intrapleural analgesia. Nurs Times 95:49–50, 1999.
79. Durrani Z, Winnie A, Ikuta P: Interpleural catheter analgesia for pancreatic pain. Anesth Analg 67:479–481, 1998.
80. AykacB, Erolcay H, Dikmen Y, et al: Comparison of intrapleural versus intravenous morphine for post-thoracotomy pain management. J
Cardiothorac Vasc Anesth 9:538–540, 1995.
81. Katz J: Current role of neurolytic agents. Adv Neurol 4:471, 1974.
82. CousinsMJ, Dwyer B, Gibb D: Chronic pain and neurolytic neural blockade. In: Cousins MJ, Bridenbaugh PO (eds): Neural Blockade in
Clinical Anesthesia and Management of Pain, 2nd ed. Philadelphia, JB Lippincott, 1988, p 1053.
83. Sweet
WH, Wepsic JG: Controlled thermocoagulation of trigeminal ganglion and rootlets for differential destruction of pain fibers. J
Neurosurg 40:143–156, 1974.
84. Broggi
G, Franzini A, Lasio G, et al: Long-term results of percutaneous retrogasserian thermorhizotomy for “essential” trigeminal neuralgia.
Neurosurgery 26:783–787, 1990.
85. Savitz MH: Percutaneous radiofrequency rhizotomy of the lumbar facets: Ten years experience. Mt. Sinai J Med 581:77–178, 1991.
86. Sluijter
ME: Radiofrequency Lesion in the Treatment of Cervical Pain Syndromes. (Radionics Procedure Technique Series). Burlington, Mass,
Radionics, 1990.
87. Mehta M, Sluijter ME: The treatment of chronic back pain: A preliminary survey of the effect of radiofrequency denervation of the posterior
vertebral joints. Anaesthesia 34:768–775, 1979.
744
88. Stolker RJ, Verves ACM, Groen GJ: Percutaneous facet denervation in chronic thoracic spinal pain. Acta Neurochir (Wien) 122:82–90, 1993.
89. Laslett M, Williams M: The reliability of selected pain provocation tests for sacroiliac joint pathology. Spine 19:1243–1249, 1994.
90. Wilkinson HA: Percutaneous radiofrequency upper thoracic sympathectomy: A new technique. Neurosurgery 15:811–814, 1984.
91. Pernak J: Percutaneous radiofrequency thermal lumbar sympathectomy. Pain Clin 1:99–106, 1995.
92. Noe CE, Haynesworth RF: Lumbar radiofrequency sympatholysis. J Vasc Surg 17:801–806, 1993.
93. Van Kleef M, Barendse G, Dingemans W, et al: Effects of producing a radiofrequency lesion adjacent to the dorsal root ganglion in patients
with thoracic segmental pain. Clin J Pain 11:325–332, 1995.
94. Evans P: Cryoanalgesia. The application of low temperatures to nerves to produce anesthesia or analgesia. Anaesthesia 36:1003–1013, 1981.
95. Holden HB: Practical Cryosurgery. Chicago, Pitman Medical Publishing Company, 1975.
96. Lloyd J, Barnard J, Glynn C: Cryoanalgesia: A new approach to pain relief. Lancet, 2:932–934, 1976.
745
Section V Chapter 30 - Radiographic Imaging in Regional Anesthesia
Chapter 30 - Radiographic Imaging in Regional Anesthesia
Leland Lou
Jeffrey Carruth
Use of radiography in regional anesthesia and pain management has grown more important as the field has
developed. Radiographic diagnostic tests such as plain films, computed tomography (CT), magnetic resonance
imaging (MRI), and bone scans are frequently obtained to find simple fractures or degenerative joints, disc bulges,
herniations, and spinal cord or nerve impingement. During the performance of many procedures, fluoroscopy or CT
is used to place the nerve blocks with precision. Because of the rapid growth of radiographic use by nonradiologists,
the understanding of the principles of radiographic imaging, the interpretations of the studies, and knowledge of the
materials and equipment used become less understood.
The first part of the chapter briefly reviews some of the more common diagnostic tests, with special attention to the
information that they can provide. Another section examines the principles of fluoroscopy function and clinical
application. Radiation safety is discussed, with emphasis on the meaning of radiation to living tissue and methods
for limiting exposure. Finally, the commonly used radiographic contrasts are mentioned with regard to how they
relate to practical usefulness as well as their potential dire consequences.
Radiologic Views
Radiographic views are named on the basis of the direction in which the x-ray beam passes through the patient.
Similarly, fluoroscopic views are named with respect to the patient’s position on the table and to the x-ray tube that
is positioned under the table. A posteroanterior (PA) radiograph is produced when the x-ray beam passes through the
back of the patient and exits through the front to expose an x-ray film or fluorescent screen (fluoroscopy) in front of
the patient. An anteroposterior (AP) view is the mirror opposite of the PA view. The craniocaudad (CC) view is
made when the beam passes though the patient in a vertical cranial to caudad direction. Views can also be identified
by the position of the patient (i.e., right lateral, decubitus, prone, and erect). A left posterior oblique (LPO) view is
taken when the patient’s left side is down and the right side is elevated toward the receiving fluorescent screen. The
x-ray beam passes from below the table to the screen above the patient ( Fig. 30–1 ).
Principles of Radioimaging
X-rays are radiant energy in much the same way as visible light. The short wavelength of x-rays makes the
[1] [2]
penetration of m The short wavelength of x-rays makes the penetration of many different types of matter easier than
penetration by light. Generation of the x-ray beam is by directing an electron beam at a tungsten target within an x-
ray tube. X-rays that are released pass through the body, undergo absorption, and scatter, creating an image
discernible as the human anatomy ( Fig. 30–2 ).
Indication for Radiologic Imaging
PLAIN FILMS
Plain radiographic films are produced by activation of fluorescent particles on the film’s surface by an artificially
generated x-ray after they have passed through the subject. During the developing process of the exposed film,
subsequent introduction of light waves creates an image on the film within the cassette. This processed film is the
“x-ray film” that we commonly examine for abnormalities. When this film is overexposed, the processed plain film
is dark and occasionally readable with the assistance of a “hot” light. For underexposed films, the processed film
may be opaque or “white,” with no discernible features. Proper films are usually obtained with the use of standard
formulas, which direct the technician as to the appropriate radiation output, or kV (kilovolt) needed for adequate
exposure
756
Figure 30-1 Different directions and views of fluoroscope: A, Anteroposterior view; B, lateral view; C, oblique view; D, caudal cephalad view; E,
cephalo-caudal view. The nomenclature is based on the direction of the x-ray beam in relation to the body (i.e., the anteroposterior view refers to
the direction of the x-ray beam from the chest to the back).
757
Figure 30-2 Diagram of the x-ray and fluoroscopic machine. The origin of the x-ray beam is coming from A the x-ray tube, which is the source
of the generated x-rays. The image intensifier B or undeveloped radiographic film absorbs the residual x-rays after they pass through the body.
From the absorbed x-rays, the actual radiographic image is created.
based on size and on the distance of the x-ray tube from the patient.
FLUOROSCOPY
The advent of fluoroscopy has made real-time radiographic visualization possible. The continuous x-ray beam
passes through the patient and falls onto a fluorescent screen. By using an image intensifier, the continuously
changing light pattern on the fluorescing screen is electronically amplified and displayed on a television monitor. [3]
Fluoroscopy in interventional pain procedures is very helpful because of the need for continuous step-by-step
monitoring of each directed move by the physician. As the physician becomes accustomed to the views afforded by
fluoroscopy, procedures can be performed with great accuracy. Within the various confines of the hollow viscous
and bony projections of the human anatomy, fluoroscopy can open visual pathways for passage of instruments in a
way that is relatively safe and efficacious.
COMPUTED TOMOGRAPHY
CT images are produced from mathematically reconstructed x-ray images that have been directed in thin slices
through a patient. A detector on the opposite side of the patient measures the x-ray transmission through the slice.
These measurements are continuously made at different speeds depending on whether conventional or helical CT is
used. The transmitted x-rays are used as pixel data and by a computer algorithm transformed into an image. The
computer algorithm also allows for chosen reconstruction and determination of thickness of the scanned slices. [4]
Slice thickness usually ranges from 1 to 10 mm. Compared with MRI, the advantages of CT include rapid scan
acquisition, increased bone detail, and better demonstration of calcifications. Images obtained by CT are usually in
an axial plane. Sagittal, coronal, and oblique planes, and even three-dimensional images may be produced through
computer generation from original images.
Compared with conventional CT, which obtains images one slice at a time, helical CT acquires images much more
rapidly via constant speed movement of the patient table through the CT gantry. Continuous image data can be
acquired during one breath hold by the patient. This speed allows scanning during optimal contrast opacification and
eliminates artifacts caused by variations in patient breathing and movement. With intravenously administered
contrast, multiple sequential slices may be reconstructed into highly detailed three-dimensional images.
CONVENTIONAL COMPUTED TOMOGRAPHY
758
Conventional CT takes two to three times the total scan time of the helical CT when using the one breath hold per
slice standard. This technique also makes contrast-enhanced images slightly less optimal. Using a cluster technique,
conventional scanners can approach the speed of helical scanners. However, multiple scans are acquired with each
breath hold. Once the images are obtained, complex algorithms are used with the assistance of computed
calculations to generate three-dimensional images. [1]
MAGNETIC RESONANCE IMAGING
MRI does not involve radiation. Magnetic fields and radio waves are used to measure and analyze multiple tissue
parameters such as hydrogen (proton) density, T1 and T2 relaxation times of tissue, and tissue blood flow. Magnetic
resonance (MR) provides soft tissue contrast, which is significantly better than any other imaging technique. The
tissues are identified by characteristic differences of the T1 and T2 relaxation times. T1 measures how quickly the
proton can be magnetized and T2 measures how quickly the protons lose their magnetism. [3] [5] [6] [7] [8] [9]
Because of this property, the different tissue types can be measured for distinct characteristic rates of energy release
using a strong primary magnetic field to align the protons in one direction. A radiofrequency pulse is then used to
knock these protons out of alignment. Once the radiofrequency pulse is terminated, the energy released by the
realignment of the protons is monitored, localized, and processed using a computer algorithm for creation of a
tomographic anatomic image. The “cut” of the images can be manipulated by adjusting the direction of the
orientation of the x-axis, the y-axis, and the z-axis of the magnetic field. Different manufacturers use three major
pulse sequence techniques and their variations to form MR images. These techniques now make a single breath-hold
image possible, but they decrease the induction and monitoring times for image creation. With early MR techniques,
the movement of breathing decreased the quality of the images. Gradient recalled echo pulse sequences are now
used to perform fast MR and MR angiography by the application of “flip angles” (i.e., < 90 degrees), which
intensify the signals during T2 relaxation by creating magnetic field distortions. This process causes a T2* (T2 star)
time, which is shorter than the “true” T2 decay times of spin echo (SE) imaging. [5]
SE imaging uses pulse sequences of standard T1-weighted imaging, T2-weighted imaging, and proton density-
weighted images. The T1-weighted imaging is important for obtaining the best anatomic details and for identifying
subacute hemorrhages and fat. T2-weighted imaging enhances the detection of pathologic lesions by exploiting the
differences in the T2 relaxation times. With the proton density-weighted images, the tissue layers are emphasized,
making this scan the most useful for brain imaging.
Inversion recovery pulse sequences take advantage of the differences in T1 relaxation times between tissues. In
particular, the tissues with a short T1 time produce a brighter signal. To take advantage of this property, short T1
inversion recovery (STIR) sequences are most frequently used. Stated simply, the short T1 relaxation time tissues,
like fat, are suppressed (dark), and the high water content tissues such as muscles are enhanced in STIR images.
This yields images that accentuate pathologic lesions against a dark background. Echo planar imaging can be
performed in 20 seconds. MRI is the standard for noninvasive soft tissue imaging.
BONE SCANNING
The value of bone scanning relies on its ability to show physiologic changes rather than anatomic detail. Using an
intravenous injection of Technetium TC-99M methylene diphosphonate or a similar diphosphonate compound,
scintigraphic images can be obtained in 2 to 3 hours. In some cases, three-phase bone scans may be performed by
injecting a tracer, obtaining images of vascular regions in rapid sequence, and obtaining a blood pool image
followed by static images 2 to 3 hours later. When a comparison of earlier images (flow and blood pool) are
[3] [10] [11] [12]
made with delayed images (static) differences in vascularity may indicate inflammatory processes or changes
consistent with reflex sympathetic dystrophy. The radiation dose that the patient is exposed to is also considered low
compared with the exposure during routine lumbar spine x-rays.
Radiographic Contrast Agents
Over recent years, safer and more expensive low-osmolar agents have replaced cheaper high-osmolar ionic agents.
These water-soluble contrast agents consist of molecules containing iodine atoms and are used widely for CT,
urography, and fluoroscopic interventional procedures. Low-osmolar contrast agents have an osmolarity that is
reduced three times that of blood. This is one of the main reasons for a significant decrease in the number of adverse
reactions associated with the use of these agents. Decreased osmolarity equates to less hemodynamic alteration with
contrast injection.
[3]
759
In conjunction with fluoroscopy, contrast is an essential element for accurate needle placement, and contrast agents
have been used to delineate different tissue planes and monitor the spread of injected solutions such as local
anesthetics or neurolytic substances. They are often used to confirm epidural placement of permanent catheters and
to detect subdural or subarachnoid catheter placement or intravascular location. Because contrast agents may be
injected within the central nervous system (CNS) or intravascularly, the potential toxicity of the different agents
must be considered. The amount of contrast agent used during most regional anesthesia procedures is usually small;
therefore, the clinical effects described with larger volumes during radiographic procedures are usually not produced.
The possibility of a true anaphylactic reaction to contrast agents is extremely rare, but reactions can and do occur.
One must be able to provide airway support and intravascular volume expansion as well as deliver 100% oxygen
and epinephrine to treat the hypotension and hypoxia that may occur from vasodilatation, increased capillary
permeability, and bronchospasm in an anaphylactic reaction ( Table 30–1 ).
Commonly used contrast agents have a fully substituted, triiodinated benzene ring structure and may have an ionic
or nonionic formulation. The nonionic contrast agents provide opacification of the CNS and reduce CNS toxicity
after subarachnoid injection. Metrizamide,
TABLE 30-1 -- MANAGEMENT OF ANAPHYLAXIS *

Initial Therapy
1. Stop administration of antigen (contrast agent)
2. Maintain airway with 100% oxygen
3. Start IV volume expansion (2–4 L crystalloid) with hypotension
4. Discontinue any supplemental analgesic or sedative agents
5. Give epinephrine (4–8 µg IV bolus) with hypotension, titrate as needed; bolus (0.1–0.5 mg IV) with cardiovascular collapse
Secondary Treatment
1. Antihistamines (diphenhydramine 0.5–1 mg/kg)
2. Catecholamine infusions (starting doses: epinephrine 2–4 µg/ min) norepinephrine (2–4 µg/min) or isoproterenol (0.5–1 µg/ min) as a drip; titrate to desired effects)
3. Aminophylline (5–6 mg/kg over 20 min) with persistent bronchospasm
4. Corticosteroids (hydrocortisone 0.25–1 g); alternately, methylprednisolone (1–2 g) †
5. Sodium bicarbonate (0.5–1 mEq/kg) with persistent hypotension or acidosis
6. Airway evaluation (before extubation)
IV, intravenous.
*Doses are representative for a 70-kg adult.
†Methylprednisolone may be the drug of choice if the reaction may be mediated by complement.
the first nonionic formulation to be used, has for years provided state of the art imaging during myelography. [14]
However, it is formulated as a powder that must be prepared before use, and the side effect of frequent seizures with
its use is unacceptably high relative to newer agents that are available. If contrast agents are used near the central
axis and the potential for subarachnoid injection exists, iopamidol or iohexol is used because these drugs have a
lower potential for CNS toxicity, are water-soluble, and are provided in an easy-to-use liquid form ( Table 30–2 ).
With iodinated contrast media that are not indicated for intrathecal use, inadvertent intrathecal administration has
been associated with serious reactions. Reactions include death, convulsion, cerebral hemorrhage, coma, paralysis,
arachnoiditis, acute renal failure, cardiac arrest, seizures, rhabdomyolysis, hyperthermia, and brain edema. In most [15]
reported cases of major motor seizures with nonionic myelographic media. There were deviations from
recommended procedure; or, in myelographic management, these agents were used in patients with a history of
epilepsy, overdosage, intracranial entry of bolus, premature diffusion of a high concentration of the medium; or the
patient was taking medications such as neuroleptic drugs or phenothiazine antinauseants; or there was failure to
maintain elevation of the patient’s head on the bed during the procedure; or there was active patient movement or
straining. These factors occurred alone or in combination.
For parenteral administration of a radiopaque agent, competent personnel and emergency facilities should be
available for at least 30 to 60 minutes in case of severe delayed reactions. The patient should be prehydrated well
before administration of any contrast agents. A positive history of allergies or hypersensitivity does not necessarily
[10]
contraindicate the use of contrast agent if a diagnostic procedure is thought to be essential, but caution should be
exercised. Premedication with antihistamines or corticosteroids should be considered to avoid or minimize a
possible allergic reaction. Severe life-threatening anaphylactoid reactions of cardiovascular origin have occurred.
The incidence of death has ranges from 6.6 per million (0.00066%) to 1 in 10,000. Most deaths have occurred
during injection or 5 to 10 minutes later. Although cardiac arrest has been the main adverse result, cardiovascular
760
disease is the main aggravation factor. Isolated reports of hypotensive collapse and shock have been reported. The
incidence is estimated to be 1 of 20,000 patients (see Table 30–1 ).
DOSAGE AND INTRATHECAL ADMINISTRATION
The volume and concentration of contrast agent administration depend on the degree and extent of contrast required
in the area under examination and on the equipment and technique employed. A total dose of 3060 mg iodine, or a
concentration of 300 mgI/mL, should not be exceeded in adults, and a total dose of 2940 mg iodine, or a
concentration of 210 mgI/mL, should not be exceeded in children in a single myelographic examination. [15]
As with all procedures, the minimum volume and dose to produce adequate visualization should be used. The
patient should be well hydrated before and after contrast administration. Seizure-prone patients should be
maintained on anticonvulsant medications. Injection should be performed slowly over 1 to 2 minutes to
TABLE 30-2 -- COMMONLY USED CONTRAST SOLUTIONS

Agent Type Area of Use
Diatrizoate (Renografin, Hypaque) Ionic Nerve plexus blocks
Iothalamate (Conray) Ionic Nerve plexus blocks
Metrizamide (Amipaque) Nonionic, water-soluble Central neural blockade
Iopamidol (Isovue) Nonionic, water-soluble Central neural blockade
Iohexol (Omnipaque) Nonionic, water-soluble Central neural blockade
prevent excessive mixing with cerebrospinal fluid, which may be removed in amounts equal to the contrast amount
to be injected to prevent distention of subarachnoid spaces.
Indications for Radiologic Imaging [10]
Plain films are ideal for identification of bony defects, such as fractures, osteoporosis, and tumors, and for location
of implanted devices, such as foreign bodies. Plain films are quick, easy to obtain, and cost-effective. For these
reasons, they are often used as “scout” or preliminary studies to determine whether more advanced studies are
needed. Contrast agents are frequently added to enhance the studies by highlighting the structures of interest.
Fluoroscopy is considered a real-time radiographic device, which provides a poorer quality image than plain films.
Because of its active imaging abilities, it is useful in assisting the performance of radiographically directed
procedures, such as interventional pain management techniques, and for observing dynamic processes, such as
gastrointestinal studies and vascular catheterizations. The limitations of this device are often most evident in obese
patients because the diameter of the fluoroscopic C-arm may be inadequate to encompass the patient.
CT is a more advanced technique than traditional radiographic studies. It uses actual radiation to penetrate the target
in much the same way as plain films, but the images are produced serially in rapid sequence. It is, therefore,
extremely useful in the examination of bony defects and joints. Radiopaque contrast, like plain films, is useful to
enhance specific targets. CT myelograms used to determine “active” spinal column instability with flexion and
extension are an excellent example.
MRI is one of the great new advances in imaging studies. Because this technique works by the principles of
monitoring the changes in energy levels of the hydrogen atom, it has provided unparalleled images of soft tissues
such as tumors, muscles and ligaments. Without the need for radiation, it also limits the exposure of patients and
staffing personnel to acute radiation toxicity and possible long-term harm, such as cancer. The addition of
gadolinium further benefits MRI for passive examination of the spine by helping to distinguish fibrosis from disc
fragments in postsurgical patients. Gadolinium also enhances vascular tissues such as tumors. Without gadolinium,
MRIs are useful in the diagnosis of acute vertebral compression fractures versus chronic vertebral compression
fractures by showing bony edema in the T2 images ( Fig. 30–3 ).
[8]
Bone scans are useful in quantification of calcium intake by the body. This is helpful in examining bony tumors, in
assessing stress fractures not seen on plain
761
Figure 30-3 Magnetic resonance image showing bone edema. The picture is a T2-weighted image. Note the “whiteness” of the affected vertebral
level versus the nonedematous levels. In this patient, the “white” vertebral body or bone edema is due to an active compression fracture.
films, and in diagnosing CRPSI I and II in the predystrophic stages by showing increased activity in the joints of
positive patients with positive test results. When scans are ordered specifically for CRPS patients, a triple phase
bone scan is preferred ( Fig. 30–4 ).
A nuclear study that is useful in the armamentarium of interventional physicians is the tagged white blood cell study.
With this study white blood cells are “tagged” with nuclear material that is sensed by a passive imaging screen over
intervals of several minutes. This study is useful in any case that involves concern with an infectious process, such
as osteomyelitis and discitis. Unfortunately, this study does not help to distinguish between an active infectious
process and a healing one.
Radiation Safety
For anyone who is involved with radiation, the foremost thought is that of radiation protection. There are certain
factors that must be in order to categorize radiation concerns. The ionization of matter by radiation and the energy
[3] [9]
absorbed by matter from radiation are two dimensions for definition when dealing with radiation measurements. A
rad (radiation-absorbed dose) represents the amount of energy deposited in tissue from an ionizing radiation source.
The term gray (Gy), which has replaced rad, defines the deposition of energy or the absorbed dose in tissue, which
is equivalent to 1 joule per kilogram of tissue. Likewise, Coulomb per kilogram has replaced roentgen (R). Standard
conversions are as follows: 1 Sv equals 1 Gy, which equals 100 rem. One R equals 1 (rad), which is also equal to 1
roentgen-equivalent–man (REM). Occupational radiation exposure is set at 50 mGy (5 rads) per calendar year. [16] [17] [18]
Film badge reports most commonly use sievert or rem units. One analogy compares 50 mGy (5 rads) as the
[19]
equivalent to exposure from a 4-minute study per day without the use of a lead apron. There are two general
categories governing radiation protection: 1) effects that become more severe with increasing dose and for which a
threshold is believed to exist are called nonstochastic; and (2) effects whose probability worsens with increasing
dose and there is no threshold are called stochastic. Examples of nonstochastic effects include cataracts, blood
changes, and sperm production.
762
Figure 30-4 A, Bone scan of the whole skeletal structure, showing the increased activity and uptake of the radioactive agents in the affected limb.
B, In the magnified view, the right first metacarpal bone is extremely dark compared with the left. This patient had osteomyelitis in the right hand
of the first metacarpal bone.
TABLE 30-3 -- MAXIMUM PERMISSIBLE DOSE EQUIVALENTS (MSV) FOR RADIATION EXPOSURE
Area 13 Weeks Yearly Cumulative
Total effective dose equivalent 12.5 50 Age × 10
Lens of eye 37.5 150
Other organs (individually) 125 500
These effects occur beyond a certain threshold, and their severity increases with increasing exposure to ionizing
radiation. Examples of stochastic effects are cancer and genetic alterations. These effects can be produced at low
absorbed doses of ionizing radiation. Radiation protection practices are therefore twofold: (1) to prevent the
development of nonstochastic diseases by setting dose equivalent limits well below the threshold limit, which
ensures that these limits will not be reached even for the total period of one’s working life; and (2) to limit the risks
of stochastic diseases to a frequency no greater than the risk for nonradiation occupations. The acceptance of any
dose involves the acceptance of a risk as well, because a possibility exists that the radiation dose will manifest itself
during the lifetime of the exposed person or in subsequent generations. The probability is still so low that the risk is
acceptable to the average person ( Table 30–3 ).
Specific factors involved in radiation protection include type of radiation, penetration power, and ionization.
Radiation emissions come in alpha and beta particles and gamma rays. In addition, there are x-rays resulting from
interaction of several phenomena with matter. Another factor to consider is that of external versus internal emission.
Gamma rays and x-rays are able to penetrate the epidermis of the skin and present the same hazard whether they are
external or internal emitters. Alpha and beta particles do not usually penetrate the skin; therefore, they are not
[16]
considered a serious radiation threat.
Conclusion
Entire textbooks have been written on each of the radiographic techniques discussed in this chapter. Although this
discussion is not all-inclusive, the intention is to provide a brief overview of each radiographic technique that may
be useful in the practice of regional anesthesia and pain management. Additionally, it is beneficial for the
practitioner to be aware of the complications related to the radiation, contrast, and other drugs used in these tests or
763
procedures. Practitioners’ knowledge of the current radiographic environment monitors and protects both
practitioners and patients.
Improvements in technology offer the hope of perfect imaging with no harm may someday be met. Until this ideal
situation exists, however, the goal of improving images often requires that current imaging techniques be used in
combination or with adjuvant drugs. Unfortunately, supplemental drugs and techniques have side effects that are
sometimes detrimental to patients. Therefore, while scientists search for the ideal imaging system, they must always
be wary of the limitations of the tests that are ordered and the potential of complications from these tests. The results
of the tests are still dependent on the most important tool of the physician—clinical examination.
REFERENCES
1. Curry TS III, Dowdey JE, Murry RC Jr: Christensen’s Introduction to the Physics of Diagnostic Radiology; 4th ed. Philadelphia, Lea Fibiger,
1990.
2. Bushberg JT, Seibert JA, Leidholdt EMJ, Boone JM: The Essential Physics of Medical Imaging. Baltimore, Williams & Wilkins, 1994.
3. Brant WE, Helms CA: Fundamentals of Diagnostic Radiology, 2nd ed. Philadelphia, Lippincott Williams & Wilkins, 1999.
4. Rao KCV, Williams JP, Lee BCP, Sherman JL: MRI and CT of the Spine. Baltimore, Williams & Wilkins, 1994.
5. Hendrick RE: Basic physics of MR imaging: An introduction. Radiographics 14:829–846, 1994.
6. Saloner D: An introduction to MR angiography. Radiographics 15:453–465, 1995.
7. Berquist TH: MRI of the Musculoskeletal System, 2nd ed. New York, Raven, 1990.
8. Edelman RR, Hesselink JR: Clinical Magnetic Resonance Imaging. Philadelphia, WB Saunders, 1990.
9. Atlas SW: Magnetic Resonance Imaging of the Brain and Spine. New York, Raven, 1991.
10. Raj PP (ed): Practical Management of Pain, 3rd ed. St Louis, Mosby, 2000.
11. Alazraki N: Radionuclide techniques. In Resnick D (ed): Bone and Joint Imaging. Philadelphia, WB Saunders, 1989.
12. Wagner HN Jr, Szabo Z, Buchanan JW: Principles of Nuclear Medicine, 2nd ed. Philadelphia, WB Saunders, 1995.
13. Waldman SD: Interventional Pain Management, 2nd ed. Philadelphia, WB Saunders, 2001.
14. Skucas J: Radiographic Contrast Agents, 2nd ed. Rockville, MD, Aspen, 1989.
15. Iohexol product profile. Nycomed, Oslo, Norway, 2000.
16. Radiation Induced Skin Injuries from Fluoroscopy. FDA Med Bull 24:2, 1994.
17. Brodsky A: Principles and Practices for Keeping Occupational Radiation Exposures at Medical Institutions as Low as Reasonably Achievable.
Washington, D.C., U.S. Nuclear Regulatory Commission 1982.
18. NationalCouncil on Radiation Protection and Measurements: NCRP Report No. 91. Recommendations on limits for exposure to ionizing
radiation, Bethesda, MD, 1987.
19. Putman CE, Ravin CE: Textbook of Diagnostic Imaging, 2nd ed. Philadelphia, WB Saunders, 1994.
764
Section V Chapter 31 - Radiofrequency for the Treatment of Chronic Pain
Chapter 31 - Radiofrequency for the Treatment of Chronic Pain
RICARDO RUIZ-LÓPEZ
Radiofrequency-Induced Lesions in Chronic Pain Therapy
Following the initial attempts of Harvey Cushing, around 1920, who used radiofrequency (RF) in electrosurgery,
research advanced toward 1950, and in the next 3 decades the technique was perfected, with the aim of improving
control of the damaged area. Similarly, the development of multifunction electrodes has become essential for
monitoring the procedure and improving safety.
Although numerous neurodestructive techniques with selective applications have been used in the central or
peripheral nervous system in recent decades, RF techniques are the most efficacious and most widely used. The
advantages of RF techniques over other neurodestructive techniques can be listed as follows:
• The lesion can be controlled.

• Electrode temperature can be controlled.
• Electrode position is verified by stimulation test and impedance registry.
• Most RF techniques require only sedation or local anesthesia.
• There is a short recovery time after the procedure.
• Morbidity and mortality rates are low.
• The lesion can be reinduced in cases of neural regeneration.
PRINCIPLES OF RADIOFREQUENCY-INDUCED LESIONS
The basic principle of the RF technique consists of an electricity-generating source applied to an insulated electrode,
whose distal end is not insulated, situated in or near the vicinity of nervous tissue. The electrical impedance of the
surrounding tissue permits the flow of current from the generating source to the same tissue. The voltage of the
[1]
generator is established between the electrode (active) and the ground plate (dispersive) placed on the patient's arm
or leg. Body tissues complete the circuit, and the RF current flows through the tissue, producing an electric field.
This electric field creates an electric force in the ions of tissue electrolytes that produces rapid motion and friction.
The frictional dispersion of the ionic current within the fluid causes tissue warming. The heat produced by RF
energy is generated in the tissues, which thus heats the tip of the electrode and not vice versa. At this moment, the
[2]
temperature of the electrode tip is the same as the most hyperthermic zone of the tissue. As the current flows from
the tip of the electrode to the tissue, the warmest zone of the lesion is found where the current is densest, that is, in
the tissue closest to the electrode tip.
[1]
In this way, the size of the lesion produced can be controlled by thermal coagulation, because lesion size depends on
the temperature of the damaged zone, the length and diameter of the active tip of the electrode, and the vascularity
of the tissue. Modern cannulas are equipped with electrodes that accurately measure the temperature.
In 1972, Alberts et al found that frequencies higher than 250 kilocycles per second (kHz), approximately 500 kHz,
[3]
should be used to avoid undesirable responses because more uniform and better circumscribed lesions are obtained.
Although direct current and low-frequency alternating current are easy to generate, they do not facilitate good
control of lesion size, the effects of the stimulation are painful at the lesion site, and therefore they are not used.
Given that high frequencies, between 300 and 500 kHz, were also used in radiotransmitters, the current was called
radiofrequency. The first RF generator commercialized by Aranow and Cosman came onto the market at the end of
the 1950s.
Thermal balance is achieved at an exposure time of approximately 60 seconds but varies in richly vascularized
tissue zones. In highly vascularized tissue, more time is required to obtain thermal balance because blood vessels
tend to destabilize this balance, allowing heat to flow away. The most appropriate method of controlling lesion size
is to maintain a constant temperature of the electrode tip for 1 to 2 minutes. Occasionally, shorter lasting lesions can
be induced with higher temperatures, as in the case of percutaneous cordotomy by RF.
The size of the lesion also depends on the diameter of the electrode and the length of the noninsulated (active) tip of
the electrode. In 1984, Cosman and co-workers first established that, with the active tip at 75°C, the size of the
[1]
765
lesion increases by approximately 20% after a lesion induction time of 30 seconds. After 60 seconds, the size of the
lesion does not increase further.
According to the experimental work of Bogduk et al, RF lesions do not spread distally from the electrode but
[4]
radially around the active tip, in the form of an oblong spheroid with an actual maximum radius of 2 mm, using a
21-gauge (G) electrode with a 3-mm active tip. Other authors have concluded that the size of the lesion does not
[5] [6]
increase significantly after 20 seconds when different lesion times are used with the same temperature.
The effects of RF current on nerve fibers is still controversial. Some studies suggest that heat may modify nerve
function so that the harmful transmission is interrupted in nonfunctional fibers while other neural functions will
remain intact. RF heat damages only nonmyelinated or thinly myelinated fibers (C and A delta fibers), which are
involved mainly in pain transmission, whereas the myelinated A and AB fibers remain intact. Other studies [7] [8] [9] [10] [11]
were unable to reproduce this “specificity phenomenon,” and presently it is assumed that all nerve fiber types are
being damaged when a conventional RF lesion is produced.
It is still required that experimental studies reproduce the conditions under which RF-induced lesions are applied in
current clinical practice.
ELECTROMAGNETIC FIELDS
Doubts have arisen recently as to whether heat alone is the decisive factor causing RF lesions because heat is not the
only factor during production of the lesion. Surrounding tissue is also exposed to an electromagnetic field (EMF),
and these fields exert notable physiologic effects, particularly on the cellular membrane. This has led to an
investigation of the so-called isothermal RF procedures. Theoretically, an EMF can be applied in three ways
[10] [11]
without generating heat:
• By breaking the circuit by disconnection from the ground (creates an EMF without producing heat
because there is no current)
• By producing an RF lesion with a temperature of 42°C (applying very low voltage)
• By applying pulsed RF (pRF), which consists of an active cycle during which an EMF is applied with
heat generation and a silent phase to permit elimination of the heat. Studies using computerized models
indicate that the active cycle should not exceed 20 msec/sec to maintain the active tip at a temperature of
42°C. Comparison of results shows pRF to be a most effective method, and a special pRF option is
available on a lesion generator (RFG-3C Plus, Radionics).
The RF-EMF procedure has the following characteristics:
• Unlike the heat-induced lesion, which increases with the application time, EMF extension is constant.
• The heat lesion is neurodestructive, whereas the EMF lesion is not; furthermore, no transient sensory
deficit has been observed.
• Vascularization around the electrode decreases the extension of the heat effect. In the EMF procedure, the
vascularization enhances the efficacy because a greater output of the generator can be used without raising
the temperature beyond 42°C.
This method offers some advantages:
• Because it is not neurodestructive, the EMF technique can be used in cases of neuropathic pain or in
target structures where conventional RF cannot be applied, such as the C8 dorsal root ganglion.
• Postlesion discomfort is less than with conventional RF.
• RF-EMF presents no permanent sensory deficit as a complication, whereas sensory deficits do sometimes
occur with conventional RF.
RF-EMF also has its disadvantages:
• RF-EMF is not useful as a technique for producing sensory deficit, as in the case of trigeminal neuralgia.
• RF-EMF is not a useful technique for seeking effects at a distance from the electrode because the heat
diffuses, whereas RF-EMF does not, for example, in the intervertebral disc.
The method still requires validation through double-blind studies.
766
Sluijter (personal communication, Sept. 2001) stated that, at Durham University, basic research has shown that by
treating C6 dorsal root ganglia in rats with pRF, the wide dynamic range (WDR) cells of the dorsal horn showed an
increased c-fos gene expression in acute and middle terms. This finding could provide a neurophysiologic basis for
the effect of pulsed RF on neural tissue.
CONCEPTS OF SPINAL MORPHOLOGY AND IMPLICATIONS FOR THERAPY
The difficulty in treating chronic spinal pain necessitates the study of the anatomy and pathoanatomy of the
components of the vertebral column commonly involved in the genesis and perpetuation of chronic spinal pain. The
backbone possesses numerous potential pain generators. In fact, every structure in the spine that is innervated can be
a potential source of pain. The internal venous plexus and the ligamentum flavum are not known to be innervated.
Some areas identified by neuroanatomic dissection include the annulus fibrosus (AF) of the disc, posterior and
anterior longitudinal ligaments, some portions of the discal sheath, zygapophyseal articulations and their capsules,
spinal nerve roots and dorsal root ganglia, sacroiliac articulation and its capsule, and associated musculature. Several
specific RF techniques have been developed for zygapophyseal articulations, nerve roots, and sacroiliac articulation.
To date, no specific RF techniques have been described for the treatment of pain of dural or ligamentous origin, or at
trigger points.
Discogenic Pain
The intervertebral disc may be a source of pain. In 1947, Inman and Saunders showed how the discs receive
[14]
innervation and are therefore potential sources of pain; however, until the last decade, this concept was side-
[15]
stepped, leading to confusion and diagnostic errors in the question of discogenic pain. From an anatomic viewpoint,
the fact that the disc may be a source of pain is not currently under debate.
Data on disc pathology are incomplete and circumstantial, although the experimental reproduction of pain does not
correlate with degeneration of the disc but with the degree of fissures found in it. [16] [17]
Three grades of intensity with which the fissures penetrate the annulus have been defined. The term internal disc[18]
disruption (IDD) signifies that the internal architecture of the disc is broken, while the external surface remains
normal, with no protrusion or herniation. Pathologically, IDD is characterized by nucleus pulposus (NP) matrix
degradation and the presence of radial fissures that reach the external third of the AF. This condition cannot be
[15] [19]
diagnosed clinically, although it is demonstrable by disc stimulation and postdiscography computed tomography
(CT). A strong correlation exists between pain reproduction and the presence of grade 3 fissures, and can be [16]
defined as paradigmatic in the field of lumbar pain.
Internal disc disruption may be painful because of enzymatic nociception, the metabolic products implicated in the
degenerative process of the disc, and mechanical activation of AF nociceptors.
Some studies of patients with chronic lumbar pain have shown the prevalence of internal disc disruption to be at
least 39%. This prevalence points to internal disc disruption as the most frequent cause of objectively demonstrable
chronic lumbar pain. [20]
Finally, it should be mentioned that pain conditions that have prompted greater clinical dedication to spinal pain,
such as muscle pain and trigger points, are associated with less scientific evidence; a great void exists of scientific
data on the pain mechanisms in these conditions, and no reproducible diagnostic tests have been established. In
contrast, the greatest amount of scientific information is available for the less frequently diagnosed conditions,
[21]
such as sacroiliac joint pain, zygapophyseal articulation pain, and internal disc disruption. Prevalence data indicate
that these conditions are common, comprising over 60% of patients with chronic lumbar pain.
Zygapophyseal Articulations
Zygapophyseal articulations (ZAs) are innervated by the medial branch of the dorsal ramus. In 1933, Ghormley [22] [23]
coined the term facet syndrome, and over the past 2 decades the entity has acquired great clinical importance.
Standard criteria for diagnosing facetal syndrome include anesthesia of one or more ZAs, although the high rate of
false-positive results has invalidated the test.
767
In two studies, the prevalence of ZA pain ranged between 15% in a sample of North American workers who
[24] [25]
underwent RF-induced lesions, and 40% in a population of elderly patients in Australia recruited in a rheumatology
unit, with confidence limits of 10% to 20% and 27% to 53%, respectively.
ZA pain thus occurs among patients with chronic lumbar pain and is very common; it constitutes an independent
disorder because it is rarely associated with discogenic pain or sacroiliac articulation pain. Postmortem studies [26] [27]
and radiologic surveys have shown that lumbar ZA very often involves osteoarthrosis. Although it has been
[28]
claimed that zygapophyseal arthritis is secondary to disc degeneration and spondylosis, it may be an independent
entity in approximately 20% of cases. Data on the diagnostic value of CT are controversial, which suggests that the
[27]
diagnosis of painful zygapophyseal arthropathy should be considered using plain radiology.
Sacroiliac Articulation
The sacroiliac articulation (SA) is innervated by branches of the dorsal rami L4-5, S1, and S2, which run to the
posterior sacroiliac and interosseous sacroiliac ligaments. In fact, the sacroiliac articulation receives branches from
[29]
the obturator nerve, lumbosacral trunk, and superior gluteal nerve, although controversy exists as to whether the
[30]
innervation stems from the dorsal and ventral zones or is exclusively posterior.
The articulation may be a source of lumbar pain, with a variable reference pattern toward the lower limb. Rigorous [31]
studies have demonstrated that SA pain can be diagnosed by using intra-articular injections of local anesthetic. In
patients with chronic lumbar pain, the prevalence of SA pain is approximately 15%. The pathology of the pain is
[26] [32]
unknown, although occasionally ventral capsula disease may be observed. Although SA pain is common in[26]
patients with chronic lumbar pain, it can be diagnosed only with the use of articulation blockade with local
anesthetics. [21]
CHARACTERISTICS OF DIVERSE RADIOFREQUENCY LESIONS
Facet Denervation
Facet denervation consists of producing an RF lesion of the medial branch of the posterior primary branch that
innervates the zygapophyseal articulation. Although incorrectly called “rhizolysis,” because the root is not damaged,
the term survives. The aim of the procedure is to interrupt completely the medial branch because the danger of
causing sequelae by deafferentiation does not exist when a small area is innervated.
The lesion is produced at 80°C for 60 seconds, when a temperature monitoring system (SMK-system) is used. The
procedure must be performed at various vertebral levels because an intersegmental crossing exists in the innervation.
The procedure is generally safe and free of complications in expert hands.
Sympatholysis
Sympatholysis by RF can be used in two pathologic circumstances: in the treatment of sympathetically maintained
pain such as complex regional pain syndrome, and in pain caused by deafferentiation of the anterior zone of the
discal annulus fibrosus, interrupting the fibers that travel with the sympathetic system toward the neuronal body in
the dorsal root ganglion (DRG).
Complications seldom arise from the sympatholysis itself. In rare instances, the lower extremity can become red,
edematous, and hyperthermic; however, recovery is generally spontaneous.
In sympatholysis of the superior cervical ganglion, Horner's syndrome is produced in approximately 2% of cases
and remits spontaneously, although it may persist for several months. Complications do not tend to arise in
sympatholysis by RF of the damaged ganglion when performed by experienced practitioners.
Radiofrequency Lesion Adjacent to the Dorsal Root Ganglion
Producing this type of lesion usually is performed in refractory cases of monosegmental pain. The lesion should not
be produced inside the DRG because it causes total fiber destruction and, consequently, deafferentiation sequelae. If
the sensory stimulation threshold is too low (below 0.3-V), the electrode should be repositioned at a safer distance.
Although not the cause of microscopic changes, the lesion does induce degenerative changes in the ganglion, which
are demonstrable by histochemical techniques. Since 1998, the application of pRF on the DRG seems to be as
[40]
effective as the conventional RF heat lesion. [9]
768
There are several advantages of pRF over conventional RF. First, as far as we know, the pRF technique is not
damaging to the nerve; second, it can be used for treating neuropathic pain conditions; and third, with little
postprocedure discomfort, pRF allows the treatment of several levels in the same operative session.
Radiofrequency Lesion of the Intervertebral Disc
This procedure is used in treating discogenic pain. The particular properties of the intervertebral disc should be
borne in mind:
• The disc is avascular.

• The center of the disc has very low electrical impedance, indicating very high conductivity to heat.
• The vertebral end plates of adjacent vertebrae act as insulators.
These properties contribute to establishing an ample lesion, with the heat expanding as far as the annulus fibrosus,
heating this structure enough to reduce the activity of fine fibers and nerve endings. The effect is probably increased
by generation of heat within the annulus, originated by the high current required to heat the active tip of the
electrode because of its low impedance and high conductivity.
It has not been possible to reproduce experimentally the discal damage caused by this procedure. Magnetic
resonance imaging studies of the disc show no variation or modification in the height of the disc several years after
the procedure. Similarly, producing a lesion in extradiscal structures is not acceptable because the annulus fibrosus
is surrounded by vascular tissue that would eliminate the heat emitted by the annulus.
Diagnostic Blockades before Production of Radiofrequency Lesion
To establish a correct diagnosis and rule out pathologic causes for which treatment is available, the following are
required: a detailed anamnesis, an appropriate physical examination, neurophysiologic studies, and other tests, if
indicated, together with psychological assessment if suffering or psychoaffective alterations are concomitant with
the chronic pain condition. [41]
Although occasionally an anatomic substrate, which may justify the patient's pain, is not found, particularly in spinal
disorders, the selective use of diagnostic blockades can aid in the diagnosis of the origin of the pain. Spinal
innervation is profuse and complex. According to current knowledge, only the yellow ligament and venous plexuses
are not innervated; thus, all remaining spinal structures should be considered potential sources of pain. [42]
It has been demonstrated that pain referred by a particular spinal segment may originate in different structures at
different levels. The only exception to multisegmental innervation of spinal structures could be the ventral dura,
which is innervated at a specific level in its lateral zone and devoid of innervation at its middle part, receiving more
or less a monosegmental innervation. [37]
It is important to consider that the multisegmental and bilateral innervation patterns may occasionally call for
bilateral blockades at several levels. Moreover, the finding that spinal innervation, particularly in the ventral
compartment, shares common pathways with autonomic nerves (e.g., sympathetic trunk and rami communicantes)
may suggest that the autonomous nervous system plays a role in the maintenance of spinal pain, with [43]
corresponding therapeutic repercussions.
Furthermore, it is necessary to stress the importance of physical examination of the patient during the latency and
pharmacologic action periods of the local anesthetic, with the aim of establishing a correlation between the response
to pain and the presence of accompanying physical signs and symptoms.
Once the temporary response to a diagnostic blockade has been verified, the RF or thermal lesion should be
considered because this type of lesion offers as its main advantage exact control or limitation of the lesioned area.
Such control does not occur in chemical neurolysis because the neurolytic fluids that are injected may spread
unpredictably, causing unexpected complications.
Similarly, the RF lesion is preferable to the cryolesion because the latter remains for shorter periods of time, usually
not exceeding several months. [44]
769
The sole aim of a diagnostic blockade is to verify the cause of the pain. Although not totally specific, it is useful in
some pain conditions. The false-positive result usually is caused by the spread of local anesthetic into tissues or
different structures off the target; thus, a radiologic contrast medium should always be used to ensure correct
location of the cannula and to judge the spread on injection of the contrast. A small volume of local anesthetic
should be administered to avoid false-positive block. The false-negative result is usually caused by the injection of
local anesthetic into a highly vascularized area or an intramuscular region. Poor communication between the
physician and the patient may cause false-positive results, a negative block, or both.
The following diagnostic blockades are currently considered useful in clinical practice:
• Sphenopalatine ganglion blockade

• Sympathetic chain blockade at different levels
• Segmental neural blockade
• Ramus communicans blockade
• Intervertebral disc blockade
The diagnostic blockade of zygapophyseal articulations, widely used in the past, has proved to be of insufficient
specificity owing to the frequent extra-articular diffusion of the local anesthetic solution; therefore, its efficacy is
now in doubt. The medial branch block with local anesthesia of the posterior ramus is probably more reliable.
In some cases, it is not easy to distinguish between pain originating from the dorsal and ventral spine compartments
because they may share common symptoms. Both compartments are closely related in the lumbar spine because
they originate in the same “triarticular complex” (three-joint complex). In these cases, selective blockades are of
[45]
value because the diagnosis of the ventral compartment syndrome is established by the positive response to
blockades of the sinuvertebral nerves, rami communicantes, and sympathetic chain. Blockades of the rami
communicantes and sympathetic chain are of prognostic value owing to the possibility of producing RF lesions in
these structures. At present, the sinuvertebral nerves, which are responsible for the posterior innervation of the
ventral compartment, cannot be selectively blocked. This represents a disadvantage because the discal disease of the
posterior zone, particularly at the L4-5 and L5-S1 levels in adults, is clinically more significant. In these cases,
Sluijter reported positive results in a series of patients following lesions of the rami communicantes. [46]
Another indication for producing RF-induced lesions in the rami communicantes is in treating pain originating from
a so-called burned-out disc, in which the disc is so degenerated that there is too little substrate for an RF disc lesion.
Radiofrequency Lesion Methodology
To produce an RF lesion, follow the following steps:
1. Access the target structure using the RF electrode cannula, using radiographic visualization and a C-arm in
different views. The tunnel vision technique is often used, with the x-ray beam parallel to the electrode.
2. Obtain neurophysiologic confirmation of the correct positioning of the cannula by electrostimulation:
3.
A. Administer sensory stimulation at 50 Hz to confirm the proximity of the target structure.
B. Administer motor stimulation at 2 Hz to confirm absence of motor fibers in the vicinity.
4. Administer local anesthesia to the target structure.
5. Induce the lesion by RF:
A. Apply conventional RF (thermocoagulation), typically at 80°C to 82°C for 60 to 90 seconds.
B. Apply pulsed RF (electromagnetic fields), typically at 40°C to 42°C for 120 seconds.
770
Figure 31-1 A, General view of a radiofrequency (RF) facility. B, Lesion generator (Radionics 3c plus). C, Electrodes and cannulas
(nondisposable).
Techniques for RF-produced lesions are described in the appendix of this chapter. It is important to remember that
an adequate facility, equipment, and needles are required, along with a trained staff, to ensure good outcome with
the procedures ( Fig. 31–1 A–C).
ACKNOWLEDGMENTS
The author wishes to thank Ms. Raquel Rodríguez for secretarial assistance and Dr. Olav Rohof for review of the
manuscript.
REFERENCES
1. Cosman ER, Nashold BS, Bedenbaugh P: Stereotactic radiofrequency lesion making: Proceedings of the American Society of Stereotactic and
Functional Neurosurgery, Durham, NC Appl Neurophysiol 46:160–166, 1983.
2. Van
Kleef M: Radio-frequency Lesions of the Dorsal Root Ganglion in the Retreatment of Spinal Pain [thesis]. Maastricht, Netherlands,
Universitaire Pers Maastricht, 1996.
3. Alberts WW, Wright EW, Feinstein B, et al: Sensory responses elicited by subcortical high frequency electrical stimulation in man. J Neurosurg
36:80–82, 1972.
4. Bogduk N, Macintosh J, Marsland A: Technical limitations to the efficacy of radiofrequency neurotomy for spinal pain. Neurosurg 20:529–535,
1987.
5. Moringlane JR, Koch R, Schäfer H, et al: Experimental radiofrequency (RF) coagulation with computer-based online monitoring of temperature
and power. Acta Neurochir 96:126–131, 1989.
6. Viñas FC, Zamorano L, Dujovny M, et al: In vivo and in vitro study of the lesions produced with a computerized radiofrequency system.
Stereotact Funct Neurosurg 58:121–133, 1992.
7. Letcher FS, Goldring S: The effect of radiofrequency current: and heat on peripheral nerve action potential in the cat. J Neurosurg 29:42–47,
1968.
8. Smith HP, McWhorter JM, Challa VR: Radiofrequency neurolysis in a clinical model. J Neurosurg 55:246–253, 1981.
9. Hamann W, Hall S: Acute effect and recovery of primary afferent nerve fibres after graded RF-lesions in anesthetized rats. Br J Anaesth 68:443,
1992.
10. Sluijter
ME, Cosman ER, Ritman WB III, et al: The effects of pulsed radiofrequency fields applied to the dorsal root ganglion—a preliminary
report. Pain Clin 11:109–117, 1998.
771
11. Sluijter ME, van Kleef M: Characteristics and mode of action of radiofrequency lesions. Curr Rev Pain 2:143–150, 1998.
12. Peacock H: Observations on the pre-natal development of the intervertebral disc in man. J Anat 85:260–274, 1951.
13. Inove H, Takeda T: Three-dimensional observation of collagen framework of lumbar intervertebral discs. Acta Orthop Scand 46:949–956,
1975.
14. Inman VT, Saunders JBC: Anatomicophysiological aspects of injuries to the intervertebral disc. J Bone Joint Surg 29:461–475, 534, 1947.
15. Bogduk N: The lumbar disc and low back pain. Neurosurg Clin North Am 2:791–806, 1991.
16. Moneta GB, Videman T, Kaivanto K, et al: Reported pain during lumbar discography as a function of anular ruptures and disc degeneration: A
reanalysis of 833 discograms. Spine 17:1968–1974, 1994.
17. Vanharanta
H, Sachs BL, Spivey MA, et al: The relationship of pain provocation to lumbar disc deterioration as seen by CT/discography.
Spine 12:295–298, 1987.
18. Sachs
BL, Vanharanta H, Spivey MA, et al: Dallas discogram description: A new classification of CT/discography in low-back disorders.
Spine 12:287–294, 1987.
19. Bogduk N, Aprill C, Derby R: Discography. In White AH (ed): Spine Care, vol 1. Diagnosis and Conservative Treatment. Mosby, St. Louis,
1995, pp 219–238.
20. Schwarzer AC, Derby R, Aprill CN, et al: The prevalence and clinical features of internal disc disruption in patients with chronic low back
pain. Spine 20:1878–1883, 1995.
21. Bogduk N: In Clinical Anatomy of the Lumbar Spine and Sacrum, 3rd ed. New York, Churchill Livingstone, 1997, pp 187–213.
22. Jackson
HC, Winkelman RK, Bickel WH: Nerve endings in the human lumbar spinal column and related structures. J Bone Joint Surg Am
48:1272–1281, 1966.
23. Bogduk N: The innervation of the lumbar spine. Spine 8:286–293, 1983.
24. Schwarzer AC, Aprill CN, Derby R, et al: Clinical features of patients with pain stemming from the lumbar zygapophyseal joints: Is the
lumbar facet syndrome a clinical entity? Spine 19:1132–1137, 1994.
25. Schwarzer AC, Wang S, Bogduk N, et al: Prevalence and clinical features of zygapophyseal joint pain: A study in an Australian population
with chronic low back pain. Ann Rheum Dis 54:100–106, 1995.
26. Schwarzer AC, Aprill CN, Bogduk N: The sacroiliac joint in chronic low back pain. Spine 20:31–37, 1995.
27. Lewin T: Orteoarthritis in lumbar synovial joints. Acta Orthop Scand Suppl 73:1–112, 1964.
28. Magora A, Schwartz A: Relation between the low back pain syndrome and x-ray findings: Part 1. Degenerative osteoarthritis. Scand J Rehabil
Med 8:115–125, 1976.
29. Paris SV: Anatomy as related to function and pain. Orthop Clin North Am 14:475–489, 1983.
30. Grob KR, Neuhuber WL, Kissiling RO: Innervation of the human sacroiliac joint. Z Rheumatol 54:117–122, 1995.
31. Fortin
JD, Dwyer AP, West S, et al: Sacroiliac joint: Pain referral maps upon applying a new injection/arthrography technique: Part I:
Asymptomatic volunteers. Spine 19:1475–1482, 1994.
32. MaigneJY, Aivaliklis A, Pfefer F: Results of sacroiliac joint double block and value of sacroiliac pain provocation tests in 54 patients with
low back pain. Spine 21:1889–1892, 1996.
33. Shealey CN: Percutaneous radiofrequency denervation of spinal facets and treatment for chronic back pain and sciatica. J Neurosurg 43:448–
451, 1975.
34. Uematsu S, Udvarhelyi GB, Benson DW, et al: Percutaneous radiofrequency rhizotomy. Surg Neurol 2:319–325, 1974.
35. Sluijter
ME, Mehta M: Treatment of chronic back and neck pain by percutaneous thermal lesions. In Lipton S (ed): Persistent Pain: Modern
Methods of Treatment, vol 3. London, Academic Press, 1981, pp 141–179.
36. Bogduk N, Tynan W, Wilson AS: The nerve supply to the human lumbar intervertebral discs. J Anat 132:39–56, 1981.
37. Groen G, Baljet B, Drukker J: The nerves and nerve plexuses of the human vertebral column. Am J Anat 188:282–296, 1990.
38. Rabischong P, Louis R, Vignaud J, et al: The intervertebral disc. Anat Clin 1:55–64, 1978.
772
39. Yoshizawa H, O'Brien JP, Thomas-Smith W, et al: The neuropathology of intervertebral discs removed for low-back pain. J Pathol 132:95–
104, 1980.
40. Cosman ER, Cosman BJ: Methods of making nervous system lesions. In RH Wilkins, SS Renchary (eds): Neurosurgery. New York, McGraw-
Hill, 1985, pp 2490–2499.
41. Waddell G, McCulloch JA, Kummel E, et al: Nonorganic physical signs in low-back pain. Spine 5:117–125, 1980.
42. Stolker RJ, Vervest ACM, Given GJ: The management of chronic spinal pain by blockades: A review. Pain 58:1–20, 1994.
43. Weinstein
JN: Anatomy and neurophysiologic mechanisms of spinal pain. In JW Frymoyer (ed): The Adult Spine. Principles and Practice.
New York, Raven Press, 1991, pp 593–610.
44. Katz J: Cryoanalgesia for posthoracotomy pain. Ann Thorac Surg 48:5, 1989.
45. Butler D, Trafimow JH, Andersson GBJ, et al: Discs degenerate before facets. Spine 15:111–113, 1990.
46. Sluijter
ME: Radiofrequency lesions of the communicating ramus in the treatment of low back pain. In Racz GB (ed): Techniques of
Neurolysis. Boston, Kluwer, 1989, pp 145–160.
47. Pitres JA, Verger TPH: Memorrio et bulletin de médicine et chirurgie de Bordeaux. 1902 pp 91–96.
48. Swerdlow M: The history of neurolytic block. In Racz GB (ed): Techniques of Neurolysis. Boston, Kluwer Academic Publishers, 1989.
49. Cushing H: The role of deep alcohol injections in the treatments of trigeminal neuralgia. JAMA 75:441–443, 1920.
50. Kirschner M: Zur Electrochirurgie. Arch Klin Chir 161:761–768, 1931.
51. Putnam TJ, Hampton AO: The technic of injection into the Gasserian ganglion under roentgenographic control. Arch Neurol Psychiatry 35:92–
98, 1936.
52. Haakansson S: Retrogasserian glycerol injection as a treatment of tic douloureaux. Adv Pain Res Ther 5:927, 1983.
53. Sweet
WH, Wepsic JG: Controlled thermocoagulation of trigeminal ganglion and root for diferential destruction of pain fibers. Part I:
Trigeminal neuralgia. J Neurosurg 39:143–156, 1974.
54. Onofrio BM: Radiofrequency percutaneous gasserian ganglion lesion: Results in 140 patients with trigeminal pain. J Neurosurg 42:132–139,
1975.
55. Jannetta
PJ: Trigeminal neuralgia: Treatment by microvascular decompression. In Wilkins RH, Rengachary SS (eds): Neurosurgery, vol 3.
New York, McGraw-Hill, 1985, pp 2357–2363.
56. Loeser JD: Tic douloureux and atypical facial pain. In Wall PD, Melzack R (eds): Textbook of Pain. New York, Churchill Livingstone, 1985,
pp 264:426–434.
57. Sweet WH: The history of the development of treatment for trigeminal neuralgia. Clin Neurosurg 294–318, 1985.
58. Forouzanfar T, Van Kleef M, Weber WEF: Radiofrequency lesions of the stellate ganglion in chronic pain syndromes: Retrospective analysis
59. Moore DM: Stellate ganglion block. Springfield, IL, Charles C Thomas, 1954.
60. Geurts
JWR, Stolker RJ: Percutaneous radiofrequency lesion of the stellate ganglion in the treatment of pain in the upper extremity reflex
61. MalmquistEl-A, Bengtsson M, Sorensen J: Efficacy of stellate ganglion block: A clinical study with bupivacaine. Reg Anesth Pain Med
17:340–347, 1992.
62. Slappendel R, Thijssen HOM, Crul BJP, et al: The stellate ganglion in magnetic resonance imaging: A quantification of the anatomic
variability. Anesthesiology 83:424–426, 1995.
63. Aprill C, Dwyer A, Bogduk N: Cervical zygapophysial joint pain patterns. II. A clinical evaluation. Spine 15:458–461, 1990.
64. Sluijter ME: Radiofrequency Lesions in the Treatment of Cervical Pain Syndromes. Burlington, VT, Radionics, 1990, pp 1–19.
65. Van Kleef M, Spaans F, Dingemans WAAM, et al: Effects and side effects of a radiofrequency lesion of the dorsal root ganglion (RF-DRG) in
patients with cervical pain syndrome. Pain 52:49–53, 1993.
66. Slappendel
R, Crul BJP, Braak GJJ, et al: The efficacy of radiofrequency lesioning of the cervical spinal dorsal root ganglion in a double
blinded randomized study: No difference between 40° C and 60° C treatments. Pain 73:159–163, 1997.
773
67. Nash TP: Percutaneous radiofrequency lesioning of dorsal root ganglia for intractable pain. Pain 24:67–73, 1986.
68. Van Kleef M, Liem L, Lousberg R, et al: Radiofrequency lesion adjacent to the dorsal root ganglion for cervicobrachial pain: A prospective
double blind randomized study. Neurosurgery 38:1127–1132, 1996.
69. LahuertaJ, Bowsher D, Campbell J, et al: Clinical and instrumental evaluation of sensory function before and after percutaneous cordotomy at
cervical level in man. Pain 42:23–30, 1990.
70. Wilkinson HA: Percutaneous radiofrequency upper thoracic sympathectomy: A new technique. Neurosurgery 15:811–814, 1984.
71. Wilkinson HA: Radiofrequency percutaneous upper thoracic sympathectomy: Technique and review of indications. N Engl J Med 311:34–36,
1984.
72. Kappis M: Erfahrungen mit lokalanästhesie bei bauchoperationen. Ver Dtsch Ges Cir 43:87, 1914.
73. Kappis M: Die anästhesierung des nervus splanchnicus. Zentralbl 45:709, 1918.
74. Montero AM, Vidal FL, Martinez LI: Percutaneous approach to the celiac plexus using CT guidance. Pain 34:285–288, 1988.
75. Raj PP, Thomas J, Heavner J, et al: The development of a technique for radiofrequency lesioning of splanchnic nerves. Curr Rev Pain 3:377–
387, 1999.
76. Raj P: Technique for Radiofrequency Lesioning of Splanchnic Nerves. Proceedings of the ESRA and ESOA Congress 2000. Athens, May
2000. Book of Abstracts, pp 91–95.
77. Abram SE, Boas RA: Sympathetic and visceral nerve blocks. In Benumof JL (ed): Clinical Procedures in Anesthesia and Intensive Care.
Philadelphia, JB Lippincott, 1993, pp 787–805.
78. Singler RC: An improved technique for alcohol neurolysis of the celiac plexus. Anesthesiology 56:137–141, 1982.
79. Rocco AG, Palombi D, Raeke D: Anatomy of the lumbar sympathetic chain. Reg Anesth Pain Med 20:13–19, 1995.
80. Bonica JJ (ed): The Management of Pain. Philadelphia, Lea & Febiger, 1953, p 441.
81. Umeda S, Arai T, Halano Y, et al: Cadaver anatomic analysis of the best site for chemical lumbar sympathectomy. Anesth Analg 66:643–646,
1987.
82. KanthaKS: Radiofrequency percutaneous lumbar sympathectomy: Technique and review of indications. In Racz G (ed): Techniques of
Neurolysis. Boston, Kluwer Academic Publishers, 1984, pp 171–183.
83. Lippit AB: The facet joint and its role in spine pain: Management with facet joint injections. Spine 7:746–750, 1984.
84. Mooney V: Clinical entities: Facet syndrome. In Weinstein IN, Wiesel SW (eds): The Lumbar Spine. Philadelphia, WB Saunders, 1990, pp
422–441.
85. Murtagh FR, Paulsen RD, Rechtine GR: The role of facet tropism in lumbar spine degenerative disease. J Spinal Disord 4:86–69, 1991.
86. Ghormley RK: Low back pain, with special reference to the articular facets, with presentation of an operative procedure. JAMA 101:1773–
1777, 1933.
87. Bogduk N, Long DM: Percutaneous lumbar medial branch neurotomy: A modification of facet denervation. Spine 5:193–200, 1980.
88. Wedley JR, Gallagher J, Hamann W, et al: An evaluation of facet joint denervation in the management of low back pain. Pain 5(suppl):391,
1990.
89. North RB, Ham M, Zahurak M, et al: Radiofrequency lumbar facet denervation: Analysis of prognostic factors. Pain 57:77–83, 1994.
90. GallagherJ, Petricciore PL, Wedley JR, et al: Radiofrequency facet joint denervation in the treatment of low back pain: A prospective
controlled double-blind study to assess its efficacy. The Pain Clinic 7:193–198, 1994.
774
APPENDIX 1: Radiofrequency Techniques
1. GASSERIAN GANGLION
Tic douloureux was the standard type of neuralgia for which neurolytic block treatment was tried. In 1902, Pitre
treated trigeminal neuralgia for the first time by injecting alcohol into the nerve. He was followed by other authors
[47]
who gave this technique a great deal of publicity. By 1905, Schlosser had reported 68 cases of severe trigeminal
[48]
neuralgia treated successfully by alcohol nerve block. According to Cushing, Hartel was the first to block the
[49]
gasserian ganglion (GG) itself with alcohol. In the early 1930s, Kirschner began to use radiofrequency neurolysis,
[50]
using diathermy to produce high-current lesions of the gasserian ganglion, for relief of trigeminal neuralgia, the first
report in medical literature to use radiofrequency for the treatment of chronic intractable pain.
Putnam and Hampton, who reported 18 cases of trigeminal neuralgia and four cases of oral carcinoma,
[51]
recommended radiographically guided control during the procedure. Their procedure used 0.5 mL of 5% phenol,
and they were the first to publish the use of phenol as a neurolytic agent for the treatment of this condition.
In 1983, Haakansson advocated injecting the GG with glycerol; however, although good results have been reported,
[52]
interest in glycerol has recently decreased. From 1969 through 1986, Sweet and Wepsic developed percutaneous
thermal retrogasserian rhizotomy for the treatment of trigeminal neuralgia. [53]
A. Indications
Idiopathic cranial nerve V neuralgia
Some secondary cranial nerve V par neuralgias (e.g., multiple sclerosis)
Alleviation of cancer pain in the head and neck
Alleviation of pain resulting from acute trigeminal herpes zoster (using pRF)
Cluster headache management (using pRF)
B. Contraindications
Neuropathic pain in the trigeminal area
Local infection, sepsis
Coagulopathies
Increased intracranial pressure
Major psychopathology
C. Material
SMK needle: 10 cm, 22-gauge (G); 0.2-cm active tip

*
D. Patient position
Patient is in a decubitus supine position
Frontal mentonian plane parallel to the table
Head secured to the table with lateral bands
E. Anesthesia
775
Superficial intravenous sedation (e.g., propofol or methohexital [Brevital]); the patient must be able to
collaborate when the stimulation test is performed.
Local anesthesia of the zone to be incised is not needed.
F. Anatomic references
1. The GG contains sensory and motor fibers of the face, nasal and oral mucosae, teeth, and anterior
two thirds of the tongue, and motor fibers for the masticatory muscles.
2. The GG links with the autonomic nervous system through the ciliary, sphenopalatine, otic, and
submaxillary ganglia, and communicates with the oculomotor, facial and glossopharyngeal nerves.
3. Entry point: 2 to 3 cm lateral to the corner of the mouth, homolateral to the lesion
4. Homolateral pupil
5. Cannula should be inserted following the bisector (45 degrees) of the sagittal plane, which passes
through the pupil and the frontal-mentonian plane at the level of external auditory meatus.
G. Radiographic technique
1. Oblique projection: Lateral inclination of approximately 30 degrees toward the side of the lesion,
with a caudal inclination of approximately 30 degrees. The mentonian arch must be seen and, in
the upper internal quadrant to it, the foramen ovale submentovertex projection ( Fig. 31–2 A).
2. Lateral projection: Performed when the cannula has been inserted into the foramen ovale. This
lateral view is useful to calculate the insertion of the cannula into the bony tunnel of the foramen
ovale. The tip of the cannula must not exceed 2 mm from the plane of the clivus (see Fig. 31–2 B).
* Refers throughout to SMK disposable cannulas, COTOP International, Amsterdam, the Netherlands.
H. Risks and complications
Hemorrhage at the insertion site; perform compression.
Perforation of the oral cavity; to avoid this, the cannula should be guided with the index finger placed
intraorally.
If leakage is abundant, dural puncture occurs. In such cases, continuation of the technique must be assessed.
If cerebrospinal fluid is not abundant, the procedure may be continued.
I. Stimulation parameters
Voltage: 0 to 1 V
Sensory: 50 Hz; paresthesia induced between 0.05 and 0.3 V must be noted in the painful zone.
Motor: 2 Hz; at 0.6 to 1 V there must be no or only minimal motor contraction of the masseter muscle. If
no motor contraction occurs, the tip of the needle is positioned in branches I or II of cranial nerve V.
J. Lesion parameters
First lesion: 60 seconds at 65°C. When the lesion has been induced, check the bilateral corneal reflex and
pain sensitivity in the neuralgic and contralateral zones.
Second lesion: 60 seconds at 70°C. Proceed in a similar manner as above.
Third lesion: 60 seconds at 72°C to 75°C. Proceed in a similar manner as above.
Fourth lesion: This may be assessed at 75°C if pain involves two branches of cranial nerve V.
K. Comments
Because RF thermocoagulation is painful, the patient is given a short anesthetic sleep using a suitable dose
of intravenous anesthetic. Intravenous anesthetic may sometimes be supplemented by intermittent nasal
776
insufflation of a nitrous oxide–oxygen mixture during each coagulation to accelerate anesthesia and
recovery. The patient must be conscious between each coagulation so that sensory testing of the face can
take place. The end point is reached when the desired division of the trigeminal nerve has become slightly
analgesic but not anesthetic. Usually, at approximately 70°C, analgesia occurs, and further coagulations are
performed at the same temperature until some analgesia is produced in the required division. At this stage,
the time for each coagulation can be increased or decreased; however, if the temperature is increased
without first trying extra time, anesthesia will suddenly develop. Analgesia produced by this method tends
to increase over the first 2 hours. If slight leakage occurs during the procedure, it should be considered a
consequence of the ganglion puncture, with the risk of a cerebrospinal fluid fistula being minimal.
Weakness of the homolateral masseter muscle may occur during the postoperative period. During the lesion
induction periods, correct ventilation of the patient must be ensured; therefore, oxygen must be
administered with a mask.
Sequential throbbing of the cannula may occasionally be observed during the early seconds of lesion
induction. This movement is due to the fact that in conventional RF, current is emitted every 0.66 seconds
but in pulsed RF current is emitted every 20 milliseconds.
Pulsed RF is not useful in the treatment of cranial nerve V neuralgia. It is indicated in treating postherpetic
cranial nerve V par neuralgia, together with other pharmacologic therapies, and in managing the painful
sequela of “anesthesia dolorosa” in the cranial nerve V territory by conventional RF, with variable results.
Figure 31-2 A, Gasserian ganglion, submental view with an approach to the foramen ovale. B, Gasserian ganglion, lateral view of the skull. The
tip of the needle must not exceed 2 to 3 mm to the plane of clivus.
2. SPHENOPALATINE GANGLION
A. Indications
Sphenopalatine (SP) neuralgia
Migraine headache
Cluster headache
Pain in I and II distributions of cranial nerve V neuralgia
B. Material
SMK needle: 10-cm, 5-mm active tip and RF curved blunt 10-cm, 10-mm active tip
777
C. Patient position
Patient in supine decubitus position
Head secured to the table with lateral bands
Superficial intravenous sedation
D. Anesthesia
Mild intravenous sedation (e.g., propofol) if needed
Local anesthesia of the zone to be incised
Patient should be monitored by electrocardiography and pulse oximetry
E. Anatomic references
The sphenopalatine ganglion (SPG) is located in the pterygopalatine fossa just posterior to the middle
turbinate, lying 1 to 9 mm deep to the lateral turbinate; it is the largest nerve center outside the cranial
cavity.
The sphenopalatine fossa is located at the end of the petrous bone, below the sphenoidal sinus ( Fig. 31–3 ).
The puncture site is located below the zygomatic arch and between the mandibular arch, in the posterior
zone.
F. Radiographic technique
Lateral projection: Define the sphenopalatine (SP) fossa, sella turcica, clivus, and petrous bone. The SP
fossa is situated below the anterior portion of the petrous bone, which underlies approximately the clinoid
apophysis, anterior to the sella turcica. Insert the needle perpendicular to the skin, as far as the SP fossa
(see Fig. 31–3 A).
Using a lateral projection, place a metallic marker above the SP fossa. Perform the puncture in the upper
zone of the mandibular arch and progress perpendicularly until the patient notices paresthesia in the
jawbone.
Anteroposterior (AP) projection: Vary the radioscope at an AP projection and advance the cannula
medially until it is adjacent to the lateral wall of the nasal cavity. Insert the cannula 1 to 2 mm until it slides
within the recess (see Fig. 31–3 B).
The tip of the needle should pass over the vomer bone by approximately 1 to 2 mm; care should be taken
not to pierce the partition between the nostrils.
G. Risks and complications
Lesion of the second branch of cranial nerve V may occur in the initial section of the puncture.
Nasal hemorrhage: Five percent of patients present with epistaxis. Do not discharge the patient until
hemorrhage resolves. In rare cases, placement of a nasal tamponade is needed and should be performed by
an otolaryngologist.
Infection
Numbness of upper teeth or hard palate
H. Stimulation parameters
778
Voltage: 0 to 1 V
Sensory: 50 Hz; 0, 3 to 0, 4 V. Sensory stimulation is considered positive when parethesias are achieved in
the palate, and particularly in the nasal region. If the stimulation occurs only in the palate, insert the
cannula slightly medial and cephalad.
Motor: 2 Hz; verify absence of maxillar contraction.
I. Lesion parameters
Prior to performing the lesion, inject 1 mL of 2% lidocaine (some authors use lidocaine injection as a
prognostic blockade).
First lesion: 60 seconds, 80°C, administered in the sphenopalatine fossSecond lesion: 60 seconds, 80°C,
administered somewhat more medially (1 to 2 mm)
Third lesion: 60 seconds, 80°C, administered somewhat more medially (3 mm)
Pulsed RF may be used. To induce a single lesion, administer for 4 minutes; or, to induce three lesions,
administer for 1 minute each, in diverse locations, in the same way as with conventional RF. However, the
10-cm, 10-mm active tip needle can be used.
J. Comments
Correct placement of the electrode is always controlled by impedance (normally, approximately 250
milliohms [mΩ]). If an air space (e.g., nostril) is reached, impedance increases significantly (to between
800 and 1000 mΩ)
Postoperative discomfort of 2 weeks' duration may ensue. Some patients present with decreased sensitivity
in the soft palate side of nose and upper lip.
3. STELLATE GANGLION
The stellate, or cervicothoracic, ganglion (SG) is formed by the two inferior cervical ganglia and the first segmental
thoracic ganglion. It is situated on the lateral edge of the transverse process muscle between the base of the seventh
cervical transverse process and the neck of the first rib. The SG contributes to the sensorimotor process of the
sympathetic function of the upper limbs, neck, and face.
SG blockade has been used for a range of pathologic conditions, including glaucoma, neuritis of the optic nerve,
heart failure, arrhythmia, and pulmonary embolism. It is currently used in the treatment of painful conditions of the
facial and cervicobrachial region, and in the treatment of hyperhidrosis and intractable angina pectoris.
Generally, the anterior paratracheal route is used for the SG approach, with the administration of local anesthetic
solutions such as bupivacaine, ropivacaine, or lidocaine. If the painful syndrome responds to the SG blockade, the
procedure is usually repeated once or several times.
Since 1992, the RF-induced lesion of the SG has been used with selected patients, at least 50% of whom reported
[62]
pain relief following previous local anesthesia blockade. The main advantage of the RF-induced lesion is the ability
to limit or control the lesion, with fewer adverse effects than other neurolytic procedures, particularly chemical
neurolysis.
A. Indications
Complex regional pain syndrome (CRPS) types I and II
Raynaud's phenomenon
Upper limb hyperhidrosis
779
Chronic, painful facial conditions
Chronic, painful cervical conditions
Intractable angina pectoris
If the pain is located in the hand, assess T2-3 sympathectomy because a significant number of sympathetic
fibers stem from T2-3. The SG is a combination of the inferior cervical sympathetic and first thoracic
ganglia and forms a diffuse structure lying on the longus colli muscle, on the lateral anterior edge of the C7
vertebral body. Inducing partial SG lesions may produce high-quality, long-term pain relief.
B. Material
POLE-RC COTOP needle: 60-mm, 24-G, for anesthetic blockade
SMK C10 needle; 22-G needle for RF lesion
C. Patient position
Patient is in a decubitus supinus position, with cervical hyperextension
D. Anesthesia
Mild intravenous sedation, if needed
Local anesthesia of the zone to be punctured
1. Sternocleidomastoid muscle, medial edge
2. Palpate the carotid artery; the carotid artery is kept aside with the tips of the fingers of the
contralateral operating hand.
1. AP projection: With caudal-cranial rotation
2. Target: C7 pedicle (internal part). The thoracic sympathetic chain runs through the bony canal
formed by the pedicle and the vertebral bodies. The needle is inserted to make contact with the C7
transverse process just lateral to its origin from the lamina. The tip of the needle must be in
contact with bone.
3. Oblique projection, 30 degrees. In an oblique projection, the needle tip should lie anterior to the
anterior border of the intervertebral foramen. The correct position of the needle tip is at the union
of the C7 vertebral body with the transverse apophysis.
4. Inject 0.3 to 0.5 mL iohexol and observe diffusion in the sympathetic chain. Inject 2% lidocaine,
which acts as a prognostic test (relieves pain in local anesthetic latency time) ( Fig. 31–4 ). Neither
the contrast nor the needle enters the foramen.
5. A total of 0.2 mL of contrast is injected to confirm the characteristic spread and to rule out
intravascular positioning of the needle tip.
G. Risks and complications
Radicular and vertebral artery puncture
Phrenic nerve and recurrent laryngeal lesion
Stimulation is important to avoid producing lesions of the phrenic nerve, recurrent laryngeal nerve, and
segmental C7 nerve.
Scale: 0 to 10 V
Sensory: 50 Hz. Stimulate up to 2 V. The patient notices pins-and-needles sensation in the arm due to
retrograde stimulation.
780
Motor: 2 Hz; up to 2.0 to 2.5 V. No significant contraction is obtained.
Direct the patient to say “e” (long vowel sound). If he or she is unable to do so correctly, the needle is near
the recurrent laryngeal nerve. Check that there is no diaphragmatic contraction by placing a hand on the
patient's chest.
Inject 0.5 mL of 0.25% bupivacaine or 2 mL of 1% lidocaine before performing the lesion (60 seconds at
80°C). Withdraw the cannula and reposition it to perform the second and third lesions (60 seconds at 80°C).
A more caudal lesion may be performed, seeking the zone that connects the head of the first rib to the T1
ventrolateral zone. The aim is to interrupt some thoracic sympathetic fibers. Always perform a stimulation
test after repositioning the needle.
Perform three lesions in a triangular pattern to interrupt the fibers of the cervical sympathetic chain.
Conventional RF: Administer 30 to 60 seconds at 80°C.
If the patient suffers intense cervical pain during the lesion induction, interrupt the procedure because the
recurrent laryngeal nerve may be damaged.
J. Comments
The lesion produced does not interrupt the entire ganglion. This technique may be repeated if the clinical
situation persists. This SG lesion does not usually produce Horner's syndrome. If this syndrome occurs, it is
transient and resolves spontaneously.
Figure 31-3 A, Lateral view of the base of the skull showing the sphenopalatine fossa. B, Posteroanterior view of the nasal and maxillary regions.
The sphenopalatine ganglion is within the lateral wall of the nasal cavity.
781
Figure 31-4 Stellate ganglion, anteroposterior view.
4. DENERVATION OF CERVICAL FACETS C2-6
Although chronic spinal pain often has a complex mechanical or radicular etiology, sympathetic involvement may
dominate the pain condition, producing individual clinical profiles in which more than one structure is involved in
the pain syndrome.
The treatment of cervical pain syndromes poses challenges for the clinician. Effective alleviation of pain, although a
difficult task, is achieved in over 80% of cases, in experienced hands.
During the last decade, much work has led to new approaches for treating amenable cervical structures with RF-
induced lesions and to identifying new syndromes based on advances in anatomy and neurophysiology. Pain
emanating from facet joints usually leads to local cervicalgia and may be amenable to treatment with RF
denervation, or medial branch neurotomy.
When selecting patients for RF denervation of cervical facets, a clear distinction must be established between
radicular, segmental, referred, and related pain prior to the therapeutic indication. The most frequent cause of
radicular pain is degenerative changes in discs and facet joints, which irritate the exiting segmental nerve in the
intervertebral foramen. These patients require assessment for surgical treatment to be sure that no surgical pathology
exists. Referred pain to the shoulder, or brachialgia, without dermatomal distribution is a common cause of cervical
facet pain in the midcervical area. In this area, referred pain to the maxillary area may be of facet origin in the upper
cervical area, owing to ongoing noxious input in the upper cervical area and participation of the caudal nucleus of
cranial nerve V, which descends the cervical spinal cord to level C3.
Attention must be paid to related pain conditions such as atypical facial pain, cervicogenic headaches, and cluster
headaches. In these chronic pain syndromes, correct physical examination, imaging studies (including functional
radiography), and differential diagnosis are essential because “cervicogenic headache” and “cervical migraine”
respond to radiofrequency treatment, whereas tension headache and “classic migraine” do not.
A. Indications
Pain originates in cervical facet articulations, which produces cervical pain, and in the scapular girdle (belt).
Referred pain (ear, facial pain, headache) is frequent.
Cervical facetal blockade with local anesthetic may be performed prior to performing the RF lesion.
782
Roots of C2, C3, and C4 have connections with the superior cervical ganglion. Roots of C4 are interrelated
with the deep petrous nerve, reaching the vidian nerve and the sphenopalatine ganglion. For this reason,
some alterations in the cervical column may produce referred pain in the maxillary region.
B. Material
COTOP 23-G, 6-cm needle (0.5-cm active tip)
C. Patient position
Patient is in a supine decubitus position
Head secured with side bands
D. Anesthesia
The facet joints are innervated by the posterior primary ramus of the segmental nerve, which leaves the
segmental nerve immediately after it exits from the foramen, and runs posteriorly adjacent to the spine in
the transversal plane from the caudal part of the intervertebral foramen.
Determine the cervical horizontal plane from the mastoid insertion of the sternocleidomastoid muscle.
Entry points are marked at the posterior border of the sternocleidomastoid muscle at the level of the caudal
part of each relevant foramen.
1. During a facet denervation, it is very important to ensure that the insertion plane of the needles is
situated posterior to the plane that joins the posterior margins of the intervertebral foramina.
Radiographic projections used are oblique projection to insert the needle, lateral projection to
progress to the lamina, and AP projection to ensure that the needle is in the cavity adjacent to the
spine.
2. Oblique: 20 to 30 degrees to correctly view intervertebral foramina. Mark 1 to 2 cm below the line
of the spinal apophyses.
3. Puncture below the external jugular vein.
4. Target: Upper edge of the pedicle, except in C2 (midportion of the pedicle or articular process).
Insert needles starting with C6 and in an upward direction (approximately 10 degrees) ( Fig. 31–5
A).
5. The puncture is perpendicular to the skin. If paresthesia occurs due to radicular puncture, the
needle is too far forward.
6. The position for performing the lesion in C2 is somewhat different. The primary posterior C2
ramus is larger than the anterior ramus. To perform a facet denervation, only some branches of the
primary posterior C2 ramus, which innervate the C2-3 facet, are damaged. The electrode should be
placed on the vertebral arch of C2 at the level of the upper edge of the intervertebral foramen of
C3.
7. Lateral projection: Advance the needle as far as the middle portion of the laminae (see Fig. 31–5
B).
8. AP projection: Check the tips of the needles in the articular process cavity. The tip of the needle
should always be in contact with bone. The frontal projection is performed after the sensitivity test
at all levels to be treated. When repositioning the needles, the tips must be carefully situated
anteriorly, maintaining contact with bone and leaving the tip just a few millimeters posterior to the
intervertebral foramen (see Fig. 31–5 C).
9. Examine for rotation of vertebrae. Rotated vertebrae could distort the theoretical position of the
needle with standard radiographic views.
G. Risk
Puncture of the vertebral artery, nerve root (if the puncture is very anterior), and the medulla (if the
puncture is very posterior). Use of curved blunt needle reduces these risks.
783
Scale: 0 to 1 V
Pulse duration: 1.00 second
Sensory: 50 Hz. A tingling or pressure sensation, of different quality from that felt previously by the patient,
is achieved with a desirable level below 0.5 V (e.g., in the neck and shoulder).
Motor: 2 Hz; should be negative. A certain degree of fasciculation in paracervical musculature may exist.
Motor stimulation may not be required if anatomic references are correct on radiography.
Inject 2% lidocaine, 0.3 mL through each cannula. Reposition needles if necessary.
60 to 90 seconds, 20 V (75°C to 80°C). Temperature is not used as a control because the mandrel is not
inserted, but is achieved by creating a direct circuit with this type of needle.
2.0 to 2.4 W; 97 to 120 mA; 19 to 20 V
If the patient feels pain during the lesion induction, decrease the voltage from 20 to 15 V in order to avoid
temperature above 80°C.
J. Comments
Reinject lidocaine whenever necessary. If a large quantity of local anesthetic is injected, the provocation
test is modified before inducing the lesion, but this is not important for the lesion.
Begin with the fifth needle and work upward (C6-2).
Mark the target 1 to 2 cm below the apophysis plane, below the jugular vein.
Guide the needle slightly anteriorly and upward, always in contact with bone.
At the C7-8 level, perform the procedure with the patient in a prone decubitus position (as in thoracic and
lumbar facet denervation).
The usual practice is to treat four to five facets in one session.
The electrical connection for needle stimulation must be made with the diathermia cable because it ensures
better contact.
A C2 lesion can be performed with pulsed RF to avoid paresthesia and postlesional occipital pain owing to
its proximity to common sensitive fibers of the great occipital nerve (Sluijter, personal communication,
Sept. 2001).
In short necks, it is often difficult to reach C6 by a lateral approach. In these cases, a posterior route must
be used, with the patient in the prone decubitus position; also, in such cases, the C5 level appears to be
situated in the cervicothoracic skin fold.
When local anesthetic is injected prior to performing the lesion, the needle should be repositioned. The
needle should be reinserted until the tip touches the periosteum, because it may be discretely rejected
owing to pressure of the liquid injected.
784
A crossing of sensitive fibers exists between the two sides of the vertebral column. The nerve plexus that is
formed from the sinuvertebral nerves is situated over the posterior longitudinal vertebral ligament and runs
through the anterior part of the vertebral canal. Occasionally, the development of pain, or
cervicobrachialgia, contralateral to the side previously subjected to facet denervation, warrants a new
operation on this side if signs of facet involvement are found.
Figure 31-5 Cervical facet denervation, C2 to C6. A, Oblique view. B, Lateral view. C, Anteroposterior view.
5. CERVICAL DORSAL ROOT GANGLION
The accepted mechanism for producing analgesia by means of an RF-induced lesion is the destruction of nervous
tissue and, consequently, the reduction of the nociceptive input. The RF lesion induced adjacent to the dorsal root
ganglion (DRG), however, causes only transitory sensory loss, whereas the relief of pain may be of much longer
duration.[1]
The pain relief could be explained by the selective action of heat on unmyelinated C fibers, but such a selective
effect has not been confirmed by pathologic studies. At present, some evidence has been published to support the
[2]
hypothesis that the effect of an electromagnetic field (EMF) may be instrumental in causing the clinical effect of the
RF lesion adjacent to the DRG. The clinical effect of EMF, however, should be attributed to the electrical field,
because the magnetic field is of insignificant intensity. [3]
Caution is mandatory, because this lesion may potentially produce pain by deafferentation. Thus, strict patient
inclusion criteria must be accomplished before performing a DRG lesion; include the following:
• Chronic pain with radicular distribution lasting more than 6 months

• Condition refractory to conservative therapies
• No indication of surgical intervention
• Absence of sensory abnormalities in the dermatome
• Positive response to prognostic segmental nerve block
A. Indications
Treatment of discogenic or segmental pain secondary to spinal nerve disease
Cervicobrachialgia of monosegmental origin
785
RF of the C2-3 DRG may be useful for treating refractory C2-3 facetal pain
B. Material
SMK 10-cm needle (active tip, 0.4–0.5 cm) with thick necks
SMK 54-mm, 22-G needle (active tip, 0.4 cm) with thin necks
C. Patient position
Patient is in a supine decubitus position
Head secured to table with side bands.
D. Anesthesia
Light intravenous sedation
Local anesthesia before RF lesioning
1. RF of the DRG is performed with the same technique, from levels C3 to C8. Access is situated at
C3, at the anterior edge of the sternocleidomastoid muscle, and common carotid artery pulsation is
observed. At lower levels, access is through the aforementioned muscle.
1. Oblique projection, 30 degrees: Locate C3 to C5 foramina (except in C2). The first round foramen
in the oblique view is the C3 foramen in the cervical column. The DRG is located between the
middle and lower thirds of the foramen. Insert the needle using the tunnel vision technique (see
earlier) as far as the foramen (the needle tip will be at 6 o'clock in the posterior foraminal canal)
( Fig. 31–6 A)
2. AP projection: The tip of the needle should reach halfway through the articular process. The
cannula must stay on the “floor” of the canal to remain at a distance from the vertebral artery.
Perform a stimulation test.
3. When the intervertebral foramen is reached, bone must be touched at the dorsal caudal part of the
canal; the needle is then withdrawn and discretely inserted 2 mm, until the ganglion or its
surroundings are reached.
4. Inject contrast: The contrast is seen in the ganglion and also extraspinally (extraforaminal). It does
not enter the medullary canal (see Fig. 31–6 B).
5. The target is not in the nerve, but adjacent to the nerve.
6. Using this technique, damage to motor fibers is avoided, and the chance of puncturing the
vertebral artery is minimized (the vertebral artery is positioned in the ventral part of the foramen).
G. Risks
Puncture of the nerve root, the vertebral artery, and the spinal cord, injection into segmental artery within
the nerve and spinal cord infarction.
Scale: 0 to 1 V
Sensory: 50 Hz. A tingling sensation in the corresponding dermatome must be obtained between 0.3 and
0.7 V.
Motor: 2 Hz. Motor fasciculations should not occur below at least 1.5 V, which is the threshold value
required to achieve sensory stimulation at 50 Hz.
Do not perform a lesion if radiating pain and muscle contraction occurs during stimulation, because it
indicates proximity to a motor nerve. In this case, the needle must be repositioned more dorsally.
786
If muscle contraction without radiating pain is obtained with motor stimulation, the lesion may be
performed, provided the motor stimulation parameter is 1.5 times higher than that required to elicit sensory
stimulation.
Inject 1 mL of 2% lidocaine and wait 10 minutes for it to take effect.
First lesion: 120 seconds, 42°C, or 45 V, pulsed RF; temperature not higher than 42°C.
A further option is to perform a thermal lesion (90 seconds, 62°C to 67°C, depending on the results of
stimulation parameters).
J. Comments
Consider injecting steroids after inducing the lesion (<40 mg of triamcinolone) to prevent neuritis. The aim
of an RF-induced lesion in the DRG is to provoke a mild lesion while preserving touch, motor function,
and proprioception. Wait 4 to 6 weeks to observe the results of the procedure. The patient may notice
sensory changes in the first few weeks. Foraminal stenosis may occur: caution must be observed with
conventional RF, because the lesion may expand due to tissue changes that affect electrical and heat
conductivity. The method requires meticulous attention to detail because cases of irreversible neurologic
damage have been reported. [8]
Figure 31-6 Dorsal root ganglia, C3 to C5. A, Oblique view. B, Anteroposterior view.
6. THORACIC SYMPATHECTOMY (T2-3)
A. Indications
Segmental radiation pain, with sympathetic burning component at upper dorsal levels
Complex regional pain syndrome (CRPS) type I (upper limb)
Hyperhidrosis of upper limbs
787
Intractable coronary pain and tachyarrhythmias
B. Material
SMK 10-cm needle, 23-G; active tip, 0.5 cm; 10-cm curved blunt Racz-Finch needle with 10-mm active tip
and introducer needle
C. Patient position
Patient is in a prone decubitus position, with pillow under the chest
D. Anesthesia
Local anesthesia of the zone to be incised
Finger plethysmography and skin temperature measurements can be used to document sympathetic
denervation.
Vertebral bodies C7, T1-3
The sympathetic chain is situated at this level, posterior and lateral to the vertebral body.
1. First view: Oblique projection, 15 to 30 degrees, toward the side of the lesion, with approximately
10 to 30 degrees cephalad-caudad rotation of C-arm to allow visualization of vertebral body of T2
and T3. Two skin wheals are raised 5 or 6 cm lateral to the midline on the side to be
sympathectomized. The needle must lie 2 to 5 mm lateral and rostral to the rostrocaudal midpoint
of the second and third thoracic vertebral body, beneath the head of the third rib ( Fig. 31–7 A).
2. Second view: Lateral projection X-ray. At this level, the sympathetic chain is more posterior than
at lower levels. The needle tip is inserted to the junction of the medial and posterior thirds of the
vertebral body (see Fig. 31–7 B).
3. Repeat the procedure at level T3.
G. Risks
Pneumothorax
Scale: 0 to 10 V
Sensory: 50 Hz; no response up to 1.5 to 2 V
Motor: 2 Hz; no response up to 2 to 2.5 V
Pulse RF: 42°C, 120 seconds.
Conventional RF: 60 seconds, 80°C, if stimulation parameters do not indicate closeness to intercostal
nerves. A second conventional RF lesion, administered for 60 seconds, can be repeated.
J. Comments
788
For T2 and T3 sympathectomy, a total of six RF lesions are made, two at each of three sites adjacent to and
ventrolateral to the second and third thoracic vertebrae.
If local anesthesia at one of the rostral sites produces Horner's syndrome, this would obscure assessing the
risk of producing Horner's syndrome from subsequent, more caudally placed lesions. Because creating
Horner's syndrome must be avoided, the most caudal site is anesthetized and treated first, saving the most
rostral site for last.
[70] [71]
At the conclusion of the procedure, the patient's chest must be examined by auscultation, and a chest
radiograph must be obtained to exclude the possibility of pneumothorax. The patient must be informed of
the possibility of delayed onset pneumothorax. Advise against air travel for a couple of days, and repeat
chest radiographs should be ordered prior to such activity. The use of the curved blunt needles has reduced
the incidence of pneumothorax.
At discharge from the day surgery unit, patients must be instructed to avoid vigorous activities for several
days.
Figure 31-7 Thoracic sympathectomy, T3. A, Anteroposterior view. B, Lateral view.
7. SPLANCHNIC NERVES
Splanchnic nerves transmit the major part of nociceptive input from the viscera. A subset of patients who fail to
obtain relief from celiac plexus block can obtain pain relief with splanchnic nerve block.
Kappis introduced splanchnic anesthesia in 1914, reporting a series of 200 cases ; however, the technique was
[72] [73]
criticized by contemporary colleagues and rapidly abandoned, owing to the high complication rate and unexpected
side effects of the chemical neurolytic agents that were used.
Interest in this technique has been regenerated by the introduction of the CT-guided approach and, recently, by the
[74]
use of RF-produced lesions. Raj and associates reported good outcome with RF lesioning using the Racz-Finch
[75] [76]
curved blunt needles.
A. Indications
Palliation of acute pancreatitis
Diagnosis of sympathetically mediated abdominal pain
789
Pain secondary to malignancies of the retroperitoneum and upper abdomen
B. Material
Curved blunt Racz-Finch 15-cm needle; active tip, 15 mm
16-G introduces cannula for skin entry prior to RF blunt needle insertion
Two 10-mL plastic syringes, one each with local anesthetic and steroid (for injection after stimulation and
before lesioning)
One 10-mL syringe with contrast (iohexol)
C. Patient position
Patient is in the prone decubitus position, with a cushion under the abdomen
D. Anesthesia
Local anesthesia of the points to be injected
The splanchnic nerves are contained in a narrow compartment formed by the vertebral body medially and
the pleura laterally, the posterior mediastinum ventrally, and the pleural attachment to the vertebra dorsally.
The compartment is limited caudally by the crura of the diaphragm. The volume of this compartment has
been determined to be approximately 10 mL on each side ( Fig. 31–8 A). [77]
F. Radiographic technique [75]
1. First view, AP projection: The T12 vertebral body is identified, and a mark is made on the T11 or
T12 vertebra.
2. Second view, oblique projection, approximately 25 to 30 degrees: The edge of the diaphragm
lateral to the vertebral body is viewed. If the diaphragm shadows the T12 vertebra and its rib, then
the T11 is identified. The point of entry for both levels is at the junction of the rib and vertebra.
The tip of the needle is advanced anteriorly, bearing in mind that the needle hugs the lateral aspect
of the T11 or T12 vertebral body, close to the costovertebral angle.
3. Third view, lateral: The needle needs to lie on the midthird portion of the lateral side of the T11 or
T12 vertebral body. The needle should remain retrocrural and posterior to the descending aorta.
The needle is aspirated for fluid, which may be blood, air, or chyle.
4. If the aspiration is negative, oblique views are then taken to confirm the final position of the
curved needle on the vertebral body. Target sites on T12 vertebral body on the lateral view: the
superior and anterior one third. On T11: the inferior and middle one third. In the oblique view,
inject 5 mL iohexol to flow medially to the interpleural space, above the crus of the diaphragm
and anterior to the foramen (see Fig. 31–8 B).
G. Stimulation parameters
Scale: 0 to 1 V. Impedance should be below 250 mΩ .
Sensory: 50 Hz; up to 1-V stimulation may be felt by the patient in the epigastric region. If stimulation is
sensed around intercostal spaces, in a girdle-like fashion, the needle needs to be pushed anteriorly.
Motor: 2 Hz; up to 3 V may be used. If intercostal muscle contraction is negative, test stimulation is
satisfactory.
H. Lesion parameters
Inject 2 to 5 mL of local anesthetic with 40 mg triamcinolone through the RF needle.
790
Lesion: 80°C, 90 seconds
A second lesion is performed at the same setting by turning the RF needle 180 degrees.
When bilateral neurolysis is required, the same procedure is performed on the opposite side.
I. Risks and complications
Pneumothorax
Kidney injury
Damage to blood vessels (aorta, inferior vena cava, and the artery of Adamkiewicz), particularly when
using chemical neurolytic agents
These complications can be observed when using a lateral entry 6 to 8 cm lateral to the spinous process of
T12 or T11 over the rib. Complications can be reduced by staying close to the paravertebral border,
approximately 3 to 4 cm lateral to the T11 to T12 spinous processes.
Figure 31-8 Splanchnic nerve, lateral view: trunk.
8. LUMBAR SYMPATHETIC CHAIN
Radiofrequency percutaneous lumbar sympathectomy is a procedure for permanent interruption of the lumbar
sympathetic chain that involves less morbidity than open surgical techniques or chemical sympatholysis.
A. Indications
Peripheral vascular disease, such as arteriosclerotic and vasospastic Raynaud's phenomena, frostbite
Complex regional pain syndrome, types I and II
B. Material
SMK 15-cm needle (active tip, 0.5 cm), Racz-Finch curved blunt 10-mm active tip needle with introducer
C. Patient position
Patient is in the prone decubitus position, with a pillow under the abdomen. It is important to eliminate as
much lumbar lordosis as possible by this maneuver.
D. Anesthesia
791
Local anesthesia of zones to be incised
The lumbar sympathetic chain carries preganglionic fibers that descend from the lower thoracic chain,
sending rami comunicantes to the first and second lumbar segmental nerves. It passes forward on the psoas
fascia lying along the anterolateral aspect of the vertebral bodies and medial border of the psoas muscle.
Beginning posteriorly, the diaphragm is pierced; the chain passes anteriorly and then falls posteriorly as it
approaches the promontory of the sacrum. The point at which the sympathetic chain no longer lies on the
psoas muscle (i.e., where the psoas muscle diverges laterally from the vertebral column) is where it varies
from the upper third of L3 to the upper third of L5. In the sagittal plane, the lumbar ganglia are most often
[79]
present opposite the middle of the body of the third vertebra, L3, and at the discs above and below. In the
horizontal plane, the ganglia lie from 0 to 0.5 cm posterior to the anterior border of the third lumbar
vertebra and 1.8 to 3.0 cm laterally from the center of the third lumbar vertebra. The aorta lies
[80] [81]
anteromedially to the left chain, whereas the vena cava lies anterior to the right chain. The segmental spinal
vessels lie posterior to both chains.The rami communicantes to and from the lumbar ganglia pass in tunnels
formed by the ligamentous attachments of the psoas muscle to the sides of each vertebral body ( Figs. 31–9
and 31–10 A, B).Great variability exists with regard to the branches given off by the sympathetic chain.
Grey rami leave the ganglia to join spinal nerve roots and may number as many as three nerves to one root,
or one ganglion may give rise to three nerves that pass to three separate spinal nerves.
1. First view, oblique projection, 15 to 20 degrees (until the vertebral body “covers” the transverse
process): Mark the point of entry of the needle below the transverse process and in line with the
lateral edge of the vertebral body. Rotate C-arm to allow visualization of vertebral body. Puncture
6 to 7 cm from the midline.
2. Second view, lateral projection: The needle tip is 2 cm behind the anterior edge of the vertebral
body (see Fig. 31–9 B)
3. Third view, AP projection: The needle tip progresses 1 cm within the vertebral body, inferior to
the pedicle (see Fig. 31–9 A). The needle is correctly positioned when the tip is behind the facetal
line while in bone contact with the vertebral body.
4. Verify the needle's position with 1 mL of contrast. If the contrast spreads into the psoas or into the
sheath, the tip is too lateral and should be repositioned more medially. If the contrast is behind the
facetal line, the tip is in the appropriate place. There should be no resistance when injecting
contrast.
G. Risks
Puncture of roots and paravertebral vessels
Lesion of genitofemoral nerve
Scale: 0 to 10 V
Sensory: 50 Hz; the patient will feel vague discomfort in the back with 0.2 to 0.5 V. If paresthesia exists in
the groin at the L2-3 level, reposition the cannula (due to proximity of the genitofemoral nerve).
Motor: 2 Hz; there are no fasciculations up to 3 V.
Inject 1 mL 2% lidocaine before producing the lesion.
RF: 80°C, 60 to 90 seconds
The lesion should extend to 10 mm in L2 and 15 mm in L3-4. This is achieved by inserting the L3 to L4
cannulas 5 mm. A 15-mm lesion is required in L5. It is advisable to use 15-cm curved blunt Racz-Finch
needles with 10-mm active tip.
792
J. Complications
Intravascular or subarachnoid injection, neuralgia, and muscular spasm.
Retrograde ejaculation is rare in sexually active men. Bilateral sympathectomy is rarely indicated.
Postoperative discomfort lasts for approximately 5 days.
Neuralgia may occur owing to the spread of the neurolytic material into a somatic nerve root. The nerve
most susceptible to this complication is the genitofemoral nerve. [81]
K. Comments
Produce a lesion of L2 if there is lumbar pain, L3 if pain is in spine or knee, L4 if pain is in lower limb, and
L4 and L5 if pain is in ankle or foot. Several lesions may be performed at different levels.
Before the RF procedure, it is advisable to perform a diagnostic blockade using 1% lidocaine (or 0.25%
bupivacaine) to avoid false-positives (e.g., injection of somatic nerves). For lower extremity sympathetic
block, the level needs to be at L2-4, and if the foot is involved, block L3-5. No sensory or motor blockade
should be produced.
Figure 31-9 A, Lumbar sympathetic trunk and abdominal autonomic ganglia: lumbar sympathectomy. B, Anteroposterior view. C, Lateral view.
9. L2 COMMUNICATING RAMUS
Percutaneous facet denervation and percutaneous partial rhizotomy have traditionally been the minimally invasive
RF techniques used in the treatment of back pain. Recent advances in knowledge of the innervation of the anterior
vertebral compartment have led to the development of performing RF lesions close to the exiting segmental nerves,
with the aim of interrupting part of the afferent impulses from the anterior mechanical compartment. Based on
anatomic considerations, the following technique describes the approach of the communicating ramus of the
segmental nerve with the lumbar sympathetic chain, suitable for interruption by means of an RF lesion (see Fig. 31–
10 A, B).
A. Indications
793
Discal pain, occurring at either single or multiple lumbar levels
Complex pain of vertebral structures
B. Material
SMK 145-mm Radionics Pole needle; active tip, 0.5 cm or 10- to 15-cm curved blunt needle used with an
introducer
C. Patient position
Patient is in the prone decubitus position, with a pillow under the abdomen
D. Anesthesia
Local anesthesia of the zone to be injected
The communicating ramus branches off the segmental nerve immediately after it exits from the foramen.
While the segmental nerve continues its path in a caudal, lateral, and anterior direction, the communicating
ramus runs anteriorly, in close contact with the vertebral body en route to the sympathetic chain.
Although there are anatomic variations, the typical communicating ramus runs deep to the psoas muscle;
however, it also may run between the psoas fibers or may be embedded in the connective tissue of the
intervertebral disc. Two communicating rami may even branch off from one segmental nerve. Therefore,
the relationship with the vertebral body is variable, but the proximal part of the communicating rami
usually runs adjacent to the middle or caudal part of the vertebral body. [46]
1. First view, oblique projection, approximately 30 degrees toward the side of the lesion: Caudal
oblique 25 to 30 degrees. Observe the following references:
a. Transverse process
b. Neural foramen
The vertebral body must be approached in the space formed in this view by the transverse process,
vertebral body, and superior edge of the segmental nerve. Beware of the rotated spine, in which the
reference points will change. Be cautious with the variability of the L2 communicating ramus; in patients
with degenerative disease, it is even more distorted.
c. Mark the point of entry of the needle below the transverse process and in line with the
lateral edge of the vertebral body. Rotate C-arm until vertebral body is visualized.
Puncture 6 to 7 cm from the midline.
d. The initial target lies under the inferior edge of the transverse process and 1 to 2 cm from
the anterior edge of the vertebral body. The needle advances, touching the periosteum of
the vertebral body in its middle portion, and finally reaches the central point of an
imaginary cross traced on the vertebral body on a lateral view. If accidental contact is
made with the segmental nerve, withdraw the needle slightly and correct the position in a
more cranial direction.
e. A prominent iliac crest may be a problem for the L5 communicating ramus. In most
patients, the area is accessible, but rotating movements have to be made with the C-arm
to determine the most advantageous projection.
f. Second view, lateral projection: The tip of the needle in the lateral view should be
situated in the middle portion of the L2 vertebral body, touching the periosteum, and in a
position behind (exactly at the lateral edge of the vertebral body) the lumbar sympathetic
chain, because the L2 communicating ramus is in contact with bone. Check the needle's
position with 1 mL of contrast (see Fig. 31–10 ).
794
g. Third view, AP projection: Correct needle position is behind the facetal articular line
while in bone contact with the vertebral body. Check the position with 1 mL of contrast.
If contrast spreads into the psoas or sheath, the tip is too lateral and must be repositioned
(more medially). If the contrast is behind the facet line, the tip is in the right place. There
should be no resistance on contrast injection. The contrast dot must be located closely
lateral to the vertebral body and just caudal to the transverse process.
2. Risks
Puncture of root and paravertebral vessels
Lesion of genitofemoral nerve
3. Stimulation parameters
Scale: 0 to 1 V
Sensory: 50 Hz; patient feels discomfort from 0.2 to 0.5 V.
Observe in L2 whether radiating pain to the groin occurs. If so, reposition the needle because proximity to
the genitofemoral nerve is indicated.
Motor: 2 Hz; no response should be elicited.
4. Lesion parameters
RF; 80°C, 60 to 90 seconds
5. Comments
The L2 communicating ramus lesion should be considered whenever sympathetic pain of discal origin is
determined. In these cases, diagnostic block followed by RF lesioning of the L2 ganglion can be carried out.
The L2 communicating ramus lesion is particularly useful when discal pain is present at several levels.
Coldness of feet can indicate sympathetic involvement.
Performing the communicating ramus lesion should be preceded by a prognostic local anesthetic (0.3 mL
1% lidocaine) in the L2 communicating ramus. After 1 to 2 minutes, if the pain disappears, the RF lesion
procedure can proceed at a setting of 80°C for 60 seconds.
In the case of spinal fibrosis postdiscectomy, the combination of pulse RF of DRG L5 (discectomy level
L5-S1) and later an L5 communicating ramus lesion, after a test with local anesthetic, can be used.
795
Figure 31-10 A, L2 Rami communicantes lateral view. B, Nerve supply of the lumbar spine, oblique view. C, Neural structures of the lumbar
vertebrae, transverse section.
10. LUMBAR DORSAL ROOT GANGLIA
If prognostic blockades of the posterior (facets) and anterior (discs) compartments have been negative and the pain
is located in the lower limb, then selective radicular blocks can be considered. It is common for a patient also to
report lumbar pain, and the determination must be made whether to treat mechanical lumbar pain with referred pain
to the limbs, or pain caused by spinal nerve pathology. Once a referred mechanical origin of the pain has been ruled
out, diagnostic blockades of spinal nerves and sympathetic chains should be performed to ensure against a
sympathetically maintained pain (SMP), because the treatment is different.
Pain by deafferentation, postherpetic neuralgia, thalamic syndrome, multiple sclerosis, and SMP should not be
treated with this procedure. The aim of this technique is to produce a well-defined lesion in the DRG while
maintaining the unaltered afferent input. It is not desirable to produce dysesthesia-paresthesia in the injured zone. If
dysesthesia-paresthesia is produced for a prolonged period of time, pain by deafferentation will be produced.
Cells of the DRG are more sensitive to heat than other structures, and for this reason the clinician uses a differential
heat-induced lesion to affect nerve pathways while leaving motor innervation, proprioception, and afferent pathways
relatively intact. High temperatures are more likely to produce afferent decrease (input) and provoke pain by
deafferentation. If several ganglia are to be treated, it is better to space the procedures at intervals over 1 month.
A. Indications
Chronic pain of spinal radicular origin, with segmental distribution, that does not respond to conservative
therapies where surgery is not indicated
B. Material
SMK 10- to 15-cm needle; active tip, 0.5 cm
C. Patient position
Patient is in the prone decubitus position, with a pillow under the abdomen
D. Anesthesia
796
Mild intravenous sedationLocal anesthetic of the points to the injection sites
E. Radiographic technique
1. First view, AP projection: Locate the level below the pedicle, parallel to the inferior vertebral plate
2. Second view, oblique projection at 15 to 20 degrees: Locate foramen to be treated. Paramedial
puncture 7 to 8 cm from midline. Trace a line between the iliac crest and foramen, parallel to the
inferior vertebral plate. Follow the direction of the previously traced line with the needle,
particularly if performing an L5 injection.
3. Third view, lateral projection: Advance the needle as far as the upper third of the foramen where
the dorsal root ganglion is located.
4. Fourth view, AP projection: Inject 1 mL of contrast and visualize the nerve root.
5. With an oblique, 30- to 40-degree view, clearly visualize the neural foramen to be injected. Direct
the needle to the upper dorsal square. Check the position of the needle tip with an AP view. It
should be on the facet line. Verify the tip of the needle in the AP and lateral positions prior to
initiating the stimulation ( Fig. 31–11 ).
F. Risks
Neuritis is rarely observed in practice because pulse RF does not produce a lesion, but reorganization of the
electromagnetic fields and the temperature should not exceed 40°C to 42°C.
G. Stimulation parameters
Scale: 0 to 1 V
Sensory: 50 Hz; reproduce the pain or paresthesia in the territory between 0.2 and 0.5 V.
Motor: 2 Hz; evoke motor fasciculations with the voltage necessary to achieve sensory stimulation,
although occasionally twice the voltage is required.
Impedance: Approximately 200 to 300 mΩ .
With sensory stimulation (50 Hz), the patient should note paresthesia in the affected dermatome with less
than 0.5 V. Paresthesia felt with less than 0.3 V verifies proximity to the ganglion. Ideal stimulation is
between 0.2 and 0.5 V, with 50 Hz.
An evident dissociation must exist between the sensory and motor stimuli such that the voltage required to
produce paresthesia with 2 Hz must be at least double the voltage necessary to produce paresthesia with 50
Hz. If this dissociation is not observed, the needle is not aligned with the ganglion, and producing this
lesion is not recommended. For example, paresthesia is evoked at 50 Hz with 0.3 V, and fasciculations are
evoked at 2 Hz with 0.6 V. Before performing the lesion, inject 2 mL of 2% lidocaine and wait 10 minutes.
H. Lesion parameters
First-pulse RF lesion: 120 seconds, 40°C to 42°C
Second-pulse RF lesion: 120 seconds, 40°C to 42°C
Third-pulse RF lesion: 120 seconds, 42°C
RF lesion: 60 seconds, 67°C (at a lower stimulation threshold, decrease the lesion temperature). The lesion
can be performed only by conventional RF when sensory stimulation is achieved with high voltages (>1 V),
indicating that the zone may be affected by scar tissue.
I. Comments
Inject 40 mg triamcinolone and 2 mL 2% lidocaine after performing the lesion. Contrast may be injected,
although in a small quantity (0.2 to 0.3 mL), to check the position of the needle.
797
For the correct approach of an RF-produced lesion of the DRG L5, bear in mind that the iliac crest will
cover the direction used in upper levels for the DRG lesion. Thus, a more medial direction must be taken.
The tip of the needle will reach the DRG directly instead of being positioned in parallel, as in upper levels.
Figure 31-11 Bilateral dorsal root ganglia, anteroposterior view.
11. DENERVATION OF LUMBAR FACETS
The dorsal spine compartment is innervated by the medial and lateral branches of the dorsal ramus. The articular
facets are innervated by the medial branch of the dorsal ramus of the superior segment and one or more segmental
levels.
The multisegmental organization of spinal innervation has an effect on spinal pain therapy because, in the absence
of a technique for selectively producing a lesion of the sinuvertebral nerve in the treatment of dorsal compartment or
articular facet syndromes, the target structures are the medial branch of the dorsal rami of spinal roots or nerves and,
in ventral compartment syndromes, the target structures are the sympathetic chain and the communicating ramus.
The dorsal compartment syndrome, or articular facet syndrome, usually presents nonspecific symptoms; its
diagnosis is therefore based on some common clinical criteria: (1) medial and/or paravertebral hemi- or bilateral
lumbar pain, either continuous or during most of the day; (2) absence of neurologic deficits; (3) pain on pressure on
paravertebral masses; and (4) pain on lumbar hyperextension.
The pain is usually deep, and nonsegmental radiating pain together with limited lumbar mobility are common.
Occasionally, the pain occurs when the patient maintains a posture or in continued exercise such as walking.
Radiologic signs are not specific, and in many cases radiographic study is normal or is accompanied by
inflammatory or degenerative signs (e.g., arthritis, dislocation, discopathy, spondyloarthritis). [85]
A. Indications
Lumbar facet pain syndrome
B. Material
SMK 10- to 15-cm needle (active tip, or curved blunt or sharp RFK, 0.5 to 1 cm)
C. Patient position
Patient is the prone decubitus position, with a large pillow under the abdominal region
D. Anesthesia
798
Superficial intravenous sedationLocal anesthesia in the points to be injected
1. First view, oblique projection, 5 to 15 degrees: Visualize the facet articulation and Luschka's canal
between the superior articular and transverse process. Tilt the craniocaudal x-ray head (toward
caudal) ( Fig. 31–12 A, B).
2. Second view, AP projection: Check the position of the needle in Luschka's canal.
3. Third view, lateral projection: The needle is in the articular mass, without reaching the foramen
(see Fig. 31–12 C). Five points should be lesioned in a patient with facet disease, at L4-5 and L5-
S1 (see Fig. 31–12 ).
First target: Superolateral margin of foramen S1
Second target: Upper medial zone of the sacral groove
Third target: Upper and medial zones of L5 transverse process
Fourth target: Upper and medial zones of L4 transverse process
Fifth target: Upper and medial zones of L3 transverse process
In the third, fourth, and fifth targets, there is union of the transverse process with upper articular face. Vary
the craniocaudal orientation of the radiogram for appropriate visualization of the target.
4. Puncture point is 5 to 6 cm from midline, with an internal tilt of approximately 10 to 15 degrees.

5. Insert needle in chosen points.
a. First needle (S1): The tip of the needle reaches the external superolateral margin of the
foramen, but does not enter the foramen.
b. Second needle (L5 in the sacral groove): The cannula slides along the edge of the
periosteum and enters 2 mm to align the cannula with the nerve.
c. With the third, fourth, and fifth cannulas, an oblique view (5 to 15 degrees) is used to
visualize the most medial aspect of the transverse apophysis. The cannulas must be
parallel to the nerve because the degree of the lesion is determined by the length of the
injured nerve. Once the five cannulas are in place, it is advisable to measure the
impedance, which is usually above 300 mΩ (range, 300 to 700 mΩ). Verify (with lateral
radiograph) that the tips of the L3, L4, and L5 cannulas are posterior to the foramina.
Minor congenital anomalies of the lumbar and sacral structures may often be seen and render determination
of the target sites more difficult. Oblique positioning, stimulation, and structural imagination on the part of
the surgeon also play important roles. Additional lesions may be required to cover the probable variant
pathways of zygapophyseal joint nerve filaments.
Decide on prepuncture examination which facets are to be treated by applying pressure 2 to 3 cm from the
midline. The level above and below the painful facet should be treated. Occasionally, it is necessary to
perform a treatment at the sacral level. Blockade of S1 to S3 requires a craniocaudal oblique radiographic
view.
d. Risks
Segmental root puncture
e. Stimulation parameters
Scale: 0 to 10 V
Sensory: 50 Hz, between 0.2 and 0.5 V: evoke paravertebral and hip paresthesia
Motor: 2 Hz; must be negative at 2 V
f. Side effects
799
Lower limb weakness, probably due to lidocaine extravazation; resolves in 1 to 2 hours
Paravertebral and gluteal discomfort for 1 to 2 weeks
Hip pain usually begins on the third day and may last 10 days. Treat with nonsteroidal anti-inflammatory
drugs (NSAIDs). The pain may be due to a spasm of the quadratum lumborum muscle.
g. Comments
Ghormley was the first to use the term facet syndrome, in 1933, to indicate the relationship between facet
joint disease and low back and leg pain. In 1971, Skyrme Rees was the first to use partial denervation of
[86]
the facet joints, using a stiletto-like knife in the structures adjacent to the lumbar facet joints. Shealy
modified the technique by using a percutaneous RF thermocoagulation probe similar to that used for
percutaneous cordotomy. [33]
Very few controlled studies have been published on the efficacy of this technique in articular facet
syndrome. Following the initial modification of the technique by Shealy, which was carried out by Bogduk
and Long in 1980, based on anatomic data, several prospective controlled studies with placebo have
[87]
reported good results. [88] [89] [90]
800
Figure 31-12 Target sites for lumbar facet denervation.
12. SACROILIAC JOINTS
A. Indications
Sacroiliac pain: The pain is usually located in the gluteus and referred to the groin, hip, and the thigh
through its anterior plane and calf. The pain is more intense in the morning and remits during the day.
Pressure on the articulation is painful. Diagnostic blockades with local anesthetic are useful for diagnostic
and predictive purposes.
B. Material
SMK, 100-mm needle; active tip, 0.5 cm
SMK, 145-mm needle; active tip, 0.5 to 1.0 cm
801
C. Patient position
Patient is in the prone decubitus position, with a large pillow under the abdominal region
D. D. Anesthesia
Local anesthesia in the points to be punctured
1. First view, oblique projection: Cephalic 15 to 25 degrees; enough to open disc space at L5-S1.
2. Second view, AP projection: Start with an oblique view, then rotate toward the AP view to
visualize the widest space at the most inferior aspect of the sacroiliac joint.
This “scout” image must show the entire sacroiliac joint visualized for needle entry at the most inferior
aspect. The C-arm is angled in such a way that the lines of the posterior and the anterior aspects of the joint
are seen to overlap.
An injection of contrast spreads throughout the sacroiliac joint in an inferior-to-superior fashion, with
opacification of the ventral and dorsal joint lines.
3. Risks
Segmental root puncture
4. Stimulation parameters
Scale: 0 to 1 V
Sensory: 50 Hz; paresthesia of the zone must be noted above 0.5 V
Motor: 2 Hz. Must be negative at 2 V.
5. Lesion parameters
Inject 1 mL 2% lidocaine before producing the RF lesion at 80°C for 90 seconds.
Multiple lesions must be completed along the entire posterior joint line. The cannula entry point must be
located more medially as the lesions are more cranial, to facilitate positioning beneath the posterior iliac
crest.
6. Side effects
Following sacroiliac joint RF denervation, some patients will experience gluteal discomfort, hip pain, or
referred posterior thigh pain. Usually, pain resolves in 10 to 15 days. Adjunct analgesic oral therapy can be
prescribed. Patchy hypoesthesia in the buttocks can be seen, but it resolves spontaneously within 2 to 4
weeks.
7. Comments
The facets and root ganglia should both be lesioned for the complete treatment. It is advisable to perform
pulsed RF lesions in DRG S1, S2, and S3, and to perform conventional RF in L4-5 and L5-S1 medial
branches. The S2 segmental root contributes greatly to the innervation of the sacroiliac joint, and lesions
produced in the S2 DRG by pulsed RF can alleviate residual symptoms after sacroiliac denervation.
802
Section V Chapter 32 - Spinal Decompressive Neuroplasty via the Caudal and Cervical Approaches
Chapter 32 - Spinal Decompressive Neuroplasty via the Caudal and

Cervical Approaches
Leland Lou
Gabor B. Racz
HISTORY
A frequently overlooked cause of low back and radicular pain is epidural fibrosis, or adhesions, or
both. The nucleus pulposus has been documented to cause an inflammatory response with a resultant
increase in fibrocytic deposition when leakage seeps into the epidural space. Scarring can develop
from postsurgical bleeding and the subsequent healing process. Epidural adhesions may contribute to
the pain production by causing irritation to the nerve root or by inducing epidural venous
engorgement. Pain is elicited by movement of the swollen, inflamed nerve root. [1]
DIAGNOSIS OF EPIDURAL ADHESIONS
Magnetic resonance imaging can be used to detect epidural fibrosis of 3 mm or larger. Because of the
effect of adhesions smaller than 3 mm, it is not a perfect test. It has been documented that myelography,
computed tomography (CT), and magnetic resonance imaging (MRI) have been unsuccessful. [2]
Epidurograms have been used with tremendous effectiveness to solve just that problem. Sicard and
Forestier published, in 1921, the first report of epidurography. Bogduk and colleagues stated that a
[3] [4] [5]
volume of 10 mL was sufficient to reach the L5 segmental level. The experience of many clinicians has
shown that the caudal epidurogram has been effective in correlating a filling defect in association with
patients’ reported level of pain.[6] [7]
Radiologic Landmarks of the Caudal Canal
From a lateral view ( Fig. 32–1 A), the caudal canal appears as a slight step-off on the most posterior part of the
sacrum. The median sacral crest is seen as an opaque line posterior to the caudal canal. Although still in the lateral
view, the sacral hiatus is usually visible as a translucent opening at the base of the caudal canal. To aid identification
of the sacral hiatus, the coccyx can be seen articulating with the inferior surface of the sacrum.
On the anteroposterior (AP) view (see Fig. 32–1 B), the intermediate sacral crests are seen as opaque vertical lines
on either side of the midline. The sacral foramina are seen as translucent, nearly circular areas lateral to the
intermediate sacral crests. Note that the presence of bowel gas can make recognition of these structures difficult.
INDICATION
The ideal indication for decompressive neuroplasty is radiculopathy due to epidural fibrosis and nerve root
entrapment. For chemically sensitive discs, failed back surgery syndrome, and associated epidural inflammations,
the placement of the catheter in the anterior lateral epidural space has been extremely effective. In spinal stenosis,
neuroplasty techniques have been helpful in some situations by decreasing edema and venous congestion, with the
expected effect of attenuating the compressive effects on the spinal cord and nerve roots.
In the lumbar region, the caudal approach is extremely beneficial for the L5 to S1 radiculopathy owing to the ease of
entering the area of natural lordosis in that region. If L4 or a higher disc is problematic, a transforaminal approach
with placement of the Racz catheter into the anterior epidural space can be done individually or in conjunction with
a caudal catheter. Thoracic neuroplasty is very rarely done but may be useful in situations such as acute herpes
803
zoster or thoracic vertebral compression fractures. For the cervical region, radicular symptoms related to failed neck
surgery, discogenic pain, and associated fibrosis from inflammation are the predominant indications.
PATIENT SELECTION
Before performance of decompressive neuroplasty, confirmation of a radiculopathy or spinal stenosis by

examination
Figure 32-1 A, Lateral radiograph of the sacrum. B, Anteroposterior radiograph of the sacrum. (From Waldman SD: Interventional Pain
Management, 2nd ed. Philadelphia, WB Saunders, 1996. Also from Lou L, Racz G, Heavner J: Percutaneous epidural neuroplasty. Pain Digest
41:435, 1996.)
and radiographic studies is preferred. Once the decision is made to proceed with neuroplasty, the patient must meet
the standard criteria for a regional anesthetic technique, such as freedom from infection, coagulopathy, skin lesions
at the site of entry, and so forth. If the patient reports bladder dysfunction that has no definitive cause during the
initial evaluation or examination, a urodynamic study is recommended to determine the source before initiation of a
neuroplasty procedure.
TECHNIQUE
Consent must always be obtained before the procedure is begun. In the consent form, all possible complications
related to the procedure must be included, such as bruising, transient hypotension, transient difficulty breathing,
numbness of the extremities, bowel or bladder dysfunction, paralysis, infection, sexual dysfunction, and the
possibility that the catheter may shear. Additionally, laboratory studies that must be performed are a complete blood
cell count, urinalysis, prothrombin time, partial prothrombin time, and bleeding time or platelet function studies.
Intravenous access is recommended in anticipation of unintended injection of local anesthetic into the subarachnoid
space, subdural space, or vessels. It may be necessary to sedate the patient with 1 to 2 mg of midazolam and 25 to 50
µg of fentanyl. This is because the solution injected into the epidural space of a patient with adhesions is frequently
quite painful. The patient typically experiences pain in the dermatomal distribution of the nerve roots that are
stretched during the lysis process. It is important that the patient be awake and responsive during the procedure to
ensure that the spinal cord is not compressed. To monitor for an intrathecal or intravascular injection during the
injection of local anesthetics and steroids, the patient is asked to report any motor weakness or numbness after each
bolus dose.
Use of fluoroscopy is essential for the performance of safe adhesiolysis. To minimize radiation exposure, it is
preferable to use a fluoroscope with memory capabilities and efficient computed image processing. For
documentation purposes, videotaping the fluoroscopy screen during the procedure or making printouts for
804
subsequent review is recommended. For personal safety, the physician should use appropriate protective measures
such as leaded gloves, apron, thyroid shield, and glasses. The addition of a leaded skirt around the fluoroscopy table
can further decrease radiation exposure. Lastly, fluoroscopy is important in obtaining the maximal benefit from this
procedure (i.e., for verification of needle placement, visualization of dye spread, and proper catheter placement).
A water-soluble nonionic contrast is used because of the possibility of unintended subarachnoid injection. Even in
the most careful hands, scar tissue may dissect during introduction of the epidural catheter or injection of the
contrast agent and may enter the subarachnoid space. Non–water-soluble ionic contrast media in the subarachnoid
space can cause spinal cord irritation, spinal cord seizures or clonus, arachnoiditis, and paralysis. [8]
The steroid that we currently use for this procedure is triamcinolone diacetate. Methylprednisolone, which we have
used in the past, forms clumps when mixed with local anesthetics or normal saline. A particulate steroid may
occlude the catheter or possibly cause an infarction of spinal tissue via vascular injection. Because the particle size
of triamcinolone acetate is about 22 µ, it cannot be injected through a bacteriostatic filter.
Hypertonic saline is used to prolong pain relief because of its local anesthetic effect. The mechanism of action of
[9]
hypertonic saline is not fully understood. A direct effect may be the lysis of scar tissue. An indirect effect may be
related to the osmotic gradient with the decrease of neural tissue edema.
The Caudal Area
On the fluoroscopy table, the patient is placed prone with a pillow under the abdomen to straighten the lumbar spine.
Monitors, including an electrocardiograph, pulse oximeter, and a blood pressure monitoring device (preferably
automated), are applied. The sacral area is then sterilely prepared and draped from the top of the iliac crest to the
bottom of the buttocks. Abduction of the legs and internal rotation of the feet facilitate entry into the sacral hiatus.
The sacral cornua and the sacral hiatus are palpated with the index finger of the nondominant hand rolled laterally
over the sacral hiatus. For entry through the skin, a spot approximately 1 to 2 cm lateral and 2 to 3 cm inferior to the
sacral hiatus in the contralateral gluteal region on the affected side is accessed for treatment. This point of entry
inherently allows the needle and the catheter to be directed toward the affected side. The entry point is infiltrated
with a local anesthetic, such as 1% lidocaine. A 16-gauge epidural needle (preferably an Epimed R-K epidural
needle) is passed through the described entry point into the sacral hiatus and through the sacrococcygeal ligament.
Using the sacral cornua as landmarks to locate the hiatus ( Fig. 32–2 ), the needle is advanced to a level below the
S3 foramen to avoid damaging the sacral nerve roots. Placement is confirmed by a lateral fluoroscopic view before
any injections to determine that the needle is within the bony
Figure 32-2 Entry point into the caudal canal. Note the lateral placement of the needle as described in the text, compared with the classic midline
approach. The circles indicate the sacral cornua.(From Waldman SD: Interventional Pain Management, 2nd ed. Philadelphia, WB Saunders,
1996. Also from Lou L, Racz G, Heavner J: Percutaneous epidural neuroplasty. Pain Digest 41:436, 1996.)
canal ( Fig. 32–3 A). This is important, because anatomic variations of the sacrum could lead to incorrect needle
placement, which may “feel” correct ( Fig. 32–3B ). Next, an AP view should verify needle tip placement toward
805
the affected side ( Fig. 32–4 ). To facilitate the passage of the catheter to the anterior epidural space, the epidural
needle is turned with the bevel facing either the 7 o’clock position for the left or the 5 o’clock position for the right.
After negative aspiration for blood and cerebrospinal fluid (CSF), 10 mL of iohexol (Omnipaque-240) or
metrizamide (Amipaque) is injected under fluoroscopy for an epidurogram. If venous runoff is noted, the needle tip
is moved during injection until contrast media is seen spreading within the epidural space. As contrast media is
injected into the epidural space, a Christmas-tree shape is noted as the dye spreads into the perineural structures
inside the bony canal and along the nerves as they exit the vertebral column. Epidural adhesions prevent dye spread
so that there is a marked absence of dye outlining the involved nerve roots ( Fig. 32–5 A). A lateral view also shows
a lack of dye outlining the scarred nerve roots.
If the needle tip is subarachnoid, dye spread is noted centrally and cephalad many levels above L5 ( Fig. 32–6 ). If
the needle tip is subdural, dye spread is also central and cephalad, but not as wide as that of an epidural injection.
The contrast enhances the view of the outline of the nerve roots and the dura from the circumferential spread within
the less resistant subdural
Figure 32-3 A, Correct needle placement into the caudal canal. B, Incorrect needle placement in the subcutaneous tissue. (From Waldman SD:
Interventional Pain Management, 2nd ed. Philadelphia, WB Saunders, 1996. Also from Lou L, Racz G, Heavner J: Percutaneous epidural
neuroplasty. Pain Digest 41:436, 1996.)
space ( Fig. 32–7 ). Injection of local anesthetic into the subarachnoid or subdural space results in a motor block that
is notably more profound and with a more rapid onset of the block than seen after injection into
Figure 32-4 An anteroposterior view, with the needle pointing to the affected
side.(From Waldman SD: Interventional Pain Management, 2nd
ed. Philadelphia, WB Saunders, 1996. Also from Lou L, Racz G, Heavner J: Percutaneous epidural neuroplasty. Pain Digest 41:436, 1996.)
806
the epidural space. A subdural block is often typified by a segmental motor block with a diffuse sensory block to the
level expected from a subarachnoid injection of local anesthetic. The motor block from subdural injection may take
20 minutes to develop.
If CSF is aspirated, it is best to abort the procedure and repeat it on another day. If blood is aspirated, the needle is
first retracted caudally in the sacral canal until no blood can be aspirated. If this is unsuccessful, an attempt can be
made to proceed with catheter placement into the proper location. Aspiration of this catheter should be negative for
blood, and lack of venous runoff should be confirmed through the injection of a contrast agent.
The ideal epidural catheter is a stainless steel, fluoropolymer-coated, spiral-tipped Racz Tun-L-Kath. A Racz [10] [11]
catheter is passed through the needle into the scar tissue ( Fig. 32–5 B). The bevel of the needle should be facing the
*
ventrolateral aspect of the caudal canal of the affected side. This turning of the needle facilitates passage of the
catheter to the desired side and decreases the chance of shearing the catheter. Because scar formation is usually
uneven, multiple passes may be necessary to place the catheter into the scarred area.
*There are multiple spring catheters available. The Tun-L-XL 24-inch with bent tip has desirable features such as steerability because of its one-
to-one technique and better tip control during placement.
Figure 32-5 A, After injection of 10 mL of contrast medium. The medium has spread to the
left side of the epidural space, avoiding the right side, from which the symptoms originate. B,
The Racz Tun-L-Kath epidural catheter is threaded to the right side of the epidural space into
the scarred area. C, Injection of 5 mL of contrast medium shows spread into the area scarred
previously. The spread was followed by injection of 9 mL of 0.2% ropivacaine with 40 mg (1
mL) of triamcinolone and, after 30 minutes, by 10 mL 10% saline. The patient had complete
pain relief after the procedure. (From Waldman SD: Interventional Pain Management, 2nd ed.
Philadelphia, WB Saunders, 1996. Also from Lou L, Racz G, Heavner J: Percutaneous
epidural neuroplasty. Pain Digest 41:437, 1996.)
807
Figure 32-6 Subarachnoid spread of contrast medium.(From Waldman SD: Interventional Pain
Management, 2nd ed. Philadelphia, WB Saunders, 1996. Also from Lou L, Racz G, Heavner J:
Percutaneous epidural neuroplasty. Pain Digest 41:437, 1996.)
Figure 32-7 Subdural spread of contrast medium. The contrast medium is spreading centrally,
without a “Christmas tree” configuration. The catheter is in the central part of the
canal.(From Waldman SD: Interventional Pain Management, 2nd ed. Philadelphia, WB
Saunders, 1996. Also from Lou L, Racz G, Heavner J: Percutaneous epidural neuroplasty.
Pain Digest 41:437, 1996.)
For this reason, it is best to use a 16-gauge R-K epidural needle, which has been specially designed to allow multiple
passes of the catheter. To facilitate steering of the catheter into the desired location, a 15-degree bend is placed at
[12]
the distal end of the catheter. After final placement of the catheter and negative aspiration, another 3 to 5 mL of
contrast media (maximal total of 20 mL) is injected through the catheter. This additional dye should be seen
spreading into the area of the previous filling defect, with an outline of the targeted nerve root ( Fig. 32–5 C). Next,
1500 units of hyaluronidase (Wydase) in solution with 10 mL of preservative-free normal saline are injected rapidly.
After negative aspiration, 10 mL of 0.2% ropivacaine and 40 mg of triamcinolone are injected through the catheter
in divided doses. This additional volume is helpful in furthering lysis of adhesions because the catheter tip is placed
in the scar tissue. The area of scarring and subsequent scar dissection should be noted and recorded. It is noteworthy
that the steroids cannot be injected through the 22-µ bacteriostatic filter; therefore, the steroid must be injected
before placement of the in-line filter.
If contrast media is not used because of a patient’s allergic history, the procedure is the same except for the absence
of dye. Aspiration should be negative for CSF and blood before any injection. Additionally, a test dose of local
anesthetic should be given to verify that the needle, and subsequently the catheter, are not subarachnoid or subdural.
When the needle and catheter are properly placed, the patient often reports pain with injection in the dermatomal
distribution of the scarred area.
When the procedure is complete ( Fig. 32–8 ), the catheter should be secured to the skin with 3–0 nylon on a cutting
needle. Caution must be taken to avoid puncturing the catheter with the needle and to avoid cutting the catheter
coating while it is being wrapped. A triple antibiotic ointment such as polymyxin, and two 2 × 2-inch split
intravenous gauze bandages are used to cover the catheter exit site. The surrounding skin is sprayed or covered with
tincture of benzoin. With a single loop of the catheter directed toward midline, all of the above area is covered with
a 4 × 6-inch sterile transparent surgical dressing. On top of the transparent dressing, we place two 4 × 4-inch gauze
over the puncture site and apply over the area four pieces of 6-inch long Hypafix tape. The Hypafix tape has the
unique property of being elastic yet porous; therefore, the patient does not “sweat it off” during the 3 days that the
catheter is kept in place. Before the sterile field is undraped the catheter is connected to an adapter and a 0.2-µ
bacteriostatic filter that is not removed for any of the three daily injections.
808
Figure 32-8 Radiographs from patient with left lower extremity pain and
foot drop. A, After 10 mL of Omnipaque 240. Note complete filling defect
on left at L4 and S1 and partial filling of the L5 spinal nerve. B, Racz Tun-
L-Kath XL catheter threaded into the L5 neural foramen. C, After injection
of another 10 mL of Omnipaque, there is opening of the L5-S1 nerve root
and cephalad spread of contrast medium. D and E, Further opening of the
filling defect and cephalad spread of contrast medium has occurred. (From
Waldman SD: Interventional Pain Management, 2nd ed. Philadelphia, WB
Saunders, 1996. Also from Lou L, Racz G, Heavner J: Percutaneous
epidural neuroplasty. Pain Digest 41:441, 1996.)
The filter is capped, and the catheter is taped to the flank of the patient. In the preoperative period and during the
hospitalization, the patient is given intravenous antibiotics in the form of cephalosporins, such as ceftriaxone
(Rocephin), 1 g daily intravenously. Prophylactic antibiotics are given to prevent bacterial colonization, which is
especially hazardous in view of the epidurally administered steroid. Additionally, for epidural abscess prophylaxis,
it is also our practice to send a patient home with an oral antibiotic for 5 additional days.
Once the patient is taken to the recovery room and vital signs are obtained, 9 mL of the 10% hypertonic saline is
infused over 20 to 30 minutes. During the infusion, the patient is placed in the lateral position, with the painful side
dependent. To maximize the effect, the position is maintained postinfusion for at least 1 hour or longer.
Occasionally, the patient may complain of severe burning pain during the infusion. The burning is usually from the
introduction of hypertonic saline to unanesthesized epidural tissue. Should this occur, the infusion must be stopped
and an additional bolus of 3 to 5 mL of local anesthetic is injected. After 5 minutes, the hypertonic saline infusion
can be restarted without incident. After completion of the hypertonic saline infusion, 1.5 mL of preservative-free
normal saline is used to flush the catheter. Once this task is completed, the cap is replaced on the filter.
The hypertonic saline has a mild, reversible, local anesthetic effect and also reduces edema of previously scarred or
inflamed nerve roots. Injection of hypertonic solutions into the normal epidural space is quite painful unless
[13] [14]
preceded by local anesthetic. If the hypertonic saline spread is greater than the coverage area of the local anesthetic,
the patient may have severe pain. The pain caused by the hypertonic saline in the epidural space rarely persists more
than 5 minutes.
The catheter is left in place for 3 days. On the second and third days, the catheter is injected once a day with 10 mL
of 0.2% ropivacaine after negative aspiration from the catheter. After 20 to 30 minutes, 9 mL of 10% saline is
infused over 20 minutes for patient comfort. As with all hypertonic saline infusion series, the catheter must be
flushed with 1.5 mL of preservative-free normal saline. On the third day, the catheter is removed 10 minutes after
the last injection. A triple antibiotic ointment is placed on the wound, which is covered by a bandage or other
appropriate dressing.
HELPFUL HINTS
We inject only one dose of steroid in the operating room under totally sterile conditions. After the bacteriostatic
filter is placed, it is not removed during the series of reinjections. We have demonstrated in our laboratory that when
809
methylprednisolone (DepoMedrol) plus local anesthetic or triamcinolone (Aristocort) and local anesthetic are
injected through a bacteriostatic filter, the filter screens out virtually all of the steroid.
[15]
During the time the catheter is indwelling, the patient should keep the insertion site dry. We also recommend that
the patient keep the area dry for 48 hours after removal to decrease the chance of infection. Showering is permitted
after this time, but immersion of the wound such as would occur in a bath or in pool therapy should be avoided for a
minimum of 7 to 10 days.
This procedure is usually followed by significant reduction of pain and improvement of motor function. With
reduction of pain, it is important to initiate aggressive physical therapy to improve muscle strength and tone, which
are usually decreased from lack of use secondary to pain. Often, it is not possible to completely lyse existing
epidural adhesions because of the extensive amount of scar tissue. If necessary, we repeat the procedure. Because of
the steroids used, a 3-month delay between procedures is necessary, during which time the patient should be
encouraged to continue intense physical therapy. This therapy should begin immediately when possible. Initiation of
neural flossing techniques, especially while the local anesthetic is still active, provides a prime opportunity to
maximize the adhesiolysis process with the least discomfort to the patient. One month of aquatic therapy and then
aggressive, graded physical therapy and work hardening are also recommended.
After negative aspiration is confirmed, all solutions should be injected slowly. Fluoroscopies often initially reveal
massive epidural scar formation. In Figure 32–8 A, after injection of 10 mL of Omnipaque-240, the dye can be seen
spreading preferentially toward the right-hand side, opening up the right L4 to L5 and S1 to S2 nerve roots, whereas
there is a complete filling defect at the left L4 and S1 nerve roots and partial filling of the L5 nerve root. In Figure
32–8 B, a Racz Tun-L-Kath XL catheter is threaded into the L5 neural foramen area and through this, an injection of
an additional 10 mL of Omnipaque opens up the L5 to S1 nerve root ( Fig. 32–8 C) and spreads cephalad as
evidenced by the disappearance of the L4 to L5 disc space when this space is masked by the spreading contrast ( Fig.
32–8 D). This is followed by the injection of 10 mL of preservative-free saline, 1500 units of hyaluronidase
spreading to L4 and L5, and, finally, 10 mL of 0.2% ropivacaine and 40 mg of triamcinolone ( Fig. 32–8 E). The
patient’s foot drop dramatically improved the next day as a result of the decompression of the L4 to L5 and S1 nerve
roots with dissection of the perineural space by the injected material.
CERVICAL, THORACIC, AND UPPER LUMBAR AREAS
The technique for lysis of epidural adhesions in these areas of the spinal cord must be modified to ensure that initial
needle placement is in the epidural space and to avoid spinal cord compression by subsequent injections.
HISTORY
Cervical epidural blockade was first reported by Dogliotti in 1933. Cervical neuroplasty is a
[16]
derivative of caudal neuroplasty. It was conceived by Racz, in 1989, as a method of addressing the
epidural fibrosis associated with failed neck surgery syndrome, disc bulges, and inflammation not
responsive to single-shot epidural steroid injection. Because of the narrowness of the space and the
potential for profound spinal cord injury, fluoroscopy was introduced as a safety tool for the pain
physician. Naturally, the use of a nonionic water-soluble radiographic contrast agent was soon added
to monitor vascular runoff. More recently, the technique has been modified to include selective nerve
root stimulation for localization of the painful nerve root. This modification is called neural
mapping.
ANATOMY
The cervical spine consists of seven vertebrae and eight nerve roots. C1 and C2 nerve roots exit the central neuraxis
posteriorly through the intralaminar space to innervate the posterior upper neck and scalp of the occipital region.
Cervical nerve roots C3 to C8 exit from the neuroforamina. These differences are important for nerve-specific
epidural catheter placement and adhesiolysis.
For the placement of the epidural needle, several key points need to be mentioned. The posterior wall of the bony
canal is composed of the spinous process and lamina. Knowledge of these landmarks is important for radiographic
810
identification. Just after the bone of the vertebrae is the ligamentum flavum. The interspinous ligament covers the
interspinous spaces.
INDICATIONS
The choice of cervical neuroplasty is dependent on many factors, the most important of which is the safety of the
initial approach. Although single-shot posterior approach cervical epidural steroids can and have been used
frequently and safely, in the more stenotic and scarred epidural spaces, the placement of the epidural needle can be
extremely hazardous. In skilled hands, the hanging-drop and loss-of-resistance techniques facilitate safe entry into
the epidural space in most situations. Unfortunately, severe and sometimes fatal consequences of complications in
this region may occur with the use of older standard methods of epidural access.
Because of the aforementioned complications, the “3-D technique,” applied to cervical epidural entry, is especially
pertinent. The first “D” of the 3-D technique is direction, followed by depth, and last, direction again. Fluoroscopy
is an important key to this technique. With the ability to see the relationship of the epidural needle to the vertebra,
the operator can advance the needle in a safe fashion.
Neural mapping is very useful in complex pain complaints. Frequently, the patient may complain of a pain that
involves multiple dermatomes. If the pain is centrally mediated, the ability to determine the actual painful nerve
roots allows directed treatment.
PATIENT POSITIONING
The standard used by our team is a left lateral decubitus position. Lateral decubitus greatly diminishes potential
movement of the patient into the needle. If an outlet direction for movement is available, the patient tends to move
away from the epidural needle. If the prone or sitting position is used, the patient must be restrained. Securing the
patient may require extensive strapping and taping of the head and torso.
TECHNIQUE
Because of the potential for dural puncture and spinal cord injury, the upper thoracic approach (T1–T2) is used.
After sterile preparation and with maintenance of sterile technique, the skin entry point is marked 1 to 1½vertebral
levels lower. Using the spinous process as midline, the site for skin entry is anesthestized with 1.5% lidocaine
administered via a 25-gauge infiltration about 1 cm paramedial on the contralateral side. The entry of the epidural
needle is facilitated by a puncture wound from an 18-gauge needle. Using fluoroscopy in the AP view, the 16-gauge
3½-inch Epimed R-K epidural needle is inserted toward the T1 to T2 interspace, with the tip of the needle directed
to midline. At skin entry, the needle appears to progress in a 70- to 80-degree angle owing to the lordosis of the
spine at that level. Once the direction of the needle is considered satisfactory and before the needle crosses into the
interlaminar zone, the fluoroscope is changed to a lateral view to make the straight line of the anterior spinous
process visible ( Fig. 32–9 ). Just before this line is breached, the fluoroscope is returned to the AP view to confirm
the proper direction of the needle. The final 2 to 3 mm of needle advancement is done with the loss-of-resistance
technique. Our practice is to use 2 mL of preservative-free normal saline and 2 mL of air.
After the needle is in place, 3 to 5 mL of Omnipaque 240 contrast material is injected to create an epidurogram ( Fig.
32–10 ). Once a scarred area is delineated, a stylet-type, saline-flushed, Epimed Tun-L-XL 24-inch catheter is
prepared for introduction through the epidural needle. A 10-degree bend is placed at the distal 2.5 to 3 cm of the
epidural catheter. The bend facilitates steering of the catheter. With purposeful twisting of the epidural catheter, the
tip is guided through the scarred area and specifically placed at that nerve root.
If a clearly scarred nerve root cannot be found, the Racz Tun-L-XL epidural catheter lends itself to
electrostimulation. The distal tip is metallic, and the stylet can be withdrawn 1 to 2 cm for clamping with alligator
clip cables. The negative electrode (black) is placed on the catheter stylet and the positive (red) alligator clamp is
placed on the epidural needle, or a 22-gauge (G) needle is placed into the skin as a ground. In these situations, the
catheter tip is either placed at the lowest suspected nerve root or progressively manipulated over each successive
superior nerve root and vice versa. The Medtronic trial screener is the pulse generator used. (Standard pulse
generator settings are 0 negative, 3 positive, and 1, 2 off; rate=50; and pulse width = 450.) Amplitude is gradually
increased to cause paresthesia.
811
Figure 32-9 The needle is directed into the intralaminar space. The tip of the needle is posterior to the “straight line” that is formed by the
spinous process. By stopping at the straight line in the lateral view, the ligamentum flavum is not entered. This technique prevents accidental
spinal cord entry. Loss-of-resistance technique is used to advance further.
Figure 32-10 Epidurogram of the cervical area shows contrast medium spreading proximally and caudally (arrow). (From Waldman SD:
Interventional Pain Management, 2nd ed. Philadelphia, WB Saunders, 1998. Also from Lou L, Racz G, Heavner J: Percutaneous epidural
neuroplasty. Pain Digest 4:439, 1996.)
With electrostimulation, the patient commonly vocalizes reproduction of pain or paresthesia in the affected painful
area. No painful experience is reported at nonaffected nerve roots. When final placement is determined, the epidural
catheter is often reinjected with 1 to 2 mL of radiographic contrast agent to evaluate the opening of the nerve root.
Once this is confirmed, the catheter is thereafter injected with 6 mL of 1500 units of hyaluronidase in preservative-
812
free 0.9% saline, in small volume increments (1–2 mL). Radiographic imaging during injection of these agents is
recommended to rule out intravascular and intrathecal injection. As an added precaution, the catheter should always
be aspirated before injection of any drugs. Lastly, 6 mL total of 0.2% ropivacaine or 0.25% bupivacaine and 40 mg
of triamcinolone diacetate are injected in boluses of 2 mL and 4 mL. It is extremely important to wait 5 minutes
between boluses of local anesthetics to guard against inadvertent spread or injection. Active monitoring of the
patient during local anesthetic injections should be maintained. All injections must be given in the lateral epidural
space.
Finally, the catheter is ready for securing. To prevent accidental displacement of the epidural catheter,
Figure 32-11 A, Anteroposterior view of a cervical catheter shows placement on the right side of the epidural space in a patient with right arm
pain. B, Lateral view of cervical catheter. (From Waldman SD: Interventional Pain Management, 2nd ed. Philadelphia, WB Saunders, 1996. Also
from Lou L, Racz G, Heavner J: Percutaneous epidural neuroplasty. Pain Digest 41:440, 1996.)
the epidural needle is removed with fluoroscopic assistance. The catheter tip is watched. After the epidural needle is
removed, the catheter is sewn into place with 2–0 nylon on a cutting needle. The permanent connector and a 0.2-µ
bacteriostatic filter are attached to the catheter. Once triple antibiotic ointment is placed at the wound site, a slotted 2
× 2 gauze is placed over the catheter exit site. A small loop of the catheter is then held in place and covered, along
with the gauze dressing, by a transparent surgical dressing.
Infusion of 5 mL of preservative-free hypertonic (10%) saline is delivered over 20 minutes in the recovery room.
The painful side is kept in the dependent position. Should the patient complain of pain, burning, or other noxious
stimuli during the infusion of hypertonic saline, the infusion must be stopped and reevaluated. Occasionally, 1 to 3
mL of additional 0.2% ropivacaine need to be injected to anesthetize the newly exposed neural tissue. After 5
minutes, the hypertonic saline infusion can be restarted without further complaints. When the hypertonic saline
infusion is complete, the epidural catheter is flushed with 1 to 2 mL of preservative-free normal saline. The epidural
catheter is then recapped.
For neuroplasty stages 2 and 3, the epidural catheter is reaccessed. Aspiration of the catheter should be negative.
Once again, 6 mL of local anesthetic (0.2% ropivacaine) is injected in divided doses with attention give to possible
intrathecal, subdural, or intravascular injection. The patient is then asked to lie in the lateral decubitus position, with
the painful side down to allow gravitational spread to the affected nerve root. Similar to the previous hypertonic
saline infusion, 5 mL are delivered over 20 minutes. Once the infusions are complete, 1 to 2 mL of preservative-free
normal saline is used to flush the catheter. After the third infusion, the suture is cut and the intact epidural catheter is
carefully removed. Finally, another application of triple antibiotic ointment is applied over the wound and the
wound covered by a bandage.
813
HELPFUL HINTS
The initial placement of the epidural needle is facilitated by perfectly aligned AP and lateral fluoroscopic images.
Slightly oblique images can cause inaccurate placement of the epidural needle. Good midline needle entry is
important if C1 and C2 are to be targeted. Paramedial epidural needle entry allows easy coverage of the C3 to C8
nerve roots but difficult catheter steering in the posterior midline for C1 and C2 coverage.
Another common situation occurs with the infusion of hypertonic saline. Frequently, the patient complains of pain at
the initiation of the infusion. Often, this can be treated not by injecting more local anesthetic but by taking more
time. In a rapidly moving environment, the local anesthetic and steroid injected in the operating theater do not fully
reach peak effect. An additional 5 to 10 minutes prevents the need for more local anesthetics.
HISTORY OF TRANSFORAMINAL NEUROPLASTY
The lumbar transforaminal injection was first developed as a method for injecting the dorsal
root ganglion.
ANATOMY
The lumbar spine consists of five lumbar vertebrae. The borders of the lumbar foramen consist of the vertebral body
and disc anteriorly, the pedicles superiorly and inferiorly, and the facet articular processes posteriorly. Within the
foramen, the nerve root exits in an anterior caudal direction. Anterior to the nerve root, radicular vessels can be
found to follow the nerve root into the epidural space. Posterior to the nerve root is the dorsal root ganglion.
INDICATION
There are occasions where the nerve roots are difficult to open or when access to the anterior space is needed.
CONTRAINDICATIONS
The main contraindications are local infection and coagulopathies.
PATIENT POSITION
The patient is in the prone position with enough table clearance to provide a full range of fluoroscopic rotation.
TECHNIQUE
After consent is given, the patient is placed in the prone position. With use of sterile preparation and technique, the
back is cleansed with a sterilizing solution from just below the scapula to the lower margin of the buttocks.
Preparation of the lumbar region only is appropriate if the upper lumbar region without sciatic involvement is the
source of the problem. With use of fluoroscopy, the desired lumbar level and side is identified. The fluoroscope is
then moved obliquely 15 to 20 degrees to the ipsilateral side of the desired foramen. Once a “Scotty dog” image is
obtained, the fluoroscope is rotated in a caudal-cephalad direction for 15 to 20 degrees. A caudal-cephalad rotation
elongates the superior articular process (“ear of the Scotty dog”). The tip of the ear, or superior articular process, in
the “gun barrel” technique is marked on the skin. This spot is the skin entry site, and local anesthetic is injected for
skin infiltration. An 18-G needle is used to make a puncture wound. Through this wound, a 16-G Epimed R-K
epidural needle is advanced anteriorly until bone is contacted. A lateral fluoroscopic is obtained before further
introduction of the needle. To facilitate passage of the needle past the articular process, the epidural needle is turned
laterally to slide past the bone and stop just after a “pop” is felt. The needle tip on a lateral view should be in the
posterior aspect of the foramen. An Epimed Tun-L-XL epidural catheter is then inserted through the epidural needle.
Occasionally, the epidural needle must be tilted at the hub laterally to aid entry of the epidural catheter into the
anterior epidural space. The catheter is advanced medial to the pedicle. After catheter placement is confirmed to be
in the anterior epidural space under anteroposterior and lateral views, the stylet is removed from the catheter and a
connector is placed on the proximal end of the epidural catheter.
814
Aspiration should be negative before 3 mL of Omnipaque-240 radiographic contrast is injected. The contrast
injection should show opening of the entered neuroforamen, with contrast exiting along the path of the nerve root.
When satisfactory contrast spread is seen, 8 mL of 1500 units hyaluronidase and preservative-free normal saline are
injected to achieve further opening of other adhesions. Finally, 8 mL of 0.2% ropivacaine or 0.25% bupivacaine
with 20 to 40 mg of triamcinolone diacetate are injected. The catheter is then secured in place with 2–0 nylon on a
cutting needle. The dressing consists of triple antibiotic ointment over the wound site, a 2 × 2 slotted gauze dressing
over the ointment, a small inferior loop of the catheter, and a covering consisting of a transparent surgical dressing.
For added security, the dressing is further covered by Micropore tape.
After the patient is transported to the recovery room and negative aspiration of the catheter is confirmed, 7 mL of
10% hypertonic saline is infused over 20 minutes. Once the infusion is complete, the epidural catheter is cleared
with 1 to 2 mL of preservative-free normal saline. The epidural catheter is then left in place for a second and third
reinjection. For the reinjections, the catheter is checked for negative aspiration. The local anesthetic is given in
divided doses (2 mL and 4–6 mL) at 5-minute intervals. As with the first injection, the hypertonic saline (7 mL) is
infused over 20 minutes and flushed with 1 to 2 mL of normal saline.
Subdural or intravascular injection should also be monitored. Removal of the catheter is performed after the third
infusion. Care must be taken to ensure intact removal of the epidural catheter.
EFFICACY
Although there are no controlled studies on the clinical effectiveness of transforaminal epidural injection, many
clinical reports have been supportive of this procedure.
DRUGS
Iohexol
Iohexol is a second-generation, nonionic, low-osmolar radiographic contrast agent. The iodine content is 46% by
weight, buffered by tromethamine to a pH of 6.8 to 7.7, and preserved with 0.1 mg/mL edetate calcium disodium.
The uniform coverage of the iodine atoms by the hydrophilic groups is responsible for their low toxicity. Many
concentrations (140, 210, 240, 300, 350 mgI/mL) of iohexol are available for subarachnoid, intravascular, and body
cavity injections. For subarachnoid administration, the concentration should never be greater than 300 mgI/mL in
adults and 210 mgI/mL in children. Owing to the toxic effects of iodine, the total dose for adults is 3.06 mg and 2.94
mg in children. There is minimal protein binding in serum. Eighty-eight percent of an intrathecal dose is renally
excreted in its unmetabolized form and can be found within the urine after 24 hours. Chemotaxic reactions are
[17]
often dose dependent and appear as hypotension, dyspnea, cardiac arrest, organ failure, and/or loss of consciousness.
The incidence of chemotaxic reactions with these radiographic contrast agents occurs in only 1 of 100,000 patients.
Intravascular injection of iohexol has been reported to have a low risk of causing renal failure. There is some
[18]
concern that this risk may be increased in patients taking oral hypoglycemics. Fortunately, these complications are
infrequent with nonionic contrast agents.
Idiosyncratic reactions include headache, myalgia, nausea, vomiting, dizziness, aseptic meningitis, and other
neurologic disturbances. The most common reaction is headache, which occurs in 18% of patients after intrathecal
iohexol. Aseptic meningitis and neurologic disturbances are much less common. Allergic or anaphylactoid
[17]
reactions with nonionic contrasts are rare and less frequent than with ionic contrasts. Ndosi and associates
[19] [20]
reported that the risk of significant reaction with concentrations of 240 mg/mL of iohexol for myelography in a
placebo-controlled double-blinded study was no greater than that related to the lumbar puncture itself. This same
study reported that headache, dizziness, nausea, vomiting, and seizure were more likely to occur with 180 and 300
mg/mL concentrations.
Hyaluronidase
Hyaluronidase is a lyophilized, white, odorless, amorphous powder that is commercially available in 150 U and
1500 U. The smaller dose is supplied fully hydrated, whereas the larger amount is a solid with 1.0 mg of thimerosol
preservative with 13.3 mg of lactose for mixing with a solute. Duran-Reynals first described the spreading factor of
[21]
hyaluronidase by describing strains of streptococcal bacteria. It can be found in bee and snake venom and in
[21]
mammalian tissues and sperm. Its primary function is to depolymerize hyaluronic acid and, to a lesser degree,
[22]
chondroitin-6-sulfate and chondroitin-4-sulfate. Hyaluronic acid is a large molecule glycosaminoglycan that binds
the ground substance proteins that form proteoglycans. These proteoglycans are found between the ground
815
substances that are between cells, and they are also in cheloids (dense scar tissue) and epidural adhesions. [23]
Disruption of these proteoglycans is accomplished by cleaving the beta-1,4 glycosidic bonds.
The breakage of proteoglycans has been found to accelerate the diffusion of injected drugs. This hypodermoclysis [24]
was subsequently found to increase the efficacy of the local anesthetic infiltrations. In the epidural space, the dura
[25]
is composed of collagen, elastin, and surface fibroblasts that are not affected by hyaluronidase. Intrathecal use of
hyaluronidase has been documented for chronic arachnoiditis, with no report of any serious adverse effects in 15
patients. [26]
Nicoll and colleagues reported a 6000 retrobulbar block prospective study with adverse effects attributed to the
[27]
spread of local anesthetic into the CNS. Because of the known homology of mammalian hyaluronidase to insect
hyaluronidase, attention should be given to possible complications in patients with venom allergies. Anaphylactic- [28]
like reactions have occurred in isolated cases. [29]
Local Anesthetic
The local anesthetic used is limited to a sensory concentration and amount. With local anesthetic, immediate pain
relief is possible in addition to preparation of the epidural tissues for infusion of the hypertonic saline. Hypertonic
saline tends to cause a burning sensation when infused without preinjection of local anesthetics. As an additional
safeguard against subdural or intrathecal injection, the local anesthetic is delivered in divided doses to monitor for
nonepidural spread. For the neuroplasty technique, it also serves as a diluent for the steroids.
Bupivacaine is significant for its cardiotoxicity, which has now been attributed to the dextroenantiomer. [30]
Levobupivacaine is exclusively composed of the S(−) monomer of racemic bupivacaine and has been proved to
have essentially the same clinical properties and potency as racemic bupivacaine, with significantly fewer adverse
effects. Ropivacaine is a third generation S(−) monomer local anesthetic of the PPX amino-amide series, with less
[31]
cardiotoxicity but potency and duration of action similar to those of racemic bupivacaine. Significant differences of
ropivacaine from bupivacaine are its vasoconstrictive properties and documented ability to reduce epidural blood
and pial blood vessel size. [32] [33]
Steroids
Methylprednisolone and triamcinolone are two of the more popular choices for epidural injection. They both interact
with two different receptor types: glucocorticoid and mineralocorticoid. The glucocorticoid is primarily responsible
for regulation of carbohydrate metabolism and the inflammatory and immune responses, whereas the
mineralocorticoid is responsible for regulation of electrolyte balance. Attempts to synthesize a steroid with anti-
inflammatory properties have been fraught with difficulty.
Collectively, methylprednisolone and triamcinolone are considered of intermediate duration, with equipotent anti-
inflammatory effects. Triamcinolone is a more glucocorticoid-specific agonist than methylprednisolone. Both of
these drugs exhibit a lower protein binding and metabolism than endogenous corticosteroids. Unfortunately, they are
all potentially suppressive of the hypothalamic-pituitary-adrenal axis.
Triamcinolone diacetate is suspended in a solution consisting of polysorbate 80, 0.20%, polyethylene glycol 3350,
3%, sodium chloride 0.85%, with benzyl alcohol 0.90% as a preservative. The pH of triamcinolone is adjusted to
approximately 6. This steroid is compatible with a variety of diluents unless a preservative is present. Flocculation
[34]
and clumping of triamcinolone is reported when it is mixed with a preserved diluent or if the steroid has been frozen
and then thawed. Methylprednisolone has been shown to flocculate when mixed with lidocaine.
Although systemic toxicity from epidural injection is not exactly known, suppression of the hypothalamic-pituitary-
adrenal axis from triamcinolone has been shown to persist for 21 days. Examples of the toxic effects are metabolic
[35]
disturbances; electrolyte imbalances; fluid shifts such as edema; muscle wasting; peptic ulcers; impaired wound
healing; and immunologic functions. Allergic reactions to the steroids are rare. The preservative polyethylene
[36] [37]
glycol in many commercial formulations may cause arachnoiditis when injected intrathecally. Case reports of [38]
epidural abscesses, aseptic meningitis, and bacterial meningitis have also been published. [39] [40]
Hypertonic Saline
Hypertonic saline was first reported in 1967 as a cold saline injection into the intrathecal space for chronic back
pain. Hitchcock later reported that the hypertonicity of the solution rather than the temperature was responsible
[41] [42]
816
for its effects. Cat studies showed a selective C-fiber blockade of dorsal rootlets that appeared to be related to the
high chloride ion concentration. Lake and Barnes’s work on frog spinal neurons showed that hypertonic saline
[43] [44]
decreased the spinal cord water content and depressed the lateral column evoked ventral root response by affecting
the γ-aminobutyric acid receptors. Racz and associates performed a study on dogs in which they looked at the
[9]
effects of hypertonic saline in the epidural space and showed that it took 20 minutes for the CSF to equilibrate, with
resultant doubling of the CSF sodium concentration.
Most of the complications cited are related to intrathecal hypertonic saline. Clinical complications of intrathecal
injection of hypertonic saline consist of cardiac, respiratory, and neurologic sequelae such as hypertension,
tachycardia, and tachypnea with pulmonary edema. The changes can occur rapidly, with associated
[45]
hemorrhaging. As to complications directly related to epidural injection, Aldrete and colleagues reported two
[46] [47]
cases of arachnoiditis from possible subdural or subarachnoid spread; otherwise, no other incidences have been
noted or reported.
Complications
Potential hazards of this procedure include unintended subarachnoid or subdural injection of local anesthetic or
hypertonic saline, paralysis, bowel and/or bladder dysfunction, and infection. Careful attention to sterile technique is
necessary because steroids suppress the immune system, making the risk of infection greater. Hypertonic saline
injected into the subarachnoid space has been reported to cause cardiac arrhythmias, paresis, and loss of sphincter
control.
[9]
As mentioned earlier, all injections should be made slowly. Rapid injections into the epidural space may cause large
increases in CSF pressure, with the risk of cerebral hemorrhage, visual disturbance, headache, or compromised
spinal cord blood flow.
At our institution, we have performed the technique described for lysis of epidural adhesions in more than 4500
patients, with very few complications. We have rarely had a subarachnoid or subdural injection of local anesthetic.
We have had two patients develop meningitis, and both responded to antibiotic therapy. We have had no patients
with paralysis from this procedure, although one individual did have transient motor weakness after a caudal
procedure, whereby solid proximal adhesion prevented runoff of injected solution. We have seen no significant
bowel or bladder problems using this technique, although a few patients have noted mild difficulty in voiding for up
to 2 weeks after the procedure. Occasionally, transient perineal numbness, which was usually self-limited and
resolved in 1 to 2 months, was reported.
In one patient who had extremely severe failed back surgery syndrome with partial paralysis and inversion of a foot,
the gradual development of arachnoiditis was not recognized because of the hardware in her back; the patient had
not had interventional radiologic studies. The patient underwent lysis of adhesions,
but the procedure was aborted because of the development of motor block after the local anesthetic without any
injection of hypertonic saline. The patient had a preexisting bowel and bladder dysfunction. However, the full extent
of her neurologic deficit was not appreciated because of the overwhelming concern for her partial paralysis, spasm,
and pain. After the recovery of the motor function, the patient was left with a bowel and bladder deficit. She was not
able to void without catheterization and developed rectal incontinence. Subsequent diagnostic studies in the form of
a myelogram showed massive constrictive arachnoiditis. Her pain was subsequently managed by the placement of a
subarachnoid morphine pump, with slow resolution of the rectal incontinence. However, because of the
arachnoiditis and preexisting neurogenic bladder, the patient had to continue performing self-catheterization.
The concern about preexisting neurogenic bladder in multisurgical failed back or spinal cord injury patients has
resulted in increased awareness and cooperation with our urologist for the purpose of carrying out urodynamic
studies and documenting the preexistence of neurogenic bladder. The typical experience is improvement of bladder
function as well as sexual function in males after the procedure for lysis of adhesions. The predocumentation of
neurogenic bladder has resulted in our getting better informed consent from our patient population, which certainly
fits the highest risk for ongoing constrictive arachnoiditis causing the development of clinically recognized bowel,
bladder, and sexual dysfunction. The surprising finding has been the lessening of previous bladder dysfunction
rather than the feared development of neurogenic bladder and related problems. Additionally, patients are warned
that epidural infection is a distinct possibility because of the instrumentation as well as the steroid injection,
especially during the first 2 to 6 weeks after the procedure. Until proved otherwise, nausea, vomiting, neck stiffness,
new pain, different pain, greater pain, weakness, numbness, and/or paralysis that develop after the procedure are
considered to be signs and symptoms of procedurally related epidural infection. Patients need to understand and
817
report either to the operative physicians or their own physicians any experience of these signs or symptoms to
receive prompt intravenous antibiotic therapy and hospitalization until the condition clears up. As indicated earlier,
this has not been a problem in our patient population, but that does not mean that awareness and precautions can be
lessened because of the potentially devastating consequences of an unrecognized and untreated epidural abscess.
In our practice, catheter shearing does seem to occur every time we have a new group of pain fellows. The difficulty
stops when they become accustomed to absence of a free, smooth-flowing sensation of the catheter within the needle,
because we often have to withdraw the catheter through the specially designed RK needle to get an optimal location.
The sheared catheters usually hang up in the subcutaneous tissues or at the sacral hiatus. Of late, we have made it
part of our consent form that if there is a sheared catheter, we request surgical intervention to retrieve it. To date, we
have had five such occurrences.
Technical Hint
To retrieve the sheared catheter, we place two needles from different angles under fluoroscopy. The fluoroscope
pinpoints the end of the sheared catheter, and this makes removal through a half-inch incision a very simple
procedure.
Efficacy
We reviewed data from 4500 patients who underwent lysis of adhesions from the beginning of 1989 through the end
of 2000. We randomly selected 100 patients of whom one group (No.=50) had one dose of triamcinolone plus local
anesthetic followed by hypertonic saline on the first day; on the second and third days, they received only the local
anesthetic injection. The second group of patients (No.=50) had, in addition, 1500 units of hyaluronidase injected in
the operating room before the injection of local anesthetic and steroid followed by 10% sodium chloride. The patient
data were reviewed for demographics and duration of pain relief. Telephone follow-up was carried out by a
noninvolved third party who strictly tabulated the patient responses that were gathered, in some instances, up to 3
years after treatment. The results, tabulated in Figures 32–12 and 32–13 , separate the patients according to gender
and according to whether or not they received hyaluronidase, and evaluated them from a point of review of having
no relief, being completely pain free at the time of review, or having partial relief measured in months. In the
nonhyaluronidase group, the failure rate was 18%, with 14% of the patients being pain free at the time of the review,
and 68% of the patients fell into various groups, with duration of pain relief measured in months. In the
hyaluronidase group, the complete failure group fell threefold to 6.1%, whereas the persistent relief group had a
12.3% rate, and 81.6% of the patients fell into the category of having various durations of pain relief.
Figure 32-12 Pain relief in patients treated with (A) and without (B) hyaluronidase.
Percentages of the 50 patients treated are shown. (From Waldman SD:
Interventional Pain Management, 2nd ed. Philadelphia, WB Saunders, 1996. Also
from Lou L, Racz G, Heavner J: Percutaneous epidural neuroplasty. Pain Digest
41:441, 1996.)
818
A prospective study involving 83 patients was performed, which evaluated the efficacy of isotonic saline, hypertonic
saline, hypertonic saline with hyaluronidase, and isotonic saline with hyaluronidase. Of the 83 patients recruited, 59
completed the study. From this group, the maximal reported relief occurred immediately after treatment, with 25%
of the completed patients stating residual benefit after 1, 3, 6, 9, and 12 months. The 1-year follow-up of these
[48]
patients did reveal 49% persistent pain relief in the targeted lesion area. [49]
Discussion
Lysis of adhesions in the epidural space clearly is a procedure that needs to follow other simpler procedures, such as
rest, nonsteroidal anti-inflammatory medications, muscle relaxants, physical therapy, activity programs, two to three
single-shot epidural steroids, and a TENS (transcutaneous electrical nerve stimulation) unit. The more informed
patients preferred to undergo procedures such as lysis of adhesions rather than surgery. The results clearly showed a
dramatic decline in further surgical interventions in our patient population as well as avoidance of surgical
intervention in appropriately selected patients with clearly documented herniated discs and nerve root compressions.
This awareness is gaining support because the U.S. regulatory agencies, as well as courts, support the recognized
effective nature of the procedure of lysis of adhesions.[6]
Scarring in the epidural space occurs frequently after surgery and causes no problems. Scarring can occur after
leakage of material from the nucleus pulposus into the epidural space. The pain associated with scar formation
[1]
originates from the nerve itself, which is irritated, swollen, angry looking, and lacking space in which to move freely.
Normally, epidural scarring involves the nerves as they enter the neural foramina as well as epidural veins that are
surrounded by scars, thereby obstructing venous runoff. The obstruction raises intravenous pressure, leading to
additional edema formation within the epidural space.
The technique described earlier overcomes the obstacle of getting the medication to a lesion-specific site by placing
the tip of a soft spring catheter within the scar and letting the injected fluid, under pressure, find the path of least
resistance within the scar and open up the perineural space. Thus, the steroid can reach the inflamed, angry nerve
root, producing its anti-inflammatory effect. The hyperosmolar sodium chloride solution also reaches and blocks the
nerve roots together with the local anesthetic, giving additional pain relief. Our previous studies demonstrate that the
chloride ion does not move across the dura readily, which is the very likely explanation for the absence of feared
complications that were previously reported after subarachnoid infusion of hypertonic saline. [44] [45] [46] [50] [51] [52] [53] [54] [55] [56]
Hitchcock’s early work with iced saline irrigation of the subarachnoid space in cancer pain was followed by
[41]
complications which included bowel and bladder dysfunction, hypertension, paralysis, raised intracranial pressure,
and seizures as consequences of the chloride ion, as well as hyperosmolar solution, expanding and putting pressure
on the spinal cord and the central nervous system. Injection of hypertonic saline into the epidural space causes very
severe pain. Therefore, local anesthetic must be injected before the injection of hypertonic saline. If there is a
significant sensory and motor block after administration of 0.2% ropivacaine, this in itself should be enough
evidence to abort the procedure and not to inject the hypertonic saline. This is most probably the explanation of why
we have such a large series of procedures without the development of many serious complications.
The addition of hyaluronidase has resulted in threefold reduction of outright failures in our patient population, and
this needs to be further investigated to determine whether we are looking at a volume effect or whether the addition
of hyaluronidase really makes the difference. We are convinced that the hyaluronidase is helpful, and we are
continuing to give hyaluronidase injections. Hyaluronidase has been studied since the first report of this enzyme, in
1929, by Duran-Reynals, who labeled it a “spreading factor.” Moore, in 1520 epidural administrations of
[21] [56]
hyaluronidase, indicated a 3% sensitivity reaction. We believe that the explanation of why we have not seen the 3%
sensitivity reaction is that we place the steroid at the exact site where the hyaluronidase is deposited, and the steroid
leaves the space more slowly than the hyaluronidase. We look very carefully for any evidence of sensitivity reaction
in our patients who receive hyaluronidase. The threefold reduction of outright therapeutic failure, we believe, is
sufficient justification for us to continue administering hyaluronidase to our patients.
Patients who benefit from lysis of adhesions include those with failed back surgery, disc disruption, vertebral body
compression fracture, metastatic carcinoma, multilevel degenerative arthritis, facet pain, epidural scarring after
infection, meningitis, severe pain that is not controlled by a spinal cord stimulator or spinal opioids, metastatic
cancer leading to compression fracture, and osteoporotic compression fractures; generally speaking, these are
conditions that lead to radiculopathy
819
Figure 32-13 Duration of pain relief in patients treated

with (A) and without (B) hyaluronidase. (From
Waldman SD: Interventional Pain Management, 2nd ed.
Philadelphia, WB Saunders, 1996. Also from Lou L,
Racz G, Heavner J: Percutaneous epidural neuroplasty.
Pain Digest 41:442, 1996.)
The overall principle is always to start the injection from below the problem area. Especially in the cervical
thoracic area, the rate of injection has to be very slow. Continuous cooperation and discussion with the patient must
be maintained, and fluoroscopic evidence for fluid runoff must be observed continuously. We use the lateral
approach in dissecting adhesions, especially in the cervical area, where placement of the catheter near the neural
foramina is less likely to lead to spinal cord compression in the anteroposterior direction. It is not unusual to succeed
in freeing the cervical nerve roots all the way to the C2 area after three or four attempts and the pain relief is
sufficient; a spinal cord stimulator can be used if the pain relief is judged to be less than satisfactory by the patient.
A separate subgroup of patients who respond remarkably well are those who have intractable greater occipital
neuritis at C2, C3, or C4. These patients have radiculopathy that responds very well to the three daily injections of
local anesthetic, steroid, and hypertonic saline. It is not uncommon that we can first inject only one side, then wait 3
months to repeat the injection series on the other side.
Measurement of pain is always difficult, but effectiveness of lysis of adhesions is evidenced, for example, by
patients who have ongoing morphine subarachnoid infusion but do not have adequate pain relief. For example, one
patient was receiving 120 mg of morphine per day through a Synchromed pump. Within 4 days after the lysis of
adhesion procedure, we were able to reduce the amount of morphine being administered to 60 mg. This effect lasted
9 months, and the patient described the experience as “the best 9 months I have had in years.” By the time the
procedure had to be repeated, 1 year after the original injection, the patient was up to 80 mg of morphine per day.
The repeat lysis of adhesions for the intractable back and leg pain in this failed back surgery patient again resulted in
similar ability to rapidly reduce the total number of milligrams of morphine administered. We have had numerous
similar experiences with patients who failed to get satisfactory relief from spinal cord stimulation. After lysis of
adhesions on the most affected nerve root area, a dramatic improvement resulted, suggesting synergism between the
neuroaugmentation by cord stimulation and lysis of adhesions.
Manchikanti and colleagues carried out a prospective randomized study on the use of lysis of adhesions as a one-
[57]
day treatment. The outcome of the study shows a significant reduction in large opioid requirement, increase in
activities of daily living, reduction in symptom magnification, and reversal of depression. Cost of pain reduction
was significantly less than other alternatives such as medications or surgery. The control group, where no
intervention was used, failed to have any of the above changes. In a very convincing manner, Manchikanti and
820
colleagues documented the efficacy and safety, as well as the cost-effectiveness, of site-specific delivery of
[57]
medication, on a 1-day basis, to the area where the pain generators are located. This consideration is particularly
important, because current medical practice focuses on the issue of cost-effectiveness on an outpatient basis. Our
prospective, randomized, double-blind study was done by using a daily reinjection for three days in what appeared
to be a more difficult patient group than the one studied by Manchikanti. Our data still showed efficacy after 12
months. [9]
The principle of a treatment ladder and a continuum of care in evaluating and treating patients suffering from back
pain and radiculopathy clearly are important. Initially, the simplest therapeutic interventions must be tried, and, if
[10]
they fail, the next level of treatment should be tried. Clearly, patients can suffer from discogenic pain and intraspinal
spinal canal radiculopathy, which are often initiated by material leaking from the disc and causing an inflammatory
response. Patients can also have facet-related pain. Discogenic pain can cause back spasm, as clearly shown by
Indahl and colleagues. In our practice, we consider the possibility that patients may have not only radiculopathy
[58]
but a separate facet joint–related pain as well. After positive diagnostic block, the logical next step is the use of
radiofrequency thermocoagulation of the posterior primary ramus and the lateral branch at the involved segment and
above. This reverses not only the pain of radiculopathy but also the pain originating from the posterior structures,
which are the facet joints. [11]
Additional considerations also include the use of epiduroscopy, whereby visualization of epidural structures has
proved conclusively the existence of distended veins; the neovascularization of intraspinal structures; the presence
of swollen, inflamed nerve roots; and scar formation. Scar formation is evidenced by color change. Consistency of
scar tissue varies and restricts mobility of spinal structures as well as nerve roots. In some instances, we have been
able to use the epiduroscopy equipment to see the ventrolateral nerve root area and to pass a catheter to it through
the epiduroscope area. The cost-effectiveness at this point clearly favors the use of catheter-based lysis or site-
specific injection of medications. However, in some instances epiduroscopy may, in fact, be a useful adjunct to the
technique, as it has been well documented that the spread within the epidural space occurs by the principle of
“compartmental filling.” Compartmental filling implies that there is a pressure-volume relationship such that when
[12]
pressure builds up in a restricted space such as a scarred area during injection of fluid, if the volume becomes high
enough, the fluid will find a weakness in the walls of the space and in the adjoining spaces. Once adjoining
compartments fill up, fluid continues to spread to further compartments. This is why site-specific delivery of the
catheter is an important principle in order to initiate the opening up of the appropriate tissue planes. The relevance of
the ventral epidural approach has been confirmed not only by the work of Groen, who documented that the ventral
[13]
epidural space is much more richly innervated than the dorsal epidural space. It has also been documented in a dog
model of epidural scarring that the ventral epidural space is where most of the scarring takes place. The target,
therefore, clearly is the ventrolateral epidural space. Stimulation to identify nociceptive pain generators and
recording them from the affected nerve roots are new innovations in various stages of development and evaluation.
Placement of injections transforaminally from the outside into the epidural space via the neuroforamen is another
evolving next step in lysis of adhesions.
In applying the continuum of care, if pain reduction is less than desirable and appropriate for the patient to achieve a
better quality of life, the combination of pharmacologic, physical and psychological therapeutic modalities needs to
continue. One must consider the use of neuroaugmentation techniques such as spinal cord stimulation or the use of
spinal opioids.
Summary
Lysis of adhesions, or percutaneous neuroplasty, is clearly a safe and effective therapeutic alternative for patients
who have persistent back pain and radiculopathy. It is also cost-effective. The targets for catheter placement are the
lateral and ventral epidural spaces, where the painful, swollen, compressed, or restricted nerve root can be
decompressed by the use of the medications that have been outlined in this chapter.
Careful attention needs to be given to the site of injection as well as to the volumes used during the injections. It is
important to verify by contrast as well as pharmacologic assessment that the tip of the catheter is in the epidural
space and not in the subdural or subarachnoid space. The volume requirements in the cervical, thoracic, and lumbar
areas are all different. Careful attention must be given to verify that there is communication from one region of the
epidural space to the other so that localized compression of the spinal cord does not occur. The lateral placement of
the catheter and the injection itself open up the perineural space to provide mobility to individual nerve roots and
821
allow the patient to perform appropriate stretching exercises without pain. They also open up the venous runoff by
removing the scar tissue that occludes draining veins in a tourniquet fashion.
Decompression of high-pressure epidural veins is the most likely explanation for the extremely low incidence, or
virtual absence, of epidural hematomas. Patient selection criteria need to be carefully observed. The prospective
studies indicate that the treatments described give patients the opportunity for long-term pain relief in a safe and
cost-effective manner.
REFERENCES
1. McCarron RF, Wimpee MW, Hudkins PG, Laros GS: The inflammatory effect of the nucleus pulposus: A possible element in the pathogenesis
of low back pain. Spine 12:760–764, 1987.
2. Barsa JE, Charlton JE: Diagnosis of epidural scarring and its possible contribution to chronic low back pain syndrome. Pain S4:S376, 1984.
3. Sicard JA, Forestier J: Méthode radiographique d’exploration de la cavité epidurale par le lipiodol. Rev Neurol 8:1264, 1921.
4. BogdukN, Brazenor G, Christiophidis N, et al: Epidural use of steroids in the management of back pain and sciatica of spinal origin. National
Health and Medical Research Council, Commonwealth of Australia, 1994, pp 7–76.
5. Bogduk N, Aprill C, Derby R: Epidural steroid injections. In White AH, Schofferman JA (eds): Spine Care: Diagnosis and Conservative
Treatment, vol 1. St Louis, Mosby, 1995, pp 302–343.
6. Racz GB, Holubec JT: Lysis of adhesions in the epidural space. In Racz GB (ed): Techniques of Neurolysis. Boston, Kluwer Academic, 1989,
pp 57–72.
7. Manchikanti L, Bakhit CE, Pampati V: Role of epidurography in caudal neuroplasty. Pain Digest 8:277–281, 1998.
8. Gupta RC, Gupta SC, Dubey RK: An experimental study of different contrast media in the epidural space. Spine 9:778–781, 1984.
9. Racz GB, Heavner JE, Singleton W, Carline M: Hypertonic saline and corticosteroid injected epidurally for pain control. In Racz GB (ed):
Techniques of Neurolysis. Boston, Kluwer Academic, 1988, pp 73–86.
10. Racz GB, Sabonghy M, Gintautas J, Kline WM: Intractable pain therapy using a new epidural catheter. JAMA 248:579–581, 1982.
11. Racz GB, Haynsworth RF, Lipton S: Experiences with an improved epidural catheter. Pain Clin 1:21–27, 1986.
12. Racz GB, Kline WN: New epidural adapter and epidural needle. In Racz GB (ed): Techniques of Neurolysis. Boston, Kluwer Academic, 1988.
13. Katz J (ed): Atlas of Regional Anesthesia. Norwalk, Ct, Appleton-Century-Crofts, 1985, p 124.
14. MacNab I: The mechanism of spondylogenic pain. In Hirsch C, Zotterman Y (eds): Cervical Pain. Oxford, England, Pergamon, 1972, pp 89–
94.
15. Racz GB, Heavner JE: Aristocort and Depo-Medrol passage through a 0.2 micron filter [abstract]. Reg Anesth 15(Suppl 1):25, 1991.
16. Dogliotti AM: Segmental peridural anesthesia. Am J Surg 20:107, 1933.
17. Omnipaque product insert. Princeton, NJ, Nycomed, Inc., 1996.
18. Lasser
EC, Lyon SG, Berry CB: Reports on contrast media reactions: Analysis of data from reports to the U.S. Food and Drug Administration.
Radiology 203:605–610, 1997.
19. Halpin SF, Guest PJ, Byrne JV: Theory and practice: How much contrast for myelography. Neuroradiology 33:411–413, 1991.
20. Ndosi
BN, Ndosi NK, Kazema RR: Myelography with Omnipaque (iohexol) using basic radiographic facilities: The main adverse effects. Cent
Afr J Med 42:192–195, 1996.
21. Duran-Reynals F: Tissue permeability and the spreading factors in infection. Bact Rev 6:197, 1942.
22. Lewandowski EW: The efficacy of solutions used in caudal neuroplasty. Pain Digest 7:323–330, 1997.
23. Benoist M, Ficat C, Baraf P: Postoperative lumbar epiduro-arachnoiditis. Diagnostic and therapeutic aspects. Spine 5:432–436, 1980.
24. Hechter O, Dopkeen SK, Yudell MH: Clinical use of hyaluronidase in hypodermoclysis. J Pediatr 30:645–656, 1947.
25. Kirby CK, Eickenhoff JE, Looby JP: Use of hyaluronidase with local anesthestic agents in nerve block and infiltration anesthesia. Surgery
822
25:101, 1949.
26. Gourie-Devi M, Satish P: Intrathecal hyaluronidase treatment of chronic spinal arachnoiditis of noninfective etiology. Surg Neurol 22:231–233,
1984.
27. Nicoll JMV, Acharya PA, Ahlen K, et al. Central nervous system complications after 6000 retrobulbar blocks. Anesth Analg 66:1298–1302,
1987.
28. King TP, Lu G, Gonzalez M: Yellow jacket venom allergens, hyaluronidase and phospholipase: Sequence similarity and antigenic cross-
reactivity with their hornet and wasp homologs and possible implications for clinical allergy. J Allergy Clin Immunol 98:588–600, 1996.
29. Wydase product insert. Philadelphia, Wyeth Laboratories, 1994.
30. Graf
BM, Martin E, Bosnjak ZJ, Stowe DF: Stereospecific effect of bupivacaine isomers on atrioventricular conduction in the isolated perfused
guinea pig heart. Anesthesiology 86:410–419, 1996.
31. LyonsG, Columb M, Wilson RC, Johnson RV: Epidural pain relief in labour: Potencies of levobupivacaine and racemic bupivacaine. Br J
Anaesth 81:899–901, 1998.
32. de Jong RH: Ropivacaine. Anesth Clin North Am 2:109–130, 1998.
33. Iida
H, Watanabe Y, Dohi S, Ishiyama T: Direct effects of ropivacaine and bupivacaine on spinal pial vessels in canine. Anesthesiology 87:75–
81, 1997.
34. Aristocort Forte product insert. Deerfield, Ill, Fujisawa USA, 1994.
35. Jacobs S, Pullan PT, Potter JM, et al: Adrenal suppression following extradural steroids. Anaesthesia 38:953–956, 1983.
36. Abram SE, O’Connor TC: Complications associated with epidural steroid injections. Reg Anesth 21:149–162, 1996.
37. Simon
DL, Kunz RD, German JD, et al: Allergic or pseudoallergic reaction following epidural steroid deposition and skin testing. Reg Anesth
14:253–255, 1989.
38. Nelson
DA, Vates TS, Thomas RB: Complications from intrathecal steroid therapy in patients with multiple sclerosis. Acta Neurol Scand
49:176–188, 1973.
39. Dougherty JH, Fraser RAR: Complications following intraspinal injections of steroids. J Neurosurg 48:1023–1025, 1978.
40. Shealy CN: Dangers of spinal injections without proper diagnosis. JAMA 197:156–158, 1966.
41. Hitchcock ER: Hypothermic subarachnoid irrigation. Lancet 1:330, 1967.
42. Hitchcock E: Osmolytic neurolysis for intractable facial pain. Lancet 1:434–436, 1969.
43. King JS, Jewett DL, Sundberg HR: Differential blockade of cat dorsal root C-fibers by various chloride solutions. J Neurosurg 36:569–583,
1972.
44. Lake DA, Barnes CD: Effects of changes in osmolality on spinal cord activity. Exp Neurol 68:555–567, 1980.
45. Lucas JT, Ducker TB, Perot PL: Adverse reactions to intrathecal saline injection for control of pain. J Neurosurg 42:557, 1975.
46. Ventafridda V, Spreafico R: Subarachnoid saline perfusion. Adv Neurol 4:477–484, 1974.
47. Aldrete JA, Zapata JC, Ghaly R: Arachnoiditis following epidural adhesiolysis with hypertonic saline. Report of two cases. Pain Digest 6:368–
370, 1996.
48. Heavner JE, Racz GB, Raj PP: Percutaneous epidural neuroplasty: Prospective evaluation of 0.9% NaCl versus 10% NaCl with or without
hyaluronidase. Reg Anesth Pain Med 24:202–207, 1999.
49. Racz GB, Heavner JE, Raj PP: Percutaneous epidural neuroplasty: Prospective one-year follow-up. Pain Digest 9:97–102, 1999.
50. MyersRR, Katz J: Neuropathology of neurolytic and semidestructive agents. In Cousins MJ, Bridenbaugh PO (eds): Neural Blockade, 2nd ed.
Philadelphia, JB Lippincott, 1990, pp 567–568.
51. Squire AW, Calvillo O, Bromage PR: Painless intrathecal hypertonic saline. Can Anesth Soc J 21:308–314, 1974.
52. Jewett DL, King JS: Conduction block of monkey dorsal rootlets by water and hypertonic saline solutions. Exp Neurol 33:225–237, 1971.
53. Kukita F, Yamagishi KF: Excitation of squid giant axons in hypotonic and hypertonic solutions. Jpn J Physiol 20:669–681, 1979.
823
54. Swerdlow M: Complications of neurolytic neural blockade. In Cousins MJ, Bridenbaugh PO (eds): Neural Blockade. Philadelphia, JB
55. Payne JN, Ruff NY: The use of hyaluronidase in caudal block anesthesia. Anesthesiology 12:162–172, 1951.
56. Moore DC: The use of hyaluronidase in local and nerve block analgesia other than spinal block. 1520 cases. Anesthesiology 12:611–626, 1951.
57. Manchikanti L, Pampati V, Fellows B, et al: Role of one day epidural adhesiolysis in management of chronic low back pain: A randomized
clinical trial. Pain Physician, 4:153–166, 2001.
58. Indahl
A, Kaigle AM, Reikeras O, Holm SH: Interaction between the porcine lumbar intervertebral disc, zygapophysial joints and paraspinal
muscles. Spine 22:2834–2840, 1997.
59. Racz GB, Noe C, Heavner JE: Selective spinal injections for lower back pain. Curr Rev Pain 3:333–341, 1999.
60. Rocco AG, Philip JH, Boas RA, Scott D: Epidural space as a starling resistor and elevation of inflow resistance in a diseased epidural space.
Reg Anesth 22:167–177, 1997.
61. Groen GJ, Baljet B, Rdukker J: Nerves and nerve plexus of the human vertebral column. Am J Anat 188:282–296, 1990.
824
Section V Chapter 33 - Sympathetic Neurolysis
Chapter 33 - Sympathetic Neurolysis
P. M. FINCH
Sympathetic Neurolysis
It has become common practice in the world of pain medicine to temporarily block or destroy parts of the
sympathetic nervous system. However, the basis for this practice is obscure and uncertain. Few, if any, placebo-
controlled trials have established the efficacy of sympathetic neurolysis in the many conditions treated by this
technique. Despite this, sympathetic neurolysis is often advocated as the first line of treatment in some pain states,
facial blushing, and Raynaud's disease.
Surgical removal of parts of the sympathetic chain commenced soon after the earliest descriptions of the autonomic
nervous system appeared in the literature, often with unexpected results. The tradition has continued, with repeated
local anesthetic blocks performed, in some cases, with little justification. Often, it cannot be established that the
recipients have experienced any more than an active placebo injection at considerable personal cost, and even risk,
in some situations. Even the basic assumption of sympathetic “overactivity” that provided the rationale for this
technique throughout the 20th century, can be challenged in the light of recent knowledge of receptor
supersensitivity.
But all is not black. Newer, minimally invasive techniques applied with a greater understanding of the anatomy and
function of the sympathetic nervous system provide undoubted therapeutic dividends. Few could argue against the
place of celiac or splanchnic block in the case of abdominal malignancy. Many individuals who could not write on
paper because of perspiration can be thankful for the effects of sympatholysis. And elderly individuals with lower
limb vascular ulcers often see improvement after the relatively safe technique of chemical sympathectomy. It is in
the treatment of pain states that sympatholysis requires the utmost caution, for the adage that “you cannot cut for
pain” holds as true for the sympathetic nervous system as for its relatives, the peripheral and central nervous systems.
Various neurolytic or long-term techniques aimed at interrupting sympathetic chain function in the cervicothoracic,
splanchnic, and lumbar areas are examined in this chapter.
HISTORY
Bernard and Brown-Séquard first described the role of the sympathetic nervous system in 1852.
Gaskell and Langley published the anatomy of the sympathetic chain in 1889, and the first surgical
cervical sympathectomy was performed in the same year for the treatment of epilepsy! Around the
turn of the 19th century, surgical removal of the stellate ganglion was tried for a number of other
conditions, including exophthalmos, glaucoma, trigeminal neuralgia, and optic nerve atrophy. LeRiche
published the technique of periarterial excision of sympathetic fibers for Raynaud's disease in 1913 [1]
and later for causalgia. However, this technique never became popular because the results were poor,
[2]
and Kramer and Todd, in 1914, described the passage of sympathetic fibers to the periphery in upper
[3]
limb nerve trunks. Kotzareff, in 1920, successfully treated upper limb hyperhidrosis by removal of
[4]
cervical ganglia but caused Horner's syndrome in the process, and Jonnesco improved the condition
[5]
of patients with angina pectoris by stellectomy in 1921.
During the 1920s and 1930s, a number of surgical approaches to the thoracic and cervical sympathetic
chain were devised, because it was realized that for complete denervation, the upper thoracic chain had
to be included in a resection. Also, Kuntz, in 1927, described the nerve that bears his name, which
[6]
bypasses the second and third thoracic ganglia in about 10% of subjects and which must be included to
completely denervate the upper limb. Throughout the 20th century, differing open surgical approaches
were thought to have advantages, including Cloward's dorsal midline approach and the extrapleural
[7]
approach with first rib resection described by Roos in 1971. Endoscopic techniques have come to
[8]
dominate this area of endeavor, with reduced morbidity and increased certainty of effect. Kux, in [9]
1954, published his experience of more than 1400 thoracoscopic sympathectomies and vagotomies,
but it was not until the last decade of the 20th century that the technique became widely used. The use
825
of chemical neurolytic agents in the chest has never been accepted, as it has for the celiac plexus or the
lumbar sympathetic chain, despite the use of computed tomography (CT) guidance. This is probably
[10]
because of the rather unpredictable spread of such agents and the proximity of several major anatomic
structures. More recently, percutaneous radiofrequency ablation of the cervicothoracic chain has been
described and refined but possibly lags behind the accuracy of direct visual approaches to the
[11] [12]
chain.
Techniques for neurolysis of the lumbar sympathetic chain appeared after 1924, when Royle in [13]
Australia attempted to modify skeletal muscle tone in patients with spastic paralysis. Such physiologic
effects as increased skin blood flow and dryness were observed and subsequently confirmed by Adson
and Brown at the Mayo Clinic, who used them to treat Raynaud's disease in 1929. Before the advent
[14]
of effective hypotensive drugs, sympathectomy was used extensively for the treatment of
hypertension, and Smithwick pioneered the technique of thoracolumbar sympathectomy for this
[14A]
condition. In the latter half of the 20th century, arterial reconstructive surgery largely supplanted the
use of sympathectomy for peripheral vascular disease, with the possible exception of vascular ulcers. It
continues to be advocated with some justification for hyperhidrosis. Percutaneous and endoscopic
techniques have become the methods of choice, as with the cervicothoracic chain.
For pain physicians, the development of treatment techniques for reflex sympathetic dystrophy (RSD)
and causalgia (complex regional pain syndrome [CRPS] types I and II) is particularly fascinating.
Descriptions of neuropathic pain states after peripheral nerve injuries appeared as early as the
Peninsular War in the early 19th century. They were particularly well described by Mitchell and
colleagues in the American Civil War, who defined the term “causalgia” as a burning pain that
[15]
develops in an extremity after traumatic partial peripheral nerve injury. Leriche, in the early 20th
[2]
century, pointed out that symptoms of causalgia had many features suggesting abnormal sympathetic
nervous system function and proposed sympathectomy by periarterial stripping.
Various attempts at treating causalgia by peripheral nerve resection invariably failed until, in 1930,
Spurling reported the apparently dramatic cure of the condition with cervicothoracic sympathectomy.
[16]
The realization that early sympathectomy improved causalgic pain states was even considered to be
one of the outstanding surgical lessons of World War II. More recent experience in the Iran-Iraq War
[17]
again suggested that sympathectomy could provide dramatic relief from causalgic pain after peripheral
nerve injury. However, destruction of the sympathetic chain, by whatever means, for RSD, the
[18]
condition described by Evans in 1946 and now termed CRPS type I, has not fared so well and may
[19]
well be disappearing from the treatment armamentarium. Although local anesthetic blocks can
sometimes provide dramatic relief from pain and edema, the mechanism of this relief is not
understood. Subsequent neurolysis of the sympathetic chain can often produce poor results and, in
some cases, can cause additional morbidity. [12]
On a more cheerful note, the celiac plexus block, initially described by Kappis in 1914, and direct
[20]
approaches to the splanchnic nerves have proved to be successful in the treatment of patients with
[21]
malignant or benign visceral pain. In fact, the technique described by Kappis was a retroaortic
splanchnic nerve block using procaine local anesthetic. Alcohol neurolysis of the splanchnic nerves
was subsequently described by Jones in 1957. Celiac plexus neurolysis, which ensures destruction of
[22]
both sympathetic efferent and visceral afferent contributions, has been described by Moore as the [23]
single most effective neurolytic block. Neurolytic celiac plexus blocks can provide long-lasting benefit
for a high percentage of patients with pancreatic and other intra-abdominal cancers, regardless of the
technique used. In recent years, refinements of approach to the splanchnic nerves, which contribute
[24]
to the celiac plexus, have focused on the use of newer forms of neurolysis such as radiofrequency
thermolesioning.
Finally, a short review of the historical aspects surrounding sympathetic neurolysis would not be
complete without mention of more recent work suggesting that sympathetic nervous system
maintenance of pain may be due to the development of adrenoreceptor denervation supersensitivity. [25]
In the last decade of the 20th century, both animal and human studies supported the concept of
[26]
increased expression of α-adrenergic receptors in primary afferent neurons after partial denervation or
tissue damage. It is this denervation supersensitivity that may produce many of the symptoms of
causalgia or rather than increased efferent sympathetic activity, as had been assumed for almost a
century. The very basis of sympathetic neurolysis for such pain states was founded on the removal of
this sympathetic “overdrive” and therefore may have been mistaken.
826
Anatomy
Before considering the various techniques of sympatholysis, the anatomy of the sympathetic chain should be
reviewed in the four main areas of interest, which include the cervicothoracic ganglia, the splanchnicceliac plexus,
the lumbar ganglia, and the superior hypogastric plexus. The sympathetic nervous system is thoracolumbar in its
central connections but extends as two ganglionated nerve trunks from the first cervical level to the coccyx. For
those seeking precision, there is, unfortunately, considerable variability in the position and anatomy of the chain.
The trunks have a variable number of ganglia that communicate with the cord via small, myelinated white rami and
with the spinal nerves via gray rami. There is considerable ramification of preganglionic fibers, both craniad and
caudad; therefore, synaptic connections can occur at levels well above or below the entry of white rami into the
sympathetic trunks. Also, single preganglionic fibers can synapse with multiple postganglionic neurons, allowing
diffuse activation and plasticity of effect.
THE CERVICOTHORACIC CHAIN
Sympathetic fibers to the head, and particularly the eye, pass via the stellate ganglion and the cervical sympathetic
chain, synapsing with postganglionic fibers in the superior cervical ganglion before joining the carotid vessels or the
nasociliary nerves. It is of interest that facial vasodilator fibers as well as vasoconstrictor fibers pass through the
stellate ganglion. Vasodilatation of the face is, therefore, in part, an active process. The actual entry point for
[27]
preganglionic fibers into the stellate ganglion has been the subject of some debate; these fibers may enter the upper
part of the ganglion via a separate paravertebral pathway. Certainly, surgical
[28]
Figure 33-1 (Figure Not Available) A, Pupillociliary pathways as recorded in contemporary 1976 literature on left side with preganglionic
neurons arising from the eighth cervical and first and second thoracic levels of the cord. They pass via the first or second ramus to enter the first
dorsal ganglion. They then pass cephalad in the cervical sympathetic chain to synapse with postganglionic neurons in the superior cervical
ganglion. B, Pathways as postulated by Palumbo in 1976. Fibers leave the ventral roots as shown and do not pass via the rami communicantes.
They enter the upper portion of the stellate ganglion as shown on the right of this drawing. (From Palumbo LT: A new concept of the sympathetic
pathways to the eye. Ann Ophthalmol 8:948, 1976. Reprinted with permission. © American Society of Contemporary Ophthalmology.)
resection of the upper thoracic chain with sparing of the lower part of the stellate ganglion would appear to reduce
the incidence of Horner's syndrome (Figs. 33–1 (Figure Not Available) A and B, 33–2).
The stellate ganglion is usually composed by fusion of the inferior cervical and the first thoracic ganglia. It lies just
anterolateral to the body of the seventh cervical and lateral to the first thoracic (T1) vertebral bodies, in the groove
between the vertebral body and the transverse process. In an anteroposterior radiologic view, it lies just lateral to the
vertical line joining the uncovertebral joints. As with other regions of the sympathetic chain, there is marked
variation in position. In an anatomic study, Katritsis and associates found that the relationships of the superior pole
[29]
of the stellate ganglion to the vertebral artery and to the transverse processes of the last cervical and the first thoracic
vertebrae showed marked variation. The cervical chain can also have a variable position; in one cadaver study, it lay
within the carotid sheath in about 16% of cases.
Figure 33-2 (Figure Not Available) Diagram of cervicothoracic sympathetic chain showing the position of the sympathetic chain in relation to
the heads of the ribs.(From Anderson JE: Grant's Atlas of Anatomy, 8th ed. Baltimore, Williams & Wilkins, 1983.)
The cervical chain could, therefore, be at risk in surgical neck dissection. The nerve of Kuntz is a large
[30]
postganglionic branch that extends caudally from the stellate ganglion and also needs to be included in resections for
complete sympathetic denervation of the upper limb. As the chain enters the chest, it comes to lie more laterally and
in close approximation to the head and neck of each rib. As viewed through a thoracoscope, the thoracic sympathetic
chain is seen through the parietal pleura as a whitish cord that runs vertically over the neck of the ribs close to the
costovertebral junction. On the left side, the T2 ganglion lies in close proximity to the aortic arch. The superior
[31]
intercostal artery, which is a branch of the subclavian artery, runs parallel and lateral to the sympathetic chain at a
distance of about 1 cm. The T2 ganglion is usually located at the second intercostal space, but in about 16% of cases,
T3 is embedded anterior to the third rib. This ganglion would, therefore, be inaccessible to a straight posterior
percutaneous needle insertion, but it may be more suited to a curved lateral approach. In the lower thorax, at the
[32]
origin of the splanchnic nerves, the sympathetic chain assumes a more anterolateral relationship to the vertebral
bodies. This is maintained into the lumbar region.
827
SPLANCHNIC-CELIAC PLEXUS
The celiac plexus is composed of both efferent and afferent nerve fibers from a number of sources, including pre-
and postganglionic sympathetic efferent fibers, parasympathetic fibers, and visceral sensory afferent fibers. It is the
preganglionic sympathetic contribution to the celiac plexus that originates in the greater (T5 to T9–T10), lesser
(T10–T11) and least (T12) splanchnic nerves. Postganglionic fibers originate in the upper lumbar splanchnic ganglia,
and the parasympathetic fibers descend into the vagus nerves. Splanchnic blocks are effective in upper abdominal
and loin pain states, both malignant and benign, and may well cause fewer adverse effects than the classical celiac
plexus block. It would, therefore, be appropriate to consider the anatomy specific to the splanchnic nerves and then
[33]
the celiac plexus itself. Experience with thoracoscopic splanchnicectomy has revealed that aberrations in the
splanchnic outflow occur frequently.
Although splanchnic nerves consistently originate in the fifth thoracic ganglion, the arrangements of the nerves and
the number of branches and their interconnections vary considerably. From their origin, the splanchnic nerves run
[21]
caudally in a narrow compartment lateral to the vertebral bodies from T5 to T12. The parietal pleura of the lung and
the crura of the diaphragm form the lateral wall of this narrow compartment, which must not be breached for
obvious reasons. Curved blunt needles help one to hug the
Figure 33-3 Diagram of splanchnic nerves running across bodies T11 and T12.(From Waldman SD, Patt RD: Celiac plexus and splanchnic nerve
block. In Waldman SD (ed): Interventional Pain Management, 2nd ed. Philadelphia, WB Saunders 2001, p 495.)
vertebral body and to avoid puncturing the pleura ( Fig. 33–3 ).

[34]
The celiac plexus has no less variable anatomy. It is formed from the right and left celiac ganglia and their
interconnections and lies anterolateral to the aorta, but it has considerable cephalocaudad variability. It can vary[35]
from the disc space of T12 to L1 to the middle of the vertebral body of L2, and the left ganglia are typically located
slightly caudad to the right. Fortunately, the degree of precision that is required of a radiofrequency lesion to the
splanchnic nerves is generally not required for the celiac plexus, because neurolytic solutions can spread
extensively ( Fig. 33–4 A).
[36]
828
THE LUMBAR GANGLIA
The bilateral ganglionated chains run ventrolateral to the lumbar vertebrae, just anterior to the attachment of the
iliopsoas fascia to the lumbar vertebrae. In fact, they lie in a groove between these two structures. The ganglia are
quite variable in position and number and have been the focus of much study because it is thought that for
[37] [38] [39] [40]
effective neurolysis the actual ganglia rather than the chain must be destroyed. Under the direct vision of an open or
endoscopic approach, this might be achieved, and likewise with the wide spread of neurolytic solutions many
ganglia might be covered, but for specific percutaneous radiofrequency neurolysis this becomes anatomically
impossible. Rocco and associates studied 68 lumbar sympathetic chains in cadavers and suggested that ganglia are
[41]
more likely to be
Figure 33-4 A, Computed tomography scan of viscera through the L1 vertebral body with celiac plexus outlined. B, CT through L2 marking the
position of the sympathetic ganglia and the anterior border of the iliopsoas fascia. C, CT through L5 demonstrating the iliopsoas muscle and the
sympathetic chain.
present in the middle of the body of the L3 vertebra and at the level of the disc spaces above and below. According
to Cowley and Yeager, who dissected both sides in 40 cadavers, the most constant of the lumbar ganglia is the
[30]
second, which lies in an anterolateral position at the level of the lower portion of the second lumbar vertebra or over
the adjacent disc space. The fifth vertebra is often a discrete structure, communicating with the fifth lumbar nerve,
but the intervening ganglia can be absent or fused with adjacent ganglia. The third lumbar ganglion usually lies on
[37]
the lower part of the body of the third lumbar vertebra or over the disc space below. The connections from the
ganglia to the spinal nerves are equally variable and complex. To further dismay those who would wish to achieve
[42]
precise neurolysis of the lumbar sympathetic chain, the attachment of the iliopsoas fascia to the anterior border of
829
the lumbar vertebrae tends to vary with the segmental level. The point at which the iliopsoas muscle diverges
laterally from the vertebral column can vary from the upper third of L3 to the upper third of L5 (see Fig. 33–4 B [41]
and C).
Crossover fibers connecting the two lumbar sympathetic chains have been postulated over the years to explain poor
results after sympathectomy. Such crossover fibers have been observed and reported by Cowley and Yeager in 10 [37]
out of 36 anatomic dissections. The use of neurolytic solutions may well denervate such crossover fibers, which
otherwise would escape the more discrete methods of neurolysis.
SUPERIOR HYPOGASTRIC PLEXUS
Pelvic pain states can be modified by neurolysis of the superior hypogastric plexus. Afferent nociceptive fibers
[43]
originate in various pelvic viscera form a midline plexus in the retroperitoneum, extending from the lower third of
the fifth lumbar vertebral body to the upper third of the first sacral vertebral body. These afferent fibers then pass
centrally via the sympathetic nerves, trunks, ganglia, and rami. Previously, surgical presacral neurectomy was
performed for some pelvic pain states. Current approaches to this plexus affect neurolysis by the spread of
neurolytic solution, in a fashion analogous to blocks of the celiac plexus (Fig. 33–5 (Figure Not Available) ).
To complete this anatomic review of the sympathetic chain, one should last examine the ganglion impar because
neurolysis of this structure has been advocated for the treatment of visceral perineal pain. Both sympathetic chains
[44]
terminate in this single ganglionated
Figure 33-5 (Figure Not Available) Oblique view of the pelvis demonstrating the hypogastric plexus.(From Bonica JJ: Causalgia and other
reflex sympathetic dystrophies. In Bonica JJ (ed) The Management of Pain. Philadelphia, Lea and Febiger, 1990.)
structure immediately anterior to the sacrococcygeal junction. With its retroperitoneal position just adjacent to the
rectum and hidden behind the sacrum, intentional destruction of the ganglion impar can present a considerable
anatomic challenge!
The Rationale for Sympathetic Neurolysis
The rationale for the various contemporary uses of sympathetic neurolysis can be considered under the following
four main groupings:
1. Cosmetic indications such as reduction of facial flushing and hyperhidrosis

2. Vascular indications including vasospastic conditions and occlusive vascular disease
3. Pain states such as complex regional pain syndrome (causalgia and reflex sympathetic dystrophy)
4. Visceral pain including carcinoma of the pancreas
COSMETIC INDICATIONS
Essential hyperhidrosis and excessive facial blushing can be so disabling to some individuals that they seek surgical
redress in the form of sympathectomy. These two symptoms can be considered as physical manifestations of social
[45]
phobic reactions, which are psychiatric conditions with criteria contained in the Diagnostic and Statistic Manual. It
has even been considered ethically sound to perform endoscopic transthoracic sympathectomy for selected patients
with social phobia resistant to psychotherapy and drug therapy. Little has changed in a hundred years!
[46]
Excessive sweating can soak clothing such as footwear and cause great difficulty with writing on paper because
documents become smeared. Sympathetic neurolysis has been advocated for this condition and is considered to be
one of the more efficacious uses of the technique, with success rates estimated to be greater than 90% in a number of
series for upper limb hyperhidrosis. However, the recurrence rate can be significant and in one study was 14.3%
after an average follow-up of 32 months. [45]
Sudden and excessive facial blushing can also be of considerable social embarrassment to some individuals and has
been described as a specific symptom of social phobia not associated with other forms of anxiety disorders. [47]
Thoracic sympathectomy is again effective in this sympathetically mediated condition, but like the condition itself,
its effectiveness can only be estimated by subjective techniques such as a visual analogue scale. Enthusiasm for [48]
sympathectomy in these conditions must be tempered by three significant postsurgical complications: Horner's
syndrome, compensatory sweating, and pathologic gustatory sweating. The incidence of Horner's syndrome can be
830
as high as 5% after open sympathectomy but is reduced by thoracoscopic techniques. Forms of excessive sweating
[49]
commonly follow endoscopic transthoracic sympathectomy and gustatory sweating, which is excessive facial
sweating while eating, has been estimated to occur in almost half of those undergoing this technique for palmar
hyperhidrosis. The reduction of flushing in response to emotional events can be replaced by equally unpleasant
[50] [51]
facial flushing and sweating while eating, so that patients are little better over the long term. [52]
VASCULAR INDICATIONS
There are two main groups of conditions for which sympatholysis might be considered. The first main group
includes the vasospastic disorders such as Raynaud's syndrome; these patients often seek help from vascular
surgeons. Techniques of neurolysis tend to be surgical, and in the upper limb, would include thoracoscopic
diathermy or resection of the upper thoracic sympathetic chain. The longer term results have not been encouraging,
although slight improvement has been seen after lower limb procedures. However, Raynaud's syndrome
predominantly involves the hands! As for other indications for sympathectomy, open surgical operations on the
chain have become less frequent and have been replaced by less invasive endoscopic or percutaneous needle
techniques. Peripheral sympathectomy, performed by adventitial stripping of sympathetic fibers and severance of
[53]
peripheral neural connections to the arterial structures in the hand, is reported to improve the symptoms of
Raynaud's phenomenon secondary to systemic disease and nonreconstructible arterial occlusion. [54]
Patients in the second group of vascular occlusive diseases tend to frequent pain medicine clinics. Often, these
patients are in poor physical shape because of concomitant peripheral vascular and ischemic heart disease but are
less disturbed by the minimally invasive techniques such as neurolytic lumbar (chemical) sympathectomy. In fact,
Brunn and Mandl first described chemical injection of the lumbar sympathetic chain using local anesthetic and
[55]
alcohol in 1924, and Haxton used phenol in 1949. Phenol in its various forms has become the chemical most
[56]
commonly employed. Claudication used to be a frequent indication for sympathectomy, but physiologic testing has
failed to document an improvement in limb hemodynamics. Patients with vaso-occlusive disease as a result of
[57]
frostbite may develop painful sequelae, which may respond to sympatholysis, and, last, sympatholysis does appear
[58]
to improve the condition of some patients with peripheral vascular ulceration and rest pain. Despite the development
of vascular reconstructive techniques, there remain many patients for whom these techniques cannot be applied, and
yet relief of symptoms can be realized by sympatholysis. Cousins and associates noted healing of skin ulcers in
[59]
70% of a large series of patients undergoing chemical sympatholysis with a mean time to healing of 2 months and
improvement in rest pain of 49%. More recent attempts to replace the somewhat uncontrolled spread of neurolytic
solutions with the discrete lesions of radiofrequency have not met with the same level of success. [60]
PAIN STATES
Sympatholytic techniques are often prescribed in the treatment of patients with neuropathic pain states such as RSD
and causalgia (CRPS) types I and II, but the rationale for this is obscure and perhaps mistaken. The pathogenesis of
complex regional pain is unclear and surrounded by speculation. Even the century-old assumption that the
sympathetic nervous system is somehow involved can be challenged. This assumption arose through observation
that the neuropathic pain of causalgia and RSD was associated with features such as sweating and blood flow
changes, suggesting a disturbance of autonomic function. It was found also that local anesthetic sympathetic blocks
could, in some cases, relieve pain. Frequently, the pain would return after long-term neurolytic or surgical
[61]
sympathectomy. A possible exception is the use of sympathectomy to treat causalgic pain states during wartime
[62]
after direct wounds to peripheral nerves. Several large clinical series have recorded dramatic improvement of
causalgic pain after sympathectomy. This finding has given rise to the concept of sympathetically maintained
[16] [17]
pain.[63]
Neurochemical studies have not supported the concept of increased postganglionic traffic to the periphery but rather
a relative denervation and the development of denervation supersensitivity. Intuitively, further sympathetic
[26] [64]
denervation could even worsen the situation. A radioisotope study reported in 1994 indicated that patients with
chronic unilateral RSD have decreased perfusion of the affected limb, symmetrical sympathetic innervation and
norepinephrine synthesis, variable decreased release and turnover of norepinephrine in the affected limb, and failure
of ganglion blockade to improve the pain in most cases. Alternative mechanisms of pain generation and
[65]
enhancement should be sought so that treatment can be based on reason and not hypothesis. For example, relative
efferent sympathetic denervation might in turn lead to the increased expression of nerve growth or neurotropic
factors that could enhance pain transmission by a variety of mechanisms. A contemporary hypothesis suggests
[66] [67]
that the sympathetic deficit in acute CRPS is the result of a central process that inhibits sympathetic outflow to the
symptomatic limb. Diminished activity of cutaneous sympathetic vasoconstrictor neurons in patients with acute
CRPS results in elevated skin temperatures and diminished levels of sympathetic neurotransmitters in the affected
extremity. Simultaneous unilateral hyperhidrosis indicates an increase in sympathetic sudomotor activity. Such a
831
centrally located thermoregulatory dysfunction therefore leads to sympathetic failure with inhibition of sympathetic
vasoconstrictors and increased sudomotor outflow. Finally, peripheral adrenergic receptor supersensitivity develops,
leading to many of the features of chronic CRPS. [68]
VISCERAL PAIN
Neurolytic block of visceral afferent fibers passing to the sympathetic chain via the celiac plexus and splanchnic
nerves has been advocated for treatment of upper abdominal cancer pain and even pain of nonmalignant origin. [21] [23]
Most studies have been uncontrolled and retrospective in nature. A meta-analysis however, supports its use in the
treatment of pain from cancer of the pancreas or other upper abdominal organs. Eisenberg and colleagues reached [24]
the following conclusions:
1. Neurolytic celiac plexus block has long-lasting benefit for 70% to 90% of patients with pancreatic and
other cancers, regardless of the technique used.
2. Adverse effects are common but transient and mild.
3. Severe adverse effects are uncommon.
In fact, some consider this form of sympatholysis the single most effective block in the pain medicine
armamentarium. To reduce the potential for serious neurologic complications, techniques for neurolysis of the
[23]
splanchnic nerves have been developed using precise thoracoscopic resection or (RF) lesioning. These newer
[34] [69]
techniques avoid the unpredictable spread of neurolytic agents but can run into difficulties because of the variable
surgical anatomy of the splanchnic nerves.
Visceral afferent fibers from the pelvic organs ascend via the hypogastric plexus and a block similar to that used for
celiac plexus can be employed. However, the long-term results, especially in treating patients with pelvic cancer
[70] [71]
pain, have been studied only in relatively small series. From an anatomic viewpoint, the hypogastric plexus is not
[44]
the easiest structure to approach. High degrees of C-arm angulation, the requirement of a curved approach, and the
presence of major vascular structures in the immediate vicinity make this an unsuitable technique for the
fainthearted!
Techniques of Sympathetic Neurolysis
STELLATE SYMPATHOLYSIS
Surgical resection of the stellate ganglion is seldom undertaken, because the likelihood of developing Horner's
syndrome is high. Surgical resection has been largely supplanted by thoracoscopic techniques aimed at the upper
thoracic ganglia and is discussed in a later section. However, nerve blocks of the stellate ganglion are commonly
performed in the diagnosis and early management of CRPS and are described in detail elsewhere. [72]
For long-term sympatholysis of the stellate ganglion, there are two techniques that can be considered. First, the
placement of neurolytic agents adjacent to the stellate ganglion has been described and modified by Racz and is [73]
considered to be safe. A weak solution of aqueous phenol is placed on the lateral portion of the body of the C7
vertebra under image intensifier control and allowed to track laterally to cause partial sympatholysis of the stellate
ganglion and cervical sympathetic chain. Needless to say, the potential for disaster is much higher with the
unpredictable spread of these agents as opposed to that of the more controllable radiofrequency lesion ( Fig. 33–6 ).
[74]
Various attempts have been made to improve the accuracy of placement of neurolytic agents, including the use of
computed tomography (CT) guidance, ultrasonography, and magnetic resonance resonance imaging. However,
[75] [76] [77]
the use of such imaging techniques increases the complexity of a relatively simple nerve block. It has been claimed
that local anesthetic and neurolytic solutions spread from the vicinity of the stellate ganglion to the upper thoracic
chain, providing a more extensive sympathectomy. However, in a cadaver study using methylene blue, it was found
that there was no spread of solution to the thoracic sympathetic chain. RF thermolesioning provides a second and
[78]
more precise means of partial sympatholysis of the stellate ganglion and the lower cervical sympathetic chain.
Geurts has reported that 40% of patients with upper extremity RSD were still pain free at a mean follow-up period
of 13.2 months. Forouzanfar, using essentially the same technique in a study of 221 patients, noted more than
[79] [12]
50% reduction of pain in 40.7% of these patients at a mean follow-up interval of 52 weeks. Both studies were
retrospective in nature and lacked controls.
832
Figure 33-6 Axial magnetic resonance image of C7/T1 demonstrating structures adjacent to the stellate ganglion, which could be affected by
neurolytic solutions.
Technique
Patients selected for RF lesioning of the stellate ganglion have invariably undergone one or more prognostic local
anesthetic blocks. The approach is paratracheal and should always be performed under control of an image
intensifier to reduce the incidence of intravascular injection. The cervical spine is seen in an anteroposterior
projection, and the transverse process of C7 is noted. A metal ruler and a black felt-tipped pen are used to place a
suitable mark on the skin.
After the carotid artery is retracted with the index finger, either a 25-gauge short bevel spinal needle or a 10-cm RF
cannula (Radionics, Burlington, Mass, SMKC10, 4-mm bare tip) is inserted so that the tip contacts the junction of
the C7 transverse process with the vertebral body. A 15-degree bend can be placed in the terminal 1 cm of the
needle or cannula, which aids directional steering and repositioning. The needle or cannula is then withdrawn 1
[34]
mm to 2 mm before contrast agent is injected, which excludes intravascular placement. The spread of contrast is
seen to be cephalocaudad and not anterolateral, following the line of the nerve roots ( Fig. 33–7 A and B).
The C-arm is then repositioned to obtain an oblique projection, thus revealing the nerve root foramina. The tip of the
cannula and the spread of contrast should be seen to be anterior to the nerve root canals.
If a prognostic block is desired, local anesthetic is injected in small increments to a total of 3 mL to 4 mL; the
patient is then transferred to the recovery area. Despite the use of image intensification, local anesthetic can
inadvertently be injected into the vertebral artery, inducing a grand mal convulsion or into a nerve root sleeve
causing extensive spread to the epidural space and possibly leading to apnea. This can largely be prevented by
careful prior study of the spread of contrast agent. Should an RF lesion be desired, stimulation is undertaken. This is
performed both at sensory (50-Hz) and motor (2-Hz) frequencies. If the electrode is close to the phrenic nerve,
motor contractions of the diaphragm can be detected by the palpating hand. If the patient is asked to phonate a
constant note (Eeeee. . . .), proximity to the recurrent laryngeal nerve will cause the note to become broken, in time
with the 2-Hz frequency of stimulation. Last, if the electrode is in proximity to a cervical nerve root, sensory and
motor stimulation are noted in a radicular pattern to the upper limbs. In these situations, the electrode is moved to a
more appropriate position by means of image intensifier control. If a sensitive infrared temperature-measuring
device (Raytek, Minitemp) is used, a temperature drop can often be seen in the hands on prolonged (1 minute)
sensory stimulation. This helps to confirm proximity of the electrode tip to the stellate ganglion or sympathetic chain.
833
Lesioning of the stellate ganglion can cause discomfort, which is referred to the ipsilateral upper scapular region. To
prevent this discomfort, local anesthetic can be injected. However, this confuses the short-term outcome of the
Figure 33-7 A, Vertical spread of contrast agent with an electrode in position for radiofrequency (RF) lesioning of the stellate ganglion. B,
Oblique projection demonstrating the spread of contrast agent anterior to the nerve root canals.
procedure. Sedation sufficient for the patient to tolerate this discomfort is probably the better technique because the
pupils can be observed for the sudden appearance of Horner's syndrome. If this occurs, the lesioning is ceased
immediately. In general, lesion temperatures are maintained in the range of 80°C to 85°C for 1 to 1½ minutes with
use of an RF lesion generator (3C plus, Radionics). Small adjustments of cannula tip position are made so that two
or three lesions are achieved. Before each new lesion is created, stimulation should be undertaken to exclude
inadvertent proximity to other neural structures. The patient is then transferred to the recovery area, where a close
watch is kept for development of complications such as pneumothorax. This technique is usually performed as a
“day admission,” and the patient is discharged after an hour or so of observation. Neuralgic symptoms in the upper
limb, especially around the shoulder area, are sometimes seen for 1 or 2 weeks after the procedure, and the patient
should be suitably reassured. If the symptoms are severe, carbamazepine can be prescribed on a temporary basis. In
my experience, this is a safe procedure if carefully performed and is simpler than the percutaneous approach to the
upper thoracic sympathetic chain.
SYMPATHOLYSIS OF THE THORACIC CHAIN
Percutaneous neurolysis of the upper thoracic sympathetic chain by means of RF lesioning or the injection of
neurolytic agents is not easy. Not only is the procedure technically difficult on account of a confusing x-ray picture,
but there is the ever-present risk of pneumothorax from penetration of the pleura. This possibility can lead to
considerable anxiety for both operator and patient alike. In addition, thoracic ganglia can be inaccessible from a
posterior percutaneous approach because, in some cases, the T3 ganglion is embedded anterior to the third rib. [31]
Thoracoscopic methods of ablating the chain can provide a more certain means of obtaining the end result of
sympatholysis. These direct vision approaches are widely practiced and are now discussed.
Before the development of endoscopic techniques, the chain was approached by the supraclavicular or transaxillary
route. But this surgery is painful and accompanied by significant risk of complications. Such complications include
[80]
Horner's syndrome, phrenic nerve injury, brachial plexus injury, chylous leak, pneumothorax, and bleeding. Chronic
postthoracotomy wound pain, which is familiar to practicing pain physicians, can be added to this list. Endoscopic
sympathectomy has largely supplanted open operation and has been described in detail by many authors. [9] [31] [45] [51] [81] [82]
Thoracoscopy provides a magnified view of the sympathetic chain and surrounding anatomy. The upper
[83] [84] [85]
thoracic ganglia, usually T2 and T3, but sometimes T2 to T4 as well, are either resected or destroyed by diathermy. [86]
Intraoperative electrical stimulation of different ganglia is claimed to assist the surgeon in determining the correct
functional level for excision. Even for the skilled operator, the identification of the T2 ganglion can be difficult,
[87]
and the sympathetic trunk is not readily visible intraoperatively in one third of cases. A simple anatomic method
[88]
for identifying the T2 ganglion was described by Chiou and Liao, who emphasized the beneficial nature of the
[31]
superior intercostal artery, which runs about 10 mm lateral and parallel to the upper thoracic sympathetic chain.
Possible complications with thoracoscopic techniques include Horner's syndrome; pneumothorax; pain at the trocar
site and respiratory pain; surgical complications, such as bleeding; and physiologic disturbances such as excessive
834
compensatory sweating. A mean length of hospital stay in one United States series was 1.8 days, which compares
[84]
favorably with percutaneous RF lesioning.
As with the stellate ganglion, percutaneous techniques employing the injection of neurolytic agents or RF lesioning
have also been described. Complications are always possible, and, despite the use of CT guidance in one
retrospective series, three cases of transitory Horner's syndrome and one case of pneumothorax were reported in 21
percutaneous (phenol) neurolyses of the upper thoracic sympathetic chain. The same criticism can be leveled at
[10]
this technique as for neurolysis of other areas of the sympathetic chain, because the spread of neurolytic agents is
uncontrolled. Phenol causes indiscriminate destruction of neural tissue depending on its concentration as it denatures
protein. Also, many of the complications of phenol blocks are caused by blood vessel damage. [89] [90]
RF lesioning of upper thoracic sympathetic ganglia has been described and popularized by Wilkinson, and,
[11] [91]
although RF lesioning is a demanding procedure, its use overcomes some of the objections to the use of neurolytic
agents in the chest. Two or three levels (T2, T3) are lesioned via a paravertebral approach. The use of curved, blunt
RF cannulas has probably reduced the risk of pneumothorax, which is the most frequent complication encountered.
[92]
[34]
Technique
When one first views the anteroposterior view of the upper thoracic vertebrae with the patient prone, the picture is
often confusing. A jumble of ribs, transverse processes, and scapulae can confuse even the most experienced
operator. An obese patient, osteoporotic bones, or a marginal C-arm radiographic system can compound the
difficulties. To obtain the best view, the C-arm must be adjusted to view the shadow of the vertebral end plates end-
on in the T2 to T3 region. The C-arm is then rotated obliquely to between 10 and 15 degrees from vertical so that the
needle or cannula can be directed down the x-ray beam.
The electrode tip must rest in the vicinity of the head of each rib as the sympathetic chain passes in close proximity
to the costovertebral joint. To check this, the C-arm must be rotated into a lateral projection. The picture then
becomes even more confusing, with the shoulders or upper arms often obscuring the vertebral bodies and their
foramina. The active tip of the cannula should rest over the posterior third of the vertebral body, as seen on a true
lateral projection.
A small amount of contrast agent is seen tracking closely adjacent to the body of the vertebra and not into nerve root
canals, blood vessels or the lung ( Fig. 33–8 A–C).
Electrical stimulation can serve two purposes. By
835
Figure 33-8 A, Curved radiofrequency cannulae directed around the lateral border of T2 and T3 vertebrae. B, The active tip of the cannula should
rest in the posterior third of the body of T2 to T4. C, Contrast agent stays in close proximity to the vertebral body of T2/T3. (Courtesy of Dr. Way
Yin, Westwood Medical Center, Midland, Texas.)
monitoring intercostal muscle contraction at motor frequencies (2 Hz), the distance of the active tip to a motor nerve
root can be estimated. If necessary (stimulation < 1.5 volts), the tip of the cannula can be moved to a more suitable
location. Stimulation at sensory frequencies (50 Hz) can also cause a cooling of the ipsilateral hand, as measured
with a sensitive infrared device. This confirms proximity to the sympathetic chain and increases the operator's
confidence in eventual sympatholysis. Lesioning between 80 degrees and 85 degrees for 1½ minutes is performed
with the patient moderately well sedated or asleep, because the procedure causes considerable pain. Local anesthetic
injected at the time of lesioning can confuse the short-term outcome and is perhaps best avoided. A temperature rise
in the ipsilateral limb and a differential of several degrees Celsius, compared with the contralateral side, indicates
successful interruption of the chain. Commonly, several lesions are performed at multiple levels to increase the
chances of sympatholysis. Needless to say, the patient is transferred to a day recovery unit and closely observed for
signs of complications such as pneumothorax.
Stanton-Hicks has described an alternative technique. He has suggested commencing cannula insertion laterally, at
[32]
the angle of the rib, but maintaining a track almost parallel to the rib on the way to the costovertebral articulation.
Using a curved blunt cannula, the tip is rotated underneath the head of the rib as it nears the body of the vertebra.
This may well position the active tip in a more suitable position to perform a lesion on the sympathetic chain, which
is distinctly lateral to the vertebral body in the upper chest. Straight posterior approaches may not reach inaccessible
ganglia embedded anterior to the rib. Even anterior approaches to the chain have been described and are considered
to offer the advantages of supine positioning of the patient and parallel RF lesioning of the sympathetic chain. [69]
SPLANCHNIC NERVE AND CELIAC PLEXUS NEUROLYSIS
Kappis originally described retroaortic and retrocrural placement of local anesthetic agents adjacent to the bodies
[20]
of T12 to L2. This technique has been modified for neurolytic and RF procedures so that curved blunt needles or
[20]
cannulae are introduced closer to the midline and follow a vertebra-hugging approach to the middle third of the
vertebral bodies of T11 and T12. The anatomy is variable, and the wider spread of neurolytic agents may,
theoretically, produce a more profound neurolysis. However, the risk of spread to vascular structures, spinal arteries
in particular, reduces their appeal. The control inherent in RF lesioning has therefore been used to devise a safer
method of splanchnicectomy. Several of the techniques of celiac plexus neurolysis involve retrocrural placement of
[33]
neurolytic solutions adjacent to the splanchnic nerves. These techniques are, therefore, forms of splanchnicectomy. [93]
As with other areas of the sympathetic chain, newer forms of imaging have been employed in order to reduce the
risk of complications. A study of retrocrural splanchnic nerve alcohol neurolysis by the CT-guided anterior
transaortic approach recorded no significant complications and provided “reasonable” pain relief in 10 patients. [94]
The use of CT guidance in such procedures has, however, not become commonplace and may unduly complicate
matters to little advantage. As with the upper thoracic chain, thoracoscopic splanchnicectomy may provide a direct
vision technique that has low morbidity and an improved likelihood of denervation. One might remember that the
surgical anatomy is not predictable owing to the racemose arrangement of the splanchnic fibers. [21]
Technique
Curved blunt spinal needles or RF cannulae are introduced just lateral (3 cm–4 cm) to the lateral edge of the
vertebral bodies of T11 and T12. This introduction is aided by an oblique x-ray projection similar to the approach to
the T2 to T3 sympathetic ganglia. The degree of obliquity is about 15 degrees from the vertical and allows the RF
cannula to miss the lung base. The curve of the diaphragm can be seen, and the tip of the cannula stays medial to
[95]
this curve. The cannula tip is passed down the x-ray beam by small rotations and worked around the bodies of T11
or T12 until its tip is seen to lie in the middle third of the vertebral body, as can be viewed by lateral projection. A
small amount of contrast material (Isovue 300) is injected to exclude intravascular placement. The contrast material
is seen to spread in close proximity to the vertebral body and not into adjacent structures such as the spinal canal
( Fig. 33–9 A to 33–9D).
Stimulations conducted to exclude proximity to thoracic nerve roots and lesions are performed in the same manner
as those for the upper thoracic sympathetic ganglia (80 degrees to 85 degrees for 1½ minutes). The ease with which
the tip position is changed can be improved with the use of curved tip cannulae. A series of lesions is more
encompassing and improves the chances of sympathetic neurolysis.
836
Local anesthetic can be injected to reduce the pain of lesioning, because an immediate physiologic effect is not
sought during the procedure. The patient is then transferred to the day recovery unit and again closely monitored for
undesirable complications such as pneumothorax and hypotension.
Celiac plexus neurolysis is commonly employed for treatment of cancer pain. It is perhaps one of the most effective
of the neurolytic palliative procedures
Figure 33-9 A, Axial computed tomography view of the T11 vertebra, with the needle track for splanchnic block depicted (white line, lower
right). B, Oblique projections of T11 showing a radiofrequency cannula adopting a vertebra-hugging approach to the splanchnic nerves. C,
Iopamidol (Isovue 300), 0.5 mL is injected to exclude intravascular placement. It is seen to spread in close proximity to the vertebral body. D,
Lateral view of the bodies of T11 and T12, showing the cannula tip placed over the middle third of the body.
for pancreatic cancer pain. Many variations of the technique have been devised with the aim of depositing
[23]
neurolytic agents in the midline just anterior to the aorta over the L1 to L2 segments. A bilateral approach is usually
advocated, because the plexus is a diffuse structure with bilateral representation over a variable area. However, the
various posterior approaches have been compared and found to give similar results. A meta-analysis demonstrated
[96]
long-lasting benefit in upper abdominal cancer pain, regardless of the technique used. RF techniques are not [24]
suitable for neurolysis of the plexus because of its variable and diffuse anatomy. Single-needle techniques have been
described, including both transcrural and transaortic approaches.
[97]
These techniques possibly simplify celiac
[98] [99]
plexus neurolysis and reduce operative discomfort. Both anterior and posterior approaches have also been described
using sonographic and CT guidance.
[100]
CT is particularly helpful in determining the extent of the approach and
[101] [102]
the appropriateness of contrast (and neurolytic solution) spread. Meticulous attention to the spread of contrast can
837
perhaps reduce the incidence of vascular and neurolytic injury, because fairly large volumes of neurolytic agent,
[99]
such as absolute alcohol or phenol in a high concentration, are advocated. Possible serious complications of celiac
plexus block include paraplegia, pneumothorax, and sexual dysfunction. Neurolytic celiac plexus block for
[103] [104] [105]
nonpancreatic tumor pain is perhaps not as efficacious, but it deserves consideration. Last, the use of destructive
[106]
neurolysis of the celiac plexus for pain of benign origin is controversial because the effects tend to wear off and the
risk-benefit ratio is reduced.
Technique
In my practice, a single-needle, transaortic technique has been employed for several years without major
complications. Via a posterior paravertebral approach, a curved, sharp, 23-gauge needle is inserted on the left about
3cm to 4cm lateral to the edge of L1. The needle follows a vertebra-hugging pathway to the anterior and caudad
aspect of the L1 vertebral body. This is aided by a 15 to 20 degree oblique projection of the C-arm so that the needle
can be passed down the x-ray beam. A characteristic pop is felt as the aorta is penetrated, and then again as the
needle exits the anterior wall.
Needless to say, all bleeding via the needle must have ceased completely before the contrast agent is injected. A
careful study of the spread of the contrast excludes intravascular placement. Injections of absolute alcohol in
volumes of 15 mL to 20 mL are extremely painful and for this reason alone, it is best if the patient is fully
anesthetized. Common complaints after successful neurolysis of the celiac plexus include transient diarrhea and
postural hypotension. Both usually settle within days and, fortunately, more serious complications are rare.
LUMBAR SYMPATHOLYSIS
Chemical sympathectomy of the lumbar chain must be one of the more common procedures performed in pain
medicine centers worldwide. Indeed, percutaneous techniques of sympatholysis in this region have probably
supplanted open surgery. [53]
RF techniques have also been devised for the lumbar chain in an attempt to reduce complications such as
genitofemoral neuralgia and the retroperitoneal scarring that can accompany the use of neurolytic agents. The spread
of phenol, even with use of the single-needle technique described by Hatangdi and Boas is extensive and must
[107] [36]
encompass many more sympathetic fibers than RF lesioning. As long as the tip of the needle protrudes beyond the
iliopsoas fascia, worries about the position of sympathetic ganglia are perhaps academic. Ultrasonic and CT
guidance have been described. It is claimed that the avoidance of radiation and the ability to follow the spread of
[10] [108]
neurolytic agent with ultrasonography provide added safety. A variation of the C-arm x-ray–guided technique as
described by Klopfer is perhaps the predecessor of the currently used curved, single-needle technique.
[109] [109]
RF lumbar sympatholysis has been developed as an alternative to chemical ablation of the chain. The discrete [110]
lesions of the RF procedure probably reduce the incidence of neurologic complications and scarring. Comparisons [111]
between RF denervation and phenol neurolysis have been made in a number of studies. Haynsworth and Noe, in an [60]
earlier study, found that after 8 weeks only 12% of patients in the RF group showed signs of sympatholysis
compared with 89% in the phenol group. However, a modified technique of RF sympatholysis has been compared
[60]
with 6% phenol sympatholysis and found to produce comparable results. Poor results in pain relief have been
[112]
observed in patients undergoing RF neurolysis for RSD. The use of RF neurolysis for this condition could perhaps
be criticized on the grounds that it is a correctly performed technique but used inappropriately (see earlier).
RF lumbar sympatholysis has been reported even for treatment of patients with neuropathic and autonomic features,
who have failed to respond to back surgery. The follow-up period was 1 year, and repeat procedures for lack of
effect were performed in only 32 of 991 patients. This would indicate a high percentage of effective
sympatholysis. [113]
Technique
The technique for placement of a curved needle or RF cannula is similar to that for other areas of the sympathetic
chain. The needle is worked down the x-ray beam and around the convexity of the vertebral body so that the tip
protrudes through the iliopsoas fascia. In cases of single-needle chemical neurolysis for vascular problems in the
foot, placement at the L4 level suffices. If RF sympatholysis is required, cannulae are introduced at multiple levels,
possibly including L3 to L5. Pain states involving the knee require higher placement of the cannulae and perhaps
even a transcrural approach to between L1 and L2 ( Fig. 33–10 ).
838
The waist of the vertebral body is avoided, as frequently venous drainage from this area communicates with the
venous plexus in the epidural space. The ganglia are, in any case, more often found adjacent to the end plates of the
vertebral bodies. If the needle tip is not optimally placed on the first attempt at insertion, adjustment is relatively
[39]
easy with the curved tip used as a steerage device.
Contrast agent spreads cephalocaudad and anterior to the iliopsoas fascia. If the tip of the needle or cannula is still
retained in the iliopsoas fascia, contrast tracks obliquely and laterally, following the direction of the iliopsoas muscle.
Figure 33-10 Axial view of the L4 vertebra with a curved blunt needle in place for radiofrequency sympatholysis.
A loss-of-resistance technique can assist in determining the anterior exit from the iliopsoas fascia. From an
anteroposterior x-ray projection, the tip of the needle or RF cannula is seen to rest approximately in the line of the
lumbar facet joints ( Fig. 33–11 A and B).
Complications such as renal or ureteric injury can be avoided if the needle or RF cannula is inserted at an angle less
than 15 to 20 degrees from the vertical and then worked around the body of the vertebra with frequent rotations of
the curved tip.
Injection of neurolytic agents must be performed with extreme care. Intravascular injection of neurolytic agents such
as phenol can lead to vascular injuries of the spinal cord, renal failure, or even cardiac arrest (of which I have had
personal experience with a happy outcome!). Phenol, 10%, mixed with contrast needs to be injected to a total
volume of only 5 mL to obtain extensive spread and adequate sympatholysis. The contrast allows one to monitor the
spread of the neurolytic agent during incremental injection.
For RF lesioning, the RF cannula tip is placed over the anterior quarter of the vertebral body as seen on lateral x-ray
projection. As the tip of the cannula protrudes through the iliopsoas fascia, the spread of contrast agent is, again,
cephalocaudad, producing the same picture as the spread during neurolytic sympatholysis. RF cannulae with longer
active tips (15-cm curved cannula with a 10-mm active tip) can reduce the number of lesions
required for sympatholysis, because the size of the RF lesion is partly proportional to the length
of the uninsulated exposed tip. Before lesioning, stimulation is undertaken and, again, can serve two purposes.
Motor stimulation at 2 Hz can indicate proximity to a nerve root or a branch of the lumbar plexus. If motor
stimulation is obtained at less than 1.5 V, the cannula tip should be moved to a more suitable location. Sensory
stimulation can also cause regional cooling of the foot, indicating proximity to the sympathetic chain. Lesioning
(80°C–85°C for 1½ min) is best undertaken with the patient asleep because it can cause considerable deep
abdominal discomfort and the prior injection of local anesthetic agents can confuse the short-term effects of the
procedure. A temperature differential between the limbs can be seen within a few minutes if the sympathetic chain
or ganglia have been successfully lesioned.
839
Figure 33-11 A, Anteroposterior view of the lumbar (L) vertebra. The tips of the radiofrequency (RF) cannulae lie in the approximate line of the
lumbar facet joints. B, Lateral view of lumbar vertebra with radiofrequency cannulae in position for sympatholysis (SYM). The spread of contrast
is cephalocaudad.
The list of possible complications is significant, but these complications can be largely avoided if meticulous
[111]
attention is paid to the approach track of the needle or cannula, the final position of the tip, and the spread of
contrast agent. The postprocedural discomfort felt in the groin, particularly after chemical sympathectomy, is
thought to represent a chemical irritation of the genitofemoral nerve. It is suggested that the more discrete RF lesion
reduces the incidence of neuralgic pain. An alternative explanation may lie in convergence phenomena as
sympathetic afferents pass to the central nervous system through the nerve roots L1 to L2. The tracking of [114]
neurolytic agents to components of the lumbar plexus or contents of the spinal canal can lead to significant
neurologic deficit. Although this can be largely avoided by careful technique, such rare occurrences are inherently
more likely with the uncontrolled spread of neurolytic solutions.
SUPERIOR HYPOGASTRIC PLEXUS
Several authors have described techniques for neurolytic block of the superior hypogastric plexus. The
[43] [115] [116]
structure is diffuse and in a fashion analogous to that of blocks of the celiac plexus, is best blocked with neurolytic
solutions. Previously, presacral surgical neurectomy was performed for some pelvic pain states. Laparoscopic [70] [117]
approaches were subsequently developed and reported to be successful in treating pelvic pain that had not responded
to medical treatment. However, presacral surgical neurectomy can fail, because there can be many
[118] [119]
configurations of the hypogastric plexus. Neurolytic solutions can reach unresectable fibers by diffusing more
widely across the midline and into the intrailiac trigone. CT guidance has been advocated and perhaps gives a
[118]
better picture of the spread of solution. Anatomic difficulties can be encountered when a needle is placed anterior
[116]
to the lumbosacral disc. A transdiscal approach has, therefore, been described to overcome the obstruction of the
pelvic brim. This technique could, unfortunately, introduce yet another possible complication in the form of
[120]
discitis and even epidural abscess.
Technique
Hypogastric plexus block is not easy. The needle tip must be placed anterior to the lumbosacral disc and near the
midline. To reach this target, the needle must be long (20 cm), curved, and steerable, and the C-arm must be
adjusted to a high degree of lookdown and obliquity.
The needle is inserted about 5 cm to 7 cm lateral to the midline at about the level of the L4 to L5 disc. Using the
curved tip as a steerage mechanism, the needle is passed down the x-ray beam and worked around the lateral aspect
of the body of L5 until it reaches a point about 1 cm to 2 cm anterior to the L5 and S1 intervertebral disc.
840
As operators explore this technique, they will find that the passage of the needle tip is often obstructed by the pelvis
or the transverse process of L5 and cannot easily be manipulated into position. Prior experience with cadaver
placement is invaluable in learning this technique. Once in position, contrast agent is injected and carefully observed
for inappropriate spread.
The effects of intravascular injection of neurolytic agents are no less significant in this area. Bilateral approaches are
advisable but may not be required if the needle tip can be placed relatively near the midline. Neurolytic solutions,
[43]
in any case, tend to diffuse across the midline. The volume of neurolytic solution injected (or local anesthetic if a
test block is performed) is usually between 8 mL and 10 mL. This injection is performed slowly and with careful
observation for possible hemodynamic complications. The patient is then transferred to a suitable recovery area for
further observation.
The Future
Having considered the past and present of sympatholysis, I can now speculate on the future applications of this
technique.
Improvements in knowledge of the microscopic anatomy and function of the sympathetic nervous system may lead
to future refinements in the use of sympatholysis. For example, the visceral aspects of spinal pain may well be
relayed in sympathetic afferent fibers. It is possible that better control of spinal pain may come through such
[114] [121]
knowledge and through selective alteration of sympathetic chain function.
It is hoped that effective techniques such as celiac plexus block and splanchnic neurolysis will be used earlier rather
than later in the treatment of cancer pain. The deep epigastric pain of pancreatic cancer can be almost totally
eliminated so that palliation is accomplished without central sedation from high doses of opioids. Many patients
place great importance on retaining a clear mind in their last months.
I hope that the occasional, almost magical, effects of stellate or lumbar sympathetic blocks on florid CRPS will
receive a physiologic explanation. This effect is surely not due to the removal of sympathetic “overdrive” but
perhaps, in some way, to the resetting of central autonomic control of the periphery.
Last, a better understanding of the often profound physiologic effects of sympatholysis may also lead to a better
selection of patients for treatment of hyperhydrosis. There is little point in replacing a social phobic reaction with
equally unpleasant gustatory or compensatory sweating.
ACKNOWLEDGMENTS
The author is most grateful for the bibliographic and grammatical efforts of Jean Coleman and the effortless
typographical skills of Fran Van Der Loon. He also wishes to thank the Perth Radiological Clinic for their help with
axial CT and MR images.
REFERENCES
1. Leriche R: De le longation et de la section des nerfs perivasculaires dans certains syndromes douloureux d'origine arterielle et dans quelques
troubles trophiques. Lyon Chir X:378, 1913.
2. Leriche R: De la causalgie envisagée comme une nevrite du sympathique et de son traitement par la dénudation et l'excision des plexus nerveux
péri-arteriels. Presse Med 24:178–180, 1916.
3. Kramer JG, Todd TW: The distribution of nerves to arteries of arm with discussion of clinical value of results. Anat Res viii:243–254, 1914.
4. KotzareffA: Resection partielle du tronc sympathique cervical droit pour hyperhydrose unilaterale (régions faciale, cervicale, thoracique et
brachiale droites). Rev Med Suisse Romande 40:111–113, 1920.
5. Jonnesco T: Traitement chirurgical de l'angine de poitrane par la résection du sympathique cervico-thoracique. Presse Med I:193–194, 1921.
6. Kuntz A: Distribution of the sympathetic rami to the brachial plexus: Its relation to sympathectomy affecting the upper extremity. Arch Surg
XV:871–877, 1927.
7. Cloward RB: Hyperhydrosis. J Neurosurg 30:545–551, 1969.
841
8. Roos DB: Transaxially extrapleural thoracic sympathectomy. In Bergan JJ, Yao JST (eds): Operative techniques in vascular surgery. New York,
Grune & Stratton, 1980, p 115.
9. Kux E: Thorakoskopische Eingraffe an Nervensystem. Stuttgart, Thieme Verlag, 1954.
10. DondelingerRF: Percutaneous phenol block of the upper thoracic sympathetic chain with computed tomography guidance: A new technique.
Acta Radiol 28:511–515, 1987.
11. Wilkinson HA: Percutaneous radiofrequency upper thoracic sympathectomy. Neurosurgery 38:715–725, 1996.
12. Forouzanfar T, Van Kleef M, Weber WEJ: Radiofrequency lesions of the stellate ganglion in chronic pain syndromes: Retrospective analysis
13. Royle ND: The treatment of spastic paralysis by sympathetic ramisection. Surg Gynecol Obstet 39:701–704, 1924.
14. Adson
AW, Brown GE: The treatment of Raynaud's disease by resection of the upper thoracic and lumbar sympathetic ganglia and trunks.
Surg Gynecol Obstet XLVIII:577–603, 1929.
14A. Smithwick RH: Sympathectomy, splanchnicectomy and vagotomy. Rev Surg 30:153–173, 1973.
15. Mitchell SW, Morehouse GR, Keen WW: Gunshot Wounds and Other Injuries of Nerves. Philadelphia, JB Lippincott, 1864.
16. Spurling RG: Causalgia of the upper extremity: Treatment by dorsal sympathetic ganglionectomy. Arch Neurol Psychiat 23:784–788, 1930.
17. Richards RL: Causalgia: A centennial review. Arch Neurol 16:339–350, 1967.
18. Hassantash SA, Maier RV, Kaiser LR, et al: Sympathectomy for causalgia: Experience with military injuries. J Trauma 49:266–271, 2000.
19. Evans JA: Reflex sympathetic dystrophy. Surg Clin North Am 26:780–790, 1946.
20. Kappis M: Erfahrungen mit Localanasthesie bei Bauchoperationen. Verh Dtsch Ges Chir 43:87–89, 1914.
21. Moodley J, Singh B, Shaik AS, et al: Thorascopic splanchnicectomy: Pilot evaluation of a simple alternative for chronic pancreatic pain
control. World J Surg 23:688–692, 1999.
22. Jones RR: A technique of injection of the splanchnic nerves with alcohol. Anesth Analg 36:75–77, 1957.
23. MooreDC: Celiac (splanchnic) plexus block with alcohol for cancer pain of the upper intra-abdominal viscera. In Bonica JJ, Ventafridda V,
Fink RB, et al (eds): Advances in Pain Research and Therapy, vol 2. New York, Raven Press, 1979, pp 357–371.
24. Eisenberg E, Carr DB, Chalmers TC: Neurolytic celiac plexus block for treatment of cancer pain: A meta-analysis. Anesth Analg 80:290–295,
1995.
25. Perl ER: Causalgia, pathological pain, and adrenergic receptors. Proc Natl Acad Sci U S A 96:7664–7667, 1999.
26. Drummond PD, Finch PM, Smythe GA: Reflex sympathetic dystrophy: The significance of differing plasma catecholamine concentrations in
affected and unaffected limbs. Brain 114:2025–2036, 1991.
27. Drummond PD, Finch PM: Reflex control of facial flushing during body heating in man. Brain 112:1351–1358, 1989.
28. Palumbo LT: A new concept of the sympathetic pathways to the eye. Ann Ophthalmol 8:947–954, 1976.
29. Katritsis
ED, Lykaki-Anastopoulou G, Papadopoulos NJ: The relations of the superior pole of the stellate ganglion to the vertebral artery. Anat
Anz 150:259–263, 1981.
30. Lyons
AJ, Mills CC: Anatomical variants of the cervical sympathetic chain to be considered during neck dissection. Br J Oral Maxillofac Surg
36:180–182, 1998.
31. Chiou TSM, Liao K-K: Orientation landmarks of endoscopic transaxillary T-2 sympathectomy for palmar hyperhidrosis. J Neurosurg 85:310–
315, 1996.
32. Stanton-Hicks M: Personal e-mail communication with the author, 2000.
33. Raj PP, Thomas J, Heavner J, et al: The development of a technique for radiofrequency lesioning of splanchnic nerves. Curr Rev Pain 3:377–
387, 1999.
34. Finch PM, Racz GB, McDaniel K: A curved approach to nerve blocks and radiofrequency lesioning. Pain Digest 7:251–257, 1997.
35. Ward EM, Rorie DK, Nauss LA, et al: The celiac ganglia in man: Normal anatomic variations. Anesth Analg 58:461–465, 1979.
36. Goucke CR, Lovegrove FTA, Finch PM: Lumbar sympathectomy: Spread of radiopharmaceuticals following a single-needle technique. Br J
842
Anaesth 59: 944–945, 1987.
37. Cowley RA, Yeager GH: Anatomic observations on the lumbar sympathetic nervous system. Surgery 25:880, 1949.
38. Perlow S, Vehe KL: Variations in the gross anatomy of the stellate and lumbar sympathetic ganglia. Am J Surg 30:454, 1935.
39. Umeda S, Arai T, Halano Y, et al: Cadaver anatomic analysis of the best site for chemical lumbar sympathectomy. Anesth Analg 66:643–646,
1987.
40. WeylandA, Weyland W, Carduck HP, et al: Which paravertebral approach is optimal for lumbar sympathetic blocks? Resultsof computer
tomographic simulation studies. Pain 5 (Suppl): 489, 1990.
41. Rocco AG, Palombi D, Raeke D: Anatomy of the lumbar sympathetic chain. Reg Anesth 20:13–19, 1995.
42. Simeone FA: The lumbar sympathetic. Acta Chir Belg 1:17–26, 1977.
43. Leon-Casasola
OA, Kent E, Lema MJ: Neurolytic superior hypogastric plexus block for chronic pelvic pain associated with cancer. Pain
54:145–151, 1993.
44. Loev MA, Varklet VL, Wilsey BL, et al: Cryoablation: A novel approach to neurolysis of the ganglion impar. Anesthesiology 88:1391–1393,
1998.
45. YilmazEN, Dur AHM, Cuesta MA, et al: Endoscopic versus transaxillary thoracic sympathectomy for primary axillary and palmar
hyperhidrosis and/or facial blushing: 5-year experience. Eur J Cardiothorac Surg 10:168–172, 1996.
46. Telaranta T: Treatment of social phobia by endoscopic thoracic sympathectomy. Eur J Surg 580:(Suppl)27–32, 1998.
47. Crozier WR: Social psychological perspectives in shyness, embarrassment and shame. In Crozier WR (ed): Shyness and Embarrassment.
Cambridge, Cambridge University Press, 1990, pp 19–58.
48. Drott
C, Claes G, Olsson-Rex L, et al: Successful treatment of facial blushing by endoscopic transthoracic sympathectomy. Br J Dermatol
138:639–643, 1998.
49. Kux M: Thoracic endoscopic sympathectomy in palmar and axillary hyperhidrosis. Arch Surg 112:264–266, 1978.
50. Zacherl J, Huber ER, Imhof M, et al: Long-term results of 630 thoracoscopic sympathectomies for primary hyperhidrosis: The Vienna
experience. Eur J Surg 164(Suppl 580):43–46, 1998.
51. Herbst
F, Plast EG, Fugger R, et al: Endoscopic thoracic sympathectomy for primary hyperhidrosis of the upper limbs: A critical analysis and
long-term results in 480 operations. Ann Surg 220:86–90, 1994.
52. Drummond PD: A caution about surgical treatment for facial blushing. Br J Dermatol 142:194–195, 2000.
53. Barnes RW: Sympathectomy: Quo vadis? Cardiovasc Surg 2:9–15, 1994.
54. Koman LA, Smith BP, Pollock FE, et al: The microcirculatory effects of peripheral sympathectomy. J Hand Surg Am 20A:709–717, 1995.
55. Brunn J, Mandl F: Die paravertebrale Injektion zur Bekampfung visceraler Schmerzen. Wien Klin Wochenschr 37:511–514, 1924.
56. Haxton HA: Chemical sympathectomy. Br Med J 1:1026–1028, 1949.
57. Strandness DE, Bell JW: Critical evaluation of the results of lumbar sympathectomy. Ann Surg 160:1021–1029, 1964.
58. Shumacker HB, Kilman JW: Sympathectomy in the treatment of frostbite. Arch Surg 89:575–584, 1964.
59. CousinsMJ, Reeve TS, Glynn CJ, et al: Neurolytic lumbar sympathetic blockade: Duration of denervation and relief of rest pain. Anaesth
Intensive Care 7:121–135, 1979.
60. Haynsworth RF, Noe CE: Percutaneous lumbar sympathectomy: A comparison of radiofrequency denervation versus phenol neurolysis.
61. Bonica JJ: Causalgia and other reflex sympathetic dystrophies. In Bonica JJ (ed): The Management of Pain. Philadelphia, Lea and Febiger,
1990, pp 220–243.
62. Schwartzman RJ, Liu JE, Smullins SN, et al: Long-term outcome following sympathectomy for complex regional pain syndrome type I (RSD).
J Neurol Sci 150:149–152, 1997.
63. Roberts WJ: A hypothesis on the physiological basis for causalgia and related pains. Pain 24:297–311, 1986.
64. Goldstein DS, Tack C, Li S-T: Sympathetic innervation and function in reflex sympathetic dystrophy. Ann Neurol 48:49–59, 2000.
843
65. HardenRN, Duc TA, Williams TR, et al: Norepinephrine and epinephrine levels in affected versus unaffected limbs in sympathetically
maintained pain. Clin J Pain 10:324–330, 1994.
66. RoLS, Chen ST, Tang LM, et al: Effect of NGF and anti-NGF on neuropathic pain in rats following chronic constriction injury of the sciatic
nerve. Pain 79:265–274, 1999.
67. Owolabi JB, Rizkalla G, Tehim A, et al: Characterization of antiallodynic actions of ALE-0540, a novel nerve growth factor receptor
antagonist, in the rat. J Pharmacol Exp Ther 289:1271–1276, 1999.
68. Wasner G, Drummond P, Birklein F, et al: The role of the sympathetic nervous system in autonomic disturbances and “sympathetically
maintained pain” in CRPS (in press).
69. Elias M: The anterior approach for thoracic sympathetic ganglion block using a curved needle. Pain Clin 12:17–24, 2000.
70. Lee RB, Stone K, Magelsen D, et al: Presacral neurectomy for chronic pelvic pain. Obstet Gynecol 68:517–521, 1986.
71. Perez JJ: Laparoscopic presacral neurectomy: Results of the first 25 cases. J Reprod Med 35:625–638, 1990.
72. Raj
PP, Anderson SR: Stellate ganglion block. In Waldman SD (ed): Interventional Pain Management. 2nd ed. Philadelphia, WB Saunders,
2001, pp 363–372.
73. Racz GB: Stellate ganglion phenol neurolysis. In Racz GB (ed): Techniques of Neurolysis. Boston, Kluwer, 1989, pp 133–144.
74. Superville-Slovak B, Raminsky M, Finlayson MH: Complications of phenol neurolysis. Arch Neurol 32:226–228, 1975.
75. Erickson
SJ, Hogan QH: CT-guided injection of the stellate ganglion: Description of technique and efficacy of sympathetic blockade.
Radiology 188:707–709, 1993.
76. KapralS, Krafft P, Gosch M, et al: Ultrasound imaging for stellate ganglion block: Direct visualization of puncture site and local anesthetic
spread. Reg Anesth 20:323–328, 1995.
77. Slappendel R, Thijssen HOM, Crul BJP, et al: The stellate ganglion in magnetic resonance imaging: A quantification of the anatomic
variability. Anesthesiology 83:424–426, 1995.
78. Guntamukkala M, Hardy PA: Spread of injectate after stellate ganglion block in man: An anatomical study. Br J Anaesth 66:643–644, 1991.
79. Guerts
JWM, Stolker RJ: Percutaneous radiofrequency lesion of the stellate ganglion in the treatment of pain in upper extremity reflex
80. Sternberg A, Brickman S, Kott I: Transaxillary thoracic sympathectomy for primary hyperhidrosis of the upper limbs. World J Surg 6:458–463,
1982.
81. Ahn SS, Machleder HI, Concepcion B, Moore WS: Thoracoscopic cervicodorsal sympathectomy: Preliminary results. J Vasc Surg 20:511–519,
1994.
82. Johnson JP, Obasi C, Hahn MS, Glatleider P: Endoscopic thoracic sympathectomy. J Neurosurg 91(1 Suppl):90–97, 1999.
83. Friedel G, Linder A, Toomes H: Selective video-assisted thoracoscopic sympathectomy. Thorac Cardiovasc Surg 41:245–248, 1993.
84. Krasna MJ, Demmy TL, McKenna RJ, Mack MJ: Thoracoscopic sympathectomy: The U.S. experience. Eur J Surg 580(Suppl):19–21, 1998.
85. EpsteinAE, Rosner MJ, Hageman GR, et al: Posterior left thoracic cardiac sympathectomy by surgical division of the sympathetic chain: An
alternative approach to treatment of the long QT syndrome. Pacing Clin Electrophysiol 19:1095–1104, 1996.
86. Cartier B, Cartier P: Thoracoscopic cervicodorsal sympathectomy with diathermy. Ann Vasc Surg 13:582–585, 1999.
87. Lindquist C, Fedorcasak I, Steig PE: Electrophysiological aid in high thoracic sympathectomy for palmar hyperhidrosis. Neurosurgery 24:449–
452, 1989.
88. Kao
MC, Tsai JC, Lai DM, et al: Autonomic activities in hyperhidrosis patients before, during, and after endoscopic laser sympathectomy.
89. BrownDL, Rorie DK: Altered reactivity of isolated segmental lumbar arteries of dogs following exposure to ethanol and phenol. Pain 56:139–
143, 1994.
90. Wood KM: The use of phenol as a neurolytic agent: A review. Pain 5:205–229, 1978.
91. Wilkinson HA: Stereotactic radiofrequency sympathectomy. Pain Clin 8:107–115, 1993.
92. Yin W: Posterior parasagittal approach to thoracic paravertebral neural structures with curved needle: Methodology and technique to decrease
844
the incidence of unintentional visceral injury with thoracic percutaneous approaches for the treatment of chronic pain. ISIS Sci Newslett 4:18–40,
2000.
93. MooreDC, Bush WH, Burnett LL: Celiac plexus block: A roentgenographic, anatomic study of technique and spread of solution in patients
and corpses. Anesth Analg 60:369–379, 1981.
94. Fields
S: Retrocrural splanchnic nerve alcohol neurolysis with a CT-guided anterior transaortic approach. J Comput Assist Tomogr 20:157–
160, 1996.
95. Ishida
H, Otake T, Saito S: Location of lung and celiac arterybase in prone positioned patients undergoing celiac plexus or splanchnic nerve
blocks. Pain Clin 12:209–216, 2000.
96. Ischia
S, Ischia A, Polati E, et al: Three posterior percutaneous celiac plexus block techniques: A prospective, randomized study in 61 patients
with pancreatic cancer pain. Anesthesiology 76:534–540, 1992.
97. Hilgier M, Rykowski JJ: One needle transcrural celiac plexus block: Single shot or continuous technique, or both. Reg Anesth 19:277–283,
1994.
98. Lieberman RP, Waldman SD: Celiac plexus neurolysis with the modified transaortic approach. Radiology 175:274–276, 1990.
99. Ischia S, Luzzani A, Ischia A, et al: A new approach to the neurolytic block of the coeliac plexus: The transaortic technique. Pain 16:33–341,
1983.
100. GimenczA, Martinez-Noguera A, Donoso L, et al: Percutaneous neurolysis of the celiac plexus via the anterior approach with sonographic
guidance. AJR 161:1061–1063, 1993.
101. Choy YC, Puvenesvari S, Samad S, et al: Chronic pain management: Upper visceral malignancies coeliac plexus block with CT scanning: A
case report. Med J Malaysia 53:277–279, 1998.
102. Matamala AM, Lopez FV, Martinez LI: The percutaneous anterior approach to the celiac plexus using CT guidance. Pain 34:285–288, 1988.
103. Cherry DA, Lamberty J: Paraplegia following coeliac plexus block. Anaesth Intensive Care 12:59–61, 1984.
104. Brown DL, Bulley CK, Quiel EL: Neurolytic celiac plexus block for pancreatic cancer pain. Anesth Analg 66:869–873, 1987.
105. Black A, Dwyer R: Coeliac plexus block. Anaesth Intensive Care 1:315–318, 1973.
106. Brown DL: A retrospective analysis of neurolytic celiac plexus block for nonpancreatic intra-abdominal cancer pain. Reg Anesth 14:63–65,
1989.
107. Hatangdi VS, Boas RA: Lumbar sympathectomy: A single-needle technique. Br J Anaesth 57:285–289, 1985.
108. Kirvela O: Ultrasonic guidance of lumbar sympathetic and celiac plexus block: A new technique. Reg Anesth 17:43–46, 1992.
109. Klopfer GT: Neurolytic lumbar sympathetic blockade: A modified technique. Anaesth Intensive Care 11:43–46, 1983.
110. Pernak J: Percutaneous radiofrequency thermal lumbar sympathectomy. Pain Clinic 8:99–106, 1995.
111. Sri Kantha K: Radiofrequency percutaneous lumbar sympathectomy: Technique and review of indications. In Racz G (ed): Techniques of
Neurolysis. Boston, Kluwer Academic, 1989, pp 171–183.
112. Noe CE, Haynsworth RF Jr: Lumbar radiofrequency sympatholysis. J Vasc Surg 17:801–806, 1993.
113. Erdmann W, Pernak J, Grosveld WHJH: Results of radiofrequency sympathectomy in post-laminectomy pain syndrome in the Netherlands.
Pain Clin 8:127–131, 1995.
114. Nakamura S, Takahashi K, Takahashi Y, et al: The afferent pathways of discogenic low-back pain: Evaluation of L2 spinal nerve infiltration.
J Bone Joint Surg Br 78B:606–612, 1996.
115. Plancarte R, Amescua C, Patt RB, et al: Superior hypogastric plexus block for pelvic cancer pain. Anesthesiology 73:236–239, 1990.
116. WechslerRJ, Maurer PM, Halpern EJ, et al: Superior hypogastric plexus block for chronic pelvic pain in the presence of endometriosis: CT
techniques and results. Radiology 196:103–106, 1995.
117. Tjaden B, Schlaff WD, Kimball A, et al: The efficacy of presacral neurectomy for the relief of midline dysmenorrhea. Obstet Gynecol 76:89–
91, 1990.
118. Perez JJ: Laparoscopic presacral neurectomy: Results of the first 25 cases. J Reprod Med 6:625–630, 1990.
119. Nezhat C, Nezhat F: A simplified method of laparoscopic presacral neurectomy for the treatment of central pelvic pain due to endometriosis.
Br J Obstet Gynaecol 99:659–663, 1992.
845
120. Erdine S: Transdiscal approach for hypogastric plexus block. Slide Presentation at the Fifth Annual Advanced International Pain Conference
and Cadaver Workshop, Budapest, September 24–27, 2000.
121. Ohtori S, Takahashi K, Chiba T, et al: Sensory innervation of the cervical facet joints in rats. Spine 26:147–150, 2001.
846
Section V Chapter 34 - Epidural Steroids
Chapter 34 - Epidural Steroids
HEMMO A. BOSSCHER
MELVIN G. GITLIN
ALAN D. KAYE
Chronic back pain, radiculopathy, and associated disabilities represent a significant health problem. Back pain is
considered a major cause of absence from work and of long-term disability. The vast majority of patients suffering
acute back pain recover spontaneously in several weeks. However, a significant fraction of these have recurrence of
[1]
symptoms within a year. Many patients who have a relapse or whose back pain does not subside in time, and for
[2]
whom surgery is not indicated, are eventually referred to a pain clinic. By this time, the patient may have undergone
a variety of treatments with limited success. It is likely that at some point during therapeutic intervention, the patient
may receive spinal steroid injections. Injecting substances into the epidural or subarachnoid space to treat back pain
has been practiced for almost 100 years, and injection of epidural steroids is currently the foundation of many pain
practices. Controversy regarding efficacy and safety had epidural steroid injection led to the decline of its use in
some countries. In this chapter, current knowledge of the mechanisms by which epidurally injected
[3] [4]
corticosteroids may relieve back pain is presented, along with a review of the efficacy and safety of epidural steroid
injections.
HISTORY
Epidural steroid administration has been a long-standing component of the treatment of patients
with numerous spine-related painful conditions. In 1925, Viner reported his experience with
[5]
caudal injection of procaine, Ringer's solution, normal saline, or liquid petrolatum in the
treatment of sciatica. All patients were reported to be nearly free of symptoms at follow-up.
Evans, in 1930, reported his treatment of patients with unilateral sciatica with caudal injection
[6]
of procaine and saline. In 1952, Robecchi and Capra reported the use of hydrocortisone
[7]
injection in the first sacral root canal for treatment of a patient with back pain and sciatica. They
theorized that the therapeutic effect of this treatment was mediated by mechanical stretching of
the nerve roots forming the sciatic nerve.
Boudin and colleagues were the first to use subarachnoid steroid injections to cure sciatica in
[8]
1955, and in 1957 Lievre and associates were credited with the first use of hydrocortisone
injected epidurally via the lumbar route for the relief of low back pain.
In the United States, the successful use of epidural injections of procaine and hydrocortisone to
treat sciatica was reported in 1961.[10]
A large series of patients with back pain, who were treated with either caudal or lumbar epidural
injection of normal saline, local anesthetic, or methylprednisolone acetate, were followed over a
10-year period. The authors reported a statistically significant difference in incidence of
[11]
improvement in patients who received methylprednisolone compared with that in patients who
received local anesthetics or saline injections for recurrent or long-standing pain. They attributed
the success to the steroid's ability to reduce irritation or inflammation of the affected nerve roots.
Since then, many reports have appeared in the literature. Lack of uniformity in these studies with
respect to nomenclature is a constant finding. Evans' statement, made in 1930, still holds, “The
[6]
nomenclature adopted in the definition of the various forms of sciatica is in a state of chaos.” It is
clear that if one is unable to consistently attach a name to a syndrome, many questions about this
syndrome—in this case, whether epidural steroids are beneficial—cannot be answered.
New techniques for approaching an irritated nerve root have been developed. Two of these
techniques involve placement of a catheter in the epidural space and steering it to the affected
nerve root with fluoroscopy and epiduroscopy. [2] [12] [13]
Several investigators have suggested the transforaminal approach as an alternative to epidural
847
steroids placed in interlaminar spaces. [14] [15] [16] [17]
Epidural or subarachnoid steroid injections have been used for conditions other than back pain.
For example, epidural or subarachnoid methylprednisolone has been used for neurologic
disorders such as cluster headaches, multiple sclerosis, Guillain-Barré syndrome, and
brachalgia. Intrathecal methylprednisolone has been used to prevent headaches after lumbar
[18]
puncture for procedures such as myelography, pneumoencephalography, and diagnostic lumbar

puncture. Subarachnoid steroids may be effective in the relief of pain in patients with space-
[18]
occupying lesions of the central nervous system. Postherpetic, traumatic, or idiopathaic

[18]
neuralgias have been treated with epidural local anesthetic and methylprednisolone. [19]
Back Pain and Radiculopathy
ANATOMY
Pain is the most important and often the only symptom of the vast majority of spinal disorders. In an early stage of
the disease process, pain develops because of stimulation of pain-sensitive structures. These structures include bones,
joints, discs, nerves, muscles, and soft tissues. They may be affected by an inflammatory, infectious, neoplastic, or
traumatic disease or by a congenital or developmental mechanical defect. A distinction may be made between a
ventral and dorsal compartment, which are divided by a virtual frontal plane through the dorsal wall of the
intervertebral foramen. The dorsal compartment contains facet joints, the dorsal part of the dura, and the intrinsic
[20] [21]
back muscles and ligaments. The ventral compartment consists of the vertebral bodies, discs, anterior and posterior
ligaments, ventral dura, nerve roots, and prevertebral muscles. The innervation of these structures is complex (Fig. [22]
34–1 (Figure Not Available) ). The ventral compartment is supplied by interconnected neural networks; one is in the
anterior ligament (via the sympathetic chain) and one is in the posterior longitudinal ligament (via the sinuvertebral
nerve). The plexi are connected via the rami
Figure 34-1 (Figure Not Available) Nerves and nerve plexuses of the human vertebral column.(From Groen GJ, Baljet B, Drukker J: Nerves and
nerve plexus of the human vertebral column. Am J Anat 188:282–296, 1990.)
communicantes from which the sinuvertebral nerve arises. The dorsal compartment is supplied by the dorsal ramus,
of which the medial branch innervates the facet joints. The lateral branch innervates the paraspinal musculature and
the adjacent skin. There are neural connections between the two compartments as well. These interconnections,
along with multisegmental innervations and involvement of the autonomic nervous system, explain the lack of
specificity of pain in relation to the underlying pathology. Furthermore, the underlying pathology is rarely limited to
one anatomic structure. It is not surprising that treatment of patients with back pain by injecting corticosteroid into
the epidural space yields results that often depend on unknown pathology and are, therefore, highly unpredictable. It
is likely that epidural steroids are not very valuable in the treatment of disorders of the dorsal compartment. Pain-
sensitive structures in the ventral compartment include the posterior longitudinal ligament and the disc on the one
hand, and the nerve root and dorsal root ganglion on the other hand.
It is generally thought that back pain originating from pathology of the longitudinal ligament and disc is referred,
nociceptive pain. Under normal conditions, stimulation of these structures does not cause pain. However, in the
context of nerve injury, such as that mediated by inflammation or ischemia, these fibers may become easily
excitable or even show spontaneous activity. In contrast, pain that radiates into an extremity originating from
[23] [24]
pathology of the nerve root is thought to be neuropathic. Because the nerve root and dorsal root gangia are
innervated by sympathetic nerve fibers, neuropathic pain associated with an irritated nerve root may have a
sympathetically mediated component that may be associated with mechanical allodynia and hyperalgesia. These [25]
processes may explain back pain that results from movements of the spine with flexion and extension or radicular [26]
pain that results from minor stretch of the nerve root, such as with the straight leg raise test. The pathologic process
[27]
that causes nerve injury is the target of steroids placed in the epidural space. It follows that the effectiveness of
epidurally injected steroids may differ entirely for back pain and radiculopathy, depending strongly on the
underlying disease process.
PATHOLOGY
Mixter and Barr initially introduced the idea that disc degeneration, disc rupture with herniation, and subsequent
[28]
nerve impingement cause the syndrome of sciatica. Back pain was explained by posterior (central) disc herniation
[28]
or protrusion, with activation of nociceptors in the anulus fibrosus and in the posterior, longitudinal, and dorsal root
848
ganglia. However, some patients with large herniations have no radicular symptoms, and, in contrast, some
[29] [30] [31] [32] [33]
patients with no evidence of disc herniation have severe radiculopathy. In addition, mechanical irritation of a normal
nerve root results in neurologic deficit but not in pain. When the nerve root is swollen, hyperemic mechanical
stimulation results in pain in the distribution of the nerve root. This suggests that something other than pure
mechanical compression is a factor in the generation of back pain and sciatica.
The process of disc degeneration has been associated with alterations of the chemical and cellular balance of the disc.
Incision of the anulus has been shown to lead to disc degeneration. In a reparative response, vascular proliferation
with production of several angiogenic factors may lead to the activation of latent enzymes, causing the breakdown
of proteoglycans and collagens. Independent of the cause, release of enzymes and products of enzymatic action
[34]
may lead to a response similar to the inflammatory response seen in osteoarthritis, which in turn may lead to
chemical nerve injury. Indeed, histopathologic findings of inflammation of the nerve root could be demonstrated
[35] [36]
in samples obtained during surgery on the spine. [37]
In 1987, McCarron and coworkers used homogenized autologous nucleus pulposus material, which was injected
[38]
into the lumbar space of four dogs. The material, obtained from an intervertebral disc, was harvested from the
amputated tail of the animal and then injected into the epidural space via an indwelling epidural catheter. The results
of this study demonstrated well-developed fibrosis of the dura and epidural fat and inflammatory changes in the
spinal cord, dura, and nerve roots. The relative seclusion of the avascular nucleus pulposus relative to the immune
[38]
system may explain how extrusion of disc components could induce an autoimmune response that results in
inflammation.
A humoral and cellular immune response have both been suggested. Marshall suggested a systemic response to
[33] [36] [39]
disc injury, based on serum antibodies to human disc material found in patients with a history of recent back injury.
In a controlled study, IgG and IgM antibodies were found in a herniated disc but not in normal discs. Interestingly, [40]
IgM deposits were more prevalent with recent disc injury.
However, several substances found in the degenerated disc may cause responses associated with inflammation in the
absence of an immune response or significant cellular infiltration. Substances such as lactic acid, hydrogen ions,
histamine, nitric oxide, prostaglandins, and interleukins may be released by direct activation of certain biochemical
pathways. Phospholipase A2 (PLA2 ) activity was measured in disc material obtained from patients with
[33]
radiculopathy caused by a herniated or protruded disc who underwent laminectomy and discectomy. PLA2 activity
was found to be 20 to 10,000 times higher in the diseased disc than in normal tissue. Phospholipase is responsible
[41]
for the breakdown of phospholipids in the cell membrane with the production of prostaglandins and leukotrienes. [42] [43]
Release of these substances among other biochemical mediators occurs during the process of inflammation, or
leakage from an injured disc may induce a peripheral sensitization by decreasing the nociceptive threshold and
recruiting new nociceptors that cause back pain and radiculopathy. One study showed that PLA2 might cause
[23] [24]
demyelination, resulting in hypersensitive regions where mechanical stimulation might elicit ectopic discharge. [44]
Attractive as the theory of inflammation in the pathogenesis of back pain and radiculopathy may be, not all
investigations support the concept. Gronblad and associates compared the PLA2 content in prolapsed
[33] [45]
degenerative discs with normal discs obtained from organ donors. These investigators were unable to demonstrate a
lower activity in normal discs. Furthermore, several investigators who used immunohistologic techniques were
[45]
unable to show an inflammatory response in the periradicular tissues. [36] [40] [46]
In this regard, periradicular tissues in cadavers that were associated with a herniated disc demonstrated congestion,
venous thrombosis, and severe perineural fibrosis but no inflammatory cells. In a controlled prospective study of
patients with low back pain, radiculopathy, and radiologically proved disc herniation, Cooper and colleagues found [33]
fibrosis and endothelial cell abnormalities but no signs of inflammation in periradicular and neural tissues.
The last two studies reveal vascular changes rather then inflammation. However, the role of inflammation may be
important in early stages of disc herniation. First, it would explain the gradual, spontaneous resolution of symptoms
seen in many patients with acute back injury as well as the more favorable response to epidural steroids in patients
with (sub)acute back pain and radiculopathy. Second, this inflammatory process may result in permanent changes
that could lead to a chronic pain syndrome.
849
VASCULAR ABNORMALITIES, FIBROSIS, AND MECHANICAL TENSION
In the presence of an already narrowed intervertebral foramen, disc degeneration and protrusion by osteophytes,
facet hypertrophy, or other abnormalities of the bony structures may cause pressure on the epidural venous plexus,
causing venous obstruction. Venous dilatation can be observed with magnetic resonance imaging or epiduroscopy.
[47]
Venous obstruction may lead to decreased perfusion pressure of the nerve root. Unlike the blood supply to the
[13]
peripheral nerves, the blood supply to the nerve root is limited. Nutrition of the nerve root is provided primarily by
direct cerebro-spinal fluid transport, which may be compromised by disc herniation and scar tissue formation. [48]
Olmarker and associates studied the effects of nerve root compression on basic physiologic events such as blood
[49]
flow, nutrition, and nerve conduction in animals. The investigators demonstrated that pressures equal to the mean
[49]
arterial blood pressure decrease arterial blood flow, but venular blood flow may cease at pressures as low as 5 mm
Hg. At these pressures, nutrition of the nerve root was shown to be reduced to between 20% and 30% of normal.
Pressures changes of 50 mm Hg in the permeability of endoneural capillaries led to intraneural edema. Edema led to
fibrosis, further compromising nutrition of the nerve root. The same pressure seemed to be the critical compression
pressure, which interfered with impulse propagation.
Fibrosis develops intraneurally and also outside the nerve root as a result of ischemia, inflammation, or trauma (e.g.,
surgery). Indeed, fibrosis seems to be a consistent finding in epidurograms and can often be seen during
epiduroscopy. A defect in fibrinolytic activity is suggested in some chronic back pain patients who show
[2] [13]
accelerated fibrosis. Fibrosis in the narrow intervertebral foramen and in the epidural space lead to further
[50] [51]
venous congestion. Venous congestion in turn may lead to further edema and swelling of the nerve root. Eventually,
the nerve root becomes fixed in the foramen. Lack of a perineurium and poorly developed connective
[27] [30] [31] [47] [52] [53]
tissue make the nerve root more susceptible to mechanical deformation. Even the slightest degree of tension on an [54]
affected nerve root can reproduce the typical symptoms of radicular pain. With straight leg raising, movement of 1 [30]
to 5 mm at the intervertebral foramen has been documented. This movement may cause mechanical tension on a
[27]
nerve root if it is fixed in the intervertebral foramen by adhesions. The degree of swelling of the nerve root,
[27] [47] [55] [56]
as measured by magnetic resonance imaging, has been correlated to pain generation with straight leg raising. [56]
BACK PAIN
Typical back pain can be reproduced by pressure on the posterior longitudinal ligament and on the posterior disc
during surgery under local anesthetic. However, the mechanism of this type of pain is not well explained.
[30]
Degenerative disc disease may lead to central protrusion or extrusion of disc material, with mechanical activation of
nociceptors in the disc, ligaments, and dura. Primary ligament pain can be caused by instability of the spine, which
causes stress on the anterior and posterior longitudinal ligaments. Degenerative disease may lead to an annular tear.
[26]
This may lead to continuous leakage of nucleus pulposus material, which has been associated with chronic
inflammation. The sinuvertebral nerve contains mostly sympathetic fibers; therefore, a sympathetically maintained
[36]
pain component cannot be ruled out. Finally, persistent pain may be the result of altered central modulation of pain
[26]
signals. This can occur at the spinal or supraspinal level and makes the condition difficult to treat.
From the discussion in the previous paragraph, it is clear that to understand the mechanisms by which epidural
corticosteroid injections may relieve back pain, with or without radicular pain, one must appreciate the presence of
multiple pain generators inside and outside the epidural space, as well as the existence of differences in the
mechanism of pain generation (i.e., nociceptive vs. neuropathic pain) and a disease process in which the pathology
changes over the course of time.
Epidural Corticosteroids: Mechanism of Action
The adrenal cortex synthesizes corticosteroids (i.e., glucocorticoids, mineralocorticoids, and androgens). In humans,
cortisol is the primary glucocorticoid and aldosterone is the main mineralocorticoid. However, physiologic
production and circulating rates of these agents vary considerably and each adrenal corticosteroid differs in relative
glucocorticoid and mineralocorticoid activities. Cortisol production is roughly 10 mg/day and relative potencies of
representative corticosteroids vary considerably ( Table 34–1 ). [57]
To date, there are no studies available comparing the effectiveness of methylprednisolone with triamcinolone; they
are most likely equally effective. The optimal dose has not been determined. The usual dose for
[58]
methylprednisolone ranges from 80 to 120 mg. The dose of triamcinolone ranges from 40 to 80 mg.
[58] [59] [60]
Betamethasone is not as commonly used. Fewer complications have been reported with this drug. The usual dose is
1 mL (5.7 mg). Steroids can be mixed with either saline or local anesthetic. The advantage of local anesthetic [11] [61]
may be the presence of a sensory block that confirms the epidural administration of the steroid. An injection of 6 to
850
10 mL has been recommended for lumbar epidural injection, because this amount may be adequate to reach the
target issues. [62]
Several theories may explain the beneficial effects of corticosteroid in the treatment of back pain with or without
radiculopathy ( Fig. 34–2 ) In the affected nerve root, corticosteroids reduce inflammation caused by mechanical
compression, ischemia, distortion, or chemical irritation associated with extruded proteoglycan materials from the
injured disc.
The changes in nerve conduction and nerve fiber degeneration after epidural application of autologous nucleus
pulposus material in pigs were significantly reduced by intravenous administration of methylprednisolone, 30 mg/kg.
The inflammatory effects of PLA2
[63]
Figure 34-2 Sites of action of corticosteroids injected into the epidural space. All, anterior longitudinal ligament; Pll, posterior longitudinal
ligament; SVN, sinuvertebral nerve.
itself may be reduced by corticosteroids. More important is the inhibitory action of PLA2 , which reduces injury to
[36]
membranes and edema by generating membrane perturbants, unsaturated fatty acids, and lysoderivatives. PLA2 is
the enzyme responsible for the liberation of arachidonic fatty acids from cell membranes, leading to the production
of eicosanoids. The possibility of utilizing PLA2 inhibitor probes to modulate PLA2 -linked pathways has been
[64]
demonstrated in vitro and in vivo. [65] [66]
Steroids interfere with the PLA2 cascade and, therefore, do reduce arachidonic acid metabolites, products that
include prostaglandins and leukotrienes that sensitize small neurons and enhance pain generation. Altered
permeability in response to these inflammatory mediators causes intraneural edema and venous congestion,
eventually resulting in abnormal conduction and generation of pain. In addition, corticosteroids suppress the
autoimmune response triggered by glycoproteins from the nucleus pulpopsus and inhibit cytokine production by
[39]
leukocytes. Betamethasone decreases secretion of several leukotrienes, tumor necrosis factor, and prostaglandin E2
[67]
intervertebral disc tissue. These mechanisms may explain the effect of corticosteroids in early stages of back pain
[68]
sciatica (either individually or in combination) when inflammation is the predominant pathologic process. Because
inflammation plays a role in enhanced nociceptive activity in the posterior longitudinal ligament and disc, steroids
may actually be effective in the treatment of back pain without radiculopathy.
Corticosteroids have a direct action on mesodermal elements, including arachnoid tissue and fibrous tissue–forming
adhesions. Local application is more effective than systemic injection. Corticosteroids have been used in the
[69]
treatment and prevention of pleural and peritoneal adhesions. Long-term pain relief may be mediated by the
inhibiting effects of corticosteroids on fibrosis and adhesion formation in and around the nerve root in the
intervertebral foramina. This mode of action may be particularly important when used in conjunction with other
techniques, such as topical application of corticosteroids during surgery or as part of a decompressive neuroplasty. [2]
One would expect these techniques to be more successful when used for radicular pain.Corticosteroids exert a
[70]
membrane-stabilizing effect on injured nerve segments, reducing ectopic discharge from the affected nerve root. In [25]
experimental neurinomas, corticosteroids prevent the development of ectopic neural discharge; in chronic
neurinomas, they suppress ongoing discharge. This stabilizing effect is
[71]
851
TABLE 34-1 -- RELATIVE POTENCIES AND EQUIVALENT DOSES OF REPRESENTATIVE CORTICOSTEROIDS

Duration of Action
Agent Anti-inflammatory Potency (hours) Equivalent Dose (mg)
Cortisol 1 8–12 20
Triamcinolone (Aristocort) 5 12–36 4
6-Methylprednisolone (Depo-Medrol) 5 12–36 4
Betamethasone (Celestone) 25 36–72 0.75
Modified from Schimmer BP, Parker KL: Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of
adrenocortical hormones. In Hardman JG, Limbird LE (eds): Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed. New York, McGraw-Hill,
1996.
probably achieved through stimulation of a membrane-bound corticosteroid receptor, resulting in hyperpolarization

of the membrane. Neuropathic pain (i.e., radicular pain) is pain component that is more likely to be responsive to
[72]
this mode of action.
Corticosteroids reduce conduction in nociceptive C fibers in an animal model. It has been shown that onset of this
effect was instantaneous and that it persisted for the duration of the steroid application. This also suggests a direct [73]
membrane action rather than an intracellular receptor effect or an anti-inflammatory effect. It also explains why the
effect is seen primarily on thin unmyelinated C fibers and not on thick myelinated A fibers. Local anesthetic
properties of corticosteroids may produce immediate pain relief such as occasionally seen in a patient after epidural
steroid injections. This mode of action may also be effective in relief of pain originating from the dorsal
compartment, including pain from facet arthropathy and myofascial pain. C fiber plays an important role in pain
sympathetically mediated by a reduction in efferent or afferent activity (or both) from sympathetic fibers.
Central mechanisms in the processing of pain may be a target for corticosteroids as well. Corticosteroids have been
shown to reduce the sensitization of dorsal horn neurons by persistent activation of nociceptors in the affected nerve
root, possibly through their effect on spinal prostaglandin production. [74]
Corticosteroids may also exert a direct effect on the central nervous system by interfering with neurotransmitter
production and metabolism in the brainstem and spinal cord. Euphoric effects of corticosteroids are well known
[75] [67]
and can add to the favorable response of epidural steroid injections.
DRUG DEPOSITION
There are several ways of administering corticosteroids to the affected area. The simplest method is systemic
administration by either the oral or parenteral route. Success has been reported with the intramuscular administration
of dexamethasone. However, these results have not been confirmed in several randomized, controlled studies.
[76] [18]
Intrathecal administration was compared with epidural administration by Winnie and colleagues. [77]
Methylprednisolone, in a dose of 80 mg in 2 mL given either intrathecally or epidurally, was highly effective and
had virtually identical 80% to 100% success rates. Subsequent studies have found epidural steroids to be slightly
more effective. Although intrathecal administration in the subarachnoid space is probably safe, the controversy
[78] [79]
regarding possible serious side effects of this approach makes the routine use of this treatment modality inadvisable
at this time. [80] [81]
Technique
Several approaches to the epidural space are used; the lumbar, cervical, and caudal epidural routes are the most
common. No study has supported one particular technique. New techniques have been introduced, including the
caudal approach, which uses a Racz catheter or epiduroscopy, and the transforaminal approach to the epidural
space. [2] [14] [15] [16] [17]
Only a brief description of the lumbar epidural technique will be described here. The patient may be in the sitting
[58]
or lateral decubitus position. The patient's back is prepared aseptically with betadine solution and then draped. The
appropriate interspace is selected and the skin infiltrated with a local anesthetic. An introducer and then the epidural
needle are inserted.
Some prefer to use the 17-gauge (G) Tuohy or Weiss needle; other practitioners use a smaller (20-G) needle. A well-
lubricated glass syringe is attached to the needle. The epidural needle is inserted slowly through the supraspinous
and interspinous ligaments and the ligamentum flavum until the epidural space is reached. Either intermittent or
852
continuous pressure on the plunger of the syringe is applied while the needle is advanced slowly. Sudden loss of
resistance to pressure on the plunger signifies that the tip of the needle has reached the epidural space. Aspiration is
performed to ensure that the dura has not been unintentionally punctured. Methylprednisolone, 80 mg in 6 to 8 mL
saline, is injected. This is followed by 2 to 3 mL of saline to flush the needle of any steroid that remains. Some
anesthesiologists use 2 (50 mg) to 3 (75 mg) mL of triamcinolone. If a local anesthetic is used as a diluent, a test
dose of 2 to 3 mL should be injected first. After a negative test dose, the rest is injected in fractional (4- to 5-mL)
increments. Whether saline or local anesthetic is used, a repeat aspiration should be done before final injection of the
steroid solution.
Fluoroscopy has been advocated by several investigators. Several factors may make blind needle placement
[2] [82] [83] [84]
inadvisable. Identification of the level of the pathology, using surface anatomy, is notoriously unreliable. Correct
placement of the needle occurs in 30% to 75% of patients. Adhesions, particularly those developing after prior
[85] [86]
decompressive surgery, may make the spread to the affected nerve root difficult or impossible. Indeed, in a study
[87] [2]
of patients with “failed back surgery syndrome,” which was published in 1999, disposition of epidural steroids at the
side of the pathology occurred in only 25% of patients, despite accurate needle placement. [83]
Placement of a catheter by fluoroscopic guidance through the sacral canal or through an intervertebral foramen into
the ventral epidural space has been advocated. In a prospective study, 49% of patients had pain relief at 1-year of
follow-up. [2]
Transforaminal injection of epidural steroids has the theoretical advantage of direct placement at the site of the
pathology. However, damage to the nerve root is a potential complication. Lutz and associates reported a [16]
successful outcome in 75% of 69 patients. No complications were reported. Several other studies support this
[17]
technique, but the safety of this procedure has not yet been established. [15] [17]
Lumbar Epidural Steroid Injection: Efficacy
Lumbar epidural steroid injections (LESIs) have gained widespread acceptance as a conservative treatment for low
back pain with or without radiculopathy. The number of injections performed annually in Britain has been estimated
as approximately 30,000. Although no information is currently available, the number of LESIs performed in the
[88]
United States may exceed 300,000 yearly. According to the report of the Quebec Task Force on Spinal Disorders,
interventions practiced commonly but without scientific evidence constituted the third strongest type of evidence
possible for treatment efficacy. Indeed, many referring physicians believe strongly in epidural steroid injections.
[89] [90]
However, LESIs remain controversial. The Agency for Health Care Policy and Research rates the quality of
evidence of LESIs as “C,” which means that there is no good evidence, particularly from clinical trials, to endorse
efficacy. Many studies have attempted to address the issue. More than 4000 cases have been described in 60
[89] [91]
reports. However, the majority of these studies are small, have major flaws in design, and lack a control group.
[92]
Clearly, there is a need for a large-scale, definitive clinical trial to answer the question of efficacy of LESIs. Thus far,
one attempt to do so has failed completely. Even if one considers the data currently available to support the use of
[89]
LESIs, many questions remain unanswered. Who are the appropriate candidates for LESI? What is the ideal volume
and content of the injectate? How many injections should a patient receive in a specific time frame? [89]
The studies currently available can be divided into three groups. The first group is represented by the older studies. [10]
These are usually small, often lack a control group, and may have major design flaws. This group is
[11] [93] [94] [95]
important because these studies have made LESI accepted in clinical practice and set the standard for the method.
The second group contains the more recent randomized, controlled trials. However, these studies, [41] [96] [97] [98] [99]
reviewed by many prominent investigators, have yielded varied results. The third group is composed of systematic
reviews of the second group. Several techniques are employed to make groups comparable. But, as Watts
[4] [61] [100] [101]
pointed out, a meta-analysis does not replace a large multicenter trial and false conclusions may be drawn. [101]
EARLY STUDIES
In the United States, Goebert and colleagues were the first to report the use of epidural steroid injections in a
[10]
series of 113 patients with radicular pain. They used an injection of 10 to 30 mL of 1% procaine with 125 mg of
hydrocortisone depending on the site of injection using a cervical, thoracic, lumbar, or sacral approach. The overall
success rate in this uncontrolled study was reported at 72% in the first 3 months after injection.
Beliveau studied 48 patients with unilateral sciatica in a prospective, randomized, nonblinded, controlled study.
[93]
Caudal injections of 42 mL of 0.5% procaine in normal saline were given with 80 mg methylprednisolone versus
853
saline and procaine without the steroid. There was no difference between the groups; improvement was
approximately 70% in either group. [93]
Swerdlow and Sayle-Creer studied 325 patients with lumbociatic syndrome, who were treated by injection of
[11]
normal saline, local anesthetic, or methylprednisolone in the epidural space. The caudal or lumbar route was chosen
randomly. They found no difference between the results produced by saline or local anesthetic. Overall, treatment
with methylprednisolone gave better results. There was no difference in the effectiveness between lumbar and
caudal injections. [11]
In a larger retrospective study of 500 patients with lumbosciatic syndrome, Warr and coworkers treated a [95]
heterogeneous patient population by administering 40 mL of 0.75% lidocaine with 80 mg of methylprednisolone and

25 mg hydrocortisone injected into the lumbar epidural space. This was followed by sciatic nerve stretching and
spine manipulation. They reported a success rate of 69% and 46%, respectively, in patients with duration of
symptoms of less than 1 year and longer than 1 year. They recommended a repeated injection, because this treatment
resulted in a 58% success rate in patients who did not respond to a single injection. [95]
Another retrospective analysis was performed by Berman and colleagues on 367 patients with lumbosciatic leg
[94]
pain, which resulted in a similar 65% response rate in selected patients given 0.5% bupivacaine and 100 mg
methylprednisolone. They found that an excellent response was more likely in the subacute group (i.e., patients with
symptoms for <3 months). [94]
Hickey performed a noncontrolled, prospective study on 250 patients with low back pain and radiculopathy. Only
[102]
27% of these patients felt better after one epidural injection. The second epidural injection added 44% to the
improved group, and 39% needed three epidural injections for an overall success rate of 88%.
In the United States, the results from these early studies, among others, have led to the current standard of practice
and can be summarized as follows:
1. Epidural steroid injections (ESI) is indicated for patients with back pain accompanied by radicular pain.
Efficacy is reported between 25% and 89%, with an average of 60%. Efficacy in less specific cases, such as
spinal stenosis, spondylosis, and spondylolisthesis, is not clearly defined. [10] [11] [77] [94] [95] [101]
2. Epidural steroid injections seem to be more effective in early stages (<3 months) of back pain with or
without radiculopathy. [10] [94] [95]
3. Repeated epidural steroid injections are more effective. However, there is no clinical benefit beyond three
injections. [95] [102]
4. Onset of pain relief occurs in most patients after the second day. [103]
5. No significant difference can be demonstrated between the caudal and lumbar approaches to the epidural
space.[11]
6. Corticosteroids are more effective than either local anesthetic or saline injections. Dilution with either local
anesthetic or saline demonstrates comparable results. [11]
7. The volume of the injection depends on the site of the injection. In general, larger volumes do not offer an
advantage. [104]
RANDOMIZED CONTROLLED TRIALS
Dilke and associates conducted a double-blind, randomized trial on 100 patients with degenerative disc disease and
[98]
unilateral sciatica with neurologic deficit. Patients received either 80 mg of methylprednisolone in 10 mL saline, or
1 mL of normal saline injected into the interspinous ligament. Patients from these comparable groups who received
epidural steroids manifested improvement judged by decreased use of analgesics. A significantly larger number of
patients had clear pain relief at timed post-treatment assessments. These patients required fewer surgical referrals
and had a significant reduction in time to return to work. There was no difference with respect to neurologic deficit
and straight leg raise test.
In contrast to these positive findings, Snoek and colleagues performed a double-blind, randomized study on 51
[99]
highly selected patients with lumbar root compression syndrome. All patients had symptoms, neurologic deficit, and
myelographic findings consistent with herniated lumbar disc. The control group received 2 mL of normal saline and
the treatment group 80 mg of methylprednisolone in 2 mL of normal saline injected into the epidural space at the
level of the lesion. Although both groups showed improvement, they were not statistically different.
854
Differences in results of the studies by Dilke and Snoek could be attributed to the different injection volumes
[98] [99]
used and the timing of post-treatment assessment. Whereas Snoek evaluated patients between 24 and 48 hours after
the injection, Dilke did his posttreatment assessment after 6 days. Green and coworkers found that 37% of [103]
responders to epidural steroids manifested improvement within 2 days, and 59% experienced relief between 4 and 6
days. On the other hand, the control group in the study by Snoek was more similar to the treatment group than in
Dilkes' study.
Cuckler and colleagues studied 73 patients with lumbar radicular pain syndromes in a prospective, randomized,
[96]
double-blind study. The patients received either an epidural injection of 80 mg of methylprednisolone in 5 mL of

normal saline and 2 mL of 1% procaine or, in the control group, 5 mL of 1% procaine and 2 mL normal saline. The
authors found some short-term improvement in approximately 60% of the patients, but they could not demonstrate a
significant difference between the two groups. However, patients were initially evaluated after 24 hours, whereas
long-term assessment was done mainly by telephone. All injections were given at the L3 to L4 level regardless of
pathology, and the important second epidural steroid injection was given in both treatment and control groups for
ethical reasons.
More recently, Carette and associates conducted a blinded, placebo-controlled trial in 158 patients with sciatica
[97]
caused by herniated nucleus pulposus. Patients were randomized to receive injections with either 2 mL of
methylprednisolone in 8 mL normal saline or placebo injection of 1 mL of normal saline in the epidural space.
Injections were repeated at 3 and 6 weeks depending on the response. In this carefully conducted study, the authors
were able to show significant reduction of sensory deficit improvement in finger-to-floor distance, and relief from
leg pain in the treatment group at 3 weeks and 6 weeks but not at 3 months. Differences in other measures, such as
the straight leg raise test, motor deficit, and several pain and disability scores, did not reach statistical significance.
At 12 months, the probability of surgery in the treatment and the control groups was similar (i.e., approximately
25%). The authors concluded that the treatment might have resulted in short-term improvement; however, it offered
no significant functional benefit and did not reduce the need for surgery.
This study has been criticized for several reasons. Prior studies indicated that the success rate of epidural steroid
injections might be remarkably higher in acute back pain with sciatica, usually defined as symptoms lasting less
than 3 months. Patients complaining of leg pain for more than 4 weeks but less than 1 year (median duration of
symptoms was 13 weeks in both groups) were included in Carette's study. Therefore, patients with a more chronic
type of back pain and radiculopathy might have diluted the pool of patients. Considering the variety of patients with
respect to signs and symptoms and the number of outcome measures, one might question the statistical power of this
investigation. In addition, as is true for many clinical trials, the clinical background from which an investigation
[89]
originates may introduce a bias. In this case, the outcome measure, “requirement for surgery,” could be interpreted
differently by the neurosurgeon and the anesthesiologist.
SYSTEMATIC REVIEWS
Many investigators have reviewed the literature regarding LESI. However, conclusions and
[3] [18] [58] [60] [105]
recommendations are as variable as the results of the studies under review. Several more systematic reviews have
addressed the efficacy of LESI.
Koes and coworkers reviewed 15 trials subject to certain conditions of design, in which a detailed analysis of the
[4]
quality of the method used in each study was evaluated. In the five highest ranked studies, it was found that two
studies had a favorable outcome. Of the next six studies, four had positive outcomes. Overall, the authors concluded
that the efficacy of epidural steroid injections had not been established and that benefits, if any, seemed to be of
short duration only.
This analysis, however, was based on generalized criteria for the quality of a trial. For the specific question as to
[106] [107]
whether epidural steroids have benefit, certain essential parameters, such as patient selection or the validity of an
outcome measure, may not have been given sufficient weight.
This review was also criticized by McQuay and Moore. They stated that the study by Koes and coworkers was
[100] [4]
merely an in-depth examination of the quality of methods used in the trials rather than a meta-analysis of their
results. In contrast, efficacy was investigated by a meta-analysis of all 11 randomized studies, involving a total of
907 patients. Data analysis used O-E differences (number of responders in the experimental group minus the
numbers of responders in the control group) and odds ratios were calculated. Thus, patients in one trial were never
compared with patients in another. Little evidence of significant heterogeneity was found; short-term effects of
epidural steroid injections increased the odds ratio of pain relief to 2.6. For long-term pain-relief, the odds ratio was
1.8. The investigators concluded that epidural administration of corticosteroids was effective in the management of
855
lumbosacral radicular pain. In a similar analysis, Merry and associates arrived at the result that epidural
[100] [101] [61]
steroids were significantly more effective than either saline or local anesthetics alone.
McQuay and Moore elaborated on the work of Watts and Silagy. They concluded from these studies that
[100] [101]
epidural steroid injections were effective. To answer the question of how effective this treatment was, these
investigators reanalyzed the same data and added the study by Carette and associates, in which they used the number
needed to treat (NNT) as a measure of clinical benefit. They found that short-term pain relief of 75% or greater
occurred in 1 out of 7 patients. Long-term pain relief of 50% or greater occurred in 1 out of 13 patients ( Table 34–
2 ). They concluded
TABLE 34-2 --
Improved on Relative Benefit

Trial Improved on Epidural Steroid Control (95% CI) NNT (95 % CI)
SHORT-TERM RELIEF (1–60 d)
Beliveau[93] 1971 18/24 16/24 1.1 (0.8–1.6) 12 (3–00)
Breivik et al[108] 1976 9/16 5/19 2.1 (0.9–5.1) 3.3 (1.6–00)
Bush and Hillier[109] 1991 8/12 2/11 3.7 (0.98–13.7) 2.1 (1.2–7.5)
[97]
Carette et al 1997 25/78 23/78 1.1 (0.5–2.4) 29 (5.5–00)
Cuckler et al[96] 1985 12/19 8/31 1.1 (0.5–2.4) 33 (4–00)
Dilke et al[98] 1973 21/35 11/36 2.0 (1.1–3.4) 3.5 (1.9–14)
Klenerman et al[110] 1984 15/19 32/44 1.1 (0.8–1.5) 17 (3–00)

[111]
Mathews et al 1987 14/21 18/32 1.2 (0.8–1.8) 10 (3–00)
Popiolek et al[112] 1991 18/28 8/30 2.4 (1.3–4.6) 2.6 (1.6–7.2)
Ridley et al[113] 17/19 3/16 4.8 (1.7–1.3) 1.4 (1.1–2.1)
Snoek et al[99] 1977 8/27 5/24 1.4 (0.5–3.8) 11 (3–00)
COMBINED SHORT-TERM RELIEF (>75%) 165/319 131/345 1.5 (1.2–1.9) 7.3 (4.7–16)
LONG-TERM RELIEF (12–52 wk)
Bush and Hillier[109] 1991 10/12 7/11 1.3 (0.8–2.2) 5.0 (1.8–00)
Carette et al[97] 1997 41/74 43/77 1.0 (0.7–1.3) 00
Cuckler et al[96] 1985 11/46 4/27 1.6 (0.6–4.6) 10.99 (3.66–00)
Dilke et al[98] 1973 16/43 8/38 1.8 (0.9–3.7) 6.3 (2.8–00)
Mathews et al[111] 1987 9/23 14/34 0.95 (0.5–1.8) 00
Swerdlow and Sayle-Creer[11] 1969 76/117 98/208 1.4 (1.1–1.7) 5.6 (3.5–14)
COMBINED LONG-TERM RELIEF 163/315 174/395 1.3 (1.1–1.5) 13 (6.6–314)
Relative benefit and number needed to treat (NNT) were calculated for this table. CI, confidence interval.
From McQuay HJ, Moore RA: Local anesthetics and epidurals. In Wall PD, Melzack R (eds): The Textbook of Pain, 4th ed. New York, Churchill Livingstone, 1999.
that, given the data available, results should be interpreted in the clinical context: “In the case of chronic painful
disease, intervention may be attractive even if the success rate is far lower than would be acceptable in acute
postoperative pain.” [100]
Although these reviews support the use of epidural steroid injections, it must again be emphasized that a meta-
analysis does not replace a large multicenter study and may lead to erroneous conclusions. On the other hand, the [101]
data do not establish lack of efficacy of epidural steroid injections. Most pain management practitioners have had
some degree of success with epidural steroid injections. In addition, the findings by Watts and McQuay and
colleagues are not inconsistent with the experience in clinical practice. Therefore, until a large multicenter study
[100] [101]
is available, it seems reasonable to assume the efficacy of epidural steroids in selected patients.
Duration of the effect of epidural steroids has not been established. However, several studies have shown decay in
the overall success rate over time. [59] [86] [96] [98] [103]
In a carefully conducted study by White and colleagues, a decrease in success rate was observed, from 82% on the
[86]
first day to 7% at 6 months. Only 4 out of 300 patients were free from pain after 2 years. This poor result is thought
to be the result of a wide range of indications these investigators used for epidural steroid injections. In their [58]
randomized controlled study, Carette and associates were not able to demonstrate any difference between the
[97]
treatment and control group after 3 months.
Several factors have been shown to affect the outcome of LESIs. The nerve root is the main target of epidural
steroid injections. However, the underlying pathologic processes causing nerve root irritation may vary. Use of
epidural steroid injections is questionable in patients with spinal stenosis, spondylosis, intervertebral narrowing by
856
osteophytes, or spondylolisthesis. Because proper correlation of the clinical syndrome with the underlying pathology
is not always reliable, selection of appropriate candidates for epidural steroid injections may be difficult.
[114]
Ciocon and Galindo-Ciocon studied 30 elderly people with documented spinal stenosis. The patients received
[115]
three steroid injections via the caudal approach. An average decrease from 3.5 to 1.5 on a pain scale that ranged
from 1 to 5 was reported. The beneficial effects lasted from 4 to 10 months.
More recently, in a randomized controlled trial, Fukusaki and coworkers investigated the effect of ESI on 53
[116]
patients with degenerative spinal canal stenosis. The selection criteria included symptoms of unilateral or bilateral
pseudoclaudication and intolerable leg pain after walking a distance of less than 20 m. The investigators were unable
to show a beneficial effect of ESI in these patients.
The use of ESI in patients with prior surgery on the spine is highly controversial. One older study reported a high
success rate (76%) after three caudal injections of 125 mg of hydrocortisone acetate and 30 mL of 1% procaine [10]
More recently, Devulder and coworkers used a randomized, single-blind design to compare steroid
[12]
(methylprednisolone) with a local anesthetic (bupivacaine) combined with hyaluronidase with a local anesthetic
given by the transforaminal approach. After 6 months, 27% of all patients obtained more than 50% pain relief. There
was no difference in efficacy between the two groups. [12]
Cervical Epidural Steroid Injections
Information on cervical epidural injection is limited and may reflect a lack of experience with this technique.
Purkins, in 1986, reported experience with over 113 cervical epidural steroid injections administered to 58 patients
[117]
who had pain for more than 6 months that was attributable to such diverse etiologies as osteoarthritis, degenerative
joint disease, chronic cervical sprain, and flexion-extension injuries. Pain relief was rated as greater than 50% by
roughly two thirds of the study group after 3 weeks.
Rowlinson and Kirschenbaum reported a retrospective study of 45 cervical epidural steroid injections
[118]
administered to 25 patients who had cervical radiculopathy. Sixty-four percent of the patients achieved good or
better results after an average of 1.6 treatments. In 1989, Cicala and coworkers published the follow-up results of
[119]
79 patients who had received cervical epidural steroid injections for a variety of conditions including spondylosis,
strain, and a miscellaneous group. Of the evaluable patients at 6 months of follow-up, 56% of the spondylosis group
reported excellent results and 56% of the strain group reported excellent results. Only one patient in the
miscellaneous group reported excellent results; good results were indicated by 19%. In total, 41% of the group in its
entirety reported excellent results at 6 months.
A series of 16 patients treated with epidural steroid injections for complaints of severe intractable pain in the neck
and arm associated with numbness in an appropriate radicular distribution was reported by Warfield and
colleagues. Duration of symptoms was longer than 3 months. Up to three injections of methylprednisolone in 5
[120]
mL of normal saline were given. Twelve patients reported a beneficial response. The duration of response for all but
one patient was less than 1 year. Six patients had improved neurologic findings.These studies supported the use of
epidural steroids in patients who had neck pain with or without radiculopathy. However, no randomized controlled
studies exist to establish the role of cervical epidural steroid injections. Electromyographic results, compiled during
documentation of radicular symptoms, did not correlate well with the likelihood of response to epidural steroid
injections.
INDICATIONS
The principal indication for epidural corticosteroid injection is nerve root irritation. This irritation can result from
mechanical pressure, inflammation, ischemia, or a combination of these three processes. Nerve root irritation
expresses itself as radicular pain and may be associated with neurologic deficits in the distribution of the nerve root.
Classically, the patient has sharp, shooting pain that radiates to the leg and below the knee. Patients with upper
extremity radiculopathy may not have the distinct symptoms of shooting pains below the elbow. Frequently, there is
an increase in pain with coughing, sneezing, or straining. Onset of symptoms is often associated with lifting or
twisting injury to the spine. Repetitious strain on the spine can also be contributory, as can overall poor health,
fatigue, and anxiety. [105]
857
The most significant finding in physical examination is result of the straight leg raise test. In one study, all [56] [60] [102] [108]
patients with nerve root swelling confirmed by CT had a positive straight leg raise test at 50 degrees or less. The [56]
femoral nerve tension test and tension tests of the major nerves of the upper extremity are less specific. Presence of
neurologic deficit correlates well with nerve root irritation. [102] [118] [120]
Laboratory studies are less helpful. Eighty-five percent of patients with low back pain cannot be given a definitive
diagnosis because of poor correlation among symptoms, pathology, and imaging results. Indeed, poor correlation [114]
between radiographic findings and symptoms is a consistent finding in several studies. [121] [122] [123]
Selection of the appropriate candidate for ESI is not always easy. The patient population with back pain, whether or
not accompanied by radiculopathy, is not a homogeneous group. First, there is a wide range of pathologic processes
that may be the cause of patients' symptoms. Classically, radicular pain is associated with degeneration and
herniation of an intervertebral disc. However, stenosis of the central or foraminal canal by osteophytes, compression
fractures, or tumor infiltration may cause a typical radiculopathy as well. Second, patient-dependent factors directly
related to the pain itself (nature, onset, duration, previous treatments, including surgery) or indirectly related factors
(sleep deprivation, stress) play a roll in the success of ESI, as do factors related to socioeconomic status (age,
education, marital status, employment, litigation, compensation) and psychological issues. [124]
Factors that contributed to a less favorable outcome for patients were identified by Abram and Hopwood and
included unemployment, wage compensation, long duration of symptoms, and nonradicular pain complaints. [124]
Jamison and colleagues found the following factors to be the best predictors of poor outcome after ESI: number of
[125]
previous treatments, amount of medication taken for pain, presence of pain independent of activity, and nonradicular
nature of back pain. Sandrock and associates found the most important factors to be accuracy of diagnosis,
[125] [126]
duration of symptoms, history of previous surgery, age of patient, and proper location of the needle. As Rowlinson [126]
stated: “It is clearly a challenge to select those patients who meet criteria for epidural steroid injections and still have
enough flexibility in their attitude and behavior to respond positively to a marked reduction in pain by regaining a
productive physical and emotional approach to life.” [105]
In summary, based on the previous considerations and the literature currently available, the following criteria can be
used to select patients for epidural steroid injections:
1. Evidence of root involvement [58] [88] [92] [105] [108] [127]
2. The objective of producing short-term pain relief along with rehabilitation [88]
3. Absence of contraindications such as infection, coagulopathy, history of untoward reaction to steroids, or

poorly controlled diabetes
4. Absence of a favorable response after 4 weeks of conservative treatment [88]
Patients should belong to one of the following groups [74] [92] [105]
:
1. Patients with radicular pain and a corresponding sensory change

2. Patients with clinically significant herniation of a disc, diagnosed by characteristic physical or laboratory
findings with symptoms
3. Motivated patients who have postural back pain with radicular-like features
4. Patients with cancer in whom tumor infiltration of the nerve root may cause radicular pain
5. Patients with acute back pain and radicular symptoms superimposed on chronic back pain
Safety of Epidural Steroid Injections
Few complications of ESI have been reported in the literature, which now encompasses more than 6000 cases. More
complications are related to the invasive nature of the procedure than to the procedure itself. Symptoms may include
nausea, mild headache, dizziness, vasovagal reactions, and other transient benign phenomena. Only four minor [128]
complications of this nature and no major complications were reported in a large series of 5334 epidural steroid
injections. It is noteworthy that all these procedures were performed under fluoroscopy with epidurography. [84]
A potentially serious complication is direct damage to the nerve root. Two patients with numbness in a dermatome
were reported in a series of 58 injections ; neurologic deficit was transient in one patient but persistent in the other.
[117]
Intrinsic spinal cord damage after cervical epidural steroid injections has been reported but seems to be very rare. [129]
The most common technical complication of epidural steroid injections is unintentional puncture of the dura. The
incidence ranges somewhere between 1% and 5%. The potential danger of an inadvertent corticosteroid injection
into the subarachnoid space after accidental dural puncture exists but is probably clinically insignificant. [77] [80] [81]
858
In a large series of 790 patients undergoing cervical epidural injections, two dural punctures were reported. Both
patients developed postdural puncture headaches and were treated with autologous blood patches of 7 mL. [128] [130]
A case of epidural hematoma after cervical epidural steroid injection has been reported. Surgical decompression was
required. [131]
Injection of corticosteroids into the epidural space is generally considered to be a safe procedure, but subarachnoid
injections and epidural injections have been associated with rare but serious complications, including adhesive
arachnoiditis, meningitis, and transient and permanent paralysis.
[132] [133]
Durocutaneous fistulas have been
[134] [127] [128]
reported. These fistulas may be related to poor wound healing commonly associated with the use of corticosteroids.
[128]
Case reports have documented the development of epidural lipomatosis after the administration of multiple epidural
steroid injections. Thecal sac compression is a potential complication. Fortunately, the lipomas disappeared after
discontinuation of the injections, as demonstrated by sequential magnetic resonance imaging studies. [136]
NEUROTOXICITY
Several studies have examined the effect of epidural or subarachnoid deposteroid injections on neural tissues and
meninges.
Seghal and coworkers injected methylprednisolone into the subarachnoid space of a human and found a transient
[137]
increase in CSF protein and pleiocytosis that persisted for weeks. However, a similar response can be seen with
[137]
injections of normal saline. [138]
A single-shot epidural injection (with Aristocort) in a cat model showed minor inflammatory changes after 30 days
and nearly complete resolution after 120 days. The investigators concluded that there was no evidence of tissue
damage compared with matched controls. [139]
Depo-Medrol contains polyethylene glycol, an agent known to cause damage to connective tissue, nerves, and
muscle fibers. Cicala and associates injected Depo-Medrol 2 mg/kg into the epidural space of rabbits. After 4 or
[80] [140]
10 days, there was a complete lack of inflammatory changes or fibroblast activity. In addition, it was shown that [140]
the 3% concentration of polyethylene glycol used in clinical practice was not neurotoxic. Both Delaney and [58] [139]
Cicala used single-shot epidural steroid injections, whereas in clinical practice multiple injections may be given.
[148]
The effect of four repeated epidural Aristocort injections, each 5 days apart, was studied by Abram and colleagues [141]
in a rat model. The investigators were not able to show histologic changes or neurotoxic effects.
Latham and associates investigated the intrathecal injection of various volumes and doses of Celestone
[142]
Chronodose (betamethasone) in 20 sheep. No animal that received 1 mL (5.7 mg) of Celestone Chronodose
[142]
exhibited any pathologic reaction in the meninges or neural tissue, even after repeated injections. At larger doses (2
to 16 mL), mild to severe inflammation and subarachnoid fibrosis were found. The authors concluded that small
amounts (1 mL) of Celestone Chronodose are safe, but larger doses form a potential hazard of arachnoiditis.
ARACHNOIDITIS
Arachnoiditis has been associated with spinal corticosteroid injections in several studies. However, arachnoiditis [80] [92]
as a result of spinal corticosteroid injections should be differentiated from arachnoiditis as a result of spinal
surgery, use of contrast agents, or underlying disease for which the patient is treated. Indeed, chronic
[143] [144]
arachnoiditis may be the result of fibrosis and adhesions associated with degenerative disc disease and chronic nerve
root compression. [145]
The cause of arachnoiditis has been attributed to the additives of the corticosteroid-containing solutions. Aristocort
and Depo-Medrol contain the preservatives glycol and benzyl alcohol. Neurotoxicity at a concentration of 3%
polyethylene glycol, the concentration used in clinical practice, was not shown to be significant. However, fibrosis [146]
and adhesions leading to arachnoiditis are not equivalent to neurotoxicity. Signs of inflammation and fibrosis
observed in the investigation by Latham and coworkers may be due to the vehicle benzyl alcohol, a preservative
used in many corticosteroid preparations.
Wilkinson reviewed the literature on the safety of subarachnoid steroid injections and concluded that most of the
[81]
evidence of neurologic injury after intrathecal injections is circumstantial. If such a relationship exists, arachnoiditis
is more likely with higher doses of corticosteroids or multiple injections. Indeed, in eight series of subarachnoid
steroid injections involving 358 patients, no complications of arachnoiditis were reported. [135]
859
Based on extrapolation of the concerns with subarachnoid injections, use of epidural steroid injections has been
questioned as well—for example, through the mechanism of accidental dural puncture. The association between [80]
epidural steroid injections and arachnoiditis is very weak. Case reports of arachnoiditis after an epidural steroid
injection are exceedingly rare. In a review of 64 studies of epidural steroid injections that included nearly 7000
[147] [148]
patients, arachnoiditis was not a reported complication, but in approximately half of these patients, the issue of
[92] [136]
complications was not addressed.
ASEPTIC MENINGITIS
Few reports have documented aseptic meningitis after subarachnoid steroid injections. Even fewer have been [92] [136]
reported after epidural steroid injections. The syndrome is characterized by fever, nausea, headaches, and
[149]
neurologic signs, including burning pain in the lower extremities, convulsions, and confusion after spinal steroid
injections. CSF studies may reveal pleocytosis, roughly proportional to the steroid dose given, elevated protein, [137]
and low glucose. Cultures are negative for bacteria, fungi, and mycobacteria. Changes in cell count or protein
content of CSF are not obligatory after subarachnoid steroid injections; on the other hand, pleocytosis may occur
after the subarachnoid injection of normal saline alone. Symptoms are of short duration, as are CSF abnormalities,
[151]
and no long-term complications have been reported. [92] [127]
EPIDURAL ABSCESS AND BACTERIAL MENINGITIS
Bacterial meningitis seems unlikely in the absence of dural puncture. The few cases that are reported are either
unusual infections (i.e., tuberculosis and torula), not well documented, or both. [133] [151] [152]
Epidural abscess after epidural steroid injection has been reported but is rare. Diabetes seems to predispose
[153] [154] [155]
patients to this complication. Staphylococcus aureus is most often implicated, presumably through
[133] [151] [152]
contamination by skin flora. [156]
In a large multicenter study reported in 1999, it was found that epidural abscess as a complication of epidural
catheter placement was more common than once thought. Corticosteroids may be associated with an increased
[156]
risk of epidural abscess, as was suggested in a report by Lowell and colleagues, in which 3 of 31 patients who
[157]
received epidural methylprednisolone during lumbar microdiscectomy developed an epidural abscess. Four hundred
patients undergoing the same procedure without intraoperative application of corticosteroids did not develop this
complication.
SYSTEMIC EFFECTS
Epidurally injected corticosteroids in conventional doses have been reported to cause iatrogenic Cushing's syndrome
and adrenal suppression. [158] [159] [160]
Acute suppression of adrenocorticotropic hormone and plasma cortisol levels can occur in the absence of cushingoid
features. The duration of suppression varies from approximately 2 to 4 weeks, depending on dose and age. [159] [162]
Cushingoid lesions, including moon facies, abnormal fat depositions, and skin lesions can last for several months.
Indeed, cortisol levels are elevated for more then 2 weeks after the injection of methylprednisolone into the epidural
space. [11]
The exact mechanism by which epidural steroids suppress the neuroendocrine axis remains unclear. Slow release
from the epidural space is most likely, because intra-articular injected triamcinolone can be found in the systemic
circulation for up to 3 months. A central mechanism, through absorption into the CSF, is less likely because the
[162]
dura acts as a barrier to depot steroids. [138]
Because corticosteroids increase blood glucose concentration by an increase in glycogenolysis and neoglucogenesis,
epidural corticosteroids may increase the difficulty of controlling blood sugar levels in diabetic patients.
REFERENCES
1. Nachemson A: Advances in low back pain. Clin Orthop 200:266–278, 1985.
2. Racz GB, Heavner JE, Raj PP: Epidural neuroplasty. Semin Anesth 16:302–312, 1997.
860
3. Bogduk N, Brazer G, Christophidis N, et al: Epidural Use of Steroids in the Management of Back Pain and Sciatica of Spinal Origin. Canberra,
Australia, Australian National Health and Medical Research Council, 1994.
4. Koes BW, Scholten JPM, Mens JMA, et al: Epidural steroid injections for low back pain and sciatica: An updated systematic review of
randomized clinical trials. Pain Digest 9:241–247, 1999.
5. Viner N: Intractable sciatica—the sacral epidural injection—an effective method of giving relief. Can Med Assoc J 15:630–634, 1925.
6. Evans W: Intrasacral epidural injection in the treatment of sciatica. Lancet 2:1225–1229, 1930.
7. Robecchi A, Capra R: Lidocortisone (composto F): prime esperienze cliniche in campo reumatologico. Minerva Med 98:1259–263, 1952.
8. BoudinG, Barbizet J, Guihard J: L'hydrocortisone intrarachnidienne, ses applications cliniques en particulier dans le traitement de la meningite
tuberculeuse. Bull Soc Med Hôp (Paris) 21:817–821, 1955.
9. Lievre JA, Block-Michel H, Attali P: L'injection transsacrée: Etude clinique et radiologique. Bull Soc Med Hôp (Paris) 73:1110–1117, 1957.
10. Goebert HW, Jallo SJ, Gardner WJ, et al: Painful radiculopathy treated with epidural injections of procaine and hydrocortisone acetate: Results
in 113 patients. Anesth Analg 40:130–134, 1961.
11. Swerdlow M, Sayle-Creer W: A study of extradural medication in the relief of the lumbosciatic syndrome. Anaesthesia 25:341–345, 1970.
12. Devulder J, Deene P, De Laat: Nerve root sleeve injections in patients with failed back surgery syndrome: A comparison of three solutions.
Clin J Pain 15:132–135, 1999.
13. Heavner J: Personal communication, 2001.
14. Barendse G, van Kleef J, Sluijter M: Technique of transforaminal epidural steroid injection. Pain Digest 9:254–255, 1999.
15. Kraemer J, Ludwig J, Bickert U: Lumbar epidural perineural injection: A new technique. Eur Spine J 6:357–361, 1997.
16. Lutz
GE, Vad VB, Wisneski RJ: Fluoroscopic transforaminal lumbar epidural steroids: An outcome study. Arch Phys Med Rehabil 79:1362–
1366, 1998.
17. Viton JM, Rubino T, Peretti-Viton P: Short-term evaluation of periradicular corticosteroid injections in the the treatment of lumbar
radiculopathy associated with disc disease. Rev Rheum Engl Ed 65:195–200, 1998.
18. Kepes ER, Duncalf D: Treatment of backache with spinal injections of local anesthesia, spinal and systemic steroids: A review. Pain 22:33–47,
1985.
19. Forrest JB: The response to epidural steroid injections in chronic dorsal root pain. Can Anaesth Soc J 27:40–46, 1980.
21. Steindler
A, Luck JV: Differential diagnosis of pain low in the back: Allocation of the source of pain by the procaine hydrochloride method.
JAMA 110:106–113, 1938.
22. Groen GJ, Baljet B, Drukker J: Nerves and nerve plexus of the human vertebral column. Am J Anat 188:282–296, 1990.
23. Cavanaugh JM: Neural mechanisms of lumbar pain. Spine 16:1804–1809, 1995.
24. WoolfCJ, Safieh-Garabedian B, Ma QP: Nerve growth factor contributes to the generation of inflammatory sensory hypersensitivity.
Neuroscience 62:327–331, 1994.
25. Devor
M, Govrin-Lippman R, Raber P: Corticosteroids suppress ectopic neural discharge originating in experimental neurinomas. Pain
22:127–137, 1985.
26. Stolker B, Vervest ACM, Groen GJ: The management of chronic spinal pain by blockades: A review. Pain 58:1–20, 1994.
27. Goddard MD, Reid JD: Movements induced by straight leg raising in the lumbo-sacral roots, nerves and plexus and the intra pelvic section of
the sciatic nerve. J Neurol Neurosurg Psychiatry 28:12–18, 1965.
28. Mixter WJ, Barr JS: Rupture of the intervertebral disc with involvement of the spinal cord. N Engl J Med 211:210–215, 1934.
29. Kelly M: Pain due to pressure on nerves. Spinal tumors and the intervertebral disc. Neurology 6:32–36, 1956.
30. Kuslich SD, Ulstrom CL, Michael CJ: The tissue origin of low back pain and sciatica. Orthop Clin North Am 22:181–187, 1991.
31. Murphey F: Sources and patterns of pain in disc disease. Clin Neurosurg 15:343–350, 1968.
32. Smythe MJ, Wright V: Sciatica and the intervertebral disc: An experimental study. J Bone Joint Surg 40A:1401–1418, 1958.
861
33. Goupille P, Jayson MIV, Valat JP: The role of inflammation in disc herniation-associated radiculopathy. Semin Arthritis Rheum 28:60–71,
1988.
34. McLaughlinB, Weiss JB: Endothelial cell stimulating angiogenesis factor (ESAF) activates progelatinase (72 kDa type IV collagenase),
Prostostromelysin and procollagenase and reactivates their complexes with tissue inhibitors of metalloproteinases: A role for ESAF in non-
inflammatory angiogenisis. Biochem J 317:739–745, 1996.
35. Pankovich
AM, Korngold L: A comparison of the antigenic properties of nucleus pulposus and cartilage protein polysaccharide complexes. J
Immunol 99:431–437, 1967.
36. Saal JS: The role of inflammation in lumbar pain. Phys Med Rehab 4:191–199, 1990.
37. Lindahl O, Rexed D: Histological changes in the spinal nerve roots of operated cases of sciatica. Acta Orthop Scand 20:215–225, 1951.
38. McCarron RF, Wimpee MW, Hudkins PG, et al: The inflammatory effect of nucleus pulposus. A possible element in the pathogenesis of low
back pain. Spine 12:760–764, 1987.
39. Marshall LL, Trethewie ER, Curtain CC: Chemical radiculitis: A clinical, physiological and immunological study. Clin Orthop 129:61–67,
1977.
40. Habtemariam A, Gronblad M, Virri J: Immunocytochemical localisation of immunoglobulins in disc herniations. Spine 21:1864–1869, 1996.
41. Saal JS, Franson RC, Dobrow R, et al: High levels of inflammatory phopholipase A2 activity in lumbar disc herniations. Spine 15:674–678,
1990.
42. O'Donnel JL, O'Donnel AL: Prostaglandin E2 content in herniated lumbar disc disease. Spine 21:1653–1656, 1996.
43. Willburger RE, Wittenburger RH: Prostaglandin release from lumbar disc and facet joint tissue. Spine 19:2068–2070, 1994.
44. Chen C, Cavanaugh JM, Ozaktay C: Effect of phospholipase A2 on lumbar nerve root structure and function. Spine 22:1057–1064, 1997.
45. Gronblad M, Virri J, Ronkko S, et al: A controlled biochemical and immunohistol-chemical study of human synovial-type (group II)
phospholipase A2 and inflammatory cells in macroscopically normal, degenerated, and herniated human lumbar disc tissues. Spine 21:2531–2538,
1996.
46. Gronbald M, Virri, Tolonen J: A controlled immunohistochemical study of inflammatory cells in disc herniation tissue. Spine 19:2744–2751,
1994.
47. Hoyland JA, Freemont AJ, Jayson MIV: Intervertebral foramen venous obstruction: A cause of periradicular fibrosis? Spine 14:558–568, 1989.
48. Olmarker K, Rydevik B: Pathophysiology of sciatica. Orthop Clin North Am 22:223–233, 1991.
49. Olmarker K, Rydevik B, Holm S: Edema formation in spinal nerve roots induced by experimental, graded compression. Spine 14:569, 1989.
50. Jayson MIV, Keegan AL, Million R, Tomlinson I: A fibrinolytic defect in chronic back pain syndromes. Lancet 2:1186–1187, 1984.
51. Pountain GO, Kaegan AL, Jayson MV: Impaired fibrinolytic activity in defined chronic back pain syndromes. Spine 12:183–186, 1987.
52. Jayson MIV: Presidential address. When does acute back pain become chronic? Spine 1997; 22:1053–1056.
53. Sunderland S, Bradley KC. Stress-strain phenomina in human spinal nerve roots. Brain 84:120–125, 1961.
54. Sharpless
SK: Susceptibility of spinal roots to compression block. The research status of spinal manipulative therapy. In Goldstein M (ed):
NIH Workshop, February 2–4, 1975. NINCDS Monograph No. 15, 1975, pp 155–161.
55. Breig A: Biomechanical considerations in the straight leg raising test. Cadaveric and clinical studies of the effect of medial hip rotation. Spine
4:242–250, 1979.
56. Takata K, Inoue S, Takahashi K: Swelling of the cauda equina in patients who have herniation of lumbar disc: A possible pathogenesis of
sciatica. J Bone Joint Surg 70A:361, 1988.
57. Esteban
NV, Loughlin T, Yergey AL: Daily cortisol production rate in man determined by stable isotope dilution/mass spectometry. J Clin
Endocrinol Metab 72:39–45, 1971.
58. Benzon HT: Epidural steroids. In P Prithvi Raj (ed): Pain Medicine: A Comprehensive review. St. Louis, Mosby, 1996.
59. Arnhoff FN, Triplett HB, Pokorney B: Follow-up status on patients treated with nerve blocks for low back pain. Anesthesiology 46:170–178,
1977.
60. Yates DW: A comparison of the types of epidural injections commonly used in the treatment of low back pain and sciatica. Rheumatol Rehabil
862
17:181–186, 1978.
61. Merry
A, Schug SA, Rodgers A: Epidural steroid injections for sciatica and back pain: A meta-analysis of controlled clinical trials. Reg
Anesthesia 21:64, 1996.
62. Harley C: Extradural corticosteroid infiltration. A follow-up study of 50 cases. Ann Phys Med 9:22–28, 1967.
63. Olmarker K, Rydevik B, Nordborg C: Autologous nucleus pulposus induced neurophysiologic and histologic changes in porcine cauda equina
nerve roots. Spine 18:1425–1432, 1993.
64. Famaey JP: Phospholipases, eicosanoid production and inflammation. Clin Rheumatol 1:84–94, 1982.
65. Kaye
A, Nossaman BD, Smith DE: Effects of phopholipase A2, 12-lipoxygenase, and cyclooxygenase inhibitors in the feline pulmonary bed.
Am J Physiol 272:L573–579, 1997.
66. Andreatta-Van
LS, Romero MF, Khosla MC: Modulation of phospholipase A2 activity and sodium transport by angiotensin-(1–7). Kidney Int
44:932–936, 1993.
67. Haynes RC: Adrenocorticotropic hormone: Adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of
adrenocortical hormones. In Hardman JG, Limbird LE (eds): Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed. New
York, McGraw-Hill, 1996.
68. Takahashi H, Suguro T, Okazima Y: Inflammatory cytokines in the herniated disc of the lumbar spine. Spine 21:218–224, 1996.
69. FeldmanS, Behar AJ: Effect of intrathecal hydrocortisone on adhesive arachnoiditis and cerebrospinal fluid pleicytosis: An experimental study.
Neurology 11:251–256, 1955.
70. Haughton VM, Nguyen CM, Ho K-C: The etiology of focal spinal arachnoiditis: An experimental study. Spine 18:1193–1198, 1993.
71. Pateromichelakis S, Rood JP: Prostaglandin E2 increases mechanically evoked potentials in the peripheral nerve. Experientia 37:282–284,
1981.
72. Shao-Ying
H, Yi-Zhang C: Membrane receptor-mediated electrophysiological effects of glucocorticoid on mammalian neurons.
Endocrinology 124:687–691, 1989.
73. Johanson
A, Hao J, Sjolund B: Local corticosteroid application blocks transmission in normal nociceptive C-fibres. Acta Anesthesiol Scand
34:335–338, 1990.
74. Abram SE, Marsala M, Yaksh TL: Analgesic and neurotoxic effects of intrathecal corticosteroids in rats. Anesthesiology 81:1198–1205, 1994.
75. Fuxe K, Harfstrand A, Agnati LF, et al: Immunocytochemical studies on the localisation of glucocorticoid receptor immunoreactive nerve cells
in the lower brain stem and spinal cord of the male rat using monoclonal antibody against rat liver glucocorticoid receptor. Neurosci Lett 60:1,
1985.
76. Green NP: Dexamethasone in the management of symptoms due to herniated lumbar disc. J Neurol Neurosurg Psychiatry 38:1211–1217, 1975.
77. Winnie AP, Hartman JT, Meyers HL, et al: Pain clinic II: Intradural and extradural corticosteroids for sciatica. Anesth Analg 51:990–1003,
1972.
78. Abram SE: Subarachnoid corticosteroid injection following inadequate response to epidural steroids for sciatica. Anesth Analg 57:313–315,
1978.
79. Hartman JT, Winnie AP, Ramamrthy S, et al: Intradural and extradural corticosteroid injections for sciatic pain. Orthop Rev 3:21–24, 1974.
80. Nelson DA: Intraspinal therapy using methylprednisolone acetate. Spine 18:278–286, 1993.
81. Wilkinson HA: Intrathecal Depo-Medrol: A literature review. Clin J Pain 8:49, 1988.
82. El-Khoury G, Ehara S, Weinstein JN: Epidural steroid injection: A procedure ideally performed with fluoroscopy control. Radiology 168:554–
557, 1988.
83. Fredman B, Nun MB, Zohar E: Epidural steroids for treating “failed back surgery syndrome”: Is fluoroscopy really necessary? Anesth Analg
88:367–372, 1999.
84. JohnsonBA, Schellhas KP, Pollei SR: Epidurography and therapeutic epidural injections: Technical considerations and experience with 5334
cases. Am J Neuroradiol 20:697–705, 1999.
85. Steward HD, Quinell RC, Dann N: Epidurography in the management of sciatica. Br J Rheumatol 26:424–429, 1987.
86. White AH, Derby R, Wynne G: Epidural injections for the diagnosis and treatment of low-back pain. Spine 5:78–86, 1980.
87. Greenwood J, McGuire TH, Kimbell F: Study of the causes of failure in herniated intervertebral disc operation; analysis of 67 reoperated cases.
863
J Neurosurg 9:15–20, 1952.
88. Nash TP: Current guidelines in the use of epidural steroids in the United Kingdom. Pain Digest 9:231–232, 1999.
89. Hopwood MB: Lumbar epidural steroid injections: Is a clinical trial necessary or appropriate? Reg Anesth Pain Med 24:5–7, 1999.
90. Spitzer WO, Leblanc FE, DuPuis M: Report of the Quebec Task Force on Spinal Disorders. Spine 12:S9–S59, 1987.
91. Agency for Health Care Policy and Research: Acute low back pain problems in adults. Clinical Practice Guidelines No. 14. AHCPR
Publication No. 95-0642. December 1994.
92. Raj PP: Epidural steroid injections. Pain Digest 9:235–240, 1999.
93. Beliveau
P: A comparison between epidural anesthesia with and without corticosteroids in the treatment of sciatica. Rheumatol Phys Med
11:40–43, 1971.
94. BermanAT, Garbarinbo JL, Fisher SM, et al: The effects of epidural injection of local anesthetics and corticosteroids on patients with
lumbosciatic pain. Clin Orthop 188:144–151, 1984.
95. Warr AC, Wilkinson JA, Burn JMB, et al: Chronic lumbosciatic syndrome treated by epidural injections and manipulation. Practitioner 209:53,
1972.
96. Cuckler JM, Bernini PA, Wiesel SW, et al: The treatment of epidural steroids in the treatment of radicular pain. Anesthesia 25:346–348, 1970.
97. Carette S, Leclaire R, Marcoux S, et al: Epidural corticosteroid injections for sciatica due to herniated nucleus pulposus. N Engl J Med
336:1634–1640, 1997.
98. Dilke TFW, Burry HC, Grahame R: Extradural corticosteroid injection in the management of lumbar nerve root compression. BMJ 2:635–637,
1973.
99. Snoek
W, Weber H, Jorgensen B: Double blind evaluation of epidural methylprednisolone for herniated lumbar disc. Acta Orthop Scand
48:635–641, 1977.
100. McQuay HJ, Moore RA: An Evidence-Based Resource for Pain Relief. London, Oxford University Press, 1998.
101. Watts RW, Silagy CA: A meta-analysis on the efficacy of epidural corticosteroids in the treatment of sciatica. Anaesth Intensive Care 23:564–
569, 1995.
102. Hickey RJ: Outpatient epidural steroid injections and lumbosacral radiculopathy. N Z Med J 100:594–596, 1987.
103. Green PWB, Burke AJ, Weiss CA, et al: The role of epidural cortisone injection in the treatment of discogenic low back pain. Clin Orthop
153:121–125, 1980.
104. Heyse Moore GH: A rational approach to the use of epidural medication in the treatment of sciatic pain. Acta Orthop Scand 49:366–370, 1978.
105. Rowlinson JC: Epidural steroids: Do they have a role in pain management? APS J 3:20–27, 1994.
106. Feinstein AR: Clinical Epidemiology: The Architecture of Clinical Research. Philadelphia, WB Saunders, 1985.
107. Meinert CL: Clinical Trials: Design, Conduct and Analysis. New York, Oxford University Press, 1986.
108. Breivik
H, Hesia PE, Molnar I, et al: Treatment of chronic low back pain and sciatica. Comparison of caudal epidural injections of
bupivacaine and methylprednisolone with bupivacaine followed by saline. In Bonica J (ed): Advances in Pain Research and Therapy, vol 1. New
York, Raven Press, 1976, pp 927–932.
109. BushK, Hillier S: A controlled study of caudal epidural injections of triamcinolone plus procaine for the management of intractable sciatica.
Spine 16:572–575, 1991.
110. Klenerman L, Greenwood R, Davenport HT, et al: Lumbar epidural injections in the treatment of sciatica. Br J Rheumatol 23:35–38, 1984.
111. Mathews JA, Mills SB, Jenkins VM, et al: Back pain and sciatica: Controlled trials of manipulation, traction, sclerosant and epidural
injections. Br J Rheumatol 26:416–423, 1987.
112. Popiolek
A, Domanik A, Mazurkiewitz G: Epidural injections of steroids in the treatment of patients with sciatica in discopathy. Neurol
Neurochir Pol 25(5):640–646, 1991.
113. Ridley MG, Kingsley GH, Gibson T, et al: Outpatient epidural corticosteroid injection in the management of sciatica. Br J Rheumatol 27:295–
299, 1988.
114. Deyo RA: Fads in the treatment of low back pain. N Engl J Med 325:1039–1040, 1991.
864
115. Ciocon JO, Galindo-Ciocon D: Caudal epidural blocks for elderly patients with lumbar canal stenosis. J Am Geriatr Soc 42:593–6, 1994.
116. Fukusaki M, Kobayashi I, Hara T: Symptoms of spinal stenosis do not improve after epidural steroid injection. Clin J Pain 14:148–51, 1998.
117. Purkins EI: Cervical epidural steroids. Pain Clinic 1:3–7, 1986.
118. Rowlinson JC, Kirschenbaum LP: Epidural analgesic techniquesin the management of cervical pain. Anesth Analg 65:938–942, 1986.
119. Cicala RS, Thoni K, Angel JL: Long-term results of cervical epidural steroid injections. Clin J Pain 5:143–145, 1989.
120. Warfield CA, Biber MP, Crews DA: Epidural steroid injections as a treatment for cervical radiculitis. Clin J Pain 4:201–204, 1988.
121. Hitselberger WE, Witten RM: Abnormal myelograms in asymptomatic patients. J Neurosurg 28:204–206, 1968.
122. Thornbury JR, Fryback DG, Turski PA: Disk-caused nerve compression in patients with acute low back pain: Diagnosis. 183:731–738, 1993.
123. WieselSW, Tsourmas N, Feffer HI: A study of computer assisted tomography: 1. The incidence of positive CAT scans in an asymptomatic
group of patients. Spine 1984; 9:549–551.
124. Abram SE, Hopwood MB: Factors associated with failure of lumbar epidural steroids. Reg Anesth 18:238–243, 1993.
125. Jamison RN, VadeBocouer T, Ferrante FM: Low back pain patients unresponsive to an epidural steroid injection: Identifying predictive
factors. Clin J Pain 7:311–317, 1991.
126. Sandrock NJG, Warfield CA: Epidural and facet injections. In Warfield CA (ed): Principles and Practice of Pain Management. New York,
McGraw-Hill, 1993.
127. Abram SE: Treatment of lumbosacral radiculopathy with epidural steroids. Anesthesiology 91:1937–1941, 1999.
128. Haddox JD: Lumbar and cervical epidural steroid therapy. Anesth Clin North Am 10:179–203, 1992.
129. HodgesSD, Castleberg RL, Miller T: Cervical epidural steroid injection with intrinsic spinal cord damage. Two case reports. Spine 23:2137–
2142, 1998.
130. Waldman SD: Cervical epidural abscess after cervical epidural block with steroids. Anesth Analg 72:717–718, 1991.
131. Williams KN, Jackowski A, Evans PJ: Epidural hematoma requiring surgical decompression following repeated cervical epidural steroid
injections for chronic pain. Pain 42:197–199, 1990.
132. Ryan MD, Taylor TKF: Management of lumbar root pain by intrathecal and epidural injections of depot methylprednisolone acetate. Med J
Aust 2:532–534, 1981.
133. Shealy CN: Dangers of spinal injections without proper diagnosis. JAMA 197:156–158, 1966.
134. McLain RF, Fry M, Hecht ST: Transient paralysis with epidural steroid injection. J Spinal Disord 10:441–444, 1997.
135. Abram SE, O'Connor TC: Complications associated with epidural steroid injections. Reg Anesth 21:149–162, 1996.
136. Sandberg DI, Lavyne MH: Symptomatic spinal epidural lipomatosis after local epidural corticosteroid injections: Case report. Neurosurgery
45:162–165, 1999.
137. Sehgal AD, Tweed DC, Gardner WL, et al: Laboratory studies after intrathecal steroids. Arch Neurol 9:64–68, 1963.
138. Bedford THB: The effect of injected solutions on the cell count of the cerebrospinal fluid. Br J Pharmacol 3:80–83, 1948.
139. Delaney TJ, Rowlingson JC, Carron H, et al: Epidural steroid effects on nerves and meninges. Anesth Analg 59:610–614, 1980.
140. Cicala
RS, Turner R, Moran E, et al: Methylprednisolone acetate does not cause inflammatory changes in the epidural space. Anesthesiology
72:556–558, 1990.
141. Abram SE, Marsala M, Yaksh TL: Analgesic and neurotoxic effects of intrathecal corticosteroids in rats. Anesthesiology 81:1198–1205, 1994.
142. Latham JM, Fraser RD, Moore RJ: The pathological effects of intrathecal betamethasone. Spine 22:1558–1562, 1997.
143. Matsui H, Tsuji J, Kanamori Y: Laminectomy-induced: A post operative serial MRI study. Neuroradiology 37:660–666, 1995.
144. Dullerud R, Morland TJ: Adhesive arachnoiditis after lumbar radiculopathy with dimer-X and Depo-Medrol. Radiology 119:153–155, 1976.
145. Burton CV: Lumbosacral arachnoiditis. Spine 3:24–30, 1978.
146. Benzon HT, Gissen AJ, Strichartz GR, et al: The effect of polyethylene glycol on mammalian nerve impulses. Anesth Analg 66:553–559,
1987.
865
147. Rovira E, Garcia-Escrig M, Catala J: Chronic adhesive arachnoiditis following epidural paramethasone. Rev Neurol 25:2067–2068, 1997.
148. Sekal R: Epidural Depo-Medrol revisited. Med J Aust 3:688, 1982.
149. Morris JT, Konkol KA, Lonfield RN: Chemical meningitis following epidural methylprednisolone injection. Infect Med 11:439–440, 1994.
150. Bedford THB: The effect of injected solutions on the cell count of the cerebrospinal fluid. Br J Pharmacol 3:80–83, 1948.
151. Dougherty JH, Fraser RAR: Complications following intraspinal injections of steroids. J Neurosurg 48:1023–1025, 1978.
152. Roberts M, Sheppard GL, McCormick RC: Tuberculous meningitis after intrathecally administered methylprednisolone acetate. JAMA
200:190–192, 1967.
153. Chan S-T, Leung S: Spinal epidural abscess following steroid injection for sciatica. Spine 14:106–108, 1989.
154. Goucke CR, Graziotti P: Extradural abscess following local anaesthetic and steroid injection for chronic low back pain. Br J Anaesth 65:427–
429, 1990.
155. Knight JW, Cordingley JJ, Palazzo MG: Epidural abscess following epidural steroid and local anesthetic injection. Anaesthesia 52:576–578,
1997.
156. Wang LP, Hauerberg J, Schmidt JF: Incidence of spinal epidural abscess after epidural analgesia. Anesthesiology 91:1928–1936, 1999.
157. Lowell TD, Errico TJ, Eskenazi MS: Use of epidural steroids after discectomy may predispose to infection. Spine 25:516–519, 2000.
158. Edmonds LC, Vance ML, Hughes JM: Morbidity from paraspinal depo-corticosteroid injections for analgesia: Cushing's syndrome and
adrenal suppression. Anesth Analg 72:820, 1991.
159. Kay J, Findling JW, Raff H: Epidural triamcinolone suppresses the pituitary-adrenal axis in human subjects. Anesth Analg 78:501, 1994.
160. Knight CL, Burnell JC: Systemic side effects of extradural steroids. Anasthesia 35:593, 1980.
161. Gorski DW, Rao TLK, Glisson SN: Epidural triamcinolone and adrenal response to hypoglycemic stress in dogs. Anesthesiology 57:364–366,
1982.
162. Cook DM, Meikle AW, Bowman R: Systemic absorption of triamcinolone after a single intraarticular injection surpresses the pituitary-
adrenal axis [abstract]. Clin Res 36:121A, 1988.
866
Section V Chapter 35 - Facet Block and Denervation
Chapter 35 - Facet Block and Denervation

MAURICIO ORBEGOZO
PHILLIP S. SIZER JR.
When you take a long look at the history of zygapophyseal (facet) blocks as well as the literature providing evidence
for their effectiveness, you can see that they are characterized by periods of varying popularity. During different
historical epochs, the facet joints have been regarded as a significant factor in the pathogenesis of low back pain. At
other times, they have fallen victim to skeptics, who question the clinical relevance of the zygapophyseal joint. As
pain practitioners, some of us believe in an ideal model, wherein the pathogenesis of low back pain is a
multifactorial process. Additionally, this model suggests that there is always a prevalent factor. If this factor is
effectively treated, the cycle of pain can be interrupted and symptoms can be eradicated. Thus, in the search for this
prevalent factor, we embark on a series of diagnostic procedures and tests that do not always yield positive results.
In the case of facet joint pain, we have not discovered a clinical test or a pattern in a patient's presentation that can
reliably predict that a block could be effective. However, in the constant battle against back pain, we continue to use
facet blocks in our armamentarium and we attempt to justify performing them. In this chapter, we strive to shed
some light on this difficult topic as well as provide the pain practitioner with tools for patient selection and
techniques that are likely to increase the success rate of this difficult-to-treat pathology.
HISTORY
The first implication of the facet joint as a significant source of pain can be traced to 1911 and Joel
Ernest Goldthwaite. He referred to the zygapophyseal joints as the posterior articulations and stated
[1]
that asymmetry in their relationships could lead to low back pain and even to nerve root irritation. [1]
This concept was further elaborated by the Italian orthopaedic surgeon Vittorio Putti. In 1927, Putti [2]
observed the angles taken by the facet joints in the lumbar region and concluded that even though
there was individual variation in the facet orientation, a significant deviation could have deleterious
effects on the nerve root and produce arthritic changes in the joint itself. Around 1933, the facet
[2]
joint gained its greatest popularity, when Ghormley described the “facet syndrome.” Ghormley [3]
correctly stated that the facet joint was the only “true” joint of the vertebral column. In his
description of the “facet syndrome,” Ghormley commented on the difficulty, when formulating a
differential diagnosis, of explaining whether the facet joints produce pain or not.
In 1934, Mixter and Barr went on to suggest that the herniated intervertebral disc is a source of back
[4]
pain and nerve root compression. This could be considered as the transition point when facet joint
pain lost some of its popularity as a diagnostic favorite of clinicians. In 1941, Badgley refocused the [5]
clinician's interest on the zygapophyseal joint by suggesting that pain arising from the joints could
produce referred or radiating pain to the lower extremity in the absence of intervertebral disc
pathology. A few years earlier, Kellegren proposed the concept of the “sclerotomal” pain pattern. By
[6]
injecting 6% saline into associated spinal muscles and ligaments, he demonstrated that pain could be
referred to areas distant from the injection site, thus mimicking nerve root involvement. These
findings were later confirmed by Hirsch and colleagues. and then expanded by Mooney and
[7]
Robertson in 1976 when they performed fluoroscopically guided intra-articular injections of

[8]
hypertonic saline into the zygapophyseal joint to elicit a painful response and produce a map of pain
patterns.
Tremendous progress had been made in the previous 30 years toward the understanding of the facet
joint's role in low back pain. One of the major breakthroughs was the description of the nerve supply
to the joint by Fox and Rizzoli, and later by Nikolai Bogduk.
[9] [10] [11]
These discoveries facilitated the present standard of percutaneous facet denervation, which
constitutes the basis of our present treatment modality for facet joint pain.
Cervical facet joints have gained the attention of clinicians owing to the attention given to their
lumbar counterparts. Even though the explanation of a cervical origin for headache is ancient, the
implication of the cervical facet joints in headache can, in part, be attributed to Pawl in 1971. [12]
Similar publications are those of Hadden in 1941, Ramsey and Ramsey in 1948, Tarem and Kahn
[13] [14]
in 1962, and finally Brain and Wilkinson in 1967 and McNab and Mehta in 1973.
[15] [16] [17] [18]
Anatomy and Biomechanics

LUMBAR FACET JOINTS
As Ghormley stated, “The facet joints are the only true joints of the vertebral column.” They are the only joints that
[3]
permit movement of two intimately related cartilaginous articular surfaces in the axial skeleton. As bilateral, paired,
diarthrodial articulations, facet joints are composed of the inferior articular process of the vertebra above and the
867
superior articular process of the vertebra below ( Fig. 35–1 ). The superior parts (articular processes) are large,
concave, and face posteromedially. The inferior partes are smaller and face antero-laterally. The facet joints in [19] [20]
the lumbar vertebral column form the posterior aspect of the neural foramen. [21]
Figure 35-1 Lumbar facet joints illustrating the joints formed by the
inferior articular process (pars) (a) of the level above and the superior
articular process (pars) (b) of the level below. Note that this drawing is
from an oblique view from which most of the facet joints can be visualized
because of their orientation in the lumbar spine.
A capsule, which is lined by a synovial membrane, surrounds each joint. This capsule is approximately 1 mm thick,
inserts 2 mm below the articular margin, and encloses a space with a maximal volume capacity of 1 to 2 mL of
synovial fluid. The posterolateral aspect of this membrane is thick, tough, and fibrous. Additionally, the
[22] [23] [24]
ventromedial aspect is contiguous with the ligamentum flavum. The adipose tissue overlying the ligamentum flavum
in the superior aspect of the facet joint is intimately related to the neural root sleeve ( Fig. 35–2 ). This
[21] [25] [26] [27] [28]
relationship explains why the nerve root can be compromised in some instances of severe arthritis and joint
deformity. In the superior and inferior recesses of the facet joints, the capsule appears to be redundant, forming two
[29]
meniscoid structures; one superior and one inferior (see Fig. 35–2 ). In addition to containing synovial fluid,
[21] [28] [29]
this capsule may contribute to limiting the joint's range of motion. Finally, the articular surfaces are covered with
cartilage, which is relatively thick and prone to degenerate with age.
[30]
Biomechanically, the lumbar zygapophyseal joints are a part of a three-linked kinematic chain. This relationship [31]
between disc and joints promotes segmental stability, and time-related disc pathology can produce degeneration and
subsequent pain within the zygapophyseal joints. This chain reaction suggests that secondary disc pathology,
[32]
including zygapophyseal joint synovitis and chondropathy, arises from previous episodes of primary disc-related
disorders. In this context, the zygapophyseal joints serve two main functions. First, the joints guide and limit
[33]
motion of the vertebral column in various directions. Second, these joints share the burden of axial weight bearing
with the intervertebral disc. Two important characteristics of the joints permit them to guide and limit
[34] [35] [36] [37]
segmental range of motion. The first characteristic is the orientation of the articular surfaces. The facet [38] [39] [40] [41] [42] [43]
868
articular surfaces at L1 to L2 and L2 to L3 are oriented in a sagittal plane ( Fig. 35–3 ). As the levels progress [44]
caudally, the articular surface orientation rotates laterally from the sagittal plane toward the frontal plane
approximately 30 degrees to 75 degrees ( Fig. 35–4 ). At the level of L5 to S1 the articular surfaces can
[38] [39] [40] [41] [42] [43]
be oriented as much as 75 degrees from the sagittal plane. This configuration, in concert with the outer
[38] [39] [40] [41] [42] [43] [44]
anulus of the disc, constrains axial rotation in the upper lumbar levels where the orientation is more sagittal. The
[45] [44]
articular process orientation in the lower lumbar levels potentially allows more segmental rotation and may help to
constrain extension, as the inferior articular process of the superior bony segment can “bottom out” on the pars
interarticularis below. Conversely, this same orientation has little influence on flexion, which appears to be
[46]
primarily constrained by tension loading of the posterior anulus. [47] [48]
The second characteristic that may contribute to motion limits is the zygapophyseal capsule. To what degree the
capsular components contribute to motion control in the sagittal plane is controversial. Cyron and Hutton [23]
suggested that motion in the sagittal plane is limited by the capsular mechanism. These and other investigators [49]
suggested that the capsule is maximally stretched in hyperextension, as the articular processes slide over each
other. This may be supported by the parasagittal orientation of the elastic fibers within the internal lamina of the
[23]
fibrous capsule. However, Haher and colleagues later suggested that extension is not primarily constrained by the
[50] [51]
capsule but rather by the anulus. Thus, we can conclude that the capsule contributes to lumbar motion control, but
further investigations are necessary to elucidate the extent of that contribution.
Figure 35-2 A segmental cross-section through the facet joint and intervertebral foramen shows the mixed nerve root high up in the foramen
close to the weakened upper portion of the facet capsule and superior articular recess.(From Paris SV: Anatomy as related to function and pain.
Orthop Clin North Am 14:475–489, 1983.)
869
Figure 35-3 Anteroposterior view of the lumbar spine showing the sagittal plane
orientation of the superior lumbar zygapophyseal joints L1–2 and L2–3 (arrows).
In addition to guiding flexion and extension, the facet joint also serves as a harness for the posterior aspect of the
anulus of the intervertebral disc by preventing rupture due to extreme torsion, especially in the context of disc
degeneration. In 1970, Farfan and associates concluded that pure axial rotation of greater than 3 degrees can
[23] [45] [52]
cause rupture of the posterior anulus fibrosus. McFadden and Taylor studied the degree of pure axial rotation
[53]
achieved by the lumbar vertebral column in the sagittal plane. During this study, the authors concluded that
appreciable pure axial rotation is not available in the lumbar spine and that all rotation in the transverse plane is
accompanied by lateral flexion. Additionally, they suggested that the zygapophyseal joints permitted no gaping
during pure axial rotation, and if there were any gaping, that this
Figure 35-4 Oblique (A) and lateral (B) views of the lumbar vertebral column showing the orientation close to the frontal plane of the lower
lumbar zygapophyseal joints L4–5 and L5–S1 (arrows).
870
was a sign of segmental instability as a result of previous trauma.

The second function of the lumbar zygapophyseal joint is specifically related to weight bearing. Investigators have
demonstrated that the facet joints may bear about 16% of the total axial load in the normal lumbar vertebral
column. However, in instances of disc degeneration with resultant lumbar spondylosis, the load can increase
[34] [46] [54]
from 40% to 70%. As a result of disc degeneration, abnormal relationships between the articular surfaces of the
facet joint may lead to a subluxation. It has been universally demonstrated that when facet arthritis is observed,
[46] [55]
one finds accompanying disc degeneration at the same level. This, however, does not imply that all disc
[56]
degeneration initiates facet arthritis. For example, Schwarzer and coworkers attempted to determine the relative
[57]
contributions of the disc versus the zygapophyseal joint to patients' lumbar pain. They found that the association
occurred in only 3% of patients in a sample of 92 patients with back pain. The authors also concluded that about
75% of lumbar disc degeneration might not have evidence of facet arthritis.
Another important biomechanical characteristic is the concept of coupling. This concept suggests that a kinetic
movement of a body along a certain axis induces a simultaneous synkinetic movement over another axis. The [58]
strongest pattern of coupling in the extended lumbar spine is that of kinetic lateral (side) bending accompanied by
synkinetic contralateral axial rotation. This lumbar coupling pattern results in the pointing of the spinous processes
[58]
in the same direction as lateral bending ( Fig. 35–5 ). Additionally, abnormal or exaggerated coupling patterns
[59]
have been described as a possible sign of instability or pathology. Furthermore, Pearcy and coworkers
[60] [61]
and [62] [63] [64]
Gray and colleagues determined in radiologic studies of the moving spine that the L4 to L5 and L5 to S1 segments
[65]
were the most mobile segments, which in turn may account for the fact that these two levels are the ones responsible
for 30% of lumbar facet pathology. Concomitantly, these are the most commonly injured intervertebral discs in this
region of the spine.
In discussing the biomechanics of the lumbar region, it is important to mention that lumbar spondylosis, with disc
height loss and resultant facet subluxation,
Figure 35-5 This diagram summarizes the coupling of

lateral bending and axial rotation and depicts the
biomechanical subdivision of the spine. It can be
thought of in terms of the direction of movement of
spinous processes with left lateral bending. Note that in
the middle and lower thoracic spine, the axial rotation,
which is coupled with lateral bending, can be in either
direction. The direction of this axial rotation apparently
varies between different specimens. In the lumbar spine,
the spinous processes go to the left with left lateral
bending. The same pattern is also present at the
lumbosacral joint.
may produce compensatory mechanisms that involve spasms of the psoas major and quadratus lumborum. These
compensatory muscle activities may produce pressure on the zygapophyseal joints themselves. Consequently, in
871
treating patients with lumbar facet arthropathy, there may be a need for myoneural injections of the afore-mentioned
muscles to relieve spasm and reduce stress on the facet joint structures.
CERVICAL FACET JOINTS
The anatomy of the cervical facet joints is considerably different from that of the lumbar region. Although they are
still composed of the superior articular process of the vertebra below and the inferior articular process of the
vertebra above, their capsular anatomy, orientation, and biomechanics differ significantly from their lumbar
counterparts. The configuration of the joints also depends on the cervical level that is being addressed, as upper
cervical segments differ substantially from lower cervical segments.
The cervical spine is divided into distinct regions according to structure and function. The first two motion segments
of the cervical spine (C0–1 and C1–2) are atypical because an intervertebral disc is absent. Synovial articular facets
can be observed between C0 and C1 on the right and left sides of the foramen magnum. The cartilage covering the
articular facets of the occipital condyles is 2 to 3 mm thick. However, the processes are not always completely
covered by cartilage, potentially demonstrating two articular facets on each side. These convex surfaces sit within
[33]
biconcave, elliptic, parabolic articular surfaces on the cranial side of C1. This relationship forms a “bowl within a
bowl,” which is crucial for stability at the C0–1 motion segment. The principal motions allowed at C0–1 are
[66] [67]
flexion and extension; the total maximal range of motion is approximately 30 to 35 degrees from a fully flexed to a
fully extended position, with isolated flexion approaching 10 degrees and isolated extension measuring
approximately 25 degrees. This segment also demonstrates a small amount of voluntary lateral bending, with
[68] [69]
less than 5 degrees of involuntary rotation.
Four articular interfaces, all potential sites of inflammation or articular degradation, or both, are found between C1
and C2: two central synovial joints and two lateral synovial joints. The anterior atlantoaxial, or atlantodental, joint is
observed between the dens and the anterior arch of the atlas. Additionally, one can observe the joint between the
dens and the transverse ligament of the atlas (lower component of the cruciform ligament) just posterior to the dens,
which can also be interpreted as the bursa atlantodentalis. From a sagittal view, one can witness the two lateral
[33]
atlantoaxial joints (left and right), which are biconvex. The biconvexities are enhanced by increased thickness in
articular cartilage (1.4 to 3.2 mm), allowing for a reduced friction coefficient and rapid head movements. The
incongruences created by these joints are reduced with large, intra-articular menisci that emerge from redundant
joint capsules. These menisci can develop degradation and subsequent interposition with C1 to C2 rotation,
[70]
resulting in sharp, localized upper cervical pain. These four joint systems allow for flexion, extension, and rotation,
with very little lateral bending afforded. The widest range of motion of all articulations in the neck is available at C1
to C2, in the principal direction of rotation (40 degrees to 45 degrees in each direction). Additionally, a limited
[71] [72]
amount of anterior and posterior rocking is available at this segment (20 degrees total), without any lateral bending
[73]
allowed. Finally, the dens promotes stability in rotation and also permits 5 degrees to 10 degrees of flexion and 10
degrees of extension.
The typical cervical spine segments (C2–3 to C6–7) possess an intervertebral disc. The zygapophyseal joints from
these segments are formed by the articular processes of two adjacent cervical segments. The cartilage surfaces of a
vertebral body's superior processes face superiorly and dorsally, whereas those of the inferior processes face
anteriorly and inferiorly ( Fig. 35–6 ). The cervical facet joints are oriented in a very different plane from those in
the lumbar spine, as they are oriented 45 degrees ventral-cranial toward the orbit. Unlike the lumbar spine, this
[73] [74]
orientation is principally responsible for the coupled movements observed in the cervical disc segments.
The articular capsule can be considered a partial capsule. It is thick and lax laterally but deficient in the anterior,
medial, and posterior aspects of the joint. In addition, virtually all zygapophyseal joints in the cervical region
demonstrate a circular meniscus. The posterior aspect of the joint is contained by the insertion of the multifidus
[74] [75]
muscle, and the ligamentum flavum is not as intimately related to the anterior joint margin because it is in the
lumbar region. Thus, the aforementioned characteristics distinguish the cervical spine functionally from the lumbar
spine. Cervical segments can also be differentiated biomechanically, based on coupling behaviors. Nondisc
segments (C0–1, C1–2) synkinetically rotate in a direction opposite to kinetic lateral bending, and synkinetically
side-bend in a direction opposite to kinetic rotation. Conversely, cervical disc segments (C2–3 to C6–7) couple
ipsilaterally, where kinetic rotation is coupled with ipsilateral synkinetic lateral bending, and kinetic lateral bending
is accompanied by ipsilateral synkinetic rotation. This powerful coupling behavior in the cervical disc region forces
the spinous processes to displace in the direction opposite to the lateral bending or rotation ( Fig. 35–7 ). The [58] [76]
previously mentioned 45-degree orientation participates with the disc and the uncovertebral joint systems in
producing these coupled movements observed in the cervical disc segments. As in the lumbar spine, these
[77] [78]
coupled movements form an important aspect of the evaluation of the patient with cervical facet pain. It is important
to mention that the cervical spine is biomechanically designed for extensive range of motion. During full flexion, the
spinous processes separate, the intervertebral foraminal area increases at each segment, and only a very small
portion (5 mm) of the zygapophyseal articular surface maintains contact. [79] [80]
872
Figure 35-6 Lateral radiograph of the cervical spine showing

the orientation of the facet joints at a 45-degree angle in
relation to the horizontal plane in the cervical spine (arrows).
This determines the orientation of the articular processes. The
superior process (a) is oriented superiorly and dorsally and the
inferior process (b) is directed inferiorly and anteriorly.
Additionally, the cervical facet capsule affords a cervical disc segment of approximately 33 degrees of motion,
which far exceeds the movements that occur physiologically in the sagittal plane at any given cervical motion
segment (less than 18 degrees per segment). Thus, segmental flexion appears to be controlled by the influence of
[81]
the disc versus the capsule of the facet joints. The disc also appears to aid in limiting extension, but a greater
[82]
contribution is afforded by compression loading in the articular processes of the facet joints. [83]
Lateral bending appears to increase the compressive load on the ipsilateral zygapophyseal joint. Thus, the cervical
facet joints contribute to the strong influenceof the intervertebral disc and uncovertebral joint system in the control
of lateral bending. Isolated facet joint capsules allow approximately 17 degrees of segmental rotation. However,
[78] [83]
this range decreases considerably when the rotation is performed in a coupled fashion. Additionally, segmental
[78]
rotation appears to increase the compressive load on the contralateral zygapophyseal joint, which forces coupled
movement of ipsilateral lateral bending. Thus, the most effective way to stress the facet capsule may be through
[83]
coupled movement combinations of rotation, lateral bending, and flexion or extension. [84]
Barnsley, in an evaluation of patients after whiplash-type injuries to the cervical spine, determined that the most
commonly injured zygapophyseal joints were C2 to 3 and C5 to 6. The incidence at C2 to 3 could be explained
[85] [86]
by the fact that this segment serves as a transition between two very different biomechanical mechanisms. A [87]
similar principle could explain the incidence at C5 to 6, because this level is located between the extremely mobile
cervical spine and the relatively fixed thoracic segments. Additionally, the facets at this segment are predisposed to
injury by virtue of the location of the instantaneous axis of rotation and the tendency of the head and neck to extend
during the first phase of rearend whiplash at any velocity. Another explanation could be that the force vector
[88]
passing down through C5 to 6 is more posteriorly placed through the posterior anulus and the posterior compartment,
diverting stress toward the facet joint at this level. The C5 to 6 segment also demonstrates the largest range of
motion during flexion and extension compared with the other levels, possibly accounting for the higher incidence of
spondylosis at this level. [58] [89]
873
Figure 35-7 An important cervical spine coupling pattern. When the head and neck are bent to the right, the spinous processes go to the left. The
converse is also shown. This is a good frame of reference for describing and remembering the axial and lateral bending coupling relationships in
other regions of the spine.
Clinical Neuroanatomy
CERVICAL SPINE
In the cervical spine, the posterior compartment, comprised of facet joints and intrinsic back muscles (semispinalis
capitis, semispinalis cervicis, multifidus, and interspinalis), is innervated by the cervical posterior rami. The spinal [90]
nerve divides into anterior and posterior rami as it exits the foramen. After a short trajectoryof 2 to 5 mm, the
posterior ramus divides into a medial and a lateral branch. In the cervical region, these branches are separated by
[91] [92]
the semispinalis capitis muscle, with the medial branch lying deep to it and the lateral branch located in a plane
superficial to this muscle ( Fig. 35–8 ). At levels C3 to 4 through C7 to T1, facet joints are innervated by the
[90]
medial branches of the cervical dorsal rami originating at the level of the joint and the segment above. For example,
the C4 to 5 facet joint is innervated by the C4 and C5 medial branches. These medial branches are intimately bound
to the periosteum by the tendons of the semispinalis capitis muscle as they traverse along the waist of the articular
pillars ( Fig. 35–9 A, B; see also Fig. 39-8 ). The relationship of the medial branches to the semispinalis capitis is
very important clinically. This muscle acts as a potential reservoir for infiltrated anesthetic or neurolytic agents,
keeping the agent confined to this space, so as to consistently bathe the nerve. The close relationship between the
[90] [91]
medial branches and the periosteum on the waist of the articular pillars is constant and provides an optimal target for
needle placement during medial branch blocks. This site is preferable for several reasons: (1) the bone itself
provides a depth end point; (2) it is far from the spinal nerve, significantly reducing the risk of motor blockade and
thus preventing an equivocal result; and (3) it protects the vertebral artery from the needle because the artery lies
behind the transverse process and the articular pillar. At the C7 to T1 facet joint the medial branch of the C8
posterior cervical ramus crosses over the most medial aspect of the transverse process of T1 and continues on to the
lamina of the same vertebra. Thus, when a block of this branch is performed, a technique similar to that used for a
lumbar spine medial branch block should be implemented.
874
Figure 35-8 This drawing of a lateral view of a cervical

spine shows the relationship of the semispinalis capitis
muscle (SSCa ) with the medial branches (mb) crossing
under the tendons of this muscle as they insert on the
vertebral body. As noted, the lateral branch (lb) is in a
plane superficial to this muscle. Theoretically, this
muscle serves as a container for local anesthetic or any
other substance deposited under it. gon, Greater occipital
nerve; nlca, nodular localized cutaneous amyloidosis; ton,
third occipital nerve.
Figure 35-9 A, Anteroposterior drawing of the cervical spine shows the course of the medial branches and the innervation given by them to the
facet joints. Note how the medial branch (mb) lies in the waist of the articular pillars. These would be the targets for medial branch block and
radiofrequency needles in the AP view. Note the trajectory of the third occipital nerve (ton) on the lateral aspect of the C2 to C3 zygapophyseal
joint. B, This lateral drawing of the cervical spine shows the quadrilaterals formed by the articular pillars. These are located immediately anterior
to the spinous processes. The target in this view is the center of this quadrilateral, which is where the dotted lines intersect as shown by the black
dots in the center of the quadrilateral.
875
Of particular importance is the neuroanatomy of the C2 to C3 level. We consider this separately because it could
[90] [92]
be said that the C3 posterior cervical ramus divides into two separate and distinct medial branches. One of them is
the superficial medial branch, more commonly known as the third occipital nerve, which travels around the lateral
and dorsal aspect of the C2 to C3 zygapophyseal joint (see Fig. 35–9 A). The second C3 medial branch is the deep
medial branch, which, like any other medial branch, wraps itself around the articular pillar of C3 and provides
innervation to the C2 to 3 and C3 to 4 joints. When considering a denervation of the joint at C2 to 3, the third
occipital nerve should be addressed to obtain a satisfactory result (see Fig. 35–9 A). Additionally, complications
[92]
can arise from denervating this joint, such as vertigo and dizziness as reported by Lord and Bogduk. One of the [56]
relative advantages is that this is the only medial branch with cutaneous representation in the suboccipital region.
This could be convenient in the event of a denervation, because the success of the technique can be established by
anesthesia of this occipital region. However, Lord and Bogduk advocate abstaining from a denervation procedure to
this branch until further studies confirm the safety of the procedure. [56]
LUMBAR SPINE
The innervation of the lumbar zygapophyseal joints is similar to that of their cervical counterparts. The medial
branch of the posterior primary ramus supplies the innervation in the same manner. The joint is innervated by the
medial branch at the same level, as well as from the level above. The medial branches cross over the medial and
[93] [94]
superior aspects of the transverse process, as well as the root of the superior articular process ( Figs. 35–10 and 35–
11 ). The branch then continues medially under the mamilla-accessory ligament. This ligament connects the
[95] [96]
mamillary and accessory processes and is homologous to the semispinalis capitis in the neck because of its
relationship to the medial branch (see Fig. 35–10 ). At this point, the
Figure 35-10 This oblique drawing of the lumbar spine shows the course of the medial branch on this view. Note the presence of the mammilla-
accessory ligament (a) and the trajectory of the medial branch (mb) under this structure. We can also appreciate what the “Scotty dog” looks like
and where the “eye” (c) would be located and its relationship to the medial branch. In this figure, the eye is marked with a black dot, which is the
target for the needle for facet block and neurolysis. After the medial branch (mb) crosses under the mammilla-accessory ligament (a), it divides
into distal (d) and proximal (p) zygapophyseal branches.
branch divides into proximal and distal zygapophyseal branches. The proximal branch supplies the capsule of the
[93] [94]
joint at the same level in a caudad-to-cephalad direction. The distal branch continues caudally and innervates the
superior aspect of the capsule of the lower-level facet joint. Special mention should be made of the L5 dorsal ramus,
which travels between the ala of the sacrum, and its superior articular process. One fact of clinical importance
[10] [93] [99]
is that the medial branches at the lumbar level not only supply the facet joint but also innervate various intrinsic
muscles within the posterior compartment, along with the ligaments and the periosteum of the neural arch.
876
Figure 35-11 This anteroposterior drawing of the lumbar spine illustrates the course of the medial branches in the lumbar region from L1 to 2
and from to L5 to S1. Note how the medial branch lies in the area where the superior articular process joins with the transverse process. The
trajectory of the medial branch of L5 can also be appreciated as it crosses along the groove between the ala of the sacrum and the base of the
superior articular process, which should be the target for block or denervation at this level.
Therefore, a medial branch block at this level would also treat pain coming from the other structures mentioned and
would not suggest that the facet joint is the isolated cause of the problem. Conversely, the medial branches in the
cervical spine demonstrate very limited and discrete contributions to the intrinsic muscles, making clinically
effective blocks more diagnostically predictive of facet joint pain.
Pain Receptors of the Facet Joint

Facet joint pain has been characterized as a dull ache, diffuse and poorly localized. Nociceptive receptors and fibers
relay their information to a very broad area in the dorsal horn of the spinal cord. The capacity of the facet joint to [97]
produce pain has long been established. Several studies using neurohistochemical stains
[98] [99] [100] [101] [102] [103] [104] [105] [106] [107] [108] [109]
have identified two types of fibers that could potentially transmit nociceptive information in the zygapophyseal joint.
Both group III small, myelinated fibers (1–5 µm in diameter) and group IV unmyelinated fibers (0.5–2.0 µm in
diameter) are found in the facet joint system. Grigg and associates established that these two groups of fibers
[110] [109]
were not sensitive to mechanical stimulation under normal conditions. However, they became responsive to
stimulation in the presence of inflammation. The presence of substance P, a well-known mediator of nociceptive
stimuli, has been identified in the capsule of the facet joint itself, as well as in the subchondral bone of arthritic facet
joints. Fibers that react to other nociceptive peptides, such as calcitonin gene-related peptide and vasoactive
[109]
intestinal polypeptide, have been located in the synovial folds of the joint. Synovial entrapment has been proposed [106]
as a possible pain-producing mechanism, owing to the fact that richly vascularized, highly innervated synovial
inclusions may become sensitive sources of nociceptive stimuli when inflamed. Of particular interest is the [108]
hypothesis of a sympathetic component to facet joint pain. Investigators have identified fibers that are
immunoreactive to neuropeptides, such as CPON (C-terminal flanking peptide of neuropeptide Y), neuropeptide Y,
and tyrosine hydroxylase, which are found within the autonomic nervous system. This would explain the
perpetuation of pain by excessive activation of the sympathetic system in a similar fashion to the processes
associated with complex regional pain syndrome. [101]
Clinical Manifestations of Facet Joint Pain

Many authors have attempted to define the common signs and symptoms associated with pain originating in the
zygapophyseal joint. However, nearly every pathologic change originating from the posterior elements of the
vertebral column produces similar clinical profiles. For obvious reasons, this complicates the process of trying to
determine the location of the pain generator. Numerous investigations have attempted to elucidate the sensitivity and
877
specificity of several symptoms attributed exclusively to the facet joint, without reaching conclusive evidence. For
organizational purposes, we consider cervical and lumbar clinical manifestations separately. For practical reasons,
this chapter does not include the clinical manifestations and blocking techniques of the atlantoaxial and atlanto-
occipital joints, as these are addressed in another section.
CERVICAL FACET PAIN
Pain can emerge from the zygapophyseal joints, because their more horizontal orientation predisposes these joints to
a significant proportion of load bearing. Imposed loads are heightened by increased postural muscle tone that is
[3]
aimed at resisting the tendency of the head to fall forward. Thus, increased compressive loading and joint
[33]
orientation may predispose the zygapophyseal joint to irritation and pain generation. This tendency can be further
compounded by different conditions and events, including whiplash-type trauma, chronic instability
[111] [112] [113] [114]
associated with degenerative disc disease, and poor postural habits related to occupational factors. For acute
whiplash injuries, investigators have identified capsular tears, articular cartilage fractures, and hemarthroses of the
facet joints as the result of the trauma.198 With chronic disease, changes such as articular cartilage degradation,
subchondral cysts, osteophyte formation, and capsular hypertrophy are common. The typical pain originating in the
zygapophyseal joint is described as a dull, deep ache localized in the neck and occipital regions. Pain from the
[115]
facet joint is commonly referred to the head, upper back, and proximal upper extremity. A patient may complain of
[91]
reduced range of motion because of pain or spasm. During physical examination, pain can frequently be provoked
by deep palpation of the posterior neck. As a result of convergence in the dorsal horn of the spinal cord, patients
may experience paravertebral muscle spasm.
In the clinical examination of a patient suffering from local cervical pain, we need to differentiate five different
conditions that stem from second-degree disc-related changes: (1) internal disc disruption; (2) uncovertebral joint
synovitis; (3) uncovertebral joint arthropathy; (4) zygapophyseal joint synovitis; and (5) zygapophyseal joint
arthropathy. Although establishing a differential diagnosis is not simple initially, it acts as a guide to a more direct
treatment approach. A brief, specific, three-dimensional (3-D) examination can be used to investigate these
conditions. Five different test categories make up the examination: (1) active sagittal motions (flexion and
extension); (2) active and passive rotation; (3) active and passive lateral bending; (4) active and passive 3-D rotation;
and (5) active and passive 3-D lateral bending. Passive tests are implemented only if we are not able to gain
sufficient information from an active examination. However, the active tests are usually adequate for effective
differential provocation. In this chapter, we focus on the tests that are most provocative for facet afflictions.
Flexion and extension are the first motions performed in the examination. Sagittal motions (flexion, extension, or
retraction) produce the greatest amount of pain if the patient suffers from an internal disc disruption owing to
tension or compression events in the disc, as well as maximized intradiscal pressure. Second, we ask our patients
[116]
to side-bend. If lateral bending, and any additional 3-D movements added to the lateral bending, are the most
provocative directions of movement, we should suspect uncovertebral involvement because of maximized loading
on the joint and decreased intradiscal pressure.
[117] [118]
As previously mentioned, a coupled motion is one in which a synkinetic motion predictably occurs in
accompaniment to a kinetic motion, thus maximizing the motion in the kinetic direction and tension-loading the
capsular structures at their end range. The coupled motions of the cervical disc segments (C2–3 to C6–7) are lateral
bending and ipsilateral rotation. Conversely, combined motions limit the kinetic motion by adding a second position
that contradicts the normal segmental coupling behavior. Here, the articular surfaces get in the way of each other
and lock the segment. For the cervical spine, combined motions are lateral bending and contralateral rotation. [23]
Pain associated with facet irritation must be differentiated from internal disc disruption or uncovertebral joint
afflictions. Unlike a cervical disc affliction, flexion or extension does not provoke the greatest pain when the patient
is suffering from a facet synovial irritation, because of the previously reported laxity of the joint capsule during such
movements. This suggests that flexion and extension do not sufficiently stress the capsule of the facet joints. Rather,
rotation is required to maximally tension-load the zygapophyseal joint capsule, suggesting the primary role of the
zygapophyseal joint in limiting rotation.
If the patient suffers from zygapophyseal joint involvement, planar and or 3-D rotation produces the greatest pain,
because the zygapophyseal joints are most responsible for controlling segmental rotation in the cervical disc
segments. Thus, we use rotation to provoke problems in the facet joints. If the patient experiences the greatest pain
in rotation, we can add either a coupled or combined 3-D motion to differentiate between a synovitis and
chondropathy of the facet. For coupled motion, the patient rotates and then ipsilaterally side-bends. Additionally,
flexion and extension are each superimposed onto this coupled motion, because rotation produces osteokinematic
extension from C0 to 1 through C3 to 4 and flexion from C4 to 5 through C7 to T1. Furthermore, rotation produces
[76]
arthrokinematic extension of the ipsilateral zygapophyseal joints and flexion of the contralateral joints. [58]
If a coupled movement of rotation, ipsilateral side bending, and extension produce the greatest amount of upper
cervical pain on the same side as the direction of rotation, we should suspect facet synovitis at C2 to 3 or C3 to 4.
878
Suspicion stems from the fact that this movement combination maximally extends those facets and maximally
stresses the capsule and synovial lining on the same side as the direction of rotation. Additionally, if this same
movement produces the greatest amount of upper cervical pain on the opposite side to the direction of rotation, we
should suspect internal disc disruption of the upper cervical disc segments. Conversely, if rotation, ipsilateral side
bending, and flexion produce the greatest amount of lower cervical pain on the side opposite to the direction of
rotation, the clinician should likewise suspect facet synovitis in that region. The reason for suspicion is that this
movement combination maximally flexes those facets and maximally stresses the capsule and synovial lining on the
side opposite to the direction of rotation. Furthermore, if the greatest pain is produced in those same segments on the
same side as the direction of rotation, the clinician should suspect internal disc disruption at those levels.
Although extension increases the compression load on the facet articular surfaces and provokes symptoms
associated with facet chondropathy, similar provocation can be produced with patients suffering from an internal
disc disruption. Therefore, further clinical testing is needed to help in differentiating between the two conditions.
Based on the previously mentioned biomechanical studies, patients may experience the greatest amount of pain
[77] [83]
from a facet chondropathy during contralateral rotation combined with lateral bending that is ipsilateral to the
afflicted side (by virtue of the loading in the facet on the side of lateral bending). For example, a patient with a
clinical presentation of a chondropathy in the right C4 to 5 facet demonstrates the greatest provocation with left
rotation combined with right lateral bending. This behavior allows the clinician to differentiate between a
chondropathy and a cervical IDD (internal disc disruption), which also provokes greatest pain during extension but
not during the previously mentioned 3-D motion.
Along with the previously reviewed provocation examination, the clinical neurologic examination is extremely
important. A complete examination of the cranial nerves is essential, accompanied by a thorough upper extremity
motor and sensory evaluation. The neurologic examination should be initially directed at ruling out any other
common causes of cervical pain, such as intervertebral disc disease with nerve root involvement and rare but equally
important intracranial pathology. Although neck pain in the absence of the neurologic deficits that suggest nerve
root compression can be highly indicative of facet joint involvement, it is not absolute. Additionally, if the facet
joint is hypertrophied and osteophytic, nerve root compression from this source is possible, and differentiation from
a herniated intervertebral disc solely on clinical findings is difficult.
Cervical facet joint pain can also appear atypically. Frontal and temporal headache as well as facial pain can be rare
manifestations of facet joint disease to which the clinician must remain alert. As Pawl explained, all nociceptive
[12]
stimuli originating in the face and head enter the spinal cord and descend into the cervical segments, where they
have their second relay synapse before returning to the brain interpretive centers. Fibers from the three divisions (V1,
V2, V3) of the trigeminal nerve have been found as low as the cervical segment, and fibers from the ophthalmic
division have been identified as caudal as the fourth cervical segment. Therefore, any nociceptive stimuli
[118]
originating in the cervical region can have referred projections into the face and head. Reports of autonomic
manifestations such as lacrimation and rhinorrhea associated with a cervicogenic headache have also been
recorded. This may be explained by connections with the pterygopalatine ganglion. Headache of cervical origin
[119]
can be distinguished from headache due to other causes by diagnostic criteria described by Sjaastad and
colleagues, which are enumerated in Table 35–1 . Intervertebral disc disease can be associated with cervical facet
[120]
joint pain. One study found evidence of intervertebral disc disease in up to 41% of patients who experienced pain
[91]
relief after cervical medial branch blocks. In these cases the symptoms of facet joint pain can be masked by the
intervertebral disc symptoms. However, the presence of radiculopathy in such cases may be helpful in locating the
level of involvement of the zygapophyseal joint. It is more likely for the facet joint at the level of disc herniation to
be involved because of the added stress on the joint at this level.
TABLE 35-1 -- MAIN DIAGNOSTIC CRITERIA FOR CERVICOGENIC HEADACHE

Major symptoms and signs
Unilateral headache
Symptoms and signs of neck involvement
Pain precipitated by mechanical pressure to the ipsilateral upper posterior neck region or by awkward head positioning
Ipsilateral neck/shoulder/arm pain
Reduced range of motion in the cervical spine
Pain characteristics
Nonclustering pain episodes of varying duration (or fluctuating, continuous pain)
Moderate, usually nonthrobbing pain, starting in the neck and spreading forward
Other important criteria
Anesthetic blockade of the greater occipital nerve or the C2 nerve on the symptomatic side eliminates pain transiently
879
Female sex
History of head or neck trauma
Adapted from Sjaastad I, Fredriksen TA, Pfaffenrath V: Cervicogenic headache: Diagnostic criteria. Headache 30:725–726, 1990.
The use of diagnostic imaging in the diagnosis of cervical zygapophyseal joint pathology has been limited. [121] [122] [123]
The correlation between radiographic anomalies of the facet joint and pain is low. Changes due to acute whiplash
injuries are difficult to document on conventional radiographs, whereas computed tomography (CT) studies have
demonstrated superior results. The ability to detect joint abnormalities, such as subchondral bone cysts and articular
cartilage erosions, makes this technology more reliable. The value of the CT examination relies on a high
[124]
correlation between symptoms and the facet degenerative changes that are present. However, a high percentage of
[124]
patients without changes on CT may present with symptoms that are suggestive of facet joint arthropathy and may
respond well to facet joint block.
The diagnostic confirmation of facet joint pain comes after careful evaluation of the patient. Because a definitive
diagnosis cannot always be derived from imaging studies or the findings of a clinical examination, the diagnosis is
confirmed by measuring pain relief after facet joint injections or medial branch blocks. However, the diagnosis of
cervical facet disease by means of facet joint injections has its flaws. When a therapeutic procedure must be
performed to establish a diagnosis, there is a potential for error. Furthermore, the clinician is dependent on a
procedure whose efficacy can be evaluated only by the patient's subjective perception of pain relief. As previously
discussed, medial branches and intra-articular facet joint surfaces have no cutaneous or motor representation,
making the objective measurement of block success very difficult. Patients with whiplash injuries of the cervical
spine have consistently demonstrated acceptable results in terms of pain relief after medial branch blocks or intra-
articular injections. By using medial branch blocks, Barnsley and coworkers performed a study on patients with
[86]
chronic neck pain after whiplash injuries and calculated the prevalence of isolated cervical facet joint pain to be
approximately 54% (confidence interval of 40%–68%). One finding that supports the predictability of facet joint
blocks for zygapophyseal joint pathology is that the nerve supply emerging from the medial branch is almost solely
dedicated to the facet joint, excluding the other posterior elements. Therefore, if the block relieves pain, the pain is
most likely caused by the facet joint. One study determined that pain relief after a cervical medial branch block gave
a positive indication that the origin was the facet joint in 70% of patients with post-traumatic neck pain (range 63%–
100%). [92]
Once the cause of pain has been reasonably determined to be the facet joint, the next step is to determine which level
is involved. As previously mentioned, the referral patterns and atypical presentations have to be identified to
accurately locate the problem joint. The affected joint can effectively be determined through careful questioning of
the patient as to the area of pain origin and its subsequent radiation. An infrequently implemented method of
identifying the problem joint is to perform intra-articular irritant injections in an effort to reproduce the pain. The
joint injection or injections that approximate the patient's pain pattern are identified and a more definite approach
can then be undertaken.
Dwyer and Aprill and their colleagues performed invaluable investigations regarding localization of facet-generated
symptoms. This study was performed in two parts. The first part consisted of fluoroscopically guided intra-
[115] [125]
articular facet joint injections of contrast medium used as an irritant in the joints of normal volunteers. The
investigators mapped the areas of pain corresponding to the different injected articular levels. The second part of the
study included patients with presumed facet joint pain. A composite of the pain distributions produced by activating
the different joint levels can be observed in Figure 35–12 A. From this map, one can see that there are significant
areas of overlap between levels. However, each segment produces specific characteristics that support the
identification of the problem joint. For example, the C2 to 3 joint produces a pain referred to the occiput and the
retroauricular area. Additionally, the C4 to 5 level extends into the shoulder area, whereas the C3 to 4 level lies
between the shoulder and the occipital area. The difference between C5 to C6 and C6 to C7 can be appreciated in
the extension over the scapula. C5 to C6 extends up to the spine of the scapula and C6 to C7 extends below this
point. Another important investigation, performed by Fukui and associates in 1996, attempted to reproduce the
[126]
findings of Dwyer and Aprill and their coworkers, but they also delineated the referral patterns of each individual's
medial branch (see Fig. 35–12 B).
880
Figure 35-12 A, A composite map of the results in all volunteers, depicting the characteristic distribution of pain from zygapophyseal joints at
segments C2–3 to C6–7. B, Main referred pain distributions for the zygapophyseal joints from C0–1 to C7–T1 and the dorsal rami C3–7.
LUMBAR FACET PAIN
The implications of the lumbar facet joint as the primary and sole source of pain have been debated. In the lumbar
region, the prevalence of facet joint pain has been determined to range between 7.7% and 75%. [8] [124] [127] [128] [129] [130] [131] [132] [133]
The diagnosis of zygapophyseal joint pain on clinical grounds is challenging. Historically, a patient
[134] [135] [136] [137] [138]
who had a clinical presentation of low back pain and a normal neurologic examination was diagnosed with an
arthropathy of a lumbar zygapophyseal joint. However, provocative electrical stimulation of any structure within the
posterior column of the lumbar spine can essentially produce an identical clinical picture. Thus, unlike conclusions
[130]
for the cervical levels, investigators have reached no consensus regarding specific, nonradicular pain referral
patterns for the lumbar facet joints. The pain originating in a single lumbar facet joint is usually described as a
unilateral dull ache in the paraspinal region, occasionally radiating to the buttocks and proximal lower extremity. [3] [8]
Pain from a lumbar facet joint rarely radiates below the knee, but this is not absolute. Intra-articular injections
[139] [140]
of hypertonic saline were performed in normal individuals as well as individuals with low back pain to map the
characteristics of observed referral patterns. As we can see from Figure 35–13 , no specific pain pattern can be
[8]
determined. In general, lumbar facet joint pain has a nonradicular pattern, and the presence of arthropathy can make
the referral different from that in individuals in whom no arthropathy is seen. A composite of the results can be seen
in Figure 35–13 A.
Another study that attempted to elucidate the referral patterns of the lumbar zygapophyseal joints was performed by
Fukui and colleagues in 1997. Several intra-articular injections were performed with contrast material followed by
[141]
radiofrequency thermocoagulation after stimulation of the medial branches. In Figure 35–13 B, there is a composite
of the referral patterns. Noteworthy is the lower incidence of referred pain down the lower extremities in comparison
to the study of Mooney and Robertson. The most common referral patterns are shown in Figure 35–13 B.
[8]
Characteristically, the referral pattern for the high lumbar facet joints (L1–2 and L2–3) were more frequently
observed in the lumbar area, whereas the lower lumbar joints referred pain to the gluteal region, groin area, and
posterolateral thigh.
Usually, the patient's clinical picture is absent of any neurologic deficit, and if a deficit is detected, other causes of
back pain have to be ruled out before arriving at the diagnosis of facet joint pain. Physical examination can reveal
paraspinal pain to palpation in the lower back. Spasm of the paravertebral muscles overlying the affected joint may
also be detected. Patients suffering from lumbar facet chondropathy experience less pain with movement and
posturing in the direction of flexion. Pain is less in the morning and worsens as the day progresses. During the
examination, the greatest pain is produced during 3-D movements that lock the facets (combined movements; e.g.,
extension, lateral bending, and ipsilateral rotation). Conversely, patients with synovial irritation experience less pain
881
in extension because of increased stability invested in the joint in the extended position. These patients experience
increased pain in the evening and experience the greatest provocation during coupled movements because of
maximized stress imposed on the capsule and the synovial lining (e.g., extension, lateral bending, and contralateral
rotation).
Once again, the clinical neurologic examination is crucial. Any evidence of radiculopathy should prompt imaging
studies to rule out any other cause of the pain, such as the more common primary disc affliction, prolapse or
extrusion. As mentioned previously, facet joint pathology typically follows intervertebral disc disease. One
investigation demonstrated the presence of degenerative disc disease on CT in virtually all cases exhibiting facet
joint degenerative changes. This creates confusion in diagnosing radiculopathy and requires differentiating between
the facet joint and the intervertebral disc as the source of the referred pain.
The importance of imaging studies in the lumbar facet syndrome rests on the elimination of other diagnostic
possibilities. Conventional radiologic studies
Figure 35-13 A, Pain referral patterns produced by intra-articular injections of hypertonic saline in asymptomatic (normal) and symptomatic
(abnormal) patients. The more darkly shaded areas show the most common referral detected, and the lighter shades indicate the less common
patterns. B, Referred pain distribution: 1, lumbar spinal region; 2, gluteal region; 3, trochanter region; 4, lateral thigh region; 5, posterior thigh
region; 6, groin region. As discussed in this chapter, the higher facet referral patterns were most commonly seen in the lumbar and gluteal region,
whereas the lower facet joints had lower referral patterns as shown in this figure.
may identify very severe changes in the facet joint, but the more subtle changes go undetected. CT and magnetic
resonance imaging (MRI) studies are able to detect less obvious changes such as articular cartilage wear and
subchondral bone cysts. To understand that these are only anatomic findings and should be interpreted as such is
[124]
paramount to effective clinical diagnosis. Additionally, the correlation between these findings and the clinical
manifestations is very tenuous. One investigation demonstrated the presence of arthritic changes in 10.4% of
asymptomatic patients. Furthermore, arthritic joint changes detectable by CT or MRI appear in more than 50% of
[142]
persons older than 40 years of age who are without low back pain. Because of the highly elusive value of
[143]
radiologically appreciable changes in the facet joint and the poor correlation of these changes with symptoms, a
facet block should be undertaken if the diagnosis of lumbar facet joint pain is likely and conclusive evidence of
intervertebral disc pathology is not available. Of importance is the understated value of the radionuclide bone scan.
Although its value is undetermined in clinical trials, if positive findings are obtained, it may direct attention to a
specific pain-producing facet joint.
It is obvious that the definitive diagnosis of lumbar facet joint pain should be confirmed by either intra-articular
injections or medial branch blocks. The same dearth of physiologic tests for the adequacy of a block exists in the
lumbar spine as in the cervical spine. The success of a given block is measured subjectively by the patient's pain
relief experience. This method is subject to skewed results, possibly because of placebo effects wrongfully
interpreted as successful blocks. One means of reducing the probability of this error is to use comparative blocks. [144]
This consists of a double-blind technique using blocks performed with two local anesthetics (lidocaine and
[145] [146] [147]
bupivacaine) that differ in their duration. The response to each injection is measured, and a physiologic response can
theoretically confirm the diagnosis. The probability of a patient giving a false-positive result because of coincidence
882
has been estimated to be 1 in 500. One of the largest studies incorporated approximately 400 patients with
pathologic conditions ranging from low back pain secondary to disc disease to patients with postoperative pain.
These investigators performed lumbar facet joint injections in all cases. Results showed that from 130 variables
[133]
analyzed for their predictability of response to facet injections, the ones that correlated with significant pain relief
included older age, history of low back pain, absence of leg pain, maximal pain on extension, and normal gait.
Another retrospective review demonstrated that prolonged relief after facet joint injections was seen in 67% of
patients who experienced localized paravertebral tenderness, in 67% with pain provocation on extension, in 77%
with loss of leg sensation in a nondermatomal pattern, and in 80% of patients with upper thigh and groin pain. [132]
Several other studies failed to find common reliable signs and symptoms in patients who responded favorably to
facet joint blocks.
[148] [149]
Patient Preparation
In terms of patient preparation for these procedures, several points should be mentioned. Proper consent should be
obtained, and a careful explanation of the procedure, as well as potential complications and side effects, is crucial.
Routine laboratory workup is hardly necessary, and these tests should be done only with clear individual indications
(e.g., clotting studies in a patient who has been on chronic anticoagulation). Patients on chronic anticoagulation
should be evaluated as to the feasibility of stopping these agents before they are scheduled for a procedure. An
empty stomach is one of the safest precautions in terms of complications. A 4-hour time limit on clear and solid
foods should be stipulated. The dangers of adverse reactions, as well as the risk of intravascular injection, make
aspiration possible. Even though this procedure can be performed under local anesthesia alone, intravenous sedation
is a strong adjuvant in terms of patient comfort. The same precautions that are taken for sedation in the operating
room should be taken in these cases; that is, hemodynamic monitoring by means of an electrocardiogram,
noninvasive blood pressure monitoring, pulse oximetry, and administration of oxygen to the patient by nasal cannula.
Obviously, resuscitation equipment should be readily available, and the potential need of this equipment is another
reason why empty stomach precautions are crucial.
Technique
In general, two approaches have been used in the treatment of facet joint pain. These are intra-articular injections
and medial branch blocks. In terms of the efficacy of one over the other, there is no literature supporting either
technique. However, medial branch blocks have enjoyed a greater popularity for several reasons. Medial branches
are more accessible and therefore easier to block. Intra-articular techniques require a joint space, which in joints
with arthritic changes is not always present. Facet denervation by medial branch blocks or radiofrequency
denervation performed properly is safer because the needle tip is located further away from structures such as the
vertebral artery, epidural space, and dural sac. This in turn provides more accurate information because the diffusion
of local anesthetic into the epidural space and the dural sac from the intra-articular space may provide pain relief
that may not stem from the facet joint itself. Some authors have advocated blind techniques, but the reasons given
earlier justify the use of fluoroscopic imaging. One could go as far as to say that the only accurate and safe way of
performing these blocks is with radiologic aid in the form of fluoroscopy.
For the reasons given previously in this section, we concentrate not on intra-articular injections but rather on medial
branch blocks and radiofrequency techniques for denervation of both cervical and lumbar spine facet joints. For
facet denervation, we concentrate mainly on radiofrequency thermocoagulation. Other permanent or long-lasting
denervation techniques have been used, such as cryoneurolysis, chemical neurolysis, and even surgical denervation.
Chemical neurolysis uses substances such as alcohol, glycerin, and phenol. These have been discouraged because of
the unpredictability of the lesion and the impossibility of controlling spread and risking disastrous complications.
Cryoneurolysis, on the other hand, produces an incomplete lesion, which is convenient in peripheral nerve lesions,
because it prevents deafferentation pain. However, there are limitations imposed technically owing to the size of
[149]
the cryoprobes, which are greater than 3 mm in diameter, making them hard to maneuver and to accurately address
the target. Theoretically, cryoneurolysis also allows for a quicker regeneration of the lesion. Furthermore, the the
size and depth of the lesion are secondary to variations in surrounding tissue blood flow and thermoconductivity. [150]
Surgical ablation of the medial branches has also been performed with a specially designed knife, but [151]
complications such as excessive bleeding and formation of neuromas, have made practitioners shy away from it. [151]
Radiofrequency denervation possesses several advantages over the aforementioned procedures because of the fact
that it creates a lesion that can be well controlled and reproduced with well-circumscribed edges. Moreover, there is
a means of controlling the temperature of the probe, and the localization of the target nerve can be confirmed by
stimulation and impedance. Finally, the needles can be thick or thin and short or long, allowing varied anatomic
applications. These are the reasons why we focus on radiofrequency thermocoagulation when denervation is
considered.
883
Cervical Facet Block
PRONE TECHNIQUE
The purpose of the prone technique is to perform a block with local anesthetic or steroid, or both, of the medial
branches that innervate the facet joints. This block can be performed with the patient lying supine or prone. We
concentrate initially on the prone position because it is the safest and in our opinion the best for needle positioning
for facet radiofrequency denervation.
Figure 35-14 Drawing depicting patient in prone position for cervical facet medial branch block and denervation. Note the position of the
fluoroscopic ray in direct anteroposterior projection (solid line) and lateral view (dotted line).
In the prone position ( Fig. 35–14 ), the patient's posterior neck is prepared under sterile conditions and draped. As
with any surgical technique, a generous area should be prepared to ensure that the block is performed properly.
Under fluoroscopy, a posteroanterior (PA) view is obtained to identify the posterior aspect of the waists of the
articular pillars from C3 to C7 ( Fig. 35–15 ). In some patients, the articular pillars of the superior cervical spine (C3
and C4) may be hard to identify with the patient's head in the neutral position. Two maneuvers that help in this
situation are slightly hyperextending the patient's head or having the patient open the mouth to remove the mandible
from the radiologic field. When the waists of the articular pillars of the levels to be blocked have been identified, the
needle (a 10-cm, 22-gauge spinal needle or a short-bevel needle) is advanced in a gun-barrel fashion, with the needle
aligned with the fluoroscopic ray in such a way that the posterior end of the needle is seen over the target ( Fig. 35–
16 A). Once bone has been contacted, the fluoroscopic ray is rotated to the lateral view. In this view, the needle
should be seen in the posterior aspect of the waist of the articular pillar ( Fig. 35–16 B).
Figure 35-15 Anteroposterior view of a cervical spine showing the articular pillars from
C3–6 with two needles positioned for medial branch blocks at C4 and C5. Arrows show
the targets along the articular pillar waists at the remaining levels.
884
Extreme caution must be taken with this projection, and one must ensure that the target is addressed in a direct
fashion, because a deviation toward the midline in this view directs the needle into the epidural and subarachnoid
space, and, if the needle is deviated laterally, the vertebral artery becomes a likely target. At this point, the needle is
advanced under this view until the tip is seen in the center of the quadrilateral, where the medial branch lies ( Fig.
35–16 C and 35–9B). To advance the needle under this projection, a slight lateral deviation should be applied
carefully and slowly to position the needle tip in the lateralmost aspect of the articular pillar in the PA view.
A confirmation of the position of the needle tip should be obtained in both PA and lateral views before any local
anesthetic or steroid is injected. As the lower articular pillars (C5, C6, and C7) are approached, the lateral view may
be obscured or blocked by the bone and soft tissues of the shoulder. To obtain a satisfactory image at this point, the
patient can be asked to reach for the feet or an assistant can pull on the patient's hands to take these tissues out of the
way. Careful aspiration should be done, and, to be safe, a very small amount of water-soluble contrast material can
be injected to see the kind of spread the local anesthetic agent will have and to ensure that there will be no
intravascular spread. It is important to emphasize that very little contrast material should be used (maximum of 1
mL) in order not to obscure the views of the lower articular pillars. The maximum amount of local anesthetic agent
to be injected per level is 2 mL. Figure 35–14 shows the optimal targets in the cervical spine for medial branch
localization and block.
SUPINE TECHNIQUE
The supine technique can be used as an alternative to the prone technique.[152] It is clear that each technique has its
advantages and disadvantages, and these are discussed later in this section. In the supine position, the landmarks to
be identified are the posterior border of the sternocleidomastoid muscle, and the facet joints. [152] Once these are
identified, the area is prepared and draped in a sterile fashion. With the patient's neck in a neutral position, the
fluoroscopic ray is initially brought in laterally. Once an image is obtained and the cervical spine is in view, the ray
is rotated, under active fluoroscopy, toward the anteroposterior (AP) view, approximately 30 degrees (see Fig. 35–
16 D). At this point, the neural foramen should come into view (see Fig. 35–16 E). In order to appreciate the neural
foramen more clearly, some cephalocaudad deviation of the ray may be necessary. Immediately posterior to the
neural foramen, the articular pillars appear as elliptical structures, which can also be termed beads (see Fig. 35–16
E). The beads at each level form a string of beads (see Fig. 35–16 E). These structures are the targets for the needles.
The ideal point of contact is between the superiormost third and the middle third of the elliptical structure (see Fig.
35–16 E). One of the disadvantages of this technique is that a gun-barrel technique cannot be used. The insertion
point of the needle is slightly posterior to the sternocleidomastoid muscle or slightly posterior to the facet joint. The
needle is advanced toward the target until bone contact is made. Confirmation of the needle position should be done
under the AP view, and the tip of the needle should be seen in the waist of the articular pillar (see Fig. 35–16 F).
Caution should be used during needle advancement as there is no notion of how medial or lateral the needle is in
relation to the spinal cord, nerve root, or vertebral artery. If bone contact is not made at the point of the bead, the
needle should be withdrawn and redirected more medially or laterally as can be assessed in the AP view. It is
important to mention here that this technique is more convenient for medial branch blocks than for radiofrequency
denervation techniques.
As far as the superiority of one technique over the other, the supine technique holds the advantages of being more
comfortable for the patient and less time-consuming in experienced hands. In addition, more than one level can be
approached through the same puncture wound without having to withdraw the needle from the skin. The
disadvantages are the potential for catastrophic results because it is not a gun-barrel technique and, as stated earlier,
the direction assessment in the mediolateral plane can be difficult, leading to the possibility of directing the needle
into the spinal cord if too medial or into the vertebral artery or nerve root if too lateral. Another disadvantage also
mentioned briefly earlier is the fact that the radiofrequency probe can be hard to position parallel to the nerve to
obtain an effective lesion. As stated before, the most convenient technique for needle positioning in denervation is
the prone technique. A potential complication of the supine technique, which is not likely if the prone technique is
employed, is the possibility of causing a pneumothorax when an attempt is made to perform a block of the medial
branches of C6.
885
Figure 35-16 Radiologic views in sequence during a cervical medial branch block. A, A gun-barrel approach to the posterior aspect of the most
lateral point of the articular pillar (arrow). B, The lateral view once bone is contacted in the anteroposterior (AP) view. The tip of the needle is
seen in the posterior aspect of the articular pillar. C, The tip of the needle in the center of the articular pillar where the medial branch lies once the
needle has been “walked off” laterally and the tip advanced anteriorly. D, The approximate position of the fluoroscopic ray with the patient lying
supine on the fluoroscopy table. Note the 30-degree angulation (dotted line) to the AP plane from the lateral projection (solid line). E, A view of
the neural foramen obtained with the fluoroscopic ray positioned as described above. There is a clear view of the neural foramen anterior to the
“string of beads” created by the articular pillars, as shown by the needles. The needle positions can be seen. Needle B is in the best position,
because in the AP view F it lies closest, in the waist of the articular pillar. Needle B is closest to the junction of the superior third, with the middle
third in the oblique view (E). Needle C, although in the middle of the articular bead in the oblique view, lies slightly inferior to the waist in the
AP view.
Cervical Facet Radiofrequency Denervation

When denervating a facet joint, we use radiofrequency. It is performed in the same manner as described previously,
with some crucial differences. The needle used for radiofrequency is blunt and has a curved tip; it is 10 cm long with
a 10-mm active uninsulated tip ( Fig. 35–17 ). This is for the purpose of directing the needle as well as positioning it
in a “hugging” manner across the articular pillar waist, because this is a curved surface and a curved needle is
necessary for good contact ( Fig. 35–18 ). Because a blunt needle is being used, the skin should be penetrated
initially with an Angiocath to facilitate the introduction through the cannula. The same approach described earlier
should be used to position the active, uninsulated tip of the radiofrequency needle in the waist of the articular pillar,
contacting bone and running parallel to the medial branch. Figure 35–19 A to C shows the optimal positioning of the
needle in this area. Caution should be taken to ensure that the active tip is outside the neural foramen to avoid
lesioning of the spinal root. This is best
886
Figure 35-17 Picture of needle used for radiofrequency neurotomy. This is a picture of a Racz-Finch needle. Note the curved tip which is also
characteristically blunt (arrow). The tip of the needle is 10 mm long and uninsulated.
achieved in the lateral projection. Confirmation of optimal needle positioning should, again, be done in the PA and
lateral views. Before lesioning, careful sensory and motor stimulation should be performed. During sensory
stimulation, the generator should be set at 50 Hz and it should be carried from 0 to 0.9 to 1.0 Vs. This progression
should elicit stimulation in the cervical area corresponding to the level being stimulated, and no stimulation should
be felt by the patient in a radicular manner down the shoulder or upper extremity. Motor stimulation should be
performed with the generator set at 2 Hz and should be carried from zero to 2 Vs. At this point, motor contraction
can be seen in the paraspinous muscles in the neck, but no stimulation should be felt by the patient down the upper
extremity or in the shoulder.
Figure 35-18 Depiction of “bone-hugging” technique in the cervical spine with curved blunt needle around the waist of the articular pillar. It is
important to note that a good contact is needed with the medial branch (mb) in the articular pillar with the needle positioned parallel to the branch
that leads to the lesion.
Figure 35-19 A, The needle (arrow)

positioned for medial branch
radiofrequency neurotomy in the
anteroposterior view lying in the center
of the waist of the articular pillar at the
level of C6. B and C, Lateral view
(arrows) of a radiofrequency needle
positioned along the center of the
quadrilateral, where the medial branch
lies. In the lateral view, the tips of the
radiofrequency needles lie posterior to
the neural foramen.
887
Once these two modes of stimulation are adequate, the radiofrequency lesioning can be started after the medial
branch is anesthetized with a maximal volume of 2 mL of local anesthetic. Lesioning is carried out at 80°C for 60 to
90 seconds. Once the first cycle is complete, the radiofrequency needle is rotated 90 degrees from its first position,
and a second cycle of lesioning is performed. This has the objective of creating two lesions, with a higher likelihood
of lesioning the medial branch completely. It is very important to mention some of the characteristics of the lesion
created by the radiofrequency probe. In essence, the lesion created is elliptical, surrounding the active uninsulated
tip and not extending beyond the tip of the probe ( Fig. 35–20 ). This is why it is very important to position the
probe parallel to the structure or nerve to be lesioned. It
Figure 35-20 Depiction of radiofrequency lesion around uninsulated active tip. The shape of the lesion is elliptic around the needle tip, but note
that it does not extend beyond the needle tip.
Figure 35-21 Lateral view of the cervical spine showing radiofrequency needle (arrow) positioned for lesioning of the third occipital nerve
(superior needle), which is located in the lateral aspect of the facet joint between C2 and C3.
isalso why we encourage creating two lesions with a rotation of the needle of 90 degrees. Figure 35–21 shows the
optimal needle positioning for radiofrequency lesioning of the third occipital nerve, the only variant in the medial
branch trajectory. The needle is positioned in the lateral aspect of the C2 to 3 facet joint, where this branch lies.
There has been some controversy over lesioning this branch because it has the potential to result not only in
anesthesia of the skin overlying the suboccipital region but also in some vertigo and dizziness. It is important, [91]
however, to obtain a good denervation of this joint because as described earlier, it is one of the most commonly
involved joints in whiplash injury.
Lumbar Facet Block

Lumbar facet block has the same purpose as its cervical counterpart. The most commonly used technique is with the
patient lying prone on the fluoroscopy table ( Fig. 35–22 ). The patient's lower back is prepared in a sterile fashion
and draped. The level chosen to be blocked is identified under fluoroscopy in the PA projection. Once the level is
identified, the fluoroscopy ray is slowly rotated in an oblique fashion toward the lateral projection until a view of the
“scotty dog” is obtained ( Fig. 35–23 ). This view is described as the projection that allows visualization of the facet
joint space as well as the superior and inferior articular processes that form the joint. The Scotty dog is formed by
888
the superior pars as well as the inferior pars of the same vertebra. The ear of the dog is the superior articular process
(pars) and the front legs of the dog are formed by the inferior articular process (pars) (see Fig. 35–23 ). Once this
view has been obtained, the optimal point of contact with the bone by the needle should be the eye of the dog (see
Fig. 35–23 ). There is no such anatomic structure but it is an approximation of where the eye would be. The pedicle
of the vertebra contains this approximation (see Fig. 35–23 ). After a skin wheal
Figure 35-22 Patient in prone position for lumbar medial branch

block and radiofrequency neurotomy. Oblique view (solid) and
lateral view (dotted).
is raised and the skin is properly anesthetized, a spinal needle is advanced in a gun-barrel fashion toward the eye of
the Scotty dog. It should be emphasized that there should always be bone in front of the needle in order to avoid
complications ( Fig. 35–24 ). Once bone contact is made, the needle position should be confirmed by the lateral
projection, at which point the needle should be seen at the level of the facet line and not beyond this point, posterior
to the foraminal opening, and finally below the level of the intervertebral disc ( Fig. 35–25 A–C). If desired, an AP
view can also be used to confirm the position of the needle. In this view, the needle should be seen at the junction of
Figure 35-23 Oblique view of the lumbar spine showing the optimal view to obtain the “scotty dog”: (a) the “ear” of the Scotty dog; (b) the
“nose” or “snout,” which corresponds to the transverse process; (c) the lower articular process, which forms the “front legs” of the dog. The
clamp shows the area considered the “eye” of the Scotty dog, which is contained within the pedicle.
889
Figure 35-24 A–C, Oblique views of several segmental levels with needles (arrows) positioned at the eye of the “scotty dog” for medial branch
blocks in the lumbar spine.
the superior articular process and the medialmost aspect of the transverse process ( Fig. 35–26 ). At this point, after
careful aspiration, the local anesthetic solution is injected. This should be repeated at the level corresponding to the
medial branch, and the facet joint targeted should be innervated. For a block of the medial branch of L5, a somewhat
different approach is used. The medial branch at this level lies in the groove formed by the superior articular process
of the sacrum and the ala of this bone. To obtain this view, the ray may need to be rotated in a cephalocaudad
fashion to remove the iliac crest from the view ( Fig. 35–27 A). Once the view is obtained, the needle is directed in a
gun-barrel fashion to the superiormost aspect of the “valley” formed by the ala of the sacrum and its superior
articular process (see Fig. 35–27 B and C). In the lateral view, the needle should be seen outside and posterior to the
neural foramen (see Fig. 35–27 D).
Lumbar Facet Radiofrequency Denervation

Radiofrequency denervation of the lumbar medial branches is carried out in a manner similar to the lumbar medial
branch block. The positioning of the needle is slightly different from the one described earlier. The patient is
positioned in the same fashion, and
890
Figure 35-25 A and B, A lateral view of the lumbar spine, with needles shown for block and radiofrequency lesioning. The needles (arrows) are
placed along the facet joint line, posterior to the neural foramen (NF) and below the level of the intervertebral disc (ID). C, View of a needle (s)
(superior) that is too far anterior and into the inferior portion of the neural foramen (NF). At this point, the needle should be withdrawn or
repositioned.
the ray is oriented also to obtain a view of the Scotty dog as described previously. The needle used is the same as the
one used for cervical denervation. In a gun-barrel fashion an Angiocath cannula is advanced from the skin down to
the eye of the Scotty dog ( Fig. 35–28 A). Once the cannula is inserted, the blunt curved-tip radiofrequency needle is
advanced through the cannula in a gun-barrel fashion until bony contact is made. At this point, the tip of the needle
should contact bone at the eye of the Scotty dog. The needle is carefully directed superior and slightly lateral to this
point until the tip is “walked off” the superior edge of the transverse process superior pars junction (see Fig. 35–28
B). The tip of the needle should not extend beyond the bone because of the risk of being too deep in the neural
foramen (see Fig. 35–28 C and D). Confirmation of the needle position should be done in the lateral and AP views
as described earlier for the blocks. Fig. 35–25 A and B and Fig. 35–28 E show the optimal positioning of the
radiofrequency denervation needle in the AP and lateral views. As mentioned before, the
891
Figure 35-26 Anteroposterior radiographic view of needles (arrows) positioned for block and radiofrequency lesioning. Note the position of the
needles at the junction of the transverse process (TP) and the superior articular process (SAP) along the superior border of the transverse process
(TP).
Figure 35-27 A. Anteroposterior (AP) view, with some degree of cephalocaudad deviation illustrating an Angiocath cannula (c) directed in gun-
barrel fashion toward the bottom of the “valley” (v) formed by the ala (a) of the sacrum and the articular process (b). B and C, Oblique and AP
views, respectively, showing the tip of the needle (n) positioned for block and radiofrequency lesioning in the valley (v) between the ala (a) of the
sacrum and the superior articular process (b) of the same bone. D, Lateral view with the tip of the needle (n) (inferior needle) posterior to the
neural foramen (NF) and at the level of the ala of the sacrum.
needle tip should be outside and posterior to the neural foraminal opening and should coincide with the facet line
posteriorly as well as being below the level of the intervertebral disc.
Once the radiologic confirmation is obtained, the radiofrequency lesioning is started, provided sensory and motor
stimulations are adequate. For radiofrequency lesioning of the lumbar medial branches, the probe is heated to 80°C
for 60 to 90 seconds and followed by another cycle after a 90-degree rotation of the needle. For radiofrequency
lesioning of the L5 medial branch, the approach described before is used, but the active, uninsulated, curved tip of
892
the needle should be positioned in such a way that it lies in the valley formed by the ala of the sacrum and its
superior articular process (see Fig. 27-35D).
Complications of Facet Block and Radiofrequency Lesioning

In general, the most common complication of cervical and lumbar facet blocks and radiofrequency lesioning is a
transient increase in pain immediately after the procedure. The overall incidence is 2%, with a variable period
lasting from weeks to a maximum of 8 months. Spinal anesthesia after intra-articular lumbar facet joint injections
[93]
has been reported. This is one of the reasons why medial branch blocks and radiofrequency lesioning are
[153]
encouraged rather than intra-articular injections. With the popularity of fluoroscopy, these complications will most
likely be reduced. The strongest reason for spinal anesthesia after intra-articular injection is the close relationship
between the facet joint
Figure 35-28 A, Oblique view of the lumbar spine with an Angiocath cannula (a) directed toward the eye (e) of the “Scotty dog.” B, The same
view with a blunt-tip, curved radiofrequency needle (n) through the Angiocath positioned, and “walked off” superiorly, and placed in the groove
where the medial branch lies. C and D, Additional examples of other radiofrequency needle (n) positioning in the oblique and anteroposterior
views, respectively. Note how the tips of the needles do not go over the superior border of the medial aspect of the transverse process. E, Lateral
view of the above-positioned needle (n), confirming the characteristics of the positioning described before. It is important to confirm position in
this view to document that the needle is below the level of the intervertebral disc (ID) at the level of the facet line posteriorly and, most important,
outside the neural foramen (NF).
capsule and the ligamentum flavum in its anteromedial aspect. Chemical meningism has also been reported after a
medial branch block. This can also be explained by inadvertent dural puncture. It is important to confirm needle
[154] [155]
placement in more than one projection, particularly the lateral view, to ensure that the needle tip is outside and
posterior to the neural foramen. Certainly, an inadvertent injection into the dural sleeve with resultant deposit of
local anesthetic or steroid into the subarachnoid space can result in complications. Other less severe complications
893
include paraspinous tissue infection in the form of an abscess. This places crucial importance on the
[156] [157] [158]
preservation of sterile technique throughout the entire procedure. The same complications described for the lumbar
facet injections and blocks can occur in their cervical counterparts. Inadvertent subarachnoid and root sleeve
injections can occur as well as infections. One of the most feared complications is the inadvertent injection of local
anesthetic or non–water-soluble steroid into the vertebral artery. This is more likely to occur during intra-articular
injections rather than medial branch blocks. However, if the needle tip during a medial branch block is too far
anterior this can definitely result in vertebral artery puncture. One of the reasons why we emphasize the use of
water-soluble steroids such as dexamethasone in the cervical region is because injection of a deposit-precipitated
steroid into the central nervous system circulation via the vertebral artery can have catastrophic consequences such
as a cerebrovascular accident with resultant deficit.
One particular complication in the cervical region relates specifically to the denervation of the C2 to C3 facet joint
by targeting the third occipital nerve. This can result in anesthesia of the suboccipital region, as well as dizziness
and vertigo, most likely because of blockade of the upper cervical proprioceptive afferents. This, however, appears [92]
to be a transient complication, and no long-term effects have been reported. In terms of radiofrequency lesioning of
the medial branches, one of the less common complications is radiation neuritis. When it occurs, it is very
uncomfortable and worrisome to the patient. It is manifested by a new-onset, radicular-type, burning pain, of which
the patient usually has no earlier recollection. This pain is neuritis caused by the proximity of the radiofrequency
needle to a large nerve root. It is a self-limited process that usually responds to conservative therapy and systemic
steroids and is not expected to last more than 2 to 3 weeks. It is crucial to check the needle insulation along the shaft
before insertion, because it is at this insulation break, if it exists, that a lesion can be made on the nerve root. During
the lesioning cycle, if the patient experiences a sudden onset of burning sensation or pain down the extremity, the
cycle should be stopped immediately and the needle repositioned or the procedure aborted. It cannot be emphasized
enough that the use of fluoroscopy guarantees not only accuracy but also safety. In the cervical region, the hazards
of a needle misdirected and displaced medially can result in spinal cord injury in the cervical region. It is obvious
that any pain syndrome experienced by the patient is more tolerable than this latter complication.
Studies on Efficacy
As mentioned earlier, one cannot find any conclusive evidence in the literature showing the superiority of medial
branch blocks over intra-articular injections. One of the most complete reviews regarding the efficacy of cervical
medial branch radiofrequency denervation was done by Lord and associates in 1995. Seven series were included in
[92]
this review ( Table 35–2 ). The results demonstrated that all studies reported a percentage of patients between 37%
and 89% who experienced greater than 40% relief for a period longer than 2 months. Even though these studies were
flawed because of technical and anatomic errors, the results show encouraging evidence that medial branch
radiofrequency neurotomy may be beneficial in well-selected patients. Another study in 1996 by the same authors [159]
compared a group of control patients with a radiofrequency neurotomy group. The latter had significantly longer
pain relief (median time, 263 days) compared with the control group. The conclusion was also drawn that 71% of
patients undergoing denervation by radiofrequency had a good response when they were chosen by double
diagnostic blocks. On the other hand, Barnsley and colleagues calculated a 27% false-positive rate when double
[160]
diagnostic blocks were used. With these results, it is safe to say that there is some benefit to facet denervation when
the patients are chosen appropriately, but this still has to be proved by evidence gathered from large, prospective,
randomized, controlled trials. For lumbar medial branch blocks Schwarzer and coworkers calculated single [161]
diagnostic blocks as having a false-positive rate of 38%. Other studies have advocated comparative blocks to
[144] [145]
reduce this false-positive rate. Analgesia after medial branch blocks has been used as the selection criterion for
radiofrequency thermocoagulation neurotomy. Several studies, including those of Lora and Lora, Ogsbury and [162]
colleagues, and Silvers have reported long-term relief from neurotomy between 32% and 75%. For patients who
[163] [164]
had undergone previous surgery, prolonged relief was achieved in 26% to 50%, compared with 75% of those
without previous surgery. Another study with mixed results was that of Mehta and Sluijer. This study reported [165]
good results at 1 month in 45% of patients, with a steep decline to 28% at 1 year, and poor results in 50% at 1 year.
In contrast to the aforementioned studies, other studies have somewhat justified lumbar medial branch
radiofrequency denervation. North and associates published a retrospective review of 82 patients. Of the 42
[166]
patients who went on to medial branch neurotomy, 19 (45%) had approximately 50% relief with a mean duration of
3.2 years. Rashbaum reported 82% of patients with good pain relief (>50%) at 3 and 6 months and 68% with good
[167]
relief at 3 years. It is clear by looking at these results that the studies that had stricter selection criteria (clinical
evidence and positive response to medial branch blocks) had the better long-term results. In conclusion, a more
specific means of diagnosing facet arthropathy is needed, combined with
894
TABLE 35-2 -- SUMMARY OF OPEN STUDIES OF RADIOFREQUENCY NEUROTOMY FOR CERVICAL ZYGAPOPHYSEAL JOINT PAIN
Proportion with
No. of Results Based on Percent >40% Pain Relief
Series Patients Diagnostic Criteria Duration of Follow-up Pain Relief (%) (%)
Schaerer, 1978 50 Local tenderness and single “facet Mean, 15 mo; range, 3–25 mo Excellent (16) 50
block”
Good (34)
Fair (18)
Poor (28)
Lost to follow-up (4)
Schaerer, 1980 81 Local tenderness and single “facet Mean, 20 mo Excellent (53) 71
block”
Good (18)
Fair (14)
Poor (10)
Sluijter & Koetsveld- Baart, 1980 100 Single “facet block” Range, 16–31 mo Good (39) 61
Fair (22)
Poor (39)
Sluijter & Mehta, 1981 58 “Characteristic” symptoms and signs; 12 mo Good (58) 79
posterior primary ramus block only
in some cases Fair (21)
Poor (21)
Hildebrandt & Argyrakis, 1986 35 Single block of the zygapophyseal Mean, 14 mo; range, 3–30 mo Entire or significant (37) 37–66
joints or dorsal rami
Improved (29)
No change (34)
Schaerer, 1988 466 Local tenderness and single “facet Range, 2–128 mo Excellent (44)
block”
Good (31)
Fair (9)
Poor (12)
Vervest & Stolker, 1997 46 Localized neck pain and tenderness Excellent (37) 89
over the zygapophyseal joints
Good (52)
Unsatisfactory (11)
Data from references [9] [10] [11] [12] [13] [14] and [17] .
clinical evidence via controlled trials that medial branch neurotomy is effective.
REFERENCES
1. Goldthwait JE: The lumbosacral articulation: An explanation of many cases of lumbago, sciatica, and paraplegia. Boston Med Surg J 164:365,
1911.
2. Putti V: Lady Jones' lecture on new concepts in pathogenesis of sciatic pain. Lancet 2:53–60, 1927.
3. Ghormley RK: Low back pain with special reference to the articular facet, with presentation of an operative procedure. JAMA 101:1773–1777,
1993.
4. Mixter WJ, Barr JS: Rupture of the intervertebral disk with involvement of the spinal canal. N Engl J Med 211:210–215, 1934.
5. Badgley CE: The articular facets in relation to low back pain and sciatic radiation. J Bone Joint Surg Am 23:481–496, 1941.
6. Kellegren JH: Observations on referred pain arising from muscle. 175, 1938
7. Hirsch C, Ingelmark B, Miller M: The anatomical basis for low back pain. Acta Orthop Scand 33:1, 1963.
8. Mooney V, Robertson J: The facet syndrome. Clin Orthop 115:149–156, 1976.
9. Fox JL, Rizzoli HV: Identification of radiologic coordinates for the posterior articular nerve of Luschka in the lumbar spine. Surg Neurol
1:343–346, 1973.
10. Bogduk N, Long D: The anatomy of the so-called “articular nerves” and their relationship to facet denervation in the treatment of low back
pain. J Neurosurg 51:172–177, 1979.
895
12. Pawl RP: Headache, cervical spondylosis, and anterior cervical fusion. Surg Ann 9:391, 1971.
13. Hadden SB: Neurologic headache and facial pain. Arch Neurol 43:405, 1940.
14. Raney A, Raney RB: Headache: A common symptom of cervical disc lesions. Arch Neurol 59:603, 1948.
15. Taren JA, Kahn EA: Anatomic pathways related to pain in face and neck. J Neurosurg 19:116, 1962.
16. Brain L, Wilkinson M: Cervical Spondylosis. Philadelphia, WB Saunders, 1967.
17. McNab I: The whiplash syndrome. Clin Neurosurg 20:232, 1973.
18. Mehta M: Intractable Pain. Philadelphia, WB Saunders, 1973.
19. Lewin T, Moffet B, Viidik A: The morphology of the lumbar synovial intervertebral joints. Acta Morphol Neerl Scand 4:299–319, 1962.
20. Bogduk N, Twomey LT. Clinical Anatomy of the Lumbar Spine, 2nd ed. London Churchill Livingstone, 1991.
21. Paris SV: Anatomy as related to function and pain. Orthop Clin North Am 14:475–489, 1983.
22. Moran R, O'Connell D, Walsh M: The diagnostic value of facet joint injection. Spine 13:1407–1410, 1988.
23. Cyron BM, Hutton WC: The tensile strength of the capsular ligaments of the apophyseal joints. J Anat 132:145–150, 1981.
24. Yahia LH, Garzon S: Structure of the capsular ligaments of the facet joints. Ann Anat 175:185–188, 1993.
25. Bogduk N, Long DM: Percutaneous lumbar medial branch neurotomy. A modification of facet denervation. Spine 5:193–200, 1980.
26. Glover JR: Arthrography of the joints of the lumbar vertebral arches. Orthop Clin North Am 8:37–42, 1977.
27. Bogduk N: Back pain: Zygapophyseal blocks and epidural steroids. In Cousins MJ, Bridenbauch PO (eds): Neural Blockade in Clinical
Anesthesia and Management of Pain, 2nd ed. Philadelphia, JB Lippincott, 1989, pp 1935–1954.
28. Derbe R, Bogduk N, Schwarzer A: Precision percutaneous blocking procedures for localizing spinal pain. Part I: The posterior lumbar
compartment. Pain Digest 3:89–100, 1993.
29. Bogduk N, Engel R: The menisci of the lumbar zygapophyseal joints. A review of their anatomy and clinical significance. Spine 9:454–460,
1984.
30. Eisenstein
SM, Parry CR: The lumbar facet arthrosis syndrome: Clinical presentation and articular surface changes. J Bone Joint Surg
69(Br):3–7, 1987.
31. Kirkaldy-Willis WH: The relationship of structural pathology to the nerve root. Spine 9:49–52, 1984.
32. Dunlop RB, Adams MA, Hutton WC: Disc space narrowing and the lumbar facet joints. J Bone Joint Surg Br 66:706–710, 1984.
33. WinkelD, Aufdemkampe G, Matthijs O, et al: Diagnosis and Treatment of the Spine: Nonoperative Orthopaedic Medicine and Manual
Therapy. Gaithersberg, Md. Aspen, 1996.
34. Dunlop RB, Adams MA, Hutton WC: Disc space narrowing and the lumbar facet joints. J Bone Joint Surg Br 66:706–710, 1984.
35. Adams MA, Hutton WC: The mechanical function of the lumbar apophyseal joints. Spine 8:327–330, 1983.
36. Hickey
DS, Huskins DWL: Relation between the structure of annulus fibrosus and the function and failure of the intervertebral disc. Spine
5:100–116, 1980.
37. TwomeyLT, Taylor JR: Sagittal movements of the human vertebral column: A quantitative study of the role of the posterior elements. Arch
Phys Med Rehabil 64:322–325, 1983.
38. Horvitz T, Smith RM: An anatomical, pathological, and roentgenological study of the intervertebral joints of the lumbar spine and of the
sacroiliac joints. AJR 43:173–186, 1940.
39. Tournade
A, Patay Z, Krupa P, et al: A comparative study of the anatomical, radiological, and therapeutic features of the lumbar facet joints.
Radiology 34:257–261, 1992.
40. Maldjian
C, Mesgarzadeh M, Tehranzadeh J: Diagnostic and therapeutic features of facet and sacroiliac joint injection. Radiol Clin North Am
36:497–508, 1998.
41. Malmivaara A, Videman T, Kuosma E, et al: Facet joint orientation, facet and costovertebral joint osteoarthrosis, disc degeneration, vertebral
body osteophytosis, and Schmorl's nodes in the thoracolumbar junctional region of cadaveric spines. Spine 12:458–463, 1987.
896
42. Tulsi
RS, Hermanis GM: A study of the angle of inclination and facet and curvature of superior lumbar zygapophyseal facets. Spine 18:1311–
1317, 1993.
43. Panjabi MM, Oxland T, Takata K, et al: Articular facets of the human spine: Quantitative three-dimensional anatomy. Spine 18:1298–1310,
1993.
44. Tulsi RS, Hermanis GM: A study of the angle of inclination and facet curvature of superior lumbar zygapophyseal facets. Spine 18:1311–1317,
1993.
45. Krismer M, Haid C, Rable W: The contribution of the anulus fibers to torque resistance. Spine 21:2551–2557, 1996.
46. Yang KH, King AI: Mechanism of facet load transmission as a hypothesis for LBP. Spine 9:557–565, 1984.
47. Shirazi-Adl A: Biomechanics of the lumbar spin in sagittal/lateral moments. Spine 19:2407–2414, 1994.
48. Hedman TP, Fernie GR: Mechanical response of the lumbar spine to seated postural loads. Spine 22:734–742, 1997.
49. El-Bohy
AA, Goldberg SJ, King AI: Measurement of facet capsule stretch. Paper presented at 1987 Biomechanics Symposium Conference of
the American Society of Mechanical Engineers, Cincinnati, Vol 84, pp 161–164.
50. Yamashita T, Minaki Y, Ozaktay AC, et al: A morphological study of the fibrous capsule of the human lumbar facet joint. Spine 21:538–543,
1996.
51. Haher TR, O'Brien M, Dryer JW, et al: The role of the lumbar facet joints in spinal stability; Identification of alternative paths of loading.
Spine 19:2667–2671, 1994.
52. Farfan
HF, Cossette JW, Robertson GH, et al: The effects of torsion on the lumbar intervertebral joints: The role of torsion in the production of
disc degeneration. J Bone Joint Surg Am 52:468–497, 1970.
53. McFadden KD, Taylor JR: Axial rotation in the lumbar spine and gaping of the zygapophyseal joints. Spine 15:295–299, 1990.
54. AdamsMA, Hutton HC: The effect of posture on the role of the apophyseal joints in resisting intervertebral compressive forces. J Bone Joint
Surg Br 62:358–362, 1980.
55. Cavanaugh HM: Lumbar facet pain: Biomechanics, neuroanatomy and neurophysiology. J Biomech 29:1117–1129, 1996.
56. Lord SM, Bogduk N: Treatment of chronic cervical zygapophyseal joint pain. N Engl J Med 336:1530–1531, 1997.
57. Schwarzer AC, Aprill CN, Derby R, et al: The relative contributions of the disc and zygapophyseal joint in chronic LBP. Spine 19:801–806,
1994.
58. White AA III, Panjabi MM: Clinical Biomechanics of the Spine, 2nd ed. Philadelphia, JB Lippincott, 1990.
59. Miles M, Sullivan WE: Lateral bending at the lumbar and lumbosacral joints. Anat Rec 139:387, 1961.
60. Pearcy
MJ, Tibrewal SB: Axial rotational and lateral bending in the normal lumbar spine measured by three-dimensional radiography. Spine
9:582, 1984.
61. Tibrewal SB, Pearcy MJ, Portek I, et al: Prospective study of lumbar spinal movements before and after discectomy using biplanar radiography.
Correlation of clinical and radiographic findings. Spine 10:455, 1985.
62. Pearcy M, Portek I, Sheppard J: Three-dimensional x-ray analysis of normal movement in the lumbar spine. Spine 9:294–297, 1984.
63. Pearcy MJ, Tibrewal SB: Axial rotation and normal bending in the normal lumbar spine measured by three-dimensional radiography. Spine
9:582–587, 1984.
64. Pearcy MJ: Stereo-radiography of lumbar spine motion. Acta Orthop Scand Suppl 212:1–41, 1985.
65. Gray DP, Bajwa ZH, Warfield C.: Facet block and neurolysis. In Waldmun SD (ed): Interventional Pain Management, 2nd ed. Philadelphia
66. Adams LP, Tregidga A, Driver-Jowitt JP, et al: Analysis of motion of the head. Spine 19:266–271, 1994.
67. Vishteh
AG, Crawford NR, Melton MS, et al: Stability of the craniovertebral junction after unilateral occipital condyle resection: A
biomechanical study. J Neurosurg 90:91–98, 1999.
68. Jofe M, White A, Panjabi M: Clinically relevant kinematics of the cervical spine. In Sherk H, Dunn E, Eismont F, et al (eds): The Cervical
Spine, ed 2. Philadelphia, JB Lippincott, 1989, pp 57–69.
69. Worth DR, Selvik G: Movements of the craniovertebral joints. In Grieve GP (ed): Modern Manual Therapy of the Vertebral Column. London,
Churchill Livingstone, 1987, pp 53–63.
897
70. Wolff HD: Die Sonderstellung des Kopfgelenkbereichs: Grundlagen, Klinik, Begutachtung. Berlin, Springer-Verlag, 1988.
71. Penning L: Normal movements of the cervical spine. AJR Am J Roentgenol 130:317–326, 1978.
72. Panjabi M, Dvorak J, Duranceau J, et al: Three-dimensional movements of the upper cervical spine. Spine 13:726–730, 1988.
73. OrdwayNR, Seymour RJ, Donelson RG, et al: Cervical flexion, extension, protrusion, and retraction. A radiographic segmental analysis.
Spine 24:240–247, 1999.
74. Hland JH, Boushey DR: Anatomy and physiology of the cervical spine. Semin Arthritis Rheum 20:1–20, 1990.
75. Dvorak J: Epidemiology, physical examination, and neuro-diagnostics. Spine, 23:2663–2673, 1998.
76. Jirout J: Funktionelle Pathologie und Klinik der Wirbelsäule. Stuttgart, Gustav Fischer Verlag, 1990.
77. Clausen JD, Goel VK, Traynelis VC, et al: Uncinate processes and Luschka joints influence the biomechanics of cervical spine: Quantification
using a finite element model of the C5–C6 segment. J Orthop Res 15:342–347, 1997.
78. Onan OA, Heggeness MH, Hipp JA: A motion analysis of the cervical facet joint. Spine 23:430–439, 1998.
79. Lysell E.: Motion in the cervical spine. Acta Orthop Scand Suppl 123, 1969. [The most exhaustive and carefully done study of the kinematics
of the lower cervical spine.]
80. LuJ, Ebrahiem NA, Huntoon M, et al: Cervical intervertebraldisc space narrowing and size of intervertebral foramina. Clin Orthop 370:259–
264, 2000.
81. Holmes, et al: The range and nature of flexion-extension motion in the cervical spine. Spine 19:2505–2510, 1994.
82. Chen TY, Crawford NR, Sonntag VKH, et al: Biomechanical effects of progressive anterior cervical decompression. Spine 26:6–14, 2001.
83. Goel
VK, Clausen JD: Prediction of load sharing among spinal components of a C5–C6 motion segment using the finite-element approach.
Spine 23:684–691, 1998.
84. Winkelstein BA, Nightengale RW, Richardson WJ, et al: The cervical facet capsule and its role in whiplash injury. Spine 25:1238–1246, 2000.
85. Barnsley L, Bogduk N: Medical branch blocks are specific for the diagnosis of cervical zygapophyseal joint pain. Reg Anesth 18:343–350,
1993.
86. Barnsley L, Lord SM, Wallis BJ, et al: The prevalence of chronic cervical zygapophyseal joint pain after whiplash. Spine 20:20–26, 1995.
87. Bovim G, Berg R, Gunnar Dale L: Cervicogenic headache: Anesthetic blockades of cervical nerves and facet joint (C2/C3). Pain 49:315–320,
1992.
88. Svensson MY: Injury biomechanics. In Gunzburg R, Szpalski M (eds): Whiplash Injuries. Philadelphia, Lippincott-Raven, 1998, p 70.
89. White,
AA, Southwick, WO, DePonte, RJ, et al: Relief of pain by anterior cervical spine fusion for spondylosis, A report of 65 patients. J.
Bone Joint Surg Am 55:525, 1973.
90. Bogduk N, Anat D: The clinical anatomy of the cervical dorsal rami. Spine 7:319–330, 1982.
91. Bogduk N, Marsland A: The cervical zygapophyseal joints as a source of neck pain. Spine 13:610–617, 1988.
92. Lord
SM, Barnsley L, Bogduk N: Percutaneous radiofrequency neurotomy in the treatment of cervical zygapophyseal joint pain: A caution.
93. Lynch MC, Taylor JF: Facet joint injection for low back pain: A clinical study. J Bone Joint Surg Br 68:138–141, 1986.
94. Bous RA: Facet joint injections. In Stanton-Hicks M, Bous R (eds): Chronic Low Back Pain. New York, Raven Press, 1982, pp 199–211.
95. MaigneJ-Y, Maigne R, Guerin-Surville H: The lumbar mamillo-accessory foramen: A study of 203 lumbosacral spines. Surg Radiol Anat
13:29–32, 1991.
96. Giles
LGF: The relationship between the medial branch of the lumbar posterior ramus and the mamillo-accessory ligament. J Manipulative
Physiol Ther 14:189–192, 1991.
97. Gillette
RG, Kramis RC, Roberts WJ: Spinal projections of cat primary afferent fibers innervating lumbar facet joints and multifidus muscle.
Neurosci Lett, 157:67, 1993.
98. Suseki K, Takahashi Y, Takahashi K, et al: Innervation of the lumbar facet joints. Spine 22:477–485, 1997.
898
99. MarksRC, Houston T, Thulbourne T: Facet joint injection and facet nerve block: A randomized comparison in 86 patients with chronic low
back pain. Pain 49:325–328, 1992.
100. Yamashita T, Cavanaugh JM, El-Boly AA, et al: Mechanosensitive afferent units in the lumbar facet joint. J Bone Joint Surg Am 72:865–870,
1990.
101. Ashton IK, Aston BA, Gibson SJ, et al: Morphological basis for back pain: The demonstration of nerve fibers and neuropeptides in the lumbar
facet joint capsule but not in ligamentum flavum. J Orthop Res 10:72–78, 1992.
102. Cavanaugh JM, Ozaktay AC, Yamashita T, et al: Mechanisms of low back pain: A neurophysiologic and neuroanatomic study. Clin Orthop
335:166–180, 1997.
103. Beaman DN, Graziano GP, Glover RA, et al: Substance P innervation of lumbar spine facet joints. Spine 18:1044–1049, 1993.
104. Gronblad
M, Weintein JN, Santavirta S: Immunohistochemical observations on spinal tissue innervation: A review of hypothetical
mechanisms of back pain. Acta Orthop Scand 62:614–622, 1991.
105. Gronblad
M, Korkala O, Konttinen YT, et al: Silver impregnation and immunohistochemical study of nerves in lumbar facet joint plical tissue.
Spine 16:34–38, 1991.
106. Silees LGF, Taylor JR: Human zygapophyseal joint capsule and synovial fold innervation. Br J Rheumatol 26:93–98, 1987.
107. Wyke B: The neurology of joints: A review of general principles. Clin Rheum Dis 7:223–239, 1981.
108. Cavanaugh JM: Neural mechanisms of lumbar pain. Spine 20:1804–1809, 1995.
109. Yamashita T, Cavanaugh JM: Effect of substance P on mechanosensitive units of tissue around and in the facet joint. J Orthop Res 11:205–
214, 1993.
110. GriggP, Schaible HG, Schmidt RF: Mechanical sensitivity of group III and IV afferents from posterior articular nerve in normal and inflamed
cat knee. J Neurophysiol 55:635–643, 1986.
111. Lord SM, Barnsley L, Wallis BJ, et al: Chronic cervical zygapophyseal joint pain after whiplash. Spine 21:1737–1745, 1996.
112. Bogduk N, Aprill C: On the nature of neck pain, discography, and cervical zygapophyseal joint blocks. Pain 54:213–217, 1993.
113. Aprill C, Bogduk N: The prevalence of cervical zygapophyseal joint pain. Spine 17:744–747, 1992.
114. Taylor JR, Ywomey LY: Acute injuries to cervical joints: An autopsy study of neck sprain. Spine 18:1115–1122, 1993.
115. Dwyer A, Aprill C, Bogduk N: Cervical zygapophyseal joint pain patterns I: A study in normal volunteers. Spine 15:453–457, 1990.
116. Pospiech J, Stolke D, Wilke HJ, et al: Intradiscal pressure recordings in the cervical spine. Neurosurgery 44:379–385, 1999.
117. ClausenJD, Goel VK, Traynelis VC, et al: Uncinate processes and Luschka joints influence the biomechanics of cervical spine:
Quantification using a finite element model of the C5–C6 segment. J Orthop Res, 15:342–347, 1997.
118. Kitahata L, McAllister RG, Taub A: Identification of central trigeminal nociceptors. Adv Neurol 4:83, 1974.
119. WhiteAA, Southwick WO, Deponte RJ, et al: Relief of pain by anterior cervical spine fusion for spondylosis—a report of 65 patients. J Bone
Joint Surg Am 55:525, 1973.
120. Sjaastad I, Fredriksen TA, Pfaffenrath V: Cervicogenic headache: Diagnostic criteria. Headache 30:725–726, 1990.
121. Binet EF, Moro JJ, Marangola JP, et al: Cervical spine tomography in trauma. Spine 2:163–172, 1977.
122. Jonsson HF, Bring G, Rauschning W, et al: Hidden cervical spine injuries in traffic accident victims with skull fractures. J Spinal Disord
4:251–263, 1991.
123. Woodring JH, Goldstein SJ: Fractures of the articular processes of the cervical spine. AJR Am J Roentgenol 139:341–344, 1982.
124. Carrera GF: Lumbar facet joint injection in low back pain and sciatica. Radiology 137:661–664, 1980.
125. Aprill C, Dwyer A, Bogduk N: Cervical zygapophyseal joint pain patterns II: A clinical evaluation. Spine 15:458–461, 1990.
126. Fukui S, Ohseto K, Shiotani M, et al: Referred pain distribution of the cervical zygapophyseal joints and cervical dorsal rami. Pain 68:79–83,
1996.
127. Carette
S, Marcoux S, Truchon R, et al: A controlled trial of corticosteroid injections into the facet joints for chronic low back pain. New Engl
J Med 325:1002–1007, 1991.
899
128. Revel
ME, Listrat VM, Chevalier IL, et al: Facet joint block for LBP: Identifying predictors of a good response. Arch Phys Med Rehabil
73:824–828, 1992.
129. Fairbank
JCT, Park WM, Mcdall IW, et al: Apophyseal injection of local anesthetic as a diagnostic aid in primary low-back pain syndromes.
Spine 6:598–605, 1981.
130. Carrera GF, Williams AL: Current concepts in evaluation of the lumbar facet joints. Crit Rev Diagn Imaging 21:85–104, 1984.
131. Destouet JM, Gilualla LA, Murphy WA, et al: Lumbar facet joint injection: Indication, technique, clinical correlation and preliminary results.
Radiology 145:321–325, 1982.
132. Helbig T, Lee CK: The lumbar facet joint syndrome. Spine 1:461–464, 1988.
133. Jackson RP, Jacobs RR, Montesano PX: Facet injection in LBP: A prospective statistical study. Spine 13:966–971, 1988.
134. Lau LSW, Littlejohn GO, Miller MH: Clinical evaluation of inarticular injections for lumbar facet joint pain. Med J Aust 143:563–565, 1985.
135. Lewinnek GE, Warfield CA: Facet joint degeneration as a cause of LBP. Clin Orthop 213:215–222, 1986.
136. Lippitt AB: The facet joint and its role in spine pain: Management with facet joint injections. Spine 9:746–750, 1984.
137. Raymond J, Dumas J: Intra-articular facet block: Diagnostic test or therapeutic procedure? Radiology 151:333–336, 1984.
138. Jackson RP: The facet syndrome: Myth or reality? Clin Orthop 121:110–121, 1992.
139. Hirsch D, Ingelmark B, Miller M: The anatomical basis for LBP. Acta Orthop Scand 33:1–17, 1963.
140. McCall IW, Park WM, O'Brien JP: Induced pain referral from posterior lumbar elements in normal subjects. Spine 4:441–446, 1979.
141. Fukui
S, Ohseto K, Shiotani M, et al: Distribution of referred pain from the lumbar zygapophyseal joints and dorsal rami. Clin J Pain 13:303–
307, 1997.
142. Twomey LT, Taylor JR, Taylor MM: Unsuspected damage to lumbar zygapophyseal (facet) joints after motor vehicle accidents Med J Aust
151:210, 1989.
143. Wiesel SW, Tsourmas N, Feffer HL, et al: A study of computer assisted tomography 1: The incidence of positive CAT scans in an
asymptomatic group of patients. Spine 9:549–551, 1981.
144. Boas RA: Nerve block in the diagnosis of LBP. Neurosurg Clin North Am 2:807–816, 1991.
145. Barnsley L, Lord S, Bogduk N: Comparative local anesthetic blocks in the diagnosis of cervical zygapophyseal joint pain. Pain 55:99–106,
1993.
146. Bonica JJ: Local anesthesia and regional blocks. In Wall PD, Melzack R (eds): Textbook of Pain, 2nd ed. Edinburgh, Churchill Livingstone,
1989, pp 724–743.
147. Bonica JJ, Buckley FP: Regional analgesia with local anesthetics In Bonica JJ (ed): The Management of Pain. Philadelphia, Lea & Febiger,
1990, pp 1883–1966.
148. Schwarzer A, Derby R, Aprill C, et al: Pain from the lumbar zygapophyseal joints: A test of two models. J Spinal Disord 7:331–336, 1994.
149. Schwarzer AC, Aprill CN, Fortin J, et al: The clinical features of patients with pain stemming from the lumbar zygapophyseal joints: Is the
150. Schuster GD: The use of cryoanalgesia in the painful facet syndrome. J Neurol Orthop Surg 3:271, 1982.
151. Maigne R, LeCorre F, Judet H: Lombalgies basses d'origine dorso-lombaire: Traitement chirurgical par excision des capsules articulaires
postérieures. Nouv Presse Med 7:565, 1978
152. Wenger C: Radiofrequency lesions for the treatment of spinal pain. Pain Digest 8:1–16, 1998.
153. Goldstone JC, Pennant JH: Spinal anesthesia following facet joint injection: A report of two cases. Anaesthesia 42:754–756, 1987.
154. Thomson SJ, Lomas DM, Collett BJ: Chemical meningism after lumbar facet joint block with local anesthetic and steroids. Anaesthesia
46:563–564, 1991.
155. Berrigan T: Chemical meningism after lumbar facet joint block. Anaesthesia 47:905–906, 1992.
156. Magee M, Kannangara S, Dennieen B: Paraspinal abscess complicating facet joint injection. Clin Nucl Med 25:71–73, 2000.
900
157. Cook NJ, Hanrahan P, Song S: Paraspinal abscess following facet joint injection. Clin Rheumatol 8: 52–53, 1999.
158. Goucke CR, Graziotti P: Extradural abscess following local anaesthetic and steroid injection for chronic low back pain. Br J Anaesth 65:427–
429, 1990.
159. Lord
SM, Barnsley L, Wallis BJ, et al: Percutaneous radiofrequency neurotomy for chronic cervical zygapophyseal joint pain. N Engl J Med
335:1721–1726, 1996.
160. Barnsley L, Lord S, Wallis B, et al: False-positive rates of cervical zygapophyseal joint blocks. Clin J Pain 9:124–130, 1993.
161. Schwarzer AC, Aprill CN, Derby R, et al: The false positive rate of uncontrolled diagnostic blocks of the lumbar zygapophyseal joints. Pain
58:195–200, 1994.
162. Lora J, Long D: So-called facet denervation in the management of intractable back pain. Spine 1:121–126, 1976.
163. Ogsbury JS, Simon RH, Lehman RAW: Facet “denervation” in the treatment of low back syndrome. Pain 3:257–263, 1977.
164. Silvers R: Lumbar percutaneous facet rhizotomy. Spine 15:36–40, 1990.
165. Mehta M, Sluijter ME: The treatment of chronic back pain: A preliminary survey of the effect of radiofrequency denervation of the posterior
vertebral joints. Anaesthesia 34:768, 1979.
166. North RB, Han M, Zahurak M, et al: Radiofrequency lumbar facet denervation: Analysis of prognostic factors. Pain 57:77, 1994.
167. Rashbaum
RF: Radiofrequency facet denervation: A treatment alternative in refractory low back pain with or without leg pain. Orthop Clin
North Am 14:569, 1983.
901
Section V Chapter 36 - Nerve Root Neurolysis
Chapter 36 - Nerve Root Neurolysis
Miles Day
The origin of selective nerve root blockade can be traced back to 1906, when Sellheim performed paravertebral
blocks for urologic surgery. A few years later, Kappis (1912) described the blockade of the brachial plexus via the
[1]
cervical nerve roots. Over the ensuing century, selective root sleeve blocks became commonplace in the diagnosis
and treatment of many painful syndromes. For the purposes of this chapter, detailed knowledge of the nerve root and
surrounding anatomic structures is of utmost importance to improve the efficacy of the block, and, more important,
to decrease the incidence of complications. To complement the physician's knowledge base, the use of fluoroscopy
is heavily stressed. It is even more important if the physician chooses to use a neurolytic agent.
Anatomy
VERTEBRAL COLUMN
The spinal axis is comprised of 33 vertebral bodies: 7 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 4 coccygeal.
Each vertebra consists of two parts: the ventral vertebral body and the dorsal vertebral arch ( Fig. 36–1 ). In turn,
[2] [3]
the vertebral arch is composed of two pedicles anteriorly and two laminae posteriorly. Laterally, the pedicles and the
laminae of each vertebra join to form the transverse process. In a similar fashion, the laminae join dorsally to form
the spinous process, which is often bifid in the cervical region. The junction of the ventral vertebral body with the
dorsal vertebral arch creates the vertebral foramen, which in sequence forms the vertebral canal. The vertebral canal
is triangular in the cervical and lumbar regions but circular in the thoracic region. The vertebral bodies are
[4]
separated by the intervertebral discs which are composed of an avascular gelatin-like core, the nucleus pulposus,
surrounded by the anulus fibrosus, a collagenous lamella.
The posterior elements of each vertebra are separated by the facet joint, also known as the zygapophyseal joint. The
inferior pars articularis projecting caudally overlaps the superior pars articularis from the next most caudal vertebra. [4]
The articular surfaces are covered by hyaline cartilage and the joint itself is lined by synovium. The facet itself is
surrounded by a fibrous capsule. The cervical facets extend laterally from the junction of the laminae and pedicles
and are oriented in the coronal plane. In the thoracic spine, the facets extend superiorly and inferiorly from the
[5]
junctions of the laminae and pedicles. This orients the zygoapophyseal joints approximately 20 degrees off the
coronal plane. The superior pars articularis in the lumbar region is concave posteriorly, whereas the inferior pars
articularis is convex anteriorly. The lumbar facet joints are oriented approximately 45 degrees off the sagittal plane.
The vertebral column is reinforced by many ligaments. The major ligaments include the supraspinous ligament,
which joins the tips of successive vertebrae, and the interspinous ligament, which is located between the spinous
processes. The ligamentum flavum is located anterior to the interspinous ligament and spans from the anterior
surface of the cephalad lamina of an adjacent pair of vertebrae to the posterior aspect of the caudal lamina. The [4]
posterior longitudinal ligament reinforces the posterior border of the vertebral column, whereas the anterior
longitudinal ligament strengthens the anterior border. Other smaller ligaments are involved but are too numerous to
name individually.
The intervertebral foramina are formed by the pedicles at the cephalad and caudal ends; posteriorly, by the opposing
articular surfaces and ligamentum flavum, and anteriorly by the vertebral body superiorly and intervertebral disc
caudally ( Fig. 36–2 ). This holds true for all foramina except C1, C2, and the sacral foramina. The C1 foramen is
bordered superiorly by the caudal portion of the occipital bone, inferiorly by the posterior arch of the atlas,
anteriorly by the atlanto-occipital joint, and posteriorly by the posterior occipital-atlantal ligament. This ligament is
incomplete on each side to allow passage of the C1 nerve root and vertebral artery. The C2 intervertebral foramen
[6]
is bordered superiorly by the posterior arch of the atlas, inferiorly by the lamina of the axis, and anteriorly by the
atlantoaxial joint and its posterior capsule. Posteriorly, it is defined by the posteromedial corner between the arch of
[7]
the atlas and the lamina of the axis.
902
Figure 36-1 Comparative views of cervical, thoracic, and lumbar vertebrae, demonstrating their comparative anatomy. A, Superior view; B,
anterior view; C, left lateral view of fifth cervical vertebra. Key: 1, Bifid spinous process; 2, lamina; 3, superior articular process; 4, posterior
tubercle of transverse process; 5, intertubercular lamella of transverse process; 6, anterior tubercle of transverse process; 7, foramen of transverse
process; 8, vertebral body; 9, uncus; 10, pedicle; 11, vertebral foramen; 12, inferior articular process. D, Left lateral view of 10th thoracic
vertebra. Key: 1, body; 2, costal facet; 3, pedicle; 4, superior articular process; 5, transverse process; 6, spinous process; 7, inferior articular
process; 8, inferior vertebral arch. E, Superior view; F, posterior view; and G, left lateral view of first lumbar vertebra. Key: 1, spinous process; 2,
lamina; 3, superior articular process; 4, transverse process; 5, pedicle; 6, vertebral body; 7, vertebral foramen; 8, superior vertebral arch; 9,
inferior articular process; 10, inferior vertebral notch; 11, mamillary process; 12, accessory process. (From Hahn M, McQuillan P, Sheplock G
[eds]: Regional Anesthesia: An Atlas of Anatomy and Techniques. St. Louis, Mosby, 1996.)
The sacrum is a large, triangular bone composed of five fused sacral vertebrae ( Fig. 36–3 ). There are eight sacral
foramina, each with a ventral and a dorsal opening. The dorsal sacral foramina are located just lateral to the
intermediate sacral crests, which represent the fused articular processes of the sacral vertebrae. The dorsal S1 [8]
foramen is located approximately 1 cm medial to the posterosuperior iliac spine (PSIS), whereas the S2 foramen is 1
cm medial and 1 cm inferior to the PSIS. The S4 foramen is immediately lateral and just superior to the sacral cornu.
The S3 foramen is located midway between the S2 and S4 foramina. The sacral foramina are somewhat rounded in
form and diminish in size from above downward.
NERVE ROOTS
Exiting the neuroforamina are 31 pairs of spinal nerves: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 1 coccygeal.
The eighth cervical nerve emerges between the C7 and T1 vertebral bodies, and the remaining seven cervical nerves
emerge above their same-numbered vertebral bones. In the thoracic, lumbar, and sacral regions, the spinal nerves
emerge below their same-numbered vertebral segments.
Each nerve is formed by the union of the anterior (ventral) motor root and the posterior (dorsal) sensory root, which
remain separate within the subarachnoid space. The anterior root originates from the anterolateral columns of the
cord and is composed of from four to eight filaments. It is generally smaller than its posterior counterpart. The
posterior root originates from the posterolateral fissure of the cord and contains a ganglion that is not found in the
anterior root. Likewise, the posterior root is composed of four to eight rootlets. The two roots form a mixed
peripheral nerve only after becoming ensheathed by the dura-arachnoid distal to the dorsal root ganglion (DRG). [2]
The nerve root is covered by a thin membranous structure (root sheath), which is permeable to cerebrospinal fluid
(CSF). The nerve root sheath is continuous with the pia mater at the junction with the spinal cord. The epineurium
[9] [10]
of the peripheral nerve is continuous with the dura mater, and the endoneurium also continues from the peripheral
nerve to the nerve root. The perineurium separates into two layers at the border of these nervous tissues and only
part of it is included in the root sheath. Thus, the nerve root lacks both the perineurium and epineurium of the
peripheral nerve.
903
Figure 36-2 Parasagittal anatomic section through the lumbar spine, revealing
the facet joints, lumbar nerve roots, and related structures.(From Hahn M,
McQuillan P, Sheplock G [eds]: Regional Anesthesia: An Atlas of Anatomy and
Techniques. St. Louis, Mosby, 1996.)
Once the mixed nerve exits the intervertebral foramen, it divides into anterior and posterior rami, which innervate
their respective parts of the body. The larger anterior rami form the major nerve plexuses, whereas the smaller
posterior rami divide almost immediately into lateral and medial branches and innervate the paraspinous
musculature and the facet joints at their respective levels. Branching almost immediately from the ventral roots
[11]
from T1 to L2 are the white rami communicantes, which carry preganglionic sympathetic information to the
sympathetic ganglion. Some postganglionic sympathetic nerves exit the sympathetic ganglion and return to the
ventral division via the gray rami communicantes and others course through the sympathetic chain located along the
vertebral column.
DORSAL ROOT GANGLION
Location of the DRG is of prime importance when a radiofrequency procedure of the DRG is considered.
Considerable anatomic variance exists, as one would expect. Several anatomic studies have been performed to
elucidate the position of the DRG.
The ganglia of C1 and C2 are situated on the arches of the vertebrae over which the nerves pass. In a study
involving 15 cadavers, Lu and Ebraheim noted that the C2 nerve root and ganglion exit from the spinal cord and
[7]
travel out the foramen following an almost horizontal course. The C2 ganglia were all confined within the C2
foramen between the posterior atlantal arch and the lamina of the axis, occupied approximately 76% of the foramen
in height, and were proximal to the center of the C2 pedicle. In another study, Yabuki and Kikuchi examined 42
[12]
cadavers and devised a classification system of the cervical root ganglia. They classified the positions of the cervical
root ganglia (C4–C8) into two groups: proximally situated and distally situated. The positions were determined
according to the relation of the DRG to a line connecting the centers of the pedicles. If the proximal end of the DRG
was located proximal to the line, it was classified as a proximally situated type, and if it was distal to the line, a
distally situated type. Although this is not a universally accepted classification system, it is mentioned to alert the
physician to the variable location of the cervical DRG.
As with the cervical DRG, the location of the lumbar DRG is also variable. Sato and Kikuchi examined 35
[13]
cadavers and classified the DRG into three groups according to their positions: intraspinal, intraforaminal, and
extraforaminal. Positions of the DRG were assessed by two lines. The first line (A) connects the medial border of
the pedicles and the second line (B) connects the center of the pedicles. If the proximal end of the DRG lies
proximal to A, it is the intraspinal type; between A and B, intraforaminal; and distal to B, extraforaminal. In a
second study, Kikuchi and colleagues observed that the DRGs at L4 and L5 were mostly of the intraforaminal type,
[14]
whereas at S1 they were mostly intraspinal. They also noted variability in
904
Figure 36-3 Posterior views of adult and pediatric sacrums for comparison.(From Hahn M, McQuillan P, Sheplock G [eds]: Regional Anesthesia:
An Atlas of Anatomy and Techniques. St. Louis, Mosby, 1996.)
connecting patterns of the DRGs and ventral root at the intervertebral foramen.
To my knowledge, there are no existing studies of the anatomic variability of the thoracic DRGs.
BLOOD SUPPLY OF NERVE ROOTS AND DORSAL ROOT GANGLIA
In the cervical spinal cord, the anterior and posterior radicular arteries supply the nerve roots. These radicular
arteries are classified further as either proximal or distal. The proximal radicular artery is a branch from the anterior
or posterior spinal artery, while the distal radicular artery is a direct branch of the vertebral artery and enters the
dural root pouch on the anterior surface of its respective root. A ganglionic artery supplies the cervical DRG,
[9] [15]
which is often a direct vascular branch off the vertebral artery.
The nerve roots in the thoracic and lumbosacral regions also have a similar blood supply. The proximal radicular
arteries also branch from the anterior and posterior spinal arteries. The posterior intercostal, lumbar segmental, and
lateral sacral arteries give rise to the thoracic, lumbar, and sacral distal radicular arteries, respectively. At all levels,
a branch of the posterior radicular artery supplies the DRG.
Indications
The selective nerve root block (SNRB), when combined with a careful history, physical examination, and quality
radiographic studies, is an important tool in the diagnostic evaluation and treatment of patients with predominantly
radicular symptoms. It is helpful in patients with multiple-level abnormalities, in complex postoperative patients,
[16]
and in patients with clearly defined clinical symptoms without significant imaging findings. More specifically, an
[17]
SNRB is useful in (1) helping to ascertain the specific nociceptive pathway; (2) helping to define the mechanisms of
the chronic pain state; and (3) aiding in the differential diagnosis of the site of the pain. [18]
905
SNRBs are also performed for both prognostic and therapeutic purposes. Prognostically, the SNRB aids in
predicting the efficacy of a neurolytic or neurosurgical treatment. The prognostic block also affords the patient
[18] [19] [20]
the opportunity to experience the numbness and other side effects that follow surgical resection or neurolytic block. [18]
From this experience, the patient can decide whether or not to undergo the procedure. On a therapeutic basis,
SNRBs are useful for treating pain not amenable to other methods of analgesia. This can be on a temporary or
permanent basis depending on the medication used.Clinical indications include pain secondary to nerve root
compression, pain from tumor invasion of a nerve root or in the distribution of a nerve root, vertebral fractures,
acute herpetic neuralgia, postherpetic neuralgia, discogenic pain, segmental neuralgia, and postsurgical pain. [21] [22]
Medications
Medications used for SNRBs include local anesthetics, corticosteroids, and neurolytic agents. The most commonly
used local anesthetics are lidocaine and bupivacaine. The newer agents, ropivacaine and levobupivacaine, can also
be used and are probably safer since they are less neuro- and cardiotoxic than racemic bupivacaine. Triamcinolone
and methylprednisolone are generally the corticosteroids of choice in doses of 40 to 80 mg.
Only after appropriate patient selection and after a positive diagnostic block should the use of neurolytic agents or
neuroablative procedures be considered. Alcohol (50%–100%) and phenol (6%–12%, in saline, glycerin, or contrast)
are used solely to treat intractable cancer pain secondary to the major side effects of the agents, that is, neuritis and
paralysis. Neuroablative procedures such as radiofrequency lesioning and cryoneurolysis are utilized in treating
chronic nonmalignant pain but can also be applied to the treatment of malignant pain as well. Radiofrequency
lesioning includes conventional radiofrequency as well as electromagnetic field (EMF) pulsed radiofrequency.
Preoperative Requirements
All patients must sign a surgical consent before proceeding with any procedure and should understand fully any
possible side effects, especially if a neurolytic agent or a neuroablative procedure is planned. Patients on
anticoagulants should stop these several days before the procedure but only after clearing this with their primary
care physician. If necessary, coagulation studies (prothrombin time, partial thromboplastin time, bleeding time) can
be checked to confirm normal values. Patients should fast for at least 8 hours before the block.
Procedures
All procedures are performed using strict aseptic technique and under fluoroscopic guidance to improve efficacy and
to decrease the incidence of complications. An intravenous line is established and vital signs are monitored. An
anxiolytic or short-acting opioid can be used if needed.
A 22-gauge (G) B-bevel needle is used at most institutions, but I prefer a 20- or 22-G curved, blunt-tip needle. This
requires prior insertion of a short angiocatheter that is two sizes larger than the block needle. The curved, blunt-tip
needle is steerable and less traumatic to surrounding structures. Therefore, all the blocks described use this needle.
CERVICAL NERVE ROOTS
Selective blockade of the C3 to C8 nerve roots is performed in the same manner. The patient is placed in the supine
position with the head in the neutral position. After obtaining an anteroposterior (AP) fluoroscopic view of the
cervical spine, the C-arm is positioned obliquely until the neuroforamina are clearly visualized. The proper angle
causes the ipsilateral vertebral laminae to appear as a “string of beads.” A skin wheal is raised with local anesthetic
just posterior to the posterior border of the sternocleidomastoid muscle at the desired level. The physician should
note the location of the carotid artery in relation to the skin entry point. An angiocatheter is inserted to a depth of
approximately 1 to 2 cm. The curved, blunt-tip needle is inserted and directed toward the posterior aspect of the
neuroforamen. If aligned properly, the “bead” at the desired level is contacted before the neuroforamen is entered.
The needle is walked anteriorly until it just enters the posterior aspect of the neuroforamen. This avoids spearing of
the nerve root that exists more caudally, an event that is less likely with a blunt needle. An AP fluoroscopic view is
[22]
then obtained. The tip of the needle should be at the midpoint of the facet column.
A small amount (1 mL) of nonionic, water-soluble contrast (Omnipaque 240) is injected slowly to avoid trauma to
the nerve root. The spread of the contrast should delineate the nerve root only, with no spread into the epidural space
or onto the peripheral plexus ( Fig. 36–4 ). If resistance is felt or vascular spread is noted, the needle must be
redirected. After negative aspiration, 1.0 to 1.5 mL of local anesthetic (1%–2% lidocaine or 0.25–0.5% bupivacaine)
906
are injected under fluoroscopic guidance. The patient should not feel any pain or paresthesia during the injection.
The needle is removed and a sterile bandage is placed.
Selective blockade of the C2 nerve root is approached differently. A direct lateral approach can be used. The
angiocatheter and the curved, blunt-tip needle are inserted perpendicular to the junction of the posterior two thirds
with the anterior one third of the arch at C2. On the AP view, the needle is advanced until it is halfway across the
[23]
C1 to C2 joint line. The patient should have the mouth open to improve the anterior view of the C1 to C2 joint. To
outline the
Figure 36-4 Anteroposterior view of selective cervical nerve root block. Note that the needles are at the midpoint of the facet column. The nerve
roots are indicated (arrows).
nerve root, 1 mL of contrast is injected. After negative aspiration, local anesthetic is injected.
A posterior approach is also used at C2. An AP projection of the upper cervical spine is obtained. The atlantoaxial
joint on the desired side is identified. The angiocatheter is inserted with the curved, blunt-tip needle perpendicular to
the skin at a point just medial to the lateral aspect of the atlantoaxial joint and the needle is aimed just cephalad to
the joint. A lateral view is obtained and the needle is advanced until it is at the junction of the anterior one third and
the posterior two thirds of the arch of C2. To outline the nerve root, 1 mL of contrast and then local anesthetic are
injected.
THORACIC NERVE ROOTS
To block the thoracic nerve roots, the patient must be in the prone position. An AP view of the vertebral level to be
blocked is obtained. For the first and second thoracic nerves, the needle is directed just caudal to the transverse
process. A point 4 cm lateral to the spinous process of the desired level is marked. The needle is kept medial to this
point to avoid possible pneumothorax. The C-arm is positioned approximately 15 degrees obliquely in the coronal
plane. Using the gun-barrel technique, the needle is inserted and directed toward the junction of the inferior border
of the transverse process with the vertebral body. Once bone is contacted, the procedure is stopped and a lateral
view is obtained. The needle is advanced toward the posterior aspect of the foramen. If bone is contacted at any
point, a fluoroscopic view is obtained, with the needle rotated until bone is not felt, and then advanced. On the AP
view, the tip of the needle should be slightly medial to the lateral border of the vertebral body at the level of the
inferior pedicle shadow. Contrast and local anesthetic are injected as previously described.
The lower thoracic nerve roots are approached slightly differently. This is owing to the changing orientation of the
facet joints at the lower levels, which makes the neuroforamen more accessible. An AP view of the desired level is
obtained, and the 4-cm line is marked. The C-arm is positioned 15 to 20 degrees obliquely in the coronal plane. The
site of skin entry is the shadow of the tip of the superior pars articularis. The angiocatheter is inserted and the needle
advanced until the tip of the superior pars articularis is touched. The needle is rotated and walked around the pars.
The needle is advanced a few millimeters and a lateral view is obtained. On the lateral view, the needle is advanced
until it just enters the foramen below the inferior border of the pedicle ( Fig. 36–5 A). Proper placement of the
907
needle on the AP view is just below the pedicle, with the tip touching an imaginary line drawn vertically through the
center of each pedicle ( Fig. 36–5 B). Contrast and local anesthetic are then injected after negative aspiration.
LUMBAR NERVE ROOTS
The lumbar nerve roots are approached the same way as the lower thoracic roots, except that there is no “4-cm
Figure 36-5 A, Lateral view of the needle in the cephalodorsal quadrant of a thoracic foramen. B, Anteroposterior view of the needle just caudal
to the pedicle of a thoracic vertebra. The nerve root is clearly seen with some spread of contrast into the epidural space.
rule.” An AP fluoroscopic view of the desired level is obtained. The C-arm is positioned obliquely in the coronal
plane until the facet joint is delineated (approximately 20 degrees). Then the camera is placed 15 degrees obliquely
in the caudocephalad direction. This gives a clear picture of the superior pars articularis. The angiocatheter is
inserted and the curved, blunt-tip needle directed toward the tip of the pars. The pars is touched and the needle
walked off in the cephalad direction. In the lateral view, ideal placement of the needle is with the tip in the
cephalodorsal corner of the neuroforamen ( Fig. 36–6 A). In the AP plain view, the tip of the needle should be the
same as described for thoracic nerve roots ( Fig. 36–6 B). Contrast is injected to make the nerve root visible and then
local anesthetic is injected ( Fig. 36–6 C).
SACRAL NERVE ROOTS
Blockade of the sacral nerve roots is easily accomplished through the posterior sacral foramen. The route of access
is seen by adjusting the fluoroscopy beam to align the round posterior foramen with the curvilinear marking of the
anterior foramen. The angiocatheter is inserted with the blunt-tip needle through the posterior foramen ( Fig. 36–7 )
[23]
and the needle is advanced through the anterior foramen until the tip is just anterior to the anterior sacral plate on the
lateral view. Contrast and local anesthetic can then be injected ( Fig. 36–8 A and 8B).
A negative aspiration of blood and cerebrospinal fluid (CSF) must precede any injection. All injections should be
performed under fluoroscopic guidance to avoid intravascular or intrathecal spread.
DORSAL ROOT GANGLIONOTOMY (PARTIAL RHIZOTOMY)
Only after a successful diagnostic block should a partial rhizotomy of the DRG be attempted. This can be performed
using conventional radiofrequency, EMF pulsed–radiofrequency, cryoanalgesia, and neurolytics. Epidural neurolytic
blocks have been performed in the past, but, with the advent of radiofrequency techniques, neurolytics are
infrequently used. Therefore, only conventional and pulsed radiofrequency lesioning is discussed in this section. The
current hypothesis on the mechanism of action of EMF is that the membranes of nerves have a capacitor function
and that EMF creates a high electric field that punches holes in the capacitor, thus blocking transmission of stimuli
through A delta and C fibers. [24]
The specifics of needle placement are not discussed here because they have already been described. The following
descriptions are applicable to the C3 to C8, lower thoracic, and lumbar nerve root levels.
908
Once the radiofrequency needle has been properly placed in the posterior neuroforamen in the cervical region, and
in the superior, dorsal quadrant of the foramen in the thoracic and lumbar regions, sensory and motor testing can
commence. The goal is to position the tip of the needle directly adjacent to the DRG of the desired nerve root. A
sensory paresthesia should be felt in the desired dermatome at less than 1.0 V at 50-Hz stimulation. Ideal stimulation
should be felt between 0.4 and 0.6 V. If stimulation is felt at less than 0.4 V, the tip of the needle is too close to the
DRG, and if stimulation is felt at greater than 0.6 V, the tip is too far away from the DRG. Motor stimulation is then
performed at 2 Hz. There should be a clear dissociation between motor and sensory stimulation; that is, the voltage
required to see motor fasciculations at 2 Hz should be at least two times the voltage that produces sensory
stimulation at 50 Hz. Thus, if good sensory stimulation at 50 Hz was noted at 0.5 V, then motor fasciculations at 2
[25]
Hz should not be seen at voltages less than 1.0 V. The point of dissociation defines the position of the DRG. If
dissociation between sensory and motor stimulation cannot be obtained, the tip of the needle is not in alignment with
the DRG, and lesioning at this point is not recommended.
Figure 36-6 A, Lateral view with the needle in the cephalodorsal quadrant of the neuroforamen. B, Proper positioning of the needle in the
anteroposterior (AP) plane for a selective lumbar nerve root block. C, AP view after 1 mL of contrast material was injected. Contrast is spreading
along the nerve root.
Once the proper stimulation parameters have been achieved, 2 mL of local anesthetic with 40 mg of triamcinolone
diacetate are injected. After 3 to 5 minutes lesioning is performed at 67°C for 90 seconds with conventional
radiofrequency. With pulse EMF, local anesthetic is not required because the necessary temperature is just above
body temperature. Lesioning is carried out at 42°C for 120 seconds. There has been no reported neuritis with pulse
EMF.
At the C2 level, motor function is not a significant concern. Therefore, sensory stimulation is the only parameter that
needs to be checked. Paresthesias should be felt in the suboccipital region.
[25]
Ganglionotomy of the upper thoracic and sacral DRGs requires the creation of a burr hole through the lamina or the
posterior sacrum, respectively. Because this is beyond the expertise of most pain practitioners, it is not discussed.
An alternative at these levels is to use pulsed EMF directly on the nerve root. In my experience, I have not had any
complications with this technique.
909
COMPLICATIONS
One of the biggest concerns is damage to the nerve root during positioning of the needle. Using a blunt-tip needle
can dramatically reduce this complication. Neuritis after radiofrequency lesioning is the other big concern. This is
the reason why sensory and motor testing are so important. If the proper guidelines are not met, there is an increased
incidence of postprocedure neuritis (30%). Injection of steroid before lesioning helps reduce but not completely
eliminate the chance of neuritis.
Figure 36-7 Anteroposterior

view of a 16-gauge
angiocatheter through the right
S1 foramen.
Figure 36-8 Anteroposterior view of the right S1 nerve root after injection of contrast material via a 20-gauge curved, blunt-tipped needle in the
posterior S1 foramen. The letter “A” denotes the nerve root and the letter “B” denotes the needle. B, Lateral view. The arrow denotes the S1
nerve root.
Other complications include intravascular and intrathecal injection of medication, paralysis, bowel and bladder
incontinence, pneumothorax, hemothorax, bruising, bleeding, increased pain, and infection. [26]
EFFICACY
Krempen and colleagues prospectively evaluated 22 patients with complicated back pathology who presented with
[27]
sciatica as their chief complaint. Selective nerve root blocks were performed on each patient. Two patients who had
excellent relief of pain in the immediate postprocedure period decided against surgery. Sixteen patients had
910
excellent relief of their pain and chose to proceed with surgery. In these 16 patients, intraoperative findings revealed
2 with retained disc material, 13 with scar tissue, and 1 with impingement of the articular process on the nerve root.
Four patients received no relief with diagnostic block. No failures were reported at 8 to 24 months of follow-up.
Dooley and coworkers retrospectively reviewed 62 patients who had undergone nerve root infiltration (NRI) for
[28]
lumbosacral radiculopathy and assessed the accuracy and indications for NRI. Group 1 had typical pain reproduced
by needle placement and then relieved by NRI. Group 2 had typical pain reproduced by needle placement, but the
pain was not relieved by local anesthesia, indicating multiple nerve root involvement. Patients in groups 3 and 4 did
not have their typical pain reproduced by needle insertion, with or without relief by local anesthesia, and were
seldom relieved of their radicular pain. Group 1 members (44 patients) were 85% accurate in identifying a single
nerve root as the sole cause of radicular symptoms, and these patients proceeded with surgery. Group 2 (four
patients) showed incomplete relief and were believed to have multiple-level root symptoms. In groups 3 and 4 (14
patients), six patients deferred surgery secondary to a negative response to NRI, whereas five had surgery and were
relieved of their radicular symptoms. Supporters of this study proceed with surgery when an NRI successfully
abolishes radicular symptoms.
Loeser retrospectively studied 45 patients who had dorsal rhizotomies for relief of chronic pain. The author
[29]
extensively used nerve blocks in the preoperative evaluation of his patients, but he believed that the results of the
nerve blocks did not enable him to predict the operative results. In patients with successful preoperative nerve
blocks, 20% had a long-term operative success rate, whereas those with an unsuccessful preoperative nerve block
had a 27% long-term success rate. In total, 28% of the patients were successfully treated. Thus the diagnostic blocks
were not helpful in guiding therapy. [20]
Onofrio and Campa retrospectively examined their 12-year experience with dorsal rhizotomy in 286 patients with
[30]
intractable pain. Of the 286 patients, 112 had pain of unknown etiology and 81 had diagnostic blocks before
consideration for surgery. A positive selective root sleeve block was followed by dorsal rhizotomy. The authors
observed that the blocks were almost always unsuccessful and that they were an unreliable prognostic indicator of
the result to be expected from section of the same root.[20]
North and associates reviewed 13 patients with failed back surgery syndrome who underwent dorsal root
[31]
ganglionectomy. All preoperative selective root blocks indicated a monoradicular pain syndrome. Nearly all patients
reported 100% relief with selective nerve root blockade, whereas one reported 95% relief and another 90% relief.
The blocks were repeated and reproduced. Most but not all patients underwent additional blocks at other levels to
confirm the specificity of their responses. Follow-up data were obtained at a mean of 5.5 years after dorsal root
ganglionectomy.
Follow-up interviews to assess outcome were conducted by a disinterested third party. Treatment success (“success”
defined as at least 50% sustained relief of pain and patient satisfaction with the result) was recorded in two patients
at 2 years after surgery and in none at 5.5 years. Equivocal success (at least 50% relief, without clear-cut patient
satisfaction) was recorded in one patient at 2 and at 5.5 years postoperatively. Improvements in activities of daily
living were recorded in a minority of patients. Loss of sensory and motor function was reported frequently by
patients. A minority of patients had reduced or eliminated analgesic intake. The authors concluded that dorsal root
ganglionectomy had a limited role in the management of failed back surgery syndrome.
van Kleef and colleagues studied the effects of radiofrequency lesioning of the DRG of C4 to C5 or C6 in 20
[32]
consecutive patients with chronic pain in the cervical region. Pain scores were evaluated before and 6 weeks after
treatment. There was initial pain relief in 15 (75%) patients after 3 months and in 10 (50%) patients after 6 months.
There was a marked tendency for pain to recur in a period from 3 to 9 months after treatment.
Subarachnoid Neurolytic Blocks
Approximately 75% to 80% of cancer patients experience pain during the course of their disease. Of these
[33] [34]
patients, 1% to 5% require neural blockade for the relief of pain. Subarachnoid neurolysis has been used for
[35]
intractable pain in cancer patients who have failed other invasive therapy. Although effective, its use has declined
since the advent of programmable, implantable epidural and intrathecal pumps.Nonetheless, subarachnoid blocks
have a place in pain management as long as certain conditions are met.
The selection criteria for subarachnoid neurolysis are as follows:
911
1. Secondary to the possibility of serious complications (paralysis, bowel or bladder incontinence, neuritis),
patients should be selected who have a fairly short life expectancy (6–12 mon).
2. With rare exception, the technique should be reserved for patients who are suffering from pain that has
already been shown to be unresponsive to antioncologic therapy.
3. The pain should be severe, localized to two or three dermatomes, and intractable to adequate trials of
analgesic and adjunctive drugs.
4. The pain should be predominantly somatic in origin and should be completely relieved by prognostic local
anesthetic blocks.[36]
Patients and their families must be educated as to the advantages, disadvantages, realistic expectations, and
complications that may result from the procedure.
NEUROLYTIC AGENTS
Absolute alcohol and phenol are the two most commonly used neurolytic agents. Alcohol in concentrations of 50%
to 100% is hypobaric to CSF, is irritating to local tissues, and causes considerable temporary pain during injection. [21]
The preinjection of local anesthetic prevents this burning. It is thought that the neurolytic action of alcohol is by
[37] [38]
dehydration, with extraction of cholesterol, phospholipids, and cerebrosides, and by precipitation of mucoproteins. [21]
In neural tissue, alcohol injection leads to myelin sheath disruption and inflammatory responses, followed by
[38]
demyelination and degeneration. Phenol is typically used in concentrations ranging from 6% to 12%. It is not
[21]
commercially available and is usually prepared by hospital pharmacists. Phenol in glycerin is hyperbaric with
respect to CSF. Therefore, when used intrathecally, spread is localized. Phenol's effect is thought to be biphasic.
First, there is a conduction blockade similar to a local anesthetic effect. This is followed by chronic denervation
produced by nonselective damage to nervous tissue. The neurolytic effect appears to be the result of protein
[21] [37]
degeneration at low concentrations (<5%), whereas higher concentrations (>5%) cause protein coagulation and
nonsegmental demyelination and wallerian degeneration. [37]
TECHNIQUE
Only after a successful diagnostic and prognostic block should neurolysis with alcohol and phenol be considered.
Furthermore, because a neurolytic subarachnoid block must be carried out at the level where the dorsal root leaves
the spinal cord, a chart that indicates the bony vertebral level at which a particular nerve root leaves the spinal cord
should be reviewed. Almost invariably this is a higher level than where the nerve leaves the vertebral column.
[36]
The patient scheduled for hypobaric alcohol neurolysis is positioned in the lateral spinal position with the painful
side up and then rolled 45 degrees anteriorly ( Fig. 36–9 ). This properly positions the dorsal root. The patient is
[39]
then stabilized in this position with pillows and straps. It is imperative that the patient remain in this position
throughout the entire procedure. Movement of the patient can lead to spread of the alcohol to other regions, resulting
in unwanted complications. Under fluoroscopic guidance, a 22-G spinal needle is inserted into the spinal canal at the
appropriate level of entry for the dorsal root to be blocked. Free flow of CSF must be confirmed. Contrary to other
[36]
texts, Winnie suggests that no local anesthetic be injected before injection of the alcohol, his rationale being that no
local anesthetic can be made as hypobaric as absolute alcohol. Thus, if local anesthetic is injected first, it may not
block the intended nerve root, resulting in misinformation as to the proper placement of the neurolytic. The actual
[36]
purpose of the local anesthetic is to decrease the intense pain that follows injection of the alcohol. After
confirmation of CSF, the tuberculin syringe containing 1.0 mL of absolute alcohol is attached to the spinal needle.
Aspiration to confirm positioning should not be done, because the alcohol causes the CSF to form a white
coagulum. The alcohol should be injected in 0.1-mL increments. The first two 0.1-mL aliquots serve to fill the
[36]
spinal needle, but the third or fourth 0.1-mL increment should produce the expected painful reaction. If the burning
is experienced at the exact level of the patient's original pain, a total of 0.7 mL of the absolute alcohol should be
injected in 0.1-mL increments. If the burning is felt above or below the level of the patient's original pain, another
needle needs to be inserted above or below the original spinal needle until the burning of the alcohol corresponds to
the distribution of the patient's pain. The needle is then flushed with 0.1 to 0.2 mL of air to clear the neurolytic
solution from the needle before its removal. The patient must remain in the original block position for 45 minutes
after the last injection of alcohol to allow fixation of the neurolytic to the nerve root.
912
Figure 36-9 Proper positioning of a patient for an intrathecal Figure 36-10 Proper positioning of a patient for an intrathecal
injection of absolute alcohol for left-sided pain. Note the 45-degree injection of phenol for left-sided pain. Note the 45-degree posterior
anterior tilt, which allows the hypobaric alcohol to bathe the tilt, which allows the hyperbaric phenol to bathe the posterior
posterior sensory roots while sparing the anterior motor root. sensory roots while sparing the anterior motor roots.
Positioning for a hyperbaric phenol block is different. The patient is positioned with the painful side down and is
rotated posteriorly approximately 45 degrees ( Fig. 36–10 ). As with the alcohol block, the spinal needle is inserted
into the spinal canal at the appropriate level with the aid of fluoroscopy. The phenol is injected in the same manner
and volume as the alcohol, but the patient should experience less pain with the phenol. The needle is flushed with air
and removed. Positioning of the patient should be maintained for 45 minutes after injection.
COMPLICATIONS
Complications can be devastating to the patient as well as the family. These include bowel or bladder dysfunction,
muscle weakness or paresis, sensory loss with or without dysesthesias, postdural puncture headache, and tissue
sloughing. Fortunately, the majority of the side effects are transient. A study by Gerbershagen of 303 [40]
complications revealed that 28% of the complications resolved in 3 days, 23% resolved in 1 week, 21% resolved in
1 month, 9% resolved in 4 months, and 18% extended past 4 months. Bonica reported an incidence of 25% of
[41]
patients developing rectal, bladder, or limb paralysis. Nathan and Scott reported a 12% incidence of sphincter
[42]
dysfunction.
EFFICACY
Efficacy statistics for subarachnoid neurolytic blocks are dated. Studies by Maher and Rodrigues-Bigas and
[43]
colleagues reported good relief of pain in 65% to 70% of patients after subarachnoid phenol injection. As a whole,
[44]
good results should be expected in 50% of the patients, with another 25% receiving some beneficial effect. [36]
913
Conclusion
Knowledge of the anatomy of nerve roots and surrounding structures is important to improve the efficacy of the
nerve root block and to decrease complications. Conventional radiofrequency lesioning is a safer alternative to
neurolytic solutions for dorsal root rhizotomies secondary to fewer potential complications. Pulsed EMF may be the
wave of the future for dorsal root lesioning and warrants future prospective studies.
REFERENCES
1. FinkB: History of neural blockade. In Cousins M, Bridenbaugh P (eds): Neural Blockade in Clinical Anesthesia and Management of Pain, 2nd
ed. Philadelphia, JB Lippincott, 1988, pp 13–21.
2. McQuillan P: Central nerve blocks: Subarachnoid. In Raj P (ed): Practical Management of Pain, 3rd ed. St Louis, Mosby–Year Book, 2000, pp
631–636.
3. Raj P, Nolte H, Stanton-Hicks M: Central nerve blocks. In Raj P (ed): Pain Medicine: A Comprehensive Review. St Louis, Mosby–Year Book,
1996, pp 185–199.
4. Hogan Q: Spinal anatomy. In Hahn M, McQuillan P, Sheplock G (eds): Regional Anesthesia: An Atlas of Anatomy and Technique. St Louis,
Mosby–Year Book, 1996, pp 205–220.
5. Raj P, Neumann M: Facet blocks. In Raj P (ed): Pain Medicine: A Comprehensive Review. St Louis, Mosby–Year Book, 1996, pp 261–271.
6. Gray H: The articulations. In Pick T, Howden R (eds): Gray's Anatomy, 15th ed. New York, Bounty Books, 1977, p 229.
7. Lu J, Ebraheim N: Anatomic considerations of the C2 nerve root ganglion. Spine 23:649–652, 1998.
8. Blank J, Kahn C, Warfield C: Transsacral nerve root. In Hahn M, McQuillan P, Sheplock G (eds): Regional Anesthesia: An Atlas of Anatomy
and Technique. St Louis, Mosby–Year Book, 1996, pp 279–284.
9. Hasue M: Pain and the nerve root. Spine 18:2053–2058, 1993.
10. Yoshizawa H, Kobayashi S, Hachiya Y: Blood supply of nerve roots and dorsal root ganglia. Orthop Clin North Am 22:195–211, 1991.
11. Bose K, Balasubramaniam P: Nerve root canals of the lumbar spine. Spine 9:16–18, 1984.
12. Yabuki S, Kikuchi S: Positions of dorsal root ganglia in the cervical spine. Spine 21:1513–1517, 1996.
13. Sato K, Kikuchi S: An anatomic study of foraminal nerve root lesions in the lumbar spine. Spine 18:2246–2251, 1993.
14. Kikuchi S, Sato K, Konno S, et al: Anatomic and radiographic study of dorsal root ganglia. Spine 19:6–11, 1994.
15. Alleyne
C, Cawley CM, Barrow D, et al: Microsurgical anatomy of the dorsal cervical nerve roots and the cervical dorsal root ganglion/ventral
root complexes. Surg Neurol 50:213–218, 1998.
16. Slosar P, White A, Wetzel F: The use of selective nerve root blocks: Diagnostic, therapeutic, or placebo? Spine 23:2253–2256, 1998.
17. Link
S, El-Khoury G, Guilford WB: Percutaneous epidural and nerve root block and percutaneous lumbar sympatholysis. Radiol Clin North
Am 36:509–521, 1998.
18. Levy B: Diagnostic, prognostic, and therapeutic nerve blocks. Arch Surg 112:870–879, 1977.
19. Lamacraft G, Cousins M: Neural blockade in chronic and cancer pain. Int Anesthesiol Clin 35:131–153, 1997.
20. Guarino A, Staats P: Diagnostic neural blockade in the management of pain. Pain Digest 7:194–199, 1997.
21. Jain S: Nerve Blocks. In Warfield C (ed): Principles and Practice of Pain Management. New York, McGraw-Hill, 1993, pp 379–399.
22. Pang W, Ho S, Huang M: Selective lumbar spinal nerve block, a review. Acta Anaesthesiol Sin 37:21–26, 1999.
23. Finch
P, Taylor J: Functional anatomy of the spine. In Waldman S, Winnie A (eds): Interventional Pain Management. Philadelphia, WB
24. Sluijter M, van Kleef M: Characteristics and mode of action of radiofrequency lesioning. Curr Rev Pain 2:143–150, 1998.
25. Kline
M: Radiofrequency techniques in clinical practice. In Waldman S, Winnie A (eds): Interventional Pain Management. Philadelphia, WB
Saunders, 1996, pp 185–218.
26. Botwin K, Gruber R, Bouchlas C, et al: Complications of fluoroscopically guided transforaminal lumbar epidural injections. Arch Phys Med
1052
Rehabil, 81:1045–1050, 2000.
27. Krempen J, Smith B, DeFreest L: Selective nerve root infiltration for the evaluation of sciatica. Orthop Clin North Am 6:311–315, 1975.
28. Dooley J, McBroom R, Taguchi T, et al: I: Nerve root infiltration in the diagnosis of radicular pain. Spine 13:79–83, 1988.
29. Loeser J: Dorsal rhizotomy for the relief of chronic pain. J Neurosurg 36:745–750, 1972.
30. Onofrio B, Campa H: Evaluation of rhizotomy. Review of 12 years' experience. J Neurosurg 36:751–755, 1972.
31. North
R, Kidd D, Campbell J, et al: Dorsal root ganglionectomy for failed back surgery syndrome: A 5-year follow-up study. J Neurosurg
74:236–242, 1991.
32. van Kleef M, Spaans F, Dingemans W, et al: Effects and side effects of a percutaneous thermal lesion of the dorsal root ganglion in patients
with cervical pain syndromes. Pain 52:49–53, 1993.
33. Sehbum M, Lipman A: Management of pain in the cancer patient. Anesth Analg 76:402–416, 1993.
34. Portenoy R: Pharmacologic management of cancer pain. Semin Oncol 22(Suppl 3): 112–120, 1995.
35. Day M: Management of cancer pain patients. Pain Digest 9:118–133, 1999.
36. WinnieA: Subarachnoid neurolytic blocks. In Waldman S, Winnie A (eds): Interventional Pain Management, Philadelphia, WB Saunders,
1996, pp 401–405.
37. deLeon-Casasola O, Ditonto E: Drugs commonly used for nerve blocking: Neurolytic agents. In Raj P (ed): Practical Management of Pain, 3rd
ed. St Louis, Mosby–Year Book, 2000, pp 575–578.
38. Ferrer-Brechner T: Anesthetic techniques for the management of cancer pain. Cancer 63:2343–2347, 1989.
39. Warfield C: Nerve blocks for pain management. Hosp Pract 23(4):33–35, 39–40, 1988.
40. Gerbershagen H: Neurolysis: Subarachnoid neurolytic blockade. Acta Anaesthesiol Belg 1:45, 1981.
41. Bonica J: Diagnostic and therapeutic blocks. A reappraisal based on 15 years experience. Anesth Analg 37:58, 1958.
42. Nathan P, Scott G: Intrathecal phenol for intractable pain. Safety and dangers of the method. Lancet 1:76–80, 1958.
43. Maher R: Relief of pain in incurable cancer. Lancet 1:18–20, 1955.
44. Rodrigues-Bigas M, Petrelli N, Herrera L, et al: Intrathecal phenol rhizotoomy for management of pain in recurrent unresectable carcinoma of
the rectum. Surg Gynecol Obstet 173:41–44, 1991.
1053
Section V Chapter 37 - Neuroaugmentative Procedures for Pain
Chapter 37 - Neuroaugmentative Procedures for Pain

SAMUEL J. HASSENBUSCH
Spinal Cord Stimulation

AXIAL AND APPENDICULAR PAIN
HISTORY
Stimulation applied to the spinal cord was introduced in animals in 1967 and first reported in humans in
1968. Stimulation was initially applied via different layers around the spinal cord. At first, the
[1]
subarachnoid approach was tried. This provided good stimulation with very low voltages, but long-term
stability was a problem. Then, subdural placement of the stimulator electrode was attempted, but this, too,
was found to be a suboptimal technical placement, with poor long-term stability. At the present time,
stimulation is administered almost entirely via the epidural route, which is easier and provides fairly stable
long-term results. The electrode has traditionally been placed in the posterior aspect of the canal, thereby
providing stimulation to the dorsal columns and or dorsal horns of the spinal cord.
Since its introduction, the hardware for spinal cord stimulation has undergone marked improvement. The [2]
present hardware systems are both percutaneous and open surgical placement. The stability, long-term
performance, and reliability of the hardware are extremely high.
When spinal cord stimulation was introduced, there was debate about the best uses for it and the best sites.
These debates continued for 10 to 20 years, but these questions appeared to have been answered in the past
10 years. At present, patients who have achieved excellent results can be identified with a fair degree of
accuracy. Of equal interest are development of new applications for spinal cord stimulation and locations
and techniques for applying the stimulation in the spinal canal itself.
Computer models have also been developed to determine the point of maximal electrical stimulation to the
dorsal part of the spinal cord. This computer modeling has been especially helpful
[3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16]
with some of the newer electrode systems described later.

Regardless of the mechanism used for spinal cord stimulation or the currently available hardware,
stimulation has been shown to be a highly effective treatment modality for patients with chronic pain. Of
equal interest is that the stability of analgesia has been consistently high over a long period of time. In other
words, a high degree of pain relief with the initial placement of a spinal cord stimulator is very highly
correlated with sustained analgesia, with very little upkeep for a number of years, perhaps even decades.
Mechanism of Action
Although the purpose of this chapter is not to describe the mechanism of action of spinal cord stimulation, it may be
noted that the exact site is still unknown. An early proposal for the effectiveness of this technique was the gate-
control theory of Melzack and Wall. Other possible routes include direct stimulation of the dorsal horns of
[18] [19] [20] [21] [22]
the spinal cord, which produces gate control at a local level rather than at the dorsal column or higher levels of the
spinal cord. There is still a question as to the exact nature of the neurotransmitters that are involved in the
mechanism of spinal cord stimulation. Putative neurotransmitters involved in the effects are serotonin, substance P,
and gamma-aminobutyric acid (GABA). [22] [23]
Single Lead Technique
TRIAL
A patient can undergo a trial for spinal cord stimulation with a completely percutaneous placement of an electrode.
This can be done through epidural needle placement, and the electrode is then positioned in the posterior epidural
space under fluoroscopic guidance. The electrode is often localized somewhere between the T10 and T12 vertebral
bodies. T10 is more often used for back or buttock pain, and T11 or T12 is the more frequent choice for lower leg
pain. The electrode is often a catheter placed through the needle, which has either four or eight electrical contacts
along the catheter. The advantage of this trial for a simple pain problem is that it is inexpensive and simple.
Regardless of the outcome, the electrode can be removed very easily.
If an electrode trial provides good pain relief, considered to be at least 50% reduction in pain, a permanent system
can then be placed. There is still no consensus regarding the superiority of inpatient or outpatient trials.
[34] [35] [36] [37] [38]
Outpatient trials have the advantage of maintaining active patients in their own environment. Ability to resume
normal activity is the best determination of the degree of pain relief.
There is a second trial method whereby the actual permanent electrode is placed via a small incision. The incision is
performed to allow the electrode to be anchored to the underlying fascia or ligaments. The tail of the permanent
electrode is tunneled under the skin and brought out through a separate stab wound at a distance from the incision.
The trials are performed just as described earlier. If the trial provides good pain relief, the incision is opened in the
permanent electrode placement operation, and the tail of the electrode is separated from the temporary extension that
protruded from the skin. The tail of the permanent electrode is then continued, as in the permanent operation,
subcutaneously. This latter technique, however, requires more exposure for the initial placement as well as a repeat
917
operation to remove the permanent electrode should the trial be unsuccessful. These considerations have to be
weighed against the downfall of the straight percutaneous trial, whereby a good electrode is removed and discarded,
regardless of whether the trial is successful. If it is difficult to place the electrode during the trial, placing a
permanent electrode later may be difficult as well.
PERMANENT IMPLANTATION
Regardless of the technique used, if a patient with a simple pain pattern (e.g., pain in one leg) is being treated,
placement of a single array of electrodes is useful for a permanent system. This can be accomplished either through
a catheter-type electrode that has four or eight contacts or through an open incision and laminotomy ( Figs. 37–1 and
37–2 ). With laminotomy, a plate-type electrode is placed. Again, this can have four or eight contacts. The catheter-
type electrode is easier to place because it can be passed through a needle that was inserted into the epidural space.
The electrical contacts, however, are smaller in the catheter-type electrode and somewhat more prone to movement.
The plate-type electrode is more difficult to place, but once localized, it tends to stay without further movement. The
plate-type electrode also allows the possibility of two columns of electrical contacts rather than one single array. The
other advantage of a plate-type electrode is that its thickness tends to push on the posterior dura mater and thus
provide slightly more stimulation to the posterior part of the spinal cord. At the present time, there is no consensus
as to whether the catheter-type or the plate-type electrode is better.
Regardless of the electrode type used, the tail of the electrode is tunneled subcutaneously via an extension wire
around to an open incision where the generator/receiver
Figure 37-1 Array of catheters and laminotomy electrodes with ITREL 3 and Synergy transmitters.
will be placed. This can be placed either subcutaneously over the anterior abdominal wall or in the posterior axillary
line just below the top iliac crest. With either placement, a 6-cm incision is made and a subcutaneous pocket created.
The extension wire, or the tail of the permanent electrode, is brought out through this incision and then connected to
either the generator or the implanted receiver. Some practitioners prefer the location of the posterior axillary line for
the generator because it is below the belt line, has fewer
Figure 37-2 Placement of plate electrodes by laminotomy.
918
cosmetic problems, and is easier to place in one operation if the patient is prone. Antibiotic prophylaxis is important
regardless of which operation is performed. Many physicians give patients two to three doses of intravenous
antibiotics; in these cases, coverage with oral antibiotics is optional. Irrigating all wounds with solution containing
antibiotic is also an important aspect of infection prevention.
As noted earlier, there are two types of sources for electrical stimulation. One type is a totally implanted generator,
which is a self-contained unit. This can be reprogrammed transcutaneously in much the same manner as a
pacemaker. Another technique involves placing a receiver in the subcutaneous pocket. The actual electrical
stimulation then comes from an external transmitter, which has an antenna that is placed on top of the skin, over the
area of the receiver. At present, there is no preference for either technique. External transmitter systems generally
provide more flexibility for different types of stimulation parameters, but they are also more inconvenient for the
patient. With external transmitter systems, patients often prefer the receiver to be in the posteroaxillary line area,
because the antenna can be held in place over the skin by undergarments rather than tape.
Dual Lead Technique
Dual-lead stimulation is more beneficial for patients with bilateral pain; this method also reaches the deeper axial
fibers within the spinal cord itself. Dual-lead stimulation involves application of two columns of electrical
[39] [40] [41]
contacts to the posterior epidural space. This can be done by placing two catheter-type electrodes, each containing
four or eight contacts ( Fig. 37–3 ). Such catheters are placed in parallel, separated by approximately 3 to 5 mm and
usually centered on either side of the midline of the posterior aspect of the spinal cord. Another option using a plate-
type electrode is placement of a plate containing two columns of electrical contacts on the plate itself. Again, the
two columns are separated by 3 to 7 mm and can contain four or eight electrical contacts in each column. This type
of stimulation is most often used for axial or bilateral buttock pain. Pain in the upper and lower leg, especially on
only one side, is usually treated with a single-array electrode setting.
Another interesting technical variant is placement of the stimulator electrode array on the dorsal root entry zone
(DREZ). Although this has been reported in a very limited number of patients, the DREZ placement is interesting
[42]
in that its neurophysiologic basis for analgesia is different from that of conventional posterior epidural spinal cord
stimulation. More recently, advantages of the far lateral epidural placement of an electrode directly on the nerve
roots (e.g., between L4 and L5, or between L5 and S1) have been described. [43]
Figure 37-3 Dual octrodes placed parallel to stimulate the dorsal columns.
With all of these improvements, there still are one or two tails of electrodes that are then connected to extension
wires and tunneled to a generator or to a receiver, as described earlier.
919
Outcome Studies
Since 1967, there have been a large number of reports on the results of spinal cord stimulation in humans. [44] [45] [46] [47] [48]
Unfortunately, most of these have been either anecdotal or retrospective.

[49] [50] [51] [52] [53] [54] [55] [56] [57] [58] [59] [60] [61] [62] [63] [64]
Kumar and associates reported on 94 patients who underwent spinal cord stimulation with a mean follow-up period
of 40 months. These patients’ pain resulted from a number of different conditions, but 51% were able to control
[65]
their pain with neurostimulation alone. More than 60% of the patients had more than 50% pain relief at the 3-year
follow-up examination.
In 1991, North and colleagues described 5-year follow-up findings for 102 patients who had undergone repeated
back operations. The majority of these patients benefited from spinal cord stimulation, and it was concluded that
[66]
standard spinal decompression-and-fusion procedures were not successful in many of these patients. North and
colleagues reported perhaps the most detailed experience with spinal cord stimulation for the years 1972 to 1992. [67]
Of the 172 patients in the study with a mean follow-up period of 7 years, 52% reported more than 50% pain relief
and 60% reduction in the medication use. North and colleagues later published the results of a prospective
randomized study of spinal cord stimulation versus reoperation for failed back surgery syndrome. This is [68] [69] [70]
probably the only detailed prospective comparison of spinal cord stimulation with other surgical techniques. The
study showed a significant advantage of spinal cord stimulation over reoperation with regard to pain ratings,
medications, work status, activities of daily living, psychological status, and functional capacity. In a more recent
prospective multicenter study of the efficacy of spinal cord stimulation, 55% of patients at the 1-year follow-up
examination reported continued analgesic benefit and more than 50% pain reduction. In the same study, however, [71]
there were no statistically significant changes in medication use and work status.
For axial pain, there are fewer studies of the efficacy of spinal cord stimulation. One of the initial studies, conducted
by Law, affirmed its efficacy as did subsequent short-term studies. Long-term studies of spinal cord stimulation for
[75]
axial pain, however, are still lacking.

COMPLEX REGIONAL PAIN SYNDROME (CRPS)
Spinal cord stimulation has been reported more frequently for CRPS (formerly known as reflex sympathetic
dystrophy or causalgia) than for axial pain. Many of these reports, including those of Robaina and associates,
Barolat and Schwartzman, Broseta and colleagues, and Law, have shown the efficacy of spinal cord stimulation for
this disorder. These studies have included 2 to 300 patients with mean follow-up periods ranging from 13
[72] [73] [74] [75]
months to 27 months. In almost all these studies, the majority of patients had excellent or good pain relief with
associated moderate or marked reduction in edema, cyanosis, and pallor.
In most of the studies of spinal cord stimulation for the types of pain described earlier, the rate of return to work has
ranged from 8% to 20%, depending on the calculation of the data. Some studies suggest that this rate may be as high
as 30% if the analyses exclude patients who were already retired or not at a working age.
Indications
GENERAL
Spinal cord stimulation has been found to be effective for neuropathic pain in general and is less often used for
either visceral or somatic pain. The neuropathic pain entities include sympathetic-dependent pain; thus, spinal cord
stimulation is often considered as a first-line treatment for intractable pain caused by nerve damage resulting from
repeated back operations, epidural scarring, or arachnoiditis. It is also useful for peripheral nerve injury syndromes
such as stump pain, phantom pain, peripheral neuropathy, or CRPS. Deafferentation pain, in general, is another
indication for spinal cord stimulation. Peripheral neuropathy often responds to this modality regardless of
[76] [77] [78] [79]
whether it arises from metabolic conditions such as diabetes or from other conditions.
In many situations, the pain has both neuropathic and somatic causes. In this situation, spinal cord stimulation or
long-term spinal infusion of analgesic agents can be used.
UNILATERAL LEG PAIN
After the nature of the pain (e.g., neuropathic or somatic) is ascertained, the pattern of the pain is investigated. Pain
that is in only one leg probably responds best to spinal cord stimulation. In this situation, a single lead, either
percutaneous or plate type, may be considered. This is ideal because spinal cord stimulation can be applied to one
side of the posterior aspect of the spinal cord and the patient then perceives the stimulation in the affected leg. One
of the most important aspects of spinal cord stimulation is that the area of the perceived stimulation must be in the
area of the actual pain. The wider the area of actual pain that is covered by perceived stimulation, the better the
results.
BILATERAL LEG PAIN
For bilateral leg pain, a dual-lead stimulation is often used. In this method, each column of electrical contacts—
either two catheter-type electrodes or one plate-type electrode with two columns on the plate— provides stimulation
for each leg. With the newer stimulation systems, the voltage, as well as the pulse width for the electrical contacts in
each column, can be varied so that the amount of stimulation in one leg can differ from the amount of stimulation in
the other leg. This better approximates the situation in which the two levels of pain are not equal and are not
symmetrical.
920
BUTTOCK AND LOW BACK PAIN
It is more difficult to treat pain that is axial (i.e., pain perceived in the middle to lower back) and buttock pain. [80] [81] [82]
Dual-lead stimulation, again with either two catheter-type electrodes or one plate-type electrode with
[83] [84] [85] [86] [87]
columns of contacts, can be effective. The rationale is that stimulation applied by both columns at the same time can
provide denser and deeper stimulation to the axial fibers that are deep within the posterior midline aspect of the
spinal cord. Some adjustment of the electrical contacts for both the pulse width and the voltage is necessary to
obtain the best stimulation pattern. An acceptable stimulation pattern can almost always be obtained and produces
good results.
Axial stimulation is the most difficult aspect of the spinal cord stimulation. It is strongly suggested that some form
of dual-electrode system be used during the trial phase to ensure that the permanent system will provide adequate
stimulation for the middle and lower back. An alternative treatment for many patients is a long-term spinal infusion
of both an opioid analgesic and a nonopioid analgesic such as bupivacaine or clonidine.
Critical Analysis for Use and Future Directions
Spinal cord stimulation is very effective when properly applied. As with all of the neuroaugmentative techniques,
[69] [88]
it is assumed that standard multidisciplinary, noninvasive, systemic treatments have already failed; that further
surgical intervention has been deemed inappropriate; and that there are objective findings and a recognized pain
syndrome with plausible etiology to support the pain diagnosis. In addition, a detailed psychiatric assessment should
reveal no mental abnormalities, and patients should successfully undergo a stimulator trial.
[88]
When invasive permanent treatments are required, spinal cord stimulation can be effective. Most important is that
the pain pattern is amenable to coverage with a spinal stimulator system. The best use is for neuropathic pain in a
patient with single-leg distribution of pain. The use of spinal cord stimulation least likely to be successful would be
in the patient with predominantly somatic pain that is diffuse over the body. The technique would be intermediately
successful for the neuropathic pain in both legs, in one buttock, in both buttocks, or in the lower back, in order of
decreasing effectiveness. However, there are not many other viable options that can be effective for these patients.
One of the major advantages of spinal cord stimulation is that it is fairly easy to test in an individual patient. This
can be very cost effective and can determine whether the patient is likely to have very good pain relief or none at all.
Thus, it could be argued that for pain in which success is intermediate, such as low back and bilateral buttock pain,
if there are no other obvious options, a spinal cord stimulator trial of a dual-lead system is reasonable. It is easy to
perform, can be done on an outpatient basis in a fluoroscopy suite, and can be very inexpensive. If the patient
obtains only 10% of relief of pain, it is not reasonable to pursue this option. However, many patients obtain 80% to
100% pain relief with such a system; permanent implantation could be considered for those patients and would be
expected to have a very high degree of success over the long term.
In many ways, spinal cord stimulation is as widely used as long-term spinal infusion of analgesic. In the early 1990s,
the indications for these two modalities were separate: Well-localized neuropathic pain would be managed with
spinal cord stimulation, and more diffused somatic conditions would be amenable to long-term spinal infusion. With
the advent of dual-lead stimulation, however, it is possible to manage many of the more diffuse distributions of pain
with spinal cord stimulation. Somatic pain still appears to be better managed in general with long-term spinal
infusion. Thus, in the intermediate conditions, whether a trial spinal cord stimulation or a trial of long-term spinal
infusion is to be considered could be a matter of personal preference and of logistical and financial issues related to
the individual practice with the individual patient.
PELVIC/SACRAL PAIN
HISTORY
Sacral stimulation has historically been achieved with the percutaneous placement of a
catheter-type electrode through the skin and into the sacral foramen. The goal is
[89] [90] [91]
stimulation of sacral nerve roots responsible for various types of sacral and pelvic pain.
Mechanism of Action
Although the exact mechanism of sacral stimulation remains unclear, it is assumed that the sacral nerve roots or
sacral nerves are mediators for various types of sacral and pelvic pain. This assumption is based on observations that
the S3 nerve root influences the sensory threshold of the bladder with regard to electrical stimulation. [89]
Technique
As with traditional spinal stimulation, a trial electrode is placed over sacral nerve roots. This has historically been
achieved by placement of the electrode directly into a sacral foramen by means of a posterior needle-based
technique.
If this is successful, an incision is made, and the electrode is anchored in that area of the posterior aspect of the
sacrum. As with regular spinal cord stimulation, the extension wire is then tunneled to either a generator or a
921
receiver. This is a simpler technique; however, its disadvantage is that it provides stimulation only to one nerve root
at a time and only on one side.
A variation in the technique has been the placement
Figure 37-4 Dual retrograde sacral placement of electrodes A and B (arrows).
of a catheter-type electrode through an L3–L4 or L4–L5 epidural puncture in the treatment of pelvic and or sacral
pain ( Fig. 37–4 ). In this case, however, the needle is directed inferiorly as it enters the epidural space. The
[92] [93]
catheter-type electrode is then directed in the epidural space downward to L5 or sacral levels. This can provide
stimulation to the S2 to S4 nerve roots within the cauda equina in the dural sac. This is often done in a dual-lead
stimulation manner in which two catheters are placed parallel in this area, thus providing stimulation to right and left
sacral nerve roots. This is a fairly easy technique.
Outcome Studies
Reports about the transforaminal electrode placement technique have shown good results with lower bladder
threshold. More than 50% reductions in voiding dysfunction symptoms and marked reductions in incontinence
problems were observed in 83% of patients at follow-up periods up to 2 years. As described earlier,
[89] [91] [94] [95]
electrical stimulation in the epidural space through a retrograde electrode that is located in the epidural space over
the S1–S4 area has also been found to be useful for this type of pain. Patients with intractable sacral or pelvic pain
had good stimulation paresthesia coverage of the pain area with a 76% mean reduction in visual analogue scale pain
ratings. [93]
Indications
This form of spinal stimulation has been reported to be effective for chronic pelvic pain and bladder voiding
dysfunction, including painful bladder spasms.
Although this is a relatively new technique, especially with epidural retrograde electrode placement, it already
appears to be useful. Because the retrograde electrode placement is relatively new, it is difficult to describe the
percentage of relief or the ideal electrode location for such patients. More reported experience from different
investigators is needed before a certain statement about long-term efficacy can be made. For patients with severe
pelvic pain or bladder voiding dysfunction, however, this is often the only available technique that has shown any
promise of relief. Thus, a trial of sacral stimulation is recommended for such patients if all other treatment options
have been exhausted.
Peripheral Nerve Stimulation
922
LIMB PERIPHERAL NERVE STIMULATION
HISTORY
Initial reports of peripheral nerve stimulation (PNS) from the 1970s to 1990 showed good long-term
results and patient satisfaction, although the reports were often limited and anecdotal.
[104] [105] [106]
[96] [97] [98] [99] [100] [101] [102] [103]
Electrical stimulation applied to peripheral nerves was first developed circa 1969. The original [98] [108]
electrodes often were cuff-shaped, and the results were encouraging but limited. Interest in the [98] [99] [108]
use of PNS was renewed in the late 1980s with the application of flat or oval-shaped electrode
templates that contained four electrode contacts (e.g., Resume electrode, Medtronic Corporation,
Minneapolis, Minn.). The presence of four electrode contacts and the availability of
[110] [111] [112]
implantable, programmable low-voltage generators provided greater ability to deliver consistent and
evenly distributed stimulation to a peripheral nerve, although well-analyzed studies were absent.
Campbell and Long in 1976 reported on PNS applied for a variety of pain syndromes in 33 patients; 8
(24%) achieved excellent results, and 7 (21%) achieved intermediate results. In 1980, Law and [98]
coworkers reported that 14 (62%) of 22 patients were using the PNS stimulators as the sole mechanism
for analgesia; the average follow-up period was 25 months. In 1982, Nashold and associates reported
[99]
on the results in 35 patients with upper and lower extremity peripheral nerve injuries and found
success in 53% of those with upper extremity pain and 31% of those with lower extremity pain, with a
follow-up period ranging from 4 to 9 years. [101]
Mechanism of Action
Campbell and Taub showed a loss of the A beta component of the compound action potential recording from a
peripheral nerve that is stimulated transcutaneously. The mechanism in this case may involve blockade of the
[115]
peripheral axon. Further support has come from the observation that repeated electrical stimulation of peripheral
nerves results in failure to excite C fibers and, to a lesser degree, A fibers. [98]
Although the mechanism of pain relief remains unclear, it appears that the peripheral stimulation might activate A
beta fibers, thus providing a blocking action on nociceptive A delta and A gamma fibers, probably at the dorsal
horn. 119
[116] [117] [118] [120] [121]
The mechanisms of action for both PNS and spinal cord stimulation in the treatment of reflex sympathetic dystrophy
(RSD) remain unclear and may be different for these two modalities. The voltage level for PNS, however, probably
activates only large myelinated fibers. Recordings from peripheral stimulator electrodes have shown spontaneous
[122]
abnormal discharges in the affected nerve. Constant peripheral stimulation may provide a consistent blockade of
[122]
afferent peripheral input, allowing central processing to return to normal. Alternatively, afferent impulses from
electrical stimulation of the nerve may block, at the spinal cord level, other abnormal nociceptive inputs in a gate-
control manner. [123]
Technique
Peripheral nerve stimulation is usually applied in an open operation via exposure of the target nerve. The testing
phase is essentially the same as the permanent phase, inasmuch as the permanent electrode is implanted along the
side of the nerve with the temporary extension tail of the electrode protruding from a separate stab incision. If [124] [125]
the testing phase shows satisfactory pain and symptom reduction, the incision can be reopened, the temporary
extension tail clipped off, and a permanent extension wire and generator placed, as described earlier for spinal cord
stimulation.
Outcome Studies
There is a paucity of published reports describing the long-term success rates, criteria for success, and technical
complications of this modality. Ironically, there have been minimal or no recent reports in the literature of the
application of PNS in non-CRPS patients. It is still recommended for use in such patients on the basis of anecdotal,
unpublished information.
A prospective, consecutive series by this author in 1996 described PNS in treatment of severe RSD or CRPS for
patients with symptoms entirely or mainly in the distribution of one major peripheral nerve. Plate-type electrodes
were placed surgically on affected nerves and tested for 2 to 4 days. Implanted programmable generators were
placed if 50% pain reduction and objective improvement in physical changes were achieved. Patients were
monitored for 2 to 4 years, and a disinterested third-party interviewer performed final patient evaluations. Of 32
patients tested, 30 (94%) underwent permanent PNS placement. Long-term good or fair relief was experienced by
19 (63%) of the 30 patients. Allodynic and spontaneous pain was reduced in implanted cases from 8.3 ± 0.3 before
implantation to 3.5 ± 0.4 (mean ± standard error of the mean) at the latest follow-up examination (P < 0.001).
Changes in vasomotor tone and patient activity levels were improved markedly, but motor weakness and trophic
changes showed less improvement. Of the 30 patients, 6 (20%) returned to part-time or full-time employment after
being unemployed before stimulator treatment. Initial involvement of more than one major peripheral nerve was
correlated with poor or no relief rating (P < 0.01).
923
Calvillo and associates reported in 1998 on their experience in 36 patients with advanced CRPS and treated with
PNS and/or spinal cord stimulation. At 3 months after implantation, the pain rating, on a visual analogue scale (0
[126]
to 10), was reduced by a mean of 53%, and there were significant reductions in analgesic consumption. Ebel and
colleagues described 6 patients with CRPS who were treated with PNS with a mean follow-up of more than 3
years. All patients reported good to excellent (75% or greater) pain relief.
[127]
Indications
The best indication for peripheral nerve stimulation is the situation in which a single traumatized peripheral nerve
constitutes the major source of pain. The most common target nerves are the ulnar, median, posterior tibial,
[128] [129] [130]
and common peroneal nerves. Less common are the radial, sciatic, and femoral nerves. This form of stimulation has
also been shown to be effective for stump and phantom limb pain after amputation. [131]
PNS is another modality that has been described in the treatment of severe RSD. 109[108] [111] [112] [122] [126] [127]
PNS has proved to be a good long-term treatment for patients with pain in the distribution of one major peripheral
nerve. The best responses seem to be in the patients with CRPS; on an anecdotal basis, the least successful seem to
be those with pure sympathetic-independent ulnar neuropathy pain resulting from multiple ulnar nerve operations at
the elbow. On a technical level, improvements in electrode arrays that provide stimulation to opposing sides of a
major peripheral nerve are needed for nerves such as the sciatic nerve and the posterior tibial nerve, in which the
peroneal and tibial nerves and the medial and lateral plantar nerves, respectively, are often already segregated in
opposite halves of the major nerve.
Although it is difficult to perform a “percutaneous trial” of PNS, there appears, on an anecdotal basis, to be a high
correlation between significant temporary pain relief with a peripheral nerve block and long-term PNS success.
However, the real need in future research is a comparative study of spinal cord stimulation versus PNS for specific
types of patients. Calvillo’s series indicates that peripheral nerve stimulation and spinal cord stimulation of the same
tissue give the best pain relief at 36-months follow-up. At the present, the question about the relative roles of these
[126]
two modalities still remains unclear.

OCCIPITAL NERVE STIMULATION
HISTORY
Electrical stimulation has also been applied to the occipital nerve. Initial reports date back to the late
1970s, when the electrode was actually applied to surgically exposed C2 and C3 (greater and lesser
[96]
occipital) nerves.
Mechanism of Action
The greater occipital nerve is innervated by the medial branch of the C2 and C3 posterior primary sensory rami; the
lesser occipital nerve is innervated only by the C3 posterior primary sensory ramus. The greater occipital nerve exits
the spinal canal between the posterior arches of C1 and C2 and then traverses the paraspinal (semispinalis and
trapezius) muscles near the nuchal ridge of the occipital bone. The mechanism for occipital nerve stimulation is
thought to be the same as for PNS to any other peripheral somatic nerve (e.g., median, common peroneal).
Technique
More recently, a percutaneous electrode, similar to that for epidural spinal stimulation, has been applied to the
occipital nerve under the occipital scalp, approximately at the nuchal ridge ( Fig. 37–5 ).
[132] [133]
Outcome Studies
Although this technique is still relatively new, the follow-up success rate appears to be relatively high. In one study,
12 of 17 patients had more than 50% reduction in pain at the last follow-up visit. [132]
Indications
The indications for this relatively new technique are still not completely clear. It apparently can be used for any
form of occipital neuralgia, although the best results would probably be obtained in patients without a known
abnormality, trauma, or damage to the occipital nerve proximal to the site of the stimulator placement near the
nuchal ridge. It is not possible to state any detailed indications that are based on the specific cause (or lack thereof)
of the occipital neuralgia.
This is a very promising form of treatment for a group of patients with very few other adequate long-term options.
The ease of percutaneous testing of these patients with a catheter-type stimulator electrode also facilitates the
diagnostic phase, and is reasonably predictive of long-term success with a permanent implantation. However, the
924
one caution is that there have been no long-term (e.g., 10 years or more) follow-up evaluations of such patients
treated with this modality. Thus, there is clearly a need for more published reports of both long-term results and the
degree of efficacy for different causes of occipital neuralgia.
Intraventricular Infusion of Opioid
HISTORY
The intraventricular delivery of opioids is not new; early reports date to the mid-1960s. Because the [69]
technique is very similar to that for ventriculoperitoneal shunts, which have been available since the
late 1950s, it is not surprising that some clinicians decided to use the same type of catheters to inject
or infuse drugs into the ventricles. Despite its lengthy use, intraventricular opioid infusion has not
gained widespread and frequent clinical application. This may be a result of limited recognition of its
use as a therapeutic option and/or the increasing efficacy of intraspinal (intrathecal) delivery of
opioids and other non-narcotic medications such as bupivacaine and clonidine.
Mechanism of Action
Of the intracranial augmentative procedures currently practiced, the intraventricular infusion of opioids is one of the
most well-known techniques. Pain regulation seems to incorporate the supraspinal pathways for analgesia. The
duration of pain relief resulting from intraventricular injections appears to be significantly longer than that generated
by intraspinal delivery. Intraventricular delivery of the usual agent of analgesia, morphine sulfate, appears to provide
a substantial increase in potency in comparison with intrathecal or epidural infusions; daily morphine doses range
from 50 to 700 µg/day. This supports the general conclusion that intraventricular opioids act primarily on
[134] [135] [136]
intracranial receptors involved in the ascending antinociceptive pathway. It seems unlikely that intraventricular
Figure 37-5 Dual occipital electrode placement at C1–C2 level.
opioid infusion acts on spinal opioid receptors to any significant degree. This is further supported by the observation
that intraventricular opioid is still very effective with high potency when the long-term intrathecal delivery of opioid
has resulted in apparent tolerance with no significant further pain relief via the intraspinal route.
Technique
HARDWARE
Implanted infusion pumps, placed subcutaneously in the anterior wall of the abdomen, deliver doses of the opioid
via subcutaneous tubing connected to an implanted ventricular catheter. Adequate relief may also be achieved by
using an implanted ventricular catheter connected to a subcutaneous Ommaya reservoir–type device that delivers
injections once or twice daily. [137] [138]
925
DRUG CHOICE
Studies with sheep found that certain drugs, particularly lipophilic morphine–type drugs, encounter difficulties in the
process of diffusing through the cerebrospinal fluid (CSF) pathways to reach distant receptors. Thus, the choice of
opioid for infusion must account for the location of receptors. Using drugs like hydromorphone, morphine,
methadone, naloxone, and sucrose, as a control, Payne and coworkers tested the spread of specific opioids in CSF.
Approximately 90 minutes after intracerebroventricular (ICV) injection, morphine and sucrose were identified in the
lumbar CSF. Hydromorphone was located after 50 minutes. Because the ICV dosage of lipophilic opioids creates
[139]
CSF distributions that are distinctly different from those of hydrophilic drugs such as morphine, methadone was
never found in the lumbar CSF. [139]
After ICV administration, the lipophilicity of the opioid determines the extent of diffusion and concentration in the
brain. A few hours after injection, brain concentrations of morphine persist, although the dispersal is uneven
[139]
within the tissues. Its movement through the ventricles more closely resemble passive diffusion than active transport.
Because fentanyl, sufentanil, and etorphine are better able to bind to lipophilic receptors, the lipophilic opioids were
cleared from the CSF after only 1 hour. [139]
Outcome Studies
The progress of 20 patients (18 of whom suffered from cancer) treated with ICV morphine injections between 1990
and 1993 has been described by Seiwald and coworkers. According to their research, the administration of
[140]
morphine into the ventricle through a catheter-reservoir system is nondestructive and is a successful alternative in
the treatment of nociceptive pain. They also found that lower doses are slower to bring about pain relief.
[140]
Somatogenic pain was ameliorated in 19 (95%) of the patients, although minimal effects were seen in the
management of neurogenic pain. Intraventricular injections or infusions carry the same risks and side effects as
[140]
intraspinal infusions, with the exception of an increased chance of respiratory depression noted in the first 3 days of
the intraventricular delivery. [136] [137]
Indications
In general, the treatment is considered an option of last resort for pain relief. Best suited for patients suffering
[138]
from head and neck cancer pain, intraventricular infusion is used more often for patients with limited survival time
(1 to 3 months) who develop a tolerance to intraspinal infusion of opioids despite a good initial response to the
treatment. For effective treatment with intraventricular morphine delivery via an Ommaya reservoir, several factors
must be weighed: location of the pain, age of the patient, and the history of opioid usage. Craniofacial or diffuse
pain has been described as more responsive to the analgesic effect of ICV delivery, whereas the lower limbs
benefited more from lumbar subarachnoid administration of morphine. [141]
The intraventricular injection or infusion of opioid remains an excellent form of therapy. It has shown high efficacy
with extremely low doses. However, its future use is probably very limited in pain control because of the increasing
efficacy of spinal infusions with nonopioid analgesics and because of the technical placement of a ventricular
catheter, which, although a simple procedure, usually requires specific neurosurgical training. With future laboratory
research, however, the intraventricular route could become a very important clinical modality if effective,
specialized intracranial antinociceptive receptor systems were further identified. These systems could then be
included in routine clinical use if pharmacologic agents for ventricular delivery were studied to maximize pain relief
for difficult conditions such as neuropathic pain or for central pain resulting from various intracranial causes such as
thalamic infarctions.
Deep Brain Stimulation
HISTORY
In the late 1960s and early 1970s, as the severe morbidity rates and limited scope of some early
ablative procedures became apparent, interest in augmentative alternatives such as deep brain
stimulation increased. The first stimulations of periventricular and periaqueductal gray matter were
[142]
performed on humans in 1972. Deep brain stimulation (DBS) is the most useful technique currently
[142]
available for central pain caused by spinal cord lesions, pain connected to the spinothalamic tract, and
pain not adequately relieved by spinal cord or peripheral nerve stimulation ( Table 37–1 ). The [142]
procedure has also been reported in the relief of chronic pain of benign etiology. [143]
Mechanism of Action
A questioning stimulation properly located in the periventricular gray/periaqueductal gray matter (PVG/PAG) sets
off an endogenous opiate system, mediated primarily by β-endorphins, that inhibits noxious pain impulses. The [142]
failure of naloxone to reverse the results of stimulation in trials indicates that the system in the thalamus and internal
capsule does not involve opiates, although the mechanism of action is still unclear. [142]
926
Technique
To implant the electrode, the patient is given a local anesthetic, and a bur hole is made 3 cm from the midline in the
coronal structure. Stereotactic guidance with computed tomography (CT) or magnetic resonance imaging (MRI)
enables these bur holes to be placed easily and accurately and thus provide for better localization of the electrode. [143]
The initial sites for implantation are generally in the PVG/PAG area, the ventral posterior lateral thalamus, or the
internal capsule. Selection of the best location for implantation in an individual patient includes evaluation of the
[143]
type of pain experienced and the severity of pain and pain relief. For nociceptive pain, stimulation of the PVG/PAG
provides maximal levels of analgesia, whereas stimulation of areas in and around the thalamus works well for
neuropathic pain. Surgeons tend to prefer treating neuropathic pain with ablations on the internal capsule because
[144]
of the small target size of thalamic targets and the numbness that may result from implantation in the thalamus
itself. [142]
When an electrode is implanted in the PVG/PAG, an exploring electrode tip is placed 10 mm posterior to the
midpoint of the anterior and posterior commissures line at a depth of 4 to 5 mm. The internal capsule can be found
[142]
in the atlas of Tasker and Emmers; end test stimulation is performed at the junction of the thalamus and internal
capsule. Many surgeons place the electrodes temporarily in both areas and allow the
[142]
TABLE 37-1 -- SUMMARY OF STRENGTHS/WEAKNESSES OF NEUROAUGMENTATIVE PROCEDURES FOR PAIN

Mechanism of
Modality Action Technique Outcome Studies Indication Rating Best Indication(s)
Spinal cord stimulation for somatic-neuropathic pain
Appendicular pain Good Excellent Excellent Excellent Neuropathic pain in
limited distribution,
one or two limbs
Axial pain Acceptable Good Marginal Acceptable Localized neuropathic
back pain
Pelvic-sacral pain Marginal Good Marginal Acceptable Focal pelvic pain,
bladder voiding
dysfunction
Peripheral nerve stimulation
Limb Acceptable Good Good Good CRPS in distribution
of one major
peripheral nerve
Occipital Good Excellent Acceptable Good Unilateral posterior
scalp pain with good
temporary relief to
occipital nerve block
Intraventricular opioid Good Excellent Good Good Diffuse somatic body
delivery pain from cancer;
head-neck cancer pain
Deep brain Excellent Excellent Good Acceptable Noncancer,
stimulation neuropathic (with or
without
visceral/somatic) pain
from diffuse or
multiple sites; central
pain from spinal cord,
cranial nerve
etiologies
Motor cortex Poor Acceptable Marginal Poor Poststroke pain (?);
stimulation intractable facial
neuralgia (?)
Spinal cord stimulation for visceral pain
Angina Acceptable Excellent Good Excellent Intractable angina not
amenable to coronary
artery bypass
Peripheral vascular Acceptable Excellent Good Excellent Rest ischemic pain
disease from end-stage
peripheral vascular
disease but without
large nonhealing
ulcer(s)
Abdominal pain Marginal Marginal Poor Poor Pancreatitis (?)
CRPS, complex regional pain syndrome.
927
patient to choose the location that best alleviates pain; others rely on preliminary stimulation to obtain placement.
After 4 days of routine tests of the apparatus, the levels that generate pain relief are determined. A radiofrequency-
receiving device can be attached 1 to 3 months after surgery so that the patient can maintain independence and
mobility. [142]
Outcome Studies
In a series of 31 patients with cancer pain and treated with DBS, 27 (87%) experienced satisfactory relief; 15 (55%)
of those patients experienced lasting relief until death. Among a group of noncancer patients receiving similar
[145]
treatment, the overall success rate was 50% to 63% after acute relief had been achieved in 61% to 80% of patients
initially. During a 15-year trial, 78% of patients opted to internalize their devices after implantation, and 79%
[146] [149]
reported long-term relief. [147]
DBS is successful in cancer patients with pain refractory to other ablative procedures; such pain includes that caused
by diffuse bone metastases, midline or bilateral pain (especially of the lower body), brachial or lumbosacral
plexopathy, and recurrent pain from head and neck cancer. [145] [148]
Placement of the electrode makes complications almost unavoidable and is the cause of complications displayed.
Complications are less frequent when the electrode is placed in the PVG region than when it is placed in the PAG
region. In the study by Kumar, hardware malfunction was responsible for the majority of the complications,
although 20% to 25% of affected patients reported the development of migraine-type headaches. The development [142]
of tolerance to stimulation is specific to placement in the PVG/PAG regions, although it has been hypothesized that
ramp stimulation (intermittent stimulation) and administration of L-tryptophan for 2 to 3 weeks can diminish the
incidence of this occurrence. Individual variation may reduce the possibility of analgesia for some patients, but the
[142]
possibility of effective pain relief is both encouraging and realistic to most patients. [143]
Indications
The best indications for DBS appear to be severe pain for which there has been a failure to obtain long-lasting relief
with spinal cord stimulation or in which the pain topography is not amenable to spinal cord stimulation. Pain in
diffuse body sites and pain in multiple widely separate areas of the body are examples of these indications.
The application for DBS is almost always for noncancer pain. Neuropathic or mixed neuropathic/somatic/visceral
pain responds best to DBS, whereas pure nociceptive pain is thought not to respond very well. Another exception, in
the experience of some investigators, has been midline neuropathic pain, which appears not to respond as well to
DBS as do other forms of neuropathic pain.
A more specific indication for DBS includes central pain from spinal or lower intracranial levels; the efficacy of
DBS for thalamic or cerebral cortical etiologies is still unclear. Other indications include phantom or stump pain,
recurrent pain, and painful dysesthesias after other ablative spinal or peripheral procedures. Finally, severe pain
from cranial nerve sources, such as trigeminal neuralgia, can be treated successfully with DBS. Postdenervation
painful syndromes, such as anesthesia dolorosa, also fall into this category.
DBS is clearly an effective treatment for pain, including some of the most difficult pain syndromes encountered by
the practicing pain medicine physician. The hardware development appears to be adequate and fairly stable at the
present time. The target sites in the brain also appear to be optimal, and there does not appear to be a large amount
of ongoing research for better sites of deep brain stimulation. The more active research at the present time appears to
be with motor cortex stimulation as a possible alternative to DBS.
Because of the difficulty in localization of the DBS electrode within the brain (albeit with percutaneous stereotactic
guidance), it seems to occupy a position as a later or last option, usually by neurosurgeons with a special interest in
this modality. With the reappearance of clinically available hardware for DBS, newer reported studies are needed to
describe better which neuropathic pain syndromes, which types of “more diffuse pain topography,” and which
postdenervation neuralgias can be treated with uniform pain relief to a high degree.
Motor Cortex Stimulation
HISTORY
A newer augmentative technique for pain relief is motor cortex stimulation. The technique of precentral gyrus
stimulation dates back to the early 1990s, with reports from Tsubokawa and colleagues and Meyerson and
[150] [151]
associates. [152]
Mechanism of Action
The mechanism of pain relief from motor cortex stimulation remains unclear, although positron emission
tomographic (PET) studies have provided some insight. Use of PET to determine regional blood flow with 15 O2
[153] [154]
-labeled water indicated increased blood flow in the lateral ipsilateral thalamus. This, in turn, appeared to cause
descending inhibition of pain impulses by activation of the brainstem. The activation of the brainstem was correlated
928
with pain relief, whereas activation of the anterior cingulate and orbitofrontal cortex might be associated with the
affective-emotional component of the chronic pain.
Technique
A bur hole or small craniotomy is made in the skull, and a plate-type electrode array is placed into the epidural space.
The array is positioned over the precentral (motor) gyrus, and then stimulation is applied. If the stimulation is
effective, the tail of the electrode is connected to a permanent extension wire and an implanted generator, as
described earlier for spinal cord stimulation. Although the usual screening technique is surgical exposure of the
epidural space and placement of the permanent electrode over the precentral gyrus, another technique involving
transcranial magnetic coil stimulation has been described. The utility of this screening technique is still unknown
[155]
because it has been reported for only two patients.

Outcome Studies
One report in 1997 involving seven patients indicated initially good results in six patients but long-term (more than
3 months) satisfactory results in only one patient. The experience of Peyron and colleagues and Mertens and
[156]
associates with 23 patients indicated that 17 (75%) of patients experienced fair or better results after a mean
[157] [158]
follow-up period of 23 months. Overall, as of 1999, more than 127 patients had been reported in world literature as
having received motor cortex stimulation. [158]
An important but relatively rare complication of motor cortex stimulation is generalized seizure, usually voltage-
related and eliminated by voltage reduction.
Indications
The best indication appears to be severe central pain after thalamic stroke or hemorrhage. Precentral gyrus
[156] [157] [158]
stimulation has also been reported to be successful with intractable facial neuralgia. Two patients, one with
[159]
trigeminal neuralgia and another with glossopharyngeal neuralgia, responded well to motor cortex stimulation after
a follow-up period of 18 months.
The present role of motor cortex stimulation is very unclear. Since the 1960s, there have been a limited number of
published reports, which have covered a limited number of patients. Technically, it is simpler to perform than deep
brain stimulation. In view of reports of better localization of the motor cortex through functional modalities such as
cortical mapping or functional MRI, it holds great promise for better results in the future.
This is important clinically because motor cortex stimulation would be used to treat the most difficult types of pain,
such as poststroke pain, central pain, and diffuse body pain. However, the present published reports and even
unpublished anecdotal experience have to be considered very limited, and the “great promise” is yet to be fulfilled.
The overriding need in this form of therapy is for multiple clinical investigators at multiple different centers to
administer this therapy to a significant number of patients and then rapidly report the results. Only then can the
practicing pain medicine physician truly appraise the clinical role of motor cortex stimulation.
Spinal Cord Stimulation for Visceral Pain

SPINAL CORD STIMULATION FOR ANGINA
HISTORY
Spinal cord stimulation in the treatment of chronic intractable angina pectoris was first
reported in 1987 by Murphy and Giles. [160]
Mechanisms of Action
The mechanisms of action by spinal cord stimulation in the treatment of angina remain unclear. Four potential
sources are suggested. There might be a sympathectomy effect with a decrease in sympathetic tone, direct inhibition
of nociceptive afferent nerves in the spinal cord, or both. Coronary microcirculation may be improved by the release
of neurochemicals. Myocardial oxygen demand might be decreased by a combination of improved cardiac
[161] [162]
function, coronary blood flow, metabolism, and oxygen consumption. It seems least likely that the stimulation
[163]
might simply decrease the perception of pain but not affect the underlying ischemia, oxygen needs, and blood flow.
Kujacic and Eliasson, in assessing the effect of spinal cord stimulation on left ventricular ejection fraction (LVEF),
[164]
found improved LVEF and less left ventricular dysfunction on the echocardiogram with spinal cord stimulation.
Augustinsson and Linderoth showed a significant improvement in coronary sinus blood flow, heart muscle lactate
[165]
metabolism, and oxygen demand. Enhanced myocardial perfusion via dynamic PET has been shown, especially for
more even flow to the entire myocardium. Finally, it appears that spinal cord stimulation increases exercise duration,
increases the time between anginal episodes, decreases the number of anginal attacks, decreases the number of
ischemic episodes, and decreases the need for sublingual nitrate consumption. [165]
929
Technique
Proper placement for electrical stimulation is dependent on reproduction of paresthesias in the area of the angina.
For cardiac coverage, placement of the electrode at the T1–T2 vertebral body level, approximately 3 to 5 mm to the
left of midline is typical. After a standard trial period, permanent implantation can be performed.
Outcome Studies
De Jongste and colleagues, in a prospective study of 22 patients with 1-year follow-up periods, found that the
[166]
number of angina attacks was significantly reduced (P < .003) and that nitroglycerin intake also decreased by a
statistically significant amount (P < .005). Sanderson and coworkers, in a study of 23 patients with a mean
[167]
follow-up period of 62 months, found a mean drop in New York Heart Association (NYHA) class from 3.1
preoperatively to 2.0 postoperatively at the last follow-up examination. Exercise tolerance increased from 407
seconds without stimulation to 499 seconds with stimulation. The overall incidence of ischemic episodes decreased,
as measured by 48-hour ST segment monitoring.
Perhaps the most extensive long-term study, by Augustinsson involved 225 patients suffering from severe angina
[168]
pectoris in NYHA functional classes III and IV. Patients were shown to have excellent analgesia with decreased
intake of medications and improved quality of life. Pacing studies also revealed that spinal cord stimulation did not
conceal signs of ischemia even when extreme workloads were imposed on the heart. As for the socioeconomic
ramifications, Rasmussen and Andersen found a significant reduction in the number of hospital admissions and
money spent for non–hospital-related costs, increased mobility, increased function in daily life, decreased perception
of pain, and increased physical activity. [169]
Indications
At the present, spinal cord stimulation is viewed as a therapy of last resort for these patients. The goals of spinal
cord stimulation are to relieve the incapacitating anginal pain that persists despite maximal medical and surgical
interventions and, ultimately, to improve functional capacity and quality of life. That said, the impressive successes
in published and anecdotal cases with spinal cord stimulation for severe angina has led some clinicians to suggest
this treatment modality as a midlevel option, perhaps to precede repeated coronary bypass or repeated endovascular
procedures.
Spinal cord stimulation in the treatment of intractable angina is one of the most exciting and promising forms of new
uses for spinal cord stimulation at the present time. This is because of the reported successes, very impressive
anecdotal case reports, ease of trailing with a percutaneous lead, cost effectiveness, and rapidly growing basic
research for its mechanism of action. Although the degree of future use is difficult to predict, it appears that it would
increase significantly over the next 3 to 5 years. The major future direction would be for a continued increase in the
basic research for the mechanism of action in this setting.
SPINAL CORD STIMULATION FOR PERIPHERAL VASCULAR DISEASE
HISTORY
Peripheral vascular effects of electrical stimulation were described in the mid-1970s by Dooley and Kasprak [170]
and Cook and associates. Further collaborative studies have since been presented to advance the techniques
[171]
and promote benefits of spinal cord stimulation for peripheral vascular disease. [160] [172] [173]
Mechanism of Action
Spinal cord stimulation has been found to improve blood flow, and the mechanism for this remains under
investigation. According to the work of Linderoth and associates, it seems unlikely that the observed
[174] [175] [176]
dilatation is secondary to activation of afferent antidromic fibers from the periphery. Results of similar studies by
the same investigators suggest that some local chemical or electrical phenomenon at the site of stimulation is
responsible, perhaps via the release of certain vasodilatory substances, as is some involvement of the sympathetic
nervous system. [174] [175] [176]
The increased blood flow with spinal cord stimulation is also thought to result from an effect on the microcirculation
rather than the macrocirculation, as indicated by changes in capillary density, decreased appearance time, and
increased red blood cell velocity in the nail bed of the great toe. Bunt and associates performed a prospective study
[177]
involving patients in Fontaine class IIIa (rest pain), IIIb (rest pain and ischemic ulcer), or IVa (rest pain and dry
gangrene) who were not considered to be candidates for any type of vascular reconstructive surgery. Transcutaneous
oxygen tension (tcPO2 ) measurements rose almost 113% on average after 3 months of stimulation. It is not clear
whether the demonstrated improvement in blood flow in the microcirculation is responsible for the analgesic effect
or whether the opposite is true.
930
Technique
Placement of the stimulating catheter is in the epidural space at the T10–T12 level. This level of stimulation covers
the lower extremities with paresthesia.
Outcome Studies
In a long-term study of spinal cord stimulation in 1059 patients with ischemia-related pain, 847 (80%) continued to
experience excellent analgesia after follow-up periods ranging from 14 to 48 months. In another study of 34 patients
monitored for more than 7 years, half of the ischemic ulcers in these patients were healed and the amputation rate
was reduced by almost 50%, in comparison to a control group. Other studies have shown that patients can return to
active rehabilitation and physiotherapy, marked reductions in pain, and high limb salvage rates. [72] [170] [178] [179] [181]
Indications
Most studies indicate that spinal cord stimulation is beneficial in patients with end-stage peripheral vascular disease
and rest pain that are not amenable to surgical reconstruction. Spinal cord stimulation is more effective for general
ischemic pain than for pain secondary to large nonhealing ulcers or gangrene. Spinal cord stimulation might
promote the healing of ulcers smaller than 3 cm2 . It remains controversial whether spinal cord stimulation should be
considered earlier in the treatment algorithm. The overall goal of this therapy is not only limb salvage but also
improved analgesia and increased function.
The use of spinal cord stimulation in the treatment of peripheral vascular disease remains confusing. It is widely
used with good results in Europe but much less used in the United States. Adequate literature supports its efficacy in
pain relief, healing of moderate or small ulcers, improved activity levels, and limb salvage. The technique has been
available and numerous published reports exist. The challenge appears not to be further research, published papers,
or technical improvements but wider dissemination of the published information and improved referral patterns from
and awareness by physicians who manage the routine, long-term care of patients with any form of peripheral
vascular disease.
SPINAL CORD STIMULATION FOR ABDOMINAL PAIN
Mechanism of Action
The putative mechanism for the efficacy of spinal cord stimulation for abdominal pain is similar to those for other
conditions: stimulation of the dorsal horn or dorsal column of the spinal cord or direct stimulation of nerve roots in
the lateral aspect of the spinal canal. The latter mechanism is probably more effective because it will cover both
somatic and visceral fibers.
Technique
Ilioinguinal and genitofemoral neuralgia has been treated with spinal epidural electrodes placed at the T11–L2 level,
about 5 to 7 mm from the midline. The use of the spinal epidural retrograde technique directed at the T12 nerve
[182]
root has also been described. [183]
Outcome Studies
Reports on the use of spinal stimulation for abdominal pain are very limited. Both the paramedian and lateral canal
(direct nerve root) electrode placement techniques seem to be reasonably effective for pain control in these
conditions. These reports are too limited and follow-up periods too short for more detailed comment about outcome
expectations.
Indications
There have been other anecdotal reports of the use of spinal stimulation with electrodes at the T11–T12 level (either
at the paramedian canal or over the nerve roots) in the treatment of severe pain from chronic pancreatitis. Other uses
of spinal cord stimulation for abdominal pain are unclear at the present time. Clinical exploration of these other
potential uses is also infrequent because of the increasing use of long-term intraspinal infusions of nonopioid
analgesics, such as bupivacaine or clonidine, in the treatment of severe visceral pain from various cancer and
noncancer syndromes.
Spinal cord stimulation for abdominal pain appears to be most clinically useful in the treatment of ilioinguinal and
genitofemoral neuralgia. The choice of technique (paramedian epidural or lateral spinal canal) remains unclear.
Future directions should focus on published reports of long-term follow-up with either technique (preferably both)
for these disorders. As for other abdominal pain conditions (e.g., pancreatitis), more extensive clinical use of spinal
cord stimulation is necessary to elucidate the selection of the best-suited patients as well as the appropriate
technique. However, the use and efficacy of spinal cord stimulation for these abdominal pain conditions may
931
improve significantly in the next few years with increasing clinical use of dual-array (e.g., two vertical columns of
four electrical contacts each) plate-type (via laminotomy) electrodes and implantable multichannel stimulator
receivers or generators. These instruments apparently have the ability to stimulate a significant larger area of the
spinal cord, nerve roots, or both and might be better able to provide complete coverage of the appropriate abdominal
areas.
Conclusions
• There has been a trend since the mid-1990s, especially among neurosurgeons, to prefer augmentative over
ablative procedures.
• Many modalities are available.
• Many improvements in technical and application information have been made since 1980.
• The practice of these procedures is more an art than a science.
• More published reports on the best outcomes are needed.
• Since 1980, there have been many improvements in technology and patient selection.
• More information about patient selection, probably more than technical improvements, is still needed.
• Long-term spinal infusion pump is the main alternative and appears to be increasing in use because of
non-narcotic analgesics, such as bupivacaine or clonidine, for infusion. Also, even newer agents that are
expected to be approved by the U.S. Food and Drug Administration (e.g., ziconotide) and other agents are
being tested at laboratory and clinical research levels.
REFERENCES
1. Shealy
CN, Mortimer JT, Reswick JB: Electrical inhibition of pain by stimulation of the dorsal columns: Preliminary clinical report. Anesth
Analg 46:489–491, 1967.
2. Long DM: The current status of electrical stimulation of the nervous system for the relief of chronic pain. Surg Neurol 49(2):142–144, 1998.
3. Rees H, Roberts MH: Antinociceptive effects of dorsal column stimulation in the rat: Involvement of the anterior pretectal nucleus. J Physiol
(Lond) 417:375–388, 1989.
4. Holsheimer
J, Struijk JJ, Wesselink W: Analysis of spinal cord stimulation and design of epidural electrodes by computer modeling.
Neuromodulation 1(1):14–18, 1998.
5. Holsheimer J, Strujik JJ: How do geometric factors influence epidural spinal cord stimulation? A quantitative analysis by computer modeling.
6. Struijk JJ, Holsheimer J, van der Heide GG, et al: Recruitment of dorsal column fibers in spinal cord stimulation: Influence of collateral
branching. IEEE Trans Biomed Eng 39:903–912, 1992.
7. Struijk JJ, Holsheimer J, Boone H: Excitation of dorsal root fibers in spinal cord stimulation: A theoretical study. IEEE Trans Biomed Eng
40:632–639, 1993.
8. Holsheimer J, Barolat G, Struijk JJ: Significance of the spinal cord position in spinal cord stimulation. Acta Neurochir 64:119–124, 1995.
9. Holsheimer
J, Struijk JJ, Tass N: Effect of electrogeometry in combination on nerve fiber selectivity in spinal cord stimulation. Med Biol Eng
Comput 33:676–682, 1995.
10. He J, Barolat G, Holsheimer J, et al: Perception threshold and electrode position for spinal cord stimulation. Pain 59:55–63, 1994.
11. Struijk
JJ, Holsheimer J, Barolat G, et al: Paresthesia thresholds in spinal cord stimulation: A comparison of theoretical results with clinical
data. IEEE Trans Rehab Eng 101–108, 1993.
12. Holsheimer J: Effectiveness of spinal cord stimulation in the management of chronic pain, analysis of technical drawbacks and solutions.
13. HolsheimerJ, Den Boer J, Struijk JJ, et al: MR assessment of the normal position of the spinal cord in the spinal canal. AJNR Am J
Neuroradiol 15:951–959, 1994.
14. Struijk JJ, Holsheimer J: Transverse tripolar spinal cord stimulation, theoretical performance of a dual channel system. Med Biol Eng Comput
34:273–279, 1996.
15. HolsheimerJ, Struijk JJ, Rukhoff NJ: Contact combinations in epidural spinal cord stimulation: A comparison by computer modeling.
16. Struijk
JJ, Holsheimer J, Van Veen BK, et al: Epidural spinal cord stimulation: Calculation of field potentials with special reference to dorsal
column nerve fibers. IEEE Trans Biomed Eng 38:104–110, 1991.
18. Melzack R, Wall P: Pain mechanisms: A new theory. Science 150:971–979, 1965.
19. Sweet WH: Handb Physiol 1:459, 1959.
932
20. Sinclair DC: Cutaneous sensation and doctrine of specific energy. Brain 78:584–614, 1955.
21. Wall P: Comments after 30 years of the gate control theory. Pain Forum 5(1):12–22, 1996.
22. SaadeNE, Tabet MS, Banna NR, et al: Inhibition of nociceptive evoked activity in spinal neurons through a dorsal column–brainstem–spinal
loop. Brain Res 339(1):115–118, 1985.
23. Linderoth B, Gazelius B, Franck J, et al: Dorsal column stimulation induces release of serotonin and substance P in the cat dorsal horn.
24. Broggi
G, Franzini A, Prati E, et al: Neurochemical and structural modifications related to pain control induced by spinal cord stimulation. In:
Neuromodulation, An Overview. New York: Futura, 1985, pp 87–95.
25. Campbell J: Examination of possible mechanisms by which stimulation of the spinal cord in man relieves pain. Appl Neurophysiol 44:181–
186, 1981.
26. Stiller
C, Cui J, O’Connor W: Release of gamma-aminobutyric acid in the dorsal horn and suppression of tactile allodynia by spinal cord
stimulation in mononeuropathic rats. Neurosurgery 39:367–375, 1996.
27. Duggan A, Foong F: Bicuculline and spinal inhibition produced by dorsal column stimulation in the cat. Pain 22:249–259, 1985.
28. Linderoth B, Meyerson B: Dorsal column stimulation: Modulation of somatosensory and autonomic function. Semin Neurosci 7:263–277,
1995.
29. Linderoth
B, Fedorcsak I, Meyerson BA: Peripheral vasodilatation after spinal cord stimulation: Animal studies of putative effector
mechanisms. Neurosurgery 28:187–195, 1991.
30. Linderoth B, Stiller C, Gunadekera L, et al: Gamma-aminobutyric acid is released in the dorsal horn by electrical spinal stimulation: An in
vivo microdialysis study in the rat. Neurosurgery 34:484–488, 1994.
31. Meyerson B, Herregodts P, Linderoth B, et al: An experimental animal model of spinal cord stimulation for pain. Stereotact Funct Neurosurg
62:256–262, 1994.
32. Meyerson B, Ren B, Herregodts P, et al: Spinal cord stimulation in animal model of mononeuropathy: Effects on the withdrawal response and
the flexor reflex. Pain 61:229–243, 1995.
33. Simpson R, Robertson C, Halter J: Glycine: A potential mediator of electrically induced pain modification. Biomed Lett 48:193–207, 1993.
34. Meilman PW, Leibrock LG, Leong FT: Outcome of implanted spinal cord stimulation in the treatment of chronic pain: Arachnoiditis versus
single nerve root injury and mononeuropathy. Clin J Pain 5:189–193, 1989.
35. De la Porte C, Van de Kelft E: Spinal cord stimulation in failed back surgery syndrome. Pain 52:55–61, 1993.
36. Leibrock LG, Meilman P, Cuka D, et al: Spinal cord stimulation in the treatment of chronic low back pain and lower extremity pain syndromes.
Nebr Med J 69(6):180–183, 1984.
37. Bel S, Bauer B: Dorsal column stimulation: Cost-to-benefit analysis. Acta Neurochir 52:121–123, 1991.
38. Meglio M, Cioni B, Rossi GF: Spinal cord stimulation in management of chronic pain: A 9-year experience. J Neurosurg 70:519–524, 1989.
39. Law J: Targeting a spinal stimulator to treat the failed back surgery syndrome. Appl Neurophys 50:437–438, 1987.
40. Law J: A new method of targeting a spinal stimulator: Quantitatively compared comparisons. Appl Neurophys 50:436, 1987.
41. Law
J: Spinal stimulation: Statistical superiority of monophasic stimulation of narrowly separated longitudinal bipoles having rostral cathodes.
Appl Neurophys 46:129–137, 1983.
42. Iacono RP, Guthkelch AN, Boswell MV: Dorsal root entry zone stimulation for deafferentation pain. Stereotact Funct Neurosurg 59(1–4):56–
61, 1992.
43. Alo
KM, Zidan AM: Selective nerve root stimulation (SNRS) in the treatment of end-stage, diabetic, peripheral neuropathy: A case report.
Neuromodulation 3(4):201–208, 2000.
44. Burchiel
K, Anderson V, Brown F, et al: Prospective multicenter study of spinal cord stimulation for relief of chronic back and extremity pain.
Spine 21:2786–2794, 1996.
45. Ohemiss D, Rashbaum R: Prospective outcome evaluation of spinal cord stimulation in patients with intractable leg pain. Spine 21:1344–1350,
1996.
46. Turner J, Loeser J: Spinal cord stimulation for chronic low back pain, a systemic literature synthesis. Neurosurgery 37:1088–1096, 1995.
47. Nielson KD, Adams JE, Hosubuchi Y: Experience with dorsal column stimulation for relief of chronic intractable pain: 1968–1973. Surg
933
Neurol 4:148–152, 1975.
48. DevulderJ, Vermeulen H, De Colvenaar L, et al: Spinal cord stimulation in chronic pain: Evaluation of results, complications, and technical
considerations in sixty-nine patients. Clin J Pain 7:21–28, 1991.
49. Probst
C: Spinal cord stimulation in 112 patients with epi-intradural fibrosis following operation for lumbar disc herniation. Acta Neurochir
107:147–151, 1990.
50. Shatin D, Mullet K: Totally implantable spinal cord stimulation for chronic pain: Design and efficacy. Pacing Clin Electrophysiol 9:577–583,
1986.
51. Spiegelmann R, Friedman W: Spinal cord stimulation: A contemporary series. J Neurosurg 28:65–71, 1991.
52. Urban B, Nashold B: Percutaneous epidural stimulation of the spinal cord for relief of pain: Long-term results. J Neurosurg 48:323–328, 1978.
53. Erickson
D, Long D: Ten-year followup of dorsal column stimulation. In Bonica JJ, Fessard A (eds): Advances in Pain Research and Therapy.
New York: Raven Press, 1983, pp 583–589.
54. Mittal B, Thomas D, Walton P, et al: Dorsal column stimulation in chronic pain: Report of 31 cases. Ann R Coll Surg Engl 69:104–109, 1987.
55. Siegfried J, Lazorthes Y: Long-term followup of dorsal column stimulation for chronic pain after multiple lumbar operations. Appl
Neurophysiol 45:201–204, 1982.
56. De
la Porte C, Siegfried J: Lumbosacral spinal fibrosis, spinal arachnoiditis: Its diagnosis and treatment by spinal cord stimulation. Spine
8:593–600, 1983.
57. Shimoji K, Hokari T, Kano T, et al: Management of intractable pain with percutaneous epidural spinal cord stimulation: Differences in pain-
relieving effects among diseases and sites of pain. Anesth Analg 77:110–116, 1993.
58. De la Porte C, Van de Kelft E: Spinal cord stimulation in failed back surgery syndrome. Pain 52:55–61, 1993.
59. Le Doux M, Langford K: Spinal cord stimulation for the failed back syndrome. Spine 18:191–194, 1993.
60. Gonzalez-Darder J, Canela P, Gonzalez-Martinez V, et al: Spinal electrical stimulation: Current indications and results in a series of 46
patients. Rev Exp Anesthesiol Reanim 39:86–90, 1992.
61. Devulder J, De Colvenaar L, Rolly G, et al: Spinal cord stimulation in chronic pain therapy. Clin J Pain 6:51–56, 1991.
62. Racz G, McCarron R: Percutaneous dorsal column stimulator for chronic pain control. Spine 14:1–4, 1989.
63. RichardsonR, Siqueira E, Cerullo LJ, et al: Spinal epidural neurostimulation for treatment of acute and chronic intractable pain: Initial and
long-term results. Neurosurgery 5:344–348, 1979.
64. Simpson B: Spinal cord stimulation in 60 cases of intractable pain. J Neurol Neurosurg Psychiat 54:196–199, 1991.
65. Kumar K, Nath R, Wyant G, et al: Treatment of chronic pain by epidural spinal cord stimulation: A 10-year experience. J Neurosurg 75:402–
407, 1991.
66. North
RB, Campbell JN, James CS, et al: Failed back surgery syndrome: 5-year follow-up in 102 patients undergoing repeated operation.
67. North
R, Kidd D, Zahurak M, et al: Spinal cord stimulation for chronic intractable pain: Experience over two decades. Neurosurgery 2:384–
395, 1993.
68. NorthR, Kidd DH, Lee MS, et al: Spinal cord stimulation versus reoperation for the failed back surgery syndrome: A prospective randomized
study design. Stereotact Funct Neurosurg 62:267–272, 1994.
69. NorthR: Spinal cord stimulation for intractable pain: Indications and technique. In Mosby CV (ed): Current Therapy in Neurological Surgery.
Philadelphia: BC Decker, 1989, pp 297–301.
70. North
R, Lanning A, et al: Spinal cord stimulation with percutaneous and plate electrodes: Side effects and quantitative comparisons.
Neurosurg Focus 2(1):1–5, 1997.
pain. Spine 21:2786–2794, 1996.
72. Robaina
F, Dominguez M, Diaz M, et al: Spinal cord stimulation for relief of chronic pain in vasospastic disorders of the upper limbs.
73. Barolat G, Schwartzman R: Epidural spinal cord stimulation in the management of reflex sympathetic dystrophy. Stereotact Funct Neurosurg
3:29–39, 1989.
934
74. Broseta J, Roldan P, Gonzalez-Darder J, et al: Chronic epidural dorsal stimulation in the treatment of causalgic pain. Appl Neurophys 5:190–
194, 1982.
75. Law J: Spinal cord stimulation for intractable pain due to reflex sympathetic dystrophy. CNI Rev 17–22, 1993.
76. Sánchez-Ledesma MJ, García-March G, Diaz-Cascajo P, et al: Spinal cord stimulation in deafferentation pain. Stereotact Funct Neurosurg
53:40–45, 1989.
77. Tasker
RR, DeCarvalho GT, Dolan EJ: Intractable pain of spinal cord origin: Clinical features and implications for surgery. J Neurosurg
77:373–378, 1992.
78. Meglio M, Cioni B, Prezioso A, et al: Spinal cord stimulation in deafferentation pain. Pacing Clin Electrophysiol 12:709–712, 1989.
79. KrainickJ, Thoden U, Riechert T, et al: Pain reduction in amputees by long-term spinal cord stimulation: Long-term follow-up study over five
years. J Neurosurg 52:346–350, 1980.
80. LawJD: Spinal stimulation in the “failed back surgery syndrome”: Comparison of technical criteria for palliating pain in the leg versus in the
low back. Acta Neurochir 117, 1992.
81. Barolat G, Zeme S, Ketcik B: Multifactorial analysis of epidural spinal stimulation. Stereotact Funct Neurosurg 56:77–103, 1991.
82. Barolat G: Experience with 509 plate electrodes implanted epidurally from C1 to L1. Stereotact Funct Neurosurg 61:60–79, 1993.
83. Barolat G: Current status of epidural spinal cord stimulation. Neurosurg Q 5(2):98–124, 1995.
84. AloKM, Yland M, Kramer D, et al: Computer-assisted and patient interactive programming of dual octrode spinal cord stimulation in the
treatment of chronic pain. Neuromodulation 1(1):30–46, 1998.
85. Barolat
G, Massaro F, He J, et al: Mapping of sensory responses to epidural stimulation of the intraspinal neural structures in man. J Neurosurg
78:233–239, 1993.
86. Alo, 1998.
87. Rossi, 1994.
88. Nelson D, et al: Psychological selection criteria for implantable spinal cord stimulators. Pain Forum 5(2):93–103, 1996.
89. Wyndaele
JJ, Michielsen D, Van Dromme S: Influence of sacral neuromodulation on electrosensation of the lower urinary tract. J Urol
163:221–227, 2000.
90. Talalla A, Bloom JW, Quang N: FES for bladder: Direct or indirect means? Pacing Clin Electrophysiol 10:240–245, 1987.
91. Schmidt RA, Jonas U, Oleson KA, et al: Sacral nerve stimulation for treatment of refractory urinary urge incontinence: Sacral nerve
stimulation study group. J Urol 162:352–357, 1999.
92. Lou L: Uncommon areas of electrical stimulation for pain relief. Curr Rev Pain 4:407–412, 2000.
93. Alo
KM, Yland MJ, Redko V, et al: Lumbar and sacral nerve root stimulation (NRS) in the treatment of chronic pain: A novel anatomic
approach and neuro stimulation technique. Neuromodulation 2(1):23–31, 1999.
94. Dijkema HE, Weil EHJ, Mijs PT, et al: Neuromodulation of sacral nerves for incontinence and voiding dysfunctions. Eur Urol 24:72–76, 1993.
95. Hassouna MM, Siegel SW, Nyeholt AA, et al: Sacral neuromodulation in the treatment of urgency-frequency symptoms: A multicenter study
on efficacy and safety. J Urol 163:1849–1854, 2000.
96. Picaza J, Hunter S, Cannon B: Pain suppression by peripheral nerve stimulation. Appl Neurophysiol 40:223–239, 1977–1978.
97. Racz
G, Lewis R, Heavner J, et al: Peripheral nerve stimulator implant for treatment of causalgia. In Stanton-Hicks M (ed): Pain and the
Sympathetic Nervous System. Boston: Kluwer, 1990, pp 225–239.
98. Campbell J, Long D: Peripheral nerve stimulation in the treatment of intractable pain. J Neurosurg 43:692–699, 1976.
99. LawJD, Swett J, Kirsch WM: Retrospective analysis of 22 patients with chronic pain treated by peripheral nerve stimulation. J Neurosurg
52:482–485, 1980.
100. Long DM, Erickson D, Campbell J, et al: Electrical stimulation of the spinal cord and peripheral nerves for pain control: A 10-year experience.
Appl Neurophysiol 44:207–217, 1981.
101. Nashold B, Goldner J, Mullen J, et al: Long-term pain control by direct peripheral nerve stimulation. J Bone Joint Surg Am 64:1–10, 1982.
935
102. Cauthen JC, Renner EJ: Transcutaneous and peripheral nerve stimulation for chronic pain states. Surg Neurol 4(1):102–104, 1975.
103. Clark K: Electrical stimulation of the nervous system for control of pain: University of Texas Southwestern Medical School experience.
Surgical Neurology 4(1):164–166, 1975.
104. Picaza
JA, Cannon BW, Hunter SE, et al: Pain suppression by peripheral nerve stimulation: Part II. Observations with implanted devices.
Surg Neurosurg 4(1):115–126, 1975.
105. Long DM: Electrical stimulation of the nervous system for pain control. Electroencephalog Clin Neurophysiol Suppl (34):343–348, 1978.
106. Nashold
BS Jr, Mullen JB, Avery R: Peripheral nerve stimulation for pain relief using a multicontact electrode system. Technical note. J
Neurosurg 51:872–873, 1979.
108. Long DM: Stimulation of the peripheral nervous system for pain control. Clin Neurosurg 31:323–343, 1983.
110. Racz GB, Browne T, Lewis R: Peripheral stimulator implant for treatment of causalgia caused by electrical burns. Tex Med 84:45–50, 1988.
111. Racz GB, Heavner JE: Comments on “A spiral nerve cuff electrode for peripheral nerve stimulation.” IEEE Trans Bio Eng 36:1140–1141,
1989.
112. RaczGB, Lewis R, Heavner JE, et al: Peripheral nerve stimulator implant for treatment of causalgia. In Stanton-Hicks M, Jänig W, Boas RA
(eds): Reflex Sympathetic Dystrophy. Norwell, MA: Kluwer, 1990, pp 135–141.
115. Campbell J, Taub A: Local analgesia from percutaneous electrical stimulation: A peripheral mechanism. Arch Neurol 28:347–350, 1973.
116. Chung JM, Lee KH, Hori Y, et al: Factors influencing peripheral nerve stimulation produced inhibition of primate spinothalamic tract cells.
Pain 19:277–293, 1984.
117. Chung JM, Fang ZR, Hori Y, et al: Prolonged inhibition of primate spinothalamic tract cells by peripheral nerve stimulation. Pain 19:259–275,
1984.
118. Ignelzi
R, Nyquist J: Excitability changes in peripheral nerve fibers after repetitive electrical stimulation: Implications in pain modulations. J
Neurosurg 51:824–833, 1979.
120. Wall
P, Gutnick M: Ongoing activity in peripheral nerves: The physiology and pharmacology of impluses originating from a neuroma. Exp
Neurol 43:580–593, 1974.
121. Meyerson B, Hakanson S: Alleviation of atypical trigeminal neuropathy by electric stimulation of the gasserian ganglion. Neurosurgery 1:59–
66, 1986.
122. Racz
GB, Lewis R, Heavner JE, et al: Peripheral nerve stimulator implant for treatment of causalgia. In Stanton-Hicks M (ed): Pain and the
Sympathetic Nervous System. Norwell, Mass.: Kluwer, 1990, pp 225–239.
123. Nam TX, Song SH, Kim YH, et al: Effect of peripheral nerve stimulation on the dorsal horn cell activity in cats with cutaneous inflammation.
Yonsei Med J 33(2):109–120, 1992.
124. Urban BJ, Nashold BS Jr: Combined epidural and peripheral nerve stimulation for relief of pain: Description of technique and preliminary
results. J Neurosurg 57:365–369, 1982.
125. Hassenbusch
SJ, Stanton-Hicks M, Schoppa D, et al: Long-term results of peripheral nerve stimulation of reflex sympathic dystrophy. J
Neurosurg 84:415–423, 1996.
126. Calvillo O, Racz G, Didie J, et al: Neuroaugmentation in the treatment of complex regional pain syndrome of the upper extremity. Acta
Orthop Belg 64(1):57–63, 1998.
127. Ebel H, Balogh A, Volz M, et al: Augmentative treatment of chronic deafferentation pain syndrome after peripheral nerve lesions. Minim
Invasive Neurosurg 43(1):44–50, 2000.
128. Shetter A, Racz G, Lewis R, et al: Peripheral nerve stimulation. In North R, Levy R (eds): Neurosurgical Management of Pain. New York:
129. Day M: Neuromodulation: Spinal cord and peripheral nerve stimulation. Curr Rev Pain 4:374–382, 2000.
130. Stanton-Hicks M, Salamon J: Stimulation of the central and peripheral nervous system for the control of pain. J Clin Neurophysiol 14:46–62,
1997.
131. Iacono RP, Linford J, Sandyk R: Pain management after lower extremity amputation. Neurosurgery 20:496–500, 1987.
132. Weiner R, Reed K: Peripheral neruostimulation for control of intractable occipital neuralgia. Neuromodulation 3:217–221, 1999.
133. Weiner RL: The future of peripheral nerve neurostimulation. Neurosurg Res 22:299–304, 2000.
936
134. Lazorthes Y: Intracerebroventricular administration of morphine for control of irreducible cancer pain. Ann N Y Acad Sci 531:123–132, 1988.
135. Tseng LF, Fujimoto JM: Differential actions of intrathecal naloxone on blocking the tail-flick inhibition induced by intraventricular beta-
endorphin and morphine in rats. J Pharmacol Exp Ther 232:74–79, 1985.
136. Dennis GC, DeWitty RL: Long-term intraventricular infusion of morphine for intractable pain in cancer of the head and neck. Neurosurgery
26:404–407, 1990.
137. Brazenor GA: Long-term intrathecal administration of morphine: A comparison of bolus injection via reservoir with continuous infusion by
implanted pump. Neurosurgery 21:484–491, 1987.
138. Siegfried J: Intracerebral neurosurgery in the treatment of chronic pain. Schweiz Rundsch Med Prax 87:314–317, 1998.
139. PayneR, Gradert TL, Inturris CE: Cerebrospinal fluid distribution of opioids after intraventricular and lumbar subarachnoid administration in
sheep. Life Sci 59:1307–1321, 1996.
140. Seiwald
M, Alesch F, Kofler A: Intraventricular morphine administration as a treatment possibility for patients with intractable pain. Wien
Klin Wochenschr 108:5–8, 1996.
141. Karavelis A, Foroglou G, Selviaridis P, et al: Intraventricular administration of morphine for control of intractable cancer pain in 90 patients.
142. Richardson DE: Deep brain stimulation for pain relief. In Wilkins RH, Rengachary SS (eds): Neurosurgery. New York: McGraw-Hill, 1985,
pp 2421–2426.
143. Goodman RR: Surgical management of pain. Neurosurg Clin North Am 1:701–717, 1990.
144. Kumar K, Toth C, Nath RK: Deep brain stimulation for intractable pain: A 15-year experience. Neurosurgery 40:736–745, 1997.
145. Young RF: Electrical stimulation of the brain for the treatment of intractable cancer pain. In Arbit E (ed): Management of Cancer-Related
Pain. Mt. Kisco, N.Y.: Futura, 1993, pp 257–269.
146. Gybels J, Kupers R: Deep brain stimulation in the treatment of chronic pain in man: where and why? Neurophysiol Clin 21:389–398, 1990.
147. Kumar
K, Wyant GM, Nath R: Deep brain stimulation for control of intractable pain in humans, present and future: A ten-year follow-up.
148. YoungRF: Clinical experience with radiofrequency and laser DREZ lesions. J Neurosurg 72:715–720, 1990.
149. YoungRF, Tronnier V, Rinaldi PC: Chronic stimulation of the Kölliker-Fuse nucleus region for relief of intractable pain in humans. J
Neurosurg 76:979–985, 1992.
150. Tsubokawa T, Katayama Y, Yamamoto T, et al: Chronic motor cortex stimulation for the treatment of central pain. Acta Neurochir Suppl
52:137–139, 1991.
151. Tsubokawa T, Katayama Y, Yamamoto T, et al: Chronic motor cortex stimulation in patients with thalamic pain. J Neurosurg 78:393–401,
1993.
152. MeyersonBA, Lindblom U, Linderroth B, et al: Motor cortex stimulation as treatment of trigeminal neuropathic pain. Acta Neurochir Suppl
58:150–153, 1993.
153. Garcia-Larrea L, Peyron R, Mertens P, et al: Position emission tomography during motor cortex stimulation for pain control. Stereotact Funct
Neurosurg 68:141–148, 1997.
154. Garcia-LarreaL, Peyron R, Mertens P, et al: Electrical stimulation of motor cortex for pain control: A combined PET-scan and
electrophysiological study. Pain 83:259–273, 1999.
155. Migita
K, Uozumi T, Arita K, et al: Transcranial magnetic coil stimulation of motor cortex in patients with central pain. Neurosurgery
36:1037–1040, 1995.
156. Fujii M, Ohmoto Y, Kitahara T, et al: Motor cortex stimulation therapy in patients with thalamic pain. No Shinkei Geka 25:315–319, 1997.
157. Peyron R, Garcia-Larrea L, Deiber MP, et al: Electrical stimulation of precentral cortical area in the treatment of central pain:
Electrophysiological and PET study. Pain 62:275–286, 1995.
158. Mertens P, Nuti C, Sindou M, et al: Precentral cortex stimulation for the treatment of central neuropathic pain. Stereotact Funct Neurosurg
73:122–125, 1999.
159. Rainov NG, Fels C, Heidecke V, et al: Epidural electrical stimulation of the motor cortex in patients with facial neuralgia. Clin Neurol
Neurosurg 99:205–209, 1997.
160. Murphy D, Giles K: Intractable angina pectoris: Management with dorsal column stimulation. Med J Aust 146:260, 1987.
161. Cui J, O’Connor W, Ungerstedt U, et al: Spinal cord stimulation attenuates augmented dorsal horn release of excitatory amino acids in
937
mononeuropathy via a GABAergic mechanism. Pain 73:87–95, 1997.
162. Cui J, Meyerson B, Sollevi A, et al: Effect of spinal cord stimulation on tactile hypersensitivity in monoeuropathic rate is potentiated by
simultaneous GABA-B and adenosine receptor activation. Neurosci Lett 247:185–186, 1998.
163. NedeljkovicS, Latif O: Spinal cord stimulation for chronic intractable angina pectoris: A unified theory on its mechanism. In Nedeljkovic S
(ed): Kardiologia. Slovakia, Bratislava Symekard, 2000, pp 1802–1809.
164. KujacicV, Eliasson T: Assessment of the influence of spinal cord stimulation on left ventricular function in patients with severe angina
pectoris: An echocardiographic study. Eur Heart J 14:1238–1244, 1993.
165. Augustinsson L, Linderoth B: Spinal cord stimulation in cardiovascular disease. Neurosurg Clin North Am 6:157–165, 1995.
166. De
Jongste M, Hautvast R, Hillege H, et al: Efficacy of spinal cord stimulation as adjuvant therapy for intractable angina pectoris: A
prospective, randomized clinical study. Working Group on Neurocardiology. J Am Coll Cardiol 23:1592–1597, 1994.
167. SandersonJ, Ibrahim B, Waterhouse D, et al: Spinal electrical stimulation for intractable angina: Long-term clinical outcome and safety. Eur
Heart J 15:810–814, 1994.
168. Augustinsson
L: Spinal cord stimulation in severe angina pectoris. Stereotact Funct Neurosurg 65:136–141, 1995.
169. RasmussenM, Andersen C: Cost-benefit analysis of electrical stimulation of the spinal cord in the treatment of angina pectoris. Ugeskr
Laeger 154:1180–1184, 1992.
170. Dooley
D, Kasprak M: Modification of blood flow to the extremities by electrical stimulation of the nervous system. South Med J 69:1309–
1311, 1976.
171. CookA, Oygar A, Baggenstos P, et al: Vascular disease of the extremities: Electrical stimulation of the spinal cord and posterior roots. N Y
State J Med 76:366–368, 1976.
172. Tallis R, Illis L, Sedgwick E, et al: Spinal cord stimulation in peripheral vascular disease. J Neurol Neurosurg Psychiat 46:478–484, 1963.
173. Meglio M, Cioni B, Dal Lago A, et al: Pain control and improvement of peripheral blood flow following epidural spinal cord stimulation.
Case report. J Neurosurg 54:821–823, 1961.
174. Linderoth B, Fedorcsak I, Meyerson BA: Peripheral vasodilatation after spinal cord stimulation: Animal studies of putative effector
mechanisms. Neurosurgery 28:187–195, 1991.
175. Linderoth B, Fedorcsak I, Meyerson BA: Is vasodilatation following dorsal column stimulation mediated by antidromic activation of small
diameter afferents? Acta Neurochir Suppl 46:99–101, 1989.
176. Linderoth B, Gunasekera L, Meyerson BA: Effects of sympathectomy on skin and muscle microcirculation during dorsal column stimulation:
Animal studies. Neurosurgery 29:874–879, 1991.
177. Jacobs J, Slaaf D, et al: Dorsal column stimulation in critical limb ischemia. Vasc Med Rev 1:215–220, 1990.
178. Steude U, Abendroth D, Sunder-Plassmann L: Epidural spinal electrical stimulation in the treatment of severe arterial occlusive disease. Acta
Neurochir Suppl 52:118–120, 1991.
179. Meglio M, Cioni B, et al: Spinal cord stimulation and peripheral blood flow, indications for spinal cord stimulation: Proceedings of a
symposium. Princeton, N.J.: Excerpta Medica, 1981, pp 60–75.
181. Broseta J: Influence of spinal cord stimulation on peripheral blood flow. Appl Neurophysiol 48:367–370, 1985.
182. Lou L: Uncommon areas of electrical stimulation for pain relief. Curr Rev Pain 4:407–412, 2000.
183. Alo K, Yland M, Redko V, et al: Lumbar and sacral nerve root stimulation (NRS) in the treatment of chronic pain: A novel anatomic
approach and neuro stimulation technique. Neuromodulation 1:23–31, 1999.
938
Section V Chapter 38 - Intrathecal Therapies for the Treatment of Chronic
P i
Chapter 38 - Intrathecal Therapies for the Treatment of Chronic
Pain
ELLIOT S. KRAMES
FRANCIS S. PECORARO
Cost of Chronic Unrelieved Pain
The costs of unrelieved pain and disability arising from chronic pain in the United States is, and will continue to be,
a major problem until appropriate, cost-effective algorithms for the management of chronic pain are created and
implemented. Chronic, unrelieved pain is not only a major drain on scarce healthcare resources but also the cause of
untold suffering for millions of people worldwide. The direct, hard costs of unrelieved pain for patients and their
families are loss of job, income savings (and therefore security), and insurance. More intangible but no less
important consequences of unrelieved pain include loss of self-esteem, depression, anger, frustration, and suffering.
The end result of the direct and indirect costs of unrelieved pain is staggering to society and to the individuals who
unfortunately suffer from it. Approximately 30% of the United States population, or approximately 70 million
persons suffer from chronic pain. Given these alarming data, it is not difficult to imagine the impact of chronic pain
[1]
on society, the family, and the individual.
On a societal level, costs are incurred by lost productivity, ever-increasing insurance premiums, medical care costs,
and the overwork burden inherent in workplace absenteeism. It is well known that chronic pain patients use health
services much more often than non pain patients. In two studies by Von Korff and colleagues, chronic pain [2] [3]
patients are almost five times more likely to visit some form of healthcare setting. Fourteen percent of the adult
population in the United States complains of low back pain, which is the most common cause of work days missed
and workers' compensation claims. Labor productivity losses due to low back pain claims are estimated to be $25
[4]
billion per year, and 31 million people per year have lost workdays secondary to low back pain. In 1990,
[5] [6] [7]
Frymoyer and associates published a study estimating the direct and indirect cost to society of low back pain,
[5]
including work-related and non–work-related costs. Their finding was a staggering $27.9 billion. Back injuries
sustained at work tend to be more expensive to manage medically and involve more lost time from work. The cost [8]
of low back pain claims to employers in industries such as construction range from $10 to $40 billion per year. The [9]
lifetime risk for low back pain in the general population is estimated at 60% to 85%, and chronic pain is the most
common cause of disability impairing quality of life. There are 11 million visits per year to healthcare
[10]
professionals for low back pain. [11] [12]
The Michigan Pain Study revealed that pain was responsible for the absenteeism of 400,000 workers, or 12% of the
Michigan work force, at some point during 1997. Of those surveyed, 35% missed more than 20 days of work in the
same year. In a 1992 study of the dollar impact on 12 diverse and large businesses in the United States, workers'
disability cost an average of $2500 per employee. [13]
The effect of chronic pain on family members can be overwhelming. Ongoing family difficulties and stress,
including caretaking burdens, family dysfunction, and loss of financial stability, can be devastating. On an [14] [15]
individual basis, chronic pain limits functioning and may lead to the development of lifelong problems. Lost [16] [17]
days at school and work and poor performance compound other complications of chronic pain for the individual.
These complications include sleep disturbance, fatigue, poor peer relationships, poor social skills and adjustment,
and depression. Chronic pain patients are more likely to complain of depression than those who are not in chronic
pain, but loss of self-esteem may be the single most serious ramification of chronic pain.
The Michigan Pain Study, mentioned earlier, surveyed 1500 Michigan residents 18 years of age and older to
determine the severity of the chronic pain problem and to evaluate how people coped, how they obtained access to
treatment, and whether available pain care was effective. Of the 1.2 million people in Michigan who suffered from
chronic pain in 1997, 42% stated that the pain affected their relationships with spouses, family members, and fellow
workers. Nearly half (48%) experienced depression, 18% overdosed on pain medication, and 10% (about 120,000)
had contemplated suicide. Five percent of these chronic pain sufferers (representing approximately 60,000 adults)
drank alcohol to relieve their pain, and 29% believed that they were losing sleep as a result of their chronic pain.
Clearly, the consequences of intractable pain are staggering for society as a whole and as an emotional and physical
toll paid by individual patients and their families. Indeed, the figures noted earlier paint a gloomy and compelling
picture of the true costs incurred by our society as a result of chronic unrelieved pain. Finding a solution should be a
939
P i
high priority for government agencies, healthcare intermediaries, and healthcare workers. It is not acceptable today
to abandon patients when less costly invasive interventions fail to relieve pain and suffering. The purpose of this
chapter is to make the case that interventional pain management and, particularly, intrathecal therapies for the
control of intractable, unrelieved pain are appropriate, and based on efficacy reports in the literature, justifiable.
Intrathecal therapy does relieve pain and suffering and this therapy is, in fact, cost-effective when one looks at the
alternatives.
Treatment Options for Chronic Pain
The optimal management of intractable, chronic pain, both malignant and nonmalignant, begins with a thorough
understanding of the complex, biopsychosocial nature of the individual's complaint. It is also very important to
acknowledge that chronic, intractable pain is not either biological or psychological but truly multidimensional.
Chronic pain is not only the end result of activation of neurobiologic mechanisms; rather, it involves
neurophysiologic, emotional, and behavioral systems as well, all of which create a unique and complex pain
presentation. Thus, each chronic pain problem has its unique set of confounding variables, which must be
individually considered in the diagnosis and formulation of an appropriate individualized treatment plan.
An interdisciplinary approach to treating pain is integrative, and efficacy in treating intractable pain is the result of
the collective efforts of all the team members. Any comprehensive interdisciplinary pain team should consist of a
physician who not only is trained in pain treatment but also has knowledge of the fields of physical therapy,
occupational therapy, and recreational therapy as well as neuropsychology. These pain-trained physicians should
also know when to refer their patients for appropriate psychological evaluation and treatment. This knowledge is
important because the physician, as interdisciplinary pain team leader, must be able to direct care in a coordinated
and cohesive manner.
Other members of the pain team should include a psychologist, a psychiatrist, or both, trained in various cognitive
behavioral therapies, pain-oriented therapies, and, perhaps, biofeedback and hypnosis. The physical and
occupational therapists are central in addressing functional restoration and may employ various modalities,
including heat, cold, ultrasonography, and transcutaneous stimulation, as well as physical therapies. It is only
through a coordinated interdisciplinary approach that patients with chronic pain may be effectively treated and given
the best chance for lasting and enduring pain benefit.
Before any pain treatment plan can be initiated, it must be understood that all treatments come with some degree of
risk of injury to the patient. It is not difficult to imagine that invasive therapies could be harmful, but even massage
and ultrasonography carry risk of harm to the patient. The least invasive therapies should, when feasible, be
attempted before more invasive therapies are used. With this understanding, in the 1970s, the World Health
Organization (WHO) set forth guidelines for treating cancer pain ( Fig. 38–1 ). These guidelines, based on the well-
recognized medical management KISS principle (Keep it Simple and Sweet), were designed to minimize the risk to
patients and at the same time provide a treatment algorithm that can be followed by all of those who treat patients
with treating pain.[18] [19]
Multiple options are available for the treatment of patients with chronic pain, including noninvasive and less costly
therapies as well as invasive and more costly therapies. In general, the least invasive therapies should be tried ( Fig.
38–2 ).
Although there continues to be a controversy in the literature over the use of opioids for the treatment of
nonmalignant pain, pain clinicians do use opioids in carefully selected patients. Concerns about addiction,
Figure 38-1 The World Health Organization “ladder” is based on pharmacologic tailoring to
the needs of the patient. Patients with mild to moderate pain are given nonopioid analgesics
such as aspirin, acetaminophen, or nonsteroidal anti-inflammatory drugs along with adjuvant
medications or medications that have analgesic potential but are not labeled as analgesics.
Adjuvant medications include membrane-stabilizing agents, steroids, and so forth. If pain
persists and does not respond to step one of the ladder, patients are continued on non-analgesics
and are started on weaker opioids plus adjuvant medications. Examples of weak to moderate
opioids are codeine and hydrocodone combinations. If pain continues to be unrelieved, stronger
opioids are then tried.
940
P i
Figure 38-2 The pain treatment continuum lists therapies by order of increasing
invasiveness and cost. Less invasive therapies should be tried before more costly or
more invasive therapies are started. This figure may suggest that therapies are tried
in series, but many of these therapies should be tried in parallel until adequate pain
control is achieved. The continuum emphasizes that spinal cord stimulation and
spinally administered opioids and nonopioid analgesics should be therapies of last
resort.
physical dependence, tolerance, and legal issues have been examined in multiple studies Several [20] [21] [22] [23] [24] [25] [26] [27] [28] [29]
studies have noted that opioid-treated patients have been able to increase their activities of daily living and that drug
abuse rates of 10% or less have been noted. Of course, there are practitioners who feel that discontinuation
[30] [31] [32] [33] [34]
of opioids is still the treatment of choice, especially for headache patients. In 1995, an American
[35] [36] [37] [38] [39] [40] [41] [42]
Pain Society (APS) survey of practitioners who dealt significantly with chronic pain patients reflected respondents'
willingness to use chronic opioids in well-selected patients. Specific guidelines and recommendations have been
[43]
formulated to aid practitioners in the safe use of opioids in patients with nonmalignant pain. The systemic [44] [45]
administration of opioids has a place in the treatment of chronic, intractable, unrelieved pain; so also does the spinal
administration of opioids. It is the purpose of this chapter to discuss appropriate indications for the use of intraspinal
analgesics and alternatives for their delivery, as well as general guidelines for the appropriate use of these agents.
History of Intraspinal Opioids
The discovery of opioid receptors and endogenous opioid compounds in the spinal cord provided a rationale [46] [47] [48]
for early attempts to deliver opioid drugs intraspinally, first in experimental animals and then in patients with [49] [50]
chronic pain. This experience with selective spinal analgesia appeared to offer specific benefits to some
[51] [52] [53]
patients and was followed by trials of continuous subarachnoid opioid infusions using implanted pumps with factory
preset flow rates. This documented efficacy of these techniques, however, is directly related to specific opioid-
[54] [55]
responsive or opioid-resistant pain syndromes. Nociceptive pain does respond to opioid therapy, because
[56] [57] [58]
noxious information transduced to electrical information and transmitted to the spinal cord is modulated
presynaptically and postsynaptically at the dorsal horn by endogenous and exogenous opioids acting at opiate
receptors. This pain is responsive to opioid therapies, whether delivered orally, parenterally, or—for the purposes of
this chapter—intraspinally. Neuropathic pain, on the other hand, is not mediated by nociceptors in the periphery but
is caused by damage to the peripheral or central nervous system or by pathologic changes in neurofunctional
relationships within these pain-processing systems. Neuropathic pain is thought to be opioid-resistant, and, unlike
nociceptive pain, may respond to higher than normal opioid doses, or may not respond to opioid therapy at all.
Although some chronic neuropathic pain syndromes may be resistant to intraspinal opioid infusion, these syndromes
may respond to other intraspinal agents such as the α2 agonists, somatostatin and its analogues, N-methyl-D-aspartate
receptor antagonists, neuron-specific Ca++ channel blocking agents, midazolam, and local anesthetic and opioid
combinations, which are discussed later. Most of these agents except clonidine, which is approved by the United
States Food and Drug Administration (FDA) for epidural use, are currently experimental and are available for
widespread clinical use.
Intraspinal Opioids
SELECTION CRITERIA FOR PAIN OF THE TERMINALLY ILL
Untreated cancer pain, even in the United States, remains an enormous problem. It has been estimated that 70% of
all patients dying of cancer experience pain in the terminal phases of their disease. In the United States, in 1995, it
[59]
was estimated that 547,000 patients died of cancer. If the 70% estimate is correct, 382,000 of these 547,000 patients
in the United States suffered intractable pain at the time of their deaths. Although there was less than a 50%
response rate to the WHO survey regarding their opioid “ladder” guidelines, if these data are correct, [60] [61] [62]
approximately 190,000 of the 382,000 patients who experienced severe pain with their disease would have had their
pain well controlled if their caregivers had used the simple guidelines of the analgesic ladder of the WHO. On the
other hand, more than 190,000 patients would not have had their pain controlled using these same guidelines. These
statistics indicate that if the WHO guidelines for the treatment of cancer pain are all that can be offered to patients
941
P i
suffering from cancer pain, a very significant proportion of patients in the United States will die without relief from
their intractable pain. Clearly, there
Figure 38-3 The World Health Organization (WHO) “ladder” is based on pharmacologic
tailoring to the needs of the patient. If pain persists and does not respond to step one of the
ladder, patients are continued on nonanalgesics and are started on weaker opioids plus
adjuvant medications. If pain still persists, the patient is given strong opioids. Many
physicians, recognizing the failure of the WHO guidelines to effectively treat all patients
with cancer pain, have incorporated a fourth rung of the WHO ladder for those patients
who fail the opioid tailoring approach of the first three rungs. This fourth rung of the ladder
incorporates interventional strategies as stated earlier in this chapter and includes
anesthetic blocking techniques, continuous spinal analgesia, neurodestructive techniques,
and implantable technologies.
must be a place for therapies that are not offered by the WHO guidelines. Many physicians, recognizing the failure
of the WHO guidelines to effectively treat all patients with cancer pain, have incorporated a “fourth rung of the
WHO ladder” for patients who fail to respond to the opioid tailoring approach of the first three rungs of the ladder
( Fig. 38–3 ).
It is imperative that physicians do not abandon their patients by walking away from them or by resorting to
“terminal sedation” because the patients' pain cannot be controlled by opioid tailoring. Physicians must choose
therapies that work and must abandon not their patients but rather the therapies that do not work. Therapies that have
proved to be efficacious but that are not included in the WHO guidelines include nonmedical interventions such as
relaxation, meditation, massage, touching, distraction, and prayer. More invasive non-WHO approaches include
simple nerve blocking techniques, central spinal canal infusions of opioids, local anesthetics and α2 agonists,
peripheral neural infusions, sympathetic nervous system blocks, neuromodulatory techniques, and various somatic
and sympathetic chemical, surgical, and thermal neurodestructive procedures.
Selection criteria for the use of intraspinal opioid therapy in patients with cancer or pain related to acquired
immunodeficiency syndrome are relatively straightforward. For cancer patients who do not benefit from systemic
delivery of opioids because of either dose-limiting toxic and intractable side effects or because they have developed
opioid nonresponsive pain syndromes, a trial of intraspinal opioids is indicated, alone or in combination with
nonopioids, such as local anesthetics or the α2 agonist clonidine.
All cancer and noncancer pain patients should have the benefit of sequential oral or transdermally administered
opioids before intraspinal opioid and nonopioid delivery are attempted. At present in the United States, the choices
for long-acting opioids include, in ascending order of cost, methadone, levorphanol, long-acting morphine
preparations, long-acting oxycodone preparations, and transdermal fentanyl. Most physicians agree that for constant
pain, long-acting opioids are preferable to use on an around-the-clock basis rather than short-acting opioids on an as-
needed basis. There should be medication allowances for pain that breaks through the baseline level of long-acting
medication. If patients find that their pain breaks through the baseline blood level of long-acting opioid more often
[63]
than not, the dose or amount of long-acting opioid is adjusted upward to provide more steady relief with less
breakthrough pain. Physicians who treat cancer pain patients should know the appropriate dose equivalents of all of
these medications and how to use them appropriately. In a later chapter, there is a discussion about parenteral
administration of opioids via the intravenous or subcutaneous route. After 3 months of therapy, either of these
methods is more costly than the intervention of intraspinal delivery of opioids and neither of these approaches is
recommended as an alternative to intraspinal opioid delivery. [64] [65]
Because these therapies are costly, some authors also recommend that intraspinal, implantable opioid and nonopioid
therapies be reserved for patients who have at least 3 months to live. Patients who do not have at least 3 months to
live, who do not tolerate systemic delivery of opioids, and who are candidates for a trial of intraspinal delivery of
opioids should be provided external delivery of spinal analgesics via an externalized catheter and external pump
delivery system. [66]
Patients who do not respond to opioids delivered parenterally and orally at high doses probably will not respond to
the intraspinal delivery of opioids alone. These patients probably have developed opioid nonresponsive pain
942
P i
syndromes, severe opioid tolerance, and should be candidates for either epidural conductance blockade or intrathecal
delivery of opioid and nonopioid combinations as discussed later in this chapter.
SELECTION CRITERIA FOR NONMALIGNANT PAIN SYNDROMES
The selection criteria for patients with nonmalignant pain is not so straightforward as with patients suffering pain
from malignant disease. Because of the controversy surrounding the use of systemically administered opioids for the
treatment of nonmalignant pain, the use of intraspinal agents for nonmalignant pain is also controversial. As stated
earlier, there is known efficacy in the use of intraspinal agents for patients with cancer pain; there is also much
support in the literature for the efficacy of intrasinal agents in patients with chronic nonmalignant pain.
[74] [75] [76]
[67] [68] [69] [70] [71] [72] [73]
Controversy notwithstanding, the selection criteria regarding intraspinal opioid use for patients with nonmalignant
pain are similar to those criteria for patients with pain of malignant origin. The glaring difference is that patients
with nonmalignant pain are not facing end of life because of their disease and may have long lives ahead of them.
With the nonmalignant pain population, the rule of “3 months to the end of life” does not exist.
Before undergoing a trial for intraspinal opioid and nonopioid delivery, all noncancer pain patients should have the
benefit of sequential oral or transdermally administered opioids, including all of the aforementioned long-acting
opioids such as methadone, levorphanol, long-acting morphine preparations, long-acting oxycodone preparations,
and transdermal fentanyl. These agents should be tried in sequence and abandoned only if undue side effects
develop. Each agent, in sequence, should be started at a low dose and titrated upward to the level of efficacy or until
side effects occur. If side effects precede analgesic effect, the drug should be abandoned and another agent tried in
this manner until all agents have been tried. Physicians treating patients with nonmalignant pain, such as patients
with cancer pain, learn the appropriate dose equivalents of all of these medications and how to use them
appropriately. If patients do not tolerate these systemically administered agents, they should become candidates for a
trial of intraspinal delivery of agents. If patients have opioid nonresponsive pain syndromes and do not respond to
the systemic delivery of the aforementioned agents, they probably will not respond to the intraspinal delivery of
opioids alone. The physician should contemplate the patient's need for intraspinal delivery of opioids and
nonopioids alike.
TRIAL OF INTRASPINAL ANALGESICS
Once it has been established that a patient who has undergone a sequential trial of systemically administered opioids
has failed to respond because of either the development of toxic side effects with every agent tried or because of
opioid-nonresponsive pain within nontoxic levels of the opioid tried, the patient should be a candidate for a trial of
intraspinal analgesia. We prefer to use the term intraspinal analgesia rather than intraspinal opioid because we can
use nonopioid agents intraspinally with success in patients who have opioid-nonresponsive pain. Agents that have
been shown to be efficacious for nonopioid-responsive pain and which are being used clinically include the local
anesthetic bupivacaine and the α2 agonist clonidine. Other agents that might be used but are considered experimental
include somatostatin or the somatostatin analogue octreotide, SNX-111, an N-channel calcium blocker, and
[77] [78] [79]
midazolam. [80] [81]
Before any patient becomes a candidate for intraspinal delivery of analgesics, more conservative therapies should be
tried and subsequently eliminated if they fail to produce adequate analgesia; likewise, there should be no
contraindications to implanting a drug delivery system and intrathecal catheter. Such contraindications include
allergy or intolerance to the trial agents, localized infection in the areas where surgery is contemplated, generalized
sepsis, and coagulopathy. The contraindications must be considered relative to the cancer patient who is dying with
poor pain control and absolute in patients with nonmalignant pain. Confronted with these contraindications in the
dying patient in pain, the physician must weigh the possible risks of the procedure with the benefits and discuss
these risks and benefits with patient and family so that they can participate in the decision.
It cannot be stressed too strongly that if one is going to use intraspinal opioids alone, it is necessary to establish
opioid responsiveness in the patient or to have a trial of nonopioids for the patient's opioid-nonresponsive pain.
There is no demonstrated magic in the intraspinal delivery of opioids. If patients do not respond to oral or systemic
opioids, the use of intrathecal opioids is not going to provide “magical” analgesia and, if it does during the trial,
experience shows that this efficacy is short-lived and probably due to the nonspecific (placebo) effects of the drug
that is trialed.
In cancer patients who have peripheral neuropathic pain syndromes, such as brachial or lumbosacral plexopathies,
and who do not respond to opioids, we recommend the external delivery of epidural analgesia with opioids with or
943
P i
without bupivacaine or clonidine. Epidural analgesia provides the sodium channel blockade of the peripheral and
central nerves that is necessary to achieve pain control. The addition of the opioid and/or clonidine provides
synergistic pain mechanistic relief that allows reduction in doses of all of the agents used. We do not recommend
[82]
the use of epidural analgesia beyond 2 to 3 months in patients with nonmalignant pain syndromes.
Any trial should, intuitively, rule in both analgesic and functional efficacy, rule out toxicity of the agent trialed, and
militate against the nonspecific or placebo effects of the drug. Trials for intraspinal opioids and nonopioids alike
have been performed by (1) single-shot epidural or intrathecal placement of the drug or drugs intended, (2) repeat
single-shot epidural or intrathecal placement of the drug or drugs intended, and (3) by continuous drug delivery via
the epidural or intrathecal route using an external pump.
Because any analgesic intervention, and especially a last-resort intervention such as intraspinal analgesia, carries
with it very strong placebo responses in both noncancer and cancer patients suffering from intractable pain, trials for
efficacy must also work against these strong responses. The only way to militate against a placebo response in any
one patient is to extend the trial as long as logistically possible. Giving a patient a singly blinded or even a doubly
blinded placebo and then deciding whether that patient is or is not a “placebo responder” makes no scientific sense
at all. To withhold therapy from a placebo responder because that patient responded to the inactive placebo or to
implant an expensive drug delivery system in a patient who responded positively to a single-shot active agent is
unacceptable. Because every individual responds both to the specific effects and the nonspecific effects (placebo
responses) of the agent given, one cannot tell from any one patient's response to a single encounter of a single agent
whether the resultant effect is specific or nonspecific. In effect, everyone is a placebo responder. Cancer patients
suffering unremitting pain who are given the chance for last-resort therapies are a population with very strong
placebo responses. A placebo response during the trial is heralded by a decreasing analgesic response over time
when pain was well controlled at the start of the trial. The only way to work against the placebo response is to
design a trial that mimics, as closely as possible, the final intended delivery system and deliver the intended agent as
long as logistically possible.
Over the years, we have come to realize that a continuous intrathecal trial, extended as long as logistically possible,
is the one trial that allows both sequential trialing of intrathecal agents and extended trials to work against potent
placebo responses. Although our trials are not perfect, because placebo responses can last longer than 12 months,
they are usually performed on an outpatient basis. In the past, we used a temporary 24-gauge (G) pediatric epidural
catheter placed intrathecally via a 20-G Tuohy needle under fluoroscopic guidance for our trials. Today, we implant
our permanent intrathecal catheters surgically for a trial. The catheter, anchored to the supraspinous or perispinous
fascia, is connected to a temporary catheter, which is tunneled away from the incision and externalized. The trial is
performed via an external pump. All of our patients are given intravenous preoperative antibiotics to prevent what
statistically could be a staphylococcal or epidermal infection. Patients are sent home with oral antibiotics to guard
against these same bacteria for the length of the trial. A 0.22-µ, antibacterial filter is placed in the line to prevent
contamination.
Enough medication is prepared for a 1- to 2-week trial. During the trial, if the patient tolerates the drug that is being
delivered but analgesia is not achieved, dosing changes are made by reprogramming the pump to accelerate the rate
of delivery. If the patient does not tolerate the drug that is being delivered, only the drug reservoir and tubing are
changed proximal to the 0.22-µ filter, which is outside of the clear dressing. Only then is the tubing changed during
the trial. Because it has become evident that the rate of infected systems is directly related to the number of times
that the system is “fiddled with,” our protocol calls for a “hands-off” policy regarding tubing, drug, and dressing
changes. The only time that the dressing is changed is within the first 48 hours, and all dressing changes are
[54]
performed by physicians who implant the catheters or nurses who are very familiar with the system.
During the trial of the agent intended, a 50% reduction in pain intensity, improvement in function, and concomitant
significant reduction in oral or systemic analgesics are usually indicative of analgesic effectiveness. One would like
to see improvement in physical functioning in patients when opioids are prescribed; however, in cancer patients, the
disease itself and not the pain may be contributing to a decrease in function. Pain control may not, in this population,
herald an improvement in function. An improvement in the quality of life may be all that can be expected in this
population. The final evaluation of efficacy in a trial of intraspinal opioids must be individualized, weighed carefully
against the risks of the procedure or changes to the lifestyle of the patient and the burden of care on the family.
Patient and family input is essential to deciding whether a trial of intraspinal analgesics is positive or not.
During the trial, because the equianalgesic dose of spinally administered opioid is significantly less than the
systemic dose, it is important to prevent acute withdrawal when the intraspinal opioid is given. To prevent acute
withdrawal from systemic administration of opioids during the trial for intraspinal opioid delivery in patients who
are opioid tolerant, we suggest that 50% of the orally administered opioid dose be given as an intrathecal equivalent
944
P i
during the first day of the trial and that the patient be allowed to take the remaining 50% of the dose orally. On each
subsequent day, the oral dose should be decreased by 20% and the intrathecal dose increased by 20%.
INTRATHECAL PUMP DELIVERY SYSTEMS
As stated earlier in this chapter, intraspinal drugs can be delivered externally through externalized epidural or
intrathecal catheters or delivered internally through implanted pump systems. Because external delivery systems are
discussed in another chapter, our discussion in this chapter is focused on implanted drug delivery systems.
The first drug delivery system approved for the delivery of intraspinal analgesics was the Infusaid model 400 pump,
which is no longer in production. The Infusaid was a factory preset flow-rate pump that delivered drug by using
vapor pressure against an expandable metal bellows, which in turn extruded drug through a rate-reducing valve to an
external nipple. Vapor pressure was provided by liquid Freon, which at ambient temperature remained liquefied, but
when implanted into the body vaporized to a pressure of approximately 400 psi.
Today, there are other factory preset, rate-specific pumps approved by the FDA, including the Arrow model 400
pump ( Fig. 38–4 ) and Medtronic's Isomed pump ( Fig. 38–5 ). The Arrow pump, like the Infusaid, relies on the use
of Freon and a metal bellows. Medtronic's Isomed pump relies on Freon gas and a metal bellows for delivery of drug.
Other pumps exist outside of the United States and include the Esox, Archimedes, Micromedes, and Anschutz, all of
which are fixed-rate pumps. Because the rate is preset and nonprogrammable, dosing changes are made by changing
the concentrations of the drug.
Medtronic's Synchromed system is the only totally programmable pump approved in the United States and Europe.
This pump relies on a dual system for drug delivery. Like the rate-specific pumps, this pump has a vapor
pressure/bellows “assist” system that extrudes drug to a rotary pumping system, which is battery controlled and
externally programmable. Rate and, therefore, dose of drug are externally programmable ( Fig. 38–6 ). Besides
increasing or decreasing the
Figure 38-4 A, The Arrow 3000 (Walpole,

Massachusetts) totally implanted fixed rate drug
delivery system. B, Cross-section of the Arrow 3000
fixed-rate pump. This drug delivery system is driven
by a propellant that exerts a vapor pressure at body
temperature on a movable metal bellows, which
extrudes drug from the drug reservoir through a filter,
a rate-limiting flow restrictor, and, finally, an outlet
catheter. Unique to this factory-rated preset pump is its
side port system.
945
P i
Figure 38-5 The IsoMed totally implanted, fixed-rate drug delivery

system (Medtronic Inc., Minneapolis, Minnesota). This pump, like the
Arrow pump, is also driven by a propellant exerting vapor pressure on a
metal bellows. Drug is extruded via a flow restrictor to an external
catheter. This pump system has a separate side port away from the
reservoir port.
continuous rate of delivery of drug, the Synchromed system can be programmed to deliver a single bolus of drug,
time-specific boluses of drug, or a complex continuous delivery of drug to meet the time-specific needs of the
patient during the day.
All available implantable pumps come with a drug reservoir access port and a side port system to allow direct
injection of drug or other agents into the implanted catheter system, which, for the most part, directly delivers drug
or agent into the intrathecal space. Reservoir volumes are different for different pumps. The Synchromed pump
volume is 20 mL, but the company (Medtronic, Minneapolis, MN) suggests that the pump be filled only to a
maximum of 18 mL to prevent overpressurization. Other pumps have differing volumes and can be ordered
according to the clinical needs of the patient. Medtronic's Isomed Pump is available in a variety of reservoir volumes
including 20 mL, 35 mL, and 60 mL, whereas the Arrow model has fixed-rate pumps with reservoir volumes of 16
mL, 30 mL, and 50 mL. Selection of the reservoir volume depends on the needs of the patient.
Most pumps have their side port systems attached to the side of the pump; however, the Arrow model has a unique
system allowing “side port” injection of the catheter system. A special needle, when inserted correctly into the
reservoir chamber, allows only side port injection and not refilling of the reservoir ( Fig. 38–7 ).
Drug Delivery System Implant Procedure
For the purposes of this chapter, the procedure for placement of both permanent catheter and pump during the same
operation are described. However, in our practice today, we implant the permanent catheter for the trial, and if the
implementation is successful, we discard the portion of the catheter trial system that is externalized and tunnel the
permanent catheter to the implanted pump. It is our practice to perform this procedure under general anesthesia,
although others prefer to use local or even spinal anesthesia. After induction of anesthesia, with the patient in the
lateral decubitus position, and after the patient is prepared and draped, an incision is made approximately 1 inch
(2.54 cm) caudal to the target spinal interspace for placement of a Tuohy needle into the intrathecal space. This
target for intrathecal entry should be at L2 and below, because entering the L1 interspace above with a Tuohy needle
places the patient at risk for perforation of the conus medullaris and the spinal cord. Once the
946
P i
Figure 38-6 The Synchromed totally implanted and

programmable drug delivery system (Medtronic, Inc.,
Minneapolis, Minnesota). This drug delivery system relies on a
rotary motor that is externally programmable. Rates of drug
delivery are externally controlled through the pictured
Synchromed programmer. The Synchromed system allows for
precision-controlled continuous delivery of drug, bolus
injections of drug, timed bolus injections of drug, and a complex
delivery of drug that combines continuous infusion with timed
specific bolus injections of drug. The Synchromed System is
battery driven. Battery life is governed by rates of use and may
last from 2 to 6 years.
Figure 38-7 The Arrow 3000 unique center side port system (Arrow International, Walpole, Massachusetts). This system utilizes a special closed
ended needle which is inserted into the center fill port. The closed end of the needle forces drug out a side hole in the needle that forces drug out
the external catheter. The pressure opens a bolus safety valve, which is normally closed.
Tuohy needle enters the appropriate intrathecal space and cerebrospinal fluid (CSF) flow is ascertained, the catheter
is advanced rostrally under fluoroscopic guidance until the tip of the catheter is as close as possible to the spinal
cord level that is processing the patient's pain. The catheter, once placed and anchored to the supraspinous fascia, is
then tunneled subcutaneously and connected to a subcutaneously placed totally implanted drug delivery system.
It is our practice to always perform this operation under fluoroscopic guidance. Placing a catheter anywhere in the
thecal sac suffices if one is to rely solely on hydrophilic opioid agents such as morphine, hydromorphone, or a
combination of these two drugs. Continuous infusion of these hydrophilic opioids is followed by the general mixing
of these agents throughout the CSF. Over time, these agents, if placed anywhere into the CSF, “bubble up” through
bulk flow, to higher spinal segments and supraspinal centers. If, at some later time, because of either poor analgesia
or side effects from the hydrophilic drug, it may be necessary to use lipophilic agents such as meperidine, fentanyl,
sufentanil, methadone, or even bupivacaine or clonidine. To facilitate appropriate spread of these lipophilic agents,
it is important to place the catheter tip as close as possible to the spinal segment mediating the patient's pain. An
947
P i
ounce of prevention is worth a pound of cure. These lipophilic agents diffuse directly into the lipid substance of the
spinal cord around the tip of the intraspinal catheter and usually do not bubble up in the cerebral spinal fluid to
higher spinal segments or supraspinal centers.
After antibiotic prophylaxis and induction of anesthesia, the patient is positioned in the left lateral decubitus position
if the operative surgeon is right-handed or vice versa. This patient positioning facilitates the surgeon's placement of
the Tuohy needle from the caudal-to-rostral plane. The intraoperative fluoroscopic unit (C-arm) is then placed cross-
table from the position of the surgeon. In our practice, before the patient is prepared and draped the vertebral
midline between T12 and L4 is identified with the C-arm positioned in the anteroposterior direction and so marked
on the back of the patient with an indelible marking pen. The patient is then prepared and draped in the customary
surgical manner.
As previously stated, the first task in this operation is to place a catheter into the intrathecal space via a 15-G Tuohy
epidural needle. It is the standard procedure of some surgeons to place the intrathecal needle through the skin with
fluoroscopic guidance before making an incision. Once the catheter is advanced to the spinal target, as determined
by the dermatome of origin of the patient's pain, an incision is made around the needle and carried down to the
supraspinous fascial plane. It is our practice, however, to make an incision from the skin to the supraspinous fascia
before placing the Tuohy needle, which is then advanced through the most cephalad apex of the incision. As stated
earlier, our location for this skin incision is between L3 and L4. The incision is then carried down through the
subcutaneous tissues to the supraspinous fascia.
Meticulous hemostasis throughout the procedure is provided by electrocautery, and the wound is copiously irrigated
with an antibiotic solution before the intraspinal Tuohy needle is placed into the wound. The appropriate length of
the incision depends on the amount of subcutaneous fat tissue and may vary from patient to patient. A small 1- to
1.5-in (2.54- to 3.81-cm) incision usually suffices in patients who are extremely thin. A larger incision may be
required for patients who are obese. Before the needle is placed, a combination of sharp and blunt dissection is used
to create a small subcutaneous “shelf” at the base of the wound, at the level of the supraspinous fascia. This shelf,
underlying the subcutaneous tissues at the base of the wound, permits excess intraspinal catheter, exiting the fascia,
to have a gentle curve and sweep for connection to the “pump” catheter. Likewise, it is important that the needle
enter the supraspinous fascia at the most rostral apex of the incision and not at the midportion or caudal end. This
maneuver also ensures that the intraspinal catheter, on exiting the supraspinous fascia, has sufficient room caudally
for a gentle and not too abrupt sweep for connection to the pump catheter. If these two maneuvers are not performed
carefully, kinking of the catheter system may occur.
To facilitate safe, easy, and relatively obstruction-free catheter placement, we recommend a shallow, angled
paramedian placement of the Tuohy needle below the spinal level of L2. This maneuver allows easy rostral
advancement of the intraspinal catheter into the intrathecal space. The more shallow and less acute the placement of
the needle, the easier it is to advance the catheter centrally and rostrally. We use a shallow, greater than 45 degree
angle and usually insert the needle tip into the supraspinous fascia from a paramedian approach at L3 or L3 to L4,
with the needle tip finally entering the thecal sac at or below the L2 interspace.
After the catheter is placed and the Tuohy needle is removed, the catheter is attached to the supraspinous fascia by
one of several types of Silastic anchors provided by the manufacturer. These anchors are placed around and over the
catheter and sutured to the supraspinous fascia with interrupted 2–0 or 3–0 silk sutures. Caution must be taken when
anchoring the catheter so as not to damage it at any time with the sharp needle or occlude it by cinching the sutures
too tight around it. Before proceeding with the next step in this operation, the exiting spinal catheter tip end should
be gently clamped and secured to the drapes to prevent excessive loss of CSF, inadvertent dislodgment of the
catheter, or both.
Before creating an incision for placement of the implanted drug infusion device, the pump must be prepared and
primed for placement according to the manufacturer's specifications and instructions. If a programmable Medtronic
Synchromed pump is to be implanted, the implant coordinator, with or without the aid of a nurse technician, must
“read” the pump telemetrically before removing it from its packaging, to ensure that the pump calibration constant is
consistent with what is written on the package. This calibration consistency is necessary to ensure that correct
dosing is achieved when the pump is programmed. This step is not necessary with nonprogrammable, rate-specific
pumps. The internal sterile packaging containing the pump is then handed off to the scrub nurse and the pump is
removed from its packaging. The Silastic covering over the nipple outlet should be removed to allow free flow of
the purged contents of the pump and a Dacron pouch, if applicable, is placed over the pump. The Dacron pouch
facilitates capsule formation around the pump after implantation. Programmable pumps, according to implanter
choice, are designed to purge either before the sterile water that is placed in all Medtronic Synchromed pumps is
removed or after the water has been removed and the analgesic drug has been placed in the reservoir of the pump.
948
P i
Nonprogrammable, rate-specific pumps also have water placed in them by the manufacturer; this water also must be
removed and replaced with drug before implantation.
Some models are provided with suture loops to stabilize the pump and prevent movement within the pump pocket.
Pumps with suture loops do not need to be placed into a Dacron pouch.
All pumps, whether programmable or nonprogrammable, should be placed into a warmer at least 30 minutes before
surgery and into a basin containing warm water during surgery. Using a 22-G Huber-type needle and the syringe
provided in the manufacturer's implant kit, the reservoir is emptied of water and filled with the suggested volume of
opioid and analgesic solution to be infused. In the case of a Medtronic programmable pump, the suggested amount is
10 mL. Although the Synchromed pump reservoir holds 18 mL, it is the manufacturer's recommendation that the
first refill not exceed 10 mL.
After the intrathecal catheter has been placed and anchored and the pump prepared and filled, an incision is begun
for the pump pocket. This incision is made in the right lower quadrant of the abdomen, at or about the umbilical
level if the operating surgeon is right-handed, or in the left lower quadrant of the abdomen if the surgeon is left-
handed. If the patient is thin, this incision is carried down to the rectus fascia for a pocket formation above the fascia.
Because of refilling and programming requirements, if the patient is obese, the incision should not be carried down
to the fascia, but should only be carried down to the mid-fat plane of the lower quadrant of the abdomen. Before
making the incision, the surgeon should always be cognizant of the aesthetic wishes of the patient; if possible, the
operation should be designed according to these wishes. The pump must not be placed too close to the iliac crest or
the inferior rib cage because this may result in undue discomfiture. After the incision is carried down to either the
rectus fascia or the mid-fat plane, a pocket just large enough to accommodate the pump is created by a combination
of sharp and blunt dissection from the incision in a caudal direction. A 1 to 2 cm portion of this pocket should be
created rostral to the incision, allowing for ease of pump placement and postimplant pump refilling.
Once the pump pocket is created, either a one-piece catheter is tunneled from the back incision to the pump pocket
or the pump segment of a two-piece catheter system is tunneled from the pump pocket to the back incision. Care
must always be taken that the tunneling device remains subcutaneous and is not forcefully pushed through muscle
and the abdominal wall into the peritoneal cavity or under the ribs, through the diaphragm, and into the intrapleural
space. Gentle subcutaneous guidance of the tunneling device with gentle pressure applied to the skin overlying the
device usually ensures safe tunneling. Before the final connections are made, any excess spinal or pump catheter is
cut and discarded.
At all points in this operation, it is essential to ascertain that there is free flow of CSF exiting the catheter system. If
a two-piece catheter system is used, it must be ascertained that CSF flow is unimpeded after the two catheters are
joined and before the spinal catheter is connected to the pump. Likewise, if a single catheter system is used, after
tunneling and before the catheter is connected to the pump, the free flow of CSF must be identified. If there is not a
free flow of CSF, there may be some obstruction to flow. This point of obstruction must be identified, localized, and
repaired before all incisions are closed.
After the catheter system and the pump are connected, the pump is carefully placed into the pump pocket. Any
redundant catheter material is placed behind the pump, safely away from any needle puncture damage that could
occur as a result of future refilling procedures. The back wound and the pump pocket wound are once again
copiously irrigated with antibiotic solution and closed in a two-layer procedure according to the preference of the
surgeon.
Pharmacologic Agents Used for Intrathecal Therapy
MORPHINE
Morphine remains the gold standard of spinally administered opioid therapy, because of its long duration of action
and relative ease of use. Morphine has an extensive history; more is known in the literature about the use of
intraspinal morphine than about any other available opioid. In the United States, only morphine has been approved
for clinical intraspinal analgesia. However, based on the literature and sound clinical judgment, other opioids are
used intraspinally when patients do not tolerate intrathecal morphine administration. These agents include
hydromorphone, meperidine, methadone, fentanyl, and sufentanil. Although physicians can use these drugs
intraspinally, they are not labeled and have not been approved by the FDA for intraspinal administration.
Time to onset of action of opioid given spinally, as well as duration of action, uptake and distribution, availability to
supraspinal centers, and central nervous system side effects are all governed by the opiate's lipid solubility and
949
P i
opiate receptor affinity. Opioids such as morphine, with low lipid solubility, enhanced hydrophilicity, and high
[83]
receptor affinity, cross the dura and enter the lipid substance of the spinal cord slowly, but they remain bound for
prolonged periods of time. Hence, the onset of analgesic action for hydrophilic opioids is slow, but analgesia is
generally prolonged. Because of this hydrophilicity, more drug remains in the CSF. Therefore, it is available to
ascend to supraspinal centers through bulk flow of CSF. Because of the hydrophilic property of drugs such as
morphine, placement of a catheter for intrathecal infusion of the drug anywhere in the thecal sac ensures analgesia
anywhere in the body. Risks of CSF side effects such as sedation, nausea and vomiting, and respiratory depression
are greater with this hydrophilic group of opioids than with drugs with higher lipid solubility and higher receptor
affinity, such as methadone, fentanyl, and sufentanil.
As expected from their physical-chemical properties, lipophilic drugs, such as fentanyl, methadone, and sufentanil,
have rapid onset of action and prolonged duration of action. Once receptors are saturated with these drugs, the drugs
become available for redistribution through spinal vessel uptake and CSF bulk flow. Oversedation then can become
a problem. Because lipophilic agents enter the substance of the lipid-containing spinal cord rapidly and are quickly
eliminated from the CSF, catheter tip placement close to the area of the spinal cord that processes the patient's pain
is essential for optimal analgesia.
The appropriate dose of opioid for epidural or intrathecal use is highly individualized and depends on the patient's
age and pain syndrome as well as the systemic dose of the drug needed for analgesia before the decision is made to
move to intraspinal delivery. As a general rule, patients with neuropathic pain may require higher doses than are
normally used for nociceptive pain. The elderly usually require smaller doses of a drug than younger patients do.
However, the dosing in all patients should be individualized. For clinical purposes, we use the following formula
when converting systemic morphine to spinal morphine:
300 mg oral morphine =
100 mg parenteral morphine =
10 mg epidural morphine =
1 mg intrathecal morphine.
Some patients do not tolerate morphine but tolerate other hydrophilic, more lipophilic agents such as
hydromorphone. Sometimes, we may choose a more lipophilic agent to decrease supraspinal effects such as severe
nausea. Patients may tolerate a drug well during the screening trial, but they may develop intolerance to the drug at
some time during ongoing intrathecal therapy. Other problems that may arise are tolerance of the drug being infused
or opioid-resistant pain syndromes. These problems can be categorized into side effects or decreasing analgesic
effects of the agent being infused, or a combination of side effects and decreasing analgesia. Patients may develop
the known side effects of therapy such as nausea and vomiting, urinary retention, generalized pruritus, constipation,
oversedation, or confusion, or they may develop other complications of intraspinal opioid therapy that have been
reported, such as polyarthralgia, amenorrhea, peripheral edema, and sexual dysfunction. An attempt should be
[84]
made to manage these symptoms pharmacologically before switching to some other agent. If these side effects
cannot be managed with symptom-specific pharmacologic agents, switching to another spinal opioid is suggested.
Because there is incomplete cross-tolerance of one opioid agonist to other opioid agonists, patients who have side
effects to one drug may not have the same effects with another drug at dose equivalencies.
Patients also may become tolerant over time to the agent being infused. Tolerance to one opioid analgesic, however,
does not necessarily mean tolerance to all. Again, taking advantage of incomplete cross-tolerance, analgesia can be
restored by switching to a different opioid at a lower dose (usually one half the expected equivalency).
HYDROMORPHONE
Pain clinicians are sometimes faced with a dilemma when a patient no longer tolerates intrathecal morphine.
Whether the patient has become tolerant to the morphine, is allergic, or experiences significant side effects of the
drug, an alternative drug is needed in the pump. Although it is not FDA-approved in the United States for such use,
many clinicians turn to hydromorphone. The µ agonist hydromorphone is 5 to 10 times more potent than morphine
and 8 to 10 times more lipid soluble. Because it has greater lipophilicity than morphine, one might expect a
[85] [86]
slightly quicker onset of action, shorter duration of action, and more segmental spread. Also, because of slightly less
rostral CSF spread, less narcotic may be expected to reach the vomiting center in the brain, the area postrema, or the
chemoreceptor trigger zone. When converting from intrathecal morphine to hydromorphone, the initial dose is
approximately 50% of the equianalgesic dose of the new drug because of incomplete cross-tolerance. Therefore, if
950
P i
one assumes that hydromorphone is approximately five times more potent than morphine, a starting dose of a 10th
of the morphine dose should be initiated in the pump. Clinically, intrathecal hydromorphone is well tolerated. When
necessary it certainly is a good alternative to morphine for intraspinal infusion.
MEPERIDINE
Meperidine is a phenylpiperidine derivative with physical characteristics, molecular weight, and pk similar to those
of local anesthetics. It is the only µ opioid agonist clinically available that is known to be efficacious as a sole
subarachnoid anesthetic. Surgical procedures to the lower limbs, the inguinal area, the perineum, and even cesarean
section can be performed under spinal meperidine alone. Subarachnoid administration of 0.5 mg/kg meperidine
[87] [88]
produces anesthesia with an onset of about 10 minutes, and postoperative analgesia for up to 6 hours or longer. [89] [90]
With higher doses, motor block is seen. Subarachnoid doses of 1 mg/kg or 100 mg have been associated with
respiratory depression, bradycardia, and hypotension. [91] [92]
Meperidine is more lipid soluble than morphine or hydromorphone. It has a quicker onset and more segmental
action than either morphine or hydromorphone. Delayed respiratory depression is not due to rostral CSF spread but
rather to redistribution from systemic uptake from the spinal site of administration and central redistribution of the
drug. More than 1035 patients reported in the literature have received intrathecal meperidine without any
[93]
documented neurotoxic effect. Even intrathecal meperidine given in labor has been shown to be safe and
[94]
efficacious. In fact, 10 mg of intrathecal meperidine was shown to be superior to 10 µg of fentanyl or 5 µg of

sufentanil for the relief of pain in stage 1 of labor.[95]
SUFENTANIL
Patients who are intolerant of intrathecal morphine may be more tolerant to the administration of intrathecal
sufentanil. Sufentanil is an anilinopiperidine with a 1000 times higher lipid partition coefficient than morphine. [96]
Therefore, sufentanil has a much more rapid onset of action and much shorter duration than morphine in the
intrathecal space. Because morphine is very lipid soluble, it rapidly diffuses into the central neural tissue when
administered intrathecally, leaving less bulk drug available for rostral movement and thus fewer central side effects
such as nausea, vomiting, pruritus, urinary retention, and respiratory depression. Although sufentanil is definitely
more segmental in its spread than morphine given intrathecally, the patient must be monitored for respiratory
depression because there is evidence of some rostral CNS movement. The mean residence time of sufentanil after
[97] [98]
an intrathecal bolus was 0.92 hours plus or minus 0.08 hours. The drug is cleared 2 to 10 times faster than
[84]
morphine.
Sufentanil also has a greater affinity to µ opioid receptors than morphine. This may be of potential benefit in
delaying the development of tolerance. Sosnowski and Yaksh postulated that agents with a higher efficacy and
[99]
receptor reserve (e.g., sufentanil) should produce less tolerance than agents of lower efficacy and receptor reserve
(e.g., morphine). Over time, rats developed less tolerance to intrathecal sufentanil than to morphine. Sufentanil
required the occupancy of fewer µ receptors than morphine to produce antinociception. [99]
Many studies have demonstrated the clinical usefulness of sufentanil in labor. Boluses of 10 µg of intrathecal
[100]
sufentanil produce analgesia within 5 minutes and have a duration of about 90 minutes. Doses of up to 150 µg
[101] [102]
boluses have been reported in the literature. Based on the potency ratio of sufentanil to morphine, when we
[103]
convert morphine to sufentanil in an implanted pump, we arbitrarily use a dose conversion of 1 µg of sufentanil to
1000 µg (1 mg) of morphine. For example, if one is giving 20 mg of morphine over 24 hours when using other
opioids, one can convert this dose to 20 µg of sufentanil over 24 hours. Because of a lack of cross-tolerance, one
should initially start off with half of the equivalent dose. Also, because of the lack of good scientific data regarding a
conversion for chronic pain use, we often underestimate the actual clinically applicable dose ratio of morphine to
sufentanil and therefore have to titrate upward to achieve clinical efficacy.
Intrathecal sufentanil has been shown to be safe in humans. Although the drug may have some weak local anesthetic
effects or cause degree of hypotension or respiratory depression, no neurotoxicity has been clinically reported in
[104]
humans. Rat, cat, and dog data have shown no detectable pathologic effects on spinal cord histology or behavioral
function. Rawal and colleagues demonstrated neurotoxic changes with doses (7.5 µg/kg) of sufentanil in
[105] [106] [107]
sheep who have a relatively smaller intrathecal space than other animals studied. The reports did demonstrate a low-
grade inflammatory response to the intrathecal catheter itself, which is thought to represent a response to a foreign
body. Therefore, one must always be cognizant of potential neurotoxic problems with the administration of any
intrathecal drug.
951
P i
FENTANYL
Fentanyl is an opioid analgesic that preferentially binds to µ receptors, which are found widely distributed
throughout the brain and spinal cord. Like sufentanil, it is lipophilic and has a fast onset of action, about 4 to 5
minutes with a peak effect of approximately 20 minutes when given epidurally. Its analgesic effect is mostly
[108] [109]
segmental because of its lipophilicity and easy diffusability. Fentanyl has low CSF spread and is equipotent when
given either epidurally or intravenously. Fentanyl plasma levels are the same when given either epidurally or
[110]
intravenously; thus, studies are inconclusive as to which route provides greater analgesia. Because fentanyl is
[111] [112]
75 to 100 times more potent than morphine sulphate, lower doses are needed to produce similar analgesia. Thus,
consideration must be given to side effects, with fentanyl, which has been noted to cause more severe side effects
than morphine sulphate. Cephalad spread of fentanyl, which could lead to respiratory depression, does occur, but
[113]
less than with morphine. Although it is uncertain whether fentanyl's exact location of action is systemic or spinal,
systemic modes of action appear to be favored at this time. Although scientific data on epidural and intrathecal
[114] [115]
fentanyl are still evolving, there does appear to be a role for fentanyl in treating both acute and chronic pain
processes.
MANAGEMENT OF NONOPIOID SPINAL ANALGESIA
Because many patients develop tolerance to opioid analgesics, have neuropathic pain that is less responsive to
opioids, or develop these pain syndromes during intraspinal opioid therapy, it has become very clear that intraspinal
opioid therapy alone is not sufficient to provide adequate analgesia for many patients. Therefore, scientists and
clinicians are looking for other intraspinal, pharmacologic solutions for patients with these opioid-resistant pain
syndromes.
Physicians, however, must remember that their first obligation to their patients is “to do no harm.” Spinally
administered opioid therapy certainly belongs irrevocably to our clinical armamentarium for pain control in cancer
patients and, more recently, in patients with nonmalignant pain. As stated previously, morphine in the United States
remains the only analgesic approved by the FDA for intraspinal use. The intraspinal use of other agents such as
clonidine, the α-2 adrenergic receptor drug, opiate peptides such as DADLE [D=a/a(2), D=leu(5)] enkephalin or
DPDPE, or other spinally active analgesic agents such as somatostatin or octreotide, NSAIDs, neuron specific Ca++
channel blocking agents, and NMDA receptor antagonists are all investigational and should only be used with
investigational protocols accepted by a review board. Intrathecal local anesthetics should be used chronically only
with careful informed consent of the patient after the risks and possible consequences of their use have been
explained.
OPIOID–LOCAL ANESTHETIC COMBINATIONS
Animal toxicity and human postmortem studies suggest clinical safety with the long-term, low-dose infusion of
intrathecal bupivacaine. There are, however, other reports in both animal and human clinical literature of
[116] [117]
potential neural toxicity when local anesthetic agents are used chronically. One study showed neurotoxicity after
subarachnoid infusions of bupivacaine, lidocaine, and 2-chloroprocaine in a chronic-use rat model. The neurotoxic [118]
effects, however, were related to both dose and duration; and bupivacaine appeared to have a lesser effect then either
lidocaine or tetracaine. There are also clinical reports in the anesthesia literature of permanent neurologic damage
and sequelae, specifically the cauda equina syndrome, when local anesthetics, specifically 5% lidocaine, were used
in concentrations needed for spinal anesthesia, particularly when delivered through small-bore intrathecal
catheters. It is unclear whether this significant clinical complication was related to the drug, catheter, technique, or
[119]
a combination of several of the above. One report suggests that no tachyphylaxis occurred with prolonged
continuous spinal infusions of bupivacaine. [120]
Several clinical reports show positive analgesic response with the use of local anesthetic–opioid intraspinal mixtures
for the treatment of cancer and non–cancer-related pain In our clinic, when patients no longer
[54] [121] [122] [123] [124] [125] [126]
receive analgesia in increasing doses of intraspinal opioids set at an arbitrary ceiling of 20 mg of morphine
intrathecal equivalents, we add the local anesthetic bupivacaine to the opioid as an admixture. Our starting dose of
bupivacaine is 3 mg per day, using the highest available concentration of bupivacaine to ensure relatively long refill
periods. This dose of bupivacaine is increased by 20% per week until analgesia or side effects occur.
CLONIDINE
Clonidine, an α2 adrenergic receptor agonist, used intrathecally or epidurally in animal studies and in humans has
been shown to provide potent analgesia whether used alone or in combination with intraspinal opioids. Clonidine is
not approved for clinical use in the United States and is experimental. Some authors have found that combining the
952
P i
α2 adrenergic receptor drug clonidine with a µ receptor ligand provides more profound analgesia at a dose lower than
would be expected if either drug were given alone. This phenomenon of one drug adding to the effect of
[127] [128] [129] [130]
another is called synergy.
Animal models of neuropathic pain have demonstrated antinociception with treatment by intrathecal clonidine and
other α2 agonists. Clonidine appears to block substance P release at the presynaptic receptor and blocks the firing
[131]
of the second order nociceptive neuron. Clonidine acts primarily at the spinal cord level, where norepinephrine
receptors are found, but it may also have supraspinal effects at the rostral ventral medulla, especially with oral
[132]
administration. Clonidine's ability to stimulate α2 adrenoreceptors in the brainstem to reduce sympathetic outflow
has been used for years in the treatment of hypertension.
Daily intrathecal dosages in humans have ranged from 3 µg/kg to 60 µg/kg. Filos and associates studied the [133]
analgesic effect of 150, 300, or 450 µg of clonidine given intrathecally after cesarean section to 30 women with
general anesthesia. Good analgesia was noted immediately for up to 80 minutes postoperatively. Currently, a
multicenter protocol is being conducted in the United States, using infusion rates of continuous intrathecal clonidine
between 0.7 µg/hr and 4 µg per hour via implanted infusion devices. Clonidine in 150 or 500 µg/mL in 20-mL vials
is used to fill the intrathecal pumps (unpublished data).
Studies in various animals and humans have demonstrated no neuropathology after administration of intraspinal
clonidine. The main side effect of clonidine given intrathecally is hypotension. Humans may also experience
decreases in heart rate. Electrolytes, glucose, and cortisol levels were found to be stable in humans after infusion of
clonidine. Other side effects include dry mouth, drowsiness, dizziness, and constipation. Sudden withdrawal of
[134]
clonidine can precipitate agitation and hypertension.
Clonidine may be useful in facilitating a spinal µ receptor holiday in patients who have become tolerant of high
doses of opioids. Clonidine may also be effective for treating neuropathic pain
[135]
and sympathetically mediated [136] [137]
pain syndromes. [138]
OCTREOTIDE
Somatostatin, a tetradecapeptide, has been noted to be widely distributed throughout the nervous system including
the supraspinal area, the dorsal root ganglion, and the intrinsic spinal cord interneurons. It was found to potentially
depress nociceptive responses by inhibitory mechanisms different from morphine and not to be reversed by
naloxone. Initial enthusiastic reports by Chrubasik and coworkers on the use of intrathecal, epidural, and
[139] [140]
intraventricular somatostatin were somewhat cooled by reports of neuropathology in cats and mice with intrathecal
somatostatin administration. [141]
However, Penn and colleagues found that octreotide (Sandostatin), a stable analogue of somatostatin, could be
[142] [143]
used safely in cancer patients. They infused intrathecal octreotide in six cancer patients who had opioid-
[142] [143]
responsive, nociceptive pain but who could not tolerate oral opioid medications. It is noteworthy that patients with
neuropathic pain were excluded. Octreotide, 50 µg/mL, adjusted for pH, was infused via an implanted pump
intrathecally at 2.5 µg per hour to a maximum dose of 20 µg per hour as needed. Daily incremental increases were
made as oral narcotics were reduced. Higher doses were needed as time progressed (13–91 d). These researchers
found that the patients had acceptable pain relief with a 40% reduction in oral opioid medications. None of the
patients in Penn's study experienced any side effects from octreotide; no changes were noted in electrolytes,
hematologic profiles, or glucose levels. They found that intrathecal octreotide infusions in dogs were not toxic to the
dogs' spinal cord or roots. Candrina and Galli found that 20 µg of intraventricular octreotide provided good pain
[144]
control in five patients with cervicofacial cancer. In the United States, the use of octreotide, as of DADLE and
clonidine, is not FDA-approved and is, therefore, experimental.
A disadvantage of octreotide may be its ineffectiveness in patients with neuropathic pain. However, there is the
possibility of using this drug during a narcotic holiday in a patient who is developing tolerance to intrathecal opioids.
Certainly, more studies are needed.
ZICONOTIDE
Ziconotide, a conopeptide, is a venom that is produced by an aquatic snail known as magnus. This venom has shown
selectivity at blocking neuronal N-type, voltage-gated calcium channels in the spinal cord. Ziconotide is the [145]
synthetic form of w-conopeptide. Once bound to the N-type calcium channels, calcium influx is inhibited, thus
preventing neurotransmitter release. This preferential blockade inhibits transmission of primary afferents located in
the dorsal horn of the superficial lamina. Although ziconotide has no action on opioid receptors, Brose, in his 1996
[133]
953
P i
study involving intrathecal delivery of ziconotide to patients with acquired immunodeficiency syndrome, and to
those with cancer, showed that if it is given in lower concentrations (0.2 µg/hr), pain relief can be produced with
minimal side effects. Analgesia was also produced at higher concentrations, but side effects, including vestibular
dysfunction, occurred.
Several side effects have been attributed to ziconotide and involve many organ systems. These organ systems
include the skin and the cardiovascular, endocrine, hepatic, urologic, and central nervous systems. A study by Penn
and Paice in 2000 involved the use of intrathecal ziconotide in three patients who had neuropathic and nociceptive
pain processes. The doses ranged from 0.2 µg per hour to 5.3 µg per hour. Although significant pain relief was
achieved at doses varying from high to low, side effects, including nausea, diarrhea, nystagmus, dysmetria, sedation,
confusion, and hallucinations, occurred at doses around 0.6 µg per hour but were not exclusive to this dose. With
intrathecal ziconotide, at doses of 0.9 µg per hour or greater, much more serious side effects occurred, including
disorientation, agitation, and in two thirds of patients, unresponsiveness. This unresponsiveness did resolve,
however, at some point after the intrathecal therapy was discontinued.
Significant side effects can occur with low and high doses of intrathecal ziconotide, and research is ongoing.
However, based on published literature, ziconotide appears to have promising analgesic properties in both
neuropathic and nociceptive pain processes. [146]
MANAGEMENT OF INTRASPINAL BACLOFEN FOR SPINAL SPASTICITY
Baclofen, although not an analgesic per se, has been a most remarkable active spinal agent. Because oral baclofen
does not readily cross the blood-brain barrier owing to its high molecular weight and hydrophilicity, and because
high doses are needed for clinical efficacy, its use is limited by the development of intolerable central nervous
system side effects. Administered directly to the spinal axis, intrathecal baclofen is quite effective at low doses that
do not readily produce central toxicity. Intrathecal baclofen therapy, therefore, is indicated for use in the treatment
of spasticity of spinal cord origin in patients who are either unresponsive to oral baclofen therapy or who experience
intolerable central nervous system side effects. Intrathecal baclofen (Lioresal Intrathecal) is approved for infusion by
the FDA in the United States.
Baclofen is structurally similar to gamma-aminobutyric acid (GABA) and intrathecally binds to the GABA B
receptor, which is found in the superficial layers of the dorsal gray matter. Monosynaptic and polysynaptic
[147]
transmission is inhibited and therefore muscle tone and spasms are reduced.
Multiple studies on the clinical use of baclofen followed Penn and Kroin's original work in 1984. A large,
[148] [149] [150] [151]
multicenter study was published by Coffey and colleagues, addressing the clinical use of baclofen in 93 patients.
[152]
Test injections of intrathecal baclofen, 50, 75, or 100 µg were given. If the patients showed a positive response to a
maximum of 100 µg, which was defined as a two-point reduction in the Ashworth muscle rigidity/tone scale and
muscle spasm scores for at least 4 hours without intolerable side effects, they were offered pump implantation for
continuous infusion of the baclofen. Intraoperatively, the pump was filled with baclofen, 500 or 1000 µg/mL and
programmed to deliver a total dose equal to double the effective screening dose per 24 hours. Postoperatively, oral
antispasmodic medications were gradually tapered to avoid withdrawal seizures. Patients' mean dose ranges at the
start and at the end of the study (mean, 19 mo; range, 5–41 mo) were 187 µg per day and 405 µg per day,
respectively. Patients were examined after hospitalization and original implantation at 2 weeks and every month
thereafter for a period of 1 year. After that, the patients were followed at 1- to 3- month intervals, depending on the
pump refill interval. Not only was a marked reduction in motor tone noted but other beneficial effects of intrathecal
baclofen were noted in this study and in other studies as well, including improvement in bladder and sphincter
function and decreased dysesthetic and spasm-related pain transmission. The amelioration in central pain by use
[153] [154]
of baclofen, however, has not been reproduced in other clinical series.
Although admixtures of agents are not approved by the FDA, physicians could, as stated in an earlier example, use
an admixture of baclofen for spasm resulting from spinal cord injury and an opioid such as morphine for
myelopathic pain. Baclofen and morphine have been shown to be compatible and stable at 37°C for at least 30 days
in an infusion pump. [155]
Except for a reduction in motor tone no long-term clinical neurologic effects were noted in the study by Coffey and
colleagues. Hepatic, hematologic, and electrolyte levels as measured remained stable for 1 year after implantation.
[152]
Drug tolerance was noted in 8% of these patients and was remedied with drug holidays. It is of interest that two
patients in Penn and Kroin's 1987 study received a drug overdose because of errors in programming. The patients
[148]
complained of lightheadedness and weakness in upper extremities. They then became drowsy, lost consciousness,
954
P i
and became hypnotic and unresponsive to deep pain. These patients were intubated and placed on a respirator until
they emerged from their comas and were extubated on day 3. No residual effects were noted.
Before implantation of an infusion device for intrathecal baclofen, patients with spinal cord spasticity must have
failed oral antispasmodic therapy, including a trial of oral baclofen. In oral trials, failure is defined as experience of
intolerable side effects resulting from the drug before efficacy is achieved.
Before implantation, patients must have benefited from a trial of intrathecal baclofen. An initial dose of 50 µg of
baclofen (Lioresal Intrathecal) is given by subarachnoid bolus injection and barbotage over at least 1 minute. The
expected onset of action of this intrathecal bolus is between 30 and 60 minutes. The patient is then observed for a
period of 4 to 8 hours to evaluate change in intensity and frequency of spasms and decrease, if any, in muscle tone.
If the clinical response to the first injection is less than desired, it is recommended that a second bolus and barbotage
of 75 µg be given 24 hours after the first, and, if this second injection is still inadequate, a third injection and
barbotage of 100 µg is given 24 hours after the second. If the patient does not respond to these three injections, it is
recommended that therapy be terminated.
After the initial screening for efficacy, the pump is filled with baclofen to deliver twice the amount of the efficacious
screening dose over 24 hours. If the patient develops tolerance to the drug, we recommend titration by 20%
increments until efficacy is reestablished. Invariably, tolerance to intrathecal baclofen does occur but is variable
from patient to patient. When the patient no longer receives benefit from intrathecal baclofen at high doses (> 800
µg/24 h), we recommend a drug holiday, achieved by reducing the medication gradually over a 2-week period. The
drug is restarted once drug sensitivity returns after a defined period of time.
The symptoms of central nervous system toxicity resulting from baclofen include dizziness, somnolence, rostral
spread of hypotonia, seizures, respiratory depression, and coma. Medtronic Corporation recommends the following
treatment for patients who have received an overdose of intrathecal baclofen. First, it is essential to maintain an
[156]
airway and to provide adequate ventilation of the patient. Physostigmine, a reversible anticholinesterase drug, is
given to reverse the effects of the baclofen. The recommended adult dose is 1 to 2 mg intravenously over 5 to 10
minutes. The recommended pediatric dose is 0.02 mg/kg intravenously, and no more than 0.5 mg per minute. After
reversal of the toxic effects of baclofen by physostigmine, the pump should be stopped and emptied of baclofen.
Once the patient recovers from the overdose, baclofen can be restarted.
Summary
Chronic, unrelieved pain remains a major drain on fiscal resources and has an impact on the individual, society, and
industry. Chronic pain remains the most common cause of disability and impairs the quality of life. The treatment of
chronic pain should always be multidimensional and interdisciplinary. There are several treatment options available
for the treatment of pain, ranging from supportive, noninvasive therapies to invasive therapies such as intraspinal
analgesia. Although pain may involve nociceptive and neuropathic sensations, there are several agents that may be
used to target specific pain states.
Medications such as α2 agonists, calcium channel blockers, and N-methyl-D-aspartate receptor antagonists, as well as
local anesthetics, which are nonopioid medications, have been shown to be successful in treating patients with
neuropathic pain. Opioid medications such as morphine, fentanyl, and hydromorphone have been efficacious in
treating nociceptive pain. Because several pain disorders have both nociceptive and neuropathic components, a
combination of the aforementioned medications may be used. Intraspinal analgesia successfully treats both
malignant and nonmalignant pain. Before intraspinal analgesia is considered, a concerted effort to exhaust all less
invasive therapies should be attempted. Moreover, before permanent implantation of an intrathecal pump delivery
system is performed, a 1- to 2-week trial should be undertaken. A 50% reduction in pain intensity, improvement in
function, and a reduction in oral or systemic analgesia are indicative of a successful intraspinal analgesia trial. There
are several types of intrathecal pump delivery systems, and the one selected should be tailored to the patient's needs
and specific pain complaint. It is noteworthy that intrathecally delivered medications eliminate pain, and, in the case
of baclofen, patients with spasticity usually respond well to intrathecal delivery. The utility of intraspinally
administered medications for the treatment of patients with pain and spasticity is growing; however, more study is
needed to improve efficacy and minimize side effects.
REFERENCES
1. BonicaJJ: Chronic non-cancer pain. In Anderson S, Bond M, Mehta M, Swerdlow, M (eds): The Management of Pain. Lancaster, UK, MTP
Press, 1987, p 13.
955
P i
2. Von Korff M, Dworkin SF, Le Resche L: Graded chronic pain status: An epidemiologic evaluation. Pain 279:91, 1990.
3. Von Korff M, Wagner EH, Dworkin SF, et al: Chronic pain and use of ambulatory health care. Psychosom Med 53:61, 1991.
4. Cheadle
A, Franklin G, Wolthagen C, et al: Factors influencing the duration of work-related disability: A population-based study of
Washington State Workers' Compensation. Am J Public Health 84:190, l994.
5. Frymoyer JW, Cats-Baril WL: An overview of the incidence and costs of low back pain. Orthop Clin North Am 22:263, 1991.
6. Carey TS, Evans A, Hadler M, et al: Care seeking among individuals with chronic low back pain. Spine 20:312, 1995.
7. Grazier KL: The frequency of occurrence, impact and cost of musculoskeletal conditions in the United States. Proceedings of the American
Academy of Orthopaedic Surgeons Conference, Rosemont, IL, 1984.
8. United States National Safety Council: Accident Facts. Chicago, 1993.
9. Meridian Research (US): Worker protection programs in construction (OSHA Contract J-9-F-1-0019). Silver Spring, MD, Occupational Safety
and Health Administration, 1994.
10. Spengler D, Bigos S, Martin NA, et al: Back injuries in industry: A retrospective study. I. Overview and cost analysis. Spine 11:241, 1996.
11. Hart
LG, Deyo R, Cherkin DC: Physician office visits for low back pain: Frequency, clinical evaluation and treatment patterns from a U.S.
national survey. Spine 20:11, 1995.
12. Bonica JJ: General considerations of chronic pain. In Bonica JJ (ed): The Management of Pain. Philadelphia, Lea & Febiger, 1990, pp 180–196.
13. The Michigan Pain Study: EPIC/MRA, 4710 W Saginaw Hwy, Lansing, MI 48917–2601, 1997.
14. Midence K, Fuggle P, Davies S: Psychosocial aspects of sickle cell disease in childhood and adolescence: A review. Br J Clin Psychol 32:271,
1993.
15. Aaslund A, Flato B, Vandvik IH: Psychosocial outcome in juvenile chronic arthritis: A nine-year follow-up. Clin Exp Rheumatol 15:561, 1997.
16. WalkerLS, Guite JW: Recurrent abdominal pain: A potential precursor of irritable bowel syndrome in adolescents and young adults. J Pediatr
132:1010, 1998.
17. Walker LS, Green JW: The functional disability inventory: Measuring a neglected dimension of child health status. J Pediatr Psychol 16:39,
1991.
18. World Health Organization (WHO). Cancer Pain Relief. Geneva, WHO, 1986.
19. World Health Organization (WHO). Cancer Pain Relief and Palliative Care: Report of a WHO Expert Committee. Geneva, WHO, 1990.
20. Tennant FS, Robinson D, Sagherian A, Seecoff R: Chronic opioid treatment of intractable nonmalignant pain. Pain Manage Jan/Feb:18, 1988.
21. Portenoy RL, Foley KM: Chronic use of opioid analgesics in non-malignant pain: Report of 38 cases. Pain 25:171, 1986.
22. Zenz M, Stumpf M, Tryba M: Long-term opioid therapy in patients with chronic nonmalignant pain. J Pain Symptom Manage 7:69, 1992.
23. FinlaysonRE, Maruta T, Morse BR, Martin MA: Substance dependence and chronic pain: Experience with treatment and follow-up results.
Pain 26:175, 1986.
24. Taylor CB, Zlutnick SI, Corley MJ, Flora J: The effects of detoxification, relaxation, and brief supportive therapy in chronic pain. Pain 8:319,
1980.
25. Portenoy RK: Opioid therapy for chronic non-malignant pain current status. Progress in pain research and management, vol 1. In Fields HL,
Lieberskind J (eds): Seattle, IASP Press, 1994, pp 247–287.
26. Perry S, Heidrich G: Management of pain during debridement: A survey of U.S. burn units. Pain 13:267, 1982.
27. Medina JL, Diamond S: Drug dependency in patients with chronic headache. Headache 17:12, 1977.
28. Zenz M, Strumpf M, Tryba M: Long-term opioid therapy in patients with chronic non-malignant pain. J Pain Symptom Manage 7:69, 1992.
29. Joranson DE: Intractable pain treatment laws and regulations. Am Pain Soc Bull 5:2, 1995.
30. Melzack R, Wall PD: Textbook of Pain, 4th ed. New York, Churchill Livingstone, 1999, p 1355.
31. Wilkinson HA: The Failed Back Syndrome: Etiology and Therapy, 2nd ed. Philadelphia, Harper & Row, 1991.
32. North RB: Spinal cord stimulation for axial low back pain: Single versus dual percutaneous electrodes. Lucerne, Switzerland, International
956
P i
Neuromodulation Society Abstracts 212, 1998.
33. Bagger JP, Jensen BS, Johannsen G: Long term outcome of spinal cord electric stimulation in patients with refractory chest pain. Clin Cardiol
21:286, 1998.
34. Broseta J, Barbera J, DeVera J, et al: Spinal cord stimulation in peripheral arterial disease. J Neurosurg 64:71, 1986.
35. Melzack R, Wall PD: Textbook of Pain, 4th ed. New York, Churchill Livingstone, 1999, p 1355.
36. LawJD: Spinal stimulation in the “failed back surgery syndrome”: Comparison of technical criteria for palliating pain in the leg versus in the
low back. Acta Neurochir 117:95, 1992.
37. Broseta J, Garcia-March G, Sanchez MJ, et al: Influence of spinal cord stimulation on peripheral blood flow. Appl Neurophysiol 48:367, 1985.
38. Buckley
FP, Sizemore WA, Charlton JE: Medication management in patients with chronic non-malignant pain. A review of the use of a drug
withdrawal protocol. Pain 26:153, 1986.
39. Finlayson RD, Maruta T, Morse BR: Substance dependence and chronic pain: Profile of 50 patients treated in an alcohol and drug dependence
unit. Pain 26:167, 1986.
40. Maruta T, Swanson, DW, Finlayson RE: Drug abuse and dependency in patients with chronic pain. Mayo Clin Proc 54:241, 1979.
41. McNairy SI, Maruta T, Ivnik RJ, et al: Prescription medication dependence and neuropsychological function. Pain 18:169, 1984.
42. Turner JA, Calsyn DA, Fordyce WE, Ready LB: Drug utilization pattern in chronic pain patients. Pain 12:357, 1982.
43. Long
term use of opioids in the treatment of chronic pain: Physicians' attitudes and practices. Dannemiller: Opioids for non-malignant pain.
Tempe, AZ 1/20–22 1995.
44. Portenoy RK: Chronic opioid therapy in nonmalignant pain. J Pain Symptom Manage 5(Suppl):S46, 1990.
45. Schofferman J: Long-term use of opioid analgesics for the treatment of chronic pain of nonmalignant origin. J Pain Symptom Manage 8:279,
1993.
46. Pert CB, Snyder S: Opiate receptors demonstration in nervous tissue. Science 179:1011, 1973.
47. Hughes J, Smith TW, Kosterlitz HW, et al: Isolation of two related pentapeptides from brain with potent opiate activity. Nature 258:577, 1975.
48. Terenius L, Wahlstrom A: Morphine like ligand in opiate receptors in human CSF. Life Sci 16:1759, 1975.
49. Yaksh TL, Rudy TA: Studies on the direct spinal action of narcotics in the production of analgesia in the rat. J Pharmacol Exp Ther 202:411,
1977.
50. Yaksh TL: Analgetic actions of intrathecal opiates in cat and primates. Brain Res 153:205, 1978.
51. Wang JF, Nauss LA, Thomas JE: Pain relief by intrathecally applied morphine in man. Anesthesiology 50:149, 1979.
52. Behar M, Olshwang D, Magora F, et al: Epidural morphine in treatment of pain. Lancet 1:527, 1979.
53. Cousins MJ, Mather LE, Glynn CJ, et al: Selective spinal analgesia. Lancet 1:1141, 1979.
54. Onofrio
BM, Yaksh TL, Arnold PG: Continuous low dose intrathecal morphine administration in the treatment of chronic pain of malignant
origin. Mayo Clin Proc 55:469, 1981.
55. Coombs DW, Saunders RL, Gaylor M, et al: Epidural narcotic infusion: Implantation technique and efficacy. Anesthesiology 55:469, 1981.
56. Arner S, Arner B: Differential effects of epidural morphine in the treatment of cancer related pain. Acta Anaesthesiol Scand 29:332, 1989.
57. Arner S, Meyerson B: Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain. Pain 33:11–23, 1988.
58. Vecht CJ: Nociceptive nerve pain and neuropathic pain [letter]. Pain 39:243, 1989.
59. Foley KM: The treatment of cancer pain. N Engl J Med 313:84, 1985.
60. Takeda F: Results of field testing in Japan of the WHO draft interim guidelines on relief of cancer pain. Pain Clin 1:83, 1986.
61. Schug SA, Zech D, Dorr U: Cancer pain management according to WHO guidelines. J Pain Symptom Manage 1:27, 1990.
62. Walker VA, Hoskin PJ, Hanks GW, White ID: Evaluation of WHO analgesic guidelines for cancer pain in a hospital-based palliative care unit.
J Pain Symptom Manage 3:145, 1988.
63. Jacox A, Carr DB, Payne R, et al: Management of cancer pain. Clinical Practice Guideline No. 9. Publication no. 94-0592. Rockville, MD,
957
P i
Agency for Health Care Policy and Research, US Department of Health and Human Services, Public Health Service, 1994.
64. Lanning RM, Hrushesky WJ: Outpatient time-specified infusion of fluoropyrimidines by implanted pump is less costly than flat delivery by
external pump. Prog Clin Biol Res 341:397, 1990.
65. Bedder MD, Burchiel JK, Larson A: Cost analysis of two implantable narcotic delivery systems. J Pain Symptom Manage 6:368, 1991.
66. Van Dongen RTM, Crul BJP, de Bock M: Long-term intrathecal infusion of morphine and morphine/bupivacaine mixtures in the treatment of
cancer pain: A retrospective analysis of 51 cases. Pain 55:107, 1993.
67. Penn RD, Paice JA: Chronic intrathecal morphine for intractable pain. J Neurosurg 67:182, 1987.
68. Onofrio BM, Yaksh TL: Long-term pain relief produced by intrathecal infusion in 53 patients. J Neurosurg 72:200, 1990.
69. Follett KA, Hitchon PW, Piper J, et al: Response of intractable pain to continuous intrathecal morphine: A retrospective study. Pain 49:21,
1992.
70. Auld AW, Maki-Jokela A, Murdock DM: Intraspinal narcotic analgesia in the treatment of chronic pain. Spine 10:777, 1984.
71. Hadley MN, Shetter AG: Intrathecal opiate administration for analgesia. Contemp Neurosurg 8:1, 1986.
72. Hassenbusch SJ, Stanton-Hicks MD, Soukup J, et al: Sufentanil citrate and morphine/bupivacaine as alternative agents in chronic epidural
infusions for intractable non-cancer pain. Neurosurgery 29:76, 1991.
73. Goodman RR: Treatment of lower extremity reflex sympathetic dystrophy with continuous intrathecal morphine infusion. Appl Neurophysiol
50:425, 1987.
74. Jacobson L: Clinical note: Relief of persistent postamputation stump and phantom limb pain with intrathecal fentanyl. Pain 37:317, 1989.
75. Prager JP, DeSalles A, Wilkinson A, et al: Loin pain hematuria syndrome: Pain relief with intrathecal morphine. Am J Kidney Dis 25:629,
1995.
76. Kanoff RBL: Intraspinal delivery of opiates by an implantable, programmable pump in patients with chronic, intractable pain of nonmalignant
origin. J Am Osteopath Assoc 94:487, 1994.
77. Meynadier J, Chrubasik J, Dubar M, Wunsch E: Intrathecal somatostatin in terminally ill patients: A report of two cases. Pain 23:9, 1985.
78. Penn RD, Paice JA, Kroin JS: Intrathecal octreotide for cancer pain. Lancet 1:738, 1990.
79. Bowersox SS, Gadbois T, Singh T, et al: Selective N-type neuronal voltage-sensitive calcium channel blocker, SNX-111, produces spinal
antinociception in rat models of acute, persistent and neuropathic pain. J Pharm Exp Ther 279:1243, 1996.
80. Bahar M, Cohen ML, Grinshpon Y, Chanimov M: Spinal anesthesia with midazolam in the rat. Can J Anaesth 44:208, 1997.
81. Coodchild CS: Nonopioid spinal analgesics: Animal experimentation and implications for clinical developments. Pain Rev 4:33, 1997.
82. CoombsDW, Saunders RL, Lachance D, et al: Intrathecal morphine tolerance: Use of intrathecal clonidine, DADLE, and intraventricular
morphine. Anesthesiology 62:358, 1985.
83. Cousins MJ, Cherry DA, Gourlay GK: Acute and chronic pain: Use of spinal opioids. In Cousins MJ, Bridenbaugh PO (eds): Neural Blockade
in Clinical Anesthesia and Management of Pain, 2nd ed. Philadelphia, JB Lippincott, 1988, pp 955–1029.
84. Naumann C, Erdine S, Koulousakis A, et al: Drug adverse events and system complications of intrathecal opioid delivery for pain: Origins,
detection, manifestation, and management. Neuromodulation 2;92, 1999.
85. ShulmanMS, Walkerlin G, Yamaguchi L, Brodsky JB: Experience with epidural hydromorphone for post-thoracotomy pain relief. Anesth
Analg 66:1331, 1987.
86. Mahler PI, Forrest W: Relative analgesic potencies of morphine and hydromorphone in postoperative pain. Anesthesiology 42:602, 1975.
87. Patel
D, Janardhan Y, Merai B, et al: Comparison of intrathecal meperidine and lidocaine in endoscopic urologic procedures. Can J Anaesth
37:567, 1990.
88. Thi TV, Orliaguet G, Liu N, et al: A dose-range study of intrathecal meperidine combined with bupivacaine. Acta Anaesthesiol Scand 36:516,
1992.
89. Trivedi NS, Halpern M, Robalino J, Shevde K: Spinal anaesthesia with low dose meperidine for knee arthroscopy in ambulatory surgical
patients. Reg Anesth 15:43, 1990.
90. Patel
D, Janardhan Y, Merai B, et al: Comparison of intrathecal meperidine and lidocaine in endoscopic urologic procedures. Can J Anaesth
37:567, 1990.
91. Ong B, Segstro R: Respiratory depression associated with meperidine spinal anaesthesia. Can J Anaesth 41:725, 1994.
958
P i
92. Cozian A, Pinaud M, Lepage JY, et al: Effects of meperidine spinal anesthesia on hemodynamics, plasma catecholamines, angiotensin I,
aldosterone, and histamine concentrations in elderly men. Anesthesiology 64:815, 1986.
93. Maurette P, Tauzin-Fin P, Vincon G, Brachet-Lierman A: Arterial and ventricular CSF pharmacokinetics after intrathecal meperidine in
humans. Anesthesiology 70:961, 1989.
94. Thi TV, Orliaguet G, Liu N, et al: A dose-range study of intrathecal meperidine combined with bupivacaine. Acta Anaesthesiol Scand 36:516,
1992.
95. HonetJE, Ardoosh VA, Norris MC, et al: Comparison among intrathecal fentanyl, meperidine and sufentanil for labor analgesia. Anesth Analg
75:734, 1992.
96. Hansdottir
V, Hedner T, Woestenborghs CE, Nordberg G: The CSF and plasma pharmacokinetics of sufentanil after intrathecal administration.
97. Hays RL, Palmer CM: Respiratory depression after intrathecal sufentanil during labor. Anesthesia 81:511, 1994.
98. StevensRA, Petty RH, Hill HF, et al: Redistribution of sufentanil to cerebrospinal fluid and systemic circulation after epidural administration
in dogs. Anesth Analg 76:323, 1993.
99. Sosnowski M, Yaksh TL: Differential cross-tolerance between intrathecal morphine and sufentanil in the rat. Anesthesiology 73:1147, 1990.
100. D'Angelo
R, Anderson MT, Philip J, Eisenach JC: Intrathecal sufentanil compared to epidural bupivacaine for labor analgesia. Anesthesiology
80:1209, 1994.
101. Cohen SE, Cherry CM, Holbrook RH, et al: Intrathecal sufentanil for labor analgesia—sensory changes, side effects, and fetal heart rate
changes. Anesth Analg 77:1155, 1993.
102. Camann WR, Denny RA, Holby ED, Datta S: A comparison of intrathecal, epidural, and intravenous sufentanil for labor analgesia.
103. Ionescu
TI, Taverne RHT, Houwelling PL, et al: Pharmacokinetic study of extradural and intrathecal sufentanil anaesthesia for major surgery.
Br J Anaesth 66:458, 1991.
104. Hays RL, Palmer CM: Respiratory depression after intrathecal sufentanil during labor. Anesthesiology 81:511, 1994.
105. Sabbe MB, Grafe MR, Mjanger E, et al: Spinal delivery of sufentanil, alfentanil, and morphine in dogs. Physiologic and toxicologic
investigations. Anesthesiology 81:899, 1994.
106. Yaksh
T, Houeihed RY, Durant P: Studies of the pharmacology and pathology of intrathecally administered 4-anilinopiperidine analogues and
morphine in the rat and cat. Anesthesiology 66:458, 1986.
107. Rawal N, Nuutinen L, Raj PP, et al: Behavioral and histopathologic effects following intrathecal administration of butorphanol, sufentanil,
and nalbuphine in sheep. Anesthesiology 75:1025, 1991.
108. Rutler DV, Skewes DG, Morgan M: Extradural opioids for postoperative analgesia. Br J Anaesth 53:915, 1981.
110. ReynoldsL, Kedlaya D: Spinal administration of opioids for pain of malignant origin. In Waldman SD: Interventional Pain Management, 2nd
ed. Philadelphia, WB Saunders, 2001, p 409.
111. Sandler
A, Stringer D, Panos L, et al: A randomized double-blind comparison of lumbar epidural and intravenous fentanyl infusions for post-
thoracotomy pain relief. Anesthesiology 77:626, 1992.
112. Guinard JP, Mavrocordatos P, Chioler R, et al: A randomized comparison of intravenous versus lumbar and thoracic epidural fentanyl for
113. Miyoshi HR, Leckband SG: Systemic opioid analgesia. In Loeser JD (ed): Bonica's Management of Pain, 3rd ed. Philadelphia, Lippincott,
Williams & Wilkins, 2001, p 1697.
114. Loper
KA, Ready BL, Downey M, et al: Epidural and intravenous fentanyl infusions are clinically equivalent after knee surgery. Anesth
Analg 70:72, 1990.
115. Glass P, Estok P, Ginsberg B, et al: Use of patient-controlled analgesia to compare the efficacy of epidural to intravenous fentanyl
administration. Anesth Analg 74:345, 1992.
116. Kroin JS, McCarthy RJ, Penn RD, et al: The effect of chronic subarachnoid bupivacaine infusion in dogs. Anesthesiology 66:737, 1987.
117. Sjoberg M, Karlsson PA, Nordborg C, et al: Neuropathologic findings after long-term intrathecal infusion of morphine and bupivacaine for
pain treatment in cancer patients. Anesthesiology 76:173, 1992.
959
P i
118. Li DF, Hahar M, Cole G, et al: Neurological toxicity of the subarachnoid infusion of bupivacaine, lignocaine, or 2-chloroprocaine in the rat.
Br J Anaesth 57:424, 1985.
119. Rigler ML, Drasner K, Krejcie TC, et al: Cauda equina syndrome after continuous spinal anesthesia. Anesth Analg 72:275, 1991.
120. Raj
PR, Denson DD, de Jong RH: No tachyphylaxis with prolonged, continuous bupivacaine. In Wust HJ, Stanton-Hicks M (eds): New
Aspects in Regional Anaesthesia 4: Major Conduction Block: Tachyphylaxis, Hypotension, and Opiates. New York, Springer-Verlag, 1986, pp
10–18.
121. Coombs DW, Pageau MG, Saunders RL, et al: Intraspinal narcotic tolerance: Preliminary experience with continuous bupivacaine HCL
infusion via implanted infusion device. Int Artif Organs 5:379, 1982.
122. TanelianDL, Cousins MJ: Failure of epidural opioid to control cancer pain in a patient previously treated with massive doses of intravenous
opioid. Pain 36:359, 1989.
123. Berde
CB, Sethna NF, Conrad LS, et al: Subarachnoid bupivacaine analgesia for seven months for a patient with a spinal cord tumor.
124. Nitescu
P, Lennart A, Linder L, et al: Epidural versus intrathecal morphine-bupivacaine: Assessment of consecutive treatments in advanced
cancer pain. J Pain Symptom Manage 5:18, 1990.
125. DuPen SL, Williams AR: Management of patients receiving combined epidural morphine and bupivacaine for the treatment of cancer pain. J
126. Krames, ES, Lanning RM: Intrathecal infusional analgesia for nonmalignant pain: Analgesic efficacy of intrathecal opioid with or without
bupivacaine. J Pain Symptom Manage 8:539, 1993.
127. Kitahata LM: Spinal analgesia with morphine and clonidine. Anesth Analg 68:191, 1989.
128. Spaulding TC, Fielding S, Venafro JJ, et al: Anti-nociceptive activity of clonidine and its potentiation of morphine analgesia. Eur J Pharmacol
58:19, 1979.
129. WilcoxGL, Carlson KH, Jochim A, et al: Mutual potentiation of anti-nociceptive effects of morphine and clonidine on motor and sensory
responses in rat spinal cord. Brain Res 405:84, 1987.
130. Eisenach JC, Rauck RL, Buzzanell C, et al: Epidural clonidine analgesia for intractable cancer pain: Phase 1. Anesthesiology 71:647, 1989.
131. YakshTL, Reddy SVR: Studies on the primate on the analgetic effects associated with intrathecal actions of opiates, alpha-adrenergic
agonists and baclofen. Anesthesiology 54:451, 1981.
132. Spaulding JC, Venafro JJ, Ma MG, Fielding S: The dissociation of the antinociceptive effect of clonidine from supraspinal structures.
Neuropharmacology 18:103, 1981.
133. Filos KS, Goudas LC, Patroni O, Polyzoo V: Hemodynamic and analgesic profile after intrathecal clonidine in humans. Anesthesiology
81:591, 1994.
134. Eisenach JC, Rauck RL, Buzzanell C, et al: Epidural clonidine analgesia for intractable cancer pain: Phase 1. Anesthesiology 71:647, 1989.
135. Coombs DW, Saunders RL, LaChance D, et al: Intrathecal morphine tolerance: Use of clonidine, DADLE, and intraventricular morphine.
136. Eisenach JC: Overview: First international symposium on alpha-2 adrenergic mechanisms of spinal anesthesia. Reg Anesth 18:I, 1993.
137. DuPen S, Eisenach JC, Allin D, Zaccaro D: Epidural clonidine for intractable cancer pain. Reg Anesth 45(suppl. 18):7, 1993.
138. Rauck RL, Eisenach JC, Kackson KE, et al: Epidural clonidine for refractory reflex sympathetic dystrophy. Anesthesiology 75:A657, 1991.
139. Sandkuhler
J, Fu QG, Helmchen C: Spinal somatostatin superfusion in vitro effects of cat nociceptive dorsal horn neurons: Comparison with
spinal morphine. Neuroscience 34:565, 1990.
140. Chrubasik J, Meynadier J, Blond S, et al: Somatostatin, a potent analgesic substance. Lancet 11:1208, 1984.
141. GaumannDM, Yaksh TL, Post C, et al: Intrathecal somatostatin in cat and mouse studies on pain, motor behavior and histopathology. Anesth
Analg 68:623, 1989.
142. Penn RD, Paice JA, Kroin JS: Intrathecal octreotide for cancer pain. Lancet 1990;1:738.
143. Penn RD, Paice JA, Kroin JS: Octreotide: a potent new non-opiate analgesic for intrathecal infusion. Pain 49:13, 1992.
144. Candrina R, Galli G: Intraventricular octreotide for cancer pain. J Neurosurg 76:336, 1992.
960
P i
145. Mathur: Neuronal N-type calcium channels: New prospect in pain therapy. Pharma News 5:25, 1999.
146. Penn RD, Paice JA: Adverse effects associated with the intrathecal administration of ziconotide. Pain 85:291, 2000.
147. Price GW, Wilkin GP, Turnbull MJ, Bowery NG: Are baclofen-sensitive GABA-b receptors present on primary afferent terminals of the
spinal cord? Nature 307:71, 1984.
148. Penn RD, Kroin JS: Long term intrathecal baclofen infusion for treatment of spasticity. J Neurosurg 66:181, 1987.
149. Penn RD, Savoy SM, Corcus D, et al: Intrathecal baclofen for severe spasticity. N Engl J Med 320:1517, 1989.
150. Lazorthes Y, Sallerin-Caute B, Verdie JC, et al: Chronic intrathecal baclofen administration for control of severe spasticity. J Neurosurg
72:393, 1990.
151. Penn RD, Kroin JS: Intrathecal baclofen alleviates spinal cord spasticity. Lancet 1:1078, 1984.
152. Coffey
RJ, Cahill D, Steers W, et al: Intrathecal baclofen for intractable spasticity of spinal origin: Results of a long-term multicenter study. J
Neurosurg 78:226, 1993.
153. Nanninga J, Frost F, Penn R: Effect of intrathecal baclofen on bladder and sphincter function. J Urol 142:100, 1989.
154. Herman R, D'Luzansky S, Ippolito R: Intrathecal baclofen suppresses central pain in patients with spinal lesions. Clin J Pain 8:338, 1992.
155. Tsui M, Lam S: Stability of intrathecal baclofen and morphine. Aust J Hosp Pharm 22:258, 1992.
156. Synchromed Infusion System Clinical Reference Guide: Medtronic Inc., Minneapolis, MN, 1993.
961
Section V Chapter 39 - Epiduroscopy
Chapter 39 - Epiduroscopy
Susan R. Anderson
Epiduroscopy is the percutaneous placement of a fiberoptic scope into the epidural space. The technique presented
in this chapter describes entry of the epidural space through the sacral hiatus. The epiduroscope is used as a
diagnostic tool that has educational applications and future ramifications in the interventional treatment of pain.
HISTORY
In 1931, Burman removed 11 vertebral columns from cadavers and examined the anatomy with
arthroscopic equipment. Stern described a spinascope and trocar for in vivo examination of the spinal
[1] [2]
canal in 1936. Although a working model was built, it was never actually used.
[2] [3]
The first in vivo examination of the spinal canal was performed by Pool in 1937. The first [2] [4]
examination was complicated by hemorrhage. However, before the loss of visualization, a glimpse was
gained of the lumbosacral nerves.
Subsequently, Pool examined seven more patients without complication and observed the cauda equina.
He also noted the flow of blood through the epidural blood vessels. By 1942, Pool was able to report [2] [4]
on 400 cases he had performed. The technique was used for diagnostic preparation for surgery. Pool [2] [5] [6]
was able to identify neuritis, herniated nucleus pulposus, hypertrophied ligamentum flavum, neoplasms,
and arachnoid adhesions. [5] [6]
From 1942 until 1967, there were no further reports of endoscopy. The rationale is that there were
technical limitations in light sources and photographic equipment. The lights needed to be smaller and
easier to manipulate and images needed to be captured on film rather than sketched.
Without knowing about the work done on endoscopy in the United States, Ooi and colleagues in Japan
developed an endoscope in the 1960s. The advent of the fiberoptic light source in the 1970s made
[2] [7] [8] [9]
the scope more amenable to percutaneous placement and simplified the procedure. From 1967 to 1977, [2]
Ooi and colleagues performed 208 myeloscopies using various types of equipment. Their progress
[10] [11]
was reported in several publications, culminating in 1981 with their publication on myeloscopy and
blood flow changes of the cauda equina during Lasegue’s test. [2] [12]
Blomberg of Sweden described a method of performing epiduroscopy and spinaloscopy. Using this
[13] [2]
technique, Blomberg noted that the epidural space contents varied in regard to fat and connective tissue.
He also noted that adhesions between the dura mater and ligamentum flavum could restrict the opening
of the epidural space despite flushing with normal saline. Blomberg was also able to visualize the
[2] [13]
entry of Tuohy needles through the ligamentum flavum into the epidural space. Dural tenting was seen
when an epidural catheter was threaded through the Tuohy needle into the epidural space. [2] [13]
In 1989, Blomberg and Olsson performed 10 epiduroscopies on patients scheduled for partial
[14]
laminectomies. They believed that the conclusions drawn from the previous cadaveric work did not
[2]
relate to the clinical setting because of the lack of circulation or cerebospinal fluid (CSF) pressure in the
cadavers. They determined that the epidural space was, indeed, only a potential space that remained
[2] [14]
open for brief periods when fluid or air was injected. They also confirmed the presence of a
[2] [14]
dorsomedian connective tissue band within the epidural space. They determined that the midline
approach to the epidural space was often associated with bleeding and that a paramedian approach was
less likely to cause this complication. [2] [15]
In 1991, Shimoji and associates observed the epidural space after withdrawing the endoscope from the
[16]
subarachnoid space. By looking at the epidural space in this manner, they confirmed it as a potential
[2]
962
space. It was believed that the CSF infiltrated and opened the space for visualization. They were the first
group to publish their endoscopic experience using both a fiberoptic light source and a flexible
fiberoptic catheter instead of the traditional rigid metal endoscopes. The investigators identified the
[2] [16]
spinal level by using concomitant radiography. They were able to observe aseptic adhesive arachnoiditis
where nerve roots were mated or clumped by filamentous tissue. Of five patients with the diagnosis
[2] [16]
of arachnoiditis, three had a reduction or resolution of pain. Shimoji and associates reported
[16] [16]
complications of headache, fever, and dysesthesia. The headaches were transient postdural puncture
headaches. The episodes of dysesthesia were provoked during the procedure but resolved by withdrawal
of the scope.[2] [16]
Anatomy and Physiology
The epidural space is largely a potential space, with an average depth of probably no more than 3 mm. In vivo, the
actual depth of the space is highly dependent on the relationship of epidural to CSF pressure. Determination of
epidural space morphology in cadavers has yielded variable results, depending on whether attempts were made to
approximate physiologic CSF volumes in the specimens.[17] Distention of the epidural space with irrigating
solutions occurs only when the pressure within the epidural space exceeds the CSF pressure, thereby displacing the
CSF. Distention of the epidural space is nonuniform, with the dorsomedial portion being the most distensible. The
dorsolateral epidural space distends minimally, and the ventral epidural space distends little if at all. At its point of
maximal distention, the depth of the epidural space is 9 mm.[17]
These anatomic characteristics limit one’s ability to examine the epidural structures fully. It is usually possible to
obtain tangential views of the dura and the proximal nerve root sleeves and to identify the junctions of the sleeves
with the thecal sac. It is very difficult to visualize the lateral recesses or to view the lateral portions of the sleeves
and impossible to examine the anterior epidural space. Because distention of the epidural space involves
displacement of CSF, injection of irrigation solution during epiduroscopy causes a transitory but substantial rise in
lumbar CSF pressures. Concurrent lumbar CSF pressure monitoring in patients undergoing epiduroscopy has shown
increases in lumbar CSF pressure to 60 mm Hg with 30 mL of irrigant injected over a 60-second period.
Indications
Diagnosis.Examination of the epidural space in patients with chronic radicular pain symptoms without radiographic
or magnetic resonance imaging evidence of disc injury has shown the presence of inflammation involving the nerve
root corresponding to the symptomatic area. These findings suggest that factors other than direct mechanical
[18]
compression may cause radicular symptoms; possible mechanisms include a “leaking disk.” Myeloscopy may
therefore be useful in confirming a physiologic basis for radicular pain when other diagnostic studies are negative.
With epiduroscopy, direct clinical observation is possible for adhesions and fibrosis, tissue changes after epidural
blocks, structural changes with aging, neuritis, HNP, and hypertrophied ligamentum flavum.
For epidural steroid injection in patients with previous spine surgery.Using fluoroscopy, Fredman and
associates showed that in patients with previous back surgery, epidurally injected depot-steroid solution spreads to
[19]
reach the level of pathology in only 26% of cases. Myeloscopy allows more accurate placement of drugs within the
epidural space, which may improve the efficacy of epidural steroids in “failed back surgery syndrome.” Additional
studies are needed to evaluate this assertion.
Lysis of perineural adhesions.Perineural epidural scarring has been postulated as a cause of chronic pain after
laminectomy. During myeloscopy, these adhesions may be lysed by manipulation of the fiberscope tip, by pressure
of the irrigating solution, or by a probe introduced through a second portal.
Puncture and aspiration of epidural cycts.Some investigators have successfully fenestrated both synovial cysts
and CSF inclusion cysts by using the tip of the myeloscope.
Contraindications
Injection of large volumes of fluids and epiduroscopy should be avoided in patients with a coagulopathy, a local
infection, a cerebrovascular disease, or a lesion that occupies CNS space. Patients with sacral nerve injury may be at
further risk for bladder and bowel dysfunction during or after administration of large volumes of epidural saline. [15]
963
Technique
There are currently at least three steerable catheters available for use within the spinal canal. Catheter outer
diameters range from 1.4 mm to 2.1 mm. The fiberscopes are 0.8 mm to 1.0 mm, providing up to 10,000 pixels. The
current technique for epiduroscopy involves the introduction of the catheter through the sacral hiatus. At Texas Tech
University Health Sciences Center, this is performed in the operating room suite. After an adequate preoperative
workup, which includes lumbosacral magnetic resonance imaging, urology evaluation (if necessary), and laboratory
tests (normal values in complete blood count, prothrombin time; partial thromboplastin time), the patient is placed in
the prone position on a fluoroscopy table. The procedure is performed under local anesthetic with monitored
anesthesia care. The patient is given 1 g of ceftriaxone (Rocephin) intravenously before the start of the case.
(Ciprofloxacin [Cipro] 400 mg; may be substituted for 1 hour before the procedure if allergy is a concern.) A pillow
may be placed under the lower abdomen to decrease the lordosis of the lumbar spine. The patient is prepared and
draped in a sterile manner.
A skin wheal is raised over the sacral hiatus with use of 1% lidocaine, 1 to 2 mL and a 25-gauge(G) needle. An 18-
G needle is used to penetrate the skin. A 16-G RK epidural needle is then inserted through the puncture site and into
the sacral hiatus ( Fig. 39–1 ). This may be verified by both the anteroposterior and lateral fluoroscopic views. An
epidurogram is then performed
Figure 39-1 Placement of 16-gauge RK epidural needle through the sacral hiatus into the epidural space.
with 10 mL of water-soluble, nonionic dye ( Fig. 39–2 ). When the epidurogram has been obtained, a guidewire is
inserted through the needle and advanced to approximately the L5 or S1 level.
A small incision is made with an 11-blade scalpel to the level of the sacral ligament to decrease the “drag” of the
skin and subcutaneous tissues on the introducers and sheaths. A 9 French (Fr) introducer is inserted over the
guidewire into the sacral space ( Figs. 39–3 and 39–4 ). This is then removed and the introducer with sheath is
placed over the guidewire into the space. It is important to check the guidewire for freedom of movement to prevent
kinking. The 9 Fr introducer and sheath are then removed and a 10 Fr introducer is placed over the guidewire into
the sacral space. If there is ease of movement, the 10 Fr introducer with sheath is then placed into the sacral space.
Figure 39-2 Epidurogram performed with 10 mL of water-soluble nonionic dye.

Note the filling defect at L5. Arrow indicates the tip of the epidural needle.
964
Figure 39-3 Removal of the needle over the guidewire.
This method is used to slowly dilate the space because there are anatomic differences in size. The 10 Fr introducer
and the guidewire are then removed, leaving the sheath in place ( Fig. 39–5 ). The steerable catheter is inserted
through the introducer sheath. Fluoroscopy is necessary to verify the proper intraspinal placement. During the
epiduroscopy procedure, care must be taken to use the minimal amount of saline for irrigation and local distention.
Injection rates should not exceed
Figure 39-4 A 9 French introducer is placed over the guidewire

and threaded into the epidural space. This is to dilate the ligament
at the sacral hiatus.
30 mL per minute. The total infused volume should not exceed 60 mL. (There is often considerable retrograde flow
of irrigation fluid out of the catheter or introducer; this should not be counted with the amount actually infused).
Continuous CSF pressure monitoring through a lumbar subarachnoid needle should be considered during prolonged
cases with larger irrigation volumes. In addition to monitoring the volume infused, it is strongly suggested that the
time spent in the epidural space with the steerable catheter also be monitored. In clinical practice at Texas Tech
University Health Sciences Center, this is no more than 30 minutes.
965
Figure 39-5 A 10 French introducer with sheath is placed over the

guidewire and into the epidural space. The 10 Fr Sheath is then left
in place for introduction of the epiduroscope.
The steerable catheter facilitates 3-dimensional direct clinical observation. The operator may observe the normal
peridural fat in the sacral canal ( Fig. 39–6 ). Dense granuloma tissue may be noted ( Fig. 39–7 ). Swollen, angry
nerve roots may be identified by the surrounding granulomatous tissue and distended vasculature that follows the
root ( Fig. 39–8 A and B). There may also be incidental findings such as an encapsulated granulomatous mass ( Fig.
39–9 ).
At Texas Tech University Health Sciences Center, epiduroscopy is combined with caudal epidural neurolysis
technique. After the epiduroscopy is performed and while the steerable scope is in place, an Epimed Tun-L-XL
catheter is placed through the working channel and advanced to the desired site of position. The fluoroscopic view
allows determination of the level of the placement. It also facilitates ventral or dorsal epidural placement. The
epiduroscope view ensures visualization of the placement of the catheter, which will be used for further therapy. The
epiduroscope is then threaded off the catheter, with attention focused on retaining the position of the catheter tip.
Once the epiduroscope is removed from the space, a skin wheal is made approximately 1 cm lateral and 2 cm caudal
to the sacral space. The skin is punctured with an 18-G needle. The RK epidural needle is then inserted through the
puncture site and tunneled subcutaneously until it exits at the sacral hiatus site. The epidural catheter is threaded
through the needle and out via the lateral incision. The needle is then carefully removed. The sacral hiatus incision
should be closed with a single, interrupted stitch with 2–0 silk or nylon. An anchor stitch should be placed to hold
the catheter in place with the 2–0 silk or nylon. The site is then covered with antibiotic ointment, two 2×2 sponges,
transparent dressing, folded 4×4, and tape. The protocol for caudal epidural neurolysis is then followed with testing
of the catheter, treatment with local anesthetic and steroid, injection of hyaluronidase, and hypertonic saline infusion.
This is completed over three injections as described by Racz and Holubec. [20]
Complications
To date, there have been no complications reported in the literature. There is one instance of epidural abscess. Some
investigators use routine prophylactic antibiotic with no subsequent infections. There are three known cases of
macular hemorrhage with visual impairment after the procedure. These may be related to increased CSF pressure
from infusion of irrigation fluid.
[2]
966
Data from Animal and Cadaver Studies
Although there is a lack of prospective, randomized, double-blind studies regarding epiduroscopy, the following
data are available from animal experiments and cadaver studies:
1. The epidural space is a potential space that opens only on introduction of an epiduroscope or epidural and
spinal needles and catheters.
2. During epiduroscopy, the epidural space can be seen only if it is kept distended by repeated injections of
saline (or air).
3. The endoscopic view is much clearer and more distinct as the scope is being withdrawn.
4. Easily recognized structures include the dura mater, ligamentum flavum, epidural fat, fibrous connective
tissue, and blood vessels. Spinal nerve roots can be difficult to identify. The presence of a dorsomedian
connective tissue band that divides the epidural space into compartments has been demonstrated in some [21]
but not in other studies.

[22] [23]
5. Direct observation of epidural pathology has demonstrated the presence of adhesions and fibrosis in the
epidural space after spinal surgery, tissue changes after regular epidural blocks, and structural changes in
[24] [25]
the epidural space with increasing age. Spinaloscopy studies in patients have demonstrated the presence
[26]
of neuritis, herniated nucleus pulposus, hypertrophied ligamentum flavum, and adhesive arachnoiditis.
[5] [16]
Technical aspects of epidural, spinal, and combined spinal-epidural technique have been described. Spinal
endoscopic studies have evaluated the risk of epidural catheter migration into the subarachnoid space, [27]
technical and mechanical problems with spinal catheter placement, and the risk of catheter migration
[28]
during performance of the combined spinal-epidural block. The risk of rotation of the epidural needle in
[22]
the epidural space and the possibility of looping of the epidural catheters have also been demonstrated. [22]
Figure 39-6 A, Normal peridural fat in the

sacral canal. B, Illustration of the normal
peridural fat shown in Figure 39–6 A .
Figure 39-7 A, Dense granuloma tissue in

the epidural space. B, Drawing of granuloma
tissue in the epidural space pictured in
Figure 39–7 A. The granulation tissue is
indicated (arrow).
967
Figure 39-8 A, Swollen, angry nerve root.

The distended vasculature that follows the
nerve root is indicated (arrow). B,
Illustration of swollen, angry nerve root
shown in Figure 39–8 A. The nerve root
with vessel is indicated (arrow).
Figure 39-9 A, Encapsulated

granulomatous mass. B , Illustration of
borders of encapsulated granulomatous edge
of the granuloma.
Problems with Epiduroscopy
For epiduroscopy to be performed, the epidural space needs to be distended by repeated injections of saline. If the
procedure takes a long time, the excessive saline volumes may generate significant epidural pressures and affect
local perfusion. Sustained epidural pressure can potentially compromise perfusion or cause barotraumas at locations
remote from injection. The amount of fluid injected must therefore be accurately monitored. Epiduroscopy
[2] [29]
should not be performed in anesthetized patients.
Identification of the correct spinal level is almost impossible without simultaneous fluoroscopy. Furthermore,
because of the presence of abundant epidural adipose tissue and the limited field of vision of superfine fiberscopes,
it may be difficult to distinguish normal discs. Perioperative epiduroscopy could identify the herniating disc in only
one of five patients.
[30]
In spite of many technical advances in spinal endoscopy, the quality of published photographs from recent studies is
relatively poor. Some authors have had to make explanatory drawings of their endoscopic findings, others have
[21]
failed to provide any photographs. Further improvements in technology will allow researchers to publish
[25] [31]
photographs that can be used for scientific evaluation by the reader. Difficulties in advancing the epiduroscope in
[32]
the epidural space have been described. Spinal endoscopy is associated with postdural puncture headache and fever.
[31]
Dysesthesia during the procedure has also been reported. However, the risk of complications is low.
[16]
Future Perspectives
Flexible ultrathin fiberscopes are already being used by some neurosurgeons as diagnostic aids during spine and
brain surgery. Current research has shown that epidural space can be accessed easily by the sacral route to obtain
three-dimensional color images of the contents for the study of normal anatomy and pathologic findings. Future
968
advances will allow the use of electrodes for dorsal column stimulation as well as the use of lasers and performance
of closed procedures (biopsies, retrieval of retained pieces of epidural catheters). Epiduroscopy in cavaders will
continue to provide for study of the characteristics of different epidural and spinal needles and catheters and will
promote the development of better and safer equipment for epidural, spinal, and combined spinal-epidural blocks.
The main questions that need to be answered are the following:
1. Does epiduroscopy provide diagnostic advantages over noninvasive and readily available imaging methods
such as computer tomography and magnetic resonance imaging?
2. Are epiduroscopy-directed targeted epidural steroid injections for intractable low back pain superior to the
less invasive and less expensive traditional epidural steroid injections? Controlled comparative clinical
trials will be necessary because the technique of epidural steroid administration in itself is quite
controversial.
3. Is epidural steroid administration a high-technology gadget looking for clinical application? The technique
is not totally innocuous, and there is a need for studies to establish appropriate indications based on risk-
benefit analysis.
Conclusion
In summary, the technology of spinal endoscopy has improved greatly in recent years. Flexible, superfine
fiberscopes can be introduced through regular epidural needles for diagnostic purposes. Although the photography
has improved, it is hoped that with the technology of digital cameras and computers, the images will become more
distinctive and less open to speculation. Although used chiefly as a diagnostic aid that is more appropriate for
educational activities, the future applications of this technique for percutaneous therapeutics are encouraging.
REFERENCES
1. Burman MS: Myeloscopy or the direct visualization of the spinal cord. J Bone Joint Surg 13:695–696, 1931.
2. Saberski LR: Spinal Endoscopy: Current concepts, In Waldman SD (ed): Interventional Pain Management. Philadelphia, WB Saunders, 2001,
pp 143–161.
3. Stern EL: The spinascope: A new instrument for visualizing the spinal canal and its contents. Med Rec (NY) 143:31–32, 1936.
4. Pool JL: Direct visualization of dorsal nerve roots of the cauda equina by means of a myeloscope. Arch Neurol Psychiatry 39:1308–1312, 1938.
5. Pool JL: Myeloscopy: Intraspinal endoscopy, Surgery 11:169–182, 1942.
6. Pool JL: Myeloscopy: Diagnostic inspection of the cauda equina by means of an endoscope. Bull Neurol Inst N Y 7:178–189, 1938.
7. Ooi Y, Morisaki N: Intrathecal lumbar endoscope. Clin Orthop Surg (Jpn) 4:295–297, 1969.
8. Ooi Y, Satoh Y, Morisaki N: Myeloscopy, Igakuno Ayumi (Jpn) 81:209–212, 1972.
9. Ooi Y, Satoh Y, Morisaki N: Myeloscopy. Orthop Surg (Jpn) 24:181–186, 1973.
10. Ooi Y, Satoh Y, Inoue K, et al: Myeloscopy. Acta Orthop Belg 44:881, 1978.
11. SatohY, Hirose K, Ooi Y, Mikanagi K: Myeloscopy in the diagnosis of low back pain syndrome. Presented at the Third Congress of
International Rehabilitation Medicine Association Basel, July 2–9, 1978.
12. Ooi
Y, Satoh Y, Inoue K, et al: Myeloscopy with special reference to blood flow changes in the cauda equina during Lasegue’s test. Int Orthop
4:307–311, 1981.
13. Blomberg R: A method for spinal canal endoscopy and spinaloscopy: Presentation of preliminary results. Acta Anaesthesiol Scand 21:113–116,
1985.
14. Blomberg R, Olsson S: The lumbar epidural space in patients examined with epiduroscopy. Anesth Analg 68:157–160, 1989.
15. BlombergR: Technical advantages of the paramedian approach for lumbar epidural puncture and catheter introduction. Anesthesiology
43:837–843, 1988.
16. Shimoji K, Fujioka H, Onodera M, et al: Observation of spinal canal and cisternae with the newly developed small-diameter, flexible
fibrescopes. Anesthesiology 75:341–344, 1991.
969
17. Harrison GR, Parkin IG, Shan JL: Resin injection studies of the lumbar extradural space. Br J Anaesth 57:333–336, 1985.
18. Rizor
RF: Epiduroscopy: Technique for examination of the lumbar epidural space. American Society of Regional Anesthesia Nineteenth
Annual Meeting. Chicago, 1994.
19. FredmanB, Ben Nun B, Zohar E, et al: Epidural steroids for treating “failed back surgery syndrome”: Is fluoroscopy really necessary? Anesth
Anal 88:3667–72, 1999.
20. Racz GB, Holubec JT: Lysis of adhesions in the epidural space. In Racz GB (ed): Techniques of Neurolysis. Boston, Kluwer Academic, 1989.
22. Holmstrom B, Rawal N, Axelesson K, et al: Risk of catheter migration during combined spinal epidural block-percutaneous epiduroscopy
study. Anesth Analg 80:747–753, 1995.
23. Igarshi T, Hirabayashi Y, Shimizu R, et al: Thoracic and lumbar extradural structure examined by extraduroscope. Br J Anaesth 81:121–125,
1998.
24. Schutze G, Kurtze H: Direct observation of the epidural space with a catheter-secured epiduroscopic unit. Reg Anesth 19:85–89, 1994.
25. KitamuraA, Sakamoto A, Aoki S, et al: Epiduroscopic changes in patients undergoing single and repeated epidural injections. Anesth Analg
82:88–90, 1996.
26. Igarashi T, Hirabayashi Y, Shimizu R, et al: The lumbar extradural structure changes with increasing age. Br J Anaesth 78:149–152, 1997.
27. BlombergRG: The lumbar subdural extraarachnoid space of humans. An anatomical study using spinaloscopy in autopsy cases. Anesth Analg
66:177–180, 1987.
28. MollmannM, Holst D, Lubesmeyer H, et al: Continuous spinal anesthesia: Mechanical and technical problems of catheter placement. Reg
Anesth 18:469–472, 1993.
29. Serpell MG, Coombs DW, Colburn RW, et al: Intrathecal pressure recordings due to saline instillation in the epidural space. In: Abstracts of
the Seventh World Congress on Pain [abstract 1535]. Paris, Raven Press, August, 1993.
30. Rosenberg PH: Fiberoptic epiduroscopy—current research [abstract]. Seventh International Pain Clinic, Istanbul, Turkey. 1996, p. 124.
31. Delhass EM: Extradural and subarachnoid catheterization using the Seldinger technique. Br J Anaesth 76:149–150, 1996.
32. Holmstrom B, Rawal N: Combined spinal-epidural block: What can we learn from epiduraloscopy? Tech Reg Anesth Pain Manage 1:107–112,
1997.
970
Section V Chapter 40 - Sphenopalatine Analgesia
Chapter 40 - Sphenopalatine Analgesia
Miles Day
HISTORY
Sluder is credited as being the first to implicate the sphenopalatine ganglion (SPG) in the pathogenesis of
facial pain. In 1908, he described an “upper-half” headache (which he later called sphenopalatine
neuralgia) and treated it successfully with a transnasal sphenopalatine ganglion block (SPGB). Over the [1]
past century, physicians performed SPGBs for pain syndromes ranging from headache and facial pain to
low back pain and dysmenorrhea. In the past and present medical literature regarding SPGB, there are
[1]
large gaps that span decades. This may indicate varying levels of interest and skepticism among physicians
regarding the involvement of the SPG in the pathogenesis of pain. Currently, SPG blockade is an effective
modality for relief of facial pain and headache. It has provided pain relief in patients when conventional
pharmacologic therapy or other interventional procedures have become less effective or altogether
ineffective.
INDICATIONS
Blockade of the SPG is used in the treatment of many painful medical syndromes involving the face and
head. Sluder was the first to describe in the literature a unilateral facial pain at the root of the nose, which
sometimes spread retro-orbitally toward the zygoma and extended back to the mastoid and occiput. The [2]
pain was commonly associated with parasympathetic features such as lacrimation and rhinorrhea, with or
without mucosal congestion. Sluder called this pain syndrome sphenopalatine neuralgia. He believed the
[2]
the cause of this pain was the spread of infection from the paranasal sinuses, which caused irritation of
the SPG. This was initially accepted as a possible causal mechanism but was questioned when other
syndromes, such as low back pain, sciatica, and dysmenorrhea, were attributed to irritation of the SPG. In
the early 1940s, Eagle sought to revive interest in sphenopalatine neuralgia when he presented his thesis
[3]
to the American Laryngological, Rhinological, and Otological Society. He agreed with Sluder on the
existence of sphenopalatine neuralgia but disagreed with him on the etiology of the disorder. Eagle [3]
believed that intranasal deformities such as deviated septum, septal spurs or ledges, and prominent
turbinates were responsible for irritation of the ganglion, which caused pain. Others have believed that a
reflex vasomotor change or possibly a vasomotor syndrome might be responsible for causing the pain. [4]
Regardless of the proposed causes, sphenopalatine neuralgia is an indication for SPGB.
Trigeminal neuralgia is a second indication for SPGB. Ruskin, in 1925, disagreed with Sluder on the
indication for SPGB and instead proposed the involvement of the SPG in the pathogenesis of trigeminal
neuralgia. As discussed in the anatomy section of the chapter, the SPG is directly connected to the
[5]
maxillary branch of the trigeminal nerve via the pterygopalatine nerves. Ruskin believed that blockade of
the SPG would in turn relieve the symptoms associated with trigeminal neuralgia via a retrograde effect.
There are few case reports in current literature that support this theory. [6]
Although new medications for the treatment of migraine and cluster headache are introduced yearly,
there are small subsets of patients who fail to respond to oral and parenteral dosing and are forced to seek
alternative methods for pain control. Blockade of the SPG has been used in such cases with varying
success.[7] [8] [9]
Another indication for SPGB is atypical facial pain. The pain is usually unilateral and described as
constant, aching, burning and not confined to the distribution of a cranial nerve. The entire face, scalp,
[10]
and neck may be involved. The pain may have a sympathetic component, which makes SPGB ideal,
because the postganglionic sympathetic nerves pass through the ganglion.
Other reported uses of SPGB include back pain, sciatica, angina, arthritis, herpes zoster ophthalmicus,
and pain from cancer of the tongue and the floor of the mouth. These are not “true” indications for
[11] [12] [13]
SPGB but instead reveal the resourcefulness of this block for cases in which conventional therapies are
ineffective.
971
Anatomy and Physiology
The sphenopalatine ganglion is the largest group of neurons outside of the cranial cavity. It lies in the
pterygopalatine fossa, which is approximately 1 cm wide and 2 cm high and resembles a “vase” when seen on a
lateral fluoroscopic view. The pterygopalatine fossa is bordered anteriorly by the posterior wall of the maxillary
sinus, posteriorly by the medial plate of the pterygoid process, medially by the perpendicular plate of the palatine
bone, superiorly by the sphenoid sinus. Laterally, it communicates with the infratemporal fossa. The foramen
[14]
rotundum, through which the maxillary branch of the trigeminal nerve passes, is located on the superolateral aspect
of the pterygopallatine fossa, whereas the opening to the pterygoid canal, which houses the vidian nerve, is located
on the inferomedial portion of the fossa. The ganglion within the fossa is located posterior to the middle turbinate of
the nose and lies a few millimeters deep to the lateral nasal mucosa. Also contained within the fossa are the
maxillary artery and its multiple branches. The maxillary branch of the trigeminal nerve exits the cranial vault
through the foramen rotundum and is located cephalad and slightly lateral to the pterygopalatine fossa.
The sphenopalatine ganglion is a complex neural center with multiple connections. It is “suspended” from the
maxillary branch of the trigeminal nerve at the pterygopalatine fossa via the pterygopalatine nerves and lies medial
to the maxillary branch when viewed in the sagittal plane ( Fig. 40–1 ). Posteriorly, it is connected to the vidian
nerve, also known as the nerve of the pterygoid canal, which is formed by the greater petrosal and deep petrosal
nerves. The ganglion itself has efferent branches and forms the superoposterior lateral nasal and pharyngeal nerves.
Caudally, the ganglion is in direct connection with the greater and lesser palatine nerves.
As the second largest neural center in the head, the ganglion has sensory, motor, and autonomic components. The [15]
sensory fibers arise from the maxillary nerve, pass through the SPG, and are distributed to the nasal membranes, the
soft palate, and some parts of the pharynx. A few motor nerves are also believed to be carried with the sensory
[3]
trunks. The autonomic
Figure 40-1 Lateral radiographic view of the region surrounding the

pterygopalatine fossa. a, pterygopalatine fossa; b, sella turcica; c,
maxillary sinus; d, mandible; e, maxilla; and f, zygoma.
innervation is more complex. The sympathetic component begins with preganglionic sympathetic fibers originating
in the intermediolateral gray columns of the upper thoracic spinal cord, forming the white rami communicantes,
coursing through the sympathetic chain, and ending in the superior cervical sympathetic ganglion. Here, the
preganglionic fibers synapse with the postganglionic fibers. The postganglionic fibers then join the carotid nerves
before branching off and traveling through the deep petrosal and vidian nerves. The postganglionic sympathetic
nerves continue their path through the sphenopalatine ganglion on their way to the lacrimal gland and the nasal and
palatine mucosa. The parasympathetic component has its preganglionic origin in the superior salivatory nucleus and
then travels through a portion of the facial nerve (VII) before forming the greater petrosal nerve. The greater
petrosal nerve in turn joins the deep petrosal nerve to form the vidian nerve, which ends in the sphenopalatine
ganglion. Within the ganglion, the preganglionic fibers synapse with their postganglionic cells and continue on to
the nasal mucosa, and one branch travels with the maxillary nerve to the lacrimal gland.
972
Pathophysiology
The role of the sphenopalatine ganglion in the pathogenesis of pain still remains controversial. Sluder believed that[2]
paranasal sinus infections caused irritation of the ganglion with resulting pain, whereas Eagle thought that nasal
[3]
deformities were responsible for the irritation of the ganglion, which, in turn, caused pain. Ruskin advocated the
[5]
involvement of the SPG in the pathogenesis of trigeminal neuralgia; the exact etiology of this disorder also remains
to be defined. Another hypothesis is that a dysequilibrium between the sympathetic and parasympathetic tone within
the ganglion result causes the release of substance P or a blockade of local enkephalins. Still another hypothesis
[16]
revolves around the belief that focal demyelination within the ganglion produces abnormal impulses in the afferent
nociceptive C fibers which lead to pain. Friedman suggested that local dilatation of the internal maxillary artery is
[16] [7]
the source of irritation of the SPG. A general consensus regarding the role and pathogenesis of the SPG remains
elusive.
Methods of Blockade
The SPG can be blocked by several techniques. The drugs frequently used are local anesthetics (4% cocaine, 2% to
4% lidocaine, or 0.5% bupivacaine/ropivacaine/levobupivacaine), depot steroids (methylprednisolone or
triamcinolone diacetate), with or without 6% phenol. To prolong the blockade, radiofrequency thermocoagulation
(RFTC) can be employed, and more recently at our institution, electromagnetic field (EMF) pulsed radiofrequency
lesioning has been used. The current hypothesis regarding the mechanism of action of EMF is that the membrane of
nerves has a capacitor function and that EMF creates a high electric field, which punches holes in the capacitor and
thus blocks transmission of stimuli through A delta and nociceptive C-fibers. Informed consent must be obtained
[17]
and complications must be explained before the block. Patients taking oral anticoagulants should stop these several
days before the procedure as long as it is not detrimental to their health. Bleeding parameters should be obtained to
confirm normal values.
Techniques of Blockade
TECHNIQUE ONE: INTRANASAL TOPICAL APPLICATION OF LOCAL ANESTHETIC ( Fig. 40–2 )
The intranasal topical application of local anesthetic is relatively easy to perform and can be taught to the patient if
effective. A 3.5-inch cotton tip applicator is dipped in the anesthetic solution (cocaine or lidocaine). The [18] [19]
applicator is inserted through the ipsilateral nare on the affected side while a parallel line is maintained with the
zygomatic arch, which corresponds to the level of the middle turbinate. A slow advance is made while the applicator
is pushed laterally toward the back of the nasal pharynx. The ganglion lies a few millimeters beneath the lateral
nasal mucosa. Once the first applicator is in place, a second applicator is inserted in the same fashion, except that it
is placed slightly superior and posterior to the first. The applicators are left in for approximately 30 to 45 minutes. If
additional medication is needed, the local anesthetic can be trickled down the shaft of the applicator. Because of the
connections with the lacrimal gland,
Figure 40-2 Transnasal sphenopalatine ganglion block.
973
blockade of the SPG results in ipsilateral tearing because of unopposed parasympathetic activity. If the block is
effective, it can be repeated, or an RFTC or EMF procedure can be performed for prolonged analgesia. I do not
recommend the use of phenol for neurolysis with this technique.
Spencer developed a variation of this approach at Concord Hospital in Concord, New Hampshire. Specific
[20]
hollow-lumen, cotton-tipped applicators (Hardwood Products, Guilford, Me) are placed as described earlier. The
white plastic disposable spray nozzle from a bottle of 10% Oral Spray (Astra, USA, Westborough, Mass) is cut to a
length of 4 cm. A sterile 2.5-mm i.d. uncuffed tracheal tube is also cut to 4 cm and used to connect the spray nozzle
to the hollow applicator. Each actuation of the metered-dose valve delivers 10 mg of lidocaine. The hollow lumen of
the applicator is primed with two to three doses (not counted toward the total dose of lidocaine). Additional doses
are administered and disconnected from the applicator. The applicators are left in place for at least 30 minutes. The
applicators can be recharged with more local anesthetic during this time as long as the dose does not exceed 4 mg/kg.
TECHNIQUE TWO: GREATER PALATINE FORAMEN APPROACH ( Fig. 40–3 ) [18]
The patient is placed in the supine position with the neck slightly extended. The greater palatine foramen is located
just medial to the gumline of the third molar. Sometimes, a dimple can be seen, which signifies the foramen. A
dental needle with a 120-degree angle is inserted through the mucosa and into the foramen. This procedure can be
performed with or without fluoroscopic guidance. The needle is advanced approximately 2.5 cm in a superior and
slightly posterior direction.
Figure 40-3 Greater palatine foramen approach.
A paresthesia may be elicited because the maxillary nerve is just cephalad to the ganglion. If fluoroscopic guidance
is used, 1 mL of a nonionic, water-soluble contrast is injected. The spread of the contrast into the pterygopalatine
fossa should be visible. Cocaine or lidocaine, 2 mL, is injected after negative aspiration and the SPGB is confirmed
as before. Data on standard radio frequency or electromagnetic field pulsed radio frequency lesioning, or phenol
injection of the sphenopalatine ganglion via this approach appears to be absent from the literature.
TECHNIQUE THREE: INFRAZYGOMATIC ARCH APPROACH[21]
This approach has been commonly performed blindly without C-arm fluoroscopy, but at Texas Tech University
Health Sciences Center, we recommend use of fluoroscopy. The patient is placed in a supine position with the head
inside the C-arm. A lateral view of the upper cervical spine and the mandible is obtained. The patient’s head is
rotated until the rami of the mandible are superimposed. The C-arm is moved slightly cephalad until the
pterygopalatine fossa is visible. When the 2 pterygopalatine plates are superimposed upon one another, they should
resemble a vase and be located just posterior to the posterior aspect of the maxillary sinus (Fig. 40–4 (Figure Not
Available) A). The needle is inserted under the zygoma and anterior to the ramus of the mandible. A curved, blunt-
tip needle is less traumatic to the underlying structures than a sharp needle. When a blunt needle is used, a 1.25-inch
angiocatheter needs to be inserted first. The needle is directed medial, cephalad, and slightly posterior toward the
pterygopalatine fossa (see Fig. 40–4 (Figure Not Available) B). An anteroposterior view is obtained to confirm the
direction and location of the needle (see Fig. 40–4 (Figure Not Available) C). The tip of the needle should be
advanced until it is adjacent to the lateral nasal mucosa. If resistance is felt at any time, the procedure should be
stopped and the needle redirected. One needs to be careful not to advance the needle through the lateral nasal
974
mucosa. If a stimulating needle is used, sensory stimulation is performed on a I–V scale at 75 pulses per second and
at a 0.25 to 0.5 millisecond pulse width. A paresthesia should be elicited at 0.5 to 0.7 V. When correctly situated
[18]
on the ganglion, the paresthesia should be felt at the root of the nose. If the paresthesia is felt in the upper teeth, the
maxillary branch of the trigeminal nerve is being stimulated, and the needle needs to be redirected in a more caudal
and medial direction. Stimulation of the greater and lesser palatine nerves results in paresthesias of the hard palate.
In this case, the needle is anterior and lateral, and should be redirected in a more posterior and medial direction.
Once properly placed, 1 to 2 mL of local anesthetic with or without steroid is injected. If pain
Figure 40-4 (Figure Not Available) A, Lateral radiographic view of a 20-gauge curved, blunt needle in the pterygopalatine fossa. B,
Anteroposterior view of the needle at the level of the middle turbinate. The tip is adjacent to the palatine bone. (Reprinted by permission of
Blackwell Science, Inc.)
relief is obtained, RFTC or EMF pulsed radiofrequency lesioning can be planned.
TECHNIQUE FOUR: RADIOFREQUENCY THERMOCOAGULATION AND ELECTROMAGNETIC FIELD PULSED RADIO

FREQUENCY LESIONING[18]
Lesioning of the sphenopalatine ganglion can be performed with either RFTC or EMF after a previous successful
block with local anesthetic. The needle used is an insulated 20-gauge or 22-gauge, 10-cm, curved, blunt tipped SMK
needle with a 5 to 10 mm active tip. After proper placement and stimulation as described in technique three,
radiofrequency (RF) lesioning is performed for 70 to 90 seconds at 67°C to 80°C. Two lesions are usually made.
Before lesioning, 1 to 2 mL of local anesthetic is injected. Electromagnetic field pulsed RF lesioning is performed at
42°C for 120 seconds. Two to three lesions (120 seconds) can be done without local anesthetic because the
temperature of the lesioning is barely higher than normal body temperature.
OTHER TECHNIQUES
There is a case report of the steriotactic radiologic treatment of sphenopalatine neuralgia in a patient using high-dose
radiation. After two treatments, the patient was pain free at a 2-year follow-up. No additional case reports using
[16]
this technique have been reported.
The Texas Tech Experience
At Texas Tech, we routinely employ all of the aforementioned techniques of sphenopalatine blockade except the
greater palatine foramen approach. The indications for blockade include all of those previously mentioned. Our
routine is to start with the intranasal technique, using two applicators soaked with 4% cocaine. Depending on the
efficacy of the block, we either repeat the block if the patient receives more than 1 month of relief or proceed to
RFTC or EMF if the analgesia lasts less than 1 month. If the patient is reliable and receives extended relief with the
intranasal block, we prescribe 2% to 4% lidocaine in a nasal spray and instruct the patient to inhale 2 puffs through
the ipsilateral nare as needed for headache or pain. The patient is cautioned not to use the lidocaine more than two to
three times per day to avoid local anesthetic toxicity. Occasionally, the intranasal technique is ineffective or partially
effective, which may be secondary to incorrect placement of the applicator, failure of the local anesthetic to reach
the SPG or incorrect clinical diagnosis. In such situations, we proceed with the infrazygomatic arch approach under
fluoroscopic guidance. If that is effective, we proceed to RFTC or EMF. To our knowledge, a prospective study
comparing RFTC with EMF of the SPG has not been performed, but it is warranted. We have also attempted
unsuccessful percutaneous electrical stimulation of the SPG in a patient with neuropathic pain in the mandibular
division of the trigeminal nerve.
On average, the intranasal approach has served us only as a diagnostic block, with very few patients receiving any
more than a few days to a couple of weeks of relief. After RFTC, our patients report partial to complete relief
ranging from 1 to 3 months (unpublished data, 1995 to present). EMF has been performed a handful of times, with
one patient reporting 13 days of complete pain relief but with gradual return of her facial pain over a month’s time.
Efficacy of Sphenopalatine Ganglion Blockade
Current literature on the efficacy of SPGB for various medical conditions is scant, and patient populations are rather
small. One study by Sanders and Zuurmond examined the efficacy of SPGB in 66 patients suffering from episodic
[8]
and chronic cluster headaches. All of the patients were previously treated with various types of pharmacologic or
surgical therapy, or both, without significant pain relief. The patients were divided into two groups, episodic and
chronic, with sample sizes of 56 and 10 patients, respectively. All received 3 RF lesions at 70°C for 60 seconds.
975
Thirty-four (60.7%) of 56 patients with episodic cluster headaches and 3 (30%) of 10 patients with the chronic type
received complete pain relief during a mean follow-up period of 29 months.
Salar and colleagues reported the use of percutaneous RFTC of the SPG for sphenopalatine neuralgia in seven
[14]
patients. Each received two lesions at 60°C and 65°C, respectively, for 60 seconds. One patient required repeat
lesioning, and two patients underwent two additional RF procedures. All of the patients were pain-free over a
follow-up period ranging from 6 to 34 months. One case report in the Nebraska Medical Journal reported complete
pain relief of trigeminal neuralgia over a 30-month interval in a woman who received 10 intranasal SPGBs. [6]
Prasanna and Murthy reported complete pain relief for at least 12 months in a patient suffering from herpes zoster
[12]
ophthalmicus who was treated with SPGBs for residual ear pain that was not alleviated with previous stellate
ganglion blocks. The same authors also reported immediate short-term pain relief with the intranasal blockade of the
SPG in 10 patients suffering intractable pain from cancer of the tongue and floor of the mouth. Puig and colleagues [13]
treated eight patients who were afflicted with sphenopalatine neuralgia with 88% phenol. Each patient was treated [22]
an average of 13 times. Each treatment involved two to four applications of 88% phenol on a cotton carrier via the
intranasal approach. Mean pain relief was 90%, with an average of 50% to 100%. The mean duration of analgesia
between treatments was 9.5 months.
Berger and associates examined the effects of topical anesthesia of the SPG for the relief of low back pain. Seven
[23]
out of 15 patients who received blocks with 4% lidocaine or 10% cocaine experienced an approximately 35%
decrease in their pain level based on their pre- and post-block VAS scores after 1 week. Four of the 15 patients had
continuing relief after 1 month. As stated before, low back pain is not a true indication for SPGB, but in situations
where other therapies have failed, it can be considered. Further studies are needed and eagerly awaited.
Blockade of the sphenopalatine ganglion is not a benign procedure. Infection is possible if proper aseptic technique
is not followed. Epistaxis can occur if the practitioner is not careful when placing the cotton-tipped applicators into
the nasal passageway, or if too much pressure is applied to the needle and it is pushed through the lateral nasal wall
when the infrazygomatic arch approach is used. Hematoma formation is possible if the large venous plexus
overlying the pterygopalatine fossa or the maxillary artery is punctured. The use of a curved, blunt-tipped needle can
potentially reduce the incidence of hematoma. RF lesioning of the SPG can result in hypesthesia or numbness of the
palate, maxilla, or posterior pharynx, but these effects are usually transient. One of our patients had transient
[8] [14]
numbness of the posterior pharynx for several months. Accurate needle placement via fluoroscopy and the use of
electrical stimulation can considerably decrease the incidence of hypesthesia and numbness.
Not long ago, we noted reflex bradycardia in some patients during RF and EMF lesioning of the sphenopalatine
ganglion. When the lesioning was halted, the bradycardia resolved. In a couple of patients, atropine was given to
complete the lesioning. To our knowledge, this has not been reported in the literature. A reflex resembling the
oculocardiac reflex may be the etiology. We suggest that the afferent information travels back through the vidian
nerve, geniculate ganglion, and nervus intermedius, to reach the solitary tract nucleus, which has interconnections to
the dorsal vagal nucleus. At Texas Tech, reflex bradycardia has been labeled the “Konen” reflex after the physician
[24]
who first described it.
Conclusion
Blockade of the sphenopalatine ganglion has been performed for more than 90 years. The role of the SPG in the
pathogenesis of pain still remains debatable. Indications supported by current literature include sphenopalatine and
trigeminal neuralgia, cluster and migraine headaches, and atypical facial pain. The aforementioned techniques are
effective if performed properly. The use of a curved, blunt-tipped needle under fluoroscopic guidance is highly
recommended.
REFERENCES
1. Waldman S: Sphenopalatine ganglion block—80 years later. Reg Anesth 18:274–276, 1993.
2. Sluder G: Etiology, diagnosis, prognosis and treatment of sphenopalatine neuralgia. JAMA 61:1201–1216, 1913.
3. Eagle W: Sphenopalatine neuralgia. Arch Otolaryngol 35:66–84, 1942.
4. Bonica J: Pain in the head. In Bonica J (ed): The Management of Pain, vol 1, 2nd ed. Malvern, Pa, Lippincott, 1990.
976
5. Ruskin S: Contributions to the study of the sphenopalatine ganglion. Laryngoscope 35:87–108, 1925.
6. ManahanA, Maleska M, Malone P: Sphenopalatine ganglion block relieves symptoms of trigeminal neuralgia: A case report. Nebraska Med J
81:306–309, 1996.
7. Cepero R, Miller R, Bressler K: Long-term results of sphenopalatine ganglioneurectomy for facial pain. Am J Otolaryngol 8:171–174, 1987.
8. SandersM, Zuurmond W: Efficacy of sphenopalatine ganglion blockade in 66 patients suffering from cluster headaches: A 12- to 70-month
follow-up evaluation. J Neurosurg 87:876–880, 1997.
9. Ryan R, Facer G: Sphenopalatine ganglion neuralgia and cluster headache: Comparisons, contrasts, and treatment. Headache 17:7–8, 1977.
10. Phero
J, McDonald J, Green D, Robins G: Orofacial pain and other related syndromes. In Raj P (ed): Practical Management of Pain. St. Louis,
Mosby, 1992.
11. Lebovits A, Alfred H, Lefkowitz M: Sphenopalatine ganglion block: Clinical use in the pain management clinic. Clin J Pain 6:131–136, 1990.
12. Prasanna A, Murthy P: Combined stellate ganglion and sphenopalatine ganglion block in acute herpes infection. Clin J Pain 9:135–137, 1993.
13. Prasanna A, Murthy S: Sphenopalatine ganglion block and pain of cancer. J Pain 8:125, 1993.
14. Salar G, Ori C, Iob I: Percutaneous thermocoagulation for sphenopalatine ganglion neuralgia. Acta Neurochir (Wien) 84:24–28, 1987.
15. Peterson
J, Schames J, Schames M, et al: Sphenopalatine ganglion block: A safe and easy method for the management of orofacial pain. J
Craniomandibular Pract 13:177–181, 1995.
16. Pollock B, Kondziolka D: Stereotactic radiosurgical treatment of sphenopalatine neuralgia. J Neurosurg 87:450–453, 1997.
17. Sluijter M, van Kleef M: Characteristics and mode of action of radiofrequency lesioning. Curr Rev Pain 2:143–150, 1998.
18. Raj P, Rauck R, Racz G: Autonomic nerve blocks. In Raj P (ed): Pain Medicine: A Comprehensive Review. St. Louis, Mosby, 1996.
19. Brown C: Sphenopalatine neuralgia. Aesthet Chron 9:99–100, 1997.
20. Spencer R: Technique for sphenopalatine ganglion block. Reg Anesth 22:483–484, 1997.
21. WaldmanS: Evaluation and treatment of common headache and facial pain syndromes. In Raj P (ed): Practical Management of Pain. St. Louis,
Mosby, 1992.
22. Puig C, Driscoll C, Kern E: Sluder’s sphenopalatine ganglion neuralgia—treatment with 88% phenol. Am J Rhinol 12:113–118, 1998.
23. Berger
J, Pyles S, Saga-Rumley S: Does topical anesthesia of the sphenopalatine ganglion with cocaine or lidocaine relieve low back pain?
Anesth Analg 65:700–702, 1986.
24. Konen A: Unexpected effects due to radiofrequency thermocoagulation of the sphenopalatine ganglion: Two case reports. Pain Digest 10:30–
33, 2000.
977
Section V Chapter 41 - Trigeminal Ganglion Procedures
Chapter 41 - Trigeminal Ganglion Procedures
Gabor B. Racz
Serdar Erdine
The trigeminal ganglion, which is an intercranial structure located just proximal and lateral to the foramen ovale, has
three branches: ophthalmic, maxillary, and mandibular. These are primarily sensory branches, except for the third
division.
This third division, the mandibular branch, exits through the foramen ovale and has motor branches that are
involved in mastication. The procedures that anesthesiologists are involved in center around the different target sites
that lend themselves to various levels of complexity. The subcutaneous infiltration of the three terminal branches as
they exit through the bony foramina is rather simple. This approach can be effective during infiltration-type
procedures for superficial surgery and for some pain conditions.
The second level of procedures involves the extracranial portion of the trigeminal nerve. The optimal target site is at
the lateral pterygoid plate. Unfortunately, this procedure does not cover the ophthalmic division, which is rarely
involved, particularly in trigeminal neuralgia.
The next level of intervention consists of the procedures performed through the foramen ovale under fluoroscopic
guidance to reach the ganglion and all three divisions. Although it is possible to proceed without fluoroscopic
[1]
control, the current trend is to perform all procedures in the foramen ovale under fluoroscopic guidance. The
injection may be 1 mL or less of local anesthetic or a material with few neurodestructive properties, such as
anhydrous glycerol. The most common transforaminal procedure is radiofrequency lesioning (RF). The possibility
has been explored that use of pulsed RF might prevent loss of sensation in affected areas as well as loss of corneal
reflex. If the diagnosis is inaccurate, and if a neurodestructive procedure rather than an injection for trigeminal
neuralgia is performed for atypical facial pain, a greater level of pain may follow. The longer lasting surgical
procedures, such as microvascular decompression (Jannetta procedure), are clearly in the domain of the
neurosurgeon. Formerly destructive intracranial procedures have virtually become of historical interest only. [2]
History
The percutaneous transovale approach to the gasserian ganglion using absolute alcohol was first described by Hartel
in 1912. During the evolution of this treatment several noteworthy reports were published. RF lesioning of the
[3]
ganglion was described by Sweet in 1965. Retrogasserian glycerol injection was reported by Hakanson in 1981.
[4] [5]
Percutaneous balloon compression was performed by Mullan and Lichtor in 1978; they published their findings in
[6]
1983.[6]
Anatomy
The trigeminal nerve is the largest among the cranial nerves. Sensation in the oral mucosa, anterior and middle
cranial fossa, tooth pulp, surrounding gingiva, and periodontal membrane is maintained by the trigeminal nerve.
This nerve originates from the gasserian ganglion, which was named after a Viennese anatomist, Johann Laurentius
Gasser. The ganglion lies within the cranium, in a cave close to the apex of the petrous area of the temporal bone.
Medially, the cavernous venous sinus binds the trigeminal ganglion; superiorly, it is bounded by the inferior surface
of the temporal lobe of the brain, and posteriorly by the brainstem.
Inferiorly, the ganglion has 3 branches intracranially: the upper, ophthalmic, and maxillary divisions. The lower
division is the mandibular branch. The upper branches are sensory, whereas the mandibular division is partly a
motor branch. The ophthalmic branch is located dorsally, the maxillary branch is intermediate, and the mandibular
branch is located ventrally. These nerves and their branches provide the cutaneous and dermatomal innervation of
the head and face.
978
Patient Selection
Most trigeminal ganglion procedures that are carried out by anesthesiologists are for patients suffering from the
excruciating pain of trigeminal neuralgia. Elderly
patients who exhibit the classic signs of pretrigeminal neuralgia may respond favorably to a combination of
extracranial injections of 4 to 5 mL of a local anesthetic and a steroid mixture and in conjunction with medication.
Selected elderly patients who suffer from severe cardiopulmonary disease and are in need of minor facial surgery
are potential candidates for trigeminal ganglion blockade.
Approaches to the trigeminal ganglion by various methods aim to relieve the pain related to the trigeminal nerve. In
the past, trigeminal ganglion block was extensively used in the treatment of trigeminal neuralgia (tic douloureux).
Since the introduction of the more innovative procedure of thermogangliolysis, there is less need for trigeminal
ganglion nerve blocks, although they are still occasionally used for pre- or postoperative pain. In addition to patients
with idiopathic trigeminal neuralgia, those with secondary neuralgic pain arising from facial involvement by a
terminal cancer or patients with multiple sclerosis may also be treated with these approaches.
Technique of the Trigeminal Ganglion Block
The technique of entering the foramen ovale is the same for all approaches, as defined by Hartel. The procedure
[3]
should be performed under biplane fluoroscopic control, which facilitates the manipulation of the needle into the
foramen ovale. The external landmarks for the puncture point are as follows:
1. Should be 2 to 3 cm lateral to the commissura labialis, at the corner of the mouth ( Fig. 41–1 )
2. 3 cm anterior to the external auditory meatus
3. Beneath the medial aspect of the pupil on the lower lid
If the head is extended, the direction of the needle should be nearly perpendicular to the table. From the point of
entry, the first targeted point is in the direction of the pupil, or just medial to the sclera. The second plane is aimed at
the level of the external auditory meatus. When the fluoroscopic visualization is carried out, the superior ramus of
the mandible as well as the lateral part of the maxilla should be seen. At the level of the external auditory meatus,
going from a medial to a lateral point, the oval structure can be observed. One of the main considerations is the
proximity of the oropharynx. Therefore, it is advisable to place a gloved hand inside the patient’s mouth to be sure
that the mucosa is not penetrated ( Fig. 41–2 ). Otherwise, there is a serious hazard of contamination of the
intercranial structures should the needle travel through the oral cavity.
The direction of the needle should be verified under fluoroscopy in the submental, lateral, and antero-posterior
Figure 41-1 The skin entry (A) is 2.5 to 3 cm from the corner of the mouth.
The target is at the meeting of two planes: External auditory meatus (B1)
and direction toward pupil (B2).
979
Figure 41-2 Aiming toward the pupil at the level of the external auditory meatus, the
right-hand index finger palpates to ensure that the needle remains external.
Figure 41-3 Stimulation of the mandibular branch with an insulated, curved, blunt 20-gauge radiofrequency needle (Radionics Inc).
Anteroposterior (A) and lateral (B) views.
(AP) directions. To obtain the submental view, the C-arm of the fluoroscope is first placed in the AP direction. If the
fluoroscope is oriented in the AP direction down the orbitomental line, the petrous ridge may be visualized through
the orbits. The target site in this dimension is a point approximately 9 mm to 1 cm medial to the lateral rim of the
internal auditory meatus. This point usually coincides with the medial extent of a dip that occurs in the petrous ridge.
The C-arm is then moved in a slightly lateral and oblique direction submentally to expose the foramen ovale. In
many patients, the foramen ovale is visible. When the foramen ovale has been observed, the needle is directed
toward the foramen through the entrance point. The mandibular nerve is on the lateral part of the ovale, whereas the
maxillary and ophthalmic divisions are more medial ( Fig. 41–3 ).
After the needle enters the foramen, the fluoroscope is placed laterally. The lateral image intensifier should confirm
that the needle is moved toward the direct angle produced by the clivus and the petrous ridge. The lateral view is
important to verify the depth of the needle inside Meckel’s cave. The aspiration test is mandatory. One half milliliter
of water-soluble, nonionized contrast dye helps to determine that the needle has not penetrated the dura. If the
needle is advanced further, there is a risk of entering the brain and causing complications.
980
Technique for Neurolysis of the Trigeminal Ganglion
The three neurolytic agents used are as follows:
1. Alcohol is the most spreadable agent and hence should be used with caution. A maximal amount of 1 mL
of alcohol is used in divided doses while a close watch is maintained for signs of bilateral spread.
2. Phenol is a viscous solution. Consequently, it spreads less and has more contact time with the target tissues;
6% phenol in glycerol is the most commonly used neurolytic agent. Some clinicians are now using 6% to
10% phenol in a contrast material (Omnipaque) instead.
3. Glycerol may be injected directly like other neurolytic agents, or the retrogasserian glycerol injection
technique may be used, as described in the next section.
The amount of neurolytic solution should not exceed 1 mL. Otherwise, it may spread to the brainstem and cause
severe complications.
Local Anesthetic Selection
The volume of injected substances can vary depending on the site of injection. The peripheral branches can be
infiltrated by 1 to 3 mL of local anesthetic. The pterygoid plate injection for the second and third divisions requires
4 to 5 mL, and the trigeminal ganglion intracranial injection volume depends on the size of Meckel’s cave. The size
determination can be important, especially if a neurolytic solution is used, after the needle enters through the
foramen ovale slightly medially into the cistern, where the trigeminal ganglion is located. Contrast injection by
iohexol (Omnipaque, Winthrop Pharmaceutical, New York) is used to determine volume requirements under
fluoroscopic guidance. This is because the trigeminal cistern can vary from 0.25 to 0.8 mL of volume, and should a
neurodestructive solution be injected, the volume can exceed the size of the cistern and spread back toward the
brainstem, causing serious complications. The average size of the trigeminal cistern is 0.4 mL. If glycerol is used,
the volume considerations are complicated, because anhydrous glycerol does not mix with iohexal. Once the volume
is determined, the iohexal needs to be aspirated. The precise amount of glycerol is then injected, and the patient is
maintained in an upright position for at least 2 hours. The choice of local anesthetic is governed by the diagnostic or
anesthetic requirements, because the motor blockade is usually not necessary. Furthermore, because of the rather
sensitive volume, if neurolytic solutions are injected, the procedure should be done under careful fluoroscopic
guidance, making sure distant structures are not involved. The amount of neurolytic solution should not exceed 1
mL. Otherwise, it may spread to the brainstem, where it may cause severe complications.
Technique for Retrogasserian Glycerol Injection
The patient is placed in the supine position. The needle should pierce the foramen just anterior to its geometric
center for placement in the trigeminal cistern. The needle is advanced until free flow of the cerebrospinal fluid is
observed. The patient is placed in the semi-sitting position, and the neck is then flexed. Contrast dye (Omnipaque
0.1–0.5 mL) is injected into the cistern. If the dye is not visible, or if it is diffused, the placement is incorrect, and
the needle must be repositioned. When the cistern is seen, the contrast dye is drawn back by free flow. The flow of
the dye is slower than the flow of cerebrospinal fluid. The same amount of glycerol is then injected into the cistern.
The patient is kept in the same semi-sitting position for the next 2 hours. During this injection, severe headache or
dysesthesia may be observed, and the patient should be warned of this possibility before injection. Some patients
receive immediate benefit, whereas other patients derive pain relief within the next 2 weeks.
COMPLICATIONS OF RETROGASSERIAN GLYCEROL INJECTION
Complications of retrogasserian glycerol injection are paresthesia, dysesthesia, anesthesia dolorosa, corneal
hypesthesia or anesthesia, diminished corneal reflex, keratitis, masticatory weakness, and deafness.
Radiofrequency Lesioning of the Ganglion
Several types of electrodes may be used for RF lesioning. These include the cordotomy-type electrodes, trigeminal
electrodes, the Tew curved electrode, and the Racz Finch curved (Radionics, Inc.) blunt electrode.
981
TRIAL STIMULATION
When the needle enters the foramen ovale, the patient is ready for trial stimulation. In many patients, the third
division is affected. The mandibular nerve has some motor fibers. If the nerve is stimulated at 2 Hz with 0.1 to 1.5
volts, the muscle contraction of the lower mandible is observed. This is also a method for verifying that the needle
has passed through the foramen ovale and is in the retrogasserian rootlets. If the first and second divisions are
affected, there should be no motor response.
The second stage is to seek for paresthesia to ensure proper localization. Stimulation at 50 to 100 Hz is carried out
with 0.1 to 0.5 volts. If the needle is properly positioned, there is a tingling sensation or electrical paresthesia in the
face. If this response is reached above 0.5 volts, the needle should be redirected to obtain the same response at a
lower voltage. However, it should be kept in mind that there may be residual sensory deficits from the previous
lesions and that the sensory threshold may be higher. When the electrode for localization is adjusted, it should also
be kept in mind that the gasserian ganglion and its retrogasserian rootlets lie on a plane running from a superomedial
to an inferolateral direction. If there is a motor response, it means that the needle is positioned too medially and
should be repositioned more laterally.
After the stimulation is completed, the needle should again be aspirated to verify that the needle is not inside a
vessel. If blood is aspirated, the needle should be replaced. If blood is aspirated again, the procedure should be
terminated and a second attempt made on another day. Impedance monitoring is not essential for trigeminal
lesioning, but if it is used, it should be 150 to 350 ohms for rootlets that are bathed in cerebrospinal fluid and 1000
ohms if the lesion is in a tissue.
Radiofrequency Lesioning
RF lesioning must be done under sedation while vital signs are monitored. If the needle is properly placed and
stimulation is felt at the appropriate nerve distribution, the patient is ready for lesioning. First, 0.5 mL of 0.25%
bupivacaine or 0.2% ropivacaine with 40 mg of triamcinolone acetate should be injected. One should wait at least 30
seconds before RF lesioning. RF lesioning is done at 60 degrees for 90 seconds. If the patient cannot tolerate this
stage, the lesioning should be stopped and retried after 30 seconds; or 0.5 mL of local anesthetic should be added
before RF lesioning.If more than one branch of the trigeminal nerve is affected, several lesionings should be
performed by repositioning the needle. After each repositioning, the stimulation tests should be repeated to seek for
paresthesia at the desired site. For lesioning in the first division, the corneal reflex should be monitored after each
lesion, and the procedure should be started at a lower temperature to preserve the corneal reflex. After the lesioning
is completed, the needle is removed. The patient is instructed to watch for any swelling of the face and to use ice to
decrease it. Cold towels or ice should be applied to prevent facial swelling resulting from penetration of the needle
through the cheek and the subsequent inflammatory response.
Complications
Complications are the same as those that occur with glycerol injection. Reduction or loss of facial sensation occurs
in most patients. In fact, RF lesioning is based on the premise that the patient will feel facial numbness for an
unpredictable period of time. Anesthesia dolorosa, keratitis, oculomotor paralysis, abducens palsy, or minor
masticatory weakness may be observed.
Technique for Percutaneous Balloon Compression
This procedure is performed under light general anesthesia. The patient positioning is the same as that used for RF
lesioning. The needle is introduced, as already described, through the foramen ovale. A No. 4 French Fogarty
catheter is advanced through the needle to Meckel’s cave. Injecting 1.5 to 2.0 mL of contrast solution inflates the
balloon of the catheter. The shape of the balloon inside the cave in the lateral position resembles a pear. Although
there is still no agreement on the optimal duration, the inflated balloon is left there for 60 seconds or more. During
the procedure, the vital signs should be monitored because bradycardia and hypertension may be observed.
Complications of Balloon Compression
Significant masseter weakness is a common complication, especially after the initial period. This weakness usually
disappears within the first 3 months. Hypesthesia, dysesthesia, anesthesia dolorosa, balloon failure, or hematoma on
the cheek may also be observed.
982
Analgesia and Sedation During Percutaneous Techniques
Patient comfort during percutaneous procedures should be ensured so that the patient does not feel much pain and is
alert enough to respond to the electrical stimulation. Generally, intravenous fentanyl (average dose 0.1 mg–0.16 mg),
midazolam (average dose 3.0–5.5 mg), and methohexital (average dose 51.4 mg) are used. In a study comparing
several regimens of high-dose fentanyl and midazolam combined with droperidol, patient comfort was improved
during the procedure. [7]
FOLLOW-UP
Immediate and later follow-up of the patient is very important. Some authors prefer to do the lesioning on an
outpatient basis, whereas some hospitalize the patient for a day. In some patients, there is immediate pain relief, but
by the next day or within the first week the pain may return. In such patients, lesioning may be repeated.
COMPLICATIONS
Percutaneous interventions of the trigeminal ganglion are not free of complications. The complications of
percutaneous lesioning include annoying dysesthesia and anesthesia dolorosa, loss of corneal reflex, neurolytic
keratitis, visual loss, retrobulbar hematoma, hematoma of the cheek, significant motor root deficit, carotid puncture,
meningitis, intracranial hemorrhage resulting from inadvertent intracranial placement of the electrode, and defects in
other cranial nerves caused by penetration through the wrong foramen. In selected series, Taha and Tew compared [8]
the results and complications of percutaneous techniques. The total number of patients was 6205 for radiofrequency
rhizotomy, 1217 for glycerol rhizotomy, and 759 for balloon compression. Facial numbness occurred in 98% of
patients after RF rhizotomy, in 72% after balloon compression, and in 60% after glycerol injection. Taha and Tew [8]
found that anesthesia dolorosa occurred in 1.5%, 1.8%, and 0.1%, respectively. Anesthesia dolorosa occurred at a
rate of 0.3% to 4% in RF lesioning. For glycerol injection, anesthesia dolorosa occurred in 0% to 2% of cases.
[9] [10] [11] [12]
With balloon compression, ipsilateral masticatory weakness, hypoesthesia, dysesthesia, and anesthesia
[13] [14] [15] [16]
dolorosa may occur in 3% to 5% of cases. [17] [18] [19]
Loss of Corneal Reflex
The overall incidence of corneal reflex loss of neurolytic keratitis was 0.6% to 1.8%, depending on the technique
used. Corneal anesthesia was the highest for RF rhizotomy at 7%. It was less for glycerol at 3.7%, and 1.5% for
balloon compression. It was zero for balloon compression and highest for RF lesioning. Loss of corneal reflex is not
a desirable condition, but, in some cases, because of the intolerable pain, it may be preferred.[8]
Motor Deficit
Motor deficit occurs during the lesioning of the third (mandibular) branch. The incidence is the highest (66%) with
balloon compression. RF rhizotomy has a 24% incidence and glycerol injection 1.7%. The motor deficit improves
within 1 year.
Carotid Artery Puncture
Carotid artery puncture occurs when the radiographic landmarks are not employed, and when the needle is
positioned too inferiorly and medially.
Retrobulbar Hematoma and Hematoma in the Cheek
If the needle is improperly advanced into the retrobulbar space, hematoma may develop. This is a dramatic
complication for the patient, although it is relieved by conservative methods without any sequelae. The eyeball is
pushed from the retrobulbar space and exophthalmos develops. Compression over the eye stops the bleeding, and
the hematoma subsides over the next few days. Hematoma in the cheek may develop if the needle passes through a
vessel when it is introduced. Compression over the cheek by cold pack after the needle is withdrawn may be helpful.
Infection is a main concern, and the incidence of infection from the series of Sweet was 24 cases of meningitis in
[20]
7000 patients. One of these patients died. There is a risk of oculomotor paralysis or cavernous sinus fistula. A fatal [21]
intracranial hemorrhage has been reported. Misplacement of needles into the skull base foramina can lead to
[22]
vascular damage and secondary hypertension that in turn can lead to bleeding. The most common problem with
[23]
neurodestructive procedures is altered sensation or numbness, which has been reported in 6% to 26% of patients
undergoing RF procedures.
983
The Outcome of Radiofrequency Lesioning: Comparison of Techniques
The three most popular techniques are RF rhizotomy, retrogasserian glycerol injection, and percutaneous
compression of the gasserian ganglion. All of these techniques have several advantages and disadvantages. The
advantages of RF lesioning are high pain relief rate, low relapse rate, and efficacy. The sensory deficit may lead to
anesthesia dolorosa, which is the main drawback of RF lesioning of the trigeminal nerve.
With retrogasserian glycerol injection, the main disadvantages are shorter duration of pain relief, higher recurrence
rate, and development of fibrosis at the foramen ovale. The advantages of gasserian ganglion compression include
slight sensory deficit and moderate rate of recurrence. However, gasserian ganglion compression cannot be confined
to a single branch; moreover, the gauge of the needle entering the foramen ovale is larger than those used in other
methods, which may damage the nerve.
TECHNICAL SUCCESS
The technical success rate for RF lesioning varies between 97.4% and 100% at the initial phase. The rate is 94% for
glycerol injection and 99% for balloon compression. In other studies, technical failure for glycerol injection was
reported to be as high as 15%. However, there is no general agreement on these results.
[8] [13]
INITIAL PAIN RELIEF
Initial pain relief was highest with RF lesioning at 98%. For glycerol rhizotomy, the rate varied between 72% and
96%. Balloon compression relieved pain in 89.9% to 100% of cases.
[24] [8] [24]
PAIN RECURRENCE
Evaluating pain recurrence is not easy because of the heterogeneity of the follow-up reports. The highest rate of
recurrence is 54% for glycerol rhizotomy, with a mean follow-up of 4 years. In several series, this varies between
[8]
18.5% and 72%, over a follow-up period of 3 to 72 months. RF lesioning had a recurrence rate of 20% in 9 years
and 15% in 5 years. For balloon compression, the recurrence rate was between 55% and 77.4% at 36 months. The
majority of recurrences occurred by 48 months. [24]
New Techniques
In the rare instances of atypical facial pain, placement of electrodes in the transforamen ovale for stimulation should
first be tried with a SCS Stim Cath. After a successful trial, a compressed quad-electrode with an active soft tip
[25]
steered to the appropriate segment of the facial pain, where virtually nothing else is clinically effective, can lead to
significant pain reduction ( Fig. 41–4 ). The needle used for placing the soft-tip, compressed
Figure 41-4 Foramen ovale electrode

placement (Medtronic soft-tip
compressed electrode). Anteroposterior
(A) and lateral (B) views. For treatment
of atypical facial pain.
984
quad-electrode is a curved-tip Pyles needle (Medtronic Inc, Minneapolis, MN) used under fluoroscopic guidance
( Fig. 41–5 ). Once the needle is at the foramen ovale, the electrode is passed through the foramen ovale by a curved
stylet with lateral fluoroscopic visualization as well as sensory stimulation. When the approximate area is reached,
the patient verifies that the involved division of the trigeminal nerve is covered. The technique calls for close
cooperation between the anesthesiologist, who uses brief periods of intravenous general anesthesia, and the operator
carrying out the procedure. The anchoring of the electrode is very important. We employ an anesthesiologist and a
plastic surgeon working as a team; the plastic surgeon anchors the electrode to the cheek and then subcutaneously 2
cm above the angle of the mandible
Figure 41-5 Using a curved, blunt needle through 16-gauge intravenous canula. Anteroposterior (A) and lateral (B) views.
and approximately 2 cm posterior. The second anchoring is carried out and followed by a subcutaneous loop of the
electrode posterior to the mandibular ramus to prevent pulling on the electrode during movement of the head or
during mastication. [26]
Conclusions
Procedures involving the trigeminal ganglion and its branches are occasionally carried out to facilitate surgical
procedures. However, much more frequently, the indications for these procedures are chronic, debilitating, painful
conditions. Clearly, the use of fluoroscopy and specially trained personnel can lead to a better outcome and the
reduction of potentially devastating complications. All three percutaneous techniques may be used to block the
trigeminal nerve during the treatment of neuralgic pain of the face. There are advantages and disadvantages to every
technique.
Among these techniques, RF lesioning still has the highest rate of initial pain relief, although facial numbness may
be annoying for the patient. Lesioning of the first branch is not always easy. However, using different electrodes to
approach the first branch may be helpful. The method can be repeated in case of recurrence.
Retrogasserian glycerol injection is also an effective method. Although initial pain relief and duration of pain relief
are less than with RF lesioning, this technique may easily be applied when RF facilities are absent. Partial sensory
loss may also occur with this technique. Fibrosis may develop at the entrance of the foramen ovale, and this may
complicate further injections.
Percutaneous balloon compression causes mild sensory loss in the majority of cases. However, it is not possible to
restrict compression to a single division. It is not used as frequently as the other techniques. All these techniques are
less morbid and more cost-effective than open surgical procedures. However, each technique must be applied
according to precise indications in well-equipped centers by experienced personnel.
985
REFERENCES
1. Brown DL: Trigeminal (gasserian) ganglion block. In Brown DL (ed): Atlas of Regional Anesthesia. Philadelphia, WB Saunders, 1992.
2. Apfelbaum RI: Trigeminal nerve and ganglion procedures. In North RB, Levy RM (eds): Neurosurgical Management of Pain. New York,
3. Hartel F: Die Leitunsanesthesie und injectionos behandlung des ganglion gasseriund der trigeminusstameb. Arch Klin Chir 100:193–292, 1912.
4. Sweet WH, Wepsic JG: Controlled thermocoagulation of trigeminal ganglion and rootlets for differential destruction of pain fibers. I.
Trigeminal neuralgia. J Neurosurg 40:143–156, 1974.
5. Hakanson S: Trigeminal neuralgia treated by the injection of glycerol into the trigeminal cistern. Neurosurgery 9:638–646, 1981.
6. Mullan S, Lichtor T: Percutaneous microcompression of the trigeminal ganglion for trigeminal neuralgia. J Neurosurg 59:L1007–L1012, 1983.
7. Brisman R: Analgesia and sedation during percutaneous radiofrequency electrocoagulation for trigeminal neuralgia. Neurosurgery 32:400–405,
1993.
8. Taha
JM, Tew JM: Comparison of surgical treatments for trigeminal neuralgia: Reevaluation of radiofrequency rhizotomy. Neurosurgery
38:865–871, 1966.
9. Broggi G, Franzini A, Lasio G, et al: Long term results of percutaneous retrogasserian thermorhizotomy for “essential” trigeminal neuralgia.
10. Burchiel
K, Steege T, Howe J, Loeser J: Comparison of percutaneous radiofrequency gangliolysis and microvascular decompression for the
surgical management of tic douloureux. Neurosurgery 9:111–119, 1981.
11. Fraoili
B, Esposito V, Guidetti B, et al: Treatment of trigeminal neuralgia by thermocoagulation, glycerolization and percutaneous
compression of gasserian ganglion and/or retrogasserial rootlets: Long term results and therapeutic protocol. Neurosurgery 24:239–245, 1989.
12. FujimakiT, Fukushima T, Miyazaki S: Percutaneous retrogasserian glycerol injection in the management of trigeminal neuralgia: Long term
follow-up results. J Neurosurg 73:212–216, 1990.
13. Burchiel K: Percutaneous retrogasserian glycerol rhizolysis in the management of trigeminal neuralgia. J Neurosurg 69:361–366, 1988.
14. Wilkinson H: Trigeminal nerve peripheral branch phenol/glycerol injections for tic douloureux. J Neurosurg 90:828–832, 1999.
15. NorthRB, Kidd DH, Piantadosi S, Carson BS: Percutaneous retrogasserian glycerol rhizotomy: Predictors of success and failure in treatment
of trigeminal neuralgia. J Neurosurg 72:851–856, 1990.
16. Sweet
WH, Poletti CE, Macon JB: Treatment of trigeminal neuralgia and other facial pains by retrogasserian injection of glycerol.
17. Lobato
RD, Rivas JJ, Rosario S, Lamas E: Percutaneous microcompression of the gasserian ganglion for trigeminal neuralgia. J Neurosurg
72:546–553, 1990.
18. Belber CJ, Rak RA: Balloon compression rhizolysis in the surgical management of trigeminal neuralgia. Neurosurgery 20:908–913, 1987.
19. BrownJA, McDaniel M, Weaver MT: Percutaneous trigeminal nerve compression for treatment of trigeminal neuralgia: Results in 50 patients.
20. SweetWH: Complications of treating trigeminal neuralgia: An analysis of the literature and response to questionnaire. In Rovit RL, Murali R,
Jannetta PJ (eds): Trigeminal Neuralgia. Baltimore, Williams & Wilkins, 1990, pp 251–279.
21. Sekhar LN, Heros RG, Kerber CW: Carotid-cavernous fistula following retrogasserian procedures. J Neurosurg 51:700–706, 1979.
22. Rish BL: Cerebrovascular accident after percutaneous radiofrequency thermocoagulation of the trigeminal ganglion. J Neurosurg 44:376–377,
1976.
23. Sweet WH, Poletti CE, Roberts JT: Dangerous rises in blood pressure upon heating of trigeminal rootlets: Increased bleeding time in patients
with trigeminal neuralgia. Neurosurgery 17:843–844, 1985.
24. BurchielK: Pain in Neurology and Neurosurgery: Tic Douloureux (Trigeminal Neuralgia). Pain 1996: An Updated Review: Refresher Course
Syllabus. Seattle, Wash., IASP Press, 1996, pp 41–60.
25. Tasker
R: Percutaneous retrogasserian glycerol rhizotomy. Predictors of success and failure in treatment of trigeminal neuralgia. J Neurosurg
72:851–856, 1990.
26. Steude
U: Chronic trigeminal nerve stimulation for the relief of persistent pain. In Gildenberg PL, Tasker RR (eds): Stereotactic and Functional
Neurosurgery. New York, McGraw-Hill, 1998, pp 1557–1567.
986
987
Section V Chapter 42 - Discography and Intradiscal Electrothermal Annuloplasty
Chapter 42 - Discography and Intradiscal Electrothermal

Annuloplasty
Susan R. Anderson
Brian Flanagan
Mark Kraft
Discography is the injection of water-soluble, nonionic contrast dye into a disc in an effort to relate a radiographic
image to the patient's pain. Discography may supply pertinent information to the physician that other, less-
[1] [2]
invasive modalities such as plain x-ray films, computed tomography, and magnetic resonance imaging are unable to
provide. Discography offers the advantage of a physiologic evaluation of the disc consisting of a volumetric,
manometric, radiographic, and pain-provocative challenge. [3] [4] [5]
HISTORY
In 1948, Linblom studied the effects of puncturing the intervertebral discs. Hirsch followed up this work in
[6] [7]
a clinical study and formulated the theory that ruptures or tears in the anulus would lead to pathologic
processes producing pain. He hypothesized that restoring pressure to a ruptured or degenerated disc would
reproduce the patient's pain. He used saline to pressurize the disc and procaine (Novocain) solution to
modulate the pain response generated. The initial technique had the patient lie prone and a transdural puncture
of the disc was performed. The study group consisted of 16 patients with low back pain unresolved by
conservative measures. Results showed reproduction of pain in all cases. There were no complications
[7]
reported in the study. The lasting value of the study was that disc puncture could be used to make a clinical
diagnosis of a patient's back pain. Erlacher, in 1952, described a peridural technique of disc puncture after
studying 200 intervertebral discs removed at autopsy. Five forms of herniation were identified, and the discs
were pressurized to 300 kp (1 mm Hg = 133.32 Pa = 0.13332 kPa). There were no disc ruptures or herniations
reported.[8]
Collins, in 1962, showed that in 84% of low back pain patients who had surgery, previous discograms that
were performed were accurate. He believed that discography would be an improvement on computed
tomography (CT) myelogram, because, with a normal myelogram, one cannot be assured that internal disc
disruption is absent. Holt, in 1968, refuted the value of discography as a diagnostic tool because of a 37%
[8]
false-positive rate on reproduction of pain. This idea was opposed by Simmons and
[9]
associates in 1987. This re-evaluation of Holt's work showed that irritant contrast agents and less advanced
radiologic equipment had been used. There was difficulty in performing disc puncture, the validity of the
[10]
patient population was questioned, and re-evaluation of data showed a 74% true-negative rate. Simmons and [10]
associates thought discography was best used for the diagnosis of nonprolapsing disc disease. Wiley, in [11]
1986, studied 1092 patients at 2517 disc levels. These patients had low back pain without evidence of root
irritation, localizing signs, or obvious herniation with spinal fusion. Wiley believed that the interpretation of
discography should be based on resistance to injection, amount injected, pain reaction, and radiologic
appearance. The chief value of discography was thought to be in the evaluation of patients with symptoms of
disc degeneration without herniation. [11]
In 1986, Crock advanced the theory of internal disc disruption. He described patients as having had trauma
[12]
to the disc inflicted by heavy lifting or high-speed application of force, which may have led to damage of the
disc contents. Patients with disc disruption have intractable back pain, with aggravation of discomfort and
[12]
loss of spinal motion on physical exercise. Crock showed that these patients had abnormal discograms, that
[12]
their pain was reproduced by as small a volume as 0.3 mL saline because of the hypersensitivity of the pain
fibers in the disc, and that their discographic patterns on radiographs were abnormal. [12]
Bogduk, in 1996, described the cardinal component of discography as disc stimulation. With use of
[13]
discography, a painful disc is provoked to determine whether that disc is the source of the patient's pain. This
pain typically occurs in patients with no herniation or disc bulge; therefore, the pain must come from the disc
itself. The pain of discography must exactly reproduce the patient's pain, and stimulation of the discs above
and below the painful disc must not reproduce the pain. Bogduk claimed that the cardinal lesion making the
disc painful is internal disc disruption. The characteristic lesion is a radial fissure extending to the innervated
[13]
988
outer third of the anulus fibrosus. Grade I fissures extend to the inner third, grade II to the middle third, and
grade III to the outer third. Seventy-five percent of grade III disruptions are associated with exact or similar
levels of pain reproduction, and 77% of discs with exact pain reproduction were found to have a grade III
tear. Bogduk stated that discography is only a diagnostic tool designed to obtain information about the
[13]
source of a patient's pain.
Anatomy and Pathophysiology
The intervertebral disc is composed of three structures: the anulus fibrosus, the nucleus pulposus, and the end plates.
The anulus surrounds the nucleus in a beltlike fashion, and the end plates cover the superior and inferior aspects of
the nucleus. Although the end plates do not completely cover the anulus, the collagen fibers of the most superficial
lamellae of the anulus insert directly into the bone of the vertebral body. These lamellae that join the anulus (and, [14] [15]
consequently, the end plates and nucleus) run obliquely from one vertebra to another. This arrangement, although
allowing some movement between adjacent vertebra, provides a very strong band between them. Before the [5]
degenerative changes associated with aging take place, the lamellae fully cover the vertebral bodies. Later, they are
absorbed secondarily into the bone. [15]
The anulus fibrosus is a concentric lamella of fibrocartilage made of collagen and fibroblasts that surround the
nucleus. Although the concept of the anulus is that of a complete ring or belt in any given quadrant, 40% of the
[5]
lamellae are incomplete, and in the posterolateral quadrant, some 50% are incomplete. The lamellae are thicker [15] [16]
toward the center of the disc. Similarly, they are thick in the anterior and lateral portions of the anulus. However,
[16] [17]
posteriorly, they are finer and more tightly packed. Consequently, the posterior portion of the anulus fibrosus is
thinner than the rest of the anulus. This ultimately leads to more tears posteriorly.
[17] [18] [19] [20] [5] [21]
The nucleus pulposus consists of a three-dimensional network of collagen fibers enmeshed in a mucoprotein gel that
contains various mucopolysaccharides. The water content of the nucleus pulposus diminishes with increasing
[22] [23]
age, whereas the polysaccharide complex decreases and is replaced by collagen.

[22] [23] [24] [25]
The proteoglycans of the [23] [26]
center allow for absorption and dispersion of forces. This allows the disc to act as a shock absorber for axial
[5] [27]
forces and like a semifluid ball bearing during flexion, extension, rotation, and lateral flexion of the vertebral
column. [5]
Because of the gelatinous center of the nucleus pulposus, the disc was postulated to act hydrostatically. This was [28] [29]
a reasonable assumption because of the high water content of 70% to 90%. This was proved in 1960 [22] [24] [29] [30] [31] [32] [33]
by Nachemson. However, this fluid content varies with the applied load (i.e., lumbar flexion) and represents an
[23] [29] [34]
equilibrium between the applied load, which causes fluid to be expelled from the disc, and the swelling pressure of
the hydrophilic proteoglycans, which act to retain the fluid. At equilibrium, there is no net fluid loss or gain. The
highest fluid content is thought to be present in the morning, after a long period and of rest, and the lowest fluid
content in the evening after a long period of sustained loading. This was verified in a study by Wilke and
[35] [36] [37]
associates. This study took a healthy volunteer and measured intradiscal pressure while the subject was performing
[38]
various activities of daily life. It was discovered that during sleeping intradiscal pressure increased substantially,
presumably because of rehydration of the disc. The pressure increased after 7 hours in the prone position to 240% of
its pressure at the time of going to bed. This may be the result of diurnal variation in fluid flux that in vivo findings
[38]
indicate to be approximately 20%. [38] [39]
Incorporating the hydrostatic behavior of the disc and the resultant intradiscal pressures from loading of the
vertebral spine, provocative discography with pressure measurements may lead to a more accurate diagnosis for the
physician. Nachemson pioneered measurement of the intradiscal pressures in the 1960s. These pressures [23] [29] [34]
correlate with more recent findings by Sato and colleagues, whose study measured the intradiscal pressure of 8
[40]
healthy volunteers and 28 patients with ongoing low back pain, sciatica, or both at L4 to L5. They discovered the
spinal load increased in the order of the following body positions: prone, 12.13 mm Hg; lateral, 20.13 mm Hg;
upright standing, 71.8, mm Hg; and upright sitting, 83.06 mm Hg. (Conversion factors for the studies were as [40]
follows: − 1 newton = 1.02 kPa and 0.13332 kPa = 1 mm Hg.) Other pressures noted were standing with flexion,
176.5 mm Hg; standing with extension, 79.99 mm Hg; sitting with flexion, 151 mm Hg; and sitting with extension,
98.26 mm Hg. [40]
These findings support the premise that maximal intradiscal pressure is attained by standing in flexion (176.5 mm
Hg). Another finding of this study was that the Valsalva maneuver consistently increased intradiscal pressure. This [40]
correlates well with history and physical examination findings on these patients. Pain is greater in the morning on
awakening, is increased with coughing or bowel movements, and is increased with bending forward. This
989
information then applied to pressures obtained in provocative discography. Pressures of 400 to 500 kPa (53 to 67
mm Hg) may be generated in a disc with a 3.0 mL Luer-Lok syringe and sustained by a manual injection technique
(thumb pressure). This, however, does not allow for determination of provocation of pain at low pressures, which
[41]
is thought to be the result of chemical irritation. By monitoring the pressure generated on injection with a
manometer system, the physician may more reliably determine a chemically sensitive disc versus a mechanically
sensitive disc by comparing the pressures on provocation with normal pressures obtained in the prone, sitting, and
standing positions. The physician may also observe the abnormality of the internal disc at the time a certain pressure
is applied. This may be important when the pressure from the discography injection could be transferred to an
adjacent abnormal, symptomatic disc, and thus, a positive pain response
TABLE 42-1 -- DISC VOLUMES AT VARIOUS LUMBAR LEVELS

Level Average Volume (mL) Volume Range (mL)
L2–L3 0.58 0.4–0.7
L3–L4 1.06 0.4–2.6
L4–L5 1.09 0.22–2.4
L5–S1 0.99 0.42–2.0
elicited. This approach allows the diagnostic test to be reproduced. It also provides consulting physicians with
[41]
objective data on which to base their treatment decisions. It should also be noted that intradiscal pressure is
significantly reduced according to the degree of disc degeneration as estimated by magnetic resonance imaging
(MRI). This correlates well with the volume of contrast injected. In general, disc volumes vary according to their
[40]
level ( Table 42–1 ). [41]
If a large volume of contrast can be injected, the disc has either degenerated or there is a fissure extending through
the outer wall. [41]
Each vertebral end plate is a layer of cartilage about 0.6 to 1 mm thick. The end plates cover the superior and [42] [43] [44] [45]
inferior surfaces of the nucleus pulposus. Because of the attachments of the anulus fibrosus to the end plates by the
lamellae, the end plates are strongly bound to the intervertebral disc. In contrast, the end plates are only weakly
attached to the vertebral bodies and can be wholly torn from the vertebral bodies in certain forms of spinal
[14] [46]
trauma. Therefore, the end plate is regarded as a part of the intervertebral disc rather than as a part of the
[45] [47]
vertebral body. Over some of the surface area of the vertebral end plate (about 10%), the subchondral bone
[42] [43] [46] [48]
of the vertebral body is deficient, and pockets of the marrow cavity abut the surface of the end plate or penetrate a
short distance into it. Aside from the disc, the end plate itself may be a possible pain source. Studies have
[45] [49] [50]
indicated that it is sensitive to the mechanical irritation of a misplaced needle. Impingement of the end plate with the
discographer's needle can cause exquisite back pain. Deflection of the end plate may cause focal increases
[51] [52] [53] [54] [55]
in the intraosseous pressure of a lumbar vertebra. Increased intraosseous pressure has been implicated as a possible
cause of low back pain. A study by Heggeness and Doherty demonstrated in vitro that end plate deflection
[55] [56] [57] [58] [55]
with discography averaged 0.3 mm. This is a further implication that the end plate may be a possible pain source
with discography. [55]
Innervation of the intervertebral discs is supplied mainly—directly or indirectly—by the sympathetic nerves. The
afferent pathways of discogenic low back pain have been believed to be in the recurrent branch of spinal nerves
called the sinuvertebral nerves. This theory was first described by Luschka and commented on by Wiberg.
[59] [60] [61]
Sinuvertebral nerves have been shown to have contributions by a somatic root from a ventral ramus of a spinal nerve
and an autonomic root from a gray ramus communicans of the sympathetic chain. Nakamura and coworkers [62] [59]
studied the origin of nerves supplying the posterior portion of the discs in rats and determined that the posterior
portion was innervated by the sympathetic nerves multisegmentally and bilaterally. In regard to discogenic pain,
Nakamura and associates claim that the main afferent pathways of pain from the lower intervertebral discs are
[63]
through the L2 spinal nerve root, presumably via sympathetic afferents from the sinuvertebral nerves. Therefore,
discogenic pain may be regarded as a visceral pain resulting from neural pathways. This theory forms the basis for
the L2 nerve root block as a possible diagnostic test for discogenic pain. Also of note for discogenic pain is that [63]
nerve fibers that normally innervate the outer third of the anulus may extend as deeply as the middle third when
discs are injured. [64]
Unless they are injured or diseased, adult human discs are avascular. The intervertebral disc is supplied with blood
vessels at its peripheral margins only. For nutrition, intervertebral discs depend on diffusion. This diffusion
[5] [21] [49]
takes place from the two closest available systems of vessels: those in the outer anulus and the capillary plexuses
beneath the vertebral end plates. [65]
990
In 1979, Brodsky and Binder performed a literature review to determine the mechanism for the provocation of pain
[51]
with discography. Their findings included (1) information on stretching the fibers of an abnormal anulus; (2)
extravasation of extradurally irritating substances such as glycosaminoglycans, lactic acid, and acidic media; (3)
pressure on nerves posteriorly caused by bulging of the anulus; (4) hyperflexion of posterior joints on disc
injection ; and (5) the presence of vascular granulation tissue, with pain caused by scar distention. Another
[11] [55]
possibility, as discussed earlier, is the presence of pain generators in the end plates that may be provoked by end-
plate deflection.[55]
Although herniated discs, degenerated discs, and bulging discs are easily recognizable pain generators on CT or
MRI, there may be an undetected pathologic process that is responsible for chronic low back pain. Internal disc
disruption (IDD) is a condition in which the internal architecture of the disc is disturbed, even though the external
appearance remains essentially normal. The clinical features of this condition are protean in nature. Pain and [12]
guarded movements are the cardinal features. Otherwise, the condition is characterized by essentially normal
[66]
radiology and CT images. Discography is the definitive test for this diagnosis. [67]
Indications
Discography has been used as a diagnostic tool to aid in the diagnosis of low back pain. Discography is used
routinely before surgical intervention for a ruptured disc and as a confirmatory procedure before spinal fusion. It is [68]
best used in young patients with history, physical examination, and radiologic findings consistent with discogenic
back pain. Gresham and colleagues described three groups in whom discography is beneficial. In group I patients,
[68]
discography helps to determine the feasibility of fusion at the time of disc removal, either with or without a positive
myelogram. In group II patients, discography is a diagnostic aid in helping to determine the presence or location of
disc pathology or helping to clarify any question about the actual need for surgery. In group III patients, discography
functions as an excluding diagnostic study in certain litigation compensation cases. [68]
Brodsky and Binder described their indications for discography in 1979:

[51]
1. Negative myelogram, with symptoms and signs not localized.

2. Clinical findings point to one level and the myelogram is positive at another level.
3. Spinal stenosis with single root symptoms or cases of complete block.
4. Arachnoiditis obscuring diagnostic myelographic pattern.
5. Previously operated patient with recurrent pain or failure of primary operation.
6. When fusion is contemplated, to evaluate adjacent discs. [51]
Guyer and Ohnmeiss further defined indications for discography in 1995. They affirmed that discography should
[1]
be performed only after conservative measures have failed and after noninvasive tests have not yielded sufficient
diagnostic information. Indications as stated were as follows : [1]
1. Further evaluation of demonstrably abnormal discs to help assess the extent of abnormality or for
correlation of the abnormality with the clinical symptoms.
2. Patients with persistent severe symptoms in whom other diagnostic tests have failed to confirm a suspected
disc as a source of pain.
3. Assessment of patients who have failed to respond to surgery to determine whether there is a painful
pseudarthrosis or a symptomatic disc in a posteriorly fused segment.
4. Assessment of discs before fusion to determine whether the discs adjacent to the segment are normal.
5. Assessment of minimally invasive surgery candidates to confirm a contained disc herniation or to
investigate dye distribution before chemonucleolysis.
Technique
Many reports have described midline transdural discography, whereas others have proposed an extradural, lateral
[6]
approach. McCullough and colleagues, in 1978, described lateral lumbar discography and discussed a firm, gritty
[8] [69]
sensation when the anulus was entered. The internal disc is commonly seen after discogram with CT scans.
In 1987, Matsui and associates described the use of tangential radiographic views to help make the internal disc
[70]
visible and to more clearly demonstrate the details of anular tears and herniated discs. The reported advantages were
precise demonstration of position and shape of herniated mass and topographic display of disc degradation. The
disadvantages are that x-ray adjustments need to be made for each individual because of disc migration; in addition
there are decreased image clarity and increased gonadal absorption of x-ray compared to CT discography. [70]
991
All patients who undergo discography in our center have had detailed history and physical examinations in addition
to MRI or CT myelogram studies. On MRI scans (T2-weighted images), the high-intensity zone may be seen. [71] [72]
This zone is a high-intensity signal (bright white) located in the substance of the posterior anulus fibrosus, which is
clearly dissociated from the signal produced by the nucleus pulposus. It is surrounded by the low-intensity (black)
signal of the anulus fibrosus and is brighter than the signal of the nucleus pulposus. All discogram examinations
[73] [102]
are carried out in a fluoroscopy suite with use of two-plane, image-intensification fluoroscopy. The patient's vital
signs are monitored and intravenous antibiotics (ceftriaxone, 1 g; ciprofloxacin, 400 mg, if allergic to penicillin, or
ciprofloxacin, 500 mg orally) are administered 30 minutes before the procedure. All patients also receive
intravenous sedation (midazolam and fentanyl titrated to effect). The patients are positioned prone and prepared and
draped in a sterile manner. The image is presented obliquely and the inferior end plate is flattened to help make the
disc space visible. A point is chosen at the mid-disc space and the skin is infiltrated with lidocaine, 1.5%, with a 30-
gauge (G) needle. Utilizing a two-needle technique, an 18-G angiocath is inserted in a “gun-barrel” manner. The
needle is removed and a 15-cm, 22-G needle is passed through the angiocath and into the disc. Alternatively, the
skin can be punctured with a 20-G needle and a 25-G needle passed into the disc. Needle placement is confirmed
with anteroposterior and lateral fluoroscopic views ( Figs. 42–1 and 42–2 ). Final needle position should be at the
midline, with avoidance of the end plate. With use of an in-line pressure transducer monitor and a video recording of
the patient's face, a known volume of water-soluble, nonionic contrast and cefazolin (1 mg/mL) is then injected
( Table 42–2 ). Based on the provocation of pain and the pressure at which that pain is produced, a disc is
determined to be symptomatic or not. Mechanically sensitive discs are defined as those that yield exact reproduction
of the patient's
Figure 42-1 Anteroposterior view of the placement of the spiral

needle in the disc before injection of the dye.
Figure 42-2 Lateral view of a three-level discogram. Note the

“cotton-ball” appearance of the middle disc with a posterior leak of
dye.
992
pain at 25 to 50 mm Hg. Chemically sensitive discs are defined as those that yield reproduction of the patient's pain
at less than 30 mm Hg. Pressure is increased to 1.5 times standing pressure (75 mm Hg) to a maximal pressure of
120 mm Hg and within 15 mm Hg of opening pressure. After this pressure increase, the patient is sent for CT scan
so the internal disc structure can be seen. This is an essential component of discography.
Figure 42-3 Anteroposterior view of placement of the navigable

catheter. Note that both radio-opaque “dots” are outside.
It should be performed within 2 hours of injection to ensure that the contrast has not been extravasated from the disc.
It may potentially help the surgeon with the choice of surgical approach. It is recommended that at least 5 to 7 slices
per disc be performed. If the end plate has a defect, thin cuts must be used. Axial images should be obtained to
afford the best views of the internal disc and associated disruption. [74]
Complications
Pease, [73]
in 1934, discussed pain generation in patients undergoing lumbar puncture. He thought that this was
Figure 42-4 Lateral view of placement of the catheter posteriorly,

within the disc. Note that it is centered between the end plates.
993
TABLE 42-2 -- EQUIPMENT LIST FOR LUMBAR DISCOGRAM WITH FLUOROSCOPY

Patient position: Prone
Pillow between legs
Pillow held in arms against chest
Sterile gloves: Surgical and lead
Skin preparation: Extremely sterile conditions must be used
Povidone iodine (Betadine) scrub
Patient preparation: Noninvasive blood pressure, SpO2 , electrocardiogram
IV in place
Basic set-up: 4-pack towel set
Nerve block tray
Kelly clamp (for finding landmarks under fluoroscopy)
Needles: 30-gauge (G) needle for skin wheal
Single-needle technique: 20-G needle for skin puncture
25-G spinal needle (at least 6 inch)
Two-needle technique: 18-G angiocatheter as introducer
22-G spinal needle (at least 6 inch)
Syringes: 10 mL control syringe
Medications: 1.5% lidocaine vial (20 mL)
50 mL water-soluble, nonionic contrast agent with cefazolin 1 mg/mL
in sterile, preservative-free saline
Midazolam, fentanyl for sedation
Antibiotic ointment to injection sites
Special equipment: Pressure measurement system
Intellisystem is recommended
due to inadvertent disc puncture. He demonstrated narrowing of the lumbar disc after introduction of a needle
intradiscally in a 2-year-old child. Pease was also concerned about the possibility of introducing organisms into the
disc space and thereby setting up the possibility of a localized infection process. [73]
De Seze and associates, in 1952, described 55 cases of patients who 12 months after discography had disc necrosis
[74]
with isolated areas of tissue degradation. In 1957, Goldie studied 122 discs removed at operation; 53 of them had
[75]
been previously studied with discography. Twenty-eight of 53 discs showed edema, rupture, and presence of hyaline
droplets, which were thought to be a reaction to contrast. [75]
In 1975, Collins reported complications in only five of more than 2000 cases of discography. These included one
[8]
infected disc space, one broken needle, one cauda equina syndrome, and one radiopaque contrast medium (Hypaque)
reaction (later determined to be a subarachnoid injection). He also reported headaches, febrile reactions, myalgias,
allergic reactions, and increased symptoms. [8]
Johnson, in 1989, described two categories of potential side effects: discitis (septic and aseptic) and disc rupture.
[76]
Goldie reported on sterile discitis in rabbits and De Seze and associates reported on discitis in humans. Johnson
[75] [74] [76]
described 34 patients undergoing serial discograms at 80 levels and found no evidence of damage to a normal disc.
He defined parameters such as type and volume of contrast medium, the gauge of the needle used, and the frequency
of anular puncture as possible causes for disc rupture. Flanagan and Chung, in 1986, reported no significant
[76] [77]
deleterious effects on the lumbar spine despite consistent disc space narrowing associated with chemonucleolysis.
In 1987, Fraser described discitis in sheep discs inoculated with bacteria. He believed that discitis is a common and
[78]
important complication that is often underestimated. This is owing to a latent period between injection and onset of
symptoms, a lack of clinical contact by the clinician performing the discogram, and a lack of awareness of
complications by the clinician. Fraser reported a 4.9% incidence of discitis without the use of prophylactic
[78]
antibiotics. In 1990, Osti and colleagues studied the incidence of discitis postdiscography after prophylaxis with
[79]
antibiotics. Antibiotics given intravenously 30 minutes before disc puncture or given intradiscally prevented
radiologic, neurologic, and histologic evidence of discitis. They proposed using a needle and a two-needle technique
994
to help decrease the incidence of discitis. An often unrecognized complication of discography is a delayed pain
response. Lehmer and associates described a 2.5% incidence of delayed pain response in individuals whose initial
[80]
discograms failed to elicit a pain response. There may be a delay of 2 to 12 hours lasting up to 2 weeks. Patients
complained of pain of a different character (in the groin, thigh, and calf), which was provoked by maneuvers to elicit
anterior spinal tenderness. It is thought that these responses represent leakage of contrast over time as well as
stimulation of the outer third of the anulus in a normal disc. Therefore, close follow-up over 24 hours is
[80]
recommended.
Outcomes
In 1990, Walsh and colleagues performed discography in 10 asymptomatic volunteers. None of the volunteers
[81]
reported significant pain at the time of injection. In 17% of discs and 50% of patients, abnormal discs were
demonstrated by CT or discography. Considering a CT or discogram positive only if significant pain and abnormal
image are present at a certain level, the study resulted in 100% specificity. [81] [82]
In cadaveric studies, Yu and associates compared discography with MRI. Discography was found to be more
[83]
sensitive than MRI in detecting anular fissures. Although MRI may seem preferable for diagnostic procedures
[82] [83]
because it is less invasive, there are studies that have identified abnormal discography in patients with normal or
equivocal MRIs. Pain provocation appears to be the invaluable factor for diagnosis. Guyer and coworkers [2] [82] [84] [85] [86]
and Osti and Fraser concluded that discography was more sensitive than MRI in identifying anular tears. They
[82] [87]
recommended that MRI be used initially but found discography to be more accurate and thus useful for patients with
normal MRI and continuing symptoms. These findings were supported in a study by Greenspan and colleagues.
[2] [82] [88]
In comparison with myelography as a diagnostic tool, Sachs and associates and Bogduk reported that CT and [89] [92]
discography provided essential diagnostic information not provided by myelography in 33% of patients. Brodsky
and Binder reported that 53% of 202 patients had negative myelograms but positive discograms, with discographic
findings confirmed in patients who later underwent surgery. [51] [82]
Conclusion
Discography is a diagnostic procedure for patients with low back pain. It is a physiologic evaluation consisting of a
volumetric, manometric, radiographic, and pain-provocative challenge. Discography may be used to identify
[16] [17]
internal disc disruption that may be amenable to treatment by a percutaneous method or to identify a painful disc
that may benefit from surgical intervention. In experienced hands and with the proper equipment, discography is a
safe, accurate, objective, and reproducible diagnostic tool. [90]
Intradiscal Electrothermal Annuloplasty
In patients diagnosed with lumbar discogenic pain by provocative discography, intradiscal electrothermal
annuloplasty (IDA) may be a reasonable treatment option. Patients with low back pain caused by intervertebral
[91]
disc disease (IDD) or a limited herniation (disc bulge) are considered potential candidates. It should be stressed that
these candidates have failed to respond to conservative therapy including medication, physical therapy, epidural
steroids, and bed rest. IDA is not indicated for patients who have back pain or radicular pain from a significant disc
[91]
herniation caused by compression of the nerve root. IDA is the percutaneous placement of a navigable thermal
[91]
catheter circumferentially around the perimeter of the anulus using radiofrequency (RF) as the energy (or heat)
source. IDA may also be referred to as IntraDiscal ElectroThermal therapy or IDET.
IDA is thought to be therapeutic in patients with an internally disrupted disc or contained disc herniation owing to
the following three mechanisms: (1) the effect of heat on nerve tissue, (2) the effect of heat on collagen, and (3) the
resulting volume reduction in the lumbar disc. It is known that in the healthy back, only the outer third of the anulus
fibrosus of the intervertebral disc is innervated. However, in diseased intervertebral discs (e.g., IDD), because of
[92]
the stimulation of nociceptive fibers in the disc, neovascularization and neural expression of substance P occurs.
These nerve fibers demonstrate ingrowth into the inner third of the anulus fibrosus and nucleus pulposus. Freemont
and associates suggested that the expression of substance P by the nerve fibers in the inner third and their
[93]
association with pain gives credence to the important role of nerve growth into the intervertebral disc in the
pathogenesis of chronic low back pain. It is known that irreversible nerve blockade occurs at 45°C. Because [94]
temperatures in the outer third of the anulus reach 46°C to 48°C, it is conceivable that the irreversible blockade of
the aberrant nerve fibers using the heat of the thermal catheter would render pain relief. Radiofrequency (RF) for [95]
the production of heat has been used in orthopedic procedures on joint capsular tissue. It is known that targeted
thermal energy in a specified therapeutic range has been shown to shrink collagen fibrils. The intervertebral [96] [97] [98]
995
disc is composed of types I and II collagen. The structure of collagen is a triple helix formation with hydrogen bonds.
These hydrogen bonds are heat sensitive. If critical temperatures are obtained (between 55°C and 65°C), the heat
sensitivity of the hydrogen bonds leads to the collapse of the molecular strands. This creates a new contracted state
called a denatured, or random, coil conformation. Studies of animal and human collagen have demonstrated
[96] [98] [99]
that collagen thickening and remodeling occurs without the development of scar tissue after treatment with this level
of heat. It is conceivable that this remodeling of collagen could lead to a tightening of the fibrous structure of
[96] [98] [99]
the anular tissue, could enhance the structural integrity of a degenerated or damaged disc, and could stabilize
fissures.
[100]
The restructuring of collagen is believed to result in a shrinkage of fibers of the anulus and disc. This is thought to
relieve pressure by decreasing the volume of the nucleus pulposus. Thus, an overall debulking of the disc occurs
while the structure is preserved. To demonstrate this point, Oratec Intervention conducted in vitro tests in the
[100]
laboratory. Nine fresh, never-frozen human cadaver lumbar discs were treated with the thermal catheter (SpineCath).
The catheter was placed in the posterior anular wall. Each disc was encased in 3 g of paraffin.
Weight and volume measurements were taken by repeated volumetric water displacement. The discs were placed [101]
in a water bath at 37°C and received a typical 15-minute thermal treatment. After the treatment, the paraffin was
removed and the discs were re-encased. New measurements were then performed. These measurements
demonstrated an average decrease in the total disc volume of 12.7% (range 10.0–16.7%). [101]
It must be noted there are some differences of opinion regarding the mechanism of the therapeutic effect. The
studies regarding the actual temperature achieved by the navigable catheter are being scrutinized. There is some
controversy as to whether the temperatures attained the range needed to remodel collagen. Further studies are
needed regarding these temperatures obtained in the disc and other structures.
Patient Selection
Candidates for IDA have had prior MRI of the lumbar spine, which is performed to assess discs, vertebral bodies,
and surrounding tissues. The images may demonstrate a high-intensity zone using the T2-weighted image that is
considered a reliable marker of painful outer anular disruption. MRI also helps to identify discitis, which is often
[102]
missed on clinical examination alone. Provocative, pressure-monitored discography is performed before IDA and
[91]
identifies the disc levels that correspond to the patient's pain.
Ideal candidates are patients with chronic low back pain and correlative findings on discography. A common
subjective finding is sitting intolerance. The discography should replicate the patient's pain at a low volume (< 1.25
cc) and demonstrate a focal anular defect. Using manometry, this would be provocation of pain at less than 25 mm
[103]
Hg for a chemically sensitive disc and less than 50 mm Hg for a mechanically sensitive disc. A disc height of 50% [41]
should be preserved. Less than this makes the procedure technically difficult.
Navigable Thermal Catheter Technique
There are many thermal delivery systems designed for irreversible neural block in the disc. RF delivered by a
percutaneous, straight needle is one such system. Benefits of RF include its safety owing to low power use and a
[104]
discrete lesion. It is cost-effective and minimally invasive. However, RF performs better in a fluid environment. The
tissue impedance of the disc results in ineffective heating. The advantage of a discrete lesion could be considered a
[105]
disadvantage because a small treatment area is created. This results in poor accessibility to pathologic tissue and few
nerves are destroyed. Finally, another limitation of RF is its insignificant decompression effect; collagen
[105]
contraction has not been demonstrated. Another delivery system uses the laser fiber, which allows significant
decompression and provides good relief of pain caused by radiculopathies. The laser fiber system also provides
moderate access to pathologic tissue. Limitations of the laser include prohibitive cost, high energy use, and lack of
[105]
temperature control leading to collagen tissue necrosis. The navigable thermal catheter technique (SpineCath from
[105]
Oratec Interventions, Inc., Menlo Park, Calif.) is a percutaneously placed catheter with a radiopaque thermal
resistive coil at the tip that allows coiling within the disc and desirable positioning against the posterior wall. This
technique provides good access to pathologic tissue. Safety is ensured by low power usage and temperature
feedback. Temperature control also allows precise treatment. The resistive coil provides a broad target zone (2-
[105]
inch heater length). Other benefits of the navigable catheter are no tissue impedance limitations as in RF, easy
[105]
placement, cost-effectiveness, and minimal invasiveness. The limitations of the catheter include a smaller
[105]
decompression effect than laser discectomy, usage limited to not purely radicular symptoms (to differentiate true
radicular symptoms from chemically induced radicular symptoms in the provocative discography), and limited
access to severely collapsed discs and post discectomy discs. Although other companies are currently developing
[105]
navigable catheter systems, the SpineCath system is the only delivery system discussed.
996
Equipment
Equipment is listed in Table 42–3 . IDA is performed under fluoroscopy with sterile preparation and drapes. The
SpineCath system from Oratec requires an intradiscal catheter, a 17-G introducer needle, an extension cable, and the
Electro Thermal Spine System with generator, foot pedal, and power cord. Other recommended supplies are similar
to those used in discography.
Technique
Before the procedure, the patient is given 1 g of intravenous ceftriaxone. The patient is placed in the prone position
on the fluoroscopy table. The lumbosacral area is prepared and draped in a sterile manner. The patient is lightly
sedated with midazolam and fentanyl. Based on the findings of Nakamura and colleagues, findings regarding the
[63]
afferent pathways of discogenic low-back pain and the infiltration of the L2 spinal nerve, a bilat
TABLE 42-3 -- EQUIPMENT * FOR INTRADISCAL ELECTROTHERMAL ANNULOPLASTY

Thermal navigable catheter (SpineCath)
17-gauge (G) needle introducer
Thermal delivery system including generator and extension cable
25-G, 1½ needle for subcutaneous infiltration
25-G, 3½ needle for infiltrating deeper tissue
18-G, ½ needle for piercing the skin
Luer-Lok syringes—10 mL, 5 mL, or 3 mL
Sterile drapes—fenestrated and C-arm drape
Povidone iodine (Betadine) and sponge sticks
Sterile towels
1.5% lidocaine plain
Antibiotics
Sedatives
*Based on recommended equipment from Oratec IDET training course.
eral L2 root sleeve (transforaminal epidural) injection is recommended before the IDA procedure. The injection is
made with local anesthetic only (no steroid) to provide postprocedural pain relief. For the placement of the
introducer needle, the proper disc level is identified under fluoroscopic view. It is important to align the inferior end
plates (bringing the superior pars “up” to the disc level) in such a way that a cephalocaudal trajectory may be
required in the lower lumbar spaces to adjust for lordosis. This trajectory may be as much as 25 degrees to 30
degrees. The fluoroscopic beam is then turned obliquely to place the spinous processes lateral, and the facet line
should appear “midline.” This may be referred to as the “Scotty dog” view. It is important to obtain the required
amount of oblique view, because less than adequate view causes a lateral placement of the needle. At the midpoint
of the superior articular process, along the lateral edge, a skin wheal is raised with 1 mL of 1.5% preservative-free
lidocaine using a 25-G needle. It is important to anesthetize not only the skin but also the subcutaneous tissues to the
level of the superior pars. Therefore, more anesthetic and a longer needle (3.5-inch, 25-G spinal needle) is required.
A nick is made over the targeted site with an 18-G needle. The 17-G introducer needle is inserted through the
opening. A “gun-barrel view” is maintained and the needle is advanced to the superior pars. It is important to make
contact with the superior pars at its most lateral aspect. This ensures that the needle is at a safe depth. The bone is
barely touched, and the trajectory of the introducer needle is not changed so as to cause lateral placement. Frequent
lateral views also provide the physician with knowledge of the needle's depth. The bevel of the introducer needle
should be facing the posterior wall of the disc as it enters the anulus. The anulus provides resistance and feels
“gritty” to the physician as the needle passes through. This is followed by a sudden loss of resistance. The needle [91]
should be placed within the nuclear cavity; this should be noted in both the anteroposterior and lateral views. Ideally,
in the lateral view, it should also be at the “equator” of the disc.
Once the introducer needle is properly placed, the navigable catheter is threaded through the needle hub. For the
SpineCath system, the curve at the tip of the catheter and the white line on the catheter handle should be aligned
with the bevel marker on the needle hub (and facing the posterior aspect of the disc). As the catheter is advanced
[106]
997
into the needle, it should be noticed when the first bold depth marker on the catheter enters the needle hub. This
indicates that the tip of the catheter has reached the tip of the introducer needle. Under continuous fluoroscopic
[106]
guidance (the lateral view is suggested), the catheter passes through the nucleus and curls inside the disc at the
interface of the nucleus and the interior anular wall. Ideal placement is in the posterior third of the disc, across the
midline of the posterior wall, and centered between the plates (the “equator”). The catheter must not be outside of
[106]
the disc wall, and when the second bold marker on the proximal shaft enters the needle, the heater end will have
completely exited the tip of the needle and entered into the disc (see Figs. 42–3 and 42–4 ). This occurrence [106]
should also be observed on the distal end by maintaining the tip and the more proximal radiopaque markers of the
resistive coil outside of the introducer needle. The physician should take care to ensure that the catheter is placed so
that it glides easily. There is some resistance with the coiling of the catheter posteriorly; however, this is not
excessive. Care must be taken not to force the catheter, or kinking will result. If the physician observes significant
resistance to movement, especially withdrawal of the catheter through the introducer needle, both the needle and the
catheter should be immediately removed together.
After proper catheter placement, the catheter is heated to 65°C. The temperature is then raised 1°C every 30 seconds
until the desired therapy level is reached. Ideally, this is between 80°C and 90°C, where it is held for 4 to 6 minutes,
to thoroughly distribute the heat. This protocol was designed for optimal patient tolerance as well as for reaching
[107]
the targeted temperatures. The total time for a therapy lasts between 14 and 17 minutes. As the temperature[107]
increases, the patient is continuously evaluated for back pain or any other signs of nerve root irritation, such as
extremity pain. It is expected that there may be reproduction of back or extremity pain concordant with the patient's
normal symptoms. It is also important to monitor the impedance. Before placement of the catheter, this should be
[107]
checked and verified that it is within the acceptable range of 120 to 200 ohms. This range should be maintained
throughout the therapy and is an indicator of a complete power circuit. [107]
Once the therapy is complete, the catheter is gently removed. This may require some rotation or “wiggling,” or both.
Intradiscal antibiotics may be administered through the needle. At Texas Tech University, 1 mL of 5 mg/mL
cefazolin is the antibiotic administered prophylactically. After removal of the introducer needle, the site is covered
with antibiotic ointment and a bandage (Band-Aid).
Postprocedure Care
It is important to educate patients regarding an increase in their typical back pain after the procedure. This usually
subsides over the first 1 to 7 days. The patient may require supplemental pain medications during this time. If the
pain persists without tapering after the first week, an oral cortisone (Prednisone) taper may be given. It is [108]
important not to overlook complaints of back pain because they may indicate infection. Other modalities for
treatment of back pain during the first month include nonsteroidal anti-inflammatory drugs, ice, rest, and opiate
analgesics.
The patient's activities are limited for the first 6 weeks. In fact, the patient should be fitted for a lumbar corset to
wear immediately after the procedure and during the 6-week time period. The function of the corset is to limit the
activity of the patient. Although patients are limited as to sitting time (20–45 min), they are encouraged to begin
[108]
walking and to perform gentle leg stretching. The patient should be in an active physical therapy program from
weeks 6 to 12 to gradually increase activity and to learn basic lumbar stabilization exercises. It is expected that the
patient may return to full physical activity (e.g., tennis, golf, running, etc.) in 4 to 6 months. [108]
Complications
Immediate complications are related to technique. Improper placement of the introducer needle may result in trauma
to neural structures, vasculature, or retroperitoneal structures, including the kidneys. It is imperative that the
[91]
physician be experienced with fluoro-guided techniques and knowledgeable regarding the functional anatomy.
Complications from the catheter include shearing, kinking, and thermal injuries owing to improper placement.
Although patients are sedated for comfort, they must be able to communicate their experiences to their physicians so
that heating may be terminated if there are complaints of new onset of low back pain or radicular pain. Late
complications of IDA are related to infection. The physician must maintain a high index of suspicion in follow-up
[91]
for discitis, epidural abscess, and meningitis. [91]
Outcomes
In a preliminary report by Saal and Saal, 25 patients with chronic discogenic back pain were treated with IDA and
[98]
had a mean follow-up period of 7 months. Of the 25 patients, 20 (80%) reported a reduction of at least 2 points in
998
visual analogue pain scores, and 18 (72%) reported an improvement in sitting tolerance as well as reduction or
discontinuance of analgesic medication. No significant complications were reported.
In a later prospective outcome study by Saal and Saal, 62 patients were followed for a minimum of 1 year. The
[109]
mean follow-up in this study was 16 months and mean preoperative duration of symptoms was 60 months. Baseline
and follow-up outcome measures demonstrated a mean change in the VAS score of 3.0. They also demonstrated a
statistically significant clinical improvement.
Karasek and Bogduk used a case-control study to compare 35 patients treated by IDA with 17 patients treated with
[110]
a physical rehabilitation program. These 53 patients were determined to have internal disc disruption by CT
discography. At 3 months, only one control patient obtained any significant degree of relief of pain compared with
23 in the IDA treatment group. Patients treated with IDA demonstrated sustained relief from pain at 6 and 12
[110]
months. They also showed improvement in disability, reduced drug use, and a return to work rate of 53%. IDA [110]
was determined to eliminate or dramatically reduce the pain of internal disc disruption in a substantial proportion of
patients. It also appeared to be superior to conventional conservative care. [110]
The long-term consequences of intradiscal thermal treatment are currently not known. It is known that degenerative
discs have a natural history of progressive degeneration. It would appear unlikely, therefore, that the long-
[98] [111] [112]
term effect produced by thermal treatment of the disc at the temperatures recommended would harm the treated
segment beyond the known consequences of the degenerative cascade. Furthermore, the temperatures have not
[98]
been shown to cause injury to the articular cartilage chondrocytes or destruction of collagen. [96] [97] [98] [113]
The above-mentioned studies show extremely encouraging success rates with the use of IDA. These studies, as
noted by Saal and Saal, should be validated with placebo-controlled randomized trials and studies that compare
[109]
IDA with alternative treatments.
Conclusion
Intradiscal electrothermal annuloplasty is a relatively recent technique to percutaneously modify the disc in patients
with chronic discogenic low back pain. To describe it bluntly, it is using heat to irreversibly block nerves and to
attempt to seal leaky discs. It is a safe outpatient procedure with encouraging initial study results. More studies are
needed to determine proper patient selection, long-term consequences, and mechanisms of pain relief.
REFERENCES
1. Guyer RD, Ohnmeiss DD: Contemporary concepts in spine care: Lumbar discography. Spine 20:2048–2059, 1995.
2. Guyer RD, Ohnmeiss DD, Hoschschuler SH, et al: The use of CT/discography to identify recurrent disc herniation not visualized by
gadolinium-enhanced MRI. Presented at the Federation of Spine Association, Anaheim, Ca, March 1991.
3. Bernard TN Jr: Don't discard discography. Radiology 162:285, 1987.
4. Bernard TN Jr, Kirkaldy-Willis WH: Making a specific diagnosis. In Kirkaldy-Willis WH (ed): Managing Low Back Pain, 2nd ed. New York,
5. Tehranzadeh J: Discography 2000. Radiol Clin North Am 36:463–495, 1998.
6. Linblom K: Diagnostic puncture of intervertebral disks in sciatica. Acta Orthop Scand 17:231, 1948.
7. Hirsch C: An attempt to diagnose the level of a disc lesion clinically by disc puncture. Acta Orthop Scand 18:132, 1948.
8. Collins HR: An evaluation of cervical and lumbar discography. Clin Orthop Rel Research. #107, Mar–Apr 1975.
9. Holt EP: The question of lumbar discography. J Bone Joint Surg 50:4, 1968.
10. Fox L: Lumbar discography: A myelographic correlation. Acta Neurol Latinoamer 12:114–124, 1966.
11. Wiley JT et al: Lumbar discography and its clinical applications. Can J Surg 11:6, 1986.
12. Crock HV: Internal disc disruption. A challenge to disc prolapse fifty years on. Spine 11:6, 1986.
13. Bogduk N: Controversy—lumbar discography. Spine 21(3):402–404, 1996.
999
14. Inoue H: Three dimensional architecture of lumbar intervertebral discs. Spine 6:138–146, 1981.
15. BogdukN: The inter-body joint and the intervertebral discs. In Clinical Anatomy of the Lumbar Spine, 3rd ed. New York, Churchill
Livingstone, 1997, p 16.
16. Marchand F, Ahmed AM: Investigation of the laminate structure of lumbar disc anulus fibrosus. Spine 15:402–410, 1990.
17. Bogduk N: The inter-body joint and the invertebral discs. In Clinical Anatomy of the Lumbar Spine, 3rd ed. New York, Churchill Livingstone,
1997, p. 15.
18. Armstrong JR: Lumbar disc lesions, 3rd ed. Edinburgh, Churchill Livingstone, 1965, p 13.
19. Jayson MIV, Barks JS: Structural changes in the intervertebral disc. Ann Rheum Dis 32:10–15, 1973.
20. Peacock A: Observations on the prenatal development of the intervertebral disc in man. J Anat 85:260–274, 1951.
21. Moore KL: Clinically Oriented Anatomy, 3rd ed. Baltimore, Williams and Wilkins, 1992, pp 342–343.
22. Hirsch
C, Paulson S, Sylven B, Snellman O: Biophysical and physiological investigations on cartilage and other mesenchymal tissues. IV.
Characteristics of human nuclei pulposi during aging. Acta Orthop Scand 22:175, 1952.
23. Nachemson A: Measurement of intradiscal pressure. Acta Orthop Scand 28:269–289, 1959.
24. Puschel J: Der Wasserhalt normaler und degenerierter Zwischenwirbelscheiben. Beitr Z Path-Anat. Allg. Path. 84:123, 1930.
25. KeyesDC, Compere EL: The normal and pathological physiology of the nucleus pulposus of the intervertebral disc. An anatomical, clinical
and experimental study. J Bone Joint Surg 14:897, 1932.
26. Sylven B: On the biology of nucleus pulposus. Acta Orthop Scand 20:275, 1950.
27. Fabris G, Lavaroni A, Leonardi M, et al: Discography. Del Centauro Udine, Italy, European Society of Neuroradiology, 1991.
28. Virgin WJ: Experimental investigations into the physical properties of the intervertebral disc. J Bone Joint Surg 33B:607–611, 1951.
29. Nachemson AL: Disc pressure measurements. Spine 6:93–97, 1981.
30. Beard
HK, Stevens RL: Biochemical changes in the intervertebral disc. In Jayson M IV (ed): The Lumbar Spine and Backache, 2nd ed. Pitman,
London, 1980, pp 407–436.
31. Naylor A: Intervertebral disc prolapse and degeneration. The biochemical and biophysical approach. Spine 1:108–114, 1976.
32. Naylor
A, Shental R: Biochemical aspects of intervertebral discs in aging and disease. In Jayson M IV (ed): The lumbar spine and backache.
New York, Grune & Stratton, 1980, pp 317–326.
1997, p. 22.
34. Nachemson A: Lumbar intradiscal pressure. Acta Orthop Scand 43 (Suppl):1–104, 1960.
35. Adams MA, Hutton WC: The effect of posture on the fluid content of lumbar intervertebral discs. Spine 8:665–671, 1983.
36. OhshimaH, Tsuji H, Hirano N, et al: Water diffusion pathway, swelling pressure, and biomechanical properties of the intervertebral disc
during compression load. Spine 14:1234–1244, 1989.
37. Lu YM, Hutton WC, Gharpuray VM: The effect of fluid loss on the viscoelastic behavior of the lumbar intervertebral disc in compression. J
Biomech Eng 120:48–54, 1998.
38. Wilke, H-J, Neef P, Caimi M, et al: New In Vivo Measurements of Pressures in the Intervertebral Disc in Daily Life. Spine 24(8):755–762,
1999.
39. Botsford DJ, Esses SI, Ogilvie-Harris DJ: In vivo diurnal variation in intervertebral disc volume and morphology. Spine 19:935–940, 1994.
40. Sato
K, Kikuchi S, Yonezawa T: In Vivo Intradiscal pressure measurement in healthy individuals and in patients with ongoing back problems.
Spine 24: 2468–2474, 1999.
41. Rauck R. Lumbar Discography. www.wfubmc.edu/pcc/Information%2ClumbarDi scography.htm.
1997, p. 16.
43. Eyring E J: The biochemistry and physiology of the intervertebral disk. Clin Orthop 67:16–28, 1969.
1000
44. Roberts
S, Menage J, Urban PG: Biochemical and structural properties of the cartilage end-plate and its relation to the intervertebral disc.
Spine 14:166–174, 1989.
45. Saunders JB de C, Inman VT: Pathology of the intervertebral disk. Arch Surg 40:380–416, 1940.
46. CoventryMB, Ghormley RK, Kernohan JW: The intervertebral disc: Its microscopic anatomy and pathology. Part I. Anatomy, development,
and physiology. J Bone Joint Surg 27:105–112, 1945.
47. MacNab I: Backache. Baltimore, Williams and Wilkins, 1977, pp 4–7.
48. Coventry MB: Anatomy of the intervertebral disc. Clin Orthop 67:9–15, 1969.
49. Maroudas A, Nachemson A, Stockwell R, Urban J: Some factors involved in the nutrition of the intervertebral disc. J Anat 120:113–130, 1975.
1997, pp. 16, 17.
51. Brodsky AE, Binder WF: Lumbar discography. Spine 4:110–120, 1979.
52. Simmons JW, April CN, Dwyer AP, Brodsky AE: A reassessment of Holt's data on the question of lumbar discography. Clin Orthop 237:120–
124, 1988.
53. Walsh TR, Weinstein JN, Spratt KF, et al: Lumbar discography in normal subjects. J Bone Joint Surg [Am] 72A:1081–1088, 1991.
54. WordGW: Lower back pain and disorders of the intervertebral disc. In Crenshaw AH (ed): Campbell's Operative Orthopaedics. St. Louis, C V
Mosby, 1987, pp 3255–3321.
55. Heggeness MH, Doherty BJ: Discography causes end plate deflection. Spine 18:1050–1053, 1993.
56. Arnoldi CC: Intraosseous hypertension: A possible cause of low back pain? Clin Orthop 115:30–34, 1976.
57. Esses SI, Botford DJ, Kostuik JP: The role of external spinal skeletal fixation in the assessment of low back disorders. Spine 14:594–601, 1989.
58. Hanaik K, Kawai K, Itoh Y, et al: Simultaneous measurement of intraosseus and cerebrospinal fluid pressures in lumbar region. Spine 10:64–
68, 1985.
59. Nakamura S, Takahashi K, Takahashi Y, et al: Origin of nerves supplying the posterior portion of lumbar intervertebral discs in rats. Spine
21:917–924, 1996.
60. Luschka HV: Die Nerven des menschlichen Wirbelkanales. Tubingen, Germany, H. Laupp, 1850.
61. Wiberg G: Back pain in relation to the nerve supply of the intervertebral disc. Acta Orthop Scand 19:211–21, 1949.
1997, p. 138.
63. Nakamura S, Takahashi K, Takahashi Y, et al: The afferent pathways of discogenic low-back pain: Evaluation of L2 spinal nerve infiltration. J
Bone Joint Surg [Br] 78B:606–12, 1996.
64. Malinsky J: The ontogenetic development of nerve terminations in the intervertebral discs of man. Acta Anat 38:96–113, 1959.
1997, p. 152.
66. Weinstein J, Claverrie W, Gibson S: The pain of discography. Spine 13:1344–1348, 1988.
67. Schwarzer AC, Aprill CN, Derby R, et al: The prevalence and clinical features of internal disc disruption in patients with chronic low back
pain. Spine 20:1878–1883, 1995.
68. GreshamJ, Miller R: Evaluation of the lumbar spine by discography and its use in selection of proper treatment of the herniated disc syndrome.
Clin Orthop Rel Res 67:Nov–Dec, 1969.
69. McCullough JA, Waddell G: Lateral Lumbar Discography. Br J Radiol 51:1978.
70. Matsui H, Tsuji H, Itoh T, et al: Significance of tangential views in lumbar discography. Clin Orthop 221:165–171, 1987.
71. Aprill C, Bogduk N: High-intensity zone: A diagnostic sign of painful lumbar disc on magnetic resonance imaging. Br J Radiol 65:361–369,
1992.
72. Videman T, Malmivaara A, Mooney N: The value of the axial view in assessing discograms. An experimental study with cadavers. Spine
1001
12:299–304, 1987.
73. Pease, Charles N: Injuries to the vertebrae and intervertebral discs following lumbar puncture. Am J Disc Child 849–860, 1934.
74. De Seze S and Levernieux J: Les accidents de la discographie. Rev Rhum 19:1027, 1952.
75. Goldie I: Intervertebral disc changes after discography. Acta Clin Scand 113:438, 1957.
76. Johnson R: Does discography injure normal discs-analysis of recent discograms. Spine 14:4, 1989.
77. Flanagan MN, Chung BV: Roentgenographic changes in 188 patients 10–20 years after discography and chemonucleolysis. Spine 11:444–448
1986.
78. Fraser RD, Osti OL, Vernon-Roberts B: Discitis after discography. J Bone Joint Surg 69:26–35, 1987.
79. Osti OL, Fraser RD, Vernon-Roberts B: Discitis after discography. The role of prophylactic antibiotics. J Bone Joint Surg 72:271–274, 1990.
80. Lehmer SM, Dawson MH, O'Brien JP: Delayed pain response after lumbar discography. Eur Spine J 3:28–31, 1994.
81. Walsh
TR, Weinstein JN, Spratt KF, et al: Lumbar discography in normal subjects: A controlled, prospective study. J Bone Joint Surg
72A:1081–1088, 1990.
82. Guyer RD, Ohnmeiss DD: Lumbar discography. In: Contemporary Concepts in Spine Care—North American Spine Society. July 1993.
83. YuSW, Haughton VM, Sether LA, Wagner M: Comparison of MR and discography in detecting radial tears of the annulus: A post-mortem
study. Am J Neuroradiol 10:1077–1081, 1989.
84. Horton
WC, Daftari TK: Which disc as visualized by magnetic resonance imaging is actually a source of pain? A correlation between magnetic
resonance imaging and discography. Spine 17(6 Suppl):S164–171, 1992.
85. Kornberg M: Discography and magnetic resonance imaging in the diagnosis of lumbar disc disruption. Spine 14:1368–1372, 1989.
86. Zucherman J, Derby R, Hsu K, et al: Normal magnetic resonance imaging with abnormal discography. Spine 13:1355–1359, 1988.
87. Osti
OL, Fraser RD: MRI and discography of annular tears and intervertebral disc degeneration. A prospective clinical comparison. J Bone
Joint Surg 74B:431–435, 1992.
88. Greenspan A, Apmaro EG, Gorczyca DP, Montesano PX: Is there a role of discography in the era of magnetic resonance imaging? Prospective
correlation and quantitative analysis of computed tomography-discography, magnetic resonance imaging, and surgical findings. J Spinal Disord
5:26–31, 1992.
89. Sachs
BL, Vanharanta H, Spivey MA, et al: Dallas discogram description: A new classification of CT/discography in low-back disorders.
Spine 12:287–294, 1987.
90. Grubb
SA, Lipscomb HJ, Guilford WB: The relative value of lumbar roentgenograms, metrizamide myelography, and discography in the
assessment of patients with chronic low-back syndrome. Spine 12:282–286, 1987.
91. Waldman SD, Siwek SM, and Waldman KA: Intradiscal electrothermal annuloplasty. In Waldman SD (ed): Interventional Pain Management,
2nd ed. Philadelphia, WB Saunders, 2000, pp 703–706.
1997, p. 102.
93. Freemont AJ, Peacock TE, Goupille P, et al: Nerve ingrowth into diseased intervertebral disc in chronic back pain. Lancet 350:178–181, 1997.
94. Brodkey JS, Miyazaki Y, Ervin FR, Mark VH: Reversible heat lesions with radiofrequency current. J Neurosurg 21:49–53, 1964.
95. SaalJA, Saal JS: Thermal characteristics of lumbar disc: Evaluation of a novel approach to targeted intradiscal thermal therapy. Presented at
the 13th Annual Meeting of the North American Spine Society. San Francisco, California, October 28–31, 1998.
96. Hayashi
K, Thabit G, Bogdanske JJ, et al: The effect of nonablative laser energy on the ultrastructure of joint capsular collagen. Arthroscopy
12:474–481, 1996.
97. Wall MS, Deng XH, Torzilli PA, et al: Thermal modification of collagen. J Shoulder Elbow Surg 8:339–344, 1999.
98. Saal
JS, Saal JA: Management of chronic discogenic low back pain with a thermal intradiscal catheter—a preliminary report. Spine 25:382–
388, 2000.
99. Hayashi K, Thabit G, Vailas AC: The effect of nonablative laser energy on joint capsular properties: An in vitro histologic and biochemical
study using a rabbit model. Am J Sports Med 24:640–646, 1996.
1002
100. IntraDiscal ElectroThermal Therapy: Training Course Syllabus. Oratec Interventions, Inc. Menlo Park, Calif, 1999, pp 11–12.
101. IntraDiscal ElectroThermal Therapy, p. 19–20.
102. Schellhas KP, Pollei SR, Gundry CR, Heithoff KB: Lumbar Disc High-intensity Zone: Correlation of Magnetic Resonance Imaging and
Discography.
104. Troussier B, Lebus JF, Chirossel JP, et al: Percutaneous intradiscal radio-frequency thermocoagulation—A cadaveric study. Spine 20:1713–
1718, 1995.
105. IntraDiscal ElectroThermal Therapy, p. 14.
109. Saal JA and Saal JS: Intradiscal electrothermal treatment for chronic discogenic low back pain: A prospective outcome study with minimum
1-year follow-up. Spine 25:2622–2627, 2000.
110. Karasek M and Bogduk N. Twelve-Month Follow-Up of a Controlled Trial of Intradiscal Thermal Anuloplasty for Back Pain due to Internal
Disc Disruption. Spine 25(20): 2601–2607, 2000.
111. Ito S, Yamada Y, Tsuboi S. An observation of ruptured annulus fibrosis in lumbar discs. J Spinal Disord 4:462–6, 1990.
112. Osti
O, Vernon-Roberts B, Moore R, et al: Annular tears and disc degeneration in the lumbar spine: A postmortem study of 135 discs. J Bone
Joint Surg [Br] 74:678–82, 1992.
113. Naseef GS, Foster TE, Trauner K, et al: The thermal properties of bovine joint capsule: The basic science of laser and radiofrequency-induced
capsular shrinkage. Am J Sports Med 25:670–4, 1997.
1003
Section V Chapter 43 - Vertebroplasty
Chapter 43 - Vertebroplasty
Susan R. Anderson
Historical Data
Vertebroplasty is the percutaneous augmentation of a vertebral body using polymethylmethacrylate.

Polymethylmethacrylate (PMMA) was first introduced in 1970 by Charnley for orthopedic use in total hip
replacements. In 1984, Deramond and associates in France performed percutaneous bone augmentation using
[1] [2] [15]
PMMA. They placed the PMMA in the cervical vertebra of a 50-year-old woman who had a C2 vertebral
hemangioma with a long-term complaint of neck pain. The patient reported complete pain relief. The procedure was
then called “percutaneous vertebroplasty.” In 1988, Duquesnel used percutaneous vertebroplasty for treatment of
[15] [3]
compression fractures caused by osteoporosis or malignancy. In the United States, Dion introduced percutaneous
vertebroplasty at the University of Virginia in 1993 to treat compression fractures. [4] [30]
Indications ( Table 43-1 )
Vertebroplasty may be used for patients suffering from compression fractures due to osteoporosis, metatstatic
tumors, or benign tumors such as vertebral angiomas. The decision to perform this technique should be made by a
[5]
multidisciplinary team as the choice between vertebroplasty, surgery, radiation therapy, medical treatment, or a
combination of these methods. Patients with the painful osteolytic lesions of myeloma experience stabilization and
[5]
pain relief from vertebroplasty. Vertebroplasty is the best treatment for severe back pain due to vertebral collapse.
Ideally, there should be no destruction of the posterior wall of the vertebra. An absolute contraindication is epidural
involvement.
TABLE 43-1 -- INDICATIONS FOR VERTEBROPLASTY

Painful osteoporotic vertebral compression fracture
Painful malignant vertebral compression fracture (e.g., myeloma)
Painful benign or malignant infiltrative processes ± vertebral collapse (e.g., hemangioma)
Osteolytic metastasis and myeloma, conditions which usually cause patients to experience severe pain and
disability, constitute the main indications for vertebroplasty. Radiotherapy is indicated whenever pain is caused
[5]
either directly or indirectly by a malignant lesion, because such treatment affords partial or complete pain relief in
more than 90% of patients. However, patients do not begin to experience relief until 10 to 14 days after the start
[5] [6]
of therapy. More important, radiotherapy results in minimal delayed (2–4 months after the start of irradiation) bone
strengthening, which is usually more effective in patients with myeloma than in those with metastases. This delay [5] [7]
in bone reconstruction increases the risk of vertebral collapse and, consequently, of neural compression. Therefore,
vertebroplasty is performed to provide pain relief or to produce bone strengthening and vertebral stabilization when
the lesion threatens the stability of the spine. Radiotherapy may be performed in conjunction with
[5] [8] [9] [10] [11]
vertebroplasty when the latter is performed for tumoral lesions, because cement injection does not prevent tumor
growth. Radiotherapy does not interfere with the mechanical properties of bone cement and complements the
[5] [12]
action of the cement with similar but delayed effects on pain and bone strengthening. Vertebroplasty can also be [5]
performed after initial radiotherapy if the latter fails to relieve pain or in cases of local recurrence. [5] [10] [13] [14]
Vertebral hemangiomas are common benign lesions of the spine that are often asymptomatic and discovered
incidentally during radiologic evaluation. Rarely, they may be painful, and there must be a close correlation between
clinical findings and radiologic features to ensure that the patient’s pain is due to the vertebral hemangioma. In such
cases, vertebroplasty is performed to provide pain relief. The PMMA is injected for pain relief, bone strengthening,
[5]
and direct embolization of the hemangiomatous body. Vertebroplasty may be used before
[5] [12] [15] [16] [17] [18] [19]
laminectomies or excision of the epidural hemangioma (when present) in cases of aggressive vertebral hemangiomas
that result in spinal cord or nerve root compression. A combination of vertebroplasty and surgery may be preceded
[5]
by
embolization of arteries feeding the vertebral hemangioma or used in conjunction with other percutaneous
injections. [5] [12]
1004
Vertebral fractures are the most common complication of osteoporosis. Age-related osteoporotic compression
[20] [21]
fractures occur in more than 500,000 patients per year in the United States. About 15% of women in the United [22]
States older than 50 years of age will suffer one or more vertebral compression fractures related to osteoporosis. The
lifetime risk of vertebral fracture for a 50-year-old white man is 5.4%. These numbers of vertebral fractures is
increasing because of an aging population, an increase in the age-specific incidence of fractures, and the occurrence
of vertebral fracture in younger individuals with secondary osteoporosis. Not all patients make a complete and
[21] [23]
early recovery from stable fractures. About 75% of them have been found to suffer from persistent back pain
symptoms. Currently, in the United States, approximately 13% to 18% of the population, or 4.6 million white
[21] [24]
females, will be affected. It is expected that one of two white females will have an osteoporotic fracture in her
lifetime. Patients may be managed conservatively with common analgesics such as paracetamol, codeine, a
combination of both these drugs, or opiates. Nonsteroidal anti-inflammatory analgesics may control pain and
[21]
inflammation if they are tolerated by the patient. Pharmacologic management must be maximized with use of
[21]
biophosphate alendronate sodium (Fosamax), Calcitonin salmon intranasal spray (Miacalcin), or a selective estrogen
receptor modulator such as raloxifene HCL (Evista). Patients should also be followed for proper calcium
[25]
supplementation and vitamin D metabolities. Other conservative measures for treatment include bed rest, external
[26] [21]
bracing, infrared heating lamp, heating pads, ice pads, and mild, stroking massage. The goal is to relieve pain so [27]
that the patient can regain mobility as soon as possible and thus avoid a vicious circle of pain, loss of bone, and
further fractures. [28]
Contraindications ( Table 43-2 )
Lack of patient consent and coagulopathy are absolute contraindications for almost any procedure, including
vertebroplasty. Relative contraindications are extensive vertebral destruction and significant vertebral collapse (i.e. a
vertebra reduced to less than one third of its original height) may lead to a technically difficult vertebroplasty
procedure. Another relative contraindication is radiculopathy in the lower extremity. Neurologic symptoms related
[5]
to compression by the abnormal vertebral body or by tumor extension necessitate a very cautious approach because
any leakage of the PMMA could increase the compression. The presence of cortical destruction or of epidural or
[5]
foraminal stenosis can
TABLE 43-2 -- CONTRAINDICATIONS TO VERTEBROPLASTY

Absolute
Epidural involvement of the infiltrative process
Lack of patient consent
Coagulopathy
Relative
Extensive vertebral destruction
Significant vertebral collapse (<⅓ of original height)
Radiculopathy into the lower extremity
Disruption of the posterior vertebral wall
Lesions above T4
Patients who cannot lie prone
also be of concern for leakage and concerns about compression. Other relative contraindications include disruption
[5]
of the posterior vertebral wall, lesions above the T4 level, and inability to lie prone. [29]
Patient Selection
Patients most likely to benefit from vertebroplasty are those with a focal, intense, deep pain associated with plain
film evidence of a new or progressive compression fracture. This may be visible in a T2-weighted image on
[30]
magnetic resonance imaging with enhancement of the corresponding level versus a dark vertebral body that is
devoid of edema ( Fig. 43-1 ). Patients who seem to respond best include those with a single level or a few levels
[29]
for treatment, fractures of less than 2 months’ duration, or a recent worsening of the fracture and no significant
sclerosis of the fractured vertebra. It should also be determined whether the patient is able to tolerate lying prone
[29]
for 1 to 2 hours. [30]
1005
Preoperative Preparation
Before the procedure, the patient should have a history and physical examination, including a thorough neurologic
evaluation. Recent magnetic resonance imaging scans should be available, particularly a T2-weighted sagittal image
and axial views through the levels of pathology to be treated. In patients with multiple compression fractures,
vertebral bodies with enhancement demonstrate edema at these levels and have a greater likelihood of response. A [29]
coagulopathy should be ruled out with laboratory investigation of prothrombin time, partial thromboplastin time,
and platelets. Computed tomography (CT) imaging for the diameter of the pedicles to be entered is helpful. Recent
plain radiographs should be examined. Finally, the patient should sign an informed consent that lists the potential
[29]
complications of bleeding at the puncture site, bone
Figure 43-1 T2-weighted magnetic resonance image of the lumbar spine in the lateral
view. Note the enhancement (brightness) of the T12 compression fracture versus the
compression fractures that remain dark and devoid of edema (arrow).
infection or new fracture of vertebrae leading to damage to the nerve roots or spinal cord, extravasation of injectate
into the surrounding epidural or paravertebral spaces, and passage of injectate into the venous system with possible
embolization to the pulmonary vasculature or compression of neural tissue. [30]
Equipment ( Table 43-3 )
Vertebroplasty should be performed in the operating room (OR) suite, with a table that allows fluoroscopic
TABLE 43-3 -- EQUIPMENT FOR VERTEBROPLASTY

25-gauge needle for skin wheal
3-mL syringe for local anesthetic
No. 11 scalpel blade
11-gauge bone biopsy needle
Codman Cranioplastic—powdered polymer—13 mL
Sterile barium sulfate powder—5 mL (6 g)
1006
Tobramycin powder—0.6–1.2 g
Codman Cranioplastic—liquid monomer—7.5 mL
Imaging guidance
viewing of the thoracic or lumbar spine. Biplanar fluoroscopy is recommended as it provides nearly simultaneous
imaging of the stylet tip position in two planes, thus decreasing the overall procedure time. Newer models of
[30]
single-plane fluoroscopy with C-arm are able to provide adequate imaging to perform this procedure safely and may
be used for alternative imaging guidance. [29]
For the OR suite, it is critical to provide extra padding for the table. Patients suffering from osteolytic or
osteoporotic lesions are at risk for further fractures. The extra padding provides important comfort measures for a
patient trying to lie prone and can protect against rib fractures. Other materials needed include a 25-gauge (G)
needle for the skin wheal, a 3-mL syringe for infiltration with a local anesthetic, a No. 11 blade scalpel, and an 11-G
bone biopsy needle. For the PMMA, Codman Cranioplastic is recommended for its radiopaque properties. Sterile [29]
barium powder is added to the powdered Cranioplastic polymer for further opacification of the PMMA. [30]
Tobramycin powder is also added to the dry mix before adding the liquid monomer.
Technique
The patient is taken to the fluoroscopy suite and placed in the prone position on the OR table, with all pressure
points padded and standard monitoring applied. Care is taken to add extra padding to the table (e.g., two egg-crate
mattresses) because of the osteoporotic spine and the risk of rib fractures. Standard monitoring includes blood
pressure, heart rate, and pulse oximetry. Oxygen is supplied via a nasal cannula. Sedative analgesics in the form of
fentanyl, midazolam or propofol are administered. Strict sterile technique is to be followed for the procedure, with
[30]
full sterile drapes, caps, masks, and gowns for all personnel in the OR. If more than one level is being performed, a
Foley catheter is inserted into the bladder. Before the start of the procedure, a prophylactic antibiotic should be
given intravenously. Ancef, 1 g, is used at our institution and is recommended. Vancomycin may be considered as a
substitute if the patient has a penicillin allergy. [29]
The level for the procedure, already identified by physical examination and MRI, is located in the anteroposterior
fluoroscopic view. The view is then rotated to oblique to maximize the oval appearance of the pedicle. The padicle
can be identified by its “Scotty dog” appearance. It is important to “flatten out” the end plates of the vertebral bodies,
using cephalocaudad or vice versa fluoroscopic vision if necessary. This locates the pedicle well within the
[29]
vertebral body in the fluoroscopic view. It is important to oblique the fluoroscopic view enough to place the facet
joints in the middle of the vertebral body and the spinous processes
Figure 43-2 Oblique fluoroscopic image demonstrating the pedicle

in the “Scotty dog” view. Note the positioning of the needle in the
superior lateral quadrant of the pedicle.
1007
laterally. This facilitates a central placement of the needle. The target for entry is the superolateral quadrant of the
pedicle in the fluoroscopic view ( Fig. 43-2 ). After this is identified, a skin wheal is raised over the center of the
pedicle by using 1 mL of 1% lidocaine and a 25-G needle. For patient comfort, it is advised to infiltrate to the
pedicle with a 25-G or 22-G needle with the local anesthetic. [29]
A small skin incision is made with a No. 11 blade scalpel to allow insertion of a large-bore biopsy needle. An 11-G
bone biopsy needle (Cook) is inserted through the incision. It is advanced in “gun-barrel fashion” in the oblique
fluoroscopic view to monitor the direction. The anteroposterior view shows the needle shaft end-on as a circle
within the center of the pedicle ( Fig. 43-3 ). Once contact has been made with bone, insertion through the cortex of
the bone may be accomplished with a twisting motion of the needle. It is important to “set” the needle point at the
exact site of entry. In the lateral view, the needle needs to be at the upper midpoint of the pedicle so that the needle
[29]
advances in the midpoint of the pedicle. The needle should follow a path that is parallel to the superior and inferior
edges of the pedicle. The needle is advanced to the junction of the anterior and middle third of the vertebral body
( Fig. 43-4 ).
Venography may be performed at the discretion of the physician. If performed, a nonionic, water-soluble contrast
[29]
dye (e.g., Omnipaque) is recommended. Venography may be used to assess the location of paravertebral and
epidural veins. If direct communication with a vein is observed, the needle may be advanced or the communication
may be embolized with the injection of cement. If leakage is observed into the disc space, there
Figure 43-3 Anteroposterior fluoroscopic image demonstrating the

needle entering the pedicle.
may be interference that blocks the visibility of the cement. It is recommended to “wash out” the contrast with saline.
After placement of the needle, the cement is prepared for injection. Codman Cranioplastic is recommended because
of its radiopaque qualities. The amount to be mixed is based on the clinical observation of an average of 7 to 8 mL
of cement injected into a lumbar vertebral body. Thirteen mL of Codman Cranioplastic polymer (powder) are mixed
with 6 g of sterile barium sulfate in a container (approximately 18 mL). [29]
Tobramycin powder (0.6 g–1.2 g) is also added. Slowly, the liquid monomer (approximately 7.5 mL) is added to
[29]
the powder mixture. The liquid monomer is titrated until the mix takes on a “toothpaste” or “cake-glaze”
[29]
consistency. There are several delivery systems available that may be used to simplify the mixing and delivery in
addition to decreasing fumes. If these systems are not available, 1-mL syringes may be filled and used one at a time
to inject the cement into the vertebral body. The injection of the cement is followed under fluoroscopic guidance in
the lateral view ( Figs. 43-5 and 43-6 ). When the spread of the cement starts to invade the posterior third of the
vertebral body, the injection should be discontinued. The cement is 90% fixed at 1 hour.
1008
Figure 43-4 Lateral fluoroscopic view of the needle entering the

vertebral body in the middle of the pedicle and advancing to the
junction of the anterior third and posterior two thirds of the
vertebral body.
Complications
Although rare, there are potential complications with vertebroplasty. Because of the size of the biopsy needle, there
is a risk of fracture of the lamina or pedicle. A preprocedural CT scan with pedicular diameter is helpful in assessing
this risk. Owing to the vascularity of the vertebral body, there is the potential risk of pulmonary venous migration of
the cement, which would result in embolic phenomenon. It is important to monitor the spread of the cement under
[31]
direct fluoroscopy to check foraminal and/or epidural extravasation. If vertebral epidural space extravasation occurs,
there may be partial or complete paraplegia. There must be emergent operative decompression if the patient is
symptomatic. This risk is more common with destruction
Figure 43-5 Lateral fluoroscopic view demonstrating the spread

of the dye within the vertebral body. It is important to
discontinue the injection as the contrast begins to migrate to the
posterior third of the vertebral body.
of the vertebral body from malignancy. An intradiscal leak of the methylmethacrylate may occur, which is
[10]
associated with cortical fracture or osteolysis of the vertebral end plates. This does not seem to prevent pain relief.
[11]
Secondary degenerative changes may develop because of this leak, but they may not be deemed important because
of the short life expectancy in these patients. The methyl methacrylate may leak into the adjacent paravertebral
[11]
tissue because of the cortical osteolysis of the vertebral body, or it may leak into the hole produced by the needle
after its removal. This may lead to a transitory femoral neuropathy because of a leak into the psoas muscle. In
[11] [11]
1009
Figure 43-6 Anteroposterior fluoroscopic view after placement of

the polymethyl methacrylate (PMMA).
addition to extravasation, the patient may complain of transient dermatomal pain from rib fracture or mild nerve root
compression. Osteoporotic patients may fracture a rib with a vigorous cough. It is imperative to carefully pad the
[29]
OR table to minimize this complication.
Postprocedural Care
After the procedure, the patient should be monitored for 3 hours in a recovery area before being discharged. The
patient should be supine for 2 hours and then may sit. A CT through the levels (3-mm slices) is recommended for
[29]
documentation purposes. The patient is discharged with routine pain medications and a recommendation for
[29]
gradual resumption of activity. Discharge instructions for the patient should include a reminder to call the physician
for the following symptoms : [29]
1. New onset of back pain

2. Chest pain
3. Lower extremity weakness
4. Temperature higher than 100°F
In addition, at the author’s institution, the patient is given a broad-spectrum antibiotic with good cerebrospinal fluid
penetration for 7 days. Follow-up is scheduled at 1 week after the procedure.
Outcomes
In a study performed by Jensen and colleagues, 30 patients were treated with PMMA with 51 vertebral fractures.
[30]
Of these patients, 90% reported immediate pain relief. Long-term pain relief (average of 255 days of follow-up) was
reported in 80% of patients. In a study by Debussche-Depriesten and associates, PMMA was performed on 5
[32]
patients who reported the ability to ambulate within 24 to 48 hours. Weill and coworkers performed 52[10]
percutaneous vertebroplasties on 37 patients with spinal metastases. Continued improvement was seen in 73% of
patients after 6 months.
Conclusion
Vertebroplasty is a percutaneous procedure with a low complication rate that provides immediate and long-term
pain relief to patients suffering from chronic vertebral compression fracture pain. It is still important to provide
conservative methods of treatment, including narcotics, adjunctive medications, and proper medical care for patients
with osteoporosis. Vertebroplasty, however, is a minimally invasive procedure that may not only provide immediate
relief but continuous prolonged relief as well. This relief from pain may increase the patient’s daily activity level
and, in turn, help to provide a better quality of life.
1010
REFERENCES
1. Follaci FM, Charnley J: A comparison of the results of femoral head prosthesis with and without cement. Clin Orthop 62:156–161, 1969.
2. Charnley J: The reaction of bone to self-curing acrylic cement. A long-term histological study in man. J Bone Surg Br 52:340–353, 1970.
3. Bascoulergue Y, Duquesnel J, Leclercq R; Percutaneous injection of methylmethacrylate in the vertebral body for the treatment of various
diseases (abstract). Radiology 169P:372, 1988.
4. MathisJM: Percutaneous Bone Augmentation to Treat Pain Associated with Vertebral Fracture. Presented at Vertebroplasty: A Hands on
Course at the University of Maryland. Baltimore November 14, 1999.
5. Cotton A, Boutry N, Cortet B, et al: Percutaneous vertebroplasty: State of the art. Radiographics 18:311–322, 1998.
6. Sheperd S: Radiotherapy and the management of metastatic bone pain. Clin Radiol 39:547–550, 1988.
7. Gilbert
HA, Kagam AR, Nussbaum H, et al: Evaluation of radiation therapy for bone metastases: Pain relief and quality of life. AJR 129:1095–
1096, 1977.
8. Kaemmerlen P, Thiesse P, Jonas P, et al: Percutaneous injection of orthopaedic cement in metastatic vertebral lesion [letter]. N Engl J Med
321:121, 1989.
9. LaprasC, Mottolese C, Deruty R, et al: Injection percutanée de methyl-methacrylate dans le traitement de l’ostéoporose et l’ostéolyse
vertébrale grave (technique de P. Galibert). Ann Chir 43:371–376, 1989.
10. Weill A, Chiras J, Simon JM, et al: Spinal metastases: Indications for and results of percutaneous injection of acrylic surgical cement.
Radiology 199:241–247, 1996.
11. Cotton A, Dewatre F, Cortet B, et al: Percutaneous vertebroplasty for osteolytic metastases and myeloma: Effects of the percentage of lesion
filling and the leakage of methyl methacrylate at clinical follow-up. Radiology 200:525–530, 1996.
12. Cotton
A, Deramond H, Cortet B, et al: Preoperative percutaneous injection of methyl methacrylate and N-butyl cyanoacrylate in vertebral
hemangiomas. AJNR 17:137–142, 1996.
13. Deramond H, Galibert P, Depriester-Debussche C: Injections intra-occéuses percutanées dans le traitement palliatif des metastases occéuses.
Forum “Metastases et Os” 80:36–40, 1993.
14. Deramond H, Depriester C, Toussain P: Vertebroplastic et radiology interventionnelle percutanée dans les metastases osséuses: technique
indications, contre-indications. Bull Cancer Radiother 80:277–282, 1996.
15. Galibert
P, Deramond H, Rosat P, Le Gars D: Note préliminaire sur le traitement des angiomes vertébraux par vertébroplastic actylique
percutanée. Neurochirurgie 33:166–168, 1987.
16. DeramondH, Darrasson R, Galibert P: Percutaneous vertebroplasty with acrylic cement in the treatment of aggressive spinal angiomas. Rachis
1:143–153, 1989.
17. GalibertP, Deramond H: La Vertébroplastic percutanée comme traitement des angiomes vertebraux et des affections dolorigènes et
fragilisantes du rachis. Chirurgie 116:326–335, 1990.
18. Deramond H, Debussche C, Pruvo JP, Galibert P: La vertébroplastic. Feuillets de Radiol 30:262–268, 1990.
19. Laredo JD, Bellaiche L, Hubault A, Deramond H: Le traitement des hemangiomes vertébraux. L’actualité rhumatologique (expansion
scientifique). 30:332–346, 1993.
20. Kanis JA, McCloskey EV: Epidemiology of vertebral osteoporosis. Bone 13:S1–S10, 1992.
21. Rapado A. General management of vertebral fractures. Bone 18:191S–196S, 1996.
22. Melton LJ III, Kan SW, Frye MA, et al: Epidemiology of vertebral fractures in women. Am J Epidemiol 129:1000–1011, 1989.
23. Scane AC, Sutcliffe AM, Francis RM: The sequelae of vertebral compression fractures in men. Osteoporos Int 4:89–92, 1994.
24. Young MH, Wales C: Long-term consequences of stable fractures of the thoracic and lumbar vertebral bodies. J Bone Joint Surg 55B:295–300,
1973.
25. Heinemann DF: Osteoporosis: An overview of the National Osteoporosis Foundation clinical practice guide. Geriatrics 55:31–36, 2000.
26. Krane
SM, Holick ME: Metabolic bone disease. In Fauci AS, et al. (eds): Harrison’s Principles of Internal Medicine, 14th ed. New York,
McGraw-Hill, 1998, pp 2247–2259.
1011
27. Sinaki
M: Musculoskeletal rehabilitation. In Riggs BL, Melton LJ (eds): Osteoporosis: Etiology, Diagnosis, and Management, 2nd ed.
Philadelphia, Lippincott-Raven, 1995, pp 435–473.
28. Leiding
G, Minne HW, Sauer P: A study of complaints and their relation to vertebral destruction in patients with osteoporosis, Bone Miner
8:217–229, 1990.
29. Zoarski
GH: Percutaneous Methacrylate Vertebroplasty. Presented at the 17th Annual Pain Symposium at Texas Tech University Health
Sciences Center, Lubbock, Texas, June 10, 2000.
30. Jensen
ME, Evans AJ, Mathis JM, et al: Percutaneous polymethylmethacrylate vertebroplasty in the treatment of osteoporotic vertebral body
compression fractures: Technical updates. AJNR 18:1897–1904, 1997.
31. Padovani B, Kasriel O, Brunner P, Peretti-Viton P: Pulmonary embolism caused by acrylic cement. A rare complication of percutaneous
vertebroplasty. AJNR 20:375–377, 1999.
32. Debussche-Depriester C, Deramond H, Fardellone P, et al: Percutaneous vertebroplasty with acrylic cement in the treatment of osteoporotic
vertebral crush fracture syndrome. Neuroradiology 33(Suppl):149–152, 1991.
1012
Section VI Chapter 44 - Neuraxial Anesthetic Techniques
Section VI - Complications of Regional Anesthesia
Carol A. Warfield
1013
Chapter 44 - Neuraxial Anesthetic Techniques
CHRISTOPHER J. JANKOWSKI
Complications from neuraxial anesthesia have been recognized since August Bier reported the first spinal anesthetic
over 100 years ago. Fortunately, serious complications of neuraxial anesthesia remain rare but can be devastating
[1]
when they occur. As morbidity and mortality from anesthesia and surgery continue to decline, the relative
importance of these problems increases. Safe, effective practice of neuraxial anesthesia requires a detailed
knowledge of the potential complications, their incidence, and the risk factors associated with their occurrence. This
is not easy. Definitive study of the complications remains problematic. Many are so rare that it is virtually
impossible to conduct controlled, prospective studies. Thus, the bulk of the existing studies are large retrospective
surveys or case reports that provide valuable information about incidence and possible associations but do not
necessarily demonstrate causality. Further, other factors besides neuraxial anesthesia may be responsible for
postoperative neurologic complications. These include surgical trauma, improper positioning, tightly applied
dressings, and preexisting neurologic conditions such as multiple sclerosis, which may be coincidentally
exacerbated during the perioperative period. Marinacci reviewed 542 patients with postoperative neurologic
[2]
complications that were thought to be caused by spinal anesthesia. Only four cases (0.74%) were the direct result of
spinal anesthesia. In the remaining cases, although there was an association with spinal anesthesia, a causal
relationship could not be established.
This chapter examines the incidence, etiology, and risk factors associated with neuraxial regional anesthetic
techniques. Special emphasis is placed on neurologic complications given the current concern with neuraxial
anesthesia and analgesia and anticoagulation. This subject is reviewed in some detail.
Incidence
Several large-scale studies have examined the risk of serious complications after neuraxial blockade. The risk of
persistent paresthesia after spinal anesthesia is between 0% and 0.08%. The incidence of cauda equina syndrome
after all types (continuous and single dose) of nonlidocaine spinal anesthesia is approximately 1 or 2 in 10,000. [3] [4] [5]
The incidence with use of continuous lidocaine spinal anesthesia may be approximately an order of magnitude
greater (see later). The risk of persistent paresthesia after epidural anesthesia is 0% to 0.16%. Permanent lower
extremity weakness after epidural anesthesia occurs at a rate of 0.006%.
Traditionally, thoracic epidural catheters were thought to carry more risk for neurologic complications than lumbar
catheters. However, in a study of more than 4000 thoracic epidural catheters, Giebler and colleagues found only a [6]
0.2% (maximum of 0.4% at 95% confidence internal) incidence of persistent paresthesias. All paresthesias resolved
with removal of the catheter. Recently, a large-scale, prospective French survey examined the incidence of
complications after regional anesthesia. Of 103,730 cases using regional anesthetics, there were 40,640 spinal and
[7]
30,413 epidural anesthetics. The procedures were performed by experienced anesthesiologists. The incidence of
complications was higher for spinal than for epidural anesthesia (Table 44-1 (Table Not Available) ). The majority
of instances of fatal cardiac arrest could not be directly attributed to spinal anesthesia. Eighty-five percent of the
patients with neurologic deficits had complete recovery within 3 months.
The incidence of serious infectious complications is very low but may not be negligible. There are no recent data
estimating the risk of meningitis, but in a combined series of over 65,000 spinal anesthetics, there were three cases
of meningitis. The same study noted no infectious complications after epidural anesthesia. In a 1-year, prospective
[8]
survey in Demark, the incidence of spinal abscess after epidural analgesia was 1 in 1930. A large number of [9]
anesthesiology departments participated in the study, and there was a wide variation in the rates of epidural
abscesses between institutions. Furthermore, the mean catheterization time in patients who developed spinal
abscesses was 11 days. Thus, it may be difficult to extrapolate these data to all practice settings.
TABLE 44-1 -- INCIDENCE OF SEVERE COMPLICATIONS RELATED TO SPINAL AND EPIDURAL ANESTHESIA
(Not Available)
From Auroy Y, Narchi P, Messiah A, et al: Serious complications related to regional anesthesia: Results of a prospective survey in France.
1014
Mechanical Nerve Injury from Needle or Catheter Placement
Direct trauma from needle or catheter placement rarely results in significant neurologic injury. However,
paresthesias during needle placement are a risk factor for lasting neurologic complications. In two large studies
examining spinal anesthetics, one retrospective and one prospective, 67% and 63%, respectively, of persistent
paresthesias were preceded by paresthesias during needle placement. Persistent paresthesia after epidural block
[7] [10]
may occur in association with paresthesias during needle placement up to 100% of the time. There are no data to
[7]
guide the clinician in deciding whether to continue the block or to move to a different interspace should a
paresthesia occur during needle placement. [11]
Indwelling neuraxial catheters may increase the incidence of paresthesias. In one study, the rate of paresthesias with
single-dose and continuous spinal anesthetics was 13% and 30%, respectively. The presence of a catheter may
[12]
increase the risk of postoperative neurologic deficit, either through direct trauma or by causing locally high
concentrations of local anesthetics around nerve roots (see later).[10] [11] [13] [14]
NEURAXIAL BLOCKS IN ANESTHETIZED PATIENTS
The data presented in the preceding paragraphs make the performance of neuraxial block on anesthetized patients
controversial. Theoretically, this practice may increase the risk of neurologic complications because patients are not
able to respond to paresthesias occurring during needle or catheter placement or to pain during intraneural injection
of local anesthetic. Thus, many clinicians condemn this practice based on these concerns and the possible
medicolegal implications of any postoperative neurologic deficit. However, there are no adequate studies evaluating
this issue. Available information consists mainly of case reports. Because of concerns for patient comfort and
[11] [15]
cooperation, most regional anesthetics in pediatric patients are placed in children who are either anesthetized or
under heavy sedation. Therefore, data from this population may help to clarify the risk of placing blocks in
[16] [17]
anesthetized patients.
A large study by Giaufre and colleagues prospectively examined more than 24,000 pediatric regional anesthetics.
[18]
Eighty-nine percent of the blocks were performed on patients under general anesthesia, 6% on those under sedation,
and on only 5% who were fully conscious. Of these, 61.5% were neuraxial blocks. As expected, there were few
complications. However, all 23 significant complications occurred in patients receiving a neuraxial block, an
incidence of 1.5 per 1000 cases. In approximately half of the complications—4 total spinals, 6 intravascular
injections, and 2 transient paresthesias—the patients’ level of consciousness during block placement may have been
an influence.
The risk of serious complications may be low when neuraxial blocks are placed in anesthetized adults as well. Abel
and associates retrospectively reviewed 4392 consecutive cases in which epidural catheters were placed in
[19]
anesthetized patients undergoing upper abdominal or thoracic surgery. There were no neurologic complications
noted, including radicular symptoms, catheter site infections, epidural abscesses, and spinal hematomas. The 95%
confidence interval yielded a risk of serious neurologic complication as high as 0.08%. It should be noted that, with
rare exception, the catheters were placed in the lumbar region and most infusions contained only opioids. This may
have contributed to the low rate of neurologic complications.
In another study, Grady and coworkers examined the incidence of neurologic complications after transphenoidal
[20]
surgery in which spinal drainage was performed. Malleable needles or spinal catheters were placed after the patients
were anesthetized. In 478 cases, there were no neurologic complications. Based on the 95% confidence interval, the
risk of neurologic sequelae may be as high as 0.8%. Again, no potentially neurotoxic substances were administered.
The last two studies are reassuring. However, given the neurotoxicity of local anesthetics (see later) and that they
were used only in a very small proportion of cases, it is difficult to extrapolate the results of these studies to all
neuraxial blocks performed under general anesthesia. Nonetheless, the safety of neuraxial blocks in anesthetized
pediatric patients was well documented in the Giaufre study.[18] The decision to perform regional anesthetic
techniques in anesthetized patients should be carefully considered. Ideally, there should be clear benefits to be
derived from the block that clearly outweigh the potential risks of placing the block in an anesthetized patient.
Finally, anesthesiologists who are unskilled in regional anesthesia should not attempt blocks in anesthetized
patients.[11]
1015
Backache
Backache is a frequent complaint after neuraxial anesthesia. Its incidence can be as high as 45% in postpartum
patients who received epidual anesthesia. However, neuraxial anesthesia may not be the sole cause.
[21] [22]
Postanesthesia backache occurs with equal frequency after either spinal or general anesthesia. Needle trauma to
[23]
intervertebral disks is a possible but unlikely cause of postspinal backache. Another hypothesis is that relaxation of
paraspinous muscles from spinal anesthesia causes the normal lordotic lumbar curve to flatten and stretches the
associated ligaments. This abnormal stretch may result in pain. It is possible that the same mechanism is responsible
for backache after general anesthesia with muscle relaxants. [24]
Preexisting back pain may the strongest predictor of postneuraxial anesthesia back pain. Although many clinicians
[25]
believe that the use of a smaller needle reduces the incidence of back pain after neuraxial blockade, there is little in
the literature to support this theory. A number of strategies have been employed to reduce the incidence of back pain
after neuraxial block. Peng and colleagues reported that the incidence of postspinal and epidural back pain was
[26]
significantly reduced by infiltrating local anesthetics around the puncture site. Others have recommended placing
[26]
corticosteroids in the local anesthetic solution for epidural anesthesia or injecting non-steroidal antiinflammatory
agents at the needle site. Wang and associates examined the effect of the nonsteroidal anti-inflammatory
[27] [28] [29] [28]
agent, tenoxicam, on the incidence of back pain after epidural anesthesia in 1000 patients. Five hundred had local
infiltration with 4 mL of 1% lidocaine at the needle insertion site and 500 had local infiltration with the lidocaine
plus 2 mg of tenoxicam. In the lidocaine-only group, the incidence of backache 1, 2, and 3 days postoperatively was
22.8%, 17.4%, and 9.2%, respectively. In contrast, the incidence was 6.8%, 4.0%, and 1.2%, respectively, in the
tenoxicam group. These data suggest that locally injected nonsteroidal anti-inflammatory agents may be effective in
preventing postepidural backache.
Although postneuraxial block back pain is common and usually benign, clinicians must consider other, more serious
and possibly rare causes of back pain when evaluating patients with these symptoms. Causes to consider include
epidural abscess, spinal hematoma, and the syndrome of transient neurologic symptoms (see later), as well as the
inadvertent injection of an irritant. More unusual causes include dissecting aortic aneurysm, ureteral obstruction, and
vertebral osteomyelitis.[30] [31] [32] [33]
Postdural Puncture Headache
In the same report in which he described the first spinal anesthetic, August Bier provided the first description of
postdural puncture headache (PDPH) associated with spinal anesthesia (Dr. Hildebrand performed a lumbar
puncture on Dr. Bier and Dr. Bier performed a subarachnoid block on Dr. Hildebrand.) : [1]
“After performing these experiments on our own bodies, we proceeded, without feeling any symptoms, to dine and
drink wine and smoke cigars. I went to bed at 11 PM, slept the whole night, awoke the next morning hale and hearty,
and went for an hour’s walk. Towards the end of the walk, I developed a slight headache, which gradually got worse
as I went about my daily business. By 3 PM, I was looking pale and my pulse was fairly weak though regular at about
70 beats per minute. In addition, I had a feeling of very strong pressure on my skull and became very dizzy when I
stood up rapidly from my chair. All these symptoms vanished at once when I lay down flat but returned when I
stood up. Towards the evening, I was forced to take to bed and remain there for 9 days because all the
manifestations recurred as soon as I got up. I felt perfectly unaffected, but any prolonged period of reading made me
feel dizzy.
The symptoms finally resolved 9 days after the lumbar puncture. Three days later, I was able to make a fairly long
journey by rail without difficulty and was able to thoroughly enjoy an 8-day hunting holiday in the mountains.
Dr. Hildebrand, for his part, went to bed at 11 PM feeling entirely well, but was, nevertheless, unable to get to sleep
because of restlessness. At midnight, a violent headache set in that quickly became insupportable. At 1 AM he began
to vomit, and this recurred once later in the night. The next morning he felt very ill but was able, with much effort,
to perform his service duties of operating and changing dressings. In the afternoon, he was constrained to lie in bed
but got up again the next morning and worked, although he continued to feel unwell for the next 3–4 days. During
this period, his appetite was poor and headache frequently recurred.”
PDPH remains one of the most common complications of neuraxial block, with an overall incidence that may be as
high as 7%.[34] The mechanism of PDPH is commonly thought to be persistent leakage of cerebrospinal fluid (CSF)
through the dural defect at a faster rate than that of CSF production. The transdural leak leads to decreased CSF
volume and pressure. When the patient is upright, gravity causes intracranial contents to place traction on the
exquisitely innervated meninges and pain-sensitive intracranial vessels, which refer pain to the frontal region via the
trigeminal nerve, to the occiput via the glossopharyngeal and vagus nerves, and to the neck and shoulders via the
1016
upper cervical nerves.[35] Compensatory distention of the intracranial blood vessels in response to the decrease in
intracranial volume caused by the CSF leak may also be a mechanism. This hypothesis is supported clinically by the
effectiveness of caffeine as a treatment for PDPH (see later). However, some have suggested a vasospastic
mechanism.[36]
Diagnosis is based on clinical features. PDPH may occur shortly after dural puncture, but typically, onset is from
several hours to 48 hours afterward. However, there are reports of PDPH occurring up to 5 months after dural
puncture. Managed conservatively, up to 90% of PDPH resolves within 10 days. As can be assumed from the
[37]
proposed pathophysiologic mechanism, the headache is bifrontal and occipital in location and often involves the
neck and shoulders. Nuchal stiffness and pain, as well as backache, are frequently present. The severity of the pain
can range from mild to debilitating. It usually is described as dull or throbbing. The most characteristic aspect of
PDPH is that the pain is postural in nature. Patients often experience complete resolution of symptoms when supine.
Associated symptoms can occur with severe PDPH, including malaise, photophobia, nausea, vomiting, cranial nerve
palsies, and ocular, vestibular, and auditory dysfunction. Seizures rarely have been reported in association with
PDPH ; however, there are confounding variables in many of these instances, making it difficult to assign
[36] [38] [39] [40] [41]
causality. Fever and localizing neurologic signs and symptoms are not part of PDPH. Their presence suggests more
severe pathology and should prompt the clinician to search for other causes.
Subdural hematoma is rare but is the most severe complication of PDPH. The presumed mechanism is caudad
displacement of intercranial contents, which causes tearing of the bridging veins. If associated with spinal or
epidural anesthesia, subdural hematoma has a 14% mortality rate, and a significant proportion of those who survive
have persistent neurologic deficits. It should be suspected if the headache is refractory, is no longer postural, or
[42]
returns after resolving, or if there is progressive neurologic disability. Given the grave consequences of subdural
hematoma after spinal or epidural anesthesia, some argue for early treatment of PDPH with an epidural blood
patch. However, the rarity of this complication precludes adequate testing of this hypothesis.
[42]
Risk Factors
The range of reported incidences of PDPH is remarkably wide, from 0% to 85%. Clearly, study design and technical
issues (see later) play a role in this variability. However, several patient-related factors have been shown to increase
the risk of PDPH.
AGE
Numerous studies have demonstrated that age is a risk factor for PDPH. The risk appears to be minimal in
[37] [43] [44] [45] [46]
prepubescent children. The incidence of PDPH rises rapidly after about age 10 years, peaks at about age 15 years,
[47]
and decreases with age in a manner that can be modeled using logistic regression. After age 50 years, the risk is [48]
minimal.
PREGNANCY STATUS
Pregnant women have a high incidence of PDPH. Vandam and Dripps reported that the highest rate of PDPH
[37]
occurred following vaginal delivery. Lowered intra-abdominal pressure after delivery may increase CSF leak by
[37]
lowering epidural pressure. It had been thought that pushing during the second stage of labor might increase CSF
[49]
leak. However, the available data do not support this theory. Hormonal changes at the time of delivery may make
[49] [50]
the cerebral vasculature especially reactive and predispose parturients to PDPH. Whatever the mechanism, the [49]
clinician should make every effort to avoid PDPH in parturients (see later).
GENDER
Early studies suggested that female gender is an independent risk factor for PDPH. Vandam and Dripps reported [37]
the incidence of PDPH in females as twice that of males—14% versus 7%. More recent literature has tended to
support this theory. However, this hypothesis has again been called into question. Lybecker and colleagues
[51] [48]
prospectively studied 1021 patients who were given spinal anesthetics, and, after multivariate analysis, found that
female gender was not a risk factor for PDPH. Unlike many other studies, their study population included no
[48]
parturients. The authors concluded that previous studies found an increase in PDPH in females because they tended
to include young parturients, thus making the female population within the study more prone to PDPH a priori.
1017
PRIOR HISTORY OF PDPH
There appears to be a higher incidence of PDPH in patients with a prior history of this disorder.[48] The
predisposing physiologic factors for this observation have not been elucidated.
Prevention
In addition to appropriate patient selection, there are several technical factors that may lessen the likelihood of
PDPH after neuraxial block.
NEEDLE SIZE AND DESIGN
Spinal needle size and design influence the incidence of PDPH. Numerous studies address this issue. A meta-
analysis, reported in 1994, demonstrated that smaller needles lowered the incidence of PDPH compared with larger
needles; and, unless there is a large discrepancy in needle size, noncutting needles lower the risk of PDPH compared
with cutting needles. Small needles cause less trauma to the dura than larger needles and, presumably, lessen the
[34]
risk of significant CSF leakage. Likewise, noncutting needles cause less dural trauma than cutting needles and
[52]
should also lessen CSF leakage. However, small needles are more difficult to manipulate and make subarachnoid
[53]
blocks more difficult to perform. Nonetheless, small, noncutting needles are useful clinical tools. In healthy young
patients the risk of PDPH with a 27-gauge (G) Whitacre needle may be as low 0% to 1.5%, an incidence similar to
that seen with epidural blockade. Many clinicians favor epidural blockade over subarachnoid anesthesia
[54] [55] [56]
because of trepidation regarding PDPH. The above data should help to allay these concerns.
BEVEL DIRECTION
When a cutting needle is used to perform a subarachnoid block, the risk of PDPH is decreased if the bevel is
oriented so that it enters the dura parallel to the longitudinal plane of the body. In the past, it was thought that dural
[57]
fibers ran longitudinally. Thus, if the needle bevel were parallel to the fibers when piercing the dura, the fibers
would, in theory, be spread apart and not transected. With removal of the needle, the fibers would return to their
original orientation and decrease the transdural leak of CSF. Although more recent in vitro and anatomic evidence
conflicts with this theory, the clinical observation is valid.
[52] [58]
MIDLINE VERSUS PARAMEDIAN APPROACH
In theory, a paramedian approach to the subarachnoid space may decrease the risk of PDPH. The oblique angle of
entry may produce a flap valve that prevents the egress of CSF. In vitro studies support this hypothesis. Clinical [53]
data from a well-designed study do not. It seems prudent to choose an approach for subarachnoid block that
[59]
minimizes the number of passes necessary for successful entry into the subarachnoid space and avoids possible
multiple dural punctures. Clearly, the optimal approach varies based on patient factors and the skill of the
anesthesiologist.
MISCELLANEOUS ISSUES
Several authors have examined the use of caffeine for the prophylaxis of PDPH. These studies have yielded
[60] [61] [62]
conflicting results. This may be due to differences in study design. However, because caffeine withdrawal is a
common cause of postoperative headache and because prophylactic intravenous administration of caffeine lowers
the incidence of postoperative headache, it may be reasonable to consider this approach.
[63] [64]
Contrary to common teaching, bedrest after a dural puncture does not prevent PDPH. [48] [65]
Bedrest merely postpones
the development of symptoms, presumably by preventing traction on the meninges.
The use of prophylactic epidural blood patches is discussed later.
Treatment
CONSERVATIVE
1018
Conservative measures for treating PDPH include bedrest, hydration, abdominal binders, analgesics, and caffeine.
Analgesics merely provide symptomatic relief. On the other hand, the remaining modalities are directed at reversing
the pathophysiologic changes responsible for PDPH until intrinsic restorative processes stop the persistent CSF leak.
Bedrest decreases the downward traction on the intracranial contents caused by gravity and the lowered CSF
pressure. Abdominal binders increase epidural venous pressure, hydration encourages CSF production, and caffeine
constricts dilated intracranial vessels.
EPIDURAL BLOOD PATCHES
Few of the many treatments that have been suggested for PDPH are clearly beneficial.[35] Epidural blood patches
have a long history of efficacy in treating PDPH. However, the mechanism by which they provide relief is unclear.
Blood injected into the epidural space may act as a plug by sealing the dural defect as it clots. Alternatively,
increased pressure from the blood within the epidural space may stop the CSF leak. Neither of these theories
explains the nearly immediate relief that many patients experience after epidural blood patch. The explanation for
this phenomenon may be that the blood in the epidural space causes cephalad displacement of CSF, which then
relieves traction on the meninges.
An epidural blood patch is performed by identifying the epidural space with an epidural needle. Next, blood is
withdrawn aseptically from an antecubital vein. The blood is then injected slowly through the epidural needle into
the epidural space until the patient experiences lumbar discomfort or until 20 mL has entered the epidural space.
Relief follows soon thereafter.
An injectate volume of 20 mL is based on the work of Crawford, who found that 20 mL provided relief 96% of the
[66]
time, whereas 6 to 15 mL was only 70% successful. Although this was not a controlled study, it has become
common practice to use an injectate volume of 20 mL. More recently, Taivainen and associates compared epidural [67]
blood patch using 10 mL with patches using 10 to 15 mL based on height. There was no statistically significant
difference in the initial and late success rates for either group. Thus, despite common clinical practice, there is no
convincing evidence that injectate volumes greater than 10 mL are associated with better relief of PDPH than
smaller volumes.
What effect treatment with previous epidural blood patch may have on subsequent epidural anesthesia is
controversial. It has been speculated that there may be long-term fibrous organization of epidurally injected blood.
In theory, this could impede flow of local anesthetic solution in the epidural space. Early reports suggested that
[68]
prior epidural blood patch had little impact on the success of future epidural anesthesia. Later reports
[69] [70]
contradicted this. Larger, more recent studies have failed to resolve the issue. Ong and colleagues identified 29
[68] [71] [72]
parturients who had epidural anesthetics after previous epidural blood patch. They noted a 59% success rate
compared with 88% to 92% in patients with no previous epidural blood patch. This group also identified 17 patients
who had epidural anesthetics after dural puncture without epidural blood patch. In this subset of patients, epidural
analgesia was successful only 65% of the time. Hebl and colleagues identified 29 parturients and other surgical
[72] [73]
patients, who received epidural anesthesia and analgesia after epidural blood patch. This group found no difference
in the success rate of an epidural block compared with a group of controls who had not had an epidural blood patch.
The methodology in both studies is similar; thus, it is difficult to explain the discrepancy in the results of the two
studies. However, it seems reasonable not to deny the benefits of epidural anesthesia and analgesia to patients who
have had prior epidural blood patch.
Early studies suggested that epidural blood patches were 90% or more effective in treating PDPH. However, [74] [75]
these studies only examined short-term relief of symptoms. Other studies examining large needle punctures,
including those done more recently, demonstrated that epidural blood patch was only 61% to 75% effective in
providing long-term relief of symptoms. [35] [67] [76]
New Treatments
Although traditional treatments have proved very effective at alleviating PDPH, conservative measures are not
always satisfactory and epidural blood patch, although safe, is an invasive procedure with associated risks. These
include, but are not limited to, unintentional dural puncture, infection, aseptic meningitis, and arachnoiditis. Several
authors have advocated in letters to the editor the use of adrenocorticotropic hormone (ACTH) or its analogues for
PDPH. They reported success rates of 70% to 83% after the first dose, rivaling those of epidural blood patch.
[77] [78] [79] [80]
Although this technique has yet to be tested in a large-scale study, their results are intriguing. The mechanism of
action of this effect remains speculative.
1019
Approach to Treatment
The approach to treating PDPH remains controversial. Many clinicians argue in favor of conservative treatment
initially, reserving epidural blood patch for patients with severe symptoms or those whose symptoms persist beyond
some arbitrary limit. Given the low incidence of PDPH when the dural puncture is made with a small-gauge,
noncutting tip needle, it is difficult to recommend invasive prophylaxis with an epidural blood patch. If there is
unintentional dural puncture with a large epidural needle, especially in parturients or other high-risk groups, some
suggest prophylactic measures, including epidural blood patch. However, there are no compelling data supporting
[81]
or countering the practice of prophylactic blood patch after unintentional dural puncture.
Neurologic Complications
DRUG TOXICITY
Local Anesthetics
Direct local anesthetic toxicity may cause neurologic complications after neuraxial anesthesia. Clinical and
laboratory evidence support this hypothesis and demonstrate that various local anesthetics have differing degrees of
neurotoxicity. Fortunately, the incidence of postoperative neurologic deficit after spinal anesthesia is rare, ranging
between 0% and 0.7%.[4] [7] [8] [10] [82] In a large study including more than 40,000 subarachnoid blocks, 12
patients had persistent neurologic symptoms, 7 with radiculopathy and 5 with cauda equina syndrome, after
atraumatic needle placement.[7] Of these, 75% received hyperbaric 5% lidocaine. A review by Johnson,[83]
reported in 2000, estimated that the risk of persistent, lumbosacral neuropathy after single-dose or continuous
lidocaine spinal anesthetics may be 1 in 1300 and 1 in 200, respectively. This is approximately an order of
magnitude higher than the risk for other local anesthetics or general anesthesia. However, reports of cauda equina
syndrome exist in association with a variety of local anesthetics.[14] [84] [85] [86] [87]
There is ample laboratory evidence to support clinical data suggesting local anesthetic neurotoxicity. [88] [89] [90] [91] [92] [93] [94] [95]
Neurologic deficits appear more likely with higher concentrations and doses of local anesthetic, and with
[96]
prolonged exposure. Because of this, it may be prudent to limit the dose of lidocaine to 60 mg and to avoid the use
[95]
of epinephrine to prolong lidocaine spinal anesthesia. In addition, the use of 5% lidocaine with 7.5% glucose may
[97]
increase the risk of maldistribution and expose neural tissue to toxic concentrations of local anesthetic. However, [11] [97]
the presence of glucose by itself does not appear to increase the neurotoxicity of intrathecal lidocaine. In [98] [99]
clinically relevant concentrations and doses, most local anesthetics do not cause nerve damage. However, based on [100]
available evidence, one must assume that all local anesthetics can be neurotoxic, depending on the perineural
concentration and duration of exposure. [96] [101] [102] [103]
Intrathecal Analgesics
In general, opioids do not appear to cause neurotoxicity. Unfortunately, morphine is the only opiate that has been
[103]
evaluated extensively in this regard. However, wide clinical experience with other opioids suggests that there is little
risk of neurotoxicity with these agents. Clonidine is becoming more popular as a neuraxial adjuvant. Extensive
preclinical testing did not reveal significant neurotoxicity. Clinical studies support this. Lack of extensive
[103] [104] [104]
clinical experience with other intrathecal analgesics, such as midazolam, ketamine, and neostigmine, among others,
precludes comment on the possible neurotoxicity of these agents.
Transient Neurologic Symptoms
The first report of transient neurologic symptoms (TNS) after spinal anesthesia occurred in 1993. Schneider and [105]
colleagues described four patients who developed severe radicular back pain after the resolution of uneventful,
[105]
single-dose, lidocaine spinal anesthetics. All operations were performed in the lithotomy position. There were no
motor or sensory deficits and no signs of bowel or bladder dysfunction. In all patients, the symptoms resolved
within 1 week. Several other case reports followed. The etiologic mechanism of TNS is not
[106] [107] [108] [109] [110] [111] [112] [113] [114]
well defined. However, it is a clinically significant phenomenon; up to 30% of patients with TNS report severe
pain. There are several reports of symptoms so severe as to require readmission to the hospital for opioid
[115]
analgesia. [106] [107] [110] [113] [114]
The incidence of TNS is between 16% and 40% when a subarachnoid block is performed with lidocaine. [116] [117] [118]
The
incidence is lower with bupivacaine, tetracaine, and procaine. [115] [119] [120]
1020
These studies suggest that intrathecal neurotoxicity of lidocaine may play a role in the development of TNS. This
hypothesis is supported by ample laboratory evidence of lidocaine neurotoxicity. However, there is clinical
[95] [98] [99]
evidence that lidocaine is not the sole cause of TNS. Freedman and colleagues performed a multicenter [115]
epidemiologic study to determine risk factors for the development of TNS. After reviewing 1863 spinal anesthetic
cases, they found that the dose of intrathecal lidocaine did not correlate with the incidence of TNS. Furthermore,
increasing the concentration of intrathecal lidocaine while maintaining the same dose does not appear to increase the
likelihood of TNS. Pollock and associates performed neurophysiologic testing on five volunteers who developed
[121] [122]
TNS after spinal anesthesia with 50 mg of 5% lidocaine. There were no changes in somatosensory evoked potentials,
early and delayed electromyography, or nerve conduction studies. Although these data suggest that neurotoxicity
[122]
is not the cause of TNS, they do not eliminate another intrathecal source.
Freedman’s study identified other risk factors for the development of TNS besides lidocaine: outpatient status,
obesity, and lithotomy position. Outpatient status suggests that early ambulation and recovery may play a role.
[115] [123]
Lithotomy position causes stretch of the lumbosacral nerves and possible reduction of tissue perfusion, which may
make nerves more vulnerable to injury. The reason for obesity being a risk factor is less clear. Some have
[105]
suggested that, because there is a lower volume of CSF in obese patients, there may have been higher concentrations
of local anesthetic in these patients. However, this hypothesis is not consistent with the lack of concentration
[115] [124]
effect noted earlier. Finally, the addition of phenylephrine to the local anesthetic may increase the risk of TNS. [125]
It is important to note several variables that do not appear to be associated with TNS: gender, age, prior history of
back pain, preexisting neurologic disorder, lidocaine dose or concentration, addition of epinephrine to the local
anesthetic, and needle size, type, or aperture direction ( Table 44-2 ). [115]
Despite data demonstrating no correlation between
TABLE 44-2 -- FACTORS THAT DO NOT INCREASE THE RISK OF TRANSIENT NEUROLOGIC SYMPTOMS IN PATIENTS
RECEIVING INTRATHECAL LIDOCAINE
Factor Category
Gender Male or female
Age < 60 yr or > 60 yr
Race White or other
ASA Class I, II, III, or IV
Height Bottom 20% in study sample or top 20%
History of back pain Yes or no
Preexisting neurologic condition Yes or no
Needle type Quincke or pencil point
Needle size 22 or 22–25 or 26–27
Position during injection Sitting or lateral
Approach for injection Midline or paramedian
Interspace for injection L2–3 or L3–4 or L4–5 or L5–S1
Bevel/aperture direction on injection Caudad or cephalad or lateral
Lidocaine dose ≤50 mg or 51–74 mg or ≥75 mg
Intrathecal epinephrine
Intrathecal fentanyl Yes or no
Intrathecal morphine Yes or no
Intrathecal dextrose Yes or no
Technical difficulty Yes or no
Paresthesia Yes or no
Blood-tinged CSF Yes or no
Final block height (pinprick) < T10 or ≥ T10
Satisfactory block for procedure Yes or no
Hypotension Yes or no
1021
TABLE 44-2 -- FACTORS THAT DO NOT INCREASE THE RISK OF TRANSIENT NEUROLOGIC SYMPTOMS IN PATIENTS
RECEIVING INTRATHECAL LIDOCAINE
Factor Category
Intravenous vasopressor Yes or no
Yes or no
CSF, cerebrospinal fluid.
From Freedman JM, Li DK, Drasher K, et al: Transient neurologic symp toms after spinal anesthesia: An epidemiologic study of 1,863 patients.
Anes thesiology 89:633–641, 1998.
lidocaine dose and concentration and incidence of TNS, some anesthesiologists believe that TNS represents a mild,
reversible form of neurotoxicity. Reasons for this include that the initial manifestation of mild cauda equina
[11] [83]
lesions, such as early cauda equina tumors, is low back or leg pain alone without other localizing neurologic
symptoms. However, this interpretation remains controversial.
[83] [126] [127] [128] [129] [130] [131]
As Horlocker and Wedel point [103] [132] [11]
out, the risk factors for serious neurotoxicity, such as cauda equina syndrome—increasing the lidocaine
concentration or dose, and adding epinephrine—do not appear to influence the development of TNS.
The decision regarding which agents to administer intrathecally should be individualized based on patient variables
and the surgical procedure (and its associated intraoperative position) including its expected duration. For brief [11]
outpatient procedures in the lithotomy position, procaine and low-dose bupivacaine with adjuvants such as low-dose
fentanyl are attractive alternatives to lidocaine. [133]
Anterior Spinal Artery Syndrome
Blood is supplied to the spinal cord by two posterior spinal arteries that deliver blood to the posterior, sensory
portion of the spinal cord, and a single midline anterior spinal artery that feeds the motor tracts. Radicular branches
of the vertebral, deep cervical, ascending cervical, posterior intercostal, lumbar, and lateral sacral arteries supply
these arteries, which are relatively far apart with little collateral flow. Therefore, portions of the spinal cord supplied
by the anterior spinal artery are at high risk for ischemic injury during situations compromising blood flow. [24]
Systemic hypotension or localized vascular insufficiency may cause spinal cord ischemia in the presence or absence
of neuraxial anesthesia. Furthermore, anatomic idiosyncrasies of some patients may make them especially
[8]
susceptible to spinal cord ischemia. Anterior spinal artery syndrome is characterized by sudden onset flaccid
[134]
paralysis with only a minor sensory component. Segmental reflexes are abolished. There are no generalized
symptoms. Laboratory and imaging studies are normal. Clinicians should take care to differentiate anterior spinal
artery syndrome from spinal abscesses and spinal hematoma ( Table 44-3 ).
Risk factors include arteriosclerosis and hypotension. In theory, the use of local anesthetic solutions containing
[135]
vasoconstrictors such as epinephrine or phenylephrine may produce localized cord ischemia, especially in patients
with microvascular disease. However, there is little evidence to support this hypothesis. Spinal blood flow is not
[13] [136]
reduced in most animal models. Most case reports of vasoconstrictor-induced neurologic deficits are confounded
[103]
by the presence of other risk factors. Large studies do not implicate the use of vasoconstrictors as a risk factor for
[7] [137]
either transient or persistent neurologic deficits. Although a study published in 1997 implicates the addition of
[3] [82]
phenylephrine to tetracaine spinal anesthetics in the development of TNS, no patients had sensory or motor
deficits. Thus, the risk of clinically significant spinal cord ischemia from vasoconstrictors remains undefined.
[125]
Spinal Hematoma
Spinal hematoma is a rare and potentially devastating complication of neuraxial anesthesia. It was initially reported
within 10 years after administration of the first spinal anesthetic. Bleeding can occur with any regional [138] [139]
anesthetic technique. However, spinal hematoma is particularly catastrophic, because it can go unnoticed by the
clinician until there is permanent neurologic compromise. An expanding hematoma in the closed space of the spinal
canal can cause compression of the spinal cord and result in neurologic ischemia and paraplegia. Signs and
symptoms of spinal hematoma vary depending on the level at which they occur, but they include new-onset
numbness, weakness, bowel and bladder dysfunction, and, rarely, severe
TABLE 44-3 -- DIFFERENTIAL DIAGNOSIS OF SPINAL ABSCESS, SPINAL HEMATOMA, AND ANTERIOR SPINAL ARTERY
SYNDROME
1022
Anterior Spinal
Spinal Abscess Spinal Hematoma Artery Syndrome
Age of patient Any age 50% over 50 years Elderly
*
Previous history Infection Anticoagulants Arteriosclerosis/hypotension
Onset 1–3 days Sudden Sudden
Generalized symptoms Fever, malaise, back pain Sharp, transient back and leg pain None
Sensory involvement None or paresthesias Variable, late Minor, patchy
Motor involvement Flaccid paralysis, later spasticity Flaccid paralysis Flaccid paralysis
*
Segmental reflexes Exacerbated, later obtunded Abolished Abolished
Myelogram/CT scan Signs of extradural compression Signs of extradural compression Normal
Cerebrospinal fluid Increased cell count Normal Normal
Laboratory data Rise in sedimentation rate Prolonged coagulation time * Normal
CT, computed tomography.
From Wedel DJ, Horlocker TT: Risks of regional anesthesia—infections, septic. Reg Anesth 21:57–61, 1996.
*Infrequent findings.
radicular back pain (see Table 44-3 ). Spinal hematoma may occur secondary to vascular trauma from a needle
[140] [141]
or catheter placed in the subarachnoid or epidural space. It may be spontaneous or occur in association with
neoplastic disease, preexisting vascular abnormalities, and coagulopathies. Oral anticoagulant therapy is [139]
associated with up to 24% of spontaneous spinal hematomas. The first spinal hematoma associated with a spinal
[142]
anesthetic in a patient with coagulopathy was reported in 1953. The ever-growing number of patients with
[143]
iatrogenic coagulopathy from antiplatelet medications, warfarin, heparin, thrombolytics, and low molecular weight
heparin (LMWH) present a challenge to the anesthesiologist considering neuraxial blocks in these individuals (see
later).
The risk of neurologic symptoms resulting from hemorrhagic complications is not known, but it is thought to be less
than 1:150,000 for epidural anesthesia and 1:220,000 for spinal anesthesia. There are insufficient data on which to [144]
base an estimate for combined spinal-epidural anesthesia. Risk factors for spinal hematoma after neuraxial blockade
include anatomic abnormalities of the spinal cord or vertebral column, vascular malformations, impaired hemostasis,
difficult needle placement, and indwelling neuraxial catheters. Indwelling neuraxial catheters also appear to
[140] [141]
increase the risk for clinically insignificant bleeding. [145] [146]
Female gender may be a risk factor for spinal hematoma. There were more than 40 spinal hematomas associated
[146]
with neuraxial anesthesia and low molecular weight heparin (see later) reported to the United States Food and Drug
Administration during a 5-year period starting in 1993. Of these, 75% were women. Although this may represent
[139]
an increased risk for spinal hematoma in women, it may also merely reflect the gender distribution of those patients
receiving low molecular weight heparin thromboprophylaxis. It is unknown what role age may play as a risk factor
for spinal hematoma after neuraxial block, but the majority of patients in the aforementioned series were elderly. As
with gender, this may represent a true risk factor or simply selection bias.
The decision to place a neuraxial block in patients receiving perioperative antiplatelet medications, warfarin, heparin,
thrombolytics, or LMWH must be made carefully. Whatever benefits there are to be gained from a neuraxial
technique must be weighed against the risk, albeit small in most instances, of spinal hematoma. It is important to
identify patients who may be at risk for abnormal bleeding. A detailed history is the most sensitive and cost-
effective method of accomplishing this. The anesthesiologist should inquire about the response to hemostatic
[147]
challenges such as major trauma or surgery. Patients should be asked whether or not they have experienced
symptoms of abnormal hemostasis, such as epistaxis, gingival bleeding, petechiae, ecchymoses, hemarthroses, deep
muscle hematomas, central nervous system bleeding, excessive obstetric and menstrual bleeding, hemoptysis,
melena, hematochezia, hematemesis, or hematuria. A family history of excessive bleeding suggests an inherited
[139]
coagulopathy, whereas excessive bleeding that begins in adulthood implies an acquired disorder. Liver and kidney
diseases and malabsorptive syndromes are associated with abnormal hemostasis. Finally, one should obtain a
complete list of medications that the patient is taking to determine the presence of anticoagulant therapy or of other
drugs that might impair coagulation.
When caring for patients receiving anticoagulant therapy, it is essential to understand the mechanisms,
pharmacokinetics, and indications for each of the drugs. This allows rational, appropriate decisions to be made
regarding the use of neuraxial anesthesia in these patients.
1023
Antiplatelet Medications
Antiplatelet agents are not usually used as the sole agent of thromboprophylaxis. There are four classes of
antiplatelet medications: aspirin and other nonsteroidal anti-inflammatory agents (NSAIDs), dipyridamole,
thienopyridines, and glycoprotein IIb IIIa (GP, IIb, IIIa) inhibitors. Because of significant differences in their
pharmacologic profiles, each of these is discussed separately.
Aspirin and Other Nonsteroidal Anti-inflammatory Agents
Aspirin is the prototypical NSAID. Its antiplatelet activity is due to an irreversible inhibition of cyclooxygenase
activity. Although the plasma half-life of aspirin is only 15 to 20 minutes, aspirin-induced platelet inhibition persists
for the life of the platelet. Because the mean life span of the platelet is about 10 days, only 50% of platelets are
[148]
functional 5 to 6 days after the last aspirin dose.
Other NSAIDs are competitive, reversible, partial inhibitors of platelet cyclooxygenase activity. In general, platelet
function returns to normal within 72 hours of the last nonaspirin NSAID dose. [148]
Neuraxial anesthesia-associated spinal hematomas have been reported in patients who were taking aspirin or
NSAIDs. However, large studies have not shown an increased risk of spinal hematoma in these patients.
[149] [150] [151] [146] [152]
Dipyridamole
Dipyridamole is a weak platelet inhibitor. It acts by inhibiting cyclic nucleotide phosphodiesterase and by blocking
uptake of adenosine into platelet-dense granules. The plasma half-life is approximately 10 hours. The associated [148]
risk of bleeding is low. However, there is a case report of spinal hematoma associated with neuraxial anesthesia and
dipyridamole use. There are insufficient data to assign risk of spinal hematoma associated with neuraxial
[153]
anesthesia and this agent. However, most authorities do not consider use of dipyridamole by itself to be a
contraindication to neuraxial anesthesia.
Thienopyridines
Thienopyridines, such as ticlopidine and clopidogrel, selectively inhibit adenosine diphosphate-induced platelet
aggregation without affecting the cyclooxygenase pathway. They do so by irreversibly inhibiting the platelet
[148]
adenosine diphosphate receptor. These agents require hepatic transformation to become active; therefore, peak
activity is not related to the plasma half-life of the parent compound. Platelet activity remains impaired for up to 7
[148]
days after the last dose. Spinal hematoma has been reported in relationship to ticlopidine. However, the risk of
[148] [154]
spinal hematoma associated with the use of these agents is not known. Until further data become available, it may be
advisable to avoid neuraxial anesthesia and analgesia in patients receiving these agents.
Glycoprotein IIb IIIa Receptor Antagonists
Glycoprotein IIb IIIa (GP IIb IIIa) receptor antagonists are strong inhibitors of platelet function. The GP IIb IIIa
receptor is a platelet membrane glycoprotein that binds circulating fibrinogen or von Willebrand factor, cross-
linking platelets as the final common pathway to platelet aggregation. Intravenous agents directed against this
[155]
receptor include the chimeric monoclonal antibody fragment abciximab, the peptide inhibitor eptifibatide, and the
nonpeptide mimetics tirofiban and lamifiban. The duration of action of these drugs varies. They are commonly
[155]
used in the cardiac catheterization laboratory. There have been no reports of neuraxial anesthesia-associated spinal
hematomas linked to these agents. However, given their strong antiplatelet effects, it may be advisable to avoid
neuraxial blocks in patients receiving these agents.
Aspirin, other NSAIDs, and dipyridamole appear not to increase the risk of spinal hematoma after neuraxial block.
At this time, there are no specific concerns regarding the timing of single-shot or catheter techniques in relationship
to the dosing of NSAIDs, postoperative monitoring, or the timing of catheter removal. Thienopyridines and GP IIb
[156]
IIIa receptor drugs may have significant platelet effects, which warrant caution regarding the use of neuraxial
techniques in patients taking these medications. Further, the concomitant use of medications that affect other
portions of the clotting cascade may increase the risk of bleeding in patients taking antiplatelet agents. There have
been case reports of spinal hematoma in patients receiving antiplatelet therapy and LMWH, and in those receiving
[157]
aspirin and standard heparin. No data are available to quantify this risk. Finally, monitoring of platelet function is
[158]
not recommended to determine the appropriateness of neuraxial block in patients receiving these agents. [156]
1024
Oral Anticoagulants
Warfarin is the most commonly used oral anticoagulant in the United States.[159] Indications for warfarin include
chronic anticoagulation for prosthetic heart valves and for the prevention of thromboembolic events in disorders
such as atrial fibrillation, rheumatic heart disease, venous thromboembolism, and dilated cardiomyopathy. Warfarin
inhibits vitamin K-dependent posttranslational gamma-carboxylation of procoagulant factors II, VII, IX, and X, and
the anticoagulant proteins C and S.[160] Warfarin activity is monitored via the prothrombin time (PT). This test is
performed by adding calcium and thromboplastin to citrated plasma.[161] There are inconsistencies in the PT tests
performed in various
laboratories because of differences in thromboplastin preparations. The international normalized ratio (INR)
standardizes the results of the PT test.
Of the affected procoagulant factors, factor VII has the shortest half-life. Thus, the initial increase in INR after
commencement of warfarin therapy is primarily due to decreased factor VII activity. However, decreased levels of
factors II and X are most responsible for the therapeutic effects of warfarin. The half lives of these factors are 36 to
48 hours, and 72 to 96 hours, respectively. Despite an initial increase in INR, patients may not be fully
anticoagulated because of the persistence of these factors. Likewise, when warfarin therapy is discontinued, the INR
returns to normal initially because of the rapid return of factor VII function. Conversely, factors II and X lag.
Therefore, a normal INR does not necessarily indicate normal coagulation status in patients who have recently
discontinued warfarin. No data exist regarding recently discontinued warfarin and risks associated with neuraxial
anesthesia and analgesia. The anesthesiologist should take into account this and other patient information when
considering neuraxial anesthesia in these patients.
There are many drugs that interact with warfarin, either potentiating or mitigating its effect ( Table 44-4 ). Several
patient factors are associated with increased sensitivity to warfarin. These include age greater than 65 years; female
gender; weight less than 100 pounds; liver, cardiac, and renal disease; and Asian ancestry. Clearly, dietary [159] [162] [163]
intake and gastrointestinal absorption of vitamin K also play a role.
There are few data regarding anticoagulation with warfarin and the risk of spinal hematoma with neuraxial
anesthesia and analgesia and indwelling epidural catheters. The first dose of warfarin thromboprophylaxis is often
given the night before surgery. It appears that neuraxial techniques can be used safely if patients receive low-dose
(<5 mg) warfarin preoperatively, provided that warfarin is given not more than 24 hours before placement of the
block. If the dose is given more than 24 hours before the placement of the block, prothrombin time should be
[164] [165]
checked to ensure that the INR is not excessively elevated. There is no consensus regarding the appropriate INR
before surgery, but most clinicians avoid surgery if the INR is greater than 1.4. In patients who are receiving
[159]
chronic anticoagulation therapy preoperatively, warfarin should be discontinued 3 to 5 days before surgery to allow
the INR level to return to baseline. The INR should be checked before the operation.
[166]
There is debate regarding the timing of removal of indwelling epidural catheters in patients receiving warfarin. If the
first warfarin dose was given more than 36 hours before removal, an INR should be checked before the catheter is
removed. Daily documentation of the INR is essential. Warfarin should be withheld, or the dose reduced, if the
[159]
INR is greater than 3. Neurologic testing should continue for at

[167]
TABLE 44-4 -- DRUG INTERACTIONS WITH WARFARIN

Pharmacodynamic Mechanism Unknown
Pharmacokinetic (Drugs That Do Not Change Warfarin (Drugs Whose Effect on Warfarin Levels Is
(Drugs That Change Warfarin Levels) Levels) Unknown)
Prolongs Prothrombin Time Prolongs Prothrombin Time Prolongs Prothrombin Time
Stereoselective inhibition of clearance of S-
isomer
Phenylbutazone Inhibits cyclic interconversion of vitamin K Evidence of interaction convincing
Metronidazole 2nd- and 3rd-generation cephalosporins Erythromycin
Trimethoprim sulfamethoxazole Other mechanisms Anabolic steroids
Disulfiram Clofibrate Evidence for interaction less convincing
Stereoselective inhibition of clearance of R- Inhibits blood coagulation
isomer
Heparin Ketoconazole
1025
TABLE 44-4 -- DRUG INTERACTIONS WITH WARFARIN

Pharmacodynamic Mechanism Unknown
Pharmacokinetic (Drugs That Do Not Change Warfarin (Drugs Whose Effect on Warfarin Levels Is
(Drugs That Change Warfarin Levels) Levels) Unknown)
Cimetidine * Increases metabolism of coagulation factors Fluconazole
*
Omeprazole Thyroxine Isoniazid
Nonstereoselective inhibitions of clearance of Piroxicam
R- and S-isomers
Tamoxifen
Amiodarone Quinidine
Vitamin E (megadose)
Phenytoin
Reduces Prothrombin Time Inhibits Platelet Function Reduces Prothrombin Time

Reduces absorption Aspirin Penicillins
Cholestyramine Other nonsteroidal anti-inflammatory drugs Griseofulvin †
Increases metabolic clearance Ticlopidine
Barbiturates Moxalactam
Rifampin Carbenicillin and high dosages of other
penicillins
Griseofulvin
Carbamazepine
From Enneking FK, Benzon H: Oral anticoagulants and regional anesthesia: A perspective. Reg Anesth Pain Med 2323(6 Suppl 2):140–145,
1998.
*Causes minimal prolongation of the prothrombin time.

†
Has been proposed to cause increased metabolic clearance.
least 24 hours after catheter removal, or longer if the INR was 1.5 or greater at the time of removal. While in use, [159]
the solution infused through the catheters should contain opioids alone or only low concentrations of local
anesthetics to allow frequent neurologic testing. [167]
Other than the aforementioned guidelines, no firm recommendations can be made. However, there has been a report
of spinal hematoma in a patient with a PT of 17.3 seconds. Therefore, it seems prudent to avoid neuraxial
[166]
anesthesia or placement and removal of epidural catheters in patients who are fully anticoagulated.
Standard Heparin
Heparin is used for perioperative thromboprophylaxis for orthopedic, general, gynecologic, and urologic surgery,
and for therapeutic anticoagulation during vascular and cardiac surgery. It is also used in a variety of medical
[168] [169]
settings. Heparin is a glycosaminoglycan that is supplied as a mixture of varying molecular weights and
anticoagulant activity. Its principal action is binding to antithrombin III and accelerating its ability to inactivate
thrombin and factors IXa, Xa, XIa, and XIIa. With prolonged therapy, some patients develop a decreased platelet
count. Heparin anticoagulation is usually monitored via the activated partial thromboplastin time (aPTT).
[168]
Low-dose (5000 U) subcutaneous heparin is given every 12 hours for perioperative thromboprophylaxis. Most
patients have no alterations in aPTT, although a minority have mild elevations and an even smaller number become
anticoagulated. Debilitated patients are at higher risk for significant elevations of the aPTT; therefore, it is
[170] [171]
advisable to monitor the aPTT before placing a neuraxial block in debilitated patients or in those concurrently
receiving other anticoagulant therapy. However, by itself, this method of thromboprophylaxis seems to be
[172]
compatible with neuraxial techniques. Liu and Mulroy found nine published series, including more than 9000
[172]
patients, in which neuraxial anesthesia was given while patients were on this therapy. There were no complications.
Although there have been reports of spinal hematomas in the presence of low-dose subcutaneous heparin, each of
these had confounding variables. Nonetheless, it seems prudent to place neuraxial blocks at the nadir of low-
[141] [172]
dose subcutaneous heparin activity.
1026
Intraoperative therapeutic doses (5000–10,000 U) of heparin are given routinely during vascular surgery. The largest
series examining this in conjunction with neuraxial anesthesia was by Rao and El-Etr. They studied more than
[173]
4000 patients with indwelling epidural and spinal catheters who were undergoing systemic heparinization during
vascular surgery. There were no spinal hematomas. Other investigators have achieved similar results. In the Rao
[174]
and El-Etr study, heparin was not administered until at least 60 minutes after catheter placement, catheters were
removed at times when circulating heparin levels were low, and patients with preexisting coagulopathies were
excluded. Most other studies follow similar guidelines. These precautions should be incorporated into daily
[173]
clinical practice.
As previously noted, difficult block placement increases the risk of hemorrhagic complications after neuraxial
techniques. Rao and El-Etr recommended canceling cases when this occurred. Other authors have disagreed.
[173] [173] [175] [176]
If traumatic block placement occurs, the anesthesiologist and surgeon should frankly weigh the risks and benefits of
proceeding. [172]
Removal of an indwelling neuraxial catheter after intraoperative anticoagulation should occur at the nadir of heparin
activity (i.e., 2 to 4 h after the last dose and 1 hour or more before the next dose). If there has been prolonged
[172]
heparin therapy, the catheter should be removed only after confirmation of coagulation status. Frequent neurologic
evaluations are required for at least 12 hours after catheter removal.
[172]
Since the 1990s, neuraxial local anesthetics and opioids administered via single-shot and catheter techniques have
been examined in patients who have had cardiac surgery requiring cardiopulmonary bypass. These techniques have
potential benefits, which include intense postoperative analgesia, attenuated surgical stress response, and thoracic
sympathectomy, which may improve coronary blood flow. However, because cardiopulmonary bypass requires
[177]
full anticoagulation with high-dose heparin (300 U/kg or more), there may be an increased risk of spinal hematoma
when these techniques are used in this patient population. Published reports of more than 30 studies involving
approximately 2000 patients have examined this technique without report of spinal hematoma. Still, definitive
studies are lacking. Chaney recommended several caveats when considering these techniques. First, patients with
[177]
preexisting coagulopathies should not be considered for these techniques. Second, traumatic blocks require a 24-
hour delay of the operation. Finally, as with heparinization for vascular surgery, the time from block placement to
heparin administration should be at least 60 minutes.
Low Molecular Weight Heparin
LMWH has been approved for thromboprophylaxis after total knee and hip arthroplasty, for major abdominal
surgery, and for the treatment of deep venous thrombosis. LMWH is produced by enzymatically or chemically
cleaving standard heparin.[148] This depolymerization significantly alters the pharmacology of LMWH compared
with standard heparin. LMWH binds less to plasma proteins and platelets than standard heparin; therefore, LMWH
has a reliable and reproducible response when the dosage is administered according to the patient’s weight. LMWH
is more than 90% bioavailable after a subcutaneous dose. The half-life is 4 to 6 hours, and the peak anticoagulant
activity occurs 3 to 4 hours after subcutaneous dosing. There is no drug accumulation with repeated doses over
periods of up to 2 weeks. However, LMWH is renally excreted and its use is not recommended in patients with renal
dysfunction. Anti-Xa levels can be used to monitor anticoagulant activity in patients with renal insufficiency, but
anti-Xa levels are not predictive of risk of bleeding.[140] [148] [178] The aPTT is not generally elevated with
LMWH therapy. Patients with heparin-induced thrombocytopenia (HIT) should not be given LMWH, because
LMWH cross-reacts with heparin-dependent antiplatelet antibodies in up to 70% of patients with HIT.[179]
LMWH was evaluated and used extensively in Europe before its release in the United States. The European
experience suggested that LMWH did not increase the risk of spinal hematoma when used in patients receiving
neuraxial blockade. In the first 5 years after its introduction into the United States, however, there were more than
40 cases of spinal hematoma associated with neuraxial anesthesia and thromboprophylaxis with LMWH. The [140]
estimated incidence of spinal hematoma associated with LMWH therapy is 1 in 3100 continuous epidural
anesthetics and 1 in 40,800 spinal anesthetics. The disparity in frequency between the United States and Europe
[180]
may be due to differences in dosing schemes. For example, in Europe, the thromboprophylaxis dose of enoxaparin is
40 mg daily, with the first dose administered 12 hours preoperatively. In the United States, the dose is 30 mg every
12 hours. The 12-hour dosing scheme eliminates the trough levels found in the daily dosing regimen. Catheter
removal may have occurred in these patients during periods when there was a relatively large amount of LMWH
activity.
The published data on spinal hematoma associated with LMWH and neuraxial block are incomplete. Thus, it is
difficult to identify factors that may increase the risk of spinal hematoma. Horlocker and Wedel reviewed the
[140]
reported cases available through early 1998. They identified the following risk factors: indwelling neuraxial catheter,
1027
especially if LMWH was administered while the catheter was in place; difficult block placement; concomitant
antiplatelet therapy; and, possibly, elderly female status.
A careful risk-benefit analysis must be made before a neuraxial block is performed in patients receiving LMWH.
This must include the patient’s overall medical condition and consideration of the consequences of alternative
anesthetic or analgesic techniques and thromboprophylactic regimens. The clinician should bear in mind the
following recommendations : [140]
1. Anti-Xa level monitoring does not predict risk of bleeding and is not recommended.
2. Concurrent use of other anticoagulant therapy may increase the risk of spinal hematomas.
3. Traumatic needle or catheter placement may increase the risk of spinal hematoma. Alternative methods of
thromboprophylaxis should be considered. If LMWH is to be used, the first dose should be delayed for 24
hours.
4. Patients receiving LMWH preoperatively have altered coagulation. A single-dose subarachnoid block may
be the safest neuraxial technique for this population. Needle placement should occur 10 to 12 hours after
the last LMWH dose (24 hours with a high-dose LMWH regimen). Neuraxial techniques should be avoided
in patients who have received LMWH 2 hours preoperatively, because peak anticoagulant activity occurs
during this time frame.
5. Indwelling neuraxial catheters are acceptable in patients who are to have LMWH thromboprophylaxis
initiated postoperatively. The catheter should be removed 2 hours before the first dose of LMWH.
6. LMWH thromboprophylaxis that is started while an indwelling catheter is in place warrants extreme
vigilance. Solutions of low-concentration local anesthetic or opioid alone should be infused to allow
frequent neurologic testing.
7. Removal of an indwelling catheter should occur at least 10 to 12 but preferably 24 hours after the last
LMWH dose. The next dose of LMWH may be given 2 hours after catheter removal.
Thrombolytics
Thrombolytic drugs, such as streptokinase, urokinase and tissue plasminogen activator (tPA), are used in the
treatment of myocardial infarction, stroke, and vascular thrombosis. As indications for these agents expand, their use
may become more widespread. Thrombolytic agents cause lysis of existing clots. This is in contrast to standard
heparin, LMWH, warfarin, and the various antiplatelet agents, all of which exert their therapeutic action by
inhibiting the formation of new clots. Furthermore, heparin is often given concurrently with these drugs so that new
clot formation is inhibited while existing clot is being lysed. Because of their mechanism of action and the
association with heparin therapy, the contraindications to the use of thrombolytic drugs are quite stringent:
1. Surgery within the previous 10 days, including organ biopsy, puncture of noncompressible vessels, serious
trauma, and cardiopulmonary resuscitation
2. Serious gastrointestinal bleeding during the previous 3 months
3. History of severe hypertension (diastolic blood pressure > 100 mm Hg)
4. Active bleeding or hemorrhagic disorder
5. Previous stroke or ongoing intracranial pathology [181]
Despite these rigid criteria, there have been several case reports of spontaneous spinal hematomas associated with
the use of thrombolytic agents. There are no published studies addressing neuraxial anesthesia and
[182] [183] [184]
thrombolytic therapy. There have been three case reports, with varying neurologic outcomes. Rosenquist and
[185] [186] [187]
Brown made the following recommendations, based on the case reports:

[188]
1. Patients receiving heparin and a thrombolytic drug are at high risk for hemorrhagic complications from
neuraxial anesthesia.
2. During the preoperative evaluation, the anesthesiologist should establish whether thrombolytics have been
given preoperatively. In addition, the likelihood of intraoperative and postoperative thrombolytic therapy
should be determined.
3. Neuraxial anesthesia should rarely be considered in patients receiving thrombolytics. Based on the original
contraindications (i.e., recent puncture of noncompressible vessels), thrombolytic drugs should not be
administered to patients within 10 days of neuraxial anesthesia. The safe interval for receiving a neuraxial
block after thrombolytic therapy has not been determined.
4. If neuraxial blocks are administered at or near the time of thrombolytic therapy, neurologic monitoring
should be performed every 2 hours. If an indwelling catheter is used, the infusate should minimize sensory
and motor block and allow accurate neurologic testing.
1028
5. There are no data to guide the timing of the removal of indwelling catheters in the setting of thrombolytic
therapy. Clinicians must use caution in making these decisions. The serum fibrinogen level may be a
helpful guide.
In summary, the anesthetic management of patients receiving thromboprophylaxis or therapeutic anticoagulation is

challenging. Decisions regarding the use of neuraxial techniques must be made on a case-by-case basis, weighing
variables such as underlying risk factors for bleeding, the consequences of discontinuing or aborting anticoagulant
therapy, and the potential benefit of neuraxial techniques. Clinicians can consult the American Society of Regional
Anesthesia’s Neuraxial Anesthesia and Anticoagulation Consensus Statements for guidance (see the Appendix ).
Rarely do the benefits of neuraxial anesthesia and analgesia outweigh the risks of spinal hematoma in patients with
known coagulopathies, significant thrombocytopenia, or thrombolytic therapy within the previous 24 hours. [167] [188]
Alternative techniques exist. If a neuraxial technique is chosen, the timing of block placement and catheter removal
should be optimized based on patient characteristics and the pharmacologic variables of the anticoagulant drug to
minimize the risk of spinal hematoma. Careful and frequent neurologic testing is paramount. With a continuous
technique, the infusate should contain low concentrations of local anesthetics or opioids alone to allow accurate
assessment of neurologic status. If a spinal hematoma is suspected, rapid evaluation and treatment are critically
important to avoid permanent neurologic compromise (see Table 44-3 ). This includes emergent imaging studies
such as CT or MRI scanning and neurosurgical evaluation. Even with prompt diagnosis and treatment, the prognosis
is not favorable. In one series, only 38% of patients had partial or good neurologic recovery when decompressive
laminectomy was performed within 8 hours of diagnosis. [141]
Finally, clinicians should be mindful of the complexity of modern health care institutions. Even with careful
communication with the surgeon, anticoagulants may be ordered inappropriately for patients who have received
neuraxial anesthesia and analgesia. In one study, there was a 52% noncompliance rate in following institutional
protocols for patients receiving LMWH and a neuraxial block. This may occur because of standing orders that are
[189]
not properly altered to reflect the anesthetic or analgesic regimen or because of changes in the patient’s clinical
status necessitating vigorous and urgent anticoagulation. One solution for this is a pharmacy “fail-safe” system,
whereby all patients receiving an epidural infusion are “flagged” by pharmacy computers. When an order is given
for intravenous heparin, LMWH, thrombolytics, or abciximab in these patients, the computer alerts the pharmacist,
who then contacts the anesthesiologist caring for the patient. This system allows the anesthesiologist to be aware
[190]
of situations that may place patients with indwelling neuraxial catheters at risk for spinal hematoma and to make
appropriate interventions.
Infectious Complications
MENINGITIS AND EPIDURAL ABSCESS
Serious infectious complications after neuraxial blockade include meningitis and epidural abscess. Although feared
because of their catastrophic potential, these complications are rare. Kane[8] reviewed several studies involving
more than 50,000 epidural and 65,000 spinal anesthetics. There were no instances of epidural abscess and only three
cases of meningitis, respectively. There are several theoretical risk factors for the development of infectious
complications after neuraxial blockade, including bacteremia, iatrogenic or pathologic immunosuppression (e.g.,
glucocorticoid or cyclosporine therapy, diabetes, cancer, acquired immune deficiency syndrome), localized infection
at the site of insertion, and long-term epidural catheterization.[135] Continuous catheters theoretically can serve as a
wick, allowing the spread of bacteria from the skin surface.
MENINGITIS AFTER DURAL PUNCTURE
Dural puncture may be a risk for the development of meningitis. However, the mechanism by which bacteria
[191]
travel from the bloodstream to the central nervous system is obscure. The disruption of the blood-brain barrier by
dural puncture is an obvious possibility, as is the introduction of blood containing bacteria. If these hypotheses were
valid, one would expect there to be clinical evidence of the risk of meningitis following dural puncture. Although
many patients with fevers of unknown origin and, possibly, early sepsis undergo diagnostic lumbar puncture, studies
suggesting an association between dural puncture and the development of meningitis are limited ( Table
[192] [193] [194] [195] [196]
44-5 ).
Carp and Bailey examined the incidence of meningitis after dural puncture in rats with Escherichia colibacteremia.
[197]
One group of rats underwent cisternal puncture without preexisting bacteremia. In 40 rats, there were no instances of
meningitis. Similarly, there was a 0% incidence of meningitis in bacteremic rats who did not have a cisternal
puncture. However, in rats that were bacteremic during cisternal puncture, there was a 30% incidence of meningitis.
1029
Perhaps the most clinically relevant finding of the study was that when gentamicin was administered to bacteremic
animals before dural puncture, meningitis did not occur.
These findings suggest that dural puncture during bacteremia increases the risk of meningitis. Moreover,
prepuncture antibiotics seem to prevent the development of meningitis in this model. However, one should be
cautious in applying these results to clinical practice. Although E. coli commonly produces bacteremia in surgical
patients, it rarely causes meningitis. Additionally, the authors used antibiotics to which the E. coli was susceptible.
Often, the identity of the organism causing bacteremia is not known at the time of dural puncture. Next, the authors
performed cisternal puncture rather than lumbar puncture. Furthermore, they used 26-G needles, which are relatively
large for rats and may have caused comparatively large injury to the dura. No local anesthetics were injected during
the study. Because local anesthetics are bacteriostatic, their addition might have decreased the incidence of
[198]
meningitis. Finally, the authors did not examine the
TABLE 44-5 -- MENINGITIS AFTER DURAL PUNCTURE

Patients with
Patients with Lumbar
Patients Spontaneous Puncture-Induced
Author (Yr) (No.) Population Microorganism(s) Meningitis Meningitis Comments
Wegeforth (1919) 93 Military personnel Neisseria meningitidis 38 of 93 (41%) 5 of 93, including 5 Lumbar punctures
Streptococcus pneumoniae of 6 bacteremic performed during
patients meningitis
epidemics
Pray (1941) 416 Children with Streptococcus pneumoniae 86 of 386 (22%) 8 of 30 (27%) 80% of patients
bacteremia with meningitis < 2
yr of age
Eng (1981) 1089 Adults with Atypical and typical 30 of 919 (3.3%) 3 of 170 (1.8%) Atypical organisms
bacteremia bacteria responsible for
lumbar puncture-
induced meningitis
Teele (1981) 271 Children with Streptococcus pneumoniae 2 of 31 (8.7%) 7 of 46 (15%) * All cases of
bacteremia Neisseria meningitidis meningitis
Haemophilus influenzae occurred in
children < 1 yr of
age. Antibiotic
therapy reduced
risk
Smith (1986) 11 Preterm infants NA (no cases of 0% 0%
with neonatal meningitis)
sepsis
NA, not applicable.
From Horlocker TT, Wedel DJ: Neurologic complications of spinal and epidural anesthesia. Reg Anesth Pain Med 25:83–98, 2000.
*Significant association (P < .001). Spontaneous meningitis, concurrent bacteremia and meningitis (without a preceding lumbar puncture).
Lumbar puncture-induced meningitis, positive blood culture with sterile CSF on initial examination and subsequent positive CSF culture (same
organism present in blood).
effect of postdural puncture antibiotics on the incidence of meningitis. Nonetheless, this scenario is clinically
significant, because surgeons often need to withhold antibiotic therapy until cultures are obtained. It should be noted
that the aforementioned study does not apply to a febrile patient for whom an indwelling catheter is being
considered.
EPIDURAL ABSCESS AFTER EPIDURAL CATHETERIZATION
Epidural abscess may be superficial, requiring only superficial drainage and intravenous antibiotics. Deep infections
are more rare but require surgical treatment. Spontaneous epidural abscess occurs at a rate of 0.2 to 2 per 100,000
[135]
hospital admissions per year. Epidural abscess after epidural catheterization is a rare complication, but its
[199]
incidence may be rising. Studies published in 1995 and 1996 estimated the frequency to range from 0.015% to
[200]
0.7%, although the patient population in the latter study was at high risk for epidural abscess. Although epidural [201] [202]
abscess is uncommon, early diagnosis and treatment are paramount. In a series published in 1998, only 45% of
patients with epidural abscess had full neurologic recovery. Further, those who had persistent deficits had a
significantly longer period of time between initial symptoms and treatment. The best outcome occurs when there
[200]
are fewer than 12 hours between onset of symptoms and definitive treatment. [135]
1030
Symptoms of epidural abscess usually begin several days after neural block, but they can occur months later. [135] [200]
Symptoms include back pain, fever, malaise, elevated blood leukocyte count, signs of cord compression including
sensory changes, flaccid paralysis followed by spastic paralysis, elevated cerebrospinal fluid protein and leukocytes,
and elevations of nonspecific serum markers of inflammation, such as C-reactive protein and erythrocyte
sedimentation rate (see Table 44-4 ). Magnetic resonance imaging scan is the diagnostic modality of choice.
[135] [200] [203] [204]
Staphylococci are the most frequent (57%) etiologic agents. Streptococci (18%) and gram-negative bacilli (13%),
[199]
including Pseudomonas species, are the next most frequently isolated organisms. [199] [200]
Several patient factors appear to increase the risk of epidural abscess related to epidural anesthesia. These include
diabetes mellitus, chronic renal failure, epidural or systemic steroid administration, herpes zoster, cancer (causing
immunosuppression), chronic alcohol abuse, and anorexia. In addition, thoracic catheters may be
[205] [206] [207] [208] [209] [210] [211] [212]
more apt to be associated with epidural abscesses than lumbar catheters, although the reason for this is unclear. [200]
Catheters inserted at the sacral hiatus also may be more prone to be associated with abscess formation because of the
likelihood of bacterial contamination in that region. The duration of catheter placement seems to have little impact
[135]
on the development of an infection.
The use of epidural catheters in patients with chorioamnionitis is controversial. Theoretically, these women have an
increased risk of abscess formation because of potential seeding of the catheter by blood-borne bacteria.
Unfortunately, there are limited data to guide the clinician in this circumstance. Bader and colleagues studied the [213]
use of regional anesthesia in 319 women with chorioamnionitis. There were 8 patients with positive blood cultures
among the 100 who had them taken. A regional anesthetic was given to 293. Only 43 received antibiotics before
block placement. Three of the 8 bacteremic patients had blocks. None of these received antibiotics before the
regional anesthetic was instituted. No infectious complications were noted. The authors recommended neuraxial
anesthesia in patients with suspected chorioamnionitis, because, in their view, the potential advantages of regional
anesthesia in parturients outweighed the risks of infection. [200]
Clearly, patients with indwelling epidural catheters should be monitored closely for signs of infection. Meticulous
aseptic technique is necessary when catheters are placed. Consideration should be given to patient variables, which
may increase the risk of epidural abscess formation. Finally, if infection is suspected, urgent workup and a
neurosurgical consultation are mandatory.
HERPES SIMPLEX VIRUS
Herpes simplex virus infection is epidemic in the adult population. Its clinical spectrum is wide. Herpes simplex
virus type 2 is a recurrent disease characterized by painful vesicular genital lesions. Viremia occurs with primary
infection. Symptoms are varied but can include fever, headache, and, rarely, aseptic meningitis. Secondary
infections occur sporadically, and little is known about what events may precipitate a recurrence. Secondary
infections are not associated with viremia. Cesarean delivery is preferred in parturients with active infections to
avoid exposing the neonate to the virus, because infection is associated with significant morbidity in this
population. Similarly, neuraxial anesthesia and analgesia are controversial in parturients with active infections
[214]
because of the possibility of exposing the central nervous system to the virus. The literature does not support this
concern when there is secondary infection present.
Bader and associates[215] examined the anesthetic care of 169 patients with herpes simplex virus type 2 infection
undergoing cesarean section. Five patients had primary infection. Seventy-five had spinal anesthesia and 35 had
epidural anesthesia. There were no infectious or neurologic complications in any of the patients with secondary
infections. After a spinal anesthetic, one patient with primary infection had a transient motor deficit in one leg that
could not be clearly attributed to anesthetic technique. The authors concluded that neuraxial anesthesia and analgesia
were safe in patients with secondary infections, a contention which has been supported by other authors.[216] [217]
Given these data and the fact that secondary infection is not associated with viremia, it is reasonable to apply
neuraxial techniques in those with recurrent infection. Conversely, viremia is associated with primary infection, and
complications of neuraxial blockade have been reported in the setting of primary infection.[215] Therefore,
neuraxial techniques may not be advisable in patients with primary infection.
Oral herpes is caused by herpes simplex type 1, an agent that rarely causes genital lesions. Recurrence of lesions has
been reported in parturients after epidural and intrathecal morphine in both retrospective and prospective studies. [217]
The association was controversial because numerous factors in the peripartum period could influence
[218] [219]
recurrence, and the mechanism by which epidural morphine could cause recurrence is obscure. However, in a
prospective study, Crone and colleagues found a recurrence rate of 22.5% in parturients with positive herpes
[218]
simplex virus serology who received epidural morphine compared with 0% in those who received only
1031
intramuscular morphine. Therefore, epidural morphine should be avoided in patients with known herpes simplex
virus seropositivity. There are insufficient data to make recommendations regarding the use of other opioids.
HUMAN IMMUNODEFICIENCY VIRUS
Human immunodeficiency virus (HIV) infection poses an interesting dilemma for the anesthesiologist. Newer
antiretroviral therapies allow patients to remain asymptomatic for longer periods and may increase the number of
patients undergoing operations amenable to neuraxial anesthesia. More than 80% of those dying of acquired
immunodeficiency syndrome (AIDS) have central nervous system neuropathology. Up to 50% of asymptomatic
[220]
HIV-infected patients have peripheral nervous system involvement. The most common problem of the
[220] [221]
peripheral nervous system in AIDS patients is a sensory neuropathy, with an incidence of up to 30%. Many of the [222]
neurologic manifestations of AIDS—headache, polyneuropathy, and aseptic meningitis—mimic complications of

regional anesthetic techniques. Scant literature is available regarding neuraxial blocks in HIV-infected patients. Of
[167]
concern is the possibility of introducing HIV into the central nervous system via dural puncture. Authors and
clinicians point to studies demonstrating that the majority of HIV-infected patients show signs of CSF involvement
early, and argue that it would be unlikely that dural puncture would introduce HIV into the CSF de novo. However, [167]
in these studies, a significant proportion of patients do not appear to have CSF involvement, and it appears that only
a minority of asymptomatic patients have positive HIV CSF cultures early. [223]
The available clinical data are of little help. Hughes and colleagues examined the clinical course of 30 parturients
[224]
with HIV infection. Eighteen patients received neuraxial blocks, 16 received epidurals (3 with unintentional dural
puncture), and 2 received spinals. There were no neurologic or infectious complications in any of the patients in the
immediate postpartum period or in the ensuing 4 to 6 months. There were no superficial or deep infections at the
catheter placement site. However, most of the patients in this study had CD4 lymphocyte counts greater than 200
cells/mm3 , and thus were relatively healthy. There are no data evaluating the risks of neuraxial block in patients
with advanced AIDS.
Perhaps a matter of more concern is the prospect of epidural blood patch in this patient population. In theory, blood
injected into the epidural space could be the nidus for an infection in an immunocompromised patient. However,
epidural blood patch has been performed safely in HIV-seropositive patients. [225]
The medical literature provides the clinician with little guidance concerning the use of neuraxial blocks in HIV-
infected patients. Each case should be considered individually, weighing the patient’s medical condition, the
operative procedure, and the risks and benefits of neuraxial anesthesia or analgesia versus alternative techniques.
NEURAXIAL BLOCKS IN INFECTED OR FEBRILE PATIENTS
Single-shot spinal techniques and short-term epidural catheterization appear to pose little risk to patients who may
become transiently bacteremic during surgery. Conversely neuraxial blocks in infected or febrile patients may
increase the risk of neuraxial infection, and these blocks remain controversial. Most authorities believe that
neuraxial blocks should not be performed in patients who are bacteremic and have not commenced antibiotic
therapy. If antibiotics have been started and there has been a clinical response, such as defervescence of a fever,
single-shot spinal anesthesia may be safe. However, indwelling catheters may increase the risk of neuraxial infection.
Therefore, extreme care should be taken when considering these techniques in such patients. If an indwelling cathter
is chosen, patients should be monitored vigorously for sign and symptoms of neuraxial infection.
Meningitis is a medical emergency. Its mortality approaches 30%, even with antibiotic therapy. Delays in diagnosis
and treatment can significantly worsen outcome. Clearly, rapid diagnosis and prompt, appropriate treatment are
paramount. All patients who receive neuraxial blocks and are febrile or infected should be considered to be at risk.
Signs of meningitis include severe headache, fever, meningismus, and altered mental status. Diagnosis is confirmed
via lumbar puncture. If spinal abscess is suspected, lumbar puncture should be avoided to prevent seeding of the
CSF with bacteria.
Neuraxial Blocks in Patients with Preexisting Neurologic Disorders
Preexisting neurologic disorders present challenges to the anesthesiologist. Postoperative neurologic injuries can
have a variety of causes, including surgical trauma, prolonged tourniquet ischemia, improper positioning, extended
labor and anesthetic technique. Progressive neurologic diseases, such as multiple sclerosis, may worsen
[11]
perioperatively by happenstance, regardless of the anesthetic technique or surgical procedure. Furthermore, it is

often difficult to determine the cause of postoperative neurologic injury. For example, the most common site of
1032
neurologic injury in total shoulder arthroplasty is at the level of the trunks of the brachial plexus, the same location
as needle entry for interscalene blocks. Although it is tempting to implicate interscalene block as a risk factor for
postoperative neurologic injury after these procedures, evidence points to surgical issues. Clearly, a careful,
[226]
thorough approach to diagnosis is mandatory when postoperative neurologic deficits are evaluated.
Because of the issues discussed earlier and the medicolegal implications of any increase in postoperative neurologic
deficit, many clinicians completely avoid neuraxial block in patients with preexisting neurologic disorders. However,
one can easily imagine patients with severe cardiopulmonary disease for whom neuraxial anesthesia and analgesia
would be the technique of choice for a variety of surgical procedures. Thus, decisions regarding the choice of
anesthetic techniques should be based on individual patient factors, considering overall medical status, the surgical
procedure, and patient preference, in addition to preexisting neurologic deficits. Informed consent is of paramount
importance in these instances.
Preexisting central nervous system disease may present a more difficult dilemma to the anesthesiologist in relation
to neuraxial anesthesia and analgesia. In theory, the preexisting central nervous system disease implies neural
compromise that may predispose patients to neural injury after neuraxial anesthesia. Vandam and Dripps identified[37]
11 patients with exacerbations of preexisting neurologic complications after spinal anesthesia and recommended that
spinal anesthesia not be given to those with central nervous system or spinal disease, regardless of whether the
patient is symptomatic. Other authors agree. Although central nervous system diseases such as lumbar
[8]
radiculopathy, spinal stenosis, multiple sclerosis, amyotrophic lateral sclerosis, and poliomyelitis require the
anesthesiologist’s consideration when the anesthetic plan is being determined, the presence of these diseases is not
necessarily a contraindication to neuraxial anesthesia. Unfortunately, the literature regarding the use of neuraxial
[10] [227]
blocks in these patients consists of case reports only. No controlled studies have appeared to define risk of further
neurologic injury in these patients presumably because of the difficulties encountered in designing and carrying out
such investigations. Without definitive studies for guidance, decisions regarding the use of neuraxial anesthesia
should be made on a case-by-case basis. Thus, the anesthesiologist should be aware of the pathophysiology of the
neurologic disease as well as the potential mechanisms and incidence of neurologic injury associated with neuraxial
block.
Diabetes Mellitus
Peripheral and autonomic neuropathies are part of the classic diabetic triopathy, along with retinopathy and
nephropathy. Neuropathy occurs in a large number of diabetic patients. Depending on the criteria for diagnosis and
the patient population studied, the incidence may range from 15% to 100%. In patients with a 25-year history of
[228]
type 2 diabetes mellitus, 50% have neuropathy. Even in patients without clinical symptoms of neuropathy, there
[229]
may be electrophysiologic evidence of neuropathy, consisting of slowing of nerve conduction velocities. The
electrophysiologic abnormalities can occur even in patients with histologically normal nerves. Preexisting
[230]
neurologic dysfunction may lessen local anesthetic requirements. Diabetes is associated with arteriosclerosis. This
microangiopathy affects nerve blood vessels and decreases local anesthetic uptake. As a result, nerves have
prolonged exposure to higher levels of local anesthetics. In theory, preexisting nerve damage and increased exposure
to local anesthetics may lead to neurologic injuries in diabetic patients, despite a dose of local anesthetic that would
be considered safe in the normal population. [11]
There is laboratory evidence for the theory just discussed. Kalichman and Calcutt[136] examined the effects of local
anesthetics on nerve conduction block and injury in a rat model of diabetes. They reported that local anesthetic
requirements were reduced and that there was increased risk of local anesthetic-induced nerve injury associated with
diabetes. Clinicians may conclude from the study by Kalichman and Calcutt that neuraxial block has an increased
risk of local anesthetic-induced nerve toxicity in diabetic patients compared with nondiabetic patients, and that local
anesthetic concentrations and doses should be reduced in diabetic patients. Unfortunately, there are no human
clinical studies to confirm or refute this conclusion.
Multiple Sclerosis
Multiple sclerosis is characterized by random, demyelinating lesions of the central nervous system. Peripheral
nerves are not affected. Its etiology is not well defined. The course of the disease is variable, ranging from indolent
to relapsing-remitting with chronic progression to rapidly progressive. The timing of exacerbations of the disease is
unpredictable. However, multiple factors have been associated with exacerbations, including stress, surgery, fatigue,
and fever. Clearly, an increase in symptoms can occur by coincidence perioperatively, regardless of the
[11] [231]
anesthetic technique chosen. Since the 1930s, authors have advised against the use of spinal anesthesia in patients
with multiple sclerosis. However, the evidence for avoiding neuraxial block in this population is not compelling.
[232] [233]
1033
The mechanism of neuraxial anesthesia-induced relapse of symptoms is not known but may be local anesthetic
[234] [235]
toxicity. Because of this, some authors recommend epidural anesthesia over spinal anesthetic block, since epidural
anesthesia exposes the spinal cord white matter to much lower concentrations of local anesthetic than spinal
anesthetic block. If a neuraxial block is chosen, it may be prudent to use a dilute concentration of local anesthetic.
[236]
The use of peripheral nerve blocks is not associated with relapses of multiple sclerosis. [234]
Spinal Stenosis
Spinal stenosis is a common degenerative disease of the vertebral column that often remains asymptomatic. The use
of neuraxial blockade in these patients is controversial. Cauda equina syndrome and polyradiculopathy have been
reported in patients with asymptomatic spinal stenosis who underwent neuraxial block. The mechanism of
[87] [237] [238]
injury is unclear in these instances. However, the incidence of transient paresthesias is increased when spinal
anesthetics are placed in patients with lumbar spinal pathology such as spinal stenosis, and transient paresthesias
[239]
increase the risk of persistent paresthesias after spinal anesthetics. Unfortunately, no clinical studies have
[10]
addressed the risk of neurologic injury associated with neuraxial anesthesia in patients with spinal stenosis.
Summary
Neuraxial anesthetic and analgesic techniques remain an important part of the anesthesiologist’s armamentarium.
Depending on specific patient factors and the setting in which these techniques are applied, they may offer
significant advantages. Fortunately, neuraxial techniques are associated with a low incidence of significant
complications. However, as overall perioperative safety improves, rare and potentially devastating complications
from neuraxial anesthesia and analgesia become more significant. Anesthesiologists can minimize the risk of these
complications by appropriately applying neuraxial techniques in carefully selected patients. Proper patient selection
depends on detailed knowledge of any conditions that may predispose patients to complications from neuraxial
techniques.
REFERENCES
1. Bier A: Versuche ueber cocainisirung des rueckenmarkes. Deutsche Zeitschrift fuer Chirurgie 51:361–368, 1899.
2. Marinacci
AA: Neurological aspects of complications of spinal anesthesia with medicolegal implications. Bull Los Angeles Neurol Soc
25:170–192, 1960.
3. Moore DC, Bridenbaugh LD: Spinal (subarachnoid) block. A review of 11,574 cases. JAMA 195:907–912, 1966.
4. Dripps RD, Vandam LD: Long term follow-up of patients who received 10,098 spinal anesthetics: Failure to discover major neurological
sequelae. JAMA 156:1486–1491, 1954.
5. Nicholson MJ, Eversole UH: Neurologic complications of spinal anesthesia. JAMA 132:679–685, 1946.
6. Giebler RM, Scherer RU, Peters J: Incidence of neurologic complications related to thoracic epidural catheterization. Anesthesiology 86:55–63,
1997.
7. AuroyY, Narchi P, Messiah A, et al: Serious complications related to regional anesthesia: Results of a prospective survey in France.
8. Kane RE: Neurologic deficits following epidural or spinal anesthesia. Anesth Analg 60:150–161, 1981.
9. Wang LP, Hauerberg J, Schmidt JF: Incidence of spinal epidural abscess after epidural analgesia: A national 1-year survey. Anesthesiology
91:1928–1936, 1999.
10. Horlocker
TT, McGregor DG, Matsushige DK, et al: A retrospective review of 4767 consecutive spinal anesthetics: Central nervous system
11. Horlocker TT, Wedel DJ: Neurologic complications of spinal and epidural anesthesia. Reg Anesth Pain Med 25:83–98, 2000.
12. Dripps RD: A comparison of the malleable needle and catheter techniques for continuoues spinal anesthesia. N Y State Med J 50:1595–1599,
1950.
13. MyersRR, Heckman HM: Effects of local anesthesia on nerve blood flow: Studies using lidocaine with and without epinephrine.
14. Rigler ML, Drasner K, Krejcie TC, et al: Cauda equina syndrome after continuous spinal anesthesia. Anesth Analg 72:275–281, 1991.
1034
16. Berde C: Regional anesthesia in children: What have we learned? Anesth Analg 83:897–900, 1996.
17. WoodCE, Goresky GV, Klassen KA, et al: Complications of continuous epidural infusions for postoperative analgesia in children. Can J
Anaesth 41:613–620, 1994.
18. Giaufre
E, Dalens B, Gombert A: Epidemiology and morbidity of regional anesthesia in children: A one-year prospective survey of the French-
Language Society of Pediatric Anesthesiologists. Anesth Analg 83:904–912, 1996.
19. Abel MD, Horlocker TT, Messick JM, et al: Neurologic complications following placement of 4392 epidural catheters in anesthetized patients.
Reg Anesth 23S:3, 1998.
20. Grady RE, Horlocker TT, Brown RD, et al: Neurologic complications after placement of cerebrospinal fluid drainage catheters and needles in
anesthetized patients: Implications for regionalanesthesia. Mayo Perioperative Outcomes Group. Anesth Analg 88:388–392, 1999.
21. Kely D, Hewitt SR: Lumbar epidural block in labor: A clinical analysis. Br J Anaesth 44:414–415, 1972.
22. Dawkins CJ: An analysis of the complications of extradural and caudal block. Anaesthesia 24:554–563, 1969.
23. Brown EM, Elman DS: Postoperative backache. Anesth Analg 40:683, 1961.
24. BridenbaughPO, Greene NM, Brull SJ: Spinal (subarachnoid) neural blockade. In Cousins MJ, Bridenbaugh PO (eds): Neural Blockade in
Clinical Anesthesia and Pain Management, 3rd ed. Philadelphia, Lippincott-Raven, 1998, pp 203–241.
25. Kock S, Hopf HB: Incidence and predisposing factors of persistent backache after lumbar catheter epidural anesthesia in a non-obstetrical
setting. Anasthesiol Intensivmed Notfallmed, Schmerzther 33:648–652, 1998.
26. Peng AT, Behar S, Blancato LS: Reduction of postlumbar puncture backache by the use of field block anesthesia prior to lumbar puncture
[letter]. Anesthesiology 63:227–228, 1985.
27. Hsieh
JR, Hui YL, Yu CC, et al: Local supplementation of ketoprofen reduces the incidence of low back pain after lumbar epidural anesthesia.
Chang-Keng i Hsueh Tsa Chih 22:439–444, 1999.
28. WangYL, Hsieh JR, Chung HS, et al: The local addition of tenoxicam reduces the incidence of low back pain after lumbar epidural anesthesia.
29. WangYL, Tan PP, Yang CH, et al: Epidural dexamethasone reduces the incidence of backache after lumbar epidural anesthesia. Anesth Analg
84:376–378, 1997.
30. Pinczower GR, Gyorke A: Vertebral osteomyelitis as a cause of back pain after epidural anesthesia. Anesthesiology 84:215–217, 1996.
31. Markowitz A, Farcon EL, Marx GF: Osteitis condensans ilii misdiagnosed as post-epidural block backache [letter]. Reg Anesth 17:355, 1992.
32. Kee WD: An unusual case of back pain after epidural anesthesia: Ureteral obstruction. Anesth Analg 77:1295–1297, 1993.
33. Breen TW, Ransil BJ, Groves PA, Oriol NE: Factors associated with back pain after childbirth. Anesthesiology 81:29–34, 1994.
34. Halpern S, Preston R: Postdural puncture headache and spinal needle design. Anesthesiology 81:1376–1383, 1994.
35. Brownridge P: The management of headache following accidental dural puncture in obstetric patients. Anaesth Intensive Care 11:4–15, 1983.
36. Shearer VE, Jhaveri HS, Cunningham FG: Puerperal seizures after post-dural puncture headache. Obstet Gynecol 85:255–260, 1995.
37. Vandam LD, Dripps RD: Long-term follow-up of patients who received 10,098 spinal anesthetics: Syndrome of decreased intracranial
pressure (headache and ocular and auditory difficulties). JAMA 161:586–591, 1956.
38. Frison LM, Dorsey DL: Epidural blood patch and late postpartum eclampsia. Anesth Analg 82:666–668, 1996.
39. Rosenow F, Huber M, Scheidt W, Heiss WD: Neurological cause of late postpartum seizures. Arch Gynecol Obstet 248:151–155, 1991.
40. Bolton
VE, Leicht CH, Scanlon TS: Postpartum seizure after epidural blood patch and intravenous caffeine sodium benzoate. Anesthesiology
70:146–149, 1989.
41. Paesch M: Unexpected postpartum seizures associated with post-dural puncture headache treated with caffeine. Int J Obstet Anesth 5:43–46,
1996.
42. Vos
PE, de Boer WA, Wurzer JA, van Gijn J: Subdural hematoma after lumbar puncture: Two case reports and review of the literature. Clin
Neurol Neurosurg 93:127–132, 1991.
43. Rasmussen BS, Blom L, Hansen P, Mikkelsen SS: Postspinal headache in young and elderly patients. Two randomised, double-blind studies
1035
that compare 20- and 25-gauge needles. Anaesthesia 44:571–573, 1989.
44. Flaatten H, Raeder J: Spinal anaesthesia for outpatient surgery. Anaesthesia 40:1108–1111, 1985.
45. Kaukinen S, Kaukinen L, Kannisto K, Kataja M: The prevention of headache following spinal anaesthesia. Ann Chir Gynaecol 70:107–111,
1981.
46. Meyer-Hamme K, Stratmann D, Watermann WF, Gotte A: Postspinal headache—a clinical problem. Anaesthesist 28:77–80, 1979.
47. Bolder PM: Postlumbar puncture headache in pediatric oncology patients. Anesthesiology 65:696–698, 1986.
48. Lybecker H, Moller JT, May O, Nielsen HK: Incidence and prediction of postdural puncture headache. A prospective study of 1021 spinal
anesthesias. Anesth Analg 70:389–394, 1990.
49. Meeks SK: Postpartum headache. In Chestnut DH (ed): Obstetric Anesthesia—Principles and Practice. St. Louis, Mosby, 1994, pp 606–620.
50. Ravindran
RS, Viegas OJ, Tasch MD, et al: Bearing down at the time of delivery and the incidence of spinal headache in parturients. Anesth
Analg 60:524–526, 1981.
51. Kortum K, Nolte H, Kenkmann HJ: Sex difference related complication rates after spinal anaesthesia. Reg Anaest 5:1–6, 1982.
52. Cruickshank RH, Hopkinson JM: Fluid flow through dural puncture sites. An in vitro comparison of needle point types. Anaesthesia 44:415–
418, 1989.
53. Ready LB, Cuplin S, Haschke RH, Nessly M: Spinal needle determinants of rate of transdural fluid leak. Anesth Analg 69:457–460, 1989.
54. Flaatten H, Felthaus J, Larsen R, et al: Postural post-dural puncture headache after spinal and epidural anaesthesia. A randomised, double-blind
study. Acta Anaesthesiol Scand 42:759–764, 1998.
55. Sadove MS, Levin MJ, Rant-Sejdinaj I: Neurological complications of spinal anaesthesia. Can Anaesth Soc J 8:405–416, 1961.
56. Corbey
MD, Bach AB, Lech K, Frorup AM: Grading of severity of postdural puncture headache after 27-gauge Quincke and Whitacre needles.
57. Mihic D: Postspinal headache and relationship of needle bevel to longitudinal dural fibers. Reg Anesth 10:76–81, 1985.
58. DittmannM, Schafer HG, Ulrich J, Bond-Taylor W: Anatomical re-evaluation of lumbar dura mater with regard to postspinal headache. Effect
of dural puncture. Anaesthesia 43:635–637, 1988.
59. Janik R, Dick W: Post spinal headache. Its incidence following the median and paramedian techniques. Anaesthesist 41:137–141, 1992.
60. Yucel A, Ozyalcin S, Talu GK, et al: Intravenous administration of caffeine sodium benzoate for postdural puncture headache. Reg Anesth
Pain Med 24:51–54, 1999.
61. Ilioff
G, Strelec SF, Rothfus W, Teeple E: Does prophylactic intramuscular caffeine sodium benzoate decrease incidence of post dural
puncture headache? Reg Anesth 15:65, 1990.
62. Strelec
S, Prylinski J, Sakert T, Royal M: The efficacy of multi-dose oral caffeine in prevention of post-dural puncture headache. Reg Anesth
19:79, 1994.
63. WeberJG, Klindworth JT, Arnold JJ, et al: Prophylactic intravenous administration of caffeine and recovery after ambulatory surgical
procedures. Mayo Clin Proc 72:621–626, 1997.
64. Weber JG, Ereth MH, Danielson DR: Perioperative ingestion of caffeine and postoperative headache. Mayo Clin Proc 68:842–845, 1993.
65. Carbaat PA, van Crevel H: Lumbar puncture headache: Controlled study on the preventive effect of 24 hours’ bed rest. Lancet 2:1133–1135,
1981.
66. Crawford JS: Experiences with epidural blood patch. Anaesthesia 35:513–515, 1980.
67. Taivainen
T, Pitkanen M, Tuominen M, Rosenberg PH: Efficacy of epidural blood patch for postdural puncture headache. Acta Anaesthesiol
Scandinavica 37:702–705, 1993.
68. Rainbird A, Pfitzner J: Restricted spread of analgesia following epidural blood patch. Case report with a review of possible complications.
Anaesthesia 38:481–484, 1983.
69. Naulty JS, Herold R: Successful epidural anesthesia following epidural blood patch. Anesth Analg 57:272–273, 1978.
70. Abouleish E, Wadhwa RK, de la Vega S, et al: Regional analgesia following epidural blood patch. Anesth Analg 54:634–636, 1975.
71. Crawford JS: Re: epidural blood patch [letter]. Anaesth Intensive Care 11:384, 1983.
1036
72. OngBY, Graham CR, Ringaert KR, et al: Impaired epidural analgesia after dural puncture with and without subsequent blood patch. Anesth
Analg 70:76–79, 1990.
73. Hebl JR, Horlocker TT, Chantigian RC, Schroeder DR: Epidural anesthesia and analgesia are not impaired after dural puncturewith or without
epidural blood patch. Anesth Analg 89:390–4, 1999.
74. Tarkkila
PJ, Miralles JA, Palomaki EA: The subjective complications and efficiency of the epidural blood patch in the treatment of postdural
puncture headache. Reg Anesth 14:247–50, 1989.
75. Abouleish E, Vega S, Blendinger I, Tio TO: Long-term follow-up of epidural blood patch. Anesth Analg 54:459–63, 1975.
76. Stride PC, Cooper GM: Dural taps revisited. A 20-year survey from Birmingham Maternity Hospital. Anaesthesia 48:247–55, 1993.
77. Kshatri AM, Foster PA: Adrenocorticotropic hormone infusion as a novel treatment for postdural puncture headache. Reg Anesth 22:432–434,
1997.
78. Gupta S, Agrawal A: Postdural puncture headache and ACTH [letter]. J Clin Anesth 9:258, 1997.
79. Foster P: ACTH treatment for post-lumbar puncture headache. Br J Anaesth 73:429, 1994.
80. Collier BB: Treatment for post dural puncture headache [letter]. Br J Anaesth 72:366–367, 1994.
81. Duffy PJ, Crosby ET: The epidural blood patch. Resolving the controversies. Can J Anaesth 46:878–86, 1999.
82. Phillips
OC, Ebner H, Nelson AT, Black MH: Neurologic complications following spinal anesthesia with lidocaine: A prospective review of
10,440 cases. Anesthesiology 30:284–289, 1969.
83. Johnson ME: Potential neurotoxicity of spinal anesthesia with lidocaine. Mayo Clin Proc 75:921–932, 2000.
84. Tetzlaff JE, Dilger J, Yap E, et al: Cauda equina syndrome after spinal anaesthesia in a patient with severe vascular disease. Can J Anaesth
45:667–669, 1998.
85. Jackenkroll R, Krause KH: Cauda equina syndrome following spinal anaesthesia with mepivacaine. Nervenarzt 52:473–476, 1981.
86. Ravindran
RS, Bond VK, Tasch MD, et al: Prolonged neural blockade following regional analgesia with 2-chloroprocaine. Anesth Analg
59:447–451, 1980.
87. Kubina P, Gupta A, Oscarsson A, et al: Two cases of cauda equina syndrome following spinal-epidural anesthesia. Reg Anesth 22:447–50,
1997.
88. Kanai Y, Katsuki H, Takasaki M: Graded, irreversible changes in crayfish giant axon as manifestations of lidocaine neurotoxicity in vitro.
Anesth Analg 86:569–573, 1998.
89. LambertLA, Lambert DH, Strichartz GR: Irreversible conduction block in isolated nerve by high concentrations of local anesthetics.
90. Kalichman MW, Powell HC, Myers RR: Quantitative histologic analysis of local anesthetic-induced injury to rat sciatic nerve. J Pharmacol
Exp Ther 250:406–413, 1989.
91. Kroin JS, Penn RD, Levy FE, Kerns JM: Effect of repetitive lidocaine infusion on peripheral nerve. Exp Neurol 94:166–173, 1986.
92. Ready LB, Plumer MH, Haschke RH, et al: Neurotoxicity of intrathecal local anesthetics in rabbits. Anesthesiology 63:364–370, 1985.
93. Li DF, Bahar M, Cole G, Rosen M: Neurological toxicity of the subarachnoid infusion of bupivacaine, lignocaine or 2-chloroprocaine in the
rat. Br J Anaesth 57:424–429, 1985.
94. Rosen MA, Baysinger CL, Shnider SM, et al: Evaluation of neurotoxicity after subarachnoid injection of large volumes of local anesthetic
solutions. Anesth Analg 62:802–808, 1983.
95. Drasner
K, Sakura S, Chan VW, et al: Persistent sacral sensory deficit induced by intrathecal local anesthetic infusion in the rat.
96. Bainton CR, Strichartz GR: Concentration dependence of lidocaine-induced irreversible conduction loss in frog nerve. Anesthesiology 81:657–
67, 1994.
97. Drasner K: Lidocaine spinal anesthesia: A vanishing therapeutic index? Anesthesiology 87:469–472, 1997.
98. Hashimoto
K, Sakura S, Bollen AW, et al: Comparative toxicity of glucose and lidocaine administered intrathecally in the rat. Reg Anesth Pain
Med 23:444–450, 1998.
1037
99. SakuraS, Chan VW, Ciriales R, Drasner K: The addition of 7.5% glucose does not alter the neurotoxicity of 5% lidocaine administered
intrathecally in the rat. Anesthesiology 82:236–240, 1995.
100. Selander D: Neurotoxicity of local anesthetics: animal data. Reg Anesth 18:461–468, 1993.
101. Johnson
ME: Perineural concentration of lidocaine is more relevant to spinal neurotoxicity than the concentration administered. Anesth Analg
90:766–767, 2000.
102. Gold MS, Reichling DB, Hampl KF, et al: Lidocaine toxicity in primary afferent neurons from the rat. J Pharmacol Exp Ther 285:413–421,
1998.
103. Hodgson PS, Neal JM, Pollock JE, Liu SS: The neurotoxicity of drugs given intrathecally (spinal). Anesth Analg 88:797–809, 1999.
104. Eisenach
JC, De Kock M, Klimscha W: Alpha(2)-adrenergic agonists for regional anesthesia. A clinical review of clonidine (1984–1995).
105. Schneider M, Ettlin T, Kaufmann M, et al: Transient neurologic toxicity after hyperbaric subarachnoid anesthesia with 5% lidocaine. Anesth
Analg 76:1154–1157, 1993.
106. Henderson DJ, Faccenda KA, Morrison LM: Transient radicular irritation with intrathecal plain lignocaine. Acta Anaesthesiol Scand 42:376–
378, 1998.
107. Ramasamy D, Eadie R: Transient radicular irritation after spinal anaesthesia with 2% isobaric lignocaine. Br J Anaesth 79:394–395, 1997.
108. Ramasamy D, Eadie R: Transient dysaesthesia following spinal anaesthesia with 2% lignocaine [letter]. Anaesth Intensive Care 25:90–91,
1997.
109. Hampl KF, Schneider MC, Bont A, Pargger H: Transient radicular irritation after single subarachnoid injection of isobaric 2% lignocaine for
spinal anaesthesia. Anaesthesia 51:178–181, 1996.
110. Rodriguez-Chinchilla
R, Rodriguez-Pont A, Pintanel T, Vidal-Lopez F: Bilateral severe pain at L3–4 after spinal anaesthesia with hyperbaric
5% lignocaine. Br J Anaesth 76:328–329, 1996.
111. Cozanitis DA: Leg pains after spinal anaesthesia [letter]. Can J Anaesth 42:657, 1995.
112. Pinczower GR, Chadwick HS, Woodland R, Lowmiller M: Bilateral leg pain following lidocaine spinal anaesthesia. Can J Anaesth 42:217–
220, 1995.
113. Sjostrom S, Blass J: Severe pain in both legs after spinal anaesthesia with hyperbaric 5% lignocaine solution. Anaesthesia 49:700–702, 1994.
114. SnyderR, Hui G, Flugstad P, Viarengo C: More cases of possible neurologic toxicity associated with single subarachnoid injections of 5%
hyperbaric lidocaine [letter]. Anesth Analg 78:411, 1994.
116. Hampl
KF, Schneider MC, Pargger H. A similar incidence of transient neurologic symptoms after spinal anesthesia with 2% and 5% lidocaine.
Anesth Analg 83:1051–1054, 1996.
117. Pollock JE, Neal JM, Stephenson CA, Wiley CE: Prospective study of the incidence of transient radicular irritation in patients undergoing
spinal anesthesia. Anesthesiology 84:1361–1367, 1996.
118. Hampl KF, Schneider MC, Ummenhofer W, Drewe J: Transient neurologic symptoms after spinal anesthesia. Anesth Analg 81:1148–1153,
1995.
119. Bergeron L, Girard M, Drolet P, et al: Spinal procaine with and without epinephrine and its relation to transient radicular irritation. Can J
Anaesth 46:846–849, 1999.
120. Axelrod
EH, Alexander GD, Brown M, Schork MA: Procaine spinal anesthesia: A pilot study of the incidence of transient neurologic
symptoms. J Clin Anesth 10:404–409, 1998.
121. Pollock JE, Liu SS, Neal JM, Stephenson CA: Dilution of spinal lidocaine does not alter the incidence of transient neurologic symptoms.
122. Pollock
JE, Burkhead D, Neal JM, et al: Spinal nerve function in five volunteers experiencing transient neurologic symptoms after lidocaine
subarachnoid anesthesia. Anesth Analg 90:658–665, 2000.
123. Douglas MJ: Neurotoxicity of lidocaine—does it exist? Can J Anaesth 42:181–185, 1995.
124. Hogan QH, Prost R, Kulier A, et al: Magnetic resonance imaging of cerebrospinal fluid volume and the influence of body habitus and
abdominal pressure. Anesthesiology 84:1341–1349, 1996.
1038
125. Sakura S, Sumi M, Sakaguchi Y, et al: The addition of phenylephrine contributes to the development of transient neurologicsymptoms after
spinal anesthesia with 0.5% tetracaine. Anesthesiology 87:771–778, 1997.
126. Milnes JN: Early diagnosis of tumours of cauda equina. J Neurol Neurosurg Psychiatr 16:158–165, 1953.
127. Fischer G, Tommasi M: Spinal ependymomas. In Vinken PJ, Vryun GW, Klawans HLJ (eds): Handbook of Clinical Neurology. Amsterdam,
the Netherlands, North-Holland Publishing, 1976, pp 353–387.
128. Parenti G, Fiori L, Marconi F, Tusini G: Primary cauda equina tumors. J Neurosurg Sci 37:149–156, 1993.
129. Ker NB, Jones CB: Tumours of the cauda equina: The problem of differential diagnosis. J Bone Joint Surg Br 67:358–362, 1985.
130. Sonneland PR, Scheithauer BW, Onofrio BJ: Myxopapillary ependymoma: A clinicopathologic and immunocytochemical study of 77 cases.
Cancer 56:883–893, 1985.
131. Norstrom CW, Kernohan JW, Lov JG: One hundred primary caudal tumors. JAMA 178:1071–1077, 1961.
132. Moore DC, Thompson GE: Commentary: Neurotoxicity of local anesthetics—an issue or a scapegoat? Reg Anesth Pain Med 23:605–610,
1998.
133. Ben-David B, Solomon E, Levin H, et al: Intrathecal fentanyl with small-dose dilute bupivacaine: Better anesthesia without prolonging
recovery. Anesth Analg 85:560–565, 1997.
134. Anonymous: Spinal stroke [editorial]. Lancet 2:1299–1300, 1974.
135. Wedel DJ, Horlocker TT: Risks of regional anesthesia— infectious, septic. Reg Anesth 21:57–61, 1996.
136. Kalichman
MW, Calcutt NA: Local anesthetic-induced conduction block and nerve fiber injury in streptozotocin-diabetic rats. Anesthesiology
77:941–947, 1992.
137. DahlgrenN, Tornebrandt K: Neurological complications after anaesthesia. A follow-up of 18,000 spinal and epidural anaesthetics performed
over three years. Acta Anaesthesiol Scand 39:872–880, 1995.
138. Usubiaga JE: Neurological complications following epidural anesthesia. Int Anesthesiol Clin 13:1–153, 1975.
139. Horlocker
TT, Wedel DJ: Anticoagulation and neuraxial block: Historical perspective anesthetic implications, and risk management. Reg
Anesth Pain Med 23:129–134, 1998.
140. Horlocker
141. Vandermeulen EP, Van Aken H, Vermylen J: Anticoagulants and spinal-epidural anesthesia. Anesth Analg 79:1165–1177, 1994.
142. Groen RJ, Ponssen H: The spontaneous spinal epidural hematoma. A study of the etiology. J Neurol Sci 98:121–138, 1990.
143. Salzman EW, Rosenberg RD, Smith MH, et al: Effect of heparin and heparin fractions on platelet aggregation. J Clin Invest 65:64–73, 1980.
144. Tryba M: Epidural regional anesthesia and low molecular heparin: Anasthesiolo Intensivmedizin, Notfallmed Schmerzther 28:179–181, 1993.
145. Lindgren L, Silvanto M, Scheinin B, et al: Erythrocyte counts in the cerebrospinal fluid associated with continuous spinal anaesthesia. Acta
146. Horlocker TT, Wedel DJ, Schroeder DR, et al: Preoperative antiplatelet therapy does not increase the risk of spinal hematoma associated with
regional anesthesia. Anesth Analg 80:303–309, 1995.
147. Colon-Otero G, Cockeriii KJ, Bowie EJ: How to diagnose bleeding disorders. Postgrad Med 90:145–150, 1991.
148. Heit JA: Low-molecular-weight heparin: Biochemistry, pharmacology, and concurrent drug precautions. Reg Anesth Pain Med 23:135–139,
1998.
149. Greensite FS, Katz J: Spinal subdural hematoma associated with attempted epidural anesthesia and subsequent continuous spinal anesthesia.
Anesth Analg 59:72–73, 1980.
150. Gerancher
JC, Waterer R, Middleton J: Transient paraparesis after postdural puncture spinal hematoma in a patient receiving ketorolac.
151. Williams KN, Jackowski A, Evans PJ: Epidural haematoma requiring surgical decompression following repeated cervical epidural steroid
injections for chronic pain. Pain 42:197–199, 1990.
152. Anonymous: CLASP: A randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women.
1039
CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) Collaborative Group. Lancet 343:619–629, 1994.
153. MishimaK, Aritake K, Morita A, et al: A case of acute spinal epidural hematoma in a patient with antiplatelet therapy. No Shinkei Geka
17:849–853, 1989.
154. Mayumi T, Dohi S: Spinal subarachnoid hematoma after lumbar puncture in a patient receiving antiplatelet therapy. Anesth Analg 62:777–
779, 1983.
155. Lincoff
AM, Califf RM, Topol EJ: Platelet glycoprotein IIb/IIIa receptor blockade in coronary artery disease. J Am Coll Cardiol 35:1103–
1115, 2000.
156. Urmey WF, Rowlingson J: Do antiplatelet agents contribute to the development of perioperative spinal hematoma? Reg Anesth Pain Med
23:146–151, 1998.
157. Sternlo JE, Hybbinette CH: Spinal subdural bleeding after attempted epidural and subsequent spinal anaesthesia in a patient on
thromboprophylaxis with low molecular weight heparin. Acta Anaesthesiol Scand 39:557–559, 1995.
158. Eastwood DW: Hematoma after epidural anesthesia: Relationship of skin and spinal angiomas. Anesth Analg 73:352–354, 1991.
159. Enneking FK, Benzon H: Oral anticoagulants and regional anesthesia: A perspective. Reg Anesth Pain Med 23(6 Suppl 2):140–145, 1998.
160. Kessler
CM: The pharmacology of aspirin, heparin, coumarin, and thrombolytic agents. Implications for therapeutic use in cardiopulmonary
disease. Chest 99:97S–112S, 1991.
161. Hirsch J: Oral anticoagulant drugs. New Engl J Med 324:1865–1875, 1991.
162. Chan TY: Adverse interactions between warfarin and nonsteroidal antiinflammatory drugs: Mechanisms, clinical significance, and avoidance.
Ann Pharmacother 29:1274–1283, 1995.
163. Rivey
MP, Wood RD, Allington DR, et al: Pharmacy-managed protocol for warfarin use in orthopedic surgery patients. Am J Health Syst
Pharm 52:1310–1316, 1995.
164. Odoom JA, Sih IL: Epidural analgesia and anticoagulant therapy. Experience with one thousand cases of continuous epidurals. Anaesthesia
38:254–259, 1983.
165. Horlocker TT, Wedel DJ, Schlichting JL: Postoperative epidural analgesia and oral anticoagulant therapy. Anesth Analg 79:89–93, 1994.
166. White RH, McKittrick T, Hutchinson R, Twitchell J: Temporary discontinuation of warfarin therapy: Changes in the international normalized
ratio. Ann Intern Med 122:40–42, 1995.
167. Horlocker TT: Complications of spinal and epidural anesthesia. Anesthesiol Clin North Am 18:461–485, 2000.
168. HirshJ, Raschke R, Warkentin TE, et al: Heparin: Mechanism of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and
safety. Chest 108:258S–275S, 1995.
169. Collins R, Scrimgeour A, Yusuf S, Peto R: Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of
subcutaneous heparin. Overview of results of randomized trials in general, orthopedic, and urologic surgery. N Engl J Med 318:1162–1173, 1988.
170. Gallus AS, Hirsh J, Tutle RJ, et al: Small subcutaneous doses of heparin in prevention of venous thrombosis. N Engl J Med 288:545–551,
1973.
171. Dehring DJ, Arens JF: Pulmonary thromboembolism: Disease recognition and patient management. Anesthesiology 73:146–164, 1990.
172. Liu SS, Mulroy MF: Neuraxial anesthesia and analgesia in the presence of standard heparin. Reg Anesth Pain Med 23:157–163, 1998.
173. Rao TL, El-Etr AA: Anticoagulation following placement of epidural and subarachnoid catheters: an evaluation of neurologic sequelae.
174. Baron HC, LaRaja RD, Rossi G, Atkinson D: Continuous epidural analgesia in the heparinized vascular surgical patient: A retrospective
review of 912 patients. J Vasc Surg 6:144–146, 1987.
175. Wildsmith JA, McClure JH: Anticoagulant drugs and central nerve blockade. Anaesthesia 46:613–614, 1991.
176. Wulf H: Epidural anaesthesia and spinal haematoma. Can J Anaesth 43:1260–1271, 1996.
177. Chaney MA: Intrathecal and epidural anesthesia and analgesia for cardiac surgery. Anesth Analg 84:1211–1221, 1997.
178. Hirsh J, Levine MN: Low molecular weight heparin. Blood 79:1–17, 1992.
179. Ramakrishna R, Manoharan A, Kwan YL, Kyle PW: Heparin-induced thrombocytopenia: Cross-reactivity between standard heparin, low
molecular weight heparin, dalteparin (Fragmin) and heparinoid, danaparoid (Orgaran). Br J Haematol 91:736–768, 1995.
1040
180. Schroeder DR: Statistics: Detecting a rare adverse drug reaction using spontaneous reports. Reg Anesth Pain Med 23:183–189, 1998.
181. Majerus PW, Broze GJ, Miletich JP, Tollefsen DM: Anticoagulant, thrombolytic, and antiplatelet drugs. In: Hardman JG, Limbird LE,
Mollnoff PB, et al: Goodman and Gilman’s The Pharmcologic Basis of Therapeutics, 9th ed. New York, McGraw-Hill, 1996, pp 1341–1359.
182. VanSchaeybroeck P, Van Calenbergh F, Van De Werf F, et al: Spontaneous spinal epidural hematoma associated with thrombolysis and
anticoagulation therapy: Report of three cases. Clin Neurol Neurosurg 100:283–287, 1998.
183. Krolick MA, Cintron GB: Spinal epidural hematoma causing cord compression after tissue plasminogen activator and heparin therapy. South
Med J 84:670–671, 1991.
184. Mustafa MH, Gallino R: Spontaneous spinal epidural hematoma causing cord compression after streptokinase and heparin therapy for acute
coronary artery occlusion. South Med J 81:1202–1203, 1988.
185. RabitoSF, Ahmed S, Feinstein L, Winnie AP: Intrathecal bleeding after the intraoperative use of heparin and urokinase during continuous
spinal anesthesia. Anesth Analg 82:409–411, 1996. 1996.
186. Onishchuk JL, Carlsson C: Epidural hematoma associated with epidural anesthesia: Complications of anticoagulant therapy. Anesthesiology
77:1221–1223, 1992.
187. Dickman CA, Shedd SA, Spetzler RF, et al: Spinal epidural hematoma associated with epidural anesthesia: Complications of systemic
heparinization in patients receiving peripheral vascular thrombolytic therapy. Anesthesiology 72:947–950, 1990.
188. Rosenquist RW, Brown DL: Neuraxial bleeding: Fibrinolytics/thrombolytics. Reg Anesth Pain Med 23:152–156, 1998.
189. McEvoy MD, Bailey M, Taylor D, Del Schutte H Jr: Noncompliance in the inpatient administration of enoxaparin in conjunction with
epidural or spinal anesthesia. J Arthroplasty 15:604–607, 2000.
190. KeeganMT, Horlocker TT: Epidural catheter removal before unanticipated anticoagulation: The pharmacy fail-safe [letter]. Anesthesiology
91:328, 1999.
191. Weed
LH, Wegeforth LH, Ayer JB, Felton LD: The production of meningitis by release of cerebrospinal fluid during experimental septicemia.
JAMA 72:190–193, 1919.
192. Pray LG: Lumbar puncture as a factor in the pathogenesis of meningitis. Am Dis Child 295:62–68, 1941.
193. Eng RH, Seligman SJ: Lumbar puncture-induced meningitis. JAMA 245:1456–1469, 1981.
194. Smith KM, Deddish RB, Ogata ES: Meningitis associated with serial lumbar punctures and post-hemorrhagic hydrocephalus. J Pediatr
109:1057–60, 1986.
195. Teele DW, Dashefsky B, Rakusan T, Klein JO: Meningitis after lumbar puncture in children with bacteremia. N Engl J Med 305:1079–1081,
1981.
196. Wegeforth P: Lumbar puncture as a factor in the causation of meningitis. Am J Med Sci 158:183–202, 1919.
197. Carp H, Bailey S: The association between meningitis and dural puncture in bacteremic rats [see comments]. Anesthesiology 76:739–42, 1992.
198. James FM, George RH, Naiem H, White GJ: Bacteriologic aspects of epidural analgesia. Anesth Analg 55:187–190, 1976.
199. Baker AS, Ojemann RG, Swartz MN, Richardson EP Jr: Spinal epidural abscess. N Engl J Med 293:463–468, 1975.
200. Kindler
CH, Seeberger MD, Staender SE: Epidural abscess complicating epidural anesthesia and analgesia. An analysis of the literature. Acta
201. KindlerC, Seeberger M, Siegemund M, Schneider M: Extradural abscess complicating lumbar extradural anaesthesia and analgesia in an
obstetric patient. Acta Anaesthesiol Scand 40:858–861, 1996.
202. Holt HM, Andersen SS, Andersen O, et al: Infections following epidural catheterization. J Hosp Infect 30:253–260, 1995.
203. MamourianAC, Dickman CA, Drayer BP, Sonntag VK: Spinal epidural abscess: Three cases following spinal epidural injection
demonstrated with magnetic resonance imaging. Anesthesiology 78:204–207, 1993.
204. Larsson EM, Holtas S, Cronqvist S: Emergency magnetic resonance examination of patients with spinal cord symptoms. Acta Radiol 29:69–
75, 1988.
205. Wang JS, Fellows DG, Vakharia S, Rosenbaum AE, Thomas PS: Epidural abscess—early magnetic resonance imaging detection and
conservative therapy. Anesth Analg 82:1069–1071, 1996.
206. Pegues DA, Carr DB, Hopkins CC: Infectious complications associated with temporary epidural catheters. Clin Infect Dis 19:970–972, 1994.
1041
207. Nordstrom O, Sandin R: Delayed presentation of an extradural abscess in a patient with alcohol abuse. Br J Anaesth 70:368–369, 1993.
208. Sowter MC, Burgess NA, Woodsford PV, Lewis MH: Delayed presentation of an extradural abscess complicating thoracic extradural
analgesia. Br J Anaesth 68:103–105, 1992.
209. Dawson P, Rosenfeld JV, Murphy MA, Hellyar AG: Epidural abscess associated with postoperative epidural analgesia. Anaesth Intensive
Care 19:569–572, 1991.
210. Strong WE: Epidural abscess associated with epidural catheterization: A rare event? Report of two cases with markedly delayed presentation.
211. Ericsson M, Algers G, Schliamser SE: Spinal epidural abscesses in adults: Review and report of iatrogenic cases. Scand J Infect Dis 22:249–
257, 1990.
212. Sollmann WP, Gaab MR, Panning B: Lumbar epidural hematoma and spinal abscess following peridural anesthesia. Reg Anaesth 10:121–124,
1987.
213. Bader AM, Gilbertson L, Kirz L, Datta S: Regional anesthesia in women with chorioamnionitis. Reg Anesth 17:84–86, 1992.
214. Scott L, Hollier L, Dias K: Perinatal herpesvirus infections. Infect Dis Clin North Am 11:27–53, 1997.
215. Bader AM, Camann WR, Datta S: Anesthesia for cesarean delivery in patients with herpes simplex virus type-2 infections. Reg Anesth
15:261–263, 1990.
216. Crosby ET, Halpern SH, Rolbin SH: Epidural anaesthesia for caesarean section in patients with active recurrent genital herpes simplex
infections: A retrospective review. Can J Anaesth 36:701–704, 1989.
217. RamanathanS, Sheth R, Turndorf H: Anesthesia for cesarean section in patients with genital herpes infections: A retrospective study.
218. Crone
LA, Conly JM, Storgard C, et al: Herpes labialis in parturients receiving epidural morphine following cesarean section. Anesthesiology
73:208–13, 1990.
219. Crone LA, Conly JM, Clark KM, et al: Recurrent herpes simplex virus labialis and the use of epidural morphine in obstetric patients. Anesth
Analg 67:318–323, 1988.
220. Shapiro HM, Grant I, Weinger MB: AIDS and the central nervous system. Implications for the anesthesiologist. Anesthesiology 80:187–200,
1994.
221. Miller RG, Parry GJ, Pfaeffl W, et al: The spectrum of peripheral neuropathy associated with ARC and AIDS. Muscle Nerve 11:857–863,
1988.
222. Leger
JM, Bouche P, Bolgert F, et al: The spectrum of polyneuropathies in patients infected with HIV. J Neurol Neurosurg Psychiatry
52:1369–1374, 1989.
223. ChalmersAC, Aprill BS, Shephard H: Cerebrospinal fluid and human immunodeficiency virus. Findings in healthy, asymptomatic,
seropositive men. Arch Intern Med 1990; 150:1538–1540, 1990.
224. Hughes
SC, Dailey PA, Landers D, Dattel BJ, et al: Parturients infected with human immunodeficiency virus and regional anesthesia. Clinical
and immunologic response. Anesthesiology 82:32–37, 1995.
225. Tom DJ, Gulevich SJ, Shapiro HM, et al: Epidural blood patch in the HIV-positive patient. Review of clinical experience. San Diego HIV
Neurobehavioral Research Center. Anesthesiology 76:943–947, 1992.
226. Lynch NM, Cofield RH, Silbert PL, Hermann RC: Neurologiccomplications after total shoulder arthroplasty. J Shoulder Elbow Surg 5:53–61,
1996.
227. Kochi T, Oka T, Mizuguchi T: Epidural anesthesia for patients with amyotrophic lateral sclerosis. Anesth Analg 68:410–412, 1989.
228. Scheen AJ: Diabetic neuropathy: Epidemiologic and predictive data. Diabetes Metab 24(Suppl)3:45–49, 1998.
229. Thomas PK: Diabetic peripheral neuropathies: Their cost to patient and society and the value of knowledge of risk factors for development of
interventions. Eur Neurol 41(Suppl 1):35–43, 1999.
230. Ward JD, Barnes CG, Fisher DJ, et al: Improvement in nerve conduction following treatment in newly diagnosed diabetics. Lancet 1:428–430,
1971.
231. Stoelting RK, Dierdorf SF: Diseases of the nervous system. In Stoelting RK, Dierdorf SF (eds): Anesthesia and Co-Existing disease, 3rd ed.
New York, Churchill-Livingstone, 1993, pp 215–217.
232. Critchley M: Discussion on the neurologic sequelae of spinal anesthesia. Proc R Soc Med 30:1007–1015, 1937.
1042
233. Jones RM, Healy TE: Anaesthesia and demyelinating disease. Anaesthesia 35:879–84, 1980.
234. Bamford C, Sibley W, Laguna J: Anesthesia in multiple sclerosis. Can J Neurol Sci 5:41–44, 1978.
235. Crawford JS: Regional anesthesia for patients with chronic neurologic disease and similar conditions. Anaesthesia 36:821–822, 1981.
236. Warren TM, Datta S, Ostheimer GW: Lumbar epidural anesthesia in a patient with multiple sclerosis. Anesth Analg 61:1022–1023, 1982.
237. Stambough JL, Stambough JB, Evans S: Acute cauda equina syndrome after total knee arthroplasty as a result of epidural anesthesia and
spinal stenosis. J Arthroplasty 15:375–379, 2000.
238. Yuen EC, Layzer RB, Weitz SR, Olney RK: Neurologic complications of lumbar epidural anesthesia and analgesia. Neurology 45:1795–1801,
1995.
239. Tetzlaff JE, Dilger JA, Wu C, et al: Influence of lumbar spine pathology on the incidence of paresthesia during spinal anesthesia. Reg Anesth
Pain Med 23:560–563, 1998.
APPENDIX 1: ASRA Neuraxial Anesthesia and Anticoagulation Consensus Statements
RECOMMENDATIONS FOR NEURAXIAL ANESTHESIA AND ANTICOAGULATION *
The American Society of Regional Anesthesia (ASRA) convened a group of experts in the fields of hemostasis,
biostatistics, neuraxial anesthesia, and federal drug regulation to participate in a consensus conference on
anticoagulants and neuraxial anesthesia and analgesia. The impetus for the conference was developing evidence that
the use of low molecular weight heparin (LMWH) thromboembolism prophylaxis in the United States is associated
with a higher frequency of clinically significant neuraxial bleeding when combined with neuraxial anesthesia and
analgesia regimens than LMWH thromboembolism prophylaxis regimens in European surgical patients. The
original manuscripts that developed from the consensus conference held May 2–3, 1998, in Chicago, Illinois, were
published as a supplement to Regional Anesthesia and Pain Medicine. The original manuscripts used in
*†‡§¶
conjunction with these abridged consensus statements provide the necessary background for a more complete
understanding of the clinical issues discussed in the consensus conference.
ORAL ANTICOAGULANTS AND NEURAXIAL BLOCK *
When oral anticoagulation therapy and neuraxial anesthesia are used together, physicians must be aware of the
interactions of warfarin on the coagulation cascade and the role of the prothrombin time and INR in monitoring its
effect. To minimize the risk of complications from this practice we believe:
1. For patients on chronic oral anticoagulation, the anticoagulant therapy must be stopped and the
prothrombin time and INR measured prior to initiation of neuraxial block. Early after discontinuation of
warfarin therapy, the prothrombin time and the INR reflect predominantly factor VII levels, and in spite of
acceptable factor VII levels, factors II and X levels may not be adequate for normal hemostasis.
2. The concurrent use of medications that affect other components of the clotting mechanisms may increase
the risk of bleeding complications for patients receiving oral anticoagulants, and do so without influencing
the prothrombin time and INR. These medications include aspirin and other NSAIDs, and heparin. One
should reflect on these drug interactions when an indwelling neuraxial catheter is being considered for a
patient.
3. For patients receiving an initial dose of warfarin prior to surgery, the prothrombin time and INR should be
checked prior to neuraxial block if the first dose was given more than 24 hours earlier, or a second dose of
oral anticoagulant has been administered.
4. Patients receiving low-dose warfarin therapy during epidural analgesia should have their prothrombin time
and INR monitored on a daily basis, and checked before catheter removal, if initial doses of warfarin were
given at least 36 hours before. Initial studies evaluating the safety of epidural analgesia in association with
oral anticoagulation utilized low-dose warfarin, with the mean daily doses of approximately 5 mg of
warfarin. Higher dose warfarin may require more intensive monitoring of the coagulation status.
5. Neurologic testing of sensory and motor function should be performed routinely during epidural analgesia
for patients on warfarin therapy. The type of analgesic solution should be tailored to minimize the degree of
sensory and motor blockade. These checks should be continued after catheter removal for at least 24 hours
and longer if the INR was 1.5 or more at the time of catheter removal.
6. An INR greater than 3 should prompt the physician to withhold or reduce the warfarin dose in patients with
indwelling neuraxial catheters. We can make no definitive recommendation for removal
1043
* From Enneking FK, Benzon HT: Oral anticoagulants and regional anesthesia: A perspective. Reg Anesth Pain Med 23(6 Suppl
2):140–145, 1998.
† From Urmey WF, Rowlingson J: Do antiplatelet agents contribute to the development of perioperative spinal hematoma? Reg
Anesth Pain Med 23:146–151, 1998.
‡ From Rosenquist RW, Brown DL: Neuraxial bleeding: Fibrinolytics/thrombolytics. Reg Anesth Pain Med 23(6 Suppl 2):152–156,
1998.
§ From Liu SS, Mulroy MF: Neuraxial anesthesia and analgesia in the presence of standard heparin. Reg Anesth Pain Med 23(6 Suppl
2):157–163, 1998.
¶ Horlocker TT, Wedel DJ: Neuraxial block and low molecular weight heparin: Balancing perioperative analgesia and
thromboprophylaxis. Reg Anesth Pain Med 23(6 Suppl 2):164–177, 1998.
of neuraxial catheters in patients with therapeutic levels of anticoagulation during neuraxial catheter
infusion. Clinical judgment must be exercised in making decisions about removing or maintaining these
catheters.
7. Reduced doses of warfarin should be given to patients who are likely to have an enhanced response to the
drug.
ANTIPLATELET DRUGS AND NEURAXIAL BLOCK *
Antiplatelet drugs, by themselves, appear to represent no added significant risk for the development of spinal
hematoma in patients having epidural or spinal anesthesia. This is an important observation since a very sizable
fraction of our surgical patients receive concomitant antiplatelet therapy during their perioperative course. We
believe:
1. The use of antiplatelet drugs alone does not create a level of risk that will interfere with the performance of
neuraxial blocks.
2. Data on the combination of antiplatelet agents with other forms of anticoagulation are lacking. However,
the concurrent use of other medications affecting clotting mechanisms, such as oral anticoagulants,
standard heparin, and LMWH, may increase the risk of bleeding complications in these patients.
3. There is no wholly accepted test, including the bleeding test, which will guide antiplatelet therapy. Careful
preoperative assessment of the patient to identify alterations of health that might contribute to bleeding is
crucial.
4. At this time, there do not seem to be specific concerns as to the timing of single-shot or catheter techniques
in relationship to the dosing of NSAIDs, postoperative monitoring, or the timing of neuraxial catheter
removal.
FIBRINOLYTIC/THROMBOLYTIC DRUGS AND NEURAXIAL BLOCK †
The physiologic state induced by the use of fibrinolytic and thrombolytic agents represents a unique problem in
performing regional anesthesia. With the advances in fibrinolytic/thrombolytic therapy, we may see increased use of
these drugs in the perioperative period, which will require further increases in vigilance. We believe:
1. Patients receiving concurrent heparin with fibrinolytic and thrombolytic drugs are at high risk of adverse
neuraxial bleeding during spinal or epidural anesthesia. This impression is based on limited case reports
and extrapolation of data from patients receiving combined fibrinolytic or thrombolytic drugs and heparin
for coronary thrombolysis.
2. Preoperative evaluation should determine whether fibrinolytic or thrombolytic drugs have been used
preoperatively, or have the likelihood of being used intraoperatively or postoperatively.
3. Patients receiving fibrinolytic and thrombolytic drugs should be cautioned against receiving spinal or
epidural anesthetics except in highly unusual circumstances. Guidelines detailing original contraindications
for thrombolytic drugs suggest avoidance of these drugs within 10 days of puncture of noncompressible
vessels. Data are not available to clearly outline the length of time neuraxial puncture should be avoided
after discontinuation of these drugs.
4. In those patients who have received neuraxial blocks at or near the time of fibrinolytic and thrombolytic
therapy, neurologic monitoring needs to be carried out for an appropriate interval. It may be that the
interval of monitoring should not be more than 2 hours between neurologic checks. Further, if neuraxial
blocks have been combined with fibrinolytic and thrombolytic therapy and ongoing epidural catheter
infusion, the infusion should be limited to drugs minimizing sensory and motor blockade.
1044
5. There is no definitive recommendation for removal of neuraxial catheters in patients who unexpectedly
receive fibrinolytic and thrombolytic therapy during a neuraxial catheter infusion. Caution must be
exercised in making decisions about removing or maintaining these catheters. The measurement of
fibrinogen may be helpful in making a decision about catheter removal or maintenance.
NEURAXIAL BLOCK AND STANDARD HEPARIN ‡
Therapeutic and full anticoagulation doses of standard (unfractionated) heparin are commonly used during
* From Urmey WF, Rowlingson J: Do antiplatelet agents contribute to the development of perioperative spinal hematoma? Reg Anesth Pain Med
23:146–151, 1998.
† From Rosenquist RW, Brown DL: Neuraxial bleeding: Fibrinolytics/thrombolytics. Reg Anesth Pain Med 23(6 Suppl 2):152–156, 1998.
‡ From Liu SS, Mulroy MF: Neuraxial anesthesia and analgesia in the presence of standard heparin. Reg Anesth Pain Med 23(6 Suppl 2):157–
163, 1998.
the perioperative period in vascular surgery and cardiac surgery patients. Low dose heparin also is frequently used
for prophylaxis against development of venous thromboembolism in general, orthopedic, and urologic surgery.
Neuraxial anesthetic techniques are often attractive for these patients, as these techniques may provide reduced
morbidity and improved postoperative analgesia. Combining standard heparin therapy or prophylaxis and neuraxial
block demands consideration of their interactions and we believe:
1. During subcutaneous (minidose) prophylaxis there is no contraindication to the use of neuraxial techniques.
The risk of neuraxial bleeding may be reduced by delay of the heparin injection until after the block, and
may be increased in debilitated patients or after prolonged therapy.
2. Combining neuraxial techniques with intraoperative anticoagulation with heparin during vascular surgery
seems acceptable with the following cautions:
• Avoid the technique in patients with other coagulopathies.

• Heparin administration should be delayed for 1 hour after needle placement.
• Remove the catheter 1 hour before any subsequent heparin administration or 2 to 4 hours after the last
heparin dose.
• Monitor the patient postoperatively to provide early detection of motor blockade and consider use of
minimal concentration of local anesthetics to enhance the early detection of a spinal hematoma.
Although the occurrence of a bloody or difficult neuraxial needle placement may increase risk, there are no
data to support mandatory cancellation of a case. Clinical judgment is needed. If a decision is made to
proceed, full discussion with the surgeon and careful postoperative monitoring are warranted.
3. Currently, sufficient data and experience are not available to determine if the risk of neuraxial hematoma is
increased when combining neuraxial techniques with the full anticoagulation of cardiac surgery.
4. Prolonged therapeutic anticoagulation appears to increase risk of spinal hematoma formation, especially if
combined with other anticoagulants or thrombolytics. Therefore, neuraxial blocks should be avoided in this
clinical setting. Whereas, if systemic anticoagulation therapy is begun with an epidural catheter in place, it
is recommended to delay catheter removal for 2 to 4 hours following therapy discontinuation and
evaluation of coagulation status.
5. The concurrent use of medications that affect other components of the clotting mechanisms may increase
the risk of bleeding complications for patients receiving standard heparin. These medications include
aspirin and other NSAIDs, LMWH, and oral anticoagulants.
NEURAXIAL BLOCK AND LOW MOLECULAR WEIGHT HEPARIN §
The decision to perform a neuraxial block on a patient receiving perioperative LMWH must be made on an
individual basis by weighing the risk of spinal hematoma with the benefits of regional anesthesia for a specific
patient. Anesthesiologists in the United States can draw on the European experience to develop their own practice
guidelines for the management of patients undergoing spinal and epidural blocks while receiving perioperative
LMWH. Although it is impossible to devise recommendations that will completely eliminate the risk of spinal
hematoma, we believe:
1. Monitoring of the anti-Xa level is not recommended. The anti-Xa level is not predictive of the risk of
bleeding and is, therefore, not helpful in the management of patients undergoing neuraxial blocks.
1045
2. Antiplatelet or oral anticoagulant medications administered in combination with LMWH may increase the
risk of spinal hematoma. Concomitant administration of medications affecting hemostasis, such as
antiplatelet drugs, standard heparin, or dextran represents an additional risk of hemorrhagic complications
perioperatively, including spinal hematoma. Education of the entire patient care team is necessary to avoid
potentiation of the anticoagulant effects.
3. The presence of blood during needle and catheter placement does not necessitate postponement of surgery.
However, initiation of LMWH therapy in this setting should be delayed for 24 hours postoperatively.
Traumatic needle or catheter placement may signify an increased risk of spinal hematoma, and it is
recommended that this consideration be discussed with the surgeon.
4. Patients on preoperative LMWH can be assumed to have altered coagulation. A single-dose spinal
anesthetic may be the safest neuraxial technique in patients receiving preoperative
§ Horlocker TT, Wedel DJ: Neuraxial block and low molecular weight heparin: Balancing perioperative analgesia and
thromboprophylaxis. Reg Anesth Pain Med 23(6 Suppl 2):164–177, 1998.
LMWH. In these patients needle placement should occur at least 10 to 12 hours after the LMWH dose,
whereas patients receiving higher doses of LMWH (e.g., enoxaparin 1 mg/kg twice daily) will require
longer delays (24 hours). Neuraxial techniques should be avoided in patients administered a dose of
LMWH 2 hours preoperatively (general surgery patients), because needle placement would occur during
peak anticoagulant activity.
5. Patients with postoperative initiation of LMWH thromboprophylaxis may safely undergo single-dose and
continuous catheter techniques. The first dose of LMWH should be administered no earlier than 24 hours
postoperatively and only in the presence of adequate hemostasis. In addition, it is recommended that
indwelling catheters be removed prior to initiation of LMWH thromboprophylaxis. If a continuous
technique is selected, the epidural catheter may be left indwelling overnight and removed the following day,
with the first dose of LMWH administered 2 hours after catheter removal.
6. The decision to implement LMWH thromboprophylaxis in the presence of an indwelling catheter must be
made with care. Extreme vigilance of the patient’s neurological status is warranted. An opioid or dilute
local anesthetic solution is recommended in these patients to allow frequent monitoring of neurological
function. If epidural analgesia is anticipated to continue for more than 24 hours, LMWH administration
may be delayed (in selected cases) or an alternate method of thromboprophylaxis may be selected (e.g.,
external pneumatic compression), based on the risk profile for the individual patient. These decisions
should be made preoperatively to allow optimal management of both postoperative analgesia and
thromboprophylaxis.
7. For any LMWH prophylaxis regimen, the timing of catheter removal is of paramount importance. Catheter
removal should be delayed for at least 10 to 12 hours after a dose of LMWH. A true normalization of the
patient’s coagulation status could be achieved if the evening dose of LMWH was not given and the catheter
was removed the following morning (24 hours after the last dose). Again, subsequent dosing should not
occur for at least 2 hours after catheter removal.
1046
Section VI Chapter 45 - Peripheral Nerve Blockade
Chapter 45 - Peripheral Nerve Blockade
MICHAEL A. WEAVER
CARL A. TANDATNICK
MARC B. HAHN
Regional anesthetic techniques are an important part of a modern anesthesiology practice. However, even in the
hands of the most skilled practitioner, complications may arise. It is important for the physician to anticipate the
potential complications and be prepared to avoid or resolve them should they arise. Complications can be
categorized as being related to patient selection, pharmacologic agent toxicity or side effects, and technique-specific
problems. By focusing on these three specific sources of complications, one may have a clearer understanding of the
potential problems and develop precise avoidance strategies.
Overview of Complications
PATIENT SELECTION
Many factors determine whether a patient is a good candidate for peripheral nerve blockade. Proper patient selection
is vital for the success of a peripheral nerve block and the avoidance of complications. Patient refusal to undergo a
peripheral nerve block is an absolute contraindication to its performance. A patient with mental retardation,
Alzheimer's disease, head injury, or any other disease process that causes lack of cooperation may be a poor
candidate for peripheral nerve blockade. Occasionally, sedatives such as benzodiazepines may cause a paradoxical
excitement that can make performance of the surgical procedure impossible despite successful nerve blockade.
Patients with airway abnormalities or facial bone deformities may seem to be good candidates for peripheral nerve
blocks; however, these patients may be difficult or impossible to mask ventilate, or intubate. If the block fails, or if a
systemic toxic reaction to the local anesthetic occurs, provisions must be made for airway control.
The presence of a central nervous system (CNS) disorder does not contraindicate the performance of peripheral
nerve blocks. Peripheral nerve blocks may be performed in patients with a history of acute or chronic chorea, spastic
cerebral palsy, intracranial lesions, hydrocephalus, or peripheral neuropathy. A concern when using peripheral
[1]
nerve blocks in patients with neurologic disorders is that the regional anesthetic may be blamed for incidental
worsening of the patient's disease state. A thorough neurologic examination should be performed before any
peripheral nerve block in any patient with underlying CNS disorders, and the results should be recorded in the
patient's chart. Multiple sclerosis is a disease process characterized by exacerbations and remissions. Despite the
[1]
fact that peripheral nerve blocks and epidural anesthesia have not been associated with postoperative exacerbations
of multiple sclerosis, a peripheral nerve block could be blamed for a postoperative neurologic deficit that might be
disease related. [2]
Patients with myopathies are good candidates for peripheral nerve blocks. Use of regional anesthesia in these
patients avoids concern for malignant hyperthermia with general anesthesia; however, it may be difficult to perform
peripheral nerve blockade in these patients because of associated deformities. All local anesthetics can be used in
these patients.
[1]
Regional anesthesia can also be used in patients with myasthenia gravis. Regional anesthesia allows the
anesthesiologist to avoid the concerns raised by the use of neuromuscular blocking agents with general anesthesia.
Again, all local anesthetic agents can be used for peripheral nerve blocks in these patients. [1]
Patients with coagulopathy may not be good candidates for peripheral nerve blocks, and general anesthesia is
usually used; however, patients with hemophilia or factor VIII deficiency may be eligible for regional anesthesia if
replacement of the deficient factor is accomplished before the surgical procedure. Axillary blocks have been
[1]
successfully and safely performed in patients with hemophilia. Peripheral nerve blocks should probably not be
[3]
performed on patients who have less than 50% of normal amounts of any coagulation factors. Aspirin should be
[1]
stopped approximately 1 week before any surgical procedures. Other nonsteroidal anti-inflammatory drugs, with the
exception of cyclooxygenase 2 inhibitors, need to be stopped several days before surgery. Despite these surgical
concerns, peripheral nerve blocks have been performed, after careful analysis of the risks and benefits, on patients
who are anticoagulated. Waldman has advised the use of small needles (25- or 27-gauge) and the application of
[4]
pressure at the injection site as methods of avoiding hematomas in anticoagulated patients. [4]
1047
Infection at the site of needle insertion is a contraindication to performance of a block. A patient who is septic or
bacteremic can undergo peripheral neural blockade, provided antibiotic therapy has been started and the patient has
shown a response to therapy, such as a decreased temperature or decreased white blood cell count. [2]
Patients who have diabetes mellitus and peripheral neuropathy can safely undergo regional anesthesia. Concern
must be focused on the possibility that new postoperative neurologic deficits may be blamed on the regional
anesthetic rather than on progression of the neuropathy. Again, thorough neurologic examination should be
performed and documented before the surgical procedure. Patients with diabetes mellitus are also seen to have more
myocardial depression with large doses of local anesthetic agent than patients without diabetes mellitus. [2]
Pharmacologic Complications
LOCAL ANESTHETIC TOXICITY
Local anesthetics can be divided into two groups based on their structure. Procaine, chloroprocaine, and tetracaine
belong to the amino-ester group, so named because of an ester linkage between the hydrophilic and hydrophobic
ends of the local anesthetic. Bupivacaine, lidocaine, ropivacaine, mepivacaine, and etidocaine belong to the amino-
amide group, which has an amide linkage between the hydrophilic and the hydrophobic ends. All local anesthetics
have the ability to produce systemic toxicity if blood levels reach a threshold. Systemic toxicity manifests as CNS
effects and cardiovascular effects. Local anesthetics can be directly toxic to nerve tissue if injected intraneurally, and
allergic reactions have been reported to both the amino-amide and the amino-esther local anesthetics.
Methemoglobinemia is a well-known side effect of high dosages of prilocaine. Finally, side effects may occur
related to the preservatives found in the local anesthetic and to the vasoconstrictors often used with local anesthetics
( Table 45–1 ). [46]
Systemic Toxicity
Systemic toxicity is usually secondary to the inadvertent injection of local anesthetic into an artery or a vein but
could occur from absorption of local anesthetics into the bloodstream from a peripheral site. The maximal [5]
recommended dosages of local anesthetics have been widely published. The maximal dosage of bupivacaine is
approximately 2 to 3 mg/kg, either with or without epinephrine. For lidocaine, the maximal recommended dosages
are 4 to 5 mg/kg without epinephrine or 7 mg/kg with epinephrine. These maximal dosages, however, are only
guidelines. It must be remembered that most systemic toxic reactions are the result of inadvertent intravascular
injection and are not related to excessive amounts of local anesthetic agents deposited in the proper area ( Table 45–
2 ). [46]
Systemic toxicity is related to the blood levels of local anesthetics as well as the levels of local anesthetic
TABLE 45-1 -- DIFFERENTIAL DIAGNOSIS OF LOCAL ANESTHETIC REACTIONS

Etiology Major Clinical Features Comments
Local anesthetic toxicity
Intravascular injection Immediate convulsion and/or cardiac toxicity Injection into vertebral or carotid artery may cause
convulsion after administration of small dose
Relative overdose Onset with 5 to 10 min. of irritability, progressing to
convulsions
Reaction to Tachycardia, hypertension, headache, apprehension May vary with vasopressor used
vasoconstrictor
Vasovagal reaction Rapid onset Rapidly reversible with elevation of legs
Bradycardia
Hypotension
Pallor, faintness
Allergy
Immediate Anaphylaxis (↓ blood pressure; bronchospasm, edema) Allergy to amides extremely rare
Delayed Urticaria Cross-allergy possible (e.g., with preservatives in local
anesthetics and food)
High spinal or epidural Gradual onset May lose consciousness with total spinal block and onset
block of cardiorespiratory effects more rapid than with high
epidural or with subdural block
Bradycardia
1048
TABLE 45-1 -- DIFFERENTIAL DIAGNOSIS OF LOCAL ANESTHETIC REACTIONS

Etiology Major Clinical Features Comments
Hypotension
Possible respiratory arrest
Concurrent medical May mimic local anesthetic reaction Medical history important
episode (e.g., asthma
attack, myocardial
infarction)
TABLE 45-2 -- COMPARABLE SAFE DOSES OF LOCAL ANESTHETICS (mg/kg)
Areas Injected
Central Blocks with Epinephrine Intercostal Blocks with Epinephrine
Drugs Peripheral Blocks Plain 1:200,000 1:200,000
2-Chloroprocaine − 20 25 −
Procaine − 14 18 −
Lidocaine 20 7 9 6
Mepivacaine 20 7 9 6
Bupivacaine 5 2 2 2
Tetracaine − 2 2 −
found within the brain and heart. Signs and symptoms of lidocaine toxicity occur with arterial concentrations in
excess of 5 µg/mL ; however, there is poor correlation between plasma concentration and manifestations of toxicity.
[6]
Both the total dose administered and the rate of administration are important in determining whether local anesthetic
side effects will occur ( Fig. 45–1 ). [7]
The site of injection effects the absorption of local anesthetics into the bloodstream. The highest blood levels of
local anesthetics occur after intercostal blocks and intrapleural blocks, followed by caudal and epidural
[5] [7]
administration of local anesthetics. Brachial plexus blocks and spinal blocks result in even lower blood
concentrations of local anesthetic agents. Vaso-constrictors
Figure 45-1 Ranking of the peak blood levels of local anesthetics after a wide
variety of regional blocks.
1049
added to the local anesthetics decrease the plasma concentration of the local anesthetics, although addition of
vasoconstrictors decreases the blood levels of lidocaine much more than addition of bupivacaine. Peak blood levels [7]
occur approximately 20 minutes after the injection. [5]
Local anesthetic toxicity can be affected by underlying disease processes. Patients with liver failure may not
metabolize amino-amide local anesthetics, resulting in toxicity at lower than expected dosages. Chronic
administration of propranolol or cimetidine can also affect liver metabolism of amino-amide local anesthetics.
Patients with pseudocholinesterase deficiency may have decreased ability to metabolize amino-ester local
anesthetics. Hypercapnia and acidosis lower the seizure threshold. It should also be noted that the lungs can absorb
up to 90% of an intravascularly administered local anesthetic. The lung acts as a significant buffer to the toxic
effects of local anesthetics. [7]
For all local anesthetics, the concentration needed to produce CNS side effects is lower than that needed to produce
cardiovascular side effects. In general, the dosage necessary to produce cardiovascular toxicity is approximately
[7]
three times higher than the dosage needed to produce CNS excitation. A ratio of the concentration necessary to
[8]
produce cardiovascular side effects to the concentration necessary to produce central nervous system excitation can
be found for any local anesthetic agent. This is referred to as the CV/CNS ratio. Lidocaine has a high CV/CNS ratio,
indicating that it takes much higher local anesthetic concentrations to produce cardiovascular side effects than to
produce CNS effects. Etidocaine and bupivacaine have lower CV/CNS ratios than other local anesthetics. Because [7]
cardiovascular toxicity can be more difficult to treat than CNS toxicity, lidocaine is considered to have a greater
margin of safety than bupivacaine.
Central Nervous System Manifestations
CNS manifestations of local anesthetic toxicity are characterized by an initial excitatory phase, which results from
suppression of inhibitory centers in the amygdala and hippocampus. The excitatory phase is followed by a
generalized depression of both the excitatory and inhibitory centers in the brain, which may result in depression of
cardiac and respiratory centers. [7]
Initial signs and symptoms of CNS toxicity include lightheadedness, dizziness, somnolence, tinnitus, difficulty
focusing the eyes, nystagmus, visual disturbances, dysphoria and agitation. Altered level of consciousness may be
the first sign of local anesthetic toxicity.
Psychotic manifestations have also been noted as an initial symptom of local anesthetic toxicity. Circumoral [9]
numbness was thought to be a sign of CNS toxicity from local anesthetics; however, circumoral numbness may be
the result of local anesthetic leaving the vascular space and affecting extravascular nerve endings rather than a true
CNS effect.
Continued administration of local anesthetic agents results in shivering, muscle twitching, and tremors, particularly
in the facial muscles and distal extremities. The patient may become unconscious. Finally, generalized tonic clonic
seizures will occur, which are followed by respiratory and circulatory depression. The symptoms of CNS
[5] [6] [7] [10] [11]
toxicity subside as the concentration of local anesthetic in the blood falls. Administration of CNS depressant drugs
can minimize the early signs and symptoms of CNS toxicity.
Seizures raise the metabolic activity in the brain and in the skeletal musculature. Oxygen demand in the brain and
musculature rises with resultant cerebral hypoxia, acidosis, and hyperkalemia. The duration of the seizure is
[5] [6]
important in determining the potential harm that may occur. The convulsive threshold is inversely proportional to
[6]
the partial pressure of carbon dioxide. An increase in the partial pressure of carbon dioxide increases cerebral blood
flow, delivering more local anesthetic to the brain. Acidosis decreases the protein binding of local anesthetics,
making more free local anesthetic available and increasing the probability of local anesthetic toxicity.
Several cases of CNS toxicity after dental blocks have been reported. Diffusion of local anesthetic agents along
nerve sheaths and retrograde arterial diffusion of local anesthetics are thought to be the mechanisms for the
toxicity. Aphasia, blindness, hemiparesis, apnea, and coma have been reported from stellate ganglion blocks
[12] [13]
secondary to presumed intra-arterial injection of local anesthetics into the carotid artery or the vertebral artery. [14] [15] [16]
Finally, several reports of transient diploplia and blindness after maxillary nerve block were reported. Retrograde [17] [18]
arterial diffusion of the local anesthetic agents to the CNS was thought to be the mechanism of these side effects.
Cardiovascular Manifestations
1050
Local anesthetics have numerous effects on the cardiovascular system. Autonomic nerves, cardiac and vascular
smooth muscle, and cardiac centers in the brain are affected. Higher local anesthetic concentrations are necessary
[6] [7]
to produce cardiovascular side effects than to produce CNS side effects. This is fortunate, because the
cardiovascular side effects are much more difficult to treat than the CNS side effects.
The cardiovascular side effects are a result of blockade of sodium channels. In cardiac musculature, the blockade of
sodium channels results in a decreased rate of depolarization of Purkinje fibers and ventricular muscle, decreased
action potential duration, and a decreased refractory period. Low concentrations of local anesthetic agents increase
[7]
vascular tone, whereas high concentration of local anesthetic agents decrease vascular tone. Initially, sympathetic
discharge can cause hypertension and tachycardia. This can be followed by myocardial depression and decreased
cardiac output. Peripheral vasodilation and hypotension occur. [7]
Local anesthetics can affect the conduction system of the heart. Virtually every type of arrhythmia has been reported,
including all types of heart block, bradycardia, ventricular tachycardia, and ventricular fibrillation. The [7]
combination of arrhythmias, heart block, myocardial depression, and peripheral vasodilation can lead to
cardiovascular collapse.
The more potent the local anesthetic, the more arrhythmogenic potential exists. Thus, bupivacaine has more
arrhythmogenic potential than lidocaine. Bupivacaine cardiac toxicity is difficult to treat because it has a prolonged
effect on the cardiac conduction system. Lidocaine effects on the sodium channel have been described as “fast in,
fast out,” meaning that the lidocaine interaction with the sodium channels occurs quickly but also ends quickly. At
low bupivacaine concentrations, the effect on sodium channels is “slow in, slow out.” At high concentrations of
bupivacaine, the effect on sodium channels becomes “fast in, slow out,” meaning that bupivacaine binds to the
channels quickly but leaves slowly. This results in prolonged effects on the conduction system that may be
refractory to treatment. Bupivacaine also increases the frequency of re-entrant arrhythmias at serum concentrations
[19]
only slightly above the concentration necessary to produce seizures. [5]
Treatment
Prevention is the best treatment for local anesthetic toxicity. Toxicity can be avoided by careful calculation of local
anesthetic doses, use of the smallest dose of local anesthetic necessary to produce the desired effect, frequent
aspiration during the block, fixation of the needle, use of intravascular markers such as epinephrine, and incremental
injection of the local anesthetic. Despite the most diligent use of these methods, local anesthetic toxicity can still
occur.
Treatment of seizures involves support of the air way and administration of 100% oxygen. Mask ventilation should
be performed if required. Fortunately, most seizures related to local anesthetic toxicity subside without further
treatment as the blood levels drop. If the patient's airway becomes obstructed or if the seizure persists,
neuromuscular blocking agents such as succinylcholine may be administered, followed by intubation and
mechanical ventilation. Persistent seizure activity may require benzodiazepine or barbiturate administration.
Thiopental, 1 to 3 mg/kg, or diazepam, 0.1 mg/kg, can be used to stop seizure activity. Midazolam may also be
[5]
used. If muscle relaxants are used, it must be remembered that they produce muscle relaxation but have no effect on
the electrical activity of the brain.
[6] [7]
If cardiac side effects occur, cardiopulmonary resuscitation may be required. Epinephrine or norepinephrine may be
required for the treatment of asystole, and atropine can be used for the treatment of bradycardia. Cardioversion and
defibrillation may be necessary. Dopamine, dobutamine, calcium chloride, epinephrine, or amrinone should be
considered for severe hypotension. For ventricular arrhythmias secondary to bupivacaine, bretylium (not lidocaine)
is the drug of choice.
[1] [7]
METHEMOGLOBINEMIA
Methemoglobinemia is associated with the use of prilocaine. Metabolism of prilocaine causes the release of ortho-
toluidine, which causes methemoglobinemia and cyanosis. Methemoglobinemia can be seen when dosages of
[5]
prilocaine exceed 8 mg/kg, or 500 to 600 mg in adults. Neonates are very sensitive to prilocaine, and dosages
[20] [21] [22]
as low as 5 mg/kg can result in methemoglobinemia. [23] [24]
Manifestations of methemoglobinemia vary with the percentage of hemoglobin that is converted to methemoglobin.
If 20% to 30% of hemoglobin is converted, the patient becomes cyanotic, short of breath, and tachycardic and may
complain of headache or vertigo. At concentrations of 55%, the patient becomes lethargic, and at concentrations
greater than 70%, death may occur. [1]
1051
Treatment of patients with methemoglobinemia is usually with 1% methylene blue. The typical dose is 1 to 2 mg/kg,
which can be repeated hourly until the maximum dosage of 7 mg/kg is reached. If the patient is minimally
symptomatic, no treatment may be necessary, because the methemoglobinemia will resolve spontaneously within 24
to 72 hours.[1]
Prilocaine should be avoided in any patient who may be predisposed to methemoglobinemia. Predisposing
conditions include hemoglobinopathies and glucose-6-phosphate delhydrogenase deficiency. In addition, patients
taking sulfonamides, nitrites, nitrates, or antimalarials should not take prilocaine.[1]
SIDE EFFECTS OF VASOCONSTRICTORS
Vasoconstrictors are added to local anesthetics to increase the duration of action of the block and to serve as
intravascular markers. The two most common vasoconstrictors are epinephrine and phenylephrine. Epinephrine is
usually added to the local anesthetic in a dosage of 5 µg/mL, or 1:200,000. This can be achieved by adding 0.1 mL
of a 1:1000 solution of epinephrine to 20 mL of local anesthetic. Phenylephrine is typically added to local
anesthetics in a 1:20,000 concentration. Dosages of greater than 0.25 mg of epinephrine or 2 mg of phenylephrine
can cause side effects. [6]
True allergies to vasoconstrictor drugs are rare; however, side effects owing to high blood concentrations are
frequent. High blood levels of vasoconstrictors can manifest as tachycardia, hypertension, palpitations, headache,
shortness of breath, nausea, vomiting, faintness, tremor, and anxiety. These side effects resemble early signs of
[6]
local anesthetic toxicity and may be mistaken for local anesthetic side effects. Addition of vasoconstrictors to local
anesthetics should be avoided in any tissue supplied by an end artery. Examples of tissues supplied by end arteries
are the fingers, toes, and penis. Ischemia and gangrene may result from injection of epinephrine into these tissues
( Fig. 45–2 ). [55]
LOCAL ANESTHETIC ALLERGY
True local anesthetic allergies are very rare. Patients who have a history of local anesthetic allergies may have
experienced intravascular injection of local anesthetics with resultant signs of toxicity, systemic responses to
vasoconstrictors, allergic reactions to preservatives mixed with local anesthetics, or anxiety
Figure 45-2 Gangrene of a finger after the use of a procaine

(Novocain)–epinephrine (Adrenalin) solution for a digital block.
reactions. True allergic reactions are much more common with amino-ester local anesthetics than with amino-amide
local anesthetics. Amino-ester local anesthetics are hydrolyzed to para-aminobenzoic acid (PABA), which is a
[1] [5] [6]
known allergen. Patients who are allergic to sunscreens may also have allergies to amino-ester local anesthetics
because sunscreens often contain PABA.
Methylparaben, which is used as a preservative in local anesthetics, is also a PABA derivative and can cause allergic
reactions that may be blamed on the local anesthetic. Cross-sensitivity between amino-amides and amino-esters has
1052
not been demonstrated. Consequently, if individuals are allergic to amino-ester local anesthetics, it is unlikely that
[5]
they are also allergic to amino-amide local anesthetics.
Manifestations of allergic reactions to local anesthetics can range from dermatitis, uriticaria, and pruritis to severe
anaphylaxis and bronchospasm. Treatment of persons with allergic reactions may require administration of oxygen,
[6]
airway assistance, ventilation, and the use of epinephrine, ephedrine, antihistamines, steroids, atropine, or
methylxanthines. [1] [6]
Diagnosis of local anesthetic allergies can be accomplished with skin testing, although this is not
[5] [6] [25] [26] [27] [28]
universally accepted. If skin testing is done, it should be done not only with the local anesthetic but also with
preservatives and other chemically related agents. There is also a high incidence of skin reactivity with amino-
[6]
amide local anesthetics, and this must be differentiated from true allergic reactions.
NEUROTOXICITY
Neurotoxic manifestations have been reported for almost every local anesthetic agent. In general, amino-esters [29]
appear to be more neurotoxic than amino-amides. Contamination of local anesthetic agents with sterilizing
[30] [31]
agents, skin cleansing agents, and detergents can result in direct neurotoxic effects. Improper dilution of crystalline
preparations has also been blamed for neural damage. High concentrations of local anesthetics are associated with
[5]
neurotoxicity; consequently, the lowest effective concentration of local anesthetic agents should be used. Use of [5] [7] [32]
0.75% bupivacaine or 2% lidocaine should be reserved for epidural anesthesia and not for peripheral nerve blocks.
Intraneural injection of the local anesthetic agent and the addition of vasoconstrictors increase the chance of
neurotoxicity. The neurotoxicity of a local anesthetic is also proportional to its potency and how long the nerve
[5] [7] [32]
tissue is exposed to the local anesthetic. [7]
Chloroprocaine was at one time thought to be neurotoxic because of neurologic sequelae that developed after
inadvertent subarachnoid injection. The pH of the chloroprocaine solution was 3.0, and chloroprocaine was mixed
with methylparabin and metabisulfite as preservatives. It is now believed that the low pH combined with the
metabisulfite preservative was responsible for the neurotoxic effects and not the chloroprocaine itself. In 1987, a [1] [33]
new formulation was created that used 0.01% EDTA (ethylenediaminetetracetic acid) as a preservative. Since then,
no new cases of neurotoxicity have been attributed to chloroprocaine.
Ischemia
Intrafascicular injection can raise endoneural pressure to the point at which the blood supply is compromised,
resulting in neural ischemia. Large amounts of local anesthetic injected into confined spaces, such as around the
ulnar nerve at the elbow or at the carpal tunnel, can compress the nerve, again resulting in ischemia. Neural [7]
ischemia can also result from any interference with the circulation. Ischemia can occur from compression by a
tourniquet, from arteriosclerosis, and from shock or another hypoperfusion state. Intraneural angiopathy, such as
occurs with diabetic neuropathy or systemic lupus erythematosus, can predispose a patient to neural ischemia. [7]
Nerve Injury
Neural injury may be produced by improper performance of a block. The incidence of nerve injury associated with
peripheral nerve blocks has been reported in 0.36% to 2% of cases. It is most frequent at the brachial plexus,
[34] [35]
probably because brachial plexus blocks are the most frequently performed peripheral nerve blocks. With nerve [7]
injury, symptoms usually appear over 2 to 3 weeks, but they can appear as early as 1 to 2 days postinjury. Symptoms
can last from
Figure 45-3 Peripheral nerve stimulator apparatus. Left to right: Peripheral

nerve stimulator with low output, variable intensity control; connecting
cables with ground electrode; sterile, disposable, insulated block needle
with extension set; 20-mL syringe containing local anesthetic solution for
neural blockade procedure (attached); 3-mL syringe containing local
anesthetic with 25-gauge needle for skin infiltration; gauze sponges; gas-
sterilized bottle of local anesthetic solution; and sterile drapes.
1053
Figure 45-4 Incidence of injury is decreased with use of fine,

short-bevel needles.
weeks to years. Nerve injury can result in complex regional pain syndrome. [7]
Two thirds of patients with postblock neurologic deficits have experienced either paresthesias during needle
placement or pain on injection of the local anesthetic. Elicitation of paresthesias increases the incidence of
[36]
postblock neuropathy, and is associated with nerve injury.

[7] [35] [37]
Nerve stimulators may be used for peripheral
[1] [5] [6]
nerve blockade. Nerve stimulators do not cause nerve injuries when used properly; however, it is questionable
whether they improve the success rate of the blocks. In an anesthetized patient, peripheral nerve blocks should be
done with a nerve stimulator. Intraneural injections that would otherwise be painful go unnoticed in an anesthetized
patient ( Fig. 45–3 ).[56]
Nerve injury risk is greater with the use of long-bevel needles than with the use of short-bevel needles. Fewer nerve [5]
injury incidents occur and vascular perforation is less frequent with the use of fine, short bevel needles ( Fig. 45–4 ).
When short-bevel needles are inserted parallel to the nerve fiber, nerve injury risk is decreased. Risk of nerve
[11] [38]
fiber, perineurium, and blood vessel damage is decreased when short-bevel needles are used instead of long-bevel
needles ( Fig. 45–5 ; also see Fig 45–4 ).
[6] [46] [38]
Pain on injection of local anesthetics may result from intraneural needle placement. If pain on injection occurs, the
injection should be stopped and the needle repositioned. Intraneural injection may manifest postoperatively as
[7]
neurologic dysfunction, which may be the result of intraneural pressure or high local anesthetic concentration. An
intraneural bleed or hematoma may occur when nerve fibers are cut by the block needle. This may compromise the
neural microvasculature secondary to an increase in endoneural pressure. The local anesthetic itself may assert a
direct neurotoxic effect on neural tissue.
Injection of local anesthetic intrafasicularly can result in diffusion of the local anesthetic over long distances within
the endoneurium, possibly reaching the spinal cord. If intraneural injection of local anesthetic produces
[6]
intravascular diffusion into the spinal cord, spinal anesthesia may result. Nerve compression can occur with the
[7]
injection of large volumes of local anesthetic
Figure 45-5 Needles used for peripheral block. A1 and A2 are

short and blunt with a 45-degree needle bevel. B1 and B2 are long
and sharp, with a 14-degree needle bevel (conventional hypodermic
needle).
1054
or with rapid injection of the local anesthetic. Epinephrine mixed with the local anesthetic increases the neural
[1]
toxicity of anesthetic solutions.

[6]
Injury to Surrounding Tissues
Surrounding tissues may be injured during peripheral nerve blocks. Vascular injury can occur with any peripheral
nerve block performed near an artery or vein. Pneumothorax is a risk of certain peripheral nerve blocks, such as
supraclavicular brachial plexus block or intercostal nerve block. The risks and benefits of these blocks should be
weighed for patients with underlying pulmonary disease. Tandon and colleagues related the occurrence of
[39] [40]
pneumomediastinum after performance of a brachial plexus block ( Fig. 45–6 ). [55]
Hematoma Formation
Hematoma formation can occur after performance of peripheral nerve blocks. Hematoma formation can interfere
with the spread of local anesthetic agents and can also obscure landmarks. A hematoma can calcify over time. It is
most common in coagulopathy states. The hematoma may compress neural structures and cause nerve injury. A
report by Mishio and associates noted the formation of a massive hematoma after a stellate ganglion block, which
[41]
caused severe airway compromise requiring tracheostomy.
Figure 45-6 Pneumothorax with mediastinal and subcutaneous

emphysema after a brachial block. Note areas of emphysema
(arrows).
Infection
Infection may occur because of contamination of the block site or instruments with bacteria during the block
procedure. Staphylococcus aureus and Pseudomonas aeruginosa are bacteria that are commonly cultured from
[1]
infections after peripheral nerve blocks. Infection may also occur if the needle punctures the bowel or other
abdominal organs. Paracervical and pudendal nerve blocks can result in the puncture of the vagina or rectum,
leading to pelvic or intra-abdominal abscess formation from vaginal and colonic flora.
Miscellaneous Complications
Block failure is a frequent occurrence with peripheral nerve blockade. The failure rate is related to the practitioner's
experience. The injection of local anesthetic into the muscle may cause myelotoxicity that results in focal necrosis.
Regeneration of muscle may occur over several weeks. Bupivacaine causes slow muscle regeneration because of
suppression of protein synthesis in the muscle. Benign and transient complications such as Horner's syndrome may
[7]
occur. Horner's syndrome is characterized by nasal mucosal congestion, unilateral ptosis, miosis, and anhidrosis.
More serious complications such as respiratory muscle paralysis due to phrenic nerve block may occur. Phrenic
nerve block is a frequent complication of interscalene brachial plexus block. [1]
1055
Side Effects and Complications of Peripheral Nerve Block
HEAD AND NECK BLOCKS
Greater and Lesser Occipital Nerve
Greater and lesser occipital nerve blocks are easy to perform and usually quite safe; however, as with any block, a
number of potential complications exist. The scalp is highly vascular, and local anesthetic toxicity can be a concern.
Ecchymosis or hematoma formation can occur. Subarachnoid administration of local anesthetic into the foramen
magnum or through a cranial defect could result in total spinal anesthesia. Nerve injury secondary to direct trauma
from the needle and compression of nerves with a large volume of local anesthetic are also possible.
Trigeminal Nerve
The trigeminal nerve and its terminal branches can be readily blocked at a number of locations. The gasserian
ganglion, the mandibular or maxillary divisions, the terminal branches (supraorbital nerves, supratrochlear nerves,
infraorbital nerves, and mental nerves) may be blocked independently. Neural blockade at any of these areas can be
associated with a variety of side effects and complications.
Blockade of the gasserian ganglion can result in hematoma formation of the face because of the vascularity in this
area. Subscleral hematoma formation of the eye has also been reported. Because the gasserian ganglion is partially
surrounded by the dura, injection of local anesthetic into the subarachnoid space, with resultant total spinal
anesthesia, is a distinct possibility. Corneal anesthesia from blockade of the ophthalmic branch of the trigeminal
nerve could result in corneal abrasion. If a neurolytic block is performed, postprocedure dysesthesia or anesthesia
dolorosa is a possibility, and patients should be warned of this. Skin sloughing from neurolytic agent leakage on the
skin surface can occur. Weakness of the muscles of mastication can occur with resultant facial asymmetry. Finally,
Horner's syndrome may also result from this block.
The maxillary and mandibular branches of the trigeminal nerve can be blocked in an area between the zygomatic
arch and the mandibular notch. The block needle is placed into the highly vascular pterygopalatine fossa.
Consequently, ecchymosa and hematoma formation may occur. In addition, intravascular injection of local
anesthetic and local anesthetic toxicity are concerns. Improper needle placement could place the local anesthetic into
the subarachnoid space, with resultant total spinal anesthesia. If the block needle is placed into the infraorbital
fissure, orbital anesthesia, ophthalmoplegia, and visual changes can occur. If neurolytic blocks are performed,
dysesthesia or anesthesia dolorosa may occur. Skin sloughing is again a possibility if neurolytic agents are used.
The distal branches of the trigeminal nerve may also be blocked. The supraorbital, supratrochlear, infraorbital, and
mental nerves may be anesthetized for diagnosis and treatment of facial pain or headache syndrome. These blocks
are quite safe, but complications can occur. Intraneural injection with resultant nerve injury and compression
neuropathy from injection of large volumes of local anesthetic are possible complications. The scalp and facial areas
around these peripheral branches are highly vascular. Ecchymosis, hematoma formation, and local anesthetic
toxicity are potential complications. If depot steroids are used in the injectate, atrophy of subcutaneous tissue and fat
may occur, resulting in severe cosmetic deformities.
Superficial Cervical Plexus
Blockade of the superficial cervical plexus is easily done and, along with deep cervical plexus block, provides
anesthesia for a variety of neck surgeries, including carotid endarterectomy. The external jugular vein runs close to
the superficial cervical plexus; intravascular injection and local anesthetic toxicity are possible. Trauma to the
external jugular vein can lead to ecchymosis and hematoma formation in the neck. Phrenic nerve block has been
reported as a side effect of superficial cervical plexus block. Improper needle positioning can cause placement of
local anesthetic into the epidural, subdural, or subarachnoid spaces.
Deep Cervical Plexus
Block of the deep cervical plexus can result in the same complications as those of superficial cervical plexus
blockade. Trauma to the external jugular vein can result in ecchymosis and hematoma formation. Intravascular
injection of local anesthetic agents into the vertebral artery causes convulsions, even in very small dosages. Block of
the phrenic nerve can occur. Because of possible bilateral phrenic nerve block, bilateral deep cervical plexus block
should be avoided. Blockade of the cervical sympathetic chain and of the recurrent laryngeal area can occur,
resulting in Horner's syndrome and hoarseness, respectively. Inadvertent injection into the subarachnoid, subdural,
or epidural space is possible with improper needle placement.
1056
Glossopharyngeal Nerve
Glossopharyngeal nerve blocks can be done intraorally or posterior to the styloid process. Regardless of the
approach used, several side effects are possible with this block. Bleeding or hematoma formation can occur because
of injury to the internal jugular vein or internal carotid artery. Local anesthetic toxicity can occur with injection into
either of these vessels. Seizures can result with injection into the internal carotid artery. Dysphagia can occur with
blockade of the motor portion of the nerve. Bilateral glossopharyngeal blocks are avoided because paralysis of
pharyngeal muscles can occur. Block of the vagal nerve occurs in many cases because of its proximity to the
glossopharyngeal nerve. Vagal block can result in hypertension, tachycardia, decreased hypoxic ventilatory drive,
and vocal cord paralysis. Large volumes of local anesthetic or imprecise needle placement can result in blockade of
the spinal accessory, facial, or hypoglossal nerves. Blockade of the spinal accessory nerve can result in weakness of
the trapezius muscle, and tongue weakness can occur with blockade of the hypoglossal nerve. As with any other
procedure that interrupts skin integrity, infection is a possible complication. Neurolytic blocks of the
glossopharyngeal nerve are infrequently done because of the multitude of nerves and vascular structures near the
glossopharyngeal nerve; however, if they are done, postblock dysethesia or anesthesia dolorosa may result.
Superior Laryngeal Nerve, Recurrent Laryngeal Nerve, and Transtracheal
Superior laryngeal nerve blocks can result in trauma to the carotid artery or external jugular vein, with ecchymosis
and hematoma formation. Intravascular injection can lead to local anesthetic toxicity. Inadvertent intratracheal
injection can occur with imprecise needle placement. Recurrent laryngeal nerve blocks can cause the same
complications as those of superior laryngeal nerve blocks. Trauma to the carotid artery or external jugular vein,
intravascular injection with resultant local anesthetic toxicity, and ecchymosis or hematoma formation can all occur
secondary to recurrent laryngeal nerve block. Bilateral recurrent laryngeal nerve blocks should be avoided because
bilateral vocal cord paralysis with airway obstruction can occur. Combined approaches, such as transtracheal block
with superior laryngeal nerve block, can lead to aspiration. Transtracheal injections usually produce a cough, which
may be undesirable in certain patients, such as those with increased intracranial pressure.
Sphenopalatine Ganglion
Sphenopalatine ganglion block can be performed to relieve headache pain in patients with migraine or cluster
headaches. Sphenopalatine ganglion block can be performed transnasally or via the greater palatine foramen. The
transnasal approach can result in epistaxis, local anesthetic toxicity from absorption through the highly vascular
nasal mucosa, and orthostatic hypotension. A block performed via the greater palatine foramen can result in
inadvertent intravascular injection or orthostatic hypotension.
Upper Extremity Blocks
BRACHIAL PLEXUS
Brachial plexus blocks are commonly performed procedures that provide anesthesia for upper extremity surgeries
and temporary postoperative pain relief. These blocks can also be used for diagnosis and treatment of a variety of
chronic pain conditions of the upper extremity. The brachial plexus can be blocked by the interscalene,
supraclavicular, infraclavicular, and axillary approaches. Axillary blockade of the brachial plexus is probably the
most commonly performed upper extremity block because it is easy to perform and has few side effects. Regardless
of the approach used, all brachial plexus blocks have several side effects and complication in common, which are
nerve injury, local anesthetic toxicity, and block failure.
Nerve injuries to the brachial plexus may be secondary to direct trauma to nerves from the block needle, from direct
toxic effects of the local anesthetic on the nerve, or from pressure generated by the large volume of local anesthetic
injected into sheaths surrounding the plexus. Fortunately, nerve injuries from attempted brachial plexus blockade are
usually self-limiting and resolve over 1 to 3 months. Permanent injuries are rare. Although not universally accepted,
there is evidence that the incidence of nerve injury may be increased with supraclavicular approaches to the plexus
and may be increased by using paresthesias to identify the brachial plexus. [7]
Local anesthetic toxicity from these blocks is relatively common secondary to the large local anesthetic dosages
used and because injection is close to major blood vessels. Most cases of local anesthetic toxicity are the result of
accidental intravenous injection and not absorption of appropriately injected local anesthetic dosages. Local
[7]
anesthetic toxicity usually manifests as seizure activity. Supraclavicular and interscalene techniques appear to have a
sixfold greater incidence of toxicity than those performed via the axillary approach, and continuous techniques show
a higher incidence of toxicity than single-shot techniques. Local anesthetic toxicity is greater in patients with
[7]
hepatic or renal insufficiency.
1057
Failure of anesthesia occurs in approximately 20% to 30% of attempted blocks. The incidence of block failure
appears to be higher with supraclavicular and interscalene approaches. Failure of brachial plexus blocks may be the
[7]
result of injection of local anesthetics outside of the sheath, inadequate volume or milligram dosage of local
anesthetics, or slow onset of anesthesia. Failure to allow adequate time for the block to become effective is probably
the major cause of failure of brachial plexus blocks. A number of methods have been devised to try to decrease the
[7]
failure rate of brachial plexus blocks. Allowing adequate time for the block to take effect is an important step in
decreasing the apparent failure rate. Elicitation of paresthesias, use of nerve stimulators, use of the transarterial
approach to the axillary block, and ultrasound guidance have all been used in attempts to decrease the failure rate of
brachial plexus blocks. Interscalene blocks often result in failure to anesthetize the ulnar nerve, and the axillary
approach frequently fails to anesthetize the musculocutaneous nerve.
Injection of a medication other than a local anesthetic is a potential complication of any form of regional anesthesia.
Tuohy reported the accidental injection of 2.5% thiopental instead of a local anethestic agent for a brachial plexus
[42]
block. There were no long-term sequelae. Patterson and Scanlon reported inadvertent injection of an antibiotic
[43]
around the brachial plexus. Again, no long-term sequelae were noted.
INTERSCALENE
The incidence of complications after interscalene and supraclavicular blocks appears to be greater than after axillary
blocks despite the more frequent performance of axillary block. Intravascular injection into the subclavian artery or
[7]
vein and local anesthetic toxicity can occur with improper needle positioning. Injection can be made into the
vertebral artery with resultant convulsions. Ecchymosis and hematoma formation can occur. Pneumothorax,
heralded by chest pain or cough, is a potential complication of interscalene block, but its occurrence is more likely
with supraclavicular block.
The phrenic nerve is frequently blocked by the interscalene approach. Phrenic nerve block can result in decreased
forced vital capacity, decreased forced expiratory volume, and decreased peak expiratory flow rates. Therefore,
bilateral interscalene blocks should be avoided and interscalene blocks discouraged in patients with advanced
pulmonary disease. Significant respiratory compromise after performance of an interscalene block in an elderly
woman who had no known respiratory disease was reported in 1998 and was thought to be caused by phrenic nerve
paralysis. A case report of dyspnea in an obese man who underwent an interscalene brachial plexus block has been
[44]
published. The authors attributed the dyspnea to decreased respiratory reserve from ipsilateral phrenic nerve block. [45]
Subarachnoid, subdural, and epidural placement of local anesthetic agents have been reported as complications of
interscalene blocks. These complications are rare but more common with interscalene blocks than with other
brachial plexus blocks. Recurrent laryngeal nerve block is a side effect of interscalene nerve block. The incidence
varies between 1.5% and 6%. Obviously, bilateral inscalene blocks should be avoided to prevent bilateral recurrent
[7]
laryngeal nerve block with resultant airway obstruction.
Intraneural injection, cervical plexus blockade, and cervical sympathetic chain blockade may occur as side effects of
interscalene blockade. Intraneural injection and resultant nerve injury may be heralded by pain during injection of
the local anesthetic solution. Bronchospasm has been reported as a side effect of interscalene anesthesia, although
the mechanism is unknown. Siler and associates reported a transient carotid bruit after an interscalene block, and
[7] [47]
Rosenberg and coworkers reported auditory impairment after an interscalene block.

[48]
SUPRACLAVICULAR
The complication usually associated with supraclavicular blockade is pneumothorax. Pneumothorax is more
common after supraclavicular block than after any other type of brachial plexus anesthesia. Avoiding medial
direction of the block needle can decrease the incidence of this complication. Intravascular injection with evidence
of local anethetic toxicity may occur. Ecchymosis and hematoma formation can occur. Accidental epidural,
subarachnoid, or subdural administration of the local anesthetic is possible but less likely than with the interscalene
block. Phrenic nerve block occurs frequently with the supraclavicular technique. Horner's syndrome can develop if
the cervical sympathetic chain is anesthetized; however, development of Horner's syndrome does not correlate with
the success of the block. Nerve injury from supraclavicular block is rare but can involve the nerve roots or the
phrenic nerve. [7]
Avoiding use of long needles and altogether avoiding the performance of blocks in anesthetized patients can
decrease the incidence of nerve injury. Persistent pain on injection of the local anesthetic solution can indicate
intraneural injection and should be avoided to reduce the risk of nerve injury. Intrapleural injection of local
1058
anesthetic agents during performance of a subraclavicular block has been reported. The patient received chest wall
anesthesia and upper extremity anesthesia but no pneumothorax. [49]
AXILLARY
Because of the proximity of the axillary artery to the area of injection, intravascular administration of local
anesthetics and local anesthetic toxicity are possible complications of axillary blocks. Hematoma formation and
ecchymosis have also been noted. Postblock residual paresthesia or dysesthesia occurs in about 2% of cases in
which paresthesias were used to find the brachial plexus. Intraneural injection with nerve damage is a potential
complication. Vasospasm and loss of circulation to the extremity may occur. Block failure and failure to anesthetize
the musculocutaneous nerve are relatively common. Venous insufficiency secondary to an axillary vein aneurysm [50]
and thrombosis of the axillary artery have been noted after axillary blocks.
[51]
MEDIAN, RADIAL, AND ULNAR NERVE BLOCKS
Elbow
Median, radial, and ulnar nerve blocks at the elbow are easy to perform and relatively safe. Intravascular injection of
the local anesthetic agents and nerve injury with persistent paresthesia or dysesthesia are potential complications.
The ulnar nerve can be compressed by large volumes of local anesthetic injected into the confined spaces at the
elbow.
Wrist
Median, radial, and ulnar nerve blocks at the wrist are relatively safe and easy. The main concerns are intravascular
injection and nerve injury leading to persistent paresthesia and dysesthesia. When the median
Figure 45-7 Slough of the thumb after the use of procaine

(Novocain)–epinephrine (Adrenalin) solution for a digital block.
nerve at the wrist is blocked, care should be taken to use small volumes and to inject the local anesthetic slowly to
avoid compression injury to the median nerve at the carpal tunnel. Compression injury can also affect the ulnar
nerve when blockade is done at the wrist, because Guyon's canal is a closed space. Again, slow injection with
smaller volumes of local anesthetic is advised to avoid compression injury.
Digital (Finger)
Mechanical compression of the blood supply to the finger by a large volume of local anesthetic can cause vascular
insufficiency and gangrene. Use of epinephrine-containing local anesthetics can result in vasoconstriction and
gangrene of the finger and should be avoided ( Fig. 45–7 ). [55]
Blocks of the Trunk
INTERCOSTAL NERVE
Pneumothorax is the complication usually associated with intercostal nerve blocks. The incidence of pneumothorax
after intercostal nerve blocks is less than 1%. Cough or chest pain produced during intercostal block may indicate
1059
formation of a pneumothorax. Administration of oxygen followed by needle aspiration of the pneumothorax or chest
tube placement may need to be done, depending on the size of the pneumothorax. Because of the proximity of the
intercostal artery and vein to the nerve, rapid absorption of local anesthetic, with neurologic or cardiovascular side
effects, may occur. If the paravertebral technique is used, subarachnoid or epidural injection can occur.
Intrapulmonary injection of local anesthetic can cause bronchospasm.
Other side effects or complications include hemothorax, hemoptysis, hematoma formation, neuritis, infection,
allergic reaction to the injected drugs, and failed blockade. If neurolytic agents are used, tissue necrosis or sloughing
can occur. Pulmonary insufficiency can occur after an intercostal block. Two reports of respiratory failure without
pneumothorax formation after bilateral intercostal blocks have been cited. This respiratory failure may be secondary
to motor blockade or loss of accessory respiratory musculature. Intercostal blocks should be avoided in patients
[52] [53]
with underlying pulmonary disease, particularly if the disease is confined to the contralateral lung. [54]
ILIOINGUINAL, ILIOHYPOGASTRIC, AND GENITOFEMORAL NERVES
These blocks are usually very safe; however, there are several complications. Hematoma or ecchymosis may occur.
Genitofemoral nerve block may be associated with puncture of the testicular artery or vein. Colon or intestinal
perforation by the block needle may occur if the needle penetration is too deep. Intra-abdominal abscess formation
may follow. The lateral femoral cutaneous nerve may occasionally be blocked during performance of ilioinguinal
and iliohypogastric nerve blocks.
SUPRASCAPULAR NERVE
Pneumothorax may occur with deep penetration by the block needle. The incidence of pneumothorax can be
lessened if the patient places the ipsilateral hand on the opposite shoulder. This position rotates the scapula away
from the chest wall, thus increasing the distance between the suprascapular notch and the chest wall. Intravascular
injection of local anesthetic agents into the suprascapular artery or vein may occur. Block failure is common with
imprecise needle placement. Muscle atrophy may follow injection of depot steroids into the supraspinatus muscle.
PENILE
Use of epinephrine-containing local anesthetic solutions should be avoided so that ischemia or necrosis of the penis
does not result from the vasoconstrictor effects of the epinephrine. Intravascular injection with local anesthetic
toxicity can occur if the block needle penetrates the corpus cavernosum. Hematoma formation from injury to the
dorsal artery or vein can also lead to gangrene of the tip of the penis.
PUDENDAL NERVE
Potential complications include intravascular injection into the pudendal artery or vein with subsequent local
anesthetic toxicity. The sciatic nerve or posterior cutaneous nerve of the thigh may be inadvertantly blocked by the
pudendal nerve. Infection and fistula formation, although theoretically possible, are quite rare.
Lower Extremity Blocks
SCIATIC NERVE
The sciatic nerve can be blocked by a variety of approaches. The block can be done in conjunction with blocks of
the femoral nerve, the obturator nerve, and the lateral femoral cutaneous nerve to provide lower extremity anesthesia
or postoperative analgesia. Block failure can be a significant problem. Ecchymosis or hematoma may occur and
nerve injury with persistent dysesthesia has been noted. These side effects may occur whether the block is done in
the anterior, posterior, or lithotomy position.
FEMORAL NERVE
Femoral nerve blocks are easily performed and can provide significant postoperative analgesia for femoral shaft
fractures or other anterior thigh procedures. When combined with a sciatic nerve block, an obturator nerve block,
and a lateral femoral cutaneous nerve block, lower extremity anesthesia can be obtained. Because of the proximity
of the femoral nerve to the femoral artery, intravascular injection or hematoma formation may occur. Direct injury
to the femoral nerve can result from intraneural injection. Often, the obturator and lateral femoral cutaneous nerves
are blocked concurrently with the femoral nerve.
1060
LATERAL FEMORAL CUTANEOUS NERVE
Block of the lateral femoral cutaneous nerve can be performed for the treatment of meralgia paresthetica or used in
conjunction with other lower extremity blocks for anesthesia of the leg. The block is safe, with relatively few side
effects. Direct nerve injury, ecchymosis, and hematoma are possible complications. Theoretically, the block needle
could enter the peritoneal cavity and cause perforation of the bowel and infection or abscess formation.
OBTURATOR NERVE
Obturator nerve blocks have complications and side effects similar to those of other lower extremity blocks.
Inadvertent intravascular injection into the obturator artery or vein with local anesthetic toxicity is a concern.
Ecchymosis or hematoma may occur if the obturator artery or vein is punctured. Inadvertent placement of the block
needle into the bladder, rectum, vagina, or spermatic cord are other potential complications.
PERIPHERAL NERVE
Knee
Block of the tibial, common peroneal, and saphenous nerves can be accomplished at the knee. Side effects and
complications of the blocks are rare. Potential side effects include injury to the nerves with persistent dysesthesia,
intravascular injection, ecchymosis, and hematoma.
Ankle
The deep peroneal, superficial peroneal, saphenous, posterior tibial, and sural nerves can all be blocked at the ankle.
The ankle block can be performed to provide anesthesia for foot surgeries. These blocks are relatively safe and have
few side effects. The major side effects include ecchymosis or hematoma formation from injury to the surrounding
blood vessels, intravascular injection of local anesthetics with local anesthetic side effects, and nerve injury. Large
volumes of local anesthetic could compress the vascular structures of the foot, causing ischemia. Epinephrine-
containing local anesthetics could also increase the incidence of ischemia.
Digital (Toe)
Epinephrine-containing local anesthetics should not be used to avoid digital ischemia. Vascular insufficiency and
gangrene could result from injection of large volumes of local anesthetic into the confined space around the digit.
Conclusion
Regional anesthetic techniques have become an important part of perioperative care. They are used as the principal
form of anesthesia for many surgical procedures. In addition, they are frequently used as an adjunct to general
anesthesia or as a means of postoperative pain management. Because of the increase in acceptance of various
regional anesthetic techniques, it is imperative that physicians understand the risks associated with specific
techniques, the side effects of various pharmacologic agents, and the selection of appropriate patients to guarantee
successful outcomes.
REFERENCES
1. Dalens B: Regional Anesthesia in Infants, Children and Adolescents. London, Williams & Wilkins, 1993.
2. Stoelting RK, Dierdorf SF: Anesthesia and Co-Existing Disease. New York, Churchill-Livingstone, 1993.
3. Sampson JF, Hamstra R, Aldrete JA. Management of hemophilia patients undergoing surgical procedures. Anesth Analg 58:133, 1979.
4. Waldman SD: Atlas of Interventional Pain Management, 2nd ed. Philadelphia, WB Saunders, 1998.
5. Mulroy MF: Regional Anesthesia: An Illustrated Procedural Guide. Boston, Little, Brown, 1989.
6. Raj PP: Handbook of Regional Anesthesia. New York, Churchill-Livingstone, 1985.
7. Finucane, BT: Complications of Regional Anesthesia. New York, Churchill Livingstone, 1999.
8. Covino BG: Toxicity and systemic effects of local anesthetic agents. Loc Anesth 81:187, 1987.
1061
9. Turner WM: Lidocaine and psychotic reaction. Ann Intern Med 97:149, 1982.
10. Scott DB: Evaluation of toxicity of local anaesthetic agents in man. Br J Anaesth 47:56, 1975.
11. Scott DB: Toxic effects of local anaesthetic agents on central nervous system. Br J Anaesth 58:732, 1986.
12. Aldrete JA, Romo-Salas F, Arora S, et al: Reverse arterial blood flow as a pathway for central nervous system toxic responses following
injection of local anesthesia Anesth Analg 57:428, 1978.
13. Bromage PR: Deaths in outpatient dental practice. Deaths following local analgesia: Possible pontine anaesthesia. Anaesthesia 30:239, 1975.
14. Korevaar WC, Burvey RE, Moore PA: Convulsions during stellate ganglion block—a case report. Anesth Analg 58:329, 1979.
15. Scott DL, Ghia JN, Teeple E: Aphasia and hemiparesis following stellate ganglion block. Anesth Analg 62:1038, 1983.
16. Szeinfeld M, Laurencio M, Pollares VS: Total reversible blindness following attempted stellate ganglion block. Anesth Analg 60:689, 1981.
17. KronmanJH, Kabani S: The neuronal basis for diploplia following local anaesthetic injection. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod 58:533, 1984.
18. Laskin DM: Diagnosis and treatment of complications associated with anaesthesia. Int Dent J 34:232, 1984.
19. Clarkson CW, Hondegtem LM: Mechanism for bupivacaine depression of cardiac conduction: Fast block of sodium chloride during the action
potential with slow recovery from block during diastole. Anesthesiology 62:396, 1985.
20. Klos CP, Hays GL: Prilocaine induced methaemoglobinemia in a child with Schwachman syndrome. J Oral Maxillofac Surg 43:621, 1985.
21. Kreutz
RV., Kinni ME. Life threatening toxic methaemoglobinemia induced by prilocaine. Oral Surg Oral Med Oral Pathol Oral Radiol Endod
56:480, 1983.
22. Warren R, Van de Mark T, Weinberg S: Methaemoglobinemia induced by high doses of prilocaine. J Oral Surg 37:866, 1979.
23. Duncan P, Kobrinsky N: Prilocaine induced methaemoglobinemia in a newborn infant. Anesthesiology 59:75, 1983.
24. Ludwig SC: Acute toxic methaemoglobinemia following dental analgesia. Ann Emerg Med 10:265, 1981.
25. Aldrete JA, Johnson DA: Evaluation of intracutaneous testing for investigation of allergy to local anesthetic agents. Anesth Analg 49:173,
1970.
26. Fisher M, Graham R: Adverse response to local anesthetics. Anaesth Intensive Care 12:325, 1984.
27. Incaudo
G, Schatz M, Patterson R, et al: Administration of local anesthetic to patients with a history of prior adverse reaction. J Allergy Clin
Immunol 61:339, 1978.
28. DeShazo RD, Nelson HS: An approach to the patient with a history of local anesthetic hypersensitivity: Experience with 90 patients. J Allerg
Clin Immunol 63:387, 1979.
29. Kane RE: Neurologic deficit following epidural or spinal anesthesia. Anesth Analg 60:150, 1981.
30. Myers RR, Kalichman MW, Reisner LS, et al: Neurotoxicity of local anesthetics: Altered perineural permeability, edema and nerve fiber
injury. Anesthesiology 64:29, 1989.
31. Gentili
F, Huchon AR, Hunter D, et al: Nerve injection injury with local anesthetic agent: A light and electric microscopic, fluorescent
microscopic and horseradish peroxidone study. Neurosurgery 6:263, 1980.
32. Munson ES, Paul WL, Embro WJ: Central nervous system toxicity of local anesthetic mixture in monkeys. Anesthesiology 46:179, 1977.
33. Gissen AJ, Datta S, Lambert D: The chloroprocaine controversy II. Is chloroprocaine neurotoxic? Reg Anesth 9:135, 1984.
34. Winchell SW, Wolfe R: The incidence of neuropathy following upper extremity nerve blocks. Reg Anesth 10:12, 1985.
35. Selender D, Edshage S, Wolff T: Parasthesia or no parasthesia? Nerve lesion after axillary block. Acta Anaesthesiol Scand 23:27, 1979.
36. Auroy Y, Narchi P, Messiah A: Serious complications related to regional anesthesia: Results of a prospective survey in France. Anesthesiology
87:479, 1997.
37. Plevak DJ, Lindstromberg JW, Danielsson DR: Paresthesia vs. nonparesthesia: The axillary block. Anesthesiology 59:A216, 1983.
38. Selander D, Dhoner KG, Lundberg G: Peripheral nerve injury due to injection needles used for regional anesthesia. An experimental study of
the acute effects of needle point trauma. Acta Anaesthesiol Scand 21:182, 1977.
1062
39. Holzer A, Kapratz S, Hellwagner K, et al: Severe pneumothorax after intercostal nerve blockade. A case report. Acta Anaesthesiol Scand
42:1124, 1998.
40. TandonS, Taxak S, Gupta KB, Janmeja AK: Pneumomediastrum: A rare complication of brachial plexus block. Indian J Chest Dis Allied Sci
40:217, 1998.
41. Mishio
M, Matsumoto T, Okuda Y, et al: Delayed severe airway obstruction due to hematoma following stellate ganglion block. Reg Anesth
Pain Med 23:516, 1998.
42. Tuohy SA, MacEvilly MA: Inadvertent injection of thiopentone to brachial plexus sheath. Br J Anaesth 54:355, 1982.
43. Patterson KW, Scanlon P: An unusual complication of brachial plexus sheath cannulation. Br J Anaesth 65:542, 1990.
44. Smith
MP, Tetzlaff JE, Brems JJ: Asymptomatic profound oxyhemoglobin desaturation following interscalene block in a geriatric patient. Reg
Anesth Pain Med 23:210, 1998.
45. RauRH, Chan YL, Chuang HI, et al: Dyspnea resulting from phrenic nerve paralysis after interscalene brachial plexus block in an obese male.
A case report. Acta Anaesthesiol Sin 35:113, 1997.
46. Hahn MB, McQuillan PM, Sheplock GJ: Regional Anesthesia. An Atlas of Anatomy and Techniques. St. Louis, Mosby–Year Book, 1996.
47. Siler PL, Lief JS, Davis JS: A complication of interscalene plexus block. Anesthesiology 38:590, 1973.
48. Rosenberg PH, Lambert TS, Tarkkila P, et al: Auditory disturbance associated with interscalene brachial plexus block. Br J Anaesth 74:89,
1995.
49. Manara AR: Brachial plexus block, unilateral thoraco-abdominal blockade following the supraclavicular approach. Anesthesia 42:757, 1987.
50. Restelli
L, Pingiroli D, Conoscente F, et al: Insufficient venous drainage following axillary approach to the brachial plexus block. Br J Anaesth
56:1051, 1984.
51. Ott L, Neuberger L, Frey HP: Obliteration of the axillary artery following axillary artery puncture. Radiology 88:271, 1967.
52. Cory PC, Mulroy MF: Postoperative respiratory failure following intercostal block. Anesthesiology 54:418, 1981.
53. Casey WF: Respiratory failure following intercostal nerve blockade. Anaesthesia 39:351, 1984.
54. Holzer
A, Kapral S, Hellwagner K, et al: Severe pneumothorax after intercostal nerve blockade. A case report. Acta Anaesthesiol Scand
42:1124, 1998.
55. Moore DC: Complications of Regional Anesthesia: Etiology— Signs and Symptoms—Treatment. Springfield, Illinois, Charles C Thomas,
1955.
56. BridenbaughPO, Crews JC: Perioperative management of patients for neural blockade. In Cousins MJ, Bridenbaugh PO (eds): Neural
Blockade in Clinical Anesthesia and Management of Pain, 3rd ed. Philadelphia, Lippincott-Raven, 1998.
1063
Section VII Chapter 46 - Efficacy of Neuraxial and Peripheral Nerve Blocks in Acute Pain
Section VII - Outcome Studies in Regional Anesthesia: Evidence-

Based Practice
Peter S. Staats
1064
Chapter 46 - Efficacy of Neuraxial and Peripheral Nerve Blocks in

Acute Pain Management
CHRISTOPHER L. WU
Over the past two decades, a growing body of knowledge has accumulated from investigation of the effect of
regional anesthesia and postoperative analgesia on patient outcomes. Use of regional anesthesia and analgesia
results in many beneficial physiologic effects and is strongly associated with favorable outcomes in several organ
systems (i.e., gastrointestinal and coagulation); however, the efficacy of regional anesthesia may not be as apparent
in other areas, such as postoperative cognitive function. By attenuating detrimental physiologic effects that occur
postoperatively, regional anesthesia and postoperative analgesia may improve perioperative patient outcomes.
There are concerns about methods used for current outcome studies that prevent us from determining the role and
efficacy of regional anesthesia and analgesia in traditional patient outcomes, such as morbidity and mortality. The
efficacy of regional anesthesia and analgesia on nontraditional outcomes, such as economic and quality of life
measurements, has not yet been fully explored. In addition, the effect of postoperative analgesia per se on patient
outcomes, as opposed to that of intraoperative analgesia, has not yet been defined.
Overview of Current Studies
There are many obstacles to be overcome in evaluating the effect of regional anesthesia and analgesia on patient
outcomes. Inadequate sample sizes, use of surrogate endpoints, incomplete measurements of pain, and inconsistent
[1]
duration of postoperative analgesia contribute to uncertainty in determining the role of regional anesthesia and
analgesia in patient outcomes. Furthermore, varying definitions of patient outcomes may alter incidence of
complications, which may affect interpretation of data, and, in turn, any conclusions made about efficacy of regional
anesthesia and analgesia on outcomes.
Inadequate sample sizes limit the clinically significant differences in a study. In general, current studies are
underpowered as a consequence of the low incidence of outcome events studied and the relatively small numbers of
patients evaluated. Enrolling lower risk subjects or those undergoing less invasive surgery may further decrease the
incidence of the outcome being evaluated. Thus, a large number of subjects must be enrolled to determine
[1] [2] [3]
whether there is a clinically significant difference in outcomes, especially if the incidence of the outcome event is
low. For instance, approximately 3000 patients are needed to determine whether an intervention could decrease the
incidence of myocardial ischemia from 30% to 20%. [4]
To perform a study with fewer patients, some authors may elect to use surrogate or intermediate endpoints
(myocardial ischemia) instead of ultimate or final endpoints (myocardial infarction or death). This assumes that
there is an association between surrogate and final endpoints and that a difference in the incidence of the surrogate
endpoint will be reflected in the final endpoint. Large number of observations are needed to validate the relationship
between surrogate and final endpoints. Thus, surrogate endpoints may not be reliable predictors of outcomes. For
instance, a meta-analysis investigating the efficacy of postoperative analgesic therapies on pulmonary outcomes
demonstrated a significant decrease in incidence of pulmonary morbidity (atelectasis, infections, overall
complications) despite no difference in surrogate pulmonary measurements, such as forced expiratory volume in 1
second (FEV1 ), functional residual capacity (FVC), or peak expiratory flow rate (PEFR). [5]
The quality and duration of postoperative analgesia have been inconsistent. In some studies, duration of
postoperative regional analgesia may be too brief to elicit any benefits that may translate into improved outcomes.
Incidence of some postoperative complications, such as myocardial ischemia and infarction, peak at a time when
regional analgesia may have already been discontinued. An appropriate regimen of postoperative regional analgesia
must be employed for an appropriate duration so that any physiologic benefits from regional analgesia may be used
to improve patient outcomes; otherwise, interpretation of results may be ambiguous at best. [6] [7]
Measurement of pain may also be incomplete. Studies that measure only pain at rest may not maximize the
analgesic regimen to allow dynamic pain control, which would potentially allow greater patient participation in
activities (deep breathing, coughing, movement) that might improve outcomes. By itself, analgesia at rest is
insufficient to improve postoperative outcomes. Providing adequate dynamic analgesia may facilitate other aspects
of patient convalescence and thus may improve patient outcomes.
1065
In general, conducting studies on the effect of regional anesthesia and postoperative analgesia on patient outcomes is
difficult at best. Many problems affect interpretation of available studies. Large sample sizes, which most likely
necessitate multicenter efforts, may be needed to definitively address the role of regional anesthesia and analgesia
on patient outcomes.
Outcomes after Regional Anesthesia and Analgesia
Postoperative pathophysiology affects many organs, with complex and intricate interactions between organ systems.
By attenuating postoperative response in one organ system, regional anesthesia and analgesia may affect responses
in other organ systems. The following sections are designed so that as the reader proceeds, discussion of each organ
system builds on knowledge obtained from previous discussions of organ systems. Each section describes typical
postoperative pathophysiology followed by physiologic effects of regional anesthesia and analgesia. Efficacy of
neuraxial and peripheral anesthesia and analgesia are discussed when appropriate.
Stress Response
POSTOPERATIVE PATHOPHYSIOLOGY
Surgical trauma results in local inflammatory and systemic endocrine metabolic responses ( Table 46-1 ). Local
responses include release of cytokines (including interleukin-1 and interleukin-6, tumor necrosis factor, and platelet
activating factor), histamine, serotonin, prostaglandins, and leukotrienes. The systemic response
TABLE 46-1 -- OVERVIEW OF THE NEUROENDOCRINE STRESS RESPONSE

Postoperative Pathophysiology Benefits of Regional Anesthesia
Hypermetabolic, catabolic state Inhibition of the stress response
↑ Catabolic hormones Complete (peripheral procedures)
↑ Heart rate/blood pressure Partial (abdominal or thoracic procedures)
↑ Serum glucose Attenuation or prevention of postoperative increase in catabolic
↑ Protein catabolism hormones
Possible potentiation of postoperative hypercoagulability and
immunosuppression
after surgical insult includes a general increase in catabolic hormones, such as catecholamines, cortisol, renin,
aldosterone, and glucagon, which result in hyperglycemia, muscle protein catabolism (negative nitrogen balance),
and increased lipolysis. In addition, there is sodium and water retention, with a shift of extracellular fluid to
intracellular compartments. A general decrease in immune function and activation of coagulation are also
[8]
associated with the stress response. The net result is a hypermetabolic, catabolic state resembling semistarvation.
Initiation of the stress response after surgery occurs via several mechanisms. Transmission of afferent neural stimuli
through somatosensory and sympathetic pathways is essential for stress response activation after surgery.
Nociceptive and neural stimuli are conveyed through thinly myelinated and unmyelinated afferent fibers to the
dorsal horn of the spinal cord, with further transmission to other areas of the central nervous system (CNS),
especially the hypothalamus. Efferent responses to this neural input are manifested as the endocrine metabolic
response described earlier.
The relative contribution of individual local inflammatory mediators to the stress response is uncertain. Local
release of biogenic amines, serine proteases, and lipid mediators such as prostaglandins, leukotrienes, serotonin,
bradykinin, and histamine, may enhance and facilitate transmission of afferent nociceptive and neural input into the
CNS. Although specific interactions culminating in the stress response are unclear, both local inflammatory and
systemic endocrine metabolic factors are important in producing stress-related manifestations seen after surgical
trauma. [8]
The stress response may be modified by many factors, such as the intensity of the surgical injury, the use of anabolic
hormones and adrenergic blockers, perioperative temperature control, and the type of anesthesia used. The extent of
the stress response is proportional to the degree of surgical trauma. Patients undergoing laparoscopic
[9] [10] [11] [12]
cholecystectomy have significantly lower levels of catecholamines and cytokines compared with those undergoing
conventional cholecystectomy. Administration of anabolic hormones such as insulin and growth hormone reduce
[12]
protein breakdown and improve nitrogen balance after trauma. Likewise, administration of adrenergic blockers
[13] [14] [15]
may attenuate the stress response. Hypothermia increases the extent of the stress response and maintenance of
[16]
perioperative normothermia reduces urinary indicators of muscle protein degradation and nitrogen loss. Unlike [17] [18]
1066
regional anesthesia, use of general anesthesia, with the possible exception of a high-dose opioid regimen, does not
significantly alter the perioperative stress response.
Although data with regard to the stress response effect on patient outcomes are inconclusive, there are many
detrimental consequences of prolonged surgical stress. Catecholamine release causes increases in heart rate, which
may result in postoperative myocardial ischemia or infarction. Hyperglycemia and insulin resistance may contribute
to poor wound healing and depression of immune function. Negative nitrogen balance and protein catabolism
[19] [20]
may hinder overall patient convalescence. Potentiation of hypercoagulable and immunosuppressive states may result
in thrombotic and infectious complications postoperatively. Teleologic reasons for the stress response (“fight or
flight”) may not be relevant or beneficial in the setting of iatrogenic surgical trauma; thus, decreasing the stress
response attenuates detrimental physiologic responses and may lead to improved patient outcomes.
PHYSIOLOGIC EFFECTS OF REGIONAL ANESTHESIA AND ANALGESIA
Regional anesthesia and analgesia can attenuate surgical stress response by suppressing afferent sympathetic and
somatosensory input. Complete inhibition of the stress response requires use of local anesthetics to provide complete
block of afferent sympathetic and somatosensory input from the site of surgical trauma (T4 to S5 sensory level or
peripheral blocks as appropriate for the surgical site). Establishment of an appropriate block before traumatic
[21] [22]
stimulus is necessary to prevent initiation of the stress response. Pain relief per se cannot completely suppress the
stress response because nociceptive input constitutes only part of the sympathetic and somatosensory input to the
CNS for stress response activation.[23] [24]
Regional anesthesia with local anesthetics for peripheral procedures or those below the umbilicus can completely
prevent stress response activation through complete suppression of sympathetic and somatosensory input.
Administration of an adequate dose of local anesthetics in the lumbar region significantly reduces or abolishes
somatosensory evoked potentials after peripheral stimulation. Compared with those receiving general anesthesia,
[25] [26]
patients receiving an adequate neuraxial block (T4 level) before surgical insult demonstrate postoperative
suppression of plasma catecholamines, cortisol, aldosterone, and renin. In addition, regional anesthesia inhibits
[8]
postoperative hyperglycemia, lipolysis, and negative nitrogen balance.
Neuraxial block with local anesthetics for upper abdominal or thoracic surgical procedures may only partially
suppress the stress response. Inadequate extent and density of sensory block contribute to the inability of neuraxial
blocks to prevent the stress response in surgical procedures above the umbilicus, which are associated with a greater
increase in stress response compared with more peripheral or less invasive surgeries. Insufficient block of phrenic,
[1] [8]
somatosensory, and sympathetic afferent pathways may result in only partial suppression of the stress response after
upper abdominal or thoracic surgery. In addition, release of local mediators such as cytokines during upper
[27] [28] [29]
abdominal or thoracic surgical procedures cannot be attenuated by regional anesthesia with local anesthetics. [30]
Despite providing complete control of postoperative pain, neuraxial opioids only partially attenuate the stress
response because of their inability to completely block transmission of peripheral afferent neural input. [23] [24] [31]
Epidural administration of opioids does not prevent postoperative increases in levels of cortisol, glucose,
vasopressin, and epinephrine in patients undergoing thoracic or abdominal procedures; however, there are
significant decreases in plasma norepinephrine levels. Compared with those who receive local anesthetics,
[32] [33] [34]
patients who receive epidural opioids for upper abdominal surgery have equivalent relief of pain but higher levels of
plasma cortisol and catecholamines postoperatively. [24] [35]
Use of postoperative analgesia, especially with local anesthetics, is important for continued stress response
attenuation. Many markers of the stress response peak in the early postoperative period and may continue to be
elevated well into the postoperative period. Use of epidural analgesia with local anesthetics for at least 24 hours
[30] [36]
after surgery improves postoperative nitrogen balance and muscle amino acid profile. Continuation of[37] [38] [39]
neuraxial opioids for 4 days postoperatively provided superior analgesia to that achieved with systemic opioids but
did not prevent increases in urinary excretion of catecholamines, cortisol, and nitrogen. [35]
EFFICACY OF NEURAXIAL BLOCK
Although perioperative stress may result in many undesirable physiologic effects, the relationship between the stress
response per se and the postoperative outcome is unclear, despite some evidence that diminishing stress improves
patient outcomes. Neuraxial block, especially with local anesthetics, suppresses the stress response and may result
[40]
in prevention of detrimental physiologic parameters, such as increases in blood pressure, heart rate, and oxygen
consumption, which may lead to adverse outcomes. Compared with those who receive general anesthesia, patients
who receive neuraxial analgesia have significantly lower blood pressure, heart rate, and levels of catecholamines
1067
and oxygen consumption in the postoperative period. By attenuating perioperative stress, regional anesthesia
[34] [41] [42]
and analgesia can provide a favorable physiologic profile and may improve patient outcomes.
Despite the potential benefits of regional anesthesia on patient outcome, few data exist that link inhibition of
surgical stress by neuraxial anesthesia and analgesia to patient outcome. Use of epidural anesthesia and analgesia in
high-risk surgical patients results in decrease in urinary cortisol excretion, incidence of cardiovascular failure, major
infectious complications, and overall postoperative complications. Patients receiving neuraxial anesthesia for lower [43]
extremity vascular surgery have lower norepinephrine levels and less incidence of graft failure. In addition, [3]
neuraxial anesthesia may improve patient outcomes through attenuation of the stress response-induced potentiation
of postoperative hypercoagulability and immunosuppression. Thus, suppression of the stress response after[1] [44]
surgery may result in improved outcomes in many areas, including cardiovascular, coagulation, and immune
systems.
EFFICACY OF PERIPHERAL NERVE BLOCK
By interrupting neural input into the CNS, peripheral nerve blocks may also minimize the surgical stress response
after surgery. For instance, patients receiving regional anesthesia (interscalene block) for shoulder surgery have
significantly lower serum epinephrine levels in the immediate postoperative period. Unlike those receiving general [22]
anesthesia, patients receiving regional anesthesia (retrobulbar block) for cataract surgery do not have a significant
increase in catecholamines, glucose, and cortisol. Peripheral blocks of the sympathetic nervous system
[45] [46]
(paravertebral and celiac plexus block) may also blunt but not abolish the stress response. Systemic absorption of [47] [48]
local anesthetic is not likely to be responsible for any suppression of the stress response in the immediate
postoperative period. Intercostal, intraperitoneal, or intrapleural administration of local anesthetics is not effective
[49]
in attenuating the stress response. Although peripheral nerve blocks are able to blunt the surgical stress
[32] [50] [51] [52] [53]
response, no comprehensive analysis of the effect of peripheral nerve block on outcome has been performed.
In summary, the stress response after surgery affects numerous organ systems and results in many detrimental
effects. Regional anesthesia and analgesia can attenuate the stress response and are especially effective in
completely suppressing the response for peripheral surgeries. Despite the physiologic benefits of regional anesthesia
in reducing surgical stress, the role of regional anesthesia and analgesia on patient outcome in this area is still
unclear. There are limited data regarding how the suppression of the stress response by regional anesthesia affects
patient outcome. A further complication is that the relationship between surgical stress per se and postoperative
outcomes is uncertain.
Coagulation
A hypercoagulable state occurs in the postoperative period and is associated with the enhancement of coagulation
and inhibition of fibrinolysis ( Table 46-2 ). Increased levels of procoagulants such as factor VIII, von Willebrand’s
factor, and fibrinogen, as well as decreased levels of anticoagulants such as antithrombin III and protein C,
contribute to the postoperative enhancement of coagulation. In addition, platelet reactivity is increased
[54] [55] [56] [57]
postoperatively and may last beyond the seventh postoperative day. Impaired fibrinolysis results from decreases [56] [58]
in endogenous anticoagulants such as protein C, antithrombin, and heparin cofactor II, and increases in fibrinolytic
inhibitors including plasminogen activator inhibitor (PAI-1). Finally, there is a postoperative increase in
[56] [59] [60] [61]
plasma viscosity. [55]
The exact etiology of postoperative hypercoagulability is unclear. Possible mechanisms include potentiation by the
stress response, endothelial damage resulting in tissue factor expression with platelet aggregation and extrinsic
coagulation cascade activation, and synergistic effects of inflammation. The stress response after surgery increases [62]
levels of cytokines, which may activate endothelial cells and result in prothrombotic and proinflammatory
responses. Interleukin-1 induces endothelial procoagulant tissue factor activity while decreasing thrombin-
[63]
mediated protein C activation. [64]
TABLE 46-2 -- OVERVIEW OF COAGULATION

Postoperative hypercoagulability Attenuation of hypercoagulable state
↑ Procoagulants and fibrinolytic inhibitors Enhancement of fibrinolytic activity
↓ Anticoagulants Attenuation of increase in procoagulant and fibrinolytic inhibitors
1068
TABLE 46-2 -- OVERVIEW OF COAGULATION

Endothelial damage/tissue factor activation ↑ Blood flow
Possible potentiation by stress response ↓ Stasis
Local anesthetic effects
Tumor necrosis factor may cause a shift in favor of clot formation, in part through increased levels of PAI-1. In [65] [66]
addition, platelet function is enhanced by interleukin-6. Despite evidence that the stress response may initiate
[67]
postoperative hypercoagulability, infusions of neuroendocrine stress hormones (epinephrine, cortisol, glucagon,

angiotensin II, and vasopressin) in healthy volunteers do not cause increases in procoagulant proteins and platelet
reactivity or decreases in fibrinolytic parameters. [68]
Other mechanisms of postoperative hypercoagulability may include endothelial damage causing tissue factor
expression and synergistic effects of inflammation on coagulation. Endothelial damage from surgical trauma
increases expression of tissue factor, which can activate the extrinsic coagulation cascade and platelet aggregation.
Tissue factor appears to have a central role in initiation of coagulation. Endothelial cells also release PAI-1, which [69]
inhibits fibrinolysis. [70]
Inflammation and coagulation appear to be closely linked processes. Severe inflammation is associated with a shift
toward coagulation because there is a decrease in fibrinolytic activity whereby the degree of fibrinolytic inhibition
directly correlates with severity of inflammation. Inflammatory cytokines mediate endothelial activation, stimulate
[71]
coagulation, and decrease activity of endogenous anticoagulants. In addition, leukocytes activated by

[72] [73] [74]
inflammatory processes potentiate activation of coagulation, increase platelet reactivity, and inhibit endogenous
anticoagulant activity. [62]
Regional anesthesia and analgesia with local anesthetics provide several beneficial effects on postoperative
coagulation. Regional anesthesia causes a sympathectomy-induced vasodilatation, which increases both arterial and
venous blood flow. Compared with patients receiving general anesthesia, those receiving epidural anesthesia
[75] [76]
with local anesthetics for both vascular and nonvascular surgery have significant increases in total leg and skin
blood flow in the postanesthetic period. In addition, use of epinephrine-containing local anesthetic solutions for
[77]
epidural anesthesia may augment lower extremity blood flow. Thus, by decreasing stasis, increasing blood flow,
[78]
and improving rheologic properties, regional anesthesia and analgesia indirectly attenuate postoperative
hypercoagulability. [62] [79]
Regional anesthesia also potentiates fibrinolytic activity by attenuating postoperative increases in factor VIII, von
Willebrand’s factor, and PAI-1. In addition, antithrombin III levels return to preoperative levels faster in patients
[54] [80]
who receive epidural anesthesia than in those receiving general anesthesia. Local anesthetics used in regional [81]
anesthesia may be systemically absorbed and favorably alter rheologic properties. Local anesthetics prevent
collagen- and ADP-induced platelet aggregation, prevent leukocyte adhesion and migration to damaged endothelium,
inhibit thrombus formation after injury, and decrease plasma and whole blood viscosity. [82] [83] [84] [85]
Postoperative hypercoagulability may result in venous and arterial thrombotic events. Impaired fibrinolytic activity
and venous stasis may contribute to venous thrombosis. Endothelial damage, enhanced platelet reactivity,
hypercoagulability, and decreased fibrinolysis may cause arterial thrombotic events. By improving extremity blood [62]
flow, enhancing fibrinolytic activity, and altering rheologic properties, regional anesthesia and analgesia with local
anesthetics attenuates postoperative hypercoagulability.
EFFICACY OF REGIONAL ANESTHESIA AND ANALGESIA
Postoperative hypercoagulability is associated with vaso-occlusive and thromboembolic events, which contribute to
approximately 200,000 to 300,000 deaths annually in the United States. Regional (neuraxial) anesthesia and [86] [87]
analgesia with local anesthetics may attenuate postoperative hypercoagulability, potentially leading to a lower
incidence of thrombotic events and improvement in patient outcomes than are seen in patients who receive general
anesthesia.
Compared with general anesthesia, regional anesthesia clearly decreases incidence of deep venous thrombosis after
orthopedic surgery. A meta-analysis of randomized, controlled trials in patients undergoing repair of
[88] [89] [90] [91]
traumatic femoral neck fractures found that use of regional anesthesia significantly decreased incidence of deep
1069
venous thrombosis (DVT). Regional anesthesia also decreased incidence of DVT in patients undergoing open
[90]
prostatectomy. Continuation of epidural analgesia with local anesthetics into the postoperative period reduced
[92]
incidence of DVT. A decrease in incidence of DVT may also occur with intravenous infusions of lidocaine,
[93] [94]
which supports evidence for the beneficial rheologic properties of local anesthetics. [95]
Regional anesthesia also decreased incidence of graft thrombosis after vascular surgery. Compared with those [3] [96]
who received general anesthesia, patients receiving epidural anesthesia alone or combined epidural-general
anesthesia had a lower rate of graft occlusion or failure and decreased tendency for coagulation. Retrospective [3] [80] [96]
data suggest that epidural analgesic supplementation to general anesthesia may be associated with a higher rate of
free flap survival and lower incidence of microvascular complications. By decreasing postoperative coagulability,
[97]
regional anesthesia and analgesia may enhance cardiovascular benefits, because platelet hyperreactivity may lead to
coronary events, including myocardial infraction and sudden death. [98]
In summary, the etiology of postoperative hypercoagulability is uncertain at this time. The network of interactions
between potential mediators is complex and, ultimately, it may be decided that many factors contribute to
development of postoperative hypercoagulability. Regional anesthesia and analgesia with local anesthetics may
decrease postoperative hypercoagulability through several mechanisms and potentially improve patient outcomes by
decreasing incidence of thrombotic complications.
Immune Function
Surgery and trauma are associated with general suppression of immune system function ( Table 46-3 ), which
reaches a nadir on approximately the third postoperative day. A gradual recovery to preoperative function occurs
over the next 1 to 3 weeks. The degree of immunosuppression is related to the severity of the surgical injury.
[44] [99] [100]
Cell-mediated (T lymphocytes, natural killer [NK] cells, mononuclear phagocytes, polymorphonuclear granulocytes,
and cytokines produced from leukocytes) and humoral (immunoglobulins and complement) aspects of immune
response are both suppressed postoperatively. After major surgery, there is a decrease in the number and reactivity
of T lymphocytes. In addition, NK cell activity is depressed in the immediate postoperative period. The number
[99] [101]
of B lymphocytes and their production of immunoglobulin both decrease postoperatively. [99]
Although the precise nature of postoperative immunosuppression is uncertain, several perioperative elements,
including the stress response and perioperative drug administration (anesthetic agents, opioids), may contribute to
immunodepression after surgery. The surgical stress response may be important in mediating some aspects of
postoperative immunosuppression. [101] [102]
TABLE 46-3 -- OVERVIEW OF IMMUNE FUNCTION

Postoperative immunosuppression Preservation of lymphocyte and natural killer
cell activity
↓ Cell-mediated (T lymphocyte) and humoral (immunoglobulin) response ↓ Postoperative use of opioids
Postoperaitve use of opioids Attenuation of stress response
Possible potentiation by stress response Local anesthetic effects
Cortisol and epinephrine may reduce neutrophil chemotaxis and decrease NK cell activity. Also, perioperative [101] [103]
administration of morphine diminishes NK cell and lymphocyte activity. In animal studies, morphine induces a
[104] [105]
decrease in lymphoid organ weight and inhibits ability to combat active infections. Immunosuppression is not [106]
reversed with administration of naloxone. Inhalational anesthetic agents may also inhibit interferon stimulation of
[106]
NK cell activity. The effect of anesthetic agents on human immune response is unclear and may be clinically
[107] [108]
significant; however, the effects resulting from surgical trauma are probably more important than those of anesthetic
agents on postoperative immunosuppression. [109]
Regional anesthesia and analgesia, especially with local anesthetics, may partially blunt postoperative suppression
of cellular immune function. Through attenuation of the stress response, regional anesthesia may preserve
postoperative immune function. Compared with those receiving general anesthesia, patients receiving regional
1070
anesthesia have preserved NK cell and lymphocyte activity. Regional anesthesia prevents postoperative
[110] [111]
lymphopenia. In addition, neutrophilic chemotactic and biocidal activity are diminished in those receiving general
[112]
but not epidural anesthesia. Regional anesthesia with local anesthetics may also prevent postoperative opioid-
[113] [114]
induced immunosuppression by decreasing the amount of opioids used for postoperative analgesia.
Systemically absorbed local anesthetics may also potentially affect leukocyte function. Local anesthetics may inhibit
leukocyte function in vitro and may exhibit anti-inflammatory properties. In addition, local anesthetics reduce [115]
release of tissue-damaging mediators, such as oxygen free radicals and lysozymes, which may impair wound
healing. Thus, systemically absorbed local anesthetics from regional analgesic infusions may decrease
[116]
postoperative inflammation, promote wound healing, and preserve postoperative immune function.
Thus, there is suppression of immune function after surgery. Regional anesthesia may attenuate postoperative
immunodepression; however, it is difficult to assess the effect of regional anesthesia per se on immune function
because of the complexity of interactions within the immune system. Current laboratory tests may not reflect in
[1] [109]
vivo immune function. Furthermore, it is difficult to assess whether any benefits determined in vitro can be applied
to clinical situations.
EFFICACY OF REGIONAL ANESTHESIA ANDANALGESIA
Immunosuppression may contribute to development of postoperative infections and increase patient morbidity and
cost of patient care. In addition, depression of immune function postoperatively may enhance tumor growth and
[117] [118]
metastases. By attenuating postoperative immunodepression, regional anesthesia and analgesia (mostly with
[119]
neuraxial techniques) may improve patient outcomes through prevention of postoperative complications associated
with immunodepression.
Several prospective studies comparing use of general anesthesia with combined epidural-general anesthetic
technique demonstrated a decrease in incidence of postoperative infectious complications in patients receiving
epidural analgesia. High-risk patients undergoing thoracic, abdominal, and vascular procedures and receiving
[43] [96] [120]
intra- and postoperative epidural analgesia had a significantly lower incidence of major infectious complications
such as pneumonia or sepsis. Other prospective studies also noted a slight but not significant decrease in
[43] [96]
pulmonary (incidence of pneumonia) and wound complications. [2] [121]
Perioperative blood transfusions are associated with perioperative immunosuppression and recurrence of tumor
growth. Regional anesthesia decreases intraoperative and postoperative blood loss in some orthopedic and
[122]
urologic procedures as well as the need for intraoperative blood transfusions. By decreasing blood loss, [123] [124] [125]
regional anesthesia may diminish the need for perioperative blood transfusions and indirectly prevent recurrence of
tumor growth.
In summary, regional anesthesia and analgesia may preserve postoperative immune function. The mechanisms by
which regional anesthesia attenuate postoperative immunosuppression are unknown, but they may become apparent
as we expand our understanding of the elaborate interactions that produce postoperative immunosuppression.
Despite laboratory and clinical data demonstrating beneficial effects of regional anesthesia on postoperative immune
function, definitive outcome studies are lacking.
Cardiovascular System
The immediate postoperative period accounts for a high incidence of cardiovascular events, including myocardial
ischemia, myocardial infarction, congestive heart failure, ventricular arrhythmias, and sudden death ( Table 46-4 ). [126]
Cardiovascular complications may be a primary cause of morbidity and mortality in high-risk populations, such as
in patients undergoing vascular surgery. A majority of myocardial ischemia
TABLE 46-4 -- OVERVIEW OF CARDIOVASCULAR FUNCTION

Sympathetic nervous system activation Inhibition of sympathetic nervous system
↑ Myocardial oxygen demand ↓ Myocardial oxygen demand
↓ Myocardial oxygen supply ↑ Myocardial oxygen supply (distribution of coronary flow to endocardial and ischemic
areas)
1071
TABLE 46-4 -- OVERVIEW OF CARDIOVASCULAR FUNCTION

Postoperative hypercoagulable state Attenuation of postoperative hypercoagulability
and infarction occurs in the first 72 hours after surgery. Silent postoperative myocardial ischemia may be
[127] [128] [129] [130]
present in approximately 35% to 40% of high-risk patients and is a predictor of patient outcome. [126] [128]
Sympathetic nervous system activation is important for development of myocardial ischemia and infarction and
cardiac arrhythmias. Sympathetic stimulation, either through a neuroendocrine stress response or inadequate
[131] [132] [133]
analgesia, may increase heart rate, inotropy, and blood pressure. An increase in myocardial metabolism and oxygen
consumption through increases in inotropy or chronotropy may increase myocardial oxygen demand and result in
myocardial ischemia and even increases in myocardial infarct size. However, increases in myocardial oxygen [134]
demand may not necessarily correlate with occurrence of myocardial ischemia. [135] [136]
Similarly, a decrease in myocardial oxygen supply through coronary vasoconstriction or thrombosis can lead to
myocardial ischemia. Sympathetic activation may cause coronary vasoconstriction, which may be more pronounced
in those with atherosclerotic disease, especially because the majority of cases of coronary stenosis may be dynamic
in nature. In addition, sympathetic stimulation can override local metabolic coronary vasodilatation.
[137] [138] [139]
Furthermore, postoperative hypercoagulability may be related in part to the neuroendocrine stress response and may
contribute to thrombotic complications. Increased coagulability is believed to be important in the development of
[80]
myocardial ischemia and infarction. Thus, by increasing myocardial oxygen demand and decreasing myocardial
[98]
oxygen supply, sympathetic nervous activation may be important in the development of postoperative cardiac
morbidity and mortality.
Regional anesthesia and analgesia provide several cardiovascular benefits, in part through attenuation of the
sympathetic nervous system, which is important in the development of postoperative myocardial complications. [140]
Inhibition of the sympathetic nervous system may have a favorable effect on myocardial oxygen consumption.
Thoracic epidural analgesia (TEA), using either opioids or local anesthetics, diminishes postoperative sympathetic
nervous system activation. Through reductions in neuroendocrine stress response and levels of postoperative
[24] [34]
pain, TEA decreases tachycardia and hypertension and increases myocardial oxygen consumption. Furthermore,
TEA may benefit the ischemic myocardium by attenuating myocardial acidosis. TEA using local anesthetics has [141]
been shown to decrease severity of myocardial ischemia and infarct size. Minimal hemodynamic changes occur [142]
with a sensory block of T1 to T5 in healthy subjects and in those with coronary artery disease. [143] [144]
Inhibition of the sympathetic nervous system may also have a favorable effect on myocardial oxygen delivery. TEA
using local anesthetics but not opioids favorably increases distribution of coronary blood flow to endocardial and
ischemic regions. Total coronary flow does not increase; however, TEA increases the diameter of stenotic but
[145] [146]
not nonstenotic epicardial coronary artery segments. TEA using local anesthetics also blocks sympathetically
[144]
mediated coronary vasoconstriction and improves ischemia-induced ventricular wall motion abnormalities during
physical stress. The favorable effect of TEA using local anesthetics on myocardial oxygen delivery may be
[147] [148] [149]
due to inhibition of α- and β-adrenergic effects. Thus, attenuation of sympathetic system activation by regional
[1]
anesthesia and analgesia results in beneficial cardiovascular effects by decreasing myocardial oxygen demand and,
more importantly, increasing myocardial oxygen supply through favorable redistribution of coronary blood flow.
Through local anesthetic absorption and neuroendocrine stress response attenuation, TEA may diminish
postoperative hypercoagulability, thereby potentially decreasing incidence of cardiovascular morbidity. Local
anesthetics inhibit platelet aggregation, decrease whole blood and plasma viscosity, and inhibit leukocyte adherence
to endothelial cells. The effect of regional anesthesia and analgesia on neuroendocrine stress response and
[82] [83] [84]
coagulation is described in greater detail under “Coagulation.” Thus, regional anesthesia and analgesia may provide
favorable cardiovascular benefits through attenuation of sympathetic activation and neuroendocrine stress response
and effects of systemically absorbed local anesthetics.
Few organized data exist regarding the efficacy of peripheral regional anesthetic techniques on cardiac outcomes.
The remaining discussion in this section focuses on neuraxial techniques. Although there are many cardiovascular
benefits of neuraxial anesthesia, studies investigating the relationship of neuraxial anesthesia on outcomes do not
1072
consistently show a favorable effect on cardiovascular outcomes with use of regional anesthesia and postoperative
analgesia.
In studies of neuraxial anesthesia and analgesia in noncardiac surgery, some authors note a beneficial effect of TEA
as part of a combined general-regional anesthetic regimen. Compared with patients receiving general anesthesia and
parenteral opioid analgesia postoperatively, those receiving epidural general anesthesia followed by epidural
analgesia have a significantly lower incidence of cardiovascular complications (congestive heart failure,
tachyarrhythmias, myocardial ischemia and infarction, and death). Other authors note no difference in
[43] [150] [151]
cardiovascular outcomes between different intraoperative anesthetic techniques; however, these results may be
difficult to interpret because of insufficient power or the uncontrolled nature and inadequate duration of
postoperative analgesia. Interestingly, one study did note an increase in myocardial ischemia at termination
[6] [152] [153] [154]
of postoperative epidural analgesia. [154]
Use of TEA has also been investigated in patients undergoing cardiac surgery. A series of articles demonstrated that
patients who received TEA as part of their anesthetic regimen had greater intraoperative hemodynamic stability,
superior analgesia, accelerated awakening, and earlier times to extubation. Other investigators have also [155] [156] [157]
noted attenuation in hemodynamic responses to surgery and reduced requirements for propranolol or nitroglycerin in
those assigned to receive TEA. In addition, TEA has been successfully used in patients with medically
[158] [159]
refractory unstable angina or severe coronary artery disease. Some data also suggest that TEA-induced
[144] [147]
sympathetic block may elevate dysrhythmogenic threshold. [160] [161]
In summary, regional anesthesia and analgesia provide many cardiovascular benefits and may offer clinical benefits,
especially in patients with cardiovascular disease and those undergoing major operations. Despite the physiologic
advantages of TEA, there is no consensus on the effect of regional anesthesia and analgesia on cardiovascular
outcome. Any definitive conclusion on this issue is lacking owing to limitations of current studies.
Pulmonary System
Respiratory function is significantly diminished after upper abdominal and thoracic surgery ( Table 46-5 ). Lower
abdominal, peripheral, or laparoscopic surgery have minimal effects on postoperative pulmonary
TABLE 46-5 -- OVERVIEW OF PULMONARY FUNCTION

Postoperative decrease in respiratory function Preservation of pulmonary function
Inadequate analgesia Superior analgesia
Spinal reflex inhibition of diaphragm Prevention of inhibitory spinal reflex
↑ Abdominal and intercostal muscle tone
function. Decreases in postoperative vital capacity (VC), functional residual capacity (FRC), and PaO2 occur within
24 hours after upper abdominal or thoracic surgery and return to preoperative levels over the next 2 weeks. A nadir
in pulmonary function occurs approximately 24 hours after surgery and may be quite pronounced (VC 40% of
preoperative levels after upper abdominal surgery). Abnormalities in gas exchange as a result of alveolar
[162]
hypoventilation, ventilationperfusion mismatches, and right-to-left shunting may lead to postoperative pulmonary
complications (PPC), including hypoxemia, atelectasis, pneumonia, and respiratory failure. Groups at higher risk for
PPC include elderly patients and those with preexisting pulmonary disease (including smoking), obesity, or severe
pain, as well as those undergoing thoracic or upper abdominal surgery. [163] [164] [165] [166] [167] [168] [169]
Postoperative pulmonary dysfunction may result from inadequate analgesia, diaphragmatic dysfunction, or increase
in upper abdominal and intercostal muscle tone. Patients with inadequate analgesia are less inclined to breathe
[1]
deeply, cough adequately, or cooperate with physical therapy. Therefore, they may be more likely to develop PPC. [5]
Although severe pain may contribute to development of PPC, analgesia per se does not completely prevent the
[162] [170]
decrease in postoperative pulmonary function. Postoperative diaphragmatic dysfunction, independent of the

[171]
degree of analgesia, occurs as a result of spinal reflex inhibition of phrenic nerve activity. Stimulation of [172]
abdominal viscera or intercostal muscle proprioceptive afferent pathways may reflexively result in a decrease in
phrenic nerve activity. Finally, increased lower intercostal and abdominal muscle tone during exhalation
[173] [174]
decreases lung volumes as a result of cephalad displacement of the diaphragm. [175]
1073
Postoperative pulmonary dysfunction may lead to postoperative hypoxemia. Constant hypoxemia, reflecting the
decrease in FRC, occurs for several days postoperatively, with a maximum decrease in PaO2 occurring in the first 72
hours after surgery. In addition, episodic postoperative hypoxemia may occur, especially during sleep.
[176] [177] [178]
Postoperative hypoxemia may result in a variety of detrimental consequences, including cardiac, cerebral, and
wound complications. [178]
Regional anesthetic techniques, such as intercostal blocks, thoracic epidural, and intrapleural and extrapleural
catheters, provide superior analgesia compared with that obtained via systemic opioids. Patients with higher levels [5]
of postoperative pain after thoracotomy may be at higher risk for long-term postoperative pain. In addition, use of [179]
local anesthetics may decrease the amount of opioids used, potentially diminishing incidence of adverse effects
associated with opioids, including nausea, vomiting, sedation, and respiratory depression. Postoperative regional
anesthetic techniques are also associated with decreased incidence and severity of early postoperative hypoxemia. [1]
Patients who have adequate analgesia and are not sedated may play a more active role in postoperative
physiotherapy, which decreases incidence of PPC. As part of a multimodal approach to postoperative care of the
[180] [181]
patient, regional anesthetic techniques that provide superior analgesia, especially ones that increase activity, may
reduce morbidity and facilitate rehabilitation. [178]
Other mechanisms independent of analgesia, such as phrenic nerve inhibition, are also important in the development
of postoperative pulmonary dysfunction. By blocking either afferent or efferent pathways, local anesthetics may
[5]
prevent reflex inhibition of the phrenic nerve and restore postoperative diaphragmatic function. Patients [182] [183]
receiving thoracic epidural local anesthetics postoperatively can maintain respiratory rates and tidal volume near
their preoperative levels. Thus, regional anesthetic techniques using local anesthetics may improve postoperative
[183]
pulmonary function by providing superior analgesia and restoring diaphragmatic function.
The physiologic benefits of epidural analgesia may not be apparent with use of either lumbar epidural catheters or
epidural opioids alone. Low analgesic sensory levels associated with lumbar epidural administration of local
anesthetics do not prevent reflex inhibition of the phrenic nerve or decreases in postoperative pulmonary function.
Although high thoracic sensory levels can be obtained with lumbar epidural analgesia, undesirable side effects,
including hypotension and motor block, may offset any benefits derived from blocking the inhibitory reflex. With
respect to use of opioids, epidural analgesia with local anesthetics generally provides analgesia superior to that
achieved with opioids. There are no significant analgesic differences between thoracic and lumbar epidural
[1] [5] [170]
administration of opioids. Furthermore, there is no difference in analgesia between epidural and intravenous
[5]
infusions of a lipophilic opioid such as fentanyl. Continuous infusions of fentanyl through lumbar epidural
[184]
catheters produce similar levels of analgesia compared with intravenous infusions of fentanyl, and plasma fentanyl
concentrations are not significantly different between the groups. [184] [185]
A meta-analysis of randomized, controlled trials investigating efficacy of postoperative analgesic therapies on

pulmonary outcome demonstrated that postoperative epidural analgesia significantly reduced incidence of
pulmonary morbidity. All randomized trials investigating the effect of analgesic therapy on pulmonary function
[5]
were considered, and 48 of 121 possible studies were included in the analysis. Trials were not limited to a particular
type of surgery; however, the majority were upper abdominal or thoracic surgeries. Compared with systemic opioids,
epidural analgesia with local anesthetics was associated with significant increase in PaO2 and decrease in incidence
of pulmonary infections and overall pulmonary complications despite no difference in surrogate measures of
pulmonary function (FEV1 , FVC, and PEFR). Compared with systemic opioids, epidural analgesia with opioids
decreased incidence of atelectasis, but there were no significant differences in incidence of pulmonary complications.
There were no significant differences between thoracic and lumbar epidural administration of opioids with respect to
analgesia or pulmonary function. [5]
For post-thoracotomy pain, TEA with local anesthetics, especially with addition of an opioid, generally provides
superior analgesia to other analgesic regimens. By providing greater dynamic pain relief for post-thoracotomy pain,
epidural analgesia with local anesthetics potentially minimizes any decrease in postoperative pulmonary dysfunction
and incidence of pulmonary morbidity. Like post-thoracotomy pain, rib fracture pain may cause a decrease in
[186] [187]
ventilatory function and increase in incidence of pulmonary morbidity. A retrospective study of 307 patients [188] [189]
older than 60 years of age found that use of epidural analgesia was an independent predictor of decreased mortality
and incidence of pulmonary complications. Significant improvements in VC and FEV1 occurred in patients with
[190]
rib fractures who received thoracic epidural bupivacaine compared with those who received lumbar epidural
morphine. [188]
1074
EFFICACY OF PERIPHERAL NERVE BLOCK
Peripheral regional techniques such as intercostal blocks and extrapleural and intrapleural catheters may be used for
postoperative analgesia after thoracic surgery. Studies investigating use of intercostal blocks in control of
postoperative pain vary widely in design. Intercostal nerve blocks provide adequate postoperative analgesia but are
often supplemented by systemic opioids. Many studies reveal an improvement in surrogate measures of
[170]
pulmonary function with intercostal blocks, and a meta-analysis found that intercostal nerve block tended to
improve pulmonary outcome measures, but the differences were not statistically significant. In addition, concerns [5]
about systemic absorption of local anesthetics and practical issues involved in repeated injections may limit
feasibility of intercostal blocks. An extrapleural catheter, which is usually inserted by the surgeon at the conclusion
of thoracic surgery, functions like a continuous intercostal block at multiple levels. Preliminary data suggest that
[191]
continuous extrapleural infusions of local anesthetics may be as effective as thoracic epidural analgesia for control
of postoperative thoracic pain; however, only surrogate endpoints were statistically evaluated. Thus, intercostal [192]
analgesia, either through single injections or continuous infusion, may be a valuable alternative when thoracic
epidural analgesia is not available.
Intrapleural administration of local anesthetics provides analgesia after thoracic surgery. Local anesthetics are
administered through an indwelling catheter either intermittently or as a continuous infusion. Mechanisms for the
analgesic action of intrapleural analgesia are not clear but may include intercostal nerve block, block of free nerve
endings in the pleura, or absorption of local anesthetics. During interpleural analgesia, there is some concern with
elevated blood levels of local anesthetics that may lead to toxicity. A meta-analysis demonstrated no improvement
[193]
in pulmonary function and no differences in patient outcomes with intrapleural administration of local anesthetics. [5]
In summary, there are several risk factors for development of PPC. Inadequate analgesia and spinal reflex inhibition
of phrenic nerve activity are important contributors to postoperative pulmonary dysfunction. TEA with local
anesthetics is superior in providing analgesia and decreasing overall incidence of pulmonary complications. Epidural
opioids may decrease incidence of atelectasis but do not significantly decrease incidence of PPC. Other regional
analgesic modalities, such as intercostal block and intrapleural and extrapleural catheters, may provide superior
analgesia compared with systemic opioids, and these alternatives show promise in decreasing PPC; however, further
data will be needed to demonstrate any effect on outcomes.
Gastrointestinal System
Loss of gastrointestinal motility commonly occurs after abdominal surgery and occasionally after peripheral surgery
( Table 46-6 ). With uncomplicated postoperative
TABLE 46-6 -- OVERVIEW OF GASTROINTESTINAL FUNCTION

Postoperative inhibition of gastrointestinal Facilitates return of gastrointestinal motility
motility
Spinal reflex inhibition Prevention of inhibitory spinal reflex
Postoperative use of opioids Decreased postoperative use of opioids
Sympathetic activation (pain, stress Inhibition of sympathetic nervous system
response)
Local anesthetic effects
ileus, return of complete gastrointestinal motility returns to the stomach within 2 to 3 days. The small intestine
recovers function within 24 hours and colonic motility returns within 48 to 72 hours after surgery. Postoperative
paralytic ileus is a more severe, protracted form of postoperative ileus (>3 days’ duration), reflecting inhibition of all
segments of bowel, especially small bowel activity. A delay in recovery of gastrointestinal function prevents
[194]
initiation of enteral feeding and may increase neuroendocrine stress response, incidence of septic complications, and
decrease of wound healing. [195] [196] [197]
Postoperative ileus is the result of inhibitory input from central and systemic sources, spinal reflexes, and local
factors. The contribution of central and systemic factors to postoperative ileus is not clear. Postoperative release of
[194]
vasopressin (either through surgical stress or induced by opioid use) may inhibit small bowel contractility, partly by
1075
decreasing mesenteric blood flow. Spinal reflex inhibition is related to activation of nociceptive afferent and
[194] [198] [199]
sympathetic efferent nerves. Postoperative pain (nociceptive afferent) initiates spinal reflex inhibition of
[200]
gastrointestinal motility. In addition, increased sympathetic efferent stimulation (neuroendocrine stress response,
inadequate analgesia) after surgery diminishes organized gastrointestinal activity. Local factors contributing to
postoperative ileus include absence of normal myoelectric activity resulting from membrane hyperpolarization. [194]
Normal gastrointestinal transit is dependent on a characteristic pattern of oscillations (with occasional contractile
spike-wave potentials) that proceeds distally in an organized manner as current passes from one cell to the next by
ion exchange through intercellular gap junctions. Smooth muscle in the colon lacks intercellular gap junctions and is
dependent on external neuronal systems for contraction. Thus, colonic activity may be most susceptible to
postoperative inhibition.
Epidural analgesia is the most common regional anesthetic modality for postoperative analgesia after abdominal
surgery. By blocking nociceptive afferent nerves, TEA with local anesthetics prevents activation of spinal reflex
inhibition of gastrointestinal motility. TEA with local anesthetics blocks sympathetic efferent fibers and provides a
predominantly parasympathetic tone (emanating from vagus and pelvic nerves), thus favoring return of
gastrointestinal propulsive activity. Increased gastrointestinal blood flow as a result of the sympathectomy from
TEA with local anesthetics also facilitates gastrointestinal motility and promotes anastomotic healing. There [201] [202] [203]
is no substantial evidence that return of gastrointestinal motility during epidural analgesia results in anastomotic
dehiscence. [203] [204]
In addition, to prevent reflex inhibition of gastrointestinal motility, local anesthetics administered through epidural
catheters may be systemically absorbed. Systemic administration of local anesthetics has been shown to facilitate the
return of gastrointestinal motility after surgery. Mechanisms for facilitating the return of bowel function by
[205] [206]
systemic administration of local anesthetics include an increase in intestinal smooth muscle excitation and decrease
in amount of opioids used. Systemic absorption of local anesthetics may also prevent reflex inhibition of
[206]
gastrointestinal motility by blocking nociceptive afferent input (peritoneal irritation). [206]
Other than local anesthetics, opioids can be administered through epidural catheters to control postoperative pain
after abdominal surgery. Administration of both systemic and neuraxial opioids inhibits gastrointestinal motility and
return of bowel function. Epidurally administered opioids compared with local anesthetics are not as effective in
facilitating return of bowel function because epidural opioids are not able to block either the afferent or efferent loop
of the spinal reflex inhibiting gastrointestinal motility. Epidural opioids may not delay return of gastrointestinal
[31]
motility to the same degree as systemic opioids. Systemic but not epidural opioids produce inhibitory myoelectric
activity in the colon. Furthermore, peripheral mechanisms may be relatively more important than central
[207]
mechanisms in inhibition of gastrointestinal motility because opioid receptors are found throughout the
gastrointestinal system. [208]
TEA with local anesthetics promotes earlier return of gastrointestinal function after abdominal surgery. An [209] [210]
overwhelming majority of studies investigating patients who received TEA with local anesthetics demonstrate the
accelerated return of postoperative gastrointestinal function (compared with those who received systemic opioids) as
demonstrated by several markers of gastrointestinal function, such as passage of flatus, first bowel movement,
barium contrast, and myoelectric activity. Compared with systemic opioids, TEA with local anesthetics also
[1]
provides superior postoperative analgesia, including pain relief with activity, which may be important in facilitating
postoperative rehabilitation after abdominal surgery. Patients receiving TEA with local anesthetics have
[178] [209] [211]
earlier fulfillment of discharge criteria and a shorter hospital stays. Epidural analgesia should be continued for
[209] [212]
at least 48 to 72 hours postoperatively to provide any benefit in recovery of gastrointestinal motility. [1]
Epidural administration of opioids may not provide earlier return of bowel function compared with TEA with local
anesthetics. Few studies have compared the effect of an epidural with the systemic administration of opioids on
return of postoperative gastrointestinal function. Some studies have demonstrated an earlier return of
[2] [164] [209] [213] [214]
bowel function with use of epidural opioids than with systemic opioids. However, not all studies show a benefit [164] [213]
in the return of gastrointestinal function or time until fulfillment of discharge criteria with epidural opioids
compared with systemic administration of opioids. [2] [209]
Thus, by providing superior analgesia, preventing the inhibitory spinal reflex, and decreasing the amount of opioids
used, TEA with local anesthetics facilitates the return of gastrointestinal motility after abdominal surgery. TEA with
local anesthetics is superior to epidural and systemic opioids in restoring postoperative bowel function. Compared
1076
with systemic opioids, epidural opioids may be associated with a lesser degree of delay in gastrointestinal motility;
however, the role of epidural opioids in this situation is not clear.
Cognitive Function
Postoperatively, patients may exhibit alterations in several aspects of general mental status, such as cognitive
function, and they may experience confusion, delirium, or dementia. Although mental function generally reaches a
nadir between the second and fifth postoperative days, with recovery to preoperative levels by 1 week after surgery,
delays in recovery of mental function are associated with poor patient outcomes. Along with physical
[215] [216]
parameters, cognitive functional measures are strong predictors of long-term mortality after hospitalization. [217]
Delirium is associated with poor outcomes, increased mortality, and longer hospital stays. [218] [219]
Postoperative cognitive dysfunction, as measured by neuropsychological tests, may be present in approximately

26% of elderly patients 1 week after major noncardiac surgery. In addition, long-term cognitive dysfunction (3
[220]
months postsurgery) may occur in about 10% of patients. Risk factors for the development of early postoperative
[220]
dysfunction include advanced age and prolonged anesthesia, postoperative infections, and respiratory complications;
however, only advanced age is a risk factor for development of late postoperative dysfunction. Interestingly, [220]
hypoxemia and hypotension were not significant risk factors (in one large-scale study) for development of either
early or late postoperative cognitive dysfunction. Some data suggest no difference in postoperative mental
[220]
deterioration between elderly and young patients. In addition, higher levels of pain predict a decrease in
[221]
postoperative mental status. [222]
Postoperative delirium may cost Medicare approximately $2 billion per year. Independent correlates for
[223]
development of postoperative delirium after elective noncardiac surgery include age (>70 years); poor preoperative
cognitive and functional status; marked abnormalities in preoperative sodium, potassium, or glucose levels; and
thoracic or aortic aneurysm procedures. In addition, perioperative use of psychoactive medications
[224]
(anticholinergic drugs, meperidine, benzodiazepines) is significantly associated with development of postoperative

delirium. Higher levels of postoperative pain at rest are also associated with development of delirium.
[225] [226] [227] [228]
The etiology of both postoperative cognitive dysfunction and delirium is unclear. Many factors, including
hypotension, hypoxia, and hyperventilation, are believed to contribute to development of postoperative cognitive
dysfunction and delirium. CNS catecholamine and cholinergic transmission may also play a role in disruption of
postoperative mental function. The effect of anesthetic agents per se on postoperative mental status is also
[229]
uncertain.
Unlike its effect on other organ systems, regional anesthesia does not exert any direct effects on postoperative
mental function. Several prospective, randomized studies have compared efficacy of general anesthesia with that of
regional anesthesia regarding postoperative mental function. Most studies do not demonstrate any advantage of
regional anesthesia over general anesthesia in preserving postoperative mental function. Only a few
[215] [227] [230] [231] [232] [233]
studies support a beneficial effect of regional anesthesia on postoperative mental function. Although many [234] [235]
studies do not demonstrate a clear benefit of regional anesthesia in decreasing incidence of postoperative cognitive
deficits or delirium, there are concerns relating to method in evaluation of postoperative mental function. [226] [229]
One area that may provide potentially beneficial effects on postoperative mental function is use of postoperative
analgesia. The effect of postoperative analgesia on mental function has not been investigated. In general, [1]
postoperative regional analgesia with local anesthetics provides superior analgesia at rest and with activity compared
with systemic opioids. Because higher levels of postoperative pain are associated with postoperative cognitive
dysfunction and delirium, using postoperative regional analgesia with local anesthetics may theoretically preserve
postoperative mental function. By using postoperative regional analgesia, patients may also receive fewer
medications (e.g., meperidine) that may be associated with development of perioperative mental dysfunction.
Because there are many potential etiologies for postoperative decline in mental function, it is unlikely that regional
anesthesia and analgesia alone can directly diminish incidence of postoperative alterations in mental function.
However, regional anesthesia may alleviate inadequate postoperative pain control, which may contribute to
deterioration of postoperative mental function, thus indirectly improving postoperative mental function. At this time,
definitive studies comparing efficacy of general anesthesia with regional anesthesia and analgesia on postoperative
1077
mental function are lacking, but the majority of current studies do not demonstrate a beneficial effect of regional
anesthesia on preservation of postoperative mental function.
Economic Outcome
CONSIDERATIONS IN ECONOMIC OUTCOME ANALYSIS
With escalating pressure on healthcare providers to control costs, there are an increasing number of articles
incorporating some type of economic analysis comparing the effects of various treatments or programs. In general,
evaluating validity of such studies can be difficult. Regional anesthesia, and postoperative analgesia may provide
[236]
many economic benefits; however, there are presently several obstacles to determining the economic impact of
regional anesthesia and analgesia. The first problem is lack of appropriate, large-scale, controlled trials to
definitively determine whether use of regional anesthesia and postoperative analgesia will decrease morbidity and
mortality or facilitate patient recovery after surgery and thus improve economic outcomes (see the discussion on
current outcome studies). In addition, economic analysis may not even be considered in some studies. [237]
The second problem in evaluating the economic impact of regional anesthesia and analgesia is the divergence and
inconsistency of economic outcome analysis. There are several dimensions of economic analysis, which include the
type of analysis (cost-effectiveness, cost-benefit, cost-utility), the types of costs and benefits (direct and indirect,
medical and nonmedical), and the perspective for analysis (patient, provider, payer, societal). The economic [238]
impact of regional anesthesia and analgesia may be altered depending on the type of analysis used. Furthermore,
current economic outcome measurements may not be accurate or applicable. For instance, a decrease in operative or
recovery time may not automatically lead to an increase in actual savings because discharge from the recovery room
and hospital are typically based on actual discharge times (not when patients are “discharge ready”), and decreases
in discharge times may not necessarily allow for reductions in staffing, which account for a significant percentage of
recovery room costs. [239] [240]
Measurement of cost in a study may not be appropriately defined, calculated, or complete, which, consequently,
may result in inaccurate conclusions. In general, the cost of a specific service reflects resources used to provide
[241]
that service. Direct costs of regional anesthesia and analgesia include operational expenditures required for
[238]
delivery of care, including equipment, catheters, drugs, and personnel. Indirect costs, which include lost income,
out-of-hospital expenditures, and decreased productivity, may be increased by complications or decreased by
benefits from regional anesthesia and analgesia. Although the (direct) cost of regional analgesia may seem higher
than that of systemic administration of traditional analgesic agents, regional analgesia may actually decrease overall
(indirect) costs, in part by decreasing incidence of complications or length of stay. Thus, obtaining comprehensive
measurements of costs and determining their applicability to different centers are complex tasks.
Despite the difficulty in economic analysis, there is some evidence that regional anesthesia and postoperative
analgesia may have a favorable economic impact. Use of intraoperative regional anesthesia is associated with
decreased length of stay after both outpatient and inpatient surgery. Regional anesthesia for shoulder surgery
decreases total surgical and nonsurgical intraoperative time and length of stay in the recovery room. Adequate [242]
postoperative pain control with regional anesthesia may allow certain procedures, such as arthroscopic knee and
shoulder reconstruction surgery, which have traditionally required short-stay hospitalizations, to be consistently
performed on an outpatient basis. Inadequate control of postoperative pain after ambulatory surgery may
[243] [244]
necessitate an overnight hospital admission or readmission after discharge. [242] [243] [245] [246]
Postoperative epidural analgesia has also been associated with a decreased length of stay in the intensive care unit
(ICU) and shorter hospital stays. A randomized trial of patients undergoing colonic surgery revealed that patients
receiving postoperative epidural analgesia with bupivacaine fulfilled discharge criteria significantly faster than those
receiving systemic opioids. Another prospective study demonstrated that compared with those who received IV
[209]
patientcontrolled analgesia morphine, patients who received postoperative epidural analgesia had shorter lengths of
stay in both the ICU and the hospital after thoracic or abdominal cancer surgery. Retrospective data also confirms [247]
that use of postoperative epidural analgesia has been associated with shorter lengths of intensive care unit and
hospital stays. [248] [249] [250] [251] [252]
Regional anesthesia and postoperative analgesia have also been shown to decrease the incidence of complications.
Epidural analgesia is associated with a decrease in postoperative pulmonary complications. Attenuation of the [5]
postoperative hypercoagulable state by regional anesthesia decreases incidence of graft failures after vascular
surgery. Use of regional anesthesia is associated with a lower incidence of deep venous thrombosis after
[3] [80]
1078
orthopedic and genitourinary surgery. Regional anesthesia is associated with a lower incidence of postoperative
[88] [92]
pulmonary complications in high-risk patients who have undergone abdominal surgery. Thus, by decreasing the
[96] [164]
length of stay and incidence of complications, use of regional anesthesia and postoperative analgesia potentially may
result in beneficial economic outcomes.
Nontraditional Outcome Measurements
CONSIDERATIONS IN NONTRADITIONAL OUTCOME ANALYSIS
Healthcare providers, especially those who interact with patients on a more acute basis, are generally more
comfortable with traditional outcome measurements (mortality and morbidity) and may be unfamiliar with
nontraditional outcome measurements, such as health-related quality of life (HRQL) or patient satisfaction. Popular
use of nontraditional outcome measurements is hindered by lack of information with regard to their value and
benefits in clinical trials, applicability of measurements to daily clinical situations, and the perception of
measurements as being “soft” or “unscientific.” In addition, studies may not incorporate appropriate or
[253]
standardized instruments in measuring nontraditional outcome measurements. There has been little research on
[254] [255]
conceptualizing models that elucidate relationships between clinical variables and HRQL measurements and
determine the effect of clinical interventions on HRQL. Thus, it may be difficult for clinicians to use
[255]
nontraditional outcome data to effect appropriate therapeutic interventions.
Use of patient satisfaction has become an important measure for evaluating quality of medical care. Despite an [256]
increasing amount of research evaluating measurement of patient satisfaction, many problems, such as lack of
standardized approaches, comparative studies, consensus, or accepted models of patient satisfaction, create
uncertainty in the value of patient satisfaction as a measure of quality patient care. Assessment of patient
[256]
satisfaction as a clinical end point and indication of quality of care have also been hindered by lack of discrimination,
reliability, and validity of current measurements. Results obtained from questionnaires created without proper
[254]
psychometric construction may not truly reflect patient satisfaction with the aspect of care being examined.
Both HRQL measurements and patient satisfaction are important components of patient outcomes. Many concerns
with method remain, including standardization and refinement of current measurements. Acceptance of
nontraditional outcome measurements by clinicians may be difficult, partly because of concerns about validity and
applicability of these measurements. However, nontraditional outcome measurements provide another opportunity
for evaluating potential differences in patient outcome between general and regional anesthesia.
The efficacy of regional anesthesia and postoperative analgesia on nontraditional outcome measurements is unclear
because data in this area are lacking. HRQL measurements have not been used extensively in evaluation of regional
anesthesia and postoperative analgesia. Some data suggest that use of regional anesthesia and postoperative
analgesia in the setting of intensive rehabilitation (early nutrition and mobilization) will facilitate earlier recovery of
HRQL measurements to preoperative levels compared with those receiving general anesthesia with postoperative
patient-controlled morphine. [257]
Measurements of HRQL in this study were not taken in the immediate postoperative period (within 1 week after
surgery) but at 3 and 6 weeks after surgery. Difficulties associated with use of HRQL in the immediate
postoperative setting include the nonspecific nature of certain HRQL measurements (generic vs. condition-specific
measures) and the possibility that the expected postsurgical decrease in general functional status will overshadow
any observable HRQL differences between postoperative analgesic treatments. Many issues will need to be
[258] [259]
resolved before a meaningful comparison of the effect of general anesthesia with that of regional anesthesia on
HRQL measurements can be made. Until that time, no definitive conclusions can be formed regarding the effect of
regional anesthesia and analgesia on HRQL measurements.
Despite the limitations of current studies with measurement of patient satisfaction, some data suggest that regional
anesthesia and postoperative analgesia may have a favorable impact on patient satisfaction. Twenty-four of 25
patients who received intraoperative regional anesthesia (interscalene block) and had received general anesthesia for
previous shoulder surgery preferred regional anesthesia. In two studies of more than 1800 patients, 78% to 93% of
[260]
patients stated a willingness to undergo a repeat block. Although these studies seem to indicate a favorable
[261] [262]
association between regional anesthesia and patient satisfaction, many factors influence patient satisfaction and
consent to undergo regional anesthesia. [263]
1079
By providing superior analgesia at rest and with activity, postoperative regional analgesia may also potentially affect
patient satisfaction as severity of postoperative pain influences the degree of patient satisfaction. Lower
postoperative pain ratings are associated with higher levels of patient satisfaction. Higher levels of
[264] [265]
postoperative pain also interfere with activity and sleep, which may affect other HRQL measurements. However, [264]
it may be difficult to assess patient satisfaction with postoperative pain management per se because there is always
the question of whether patients are able to differentiate satisfaction with pain control from other aspects of medical
care. [266]
Although nontraditional outcome measurements have become increasingly popular in evaluating quality of patient
care, few data exist on the application of nontraditional measurements, such as HRQL and patient satisfaction, in
assessing the effect of regional anesthesia and analgesia on patient outcomes. Until further properly conducted
studies are performed, no conclusions can be drawn about efficacy of regional anesthesia and analgesia on
nontraditional patient outcomes.
Efficacy of Postoperative Analgesia
Use of intraoperative regional anesthesia and postoperative regional analgesia will provide many physiologic
benefits that may reduce incidence of complications and, ultimately, improve patient outcomes. However, it may be
difficult to differentiate to what extent intraoperative anesthesia or postoperative analgesia contributes to any
improvements in patient outcomes. Some processes, such as deep venous thrombosis formation, begin
intraoperatively. Other complications, including myocardial ischemia and infarction, may peak in the
[267]
postoperative period. In most instances, physiologic disturbances begin intraoperatively and continue well into the
[127]
postoperative period, necessitating use of both intraoperative regional anesthesia and postoperative regional
analgesia to maximize any benefits on patient outcomes. Thus, the effect of postoperative regional analgesia per se
on patient outcomes is difficult to assess.
Although superior analgesia provided by postoperative regional analgesia in itself may not be adequate to improve
patient outcomes, postoperative regional analgesia may be used as part of a multimodal approach to facilitate patient
recovery after surgery. Control of postoperative pain is important in this model because analgesic regimens will
[178]
facilitate early ambulation, decrease ileus, allow early enteral nutrition, and reduce infectious complications. A [178]
multimodal approach to control postoperative pathophysiology and to accelerate rehabilitation in patients

undergoing abdominal esophagectomy reduces intensive care unit stay and provides economic benefits. Other [268]
studies also demonstrate the value of an integrated approach to facilitate postoperative patient recovery. [237] [269]
Conclusions
Regional anesthesia and analgesia provide many physiologic benefits in the perioperative period and may improve
patient outcomes. Many organ systems, including coagulation, pulmonary, and gastrointestinal, clearly benefit from
perioperative use of regional anesthetic techniques. Probable benefits for the cardiovascular system and stress
response may be provided by use of regional anesthesia and analgesia. Data on the effect of regional anesthesia on
other outcomes are equivocal (mental status) or insufficient (immune system). There are several concerns related to
methods that hinder determination of efficacy of regional anesthesia and analgesia on traditional patient outcomes.
Future studies using economic and nontraditional outcome measurements may reveal additional benefits of regional
anesthesia and analgesia on patient outcomes.
REFERENCES
1. Liu S, Carpenter RL, Neal JM: Epidural anesthesia and analgesia: Their role in postoperative outcome. Anesthesiology 82:1474–1506, 1995.
2. Hjortso N-C, Neumann P, Frosig F, et al: A controlled study on the effect of epidural analgesia with local anaesthetics and morphine on
morbidity after abdominal surgery. Acta Anaesthesiol Scand 29:790–796, 1985.
3. ChristophersonR, Beattie C, Frank SM, et al: Perioperative morbidity in patients randomized to epidural or general anesthesia for lower
extremity vascular surgery. Anesthesiology 79:422–434, 1993.
4. de Leon-Casasola OA, Lema MJ: Intensive analgesia reduces postoperative myocardial ischemia? [letter]. Anesthesiology 77:404–405, 1992.
5. Ballantyne
meta-analyses of randomized, controlled trials. Anesth Analg 86:598–612, 1998.
6. Bode RH Jr, Lewis KP, Zarich SW, et al: Cardiac outcome after peripheral vascular surgery: Comparison of general and regional anesthesia.
1080
7. Bois S, Couture P, Boudreault D, et al: Epidural analgesia and intravenous patient-controlled analgesia result in similar rates of postoperative
myocardial ischemia after aortic surgery. Anesth Analg 85:1233–1239, 1997.
8. Kehlet
H: Modification of responses to surgery by neural blockade: Clinical implications. In Cousins MJ, Bridebaugh PO (eds): Neural
Blockade in Clinical Anesthesia and Management of Pain, 3rd ed. Philadelphia, Lippincott-Raven, 1998, pp 129–175.
9. Schrenk P, Bettelheim P, Woisetschlager R, et al: Metabolic responses after laparoscopic or open hernia repair. Surg Endosc 10:628–632, 1996.
10. Woolf PD: Hormonal responses to trauma. Crit Care Med 20:216–226, 1992.
11. Chernow B, Alexander HR, Smallridge RC, et al: Hormonal responses to graded surgical stress. Arch Intern Med 147:1273–1278, 1987.
12. Glaser F, Sannwald GA, Buhr HJ, et al: General stress response to conventional and laparoscopic cholecystectomy. Ann Surg 221:372–380,
1995.
13. Ziegler TR, Gatzen C, Wilmore DW: Strategies for attenuating protein-catabolic responses in the critically ill. Annu Rev Med 45:459–480,
1994.
14. Byrne TA, Morrissey TB, Gatzen C, et al: Anabolic therapy with growth hormone accelerates protein gain in surgical patients requiring
nutritional rehabilitation. Ann Surg 218:400–418, 1993.
15. MunckA, Guyre PM, Holbrook NJ: Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr
Rev 5:25–44, 1984.
16. AhoM, Scheinin M, Lehtinen A-M, et al: Intramuscularly administered dexmedetomidine attenuates hemodynamic and stress hormone
responses to gynecologic laparoscopy. Anesth Analg 75:932–939, 1992.
17. Carli
F, Itiaba K: Effect of heat conservation during and after major abdominal surgery on muscle protein breakdown in elderly patients. Br J
Anesth 58:502–507, 1986.
18. CarliF, Emery PW, Freemantle CAJ: Effect of perioperative normothermia on postoperative protein metabolism in elderly patients undergoing
hip arthroplasty. Br J Anaesth 63:276–282, 1989.
19. McMurry JF Jr: Wound healing with diabetes mellitus. Better glucose control for better wound healing in diabetes. Surg Clin North Am
64:769–778, 1984.
20. Pomposelli
JJ, Baxter JK 3rd, Babineau TJ, et al: Early postoperative glucose control predicts nosocomial infection rate in diabetic patients.
JPEN 22:77–81, 1998.
21. EngquistA, Brandt MR, Fernandes A, Kehlet H: The blocking effect of epidural analgesia on the adrenocortical and hyperglycemic responses
to surgery. Acta Anaesthesiol Scand 21:330–335, 1977.
22. Greek
R, Maurer P, Torjman M, et al: Effect of general anesthesia vs interscalene block for shoulder surgery: Postoperative pain and
neuroendocrine responses [abstract]. Anesthesiology 79:A814, 1993.
23. Christensen
P, Brandt MR, Rem J, Kehlet H: Influence of extradural morphine on the adrenocortical and hyperglycaemic response to surgery.
Br J Anaesth 54:23–27, 1982.
24. Rutberg
H, Hakanson E, Anderberg B, et al: Effects of the extradural administration of morphine, or bupivacaine, on the endocrine response to
upper abdominal surgery. Br J Anaesth 56:233–238, 1984.
25. Lund C, Selmar P, Hansen OB, Kehlet H: Effect of intrathecal bupivacaine on somatosensory evoked potentials following dermatomal
stimulation. Anesth Analg 66:809–813, 1987.
26. Lund C, Hansen OB, Kehlet H, et al: Effects of etidocaine administered epidurally on changes in somatosensory evoked potentials after
dermatomal stimulation. Reg Anesth 16:38–42, 1991.
27. Segawa H, Mori K, Kasai K, et al: The role of the phrenic nerves in stress response in upper abdominal surgery. Anesth Analg 82:1215–1224,
1996.
28. Tsuji
H, Shirasaka C, Asoh T, Takeuchi Y: Influences of splanchnic nerve blockade on endocrine-metabolic responses to upper abdominal
surgery. Br J Surg 70:437–439, 1983.
29. Dahl
JB, Rosenberg J, Kehlet H: Effect of thoracic epidural etidocaine 1.5% on somatosensory evoked potentials, cortisol and glucose during
cholecystectomy. Acta Anaesthesiol Scand 36:378–382, 1992.
30. Naito Y, Tamai S, Shingu K, et al: Responses of plasma adrenocorticotropic hormone, cortisol, and cytokines during and after upper
abdominal surgery. Anesthesiology 77:426–431, 1992.
31. Lund C, Selmar P, Hansen OB, et al: Effect of extradural morphine on somatosensory evoked potentials to dermatomal stimulation. Br J
Anaesth 59:1408–1411, 1987.
1081
32. Scheinin B, Scheinin M, Asantila R, et al: Sympatho-adrenal and pituitary hormone responses during and immediately after thoracic surgery—
modulation by four different pain treatments. Acta Anaesthesiol Scand 31:762–767, 1987.
33. Jorgensen BC, Andersen HB, Engquist A: Influence of epidural morphine on postoperative pain, endocrine-metabolic, and renal responses to
surgery. A controlled study. Acta Anaesthesiol Scand 26:63–68, 1982.
34. Breslow
MJ, Jordan DA, Christopherson R, et al: Epidural morphine decreases postoperative hypertension by attenuating sympathetic nervous
system hyperactivity. JAMA 261:3577–3581, 1989.
35. Tsuji H, Shirasaka C, Asoh T, Uchida I: Effects of epidural administration of local anaesthetics or morphine on postoperative nitrogen loss and
catabolic hormones. Br J Surg 74:421–425, 1987.
36. Bormann BV, Weidler B, Dennhardt R, et al: Influence of epidural fentanyl on stress-induced elevation of plasma vasopressin (ADH) after
37. Brandt MR, Fernandes A, Mordhorst R, Kehlet H: Epidural analgesia improves postoperative nitrogen balance. Br Med J 1:1106–1108, 1978.
38. Christensen T, Waaben J, Lindeberg T, et al: Effect of epidural analgesia on muscle amino acid pattern after surgery. Acta Chir Scand
152:407–411, 1986.
39. Hjortso
N-C, Christensen NJ, Andersen T, Kehlet H: Effects of the extradural administration of local anaesthetic agents and morphine on the
urinary excretion of cortisol, catecholamines and nitrogen following abdominal surgery. Br J Anaesth 57:400–406, 1985.
40. Anand KJS, Hickey PR: Halothane-morphine compared with high-dose sufentanil for anesthesia and postoperative analgesia in neonatal
cardiac surgery. N Engl J Med 326:1–9, 1992.
41. Parker
SD, Breslow MJ, Frank SM, et al: Catecholamines and cortisol responses to lower extremity revascularization: Correlation with
outcome variables. Crit Care Med 23:1954–1961, 1995.
42. Hosoda
R, Hattori M, Shimada Y: Favorable effects of epidural analgesia on hemodynamics, oxygenation and metabolic variables in the
immediate post-anesthetic period. Acta Anaesthesiol Scand 37:469–474, 1993.
43. Yeager MP, Glass DD, Neff RK, Brinck-Johnsen T: Epidural anesthesia and analgesia in high-risk surgical patients. Anesthesiology 66:729–
736, 1987.
44. de Leon-Casasola OA: Immunomodulation and epidural anesthesia and analgesia. Reg Anesth 21(6 Suppl):24–25, 1996.
45. Barker
JP, Robinson PN, Vafidis GC, et al: Local analgesia prevents the cortisol and glycaemic responses to cataract surgery. Br J Anaesth
64:442–445, 1990.
46. BarkerJP, Vafidis GC, Robinson PN, Hall GM: Plasma catecholamine response to cataract surgery: A comparison between general and local
anaesthesia. Anaesthesia 46:642–645, 1991.
47. GieseckeK, Hamberger B, Jarnberg PO, Klinstedt C: Paravertebral block during cholecystectomy: Effects on circulatory and hormonal
responses. Br J Anaesth 61:652–656, 1988.
48. HamidSK, Scott NB, Sutcliffe NP, Tighe SQM, et al: Continuous coeliac plexus blockade plus intermittent wound infiltration with
bupivacaine following upper abdominal surgery: A double-blind randomised study. Acta Anaesthesiol Scand 36:534–539, 1992.
49. Wallin
G, Cassuto J, Hogstrom S, et al: Effects of lidocaine infusion on the sympathetic response to abdominal surgery. Anesth Analg
66:1008–1013, 1987.
50. Pither
CE, Bridenbaugh LD, Reynolds F: Preoperative intercostalnerve block: Effect on the endocrine metabolic response to surgery. Br J
Anaesth 60:730–732, 1988.
51. Scott NB, Mogensen T, Greulich A, et al: No effect of continuous I.P. infusion of bupivacaine on postoperative analgesia, pulmonary function
and the stress response to surgery. Br J Anaesth 61:165–168, 1988.
52. Rademaker BMP, Sih IL, Kalkman CJ, et al: Effects of interpleurally administered bupivacaine 0.5% on opioid analgesic requirements and
endocrine response during and after cholecystectomy: A randomized double-blind controlled study. Acta Anaesthesiol Scand 35:108–112, 1991.
53. Rademaker BM, Ringers J, Odoom JA, et al: Pulmonary function and stress response after laparoscopic cholecystectomy: Comparison with
subcostal incision and influence of thoracic epidural analgesia. Anesth Analg 75:381–385, 1992.
54. BredbackaS, Blomback M, Hagnevik K, et al: Pre- and postoperative changes in coagulation and fibrinolytic variables during abdominal
hysterectomy under epidural or general anaesthesia. Acta Anaesthesiol Scand 30:204–210, 1986.
55. FreyburgerG, Janvier G, Dief S, Boisseau MR: Fibrinolytic and hemorheologic alterations during and after elective aortic graft surgery:
Implications for postoperative management. Anesth Analg 76:504–512, 1993.
1082
56. McDaniel MD, Pearce WH, Yao JST, et al: Sequential changes in coagulation and platelet function following femorotibial bypass. J Vasc Surg
1:261–268, 1984.
57. Flinn
WR, McDaniel MD, Yao JST, et al: Antithrombin III deficiency as a reflection of dynamic protein metabolism in patients undergoing
vascular reconstruction. J Vasc Surg 1:888–895, 1984.
58. Naesh O, Friis JT, Hindberg I, Winther K: Platelet function in surgical stress. Thromb Haemost 54:849–852, 1985.
59. Andersson
TR, Berner NS, Larsen ML, et al: Plasma heparin cofactor II, protein C and antithrombin in elective surgery. Acta Chir Scand
153:291–296, 1987.
60. Sandset
PM, Hogevold HE, Lyberg T, et al: Extrinsic pathway inhibitor in elective surgery: A comparison with other coagulation inhibitors.
Thromb Haemost 62:856–860, 1989.
61. KassisJ, Hirsh J, Podor TJ: Evidence that postoperative fibrinolytic shutdown is mediated by plasma factors that stimulate endothelial cell
type I plasminogen activator inhibitor biosynthesis. Blood 80:1758–1764, 1992.
62. Rosenfeld BA: Benefits of regional anesthesia on thromboembolic complications following surgery. Reg Anesth 21(6 Suppl):9–12, 1996.
63. Dosquet C, Weill D, Wautier J-L: Cytokines and thrombosis. J Cardiovasc Pharmacol 25(Suppl 2):S13–S19, 1995.
64. NawrothPP, Handley DA, Esmon CT, Stern DM: Interleukin 1 induces endothelial cell procoagulant while suppressing cell-surface
anticoagulant activity. Proc Natl Acad Sci U S A 83:3460–3464, 1986.
65. van Hinsbergh VWM, Kooistra T, van den Berg EA, et al: Tumor necrosis factor increases the production of plasminogen activator inhibitor in
human endothelial cells in vitro and in rats in vivo. Blood 72:1467–1473, 1988.
66. Bauer
KA, ten Cate H, Barzegar S, et al: Tumor necrosis factor infusions have a procoagulant effect on the hemostatic mechanism of humans.
Blood 74:165–172, 1989.
67. Peng J, Friese P, George JN, et al: Alteration of platelet function in dogs mediated by interleukin-6. Blood 83:398–403, 1994.
68. Rosenfeld BA, Nguyen N-D, Sung I, Faraday N: Neuroendocrine stress hormones do not recreate the postoperative hypercoagulable state.
Anesth Analg 86:640–645, 1998.
69. Camerer E, Kolsto A-B, Prydz H: Cell biology of tissue factor: The principal initiator of blood coagulation. Thromb Res 81:1–41, 1996.
70. Gelehrter TD, Sznycer-Laszuk R: Thrombin induction of plasminogen activator-inhibitor in cultured human endothelial cells. J Clin Invest
77:165–169, 1986.
71. MassignonD, Lepape A, Bienvenu J, et al: Coagulation/fibrinolysis balance in septic shock related to cytokines and clinical state. Haemostasis
24:36–48, 1994.
72. Stouthard JML, Levi M, Hack CE, et al: Interleukin-6 stimulates coagulation, not fibrinolysis, in humans. Thromb Haemost 76:738–742, 1996.
73. Pober JS: Cytokine-mediated activation of vascular endothelium: Physiology and pathology. Am J Pathol 133:426–433, 1988.
74. ConwayEM, Rosenberg RD: Tumor necrosis factor suppresses transcription of the thrombomodulin gene in endothelial cells. Mol Cell Biol
8:5588–5592, 1988.
75. Modig J, Malmberg P, Karlstrom G: Effect of epidural versus general anaesthesia on calf blood flow. Acta Anaesthesiol Scand 24:305–309,
1980.
76. Cousins MJ, Wright CJ: Graft, muscle, skin blood flow after epidural block in vascular surgical procedures. Surg Gynecol Obstet 133:59–64,
1971.
77. HaljamaeH, Frid I, Holm J, Akerstrom G: Epidural vs general anaesthesia and leg blood flow in patients with occlusive atherosclerotic disease.
Eur J Vasc Surg 2:395–400, 1988.
78. Bading
B, Blank SG, Sculco TP, et al: Augmentation of calf blood flow by epinephrine infusion during lumbar epidural anesthesia. Anesth
Analg 78:1119–1124, 1994.
79. PoikolainenE, Hendolin H: Effects of lumbar epidural analgesia and general anaesthesia on flow velocity in the femoral vein and
postoperative deep vein thrombosis. Acta Chir Scand 149:361–364, 1983.
80. RosenfeldBA, Beattie C, Christopherson R, et al: The effects of different anesthetic regimens on fibrinolysis and the development of
postoperative arterial thrombosis. Anesthesiology 79:435–443, 1993.
81. Donadoni R, Baele G, Devulder J, Rolly G: Coagulation and fibrinolytic parameters in patients undergoing total hip replacement: Influence of
anaesthesia technique. Acta Anaesthesiol Scand 33:588–592, 1989.
82. Orr JE, Lowe GDO, Nimmo WS, et al: A haemorheological study of lignocaine. Br J Anaesth 58:306–309, 1986.
1083
83. Borg
T, Modig J: Potential anti-thrombotic effects of local anaesthetics due to their inhibition of platelet aggregation. Acta Anaesthesiol Scand
29:739–742, 1985.
84. LuostarinenV, Evers H, Lyytikainen M-T et al: Antithrombotic effects of lidocaine and related compounds on laser-induced microvascular
injury. Acta Anaesthesiol Scand 25:9–11, 1981.
85. Stewart
GJ, Knight LC, Arbogast BW, Stern HS: Inhibition of leukocyte locomotion by tocainide, a primary amine analog of lidocaine.
Laborat Invest 42:302–309, 1980.
86. Kakkar VV: Low molecular weight heparins: Prophylaxis of venous thromboembolism in surgical patients. Semin Hematol 34(Suppl 4):9–19,
1997.
87. Clagett GP, Anderson FA, Heit J, et al: Prevention of venous thromboembolism. Chest 108(Suppl):312S–334S, 1995.
88. Modig
J, Borg T, Karlstrom G, et al: Thromboembolism after total hip replacement: Role of epidural and general anesthesia. Anesth Analg
62:174–180, 1983.
89. ModigJ, Borg T, Bagge L, Saldeen T: Role of extradural and of general anaesthesia in fibrinolysis and coagulation after total hip replacement.
Br J Anaesth 55:625–629, 1983.
90. Sorenson RM, Pace NL: Anesthetic techniques during surgical repair of femoral neck fractures: A meta-analysis. Anesthesiology 77:1095–
1104, 1992.
91. Mitchell
D, Friedman RJ, Baker JD, et al: Prevention of thromboembolic disease following total knee arthroplasty. Clin Orthop Rel Res
269:109–112, 1991.
92. Hendolin H, Mattila MAK, Poikolainen E: The effect of lumbar epidural analgesia on the development of deep vein thrombosis of the legs
after open prostatectomy. Acta Chir Scand 147:425–429, 1981.
93. Dalldorf
PG, Perkins FM, Totterman S, Pellegrini VD: Deep venous thrombosis following total hip arthroplasty: Effect of prolonged
postoperative epidural anesthesia. J Arthroplasty 9:611–616, 1994.
94. Jorgensen
LN, Rasmussen LS, Nielsen PT, et al: Antithrombotic efficacy of continuous extradural analgesia after knee replacement. Br J
Anaesth 66:8–12, 1991.
95. Cooke ED, Lloyd MJ, Bowcock SA, Pilcher MF: Intravenous lignocaine in prevention of deep venous thrombosis after elective hip surgery.
Lancet 2:797–799, 1977.
97. Scott GR, Rothkopf DM, Walton RL: Efficacy of epidural anesthesia in free flaps to the lower extremity. Plast Reconstr Surg 91:673–677,
1993.
98. Trip
MD, Volkert MC, van Capelle FJL, Vreeken J: Platelet hyperreactivity and prognosis in survivors of myocardial infarction. N Engl J Med
322:1549–1554, 1990.
99. Salo M: Effects of anaesthesia and surgery on the immune response. Acta Anaesthesiol Scand 36:201–220, 1992.
100. Lennard TWJ, Shenton BK, Borzotta A, et al: The influence of surgical operations on components of the human immune system. Br J Surg
72:771–776, 1985.
101. Tonnesen E, Brinklov MM, Christensen NJ, et al: Natural killer cell activity and lymphocyte function during and after coronary artery bypass
grafting in relation to the endocrine stress response. Anesthesiology 67:526–533, 1987.
102. Toft P, Svendsen P, Tonnesen E, et al: Redistribution of lymphocytes after major surgical stress. Acta Anaesthesiol Scand 37:245–249, 1993.
103. Davis
JM, Albert JD, Tracy KJ, et al: Increased neutrophil mobilization and decreased chemotaxis during cortisol and epinephrine infusions. J
Trauma 31:725–732, 1991.
104. Bayer
BM, Daussin S, Hernandez M, Irvin L: Morphine inhibition of lymphocyte activity is mediated by an opioid dependent mechanism.
Neuropharmacology 29:369–374, 1990.
105. YeagerMP, Yu CT, Campbell AS, et al: Effect of morphine and β-endorphin on human Fc receptor-dependent and natural killer cell
functions. Clin Immunol Immunopathol 62:336–343, 1992.
106. Tubaro E, Borelli G, Croce C, et al: Effect of morphine on resistance to infection. J Infect Dis 148:656–666, 1983.
107. Markovic SN, Knight PR, Murasko DM: Inhibition of interferon stimulation of natural killer cell activity in mice anesthetized with halothane
or isoflurane. Anesthesiology 78:700–706, 1993.
1084
108. Radosevic-Stasic B, Udovic-Sirola M, Stojanov L, et al: Growth of allogenic sarcoma in mice subjected to halothane anesthesia and/or
surgical stress. Anesth Analg 69:570–574, 1989.
109. Stevenson GW, Hall SC, Rudnick S, et al: The effect of anesthetic agents on the human immune response. Anesthesiology 72:542–552, 1990.
110. Hole A, Unsgaard G: The effect of epidural and general anaesthesia on lymphocyte function during and after major orthopedic surgery. Acta
111. Tonnesen E, Wahlgreen C: Influence of extradural and general anaesthesia on natural killer cell activity and lymphocyte subpopulations in
patients undergoing hysterectomy. Br J Anaesth 60:500–507, 1988.
112. Rem J, Brandt MR, Kehlet H: Prevention of postoperative lymphopenia and granulocytosis by epidural analgesia. Lancet 1:283–285, 1980.
113. Erskine R, Janicki PK, Ellis P, James MFM: Neutrophils from patients undergoing hip surgery exhibit enhanced movement under spinal
anaesthesia compared with general anaesthesia. Can J Anaesth 39:905–910, 1992.
114. ErskineR, Janicki PK, Neil G, James MFM: Spinal anaesthesia but not general anaesthesia enhances biocidal activity in hip arthroplasty
patients. Can J Anaesth 41:632–638, 1994.
115. Rimback G, Cassuto J, Wallin G, Westlander G: Inhibition of peritonitis by amide local anesthetics. Anesthesiology 72:302–307, 1988.
116. Eriksson AS, Sinclair R, Cassuto J, Thomsen P: Influence of lidocaine on leukocyte function in the surgical ward. Anesthesiology 77:74–78,
1992.
117. Shulkin DJ, Kinosian B, Glick H, et al: The economic impact of infections. An analysis of hospital costs and charges in surgical patients with
cancer. Arch Surg 128:449–452, 1993.
118. Davey PG, Nathwani D: What is the value of preventing postoperative infections? New Horizons 6(Suppl 2):S64–S71, 1998.
119. Ben-Eliyahu S, Yirmiya R, Liebeskind JC, et al: Stress increases metastatic spread of a mammary tumor in rats: Evidence for mediation by
the immune system. Brain Behav Immun 5:193–205, 1991.
120. Cuschieri
RJ, Morran CG, Howie JC, McArdle CS: Postoperative pain and pulmonary complications: Comparison of three analgesic
techniques. Br J Surg 72:495–498, 1985.
121. Jayr
C, Thomas H, Rey A, et al: Postoperative pulmonary complications: Epidural analgesia using bupivacaine and opioids versus parental
122. AmatoAC, Pescatori M: Effect of perioperative blood transfusions on recurrence of colorectal cancer: Meta-analysis stratified on risk factors.
Dis Colon Rectum 41:570–585, 1998.
123. Shir
Y, Raja SN, Frank SM, Brendler CB: Intraoperative blood loss during radical retropubic prostatectomy: Epidural versus general
anesthesia. Urology 45:993–999, 1995.
124. Modig J, Karlstrom G: Intra- and post-operative blood loss and haemodynamics in total hip replacement when performed under lumbar
epidural versus general anaesthesia. Eur J Anaesthesiol 4:345–355, 1987.
125. Modig J: Beneficial effects on intraoperative and postoperative blood loss in total hip replacement when performed under lumbar epidural
anesthesia. Acta Chir Scand 550(Suppl):95–103, 1998.
126. Mangano DT, Browner WS, Hollenberg M, et al: Association of perioperative myocardial ischemia with cardiac morbidity and mortality in
men undergoing noncardiac surgery. N Engl J Med 323:1781–1788, 1990.
127. Mangano DT, Hollenberg M, Fergert G, et al: Perioperative myocardial ischemia in patients undergoing noncardiac surgery. I: Incidence and
severity during the 4 day perioperative period. J Am Coll Cardiol 17:843–850, 1991.
128. McCann RL, Clements FM: Silent myocardial ischemia in patients undergoing peripheral vascular surgery: Incidence and association with
perioperative cardiac morbidity and mortality. J Vasc Surg 9:583–587, 1989.
129. Ouyang P, Gerstenblith G, Furman WR, et al: Frequency and significance of early postoperative silent myocardial ischemia in patients having
peripheral vascular surgery. Am J Cardiol 64:1113–1116, 1989.
130. Raby KE, Barry J, Creager MA, et al: Detection and significance of intraoperative and postoperative myocardial ischemia in peripheral
vascular surgery. JAMA 268:222–227, 1992.
131. Mulcahy D, Keegan J, Cunningham D, et al: Circadian variation of total ischemic burden and its alterations with antianginal agents. Lancet
2:755–759, 1988.
132. WillichSN, Pohjola-Sintonen S, Bhatia SJS, et al: Suppression of silent ischemia by metoprolol without alteration of morning increase in
platelet aggregability in patients with stable coronary artery disease. Circulation 79:557–565, 1989.
133. Rocco MB, Barry J, Campbell S, et al: Circadian variation of transient myocardial ischemia in patients with coronary artery disease.
1085
Circulation 75:395–400, 1987.
134. Flatley KA, DeFily DV, Thomas JX: Effects of cardiac sympathetic nerve stimulation during adrenergic blockade on infarct size in
anesthetized dogs. J Cardiovasc Pharmacol 7:673–679, 1985.
135. Mangano DT, Siliciano D, Hollenberg M, et al: Postoperative myocardial ischemia. Therapeutic trials using intensive analgesia following
surgery. Anesthesiology 76:342–353, 1992.
136. Leung JM, O’Kelly BF, Mangano DT: Relationship of regional wall motion abnormalities to hemodynamic indices of myocardial oxygen
supply and demand in patients undergoing CABG surgery. Anesthesiology 73:802–814, 1990.
137. Gage JE, Hess OM, Murakami T, et al: Vasoconstriction of stenotic coronary arteries during dynamic exercise in patients with classic angina
pectoris: Reversibility by nitroglycerin. Circulation 73:865–876, 1986.
138. Brown BG: Coronary vasospasm: Observations linking the clinical spectrum of ischemic heart disease to the dynamic pathology of coronary
atherosclerosis. Arch Intern Med 141:716–722, 1981.
139. JohannsenUJ, Mark AL, Marcus ML: Responsiveness to cardiac sympathetic nerve stimulation during maximal coronary dilation produced
by adenosine. Circ Res 50:510–517, 1982.
140. Wallace A, Layug B, Tateo I, et al: Prophylactic atenolol reduces postoperative myocardial ischemia. Anesthesiology 88:7–17, 1998.
141. Tsuchida H, Omote T, Miyamoto M, et al: Effects of thoracic epidural anesthesia on myocardial pH and metabolism during ischemia. Acta
142. Davis RF, DeBoer LWV, Maroko PR: Thoracic epidural anesthesia reduces myocardial infarct size after coronary artery occlusion in dogs.
Anesth Analg 65:711–717, 1986.
143. Hogan Q: Cardiovascular response to sympathetic block by regional anesthesia. Reg Anesth 21(6 Suppl):26–34, 1996.
144. Blomberg S, Emanuelsson H, Kvist H, et al: Effects of thoracic epidural anesthesia on coronary arteries and arterioles in patients with
coronary disease. Anesthesiology 73:840–847, 1990.
145. Rolf N, Van de Velde M, Wouters PF, et al: Thoracic epidural anesthesia improves functional recovery from myocardial stunning in
conscious dogs. Anesth Analg 83:935–940, 1996.
146. Klassen GA, Bramwell RS, Bromage PR, Zborowska-Sluis DT: Effect of acute sympathectomy by epidural anesthesia on the canine coronary
circulation. Anesthesiology 52:8–15, 1980.
147. Blomberg S, Emanuelsson H, Ricksten S-E: Thoracic epidural anesthesia and central hemodynamics in patients with unstable angina pectoris.
Anesth Analg 69:558–562, 1989.
148. Kock M, Blomberg S, Emanuelsson H, et al: Thoracic epidural anesthesia improves global and regional left ventricular function during stress-
induced myocardial ischemia in patients with coronary artery disease. Anesth Analg 71:625–630, 1990.
149. Reiz S, Nath S, Rais O: Effects of thoracic epidural block and prenalterol on coronary vascular resistance and myocardial metabolism in
patients with coronary artery disease. Acta Anaesthesiol Scand 24:11–16, 1980.
150. Beattie WS, Buckley DN, Forrest JB: Epidural morphine reduces the risk of postoperative myocardial ischaemia in patients with cardiac risk
factors. Can J Anaesth 40:532–541, 1993.
151. de
Leon-Casasola OA, Lema MJ, Karabella D: Postoperative myocardial ischemia: Epidural versus intravenous PCA analgesia. A pilot
project. Reg Anesth 20:105–112, 1995.
152. Baron
JF, Bertrand M, Barre E, et al: Combined epidural and general anesthesia versus general anesthesia for abdominal aortic surgery.
153. Boylan JF, Katz J, Kavanagh BP, et al: Epidural bupivacaine-morphine analgesia versus patient-controlled analgesia following abdominal
aortic surgery. Anesthesiology 89:585–593, 1998.
154. Garnett
RL, MacIntyre A, Lindsay P, et al: Perioperative ischaemia in aortic surgery: Combined epidural/general anaesthesia and epidural
analgesia vs general anaesthesia and i.v. analgesia. Can J Anaesth 43:769–777, 1996.
155. Liem TH, Booij LH, Hasenbos MA, Gielen MJ: Coronary artery bypass grafting using two different anesthetic techniques. Part I.
Hemodynamic results. J Cardiothorac Vasc Anesth 6:148–155, 1992.
156. Liem TH, Hasenbos MA, Booij LH, Gielen MJ: Coronary artery bypass grafting using two different anesthetic techniques. Part 2.
Postoperative outcomes. J Cardiothorac Vasc Anesth 6:156–161, 1992.
157. Liem TH, Booij LH, Hasenbos MA, van Egmond J: Coronary artery bypass grafting using two different anesthetic techniques. Part 3.
Adrenergic responses. J Cardiothorac Vasc Anesth 6:162–167, 1992.
1086
158. Stenseth R, Bjella L, Berg EM, et al: Thoracic epidural analgesia in aortocoronary bypass surgery. I: Haemodynamic effects. Acta
159. Kirno K, Friberg P, Grzegorczyk A, et al: Thoracic epidural anesthesia during coronary artery bypass surgery: Effects on cardiac sympathetic
activity, myocardial blood flow and metabolism, and central hemodynamics. Anesth Analg 79:1075–1081, 1994.
160. Meissner A, Rolf N, van Aken H: Thoracic epidural anesthesia and the patient with heart disease: Benefits, risks, and controversies. Anesth
Analg 85:517–528, 1997.
161. Kamibayashi
T, Hayashi Y, Mammoto T, et al: Thoracic epidural anesthesia attenuates halothane-induced myocardial sensitization to
dysrhythmogenic effect of epinephrine in dogs. Anesthesiology 82:129–134, 1995.
162. Craig DB: Postoperative recovery of pulmonary function. Anesth Analg 60:46–52, 1981.
163. PedersenT, Eliasen K, Henriksen E: A prospective study of risk factors and cardiopulmonary complications associated with anaesthesia and
surgery: Risk indicators of cardiopulmonary morbidity. Acta Anaesthesiol Scand 34:144–155, 1990.
obese: Influence on postoperative ambulation and pulmonary function. Anesth Analg 63:583–592, 1984.
165. Pedersen
T, Viby-Mogensen J, Ringsted C: Anaesthetic practice and postoperative pulmonary complications. Acta Anaesthesiol Scand
36:812–818, 1992.
166. Wahba WM: Influence of aging on lung function—clinical significance of changes from age twenty. Anesth Analg 62:764–776, 1983.
167. Latimer RG, Dickman M, Day WC, et al: Ventilatory patterns and pulmonary complications after upper abdominal surgery determined by
preoperative and postoperative computerized spirometry and blood gas analysis. Am J Surg 122:622–632, 1971.
168. Garibaldi RA, Britt MR, Coleman ML, et al: Risk factors for postoperative pneumonia. Am J Med 70:677–680, 1981.
169. WarnerMA, Divertie MB, Tinker JH: Preoperative cessation of smoking and pulmonary complications in coronary artery bypass patients.
170. Kavanagh BP, Katz J, Sandler AN: Pain control after thoracic surgery: A review of current techniques. Anesthesiology 81:737–759, 1994.
171. Simonneau G, Vivien A, Sartene R, et al: Diaphragmatic dysfunction induced by upper abdominal surgery. Role of postoperative pain. Am
Rev Respir Dis 128:899–903, 1983.
172. Fratacci M-D, Kimball WR, Wain JC, et al: Diaphragmatic shortening after thoracic surgery in humans: Effects of mechanical ventilation and
thoracic epidural anesthesia. Anesthesiology 79:654–665, 1993.
173. Shannon R: Intercostal and abdominal muscle afferent influence on medullary dorsal respiratory group neurons. Respir Physiol 39:73–94,
1980.
174. Ford GT, Grant DA, Rideout SE, et al: Inhibition of breathing associated with gallbladder stimulation in dogs. J Appl Physiol 65:72–79, 1988.
175. Duggan J, Drummond GB: Activity of lower intercostal and abdominal muscle after upper abdominal surgery. Anesth Analg 66:852–855,
1987.
176. Wahba RWM: Perioperative functional residual capacity. Can J Anaesth 38:384–400, 1991.
177. Rosenberg J, Wildschiedtz G, Pedersen MH, et al: Late postoperative nocturnal episodic hypoxaemia and associated sleep patterns. Br J
Anaesth 72:145–150, 1994.
178. Kehlet H: Multimodal approach to control postoperative pathophysiology and rehabilitation. Br J Anaesth 78:606–617, 1997.
179. Katz
J, Jackson M, Kavanagh BP, Sandler AN: Acute pain after thoracic surgery predicts long-term post-thoracotomy pain. Clin J Pain
12:50–55, 1996.
180. Stiller KR, Munday RM: Chest physiotherapy for the surgical patient. Br J Surg 79:745–749, 1992.
181. Morran
CG, Finlay IG, Mathieson M, et al: Randomized controlled trial of physiotherapy for postoperative pulmonary complications. Br J
Anaesth 55:1113–1117, 1983.
182. Pasnard
J-L, Mankikian B, Bertrand M, et al: Effects of thoracic extradural block on diaphragmatic electrical activity and contractility after
upper abdominal surgery. Anesthesiology 78:63–71, 1993.
183. Manikian B, Cantineau JP, Betrand M, et al: Improvement of diaphragmatic function by a thoracic extradural block after upper abdominal
1087
184. Sandler AN, Stringer D, Panos L, et al: A randomized, double-blind comparison of lumber epidural and intravenous fentanyl infusions for
postthoracotomy pain relief: Analgesic, pharmacokinetic, and respiratory effects. Anesthesiology 77:626–634, 1992.
185. Guinard J-P, Mavrocordatos P, Chiolero R, Carpenter RL: A randomized comparison of intravenous versus lumber and thoracic epidural
fentanyl for analgesia after thoracotomy. Anesthesiology 77:1108–1115, 1992.
186. Bell
SD: The correlation between pulmonary function and resting and dynamic pain scores in post aortic surgery patients [abstract]. Anesth
Analg 72(Suppl):S18, 1991.
187. Zwarts SJ, Hasenbos MAMW, Gielen MJM, Kho H-G: The effect of continuous epidural analgesia with sufentanil and bupivacaine during
and after thoracic surgery on the plasma cortisol concentration and pain relief. Reg Anesth 14:183–188, 1989.
188. Cicala RS, Voeller GR, Fox T, et al: Epidural analgesia in thoracic trauma: Effects of lumbar morphine and thoracic bupivacaine on
pulmonary function. Crit Care Med 18:229–231, 1990.
189. Mackersie RC, Shackford SR, Hoyt DB, Karagianes TG: Continuous epidural fentanyl analgesia: Ventilatory function improvement with
routine use in treatment of blunt chest injury. J Trauma 27:1207–1212, 1987.
190. Wisner DH: A stepwise logistic regression analysis of factors affecting morbidity and mortality after thoracic trauma: Effect of epidural
analgesia. J Trauma 30:799–805, 1990.
191. Sabanathan S, Mearns AJ, Bickford-Smith PJ, et al: Efficacy ofcontinuous extrapleural intercostal nerve block on postthoracotomy pain and
pulmonary mechanics. Br J Surg 77:221–225, 1990.
192. Kaiser
AM, Zollinger A, De Lorenzi D, et al: Prospective, randomized comparison of extrapleural versus epidural analgesia for
postthoracotomy pain. Ann Thorac Surg 66:367–372, 1998.
193. Raffin L, Fletcher D, Sperandio M, et al: Interpleural infusion of 2% lidocaine with 1:200,000 epinephrine for postthoracotomy analgesia.
Anesth Analg 79:328–334, 1994. Rimback G, Cassuto J, Tollesson P-O: Treatment of postoperative paralytic ileus by intravenous lidocaine
infusion. Anesth Analg 70:414–419, 1990.
194. Livingston EH, Passaro EP Jr: Postoperative ileus. Dig Dis Sci 35:121–132, 1990.
195. Saito H, Trocki O, Alexander JW, et al: The effect of route of nutrient administration on the nutritional state, catabolic hormone secretion, and
gut mucosal integrity after burn injury. JPEN 11:1–7, 1987.
196. Moore FA, Feliciano DV, Andrassay RJ, et al: Early enteral feeding, compared with parenteral, reduces postoperative septic complications.
Ann Surg 216:172–183, 1992.
197. Shou
J, Lappin J, Minnard EA, Daly JM: Total parenteral nutrition, bacterial translocation, and host immune function. Am J Surg 167:145–
150, 1994.
198. Weiskopf RB, Reid IA, Fisher DM, et al: Effects of fentanyl on vasopressin secretion in human subjects. J Pharmacol Exp Ther 242:970–973,
1987.
199. Mitchell A, Collin J: Vasopressin effect on the small intestine: A possible factor in paralytic ileus? Br J Surg 72:462–465, 1985.
200. Glise H, Abrahamsson H: Reflex inhibition of gastric motility: Pathophysiological aspects. Scand J Gastroenterol 89(Suppl):77–82, 1984.
201. Johansson K, Ahn H, Lindhagen J, Tryselius U: Effect of epidural anaesthesia on intestinal blood flow. Br J Surg 75:73–76, 1988.
202. Udassin
R, Eimerl D, Schiffman J, Haskel Y: Epidural anaesthesia accelerates the recovery of postischemic bowel motility in the rat.
203. Aitkinhead
AR, Wishart HY, Peebles-Brown DA: High spinal nerve block for large bowel anastomosis: A retrospective study. Br J Anaesth
50:177–183, 1978.
204. Worsley MH, Wishart HY, Peebles Brown DA, Aitkenhead AR: High spinal nerve block for large bowel anastomosis. Br J Anaesth 60:836–
840, 1988.
205. GroudineSB, Fisher HAG, Kaufman RP Jr, et al: Intravenous lidocaine speeds the return of bowel function, decreases postoperative pain, and
shortens hospital stay in patients undergoing radical retropublic prostatectomy. Anesth Analg 86:235–239, 1998.
206. Rimback G, Cassuto J, Wallin G, Westlander G: Inhibition of peritonitis by amide local anaesthetics. Anesthesiology 69:881–886, 1988.
207. Frantzides
CT, Cowles V, Salaymeh B, et al: Morphine effects on human colonic myoelectric activity in the postoperative period. Am J Surg
163:144–149, 1992.
208. Murphy DB, Sutton JA, Prescott LF, Murphy MB: Opioidinduced delay in gastric emptying: A peripheral mechanism in humans.
1088
83:757–765, 1995.
210. Steinbrook RA: Epidural anesthesia and gastrointestinal motility. Anesth Analg 86:837–844, 1998.
211. Seeling
W, Bruckmooser K-P, Huffner C, et al: No reduction in postoperative complications by the use of catheterized epidural analgesia
following major abdominal surgery. Anaesthesist 39:33–40, 1990.
212. de Leon-Casasola OA, Karabella D, Lema MJ: Bowel function recovery after radical hysterectomies: Thoracic epidural bupivacaine-
morphine versus intravenous patient-controlled analgesia with morphine: A pilot study. J Clin Anesth 8:87–92, 1996.
213. Morimoto H, Cullen JJ, Messick JM Jr, Kelly KA: Epidural analgesia shortens postoperative ileus after ileal pouch-anal canal anastomosis.
Am J Surg 169:79–83, 1995.
214. Scott AM, Starling JR, Ruscher AE, et al: Thoracic versus lumbar epidural anesthesia’s effect on pain control and ileus resolution after
restorative protocolectomy. Surgery 120:688–697, 1996.
215. Riis
J, Lomholt B, Haxholdt O, et al: Immediate and long-term mental recovery from general versus epidural anesthesia in elderly patients.
216. Edwards H, Rose EA, Schorow M, King TC: Postoperative deterioration in psychomotor function. JAMA 245:1342–1343, 1981.
217. Inouye SK, Peduzzi PN, Robison JT, et al: Importance of functional measures in predicting mortality among older hospitalized patients.
JAMA 279:1187–1193, 1998.
218. Francis J, Martin D, Kapoor WN: A prospective study of delirium in hospitalized elderly. JAMA 263:1097–1101, 1990.
219. Marcantonio ER, Mangione CM, Goldman L, et al: Postoperative delirium is associated with poor outcome after non-cardiac surgery
[abstract]. J Am Geriatr Soc 41(Suppl):SA1, 1993.
220. Moller JT, Cluitmans P, Rasmussen LS, et al: Long-term postoperative cognitive dysfunction in the elderly: ISPOCD1 study. Lancet
351:857–861, 1998.
221. Chung F, Seyone C, Dyck B, et al: Age-related cognitive recovery after general anesthesia. Anesth Analg 71:217–224, 1990.
222. Duggleby W, Lander J: Cognitive status and postoperative pain: Older adults. J Pain Symptom Manage 9:19–27, 1994.
223. Levkoff SE, Besdine RW, Wetle T: Acute confusional states (delirium) in the hospitalized elderly. Ann Rev Gerontol Geriatr 6:1–26, 1986.
224. Marcantonio ER, Goldman L, Mangione CM, et al: A clinical prediction rule for delirium after elective noncardiac surgery. JAMA 271:134–
139, 1994.
225. Marcantonio ER, Juarez G, Goldman L, et al: The relationship of postoperative delirium with psychoactive medications. JAMA 272:1518–
1522, 1994.
226. Dyer CB, Ashton CM, Teasdale TA: Postoperative delirium: A review of 80 primary data-collection studies. Arch Intern Med 155:461–465,
1995.
227. Berggren D, Gustafson Y, Eriksson B, et al: Postoperative confusion after anesthesia in elderly patients with femoral neck fractures. Anesth
Analg 66:497–504, 1987.
228. Lynch EP, Lazor MA, Gellis JE, et al: The impact of postoperative pain on the development of postoperative delirium. Anesth Analg 86:781–
785, 1998.
229. Dodds C, Allison J: Postoperative cognitive deficit in the elderly surgical patient. Br J Anaesth 81:449–462, 1998.
230. Williams-Russo P, Sharrock NE, Mattis S, et al: Cognitive effects after epidural vs. general anesthesia in older adults. JAMA 274:44–50,
1995.
231. Asbjorn
J, Jakobsen BW, Pilegaard HK, et al: Mental function in elderly men after surgery during epidural analgesia. Acta Anaesthesiol
Scand 33:369–373, 1989.
232. Ghoneim MM, Hinrichs JV, O’Hara MW, et al: Comparison of psychologic and cognitive functions after general or regional anesthesia.
233. Nielson WR, Gelb AW, Casey JE, et al: Long-term cognitive and social sequelae of general versus regional anesthesia during arthroplasty in
the elderly. Anesthesiology 73:1103–1109, 1990.
234. Tzabar Y, Asbury AJ, Millar K: Cognitive failures after general anaesthesia for day-case surgery. Br J Anaesth 76:194–197, 1996.
235. Hole
A, Terjesen T, Breivik H: Epidural versus general anaesthesia for total hip arthroplasty in elderly patients. Acta Anaesthesiol Scand
24:279–287, 1980.
1089
236. Drummond MF, Richardson WS, O’Brien BJ, et al: How to use an article on economic analysis of clinical practice. Are the results of the
study valid? JAMA 277:1552–1557, 1997.
237. Johnstone RE, Martinec CL: Costs of anesthesia. Anesth Analg 76:840–848, 1993.
238. Fleisher LA, Mantha S, Roizen MF: Medical technology assessment: An overview. Anesth Analg 87:1271–1282, 1998.
239. Dexter F, Tinker JH: Analysis of strategies to decrease postanesthesia care unit costs. Anesthesiology 82:94–101, 1995.
240. Lubarsky DA: Understanding cost analyses: Part I. A practitioner’s guide to cost behavior. J Clin Anesth 7:519–521, 1995.
241. Ammar AD: Postoperative epidural analgesia following abdominal aortic surgery: Do the benefits justify the costs? Ann Vasc Surg 12:359–
363, 1998.
242. D’Alessio JG, Rosenblum M, Shea KP, Freitas DG: A retrospective comparison of interscalene block and general anesthesia for ambulatory
surgery shoulder arthroscopy. Reg Anesth 20:62–68, 1995.
243. Tierney GS, Wright RW, Smith JP, Fischer DA: Anterior cruciateligament reconstruction as an outpatient procedure. Am J Sports Med
23:755–756, 1995.
244. Nakamura SJ, Conte-Hernandez A, Galloway MT: The efficacy of regional anesthesia for outpatient anterior cruciate ligament reconstruction.
Arthroscopy 13:699–703, 1997.
245. Brown
AR, Weiss R, Greenberg C, et al: Interscalene block for shoulder arthroscopy: Comparison with general anesthesia. Arthroscopy
9:295–300, 1993.
246. Gold BS, Kitz DS, Lecky JH, Neuhaus JM: Unanticipated admission to the hospital following ambulatory surgery. JAMA 262:3008–3010,
1989.
247. de
Leon-Casasola OA, Parker BM, Lema MJ, et al: Epidural analgesia versus intravenous patient-controlled analgesia. Differences in the
postoperative course of cancer patients. Reg Anesth 19:307–15, 1994.
248. Smedstad KG, Beattie WS, Blair WS, Buckley DN: Postoperative pain relief and hospital stay after total esophagectomy. Clin J Pain 8:149–
153, 1992.
249. Major CP Jr, Greer MS, Russell WL, Roe SM: Postoperative pulmonary complications and morbidity after abdominal aneurysmectomy: A
comparison of postoperative epidural versus parenteral opioid analgesia. Am Surg 62:45–51, 1996.
250. McNeely JK, Farber NE, Rusy LM, Hoffman GM: Epidural analgesia improves outcome following pediatric fundoplication. A retrospective
analysis. Reg Anesth 22:16–23, 1997.
251. Frank E, Sood OP, Torjman M, et al: Postoperative epidural analgesia following radical retropubic prostatectomy: Outcome assessment. J
Surg Oncol 67:117–120, 1998.
252. Grass
JA, Zuckerman RL, Tsao H, et al: Patient-controlled epidural analgesia results in shorter hospital stay after cesarean section [abstract].
Reg Anesth 15(Suppl):S26, 1991.
253. Clearly PD, Greenfield S, McNeil BJ: Assessing quality of life after surgery. Control Clin Trials 12:189–203S, 1991.
254. Fung D, Cohen MM: Measuring patient satisfaction with anesthesia care: A review of current methodology. Anesth Analg 87:1089–1098,
1998.
255. Wilson IB, Clearly PD: Linking clinical variables with health-related quality of life. JAMA 273:59–65, 1995.
256. Aharony L, Strasser S: Patient satisfaction: What we know about and what we still need to explore. Med Care Rev 50:49–79, 1993.
257. Carli
F, Klubien K, De Angelis R, et al: An intensive versus graded perioperative management program for recovery after colorectal surgery:
Preliminary results on quality of life [abstract]. Reg Anesth 23(Suppl):11, 1998.
258. Kantz
ME, Harris WJ, Levitsky K, et al: Methods for assessing condition-specific and generic functional status outcomes after total knee
replacement. Med Care 30(Suppl):MS240–MS252, 1992.
259. Pocock SJ: A perspective on the role of quality-of-life assessment in clinical trials. Control Clin Trials 12:257S–265S, 1991.
260. Tetzlaff JE, Yoon HJ, Brems J: Patient acceptance of interscalene block for shoulder surgery. Reg Anesth 18:30–33, 1993.
261. Waters
JH, Leivers D, Maher D, et al: Patient and surgeon satisfaction with extremity blockade for surgery in remote locations. Anesth Analg
84:773–776, 1997.
262. Cooper K, Kelley H, Carrithers J: Perceptions of side effects following axillary block used for outpatient surgery. Reg Anesth 20:212–216,
1090
1995.
263. Papanikolaou
MN, Voulgari A, Lykouras L, et al: Psychological factors influencing the surgical patients’ consent to regional anaesthesia.
264. JamisonRN, Ross MJ, Hoopman P, et al: Assessment of postoperative pain management: Patient satisfaction and perceived helpfulness. Clin
J Pain 13:229–236, 1997.
265. McNeill
JA, Sherwood GD, Starck PL, Thompson CJ: Assessing clinical outcomes: Patient satisfaction with pain management. J Pain
Symptom Manage 16:29–40, 1998.
266. Hester
NO, Miller KL, Foster RL, Vojir CP: Symptom management outcomes: Do they reflect variations in care delivery systems? Med Care
35:NS69–NS83, 1997.
267. Sharrock NE, Ranawat CS, Urquhart B, Peterson M: Factors influencing deep vein thrombosis following total hip arthroplasty under epidural
anesthesia. Anesth Analg 76:756–771, 1993.
268. Brodner G, Posatzi E, Van Aken H, et al: A multimodal approach to control postoperative pathophysiology and rehabilitation in patients
undergoing abdominothoracic esophagectomy. Anesth Analg 86:228–234, 1998.
269. Moinche S, Bulow S, Hesselfeldt P, et al: Convalescence and hospital stay after colonic surgery with balanced analgesia, early oral feeding,
and enforced mobilisation. Eur J Surg 161:283–288, 1995.
1091
Section VII Chapter 47 - Trauma
Chapter 47 - Trauma
CRAIG T. HARTRICK
Each year, tens of millions of Americans suffer serious accidental injuries that result in physiologic compromise,
physical disability, and persistent pain. In addition to the obvious personal and social impact on patients and their
families, the economic impact secondary to lost productivity and healthcare expenses represents a significant burden
to society. The cost of post-traumatic chronic pain alone is conservatively estimated in excess of $85 billion
annually. Heightened awareness of the importance of early intervention with effective pain management measures
[1]
is reflected in both public policy and medical professional guidelines. If morbidity secondary to trauma is to be
[2] [3] [4]
minimized, guidelines for the treatment of post-traumatic pain must encompass more than the humanitarian concern
for analgesic administration. Reduction of stress, restoration of function, and prevention of subsequent
complications are all intimately related to post-traumatic analgesia.
The role of regional analgesia in the treatment of posttraumatic pain is well established empirically. Best practice
recommendations, however, ideally follow critical analysis of multiple prospective, randomized, double-blinded
studies designed to examine specific outcomes. The unpredictable nature of nonoperative trauma, with variable
degrees of physiologic compromise and stimulus intensity, presents obvious challenges to well-controlled study.
Ongoing processes secondary to multiple concurrent injuries further confound analysis.
Considerable evidence for improved patient outcomes when regional analgesia is used post-traumatically can readily
be inferred from numerous postoperative studies described elsewhere in this text. Outside the operating room,
evidence-based outcome analysis has demonstrated the efficacy of regional anesthesia in reducing morbidity in
patients after chest wall trauma and in the treatment of patients with post-traumatic musculoskeletal and neuropathic
pain. Additional nonoperative evidence for the effectiveness of neural blockade as a means of improving
[5]
physiologic function, reducing chronic pain, and preventing the subsequent development of chronic pain states in
patients after trauma are also reviewed.
Reducing the Stress Response After Trauma
The response to trauma involves initiation of intertwined neural and humoral cascades. Afferent neural barrage
leading to central sensitization and acting in concert with post-traumatic cytokine elaboration alters physiologic
function and leads to neural plasticity. Neuroinflammation with neuroimmune cell activation in the periphery after
neural trauma provides another source of ongoing afferent activity, further adding to the central sensitization and the
development of persistent pain. Interruption of these cascades can prevent further escalation of the inflammatory
[6]
response, thus interrupting this positive feedback cycle.
Moller and colleagues demonstrated that preoperative institution of epidural blockade to T4, including adrenal and
[7]
hepatic innervation, prevented the normal postoperative increase in cortisol and glucose after hysterectomy.
Although initial increases were observed when epidural anesthesia was initiated after the incision, no further
increases in cortisol or glucose were observed once afferent blockade was established. Although resting endocrine-
metabolic activity was not reestablished, a major portion of the stress response was indeed inhibited by post-
traumatic conduction blockade. Brandt and associates found that if postoperative epidural block was maintained for
[8]
just 24 hours, there was a sustained decrease in the negative nitrogen balance over the 4 days of the study period.
The observation that sympathetic blockade alters immune cell activity clinically is not unexpected, because it is
[9]
known from experimentation that sympathetic efferents play a role in inflammation. Furthermore, circulating
[10]
monocytes are recruited in wallerian degeneration associated with neuropathic hyperalgesia. Experimental animal
[11]
models of mononeuropathy exhibiting neuropathic allodynia develop significant upregulation of TNF-α and IL1-β
production from circulating monocytes. Analogous findings in patients with complex regional pain syndrome
[12]
(CRPS) are currently the subject of investigation. Moriwaki and coworkers suggested that clinical neuropathic
[13] [14]
pain has two distinct components: a neuropathic response characterized by mechanical allodynia and an
inflammatory response with characteristic rubor, calor, tumor, and loss of function that is responsive to
corticosteroids.
1092
Respiratory Function After Trauma
Oxygenation can be impaired in the trauma patient for a variety of reasons. Pulmonary injury as a result of direct
penetrating wounds, parenchymal contusions, aspiration of gastric contents, or parenchymal compression as a result
of hemothorax or pneumothorax is frequent. Hypoventilation and atelectasis due to reduced respiratory excursion
can result from pain after upper abdominal and thoracic injury or from anatomic disruption of chest wall mechanics
with flail chestsecondary to rib or sternal fractures. The severity ofpain from fractured ribs often necessitates
tracheal intubation and mechanical ventilation for respiratory insufficiency. Systemic opiate analgesia is problematic
because of its respiratory-depressant and coughsuppressant effects. Regional blockade provides excellent analgesia,
leaving the patient awake and cooperative, and thus promoting cough, deep breathing, and improved pulmonary
toilet.
Johnson studied forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1 ) in patients who had
[15]
undergone elective thoracic and abdominal procedures. On the first postoperative day, there were reported
reductions in preoperative pulmonary function of 75% for those with thoracic incisions, 68% for those with xiphoid
to pubic abdominal incisions, 61% for those with paramedian upper abdominal incisions, 53% for those with
subcostal incisions, and 38% for those with midline lower abdominal incisions. Postanesthetic respiratory failure
was most prominent when surgical insults were complicated by preexisting chronic obstructive pulmonary disease.
Blunt chest trauma that causes rib fractures in elderly patients results in twice the morbidity and mortality
experienced by younger patients when epidural analgesia is not employed. Pain relief in these patients is often
[16]
critical to the restoration of pulmonary function, prevention of further deterioration, and weaning from mechanical
ventilatory support.
Intercostal blockade, including all of the rib fracture levels as well as one intercostal nerve above and one below the
site of injury, has long been used in these situations. However, multiple levels are frequently involved, necessitating
multiple injection sites. Intercostal blocks can be particularly difficult at the uppermost thoracic levels, where
paravertebral blocks may be preferable. Furthermore, intercostal blocks must be repeated frequently, even when
long-acting local anesthetics are selected. There is also a risk of pneumothorax in patients who may already be in a
state of respiratory compromise. However, it is possible to insert a catheter percutaneously into the intercostal space
and, by injecting a large volume, block several adjacent segments. When a minimal number of contiguous ribs
[17] [18]
are involved unilaterally, this approach lends itself to continuous local anesthetic infusion.
Intrapleural administration of local anesthetic via a percutaneously placed catheter provides unilateral thoracic
dermatomal analgesia, which is ideally suited to patients with multiple rib fractures. Although the presence of
[19]
thoracostomy tubes does not preclude use of this technique (the chest tubes can be used to deliver the local
anesthetic), it works best in situations in which no such drains are required, because the anesthetic spread is
[20]
dependent on apposition of the parietal and visceral pleura.
Thoracic epidural analgesia with local anesthetic, narcotic, or both, can improve diminished compliance, increase
vital capacity and functional residual capacity, and decrease high bronchial resistance in these high-risk patients
with multiple rib fractures. Use of epidural analgesia has led to a more aggressive approach to the treatment of
[21]
such fractures, based on the recognition that the problem is primarily a functional rather than an anatomic
derangement. [22] [23]
Regional Anesthesia and Pulmonary Function After Trauma
Although Spence demonstrated that nerve block with intercostal or epidural techniques does not affect the
[24]
reduction of functional residual capacity, hypoxemia, or decreased ventilation, regional block does decrease the
retention of secretions, preserve ciliary activity, and make the cough more effective through a reduction in pain.
Bromage and colleagues reported improved FEV1 postoperatively, with segmental analgesia produced by epidural
[25]
narcotics. Benhamou and associates subsequently demonstrated that intravenous morphine after upper abdominal
[26]
surgery in high-risk patients with respiratory disease was unable to alter any objective pulmonary function, whereas
epidural morphine or epidural lidocaine was able to partially restore FVC and FEV1 to preoperative levels.
Rybro and coworkers compared morphine administration on demand after upper abdominal surgery between
[27]
patients who received medication via an intramuscular (IM) or epidural route. The epidural morphine group
demonstrated significantly reduced radiographic pulmonary changes and significantly higher PaO2 values, with a
slower rise in alveolar-arterial oxygen gradient. Rawal and colleagues compared postoperative pain relief with IM
[28]
narcotic, bupivacaine intercostal block, and single-bolus epidural morphine and found that postoperative PaO2 and
PaCO2 values reflected changes in peak expiratory flow rate. The greatest reductions in peak expiratory flow occurred
after IM drug administration, and the least occurred after epidural drug administration. Mankikian and associates [29]
1093
further described improved diaphragmatic function after thoracic epidural block with local anesthetic in patients
with upper abdominal wounds.
Prospective, randomized studies comparing intravenous opioid administration with epidural analgesia after chest
wall trauma have demonstrated a lower incidence of tracheostomy, less dependence on mechanical ventilation,
shorter stays in the intensive care setting, and inhibition of cytokine production associated with post-traumatic
complications. These studies are consistent with the postoperative experience in which meta-analysis of
[30] [31]
randomized controlled trials confirmed the superiority of epidural opioids over systemic opioids in reducing
postoperative atelectasis and the superiority of epidural local anesthetics over systemic opioids in improving
oxygenation and reducing the incidence of both postoperative pulmonary infection and overall pulmonary
complications. These effects were less dramatic with intercostal blockade. In one randomized, crossover trial,
[32] [33]
intrapleural block has been reported to be as effective as epidural analgesia in the management of multiple rib
fractures, with fewer adverse effects, but additional controlled studies are needed comparing the two techniques. The
best available evidence strongly supports the use of regional analgesia, especially via the epidural route, after the
chest sustains blunt trauma associated with sternal or rib fractures.
Acute Pain Management and Functional Outcome
The benefits of peripheral nerve block for trauma patients are often not fully exploited, either because of
inexperience of available personnel, time constraints, or the fear of masking an evolving compartment syndrome.
These techniques deserve increased use because they usually produce total and long-lasting analgesia with minimal
side effects. Furthermore, in patients requiring immediate surgical intervention, they obviate the need for general
anesthesia and shorten the patient's hospital stay. [34]
Outcome after closed reduction of extremity fractures in the emergency department may be assessed by patient
satisfaction with analgesia as well as the quality of the subsequent alignment of the bone. Local anesthetics have
long been injected into fracture hematomas to facilitate reduction. The use of intravenous regional (Bier) blocks has
been compared with fracture hematoma injection in the treatment of Colles' fracture in both adults and children. A [35]
prospective, randomized study has demonstrated less pain during manipulation, improved grip strength at 6 months,
improved anatomic alignment, and less remanipulation with intravenous regional blockade. [36] [37] [38]
Brachial plexus block can be accomplished with use of several different approaches. The choice of technique
depends on the site of injury and the ability to position the arm. In general, higher lesions (upper arm injury,
shoulder) require analgesia extending into the C5 dermatome; this is best achieved with an interscalene block.
Shoulder manipulation for treatment of dislocations is a common use. This technique is also suitable for Colles'
[39]
fracture because the anatomic snuffbox is sometimes difficult to cover adequately in lower approaches to the
[40]
brachial plexus.
Continuous infusion of local anesthetic can be used to prolong neural blockade without the tachyphylaxis seen in
patients who undergo repeated bolus techniques. The infusion technique also allows the degree of blockade to be
modulated by adjusting the concentration of local anesthetic so as to provide analgesia without complete anesthesia.
This is particularly useful after reimplantation procedures or other vascular injuries resulting in vasospasm. The
prolonged sympathectomy provided permits improved blood flow to the area of injury. Although the axillary
approach can be used, the infraclavicular approach lends itself to continuous infusion because the catheter is easily
[41]
fixed to the pectoral region. The stability of this location has facilitated the use of home infusion devices for
outpatient application. In a prospective, randomized study, the introduction of a patient-controlled component
[42] [43] [44]
to the brachial plexus catheter system represented a further refinement, which was reported to improve patient
satisfaction while lowering the total mass of local anesthetic required.
Femoral nerve block can be easily performed and provides excellent analgesia for femoral fractures in both adults
and children. The quality of the analgesia depends on the fracture site; excellent relief can be obtained for
[45] [46]
midshaft fractures, good relief for lower third fractures, and partial relief for upper third fractures. The method is [47]
also amenable to continuous infusion. By increasing the volume of injectate, femoral nerve block can be extended
[48]
cephalad, becoming a lumbar plexus block. The inclusion of the lateral femoral cutaneous and obturator nerves
[49] [50]
can provide improved analgesia for the upper thigh and the knee joint. Modulation of the density of the block is
more difficult with the lower than with the upper extremity because the femoral nerve is quite easily blocked with
relatively little local anesthetic. Fascia iliaca compartment block has been suggested to provide reliable analgesia in
children. Psoas compartment lumbar plexus block is still another alternative. Although nerve block has not been
[51] [52]
demonstrated to be of similar value in the management of hip fracture, the best available evidence does suggest
[53]
that the use of regional anesthesia for repair results in reduced short-term mortality. Catheter techniques lend
[54]
themselves to continuous infusion and PCEA (patient-controlled epidural analgesia) administration. The addition [55]
1094
of a basal infusion to PCEA reduces unwanted side effects such as excessive numbness, hypotension, and sedation
by reducing the need for high infusion rates and rescue boluses. Lumbar epidural infusion is a simple yet effective
means of producing continuous analgesia for the lower extremity. As such, this approach enjoys widespread usage
in hemodynamically stable patients. More importantly, the degree of neural blockade is readily modified by
changing the amount of local anesthetic delivered.
Continued tissue swelling after crushing or blunt traumatic extremity injury may predispose the patient to
subsequent development of a compartment syndrome. Swelling within the confines of a fascial compartment
resulting from hemorrhage or reactive edema formation after trauma can produce pressures sufficient to limit the
blood supply to both muscle and nerve contained therein. Untreated, these conditions can, within hours, produce
permanent neural damage, resulting in significant pain and functional impairment. However, even with prompt
surgical decompression through fasciotomy, significant numbers of patients go on to suffer persistent disability
secondary to chronic neuropathy. When an analgesic is selected, consideration should be given to the potential
[56]
masking of evolving neurologic sequelae of both peripheral and central origins. The pain associated with acute
compartment syndrome in the lower extremity typically breaks through properly controlled epidural analgesia. [57] [58] [59]
Furthermore, if weakness develops during the infusion, the local anesthetic can be removed to facilitate prompt
[60]
assessment.
The quality of physical rehabilitation after injury may well depend in some cases on the efficacy of analgesic
therapy immediately after injury. After total knee arthroplasty, improved analgesia allows the patient more active
participation in physical measures, which, in turn, promotes improved surgical outcome. In a randomized, controlled
trial, both continuous epidural infusion and continuous femoral block maintained for 72 hours resulted in improved
analgesia and range of continuous passive motion compared with intravenous patient-controlled analgesia (PCA)
therapy. At postoperative day 7, both regional anesthesia groups exhibited significantly greater mobilization.
[61]
Furthermore, the duration of rehabilitation required was significantly less for both regional anesthesia groups
compared with the PCA group. Similarly, a single injection of sustained-release encapsulated epidural morphine
with a duration of less than 48 hours has been associated with improved ambulatory tolerance at 72 hours in a
double-blinded, randomized, placebo-controlled trial. [62]
Regional Analgesia and Prevention of Chronic Post-Traumatic Pain
CHRONIC PAIN AFTER TRAUMA
Pain persisting beyond the normal recovery period, and often greatly exceeding what might be anticipated relative to
the residual pathology, can be considered chronic post-traumatic pain. Although it is widely assumed that
psychological factors become increasingly important as acute pain becomes chronic, it is perhaps less well
appreciated that a number of pathophysiologic changes also occur in both central and peripheral pain pathways.
Consequently, the response of patients with chronic pain to various therapeutic interventions, including the response
to local anesthetic blockade, often varies from what might be expected in the acute pain setting. Modification of
[63] [64]
the approach to treatment is required.
PREDISPOSITION
It is poorly understood why some patients suffer traumatic injuries that result in chronic pain states, whereas other
patients with similar injuries escape this fate. Genetic predisposition to chronic neuropathic pain has been suggested
by both experimental and clinical studies. Premorbid psychological factors have also been implicated in the
[65] [66] [67] [68]
subsequent development of chronic post-traumatic pain and are described elsewhere in this text. Nevertheless, the
persistence and intensity of acute pain may be crucial to the initiation of processes leading to chronic pain in
susceptible individuals. This impression is based on clinical studies involving phantom pain
[69]
and low back
[70] [71] [72] [73]
pain. The intensity of acute pain predicted the severity and persistence of pain in these conditions.
[74] [75] [76]
Overwhelming afferent barrage from severe pain may lead to the pathophysiologic alterations associated with
chronic pain in a manner consistent with the central neuroplasticity previously discussed. [77]
Site of injury is certainly an important factor in the development of persistent pain. Sports-related injuries that seem
more likely to become chronic pain problems include injuries involving the spine and spinal cord, brachial plexus
injuries including thoracic outlet syndrome and other syndromes of neurovascular compression, and certain
extremity injuries. Mechanical shoulder and knee injuries producing recurrent joint dislocation, bursitis, post-
traumatic arthritis or tendinitis, and myofascial dysfunction involving muscle groups about the joint are particularly
common. The risk factors predicting musculoskeletal injuries from overuse, however, relate to poor conditioning, [78] [79]
predisposing anatomic characteristics,

[80]
and intensity of activity, but not to “accident-prone” psychological
[81] [82] [83] [84]
factors. Patients with extremity injuries are also most likely to develop CRPS type I, which is reflex sympathetic
[85]
1095
dystrophy (RSD). The sympathetic dysfunction seen in the upper extremity after shoulder injury has long been
referred to as shoulder-hand syndrome. RSD of the knee has been more recently recognized to be a fairly common
[86]
ailment. [87]
Similarly, chronic pain conditions seem to occur more commonly after surgical trauma involving the extremities,
especially the hands and feet. Patients who have undergone spinal surgery, thoracotomy, extensive facial and scalp
surgery, cholecystectomy, and radical mastectomy also seem particularly vulnerable to persistent pain problems. [88] [89]
Chronic post-traumatic pain in the lower abdomen and groin occurs frequently after appendectomy, inguinal
herniorrhaphy, varicocele ligation, obstetric or gynecologic procedures with Pfannenstiel incisions, nephrectomy,
femoral thrombectomy, femoral-popliteal bypass grafting, vein stripping, lumbar sympathectomy, and uterine
suspension procedures. Visceral, myofascial, neuropathic, and psychogenic factors are contributory. Hitchcock
[90] [91]
and Alvarez reported a 2% incidence of chronic postincisional scar pain. They found the most common sites (in
[92]
decreasing order) to be the lower abdomen, thorax, lumbosacral area, head and neck, flank, and palm. Neuroma
formation was diagnosed in 43.3% of cases, whereas 23.3% had deafferentation pain. Psychological factors were
thought to be important in 33.3% of cases.
QUALITY OF ACUTE PAIN MANAGEMENT IN THE PREVENTION OF CHRONIC PAIN
As previously mentioned, there is increasing evidence that the quality of acute pain management is an important
factor in the subsequent development or prevention of chronic pain after trauma. Melzack and colleagues reported [93]
that patients with persistent postsurgical pain tended to be older individuals for whom lower doses of analgesics had
been initially prescribed, resulting in ineffective analgesia in the early postoperative days. Pain persisted for a longer
period in these individuals than in individuals for whom early analgesic therapy was more effective. Similarly,
unrelieved preoperative pain may trigger central sensitization before surgical intervention, thereby thwarting
preemptive analgesic efforts. A “critical time interval” has been proposed during which effective acute pain
[94]
management prevents delayed pain sequelae. This critical period of plasticity may be, in part, mediated by γ-
[95]
aminobutyric acid. Reorganization of central dendritic connections through synaptic clustering can be prevented by
[96]
preemptive intracellular sodium channel, calcium channel, and N-methy-D-aspartate (NMDA) receptor blockade. [97]
PREEMPTIVE ANALGESIA
This form of pain relief may be defined generally as an antinociceptive treatment that prevents the establishment of
altered central processing (which amplifies subsequent pain states). Although numerous animal studies have
documented the theoretical usefulness of pretraumatic application of various analgesics, clinical evidence of this
phenomenon in humans has been less convincing. Differences between laboratory and clinical settings should not be
dismissed as species-specific variation. The disparity in results may instead be accounted for by differences in
terminology, target, and timing.
Background
The concept of preemptive analgesia was first described clinically by Crile in 1913. It was noted that regional
[98]
blockade prevented subsequent development of painful scars after surgery. Seventy years later, Woolf provided
[99]
experimental evidence for the central component in the post-traumatic hypersensitivity theory originally postulated
by Crile. The volumes of studies produced since 1983 have elucidated two related yet distinctly different
phenomena with respect to preemptive analgesia.
In the narrowest sense, preemptive analgesia refers to administration, before a noxious stimulus, of antinociceptive
agents that seem to be more effective than the same agents applied post-traumatically. This improved efficacy may
manifest itself through either enhanced apparent potency or by increased duration, when the treatment effect seems
to outlast the expected duration of direct analgesic effect. These hypotheses are most often tested clinically in the
setting of acute postoperative pain.
In the recent past, acute and chronic pain were thought to arise from very different pathophysiologic circumstances.
It is now apparent, however, that the cascade of events initiated after acute injury may, in some individuals, lead to
the development of chronic pain. The prevention of long-term painful postoperative sequelae described by Crile was
echoed in the report by Bach and associates, who described the incidence of phantom limb pain reduction 1 year
[70]
after amputation in association with preoperative epidural analgesia. This finding has since been prospectively
studied, and although it had been confirmed by some, it was subsequently refuted by data from a randomized,
[100] [101]
double-blinded trial. Thus, in the broader sense, preemptive analgesia may also refer to the administration, before
[102]
1096
injury, of agents that prevent the ensuing cascade of events that could lead to the development of chronic pain.
Understanding the pathophysiology of injury is a key factor in the selection of appropriate target agents for study.
Target
High-intensity noxious stimulation alters central processing of afferent neural information. Studies elucidating the
mechanisms for this central hypersensitivity have documented a host of neurochemical changes, including
enhancement of dorsal horn neuronal activity after repetitive C-fiber barrage (wind-up), receptive field expansion
with decreased dorsal horn threshold resulting in both temporal and spatial summation, and increased immediate
early gene and dynorphin expression. [103] [104] [105] [106] [107] [108] [109]
Primary afferent nociceptor projections to laminae I and V of the dorsal horn are normally associated with small,
discrete, receptive fields. Prolonged high-intensity discharge, however, may alter this spinal circuitry, both
functionally and anatomically, through synaptic plasticity (sprouting). Stimulation results in the release of substance
P, calcitonin gene-related peptide, and glutamate from axon terminals of primary afferent nociceptors. Glutamate
then binds NMDA receptors in the dorsal horn. Resultant increases in intracellular calcium cause increased synthesis
of a second messenger, nitric oxide. Unlike other neurotransmitters, NO, being a highly diffusible gas, is not
restricted to interaction with nerve terminals immediately adjacent to the site of release. Instead, NO disperses freely
to surrounding regions of the spinal cord, where, having entered the presynaptic terminals of the primary afferents, it
induces the release of even more substance P and CGRP. This positive feedback results in hyperalgesia.
[110] [111]
Sensitization of wide dynamic range neurons that receive both noxious and non-noxious input gives rise to the
development of allodynia.
The generation of these hypersensitive post-traumatic pain states depends on NMDA receptor activation. [112] [113]
Further, preemptive NMDA antagonist administration prevents wind-up and the subsequent development of
allodynia in experimental animal models and in humans.
[114] [115]
Timing
Noxious stimulation potently induces the expression of immediate early genes such as c-fos within minutes of injury.
This response coincides with nociceptive behavior and is abolished in parallel with the preemptive application of
[116]
NMDA antagonists, thereby preventing long-term hyperalgesia. The preemptive administration of a single dose of
[117]
intrathecal ketamine delays the development of neuropathic pain in the rat for several days, clearly exceeding the [118]
expected duration of the analgesic. However, this treatment by itself fails to affect the ultimate severity or frequency
of the neuropathic condition. Ongoing neuronal activity likely involves additional factors unrelated to the NMDA
receptor. This finding is not unexpected, because tissue trauma results in the elaboration of a host of inflammatory
mediators, that, acting in concert, can be characterized as a “sensitizing soup.” [119] [120]
Nociceptive neuronal activity after administration of subcutaneous formalin in rats is known to follow a biphasic
response in which an early acute nociceptive phase, responding to opioid or local anesthetic, precedes a second
period of dorsal horn excitation, known as the inflammatory phase. Local anesthetic application after phase 1
[121] [122]
prevents phase 2 and thus the expression of c-fos. The secondary wave of neural input sustains the hypersensitivity
state. NMDA antagonists have been reported to block the second but not the initial phase of this biphasic response. [123]
Although a biphasic mechanism has not been demonstrated in a model of neuropathic pain, a similarly complex
process seems likely. Thus, successful prevention of long-term consequences of post-traumatic pain may require
different antagonists timed appropriately for each phase of the hypersensitivity process.
Similar results are seen with local anesthetic blockade of afferent input, with improved efficacy when the [124] [125]
analgesia is extended to include the early postoperative period. It is now apparent that the complexity of the
[126]
neurochemical response to trauma necessitates an ongoing treatment process if long-term sequelae are to be
prevented. [119]
Clinical Studies
Clinical studies have supported a role for local anesthetic blockade, spinal narcotic, nonsteroidal anti-inflammatory
drugs, and ketamine administered before noxious stimulus in acute pain studies in humans. [115] [126] [127] [128] [129] [130] [131] [132] [133] [134]
A prospective, randomized, double-blinded placebo-controlled study demonstrated an opioid-sparing effect

[135] [136] [137]
with preemptive dextromethorphan, an NMDA antagonist. However, the notion that multiple simultaneous or
[138]
sequential neurochemical events are involved in the development of wind-up has led to the prophylactic use of
therapies combining analgesics with differing mechanisms of action.
1097
Choe and colleagues provided clinical evidence for efficacy of preemptive analgesia with use of epidural
[139]
morphine in combination with epidural ketamine in a randomized, double-blinded study. Significantly improved
analgesia was associated with preincisional use compared with postincisional administration. Perhaps the most
innovative use of the available experimental evidence to date was a multimodal approach combining epidural local
anesthetic and epidural narcotic infusion, a nonsteroidal antiinflammatory drug, and metamizole to induce
descending central inhibition. A significant reduction in postoperative analgesic requirements after major
[140]
abdominal surgery was observed when therapy was administered before incision compared with the institution of
this same therapy just before wound closure. A similar preemptive effect was seen when preincisional epidural
ketamine, morphine, and bupivacaine were administered in combination in a randomized, single-blinded, placebo-
controlled study. [141]
However, if the only beneficial effect of preemptive analgesic efforts was that of reducing the amount of
supplemental opioid required postoperatively, the clinical usefulness of these efforts would be quite limited in a
cost-conscious medical environment. Long-term pain reduction and the prevention of chronic pain, on the other
hand, are far more important and potentially cost-effective goals. Evidence is accumulating of long-term
consequences after occurrence of unrelieved acute pain. Additionally, controlled clinical studies have now
[142] [143]
reported reduced chronic pain and improved function after preemptive analgesic interventions. Obata and [144] [145]
associates examined the effect of preincisional versus postoperative epidural local anesthetic blockade in a
[146]
randomized, double-blinded study of post-thoracotomy pain. They reported a significantly reduced incidence of
post-thoracotomy pain at 6 months of follow-up when continuous epidural blockade was instituted before incision.
Directions for further clinical study depend on preliminary investigations employing animal models. Unfortunately,
existing animal models for pain studies imperfectly mimic human chronic pain states. Further, inability to control [147]
the intensity of the stimulus or the confounding effects of anesthesia, or to ensure sufficient afferent blockade, add to
the technical challenges. The greatest limitation, however, may be the inability to predict which subjects are
[119] [148] [149]
likely to go on to develop chronic sequelae.
It has been a widespread belief, despite the paucity of significant supporting evidence, that certain personality traits
may be predisposing factors in the development of chronic neuropathic pain. However, there is considerable
evidence, based on experimental animal studies, to support a heritable basis for some neurologic conditions,
including neuropathic pain. Mailis and Wade have identified HLA antigens associated with RSD in women
[66] [67] [150] [68]
who failed to respond to sympathetic blocks. They believe that the gene conferring susceptibility to RSD may be
located on or near the MHC (major histocompatibility complex) region of the short arm of chromosome 6. The
ability to identify patients predisposed to neuropathic conditions would represent a tremendous advance, guiding
both further study of the condition as well as judicious use of treatment resources. Nevertheless, the most dramatic
application may rely on the precise description of the responsible gene or genes, thus permitting future gene therapy
to promote physiologic modulation through altered expression of that gene. [151]
Treatment of Chronic Post-Traumatic Pain
Frequently encountered post-traumatic chronic pain syndromes are the so-called whiplash injury and CRPS type 1
(RSD). Although evidence-based outcome studies are generally lacking with respect to regional anesthesia and
chronic pain, well-controlled trials have been performed for these two maladies and are worthy of mention. In both
cases, specific entry criteria predicted successful outcome.
Lord and colleagues reported that chronic cervical-zygapophyseal joint pain after whiplash injury is responsive to
[152]
a specific regional anesthetic treatment strategy using radiofrequency ablation. First, prognostic medial branch
blocks were employed in a double-blinded, placebo-controlled fashion to select appropriate study subjects. Then,
subjects were randomized in a double-blinded fashion into either active or sham treatment groups. This careful
screening process was rewarded when subjects in the active group experienced long-lasting reduction in pain. Hord
and coworkers treated patients who had CRPS type 1 (RSD) with intravenous regional bretylium and lidocaine
[153]
and demonstrated the effectiveness of this combination in a double-blinded, randomized trial. Patient selection
criteria included responsiveness to sympathetic block with concurrent abnormalities in response to cold stress testing.
Kingery, in a review of controlled trials for neuropathic pain, also suggested support for this technique, as well as
[154]
limited support for the use of epidural clonidine.
Obtaining evidence for the efficacy of sympathectomy in the treatment of patients with chronic pain is confounded
by difficulties in selecting appropriate patients. Careful entry criteria are generally lacking in most studies, and many
failures are probably secondary to misdiagnosis. Although some authorities have suggested a blinded
[155]
phentolamine test as prognostic, it can be shown experimentally that sympathetic blockade can reduce pain in
animal models that are unresponsive to phentolamine. Conversely, phentolamine may relieve pain that is resistant
[156]
1098
to permanent sympathectomy. As in the captioned studies described earlier, carefully conducted double-blinded,
placebo-controlled, prognostic sympathetic blocks may be most suitable for selection of appropriate candidates for
sympathectomy.
Recapitulation
Use of regional anesthesia clearly improves patient outcome after chest wall trauma. Improved functional outcomes
have also been demonstrated in patients who were treated with several other post-traumatic applications using nerve
blocks. Evidence continues to accumulate for the notion that effective blockade of acute pain with regional analgesia
prevents the development of chronic pain and improves long-term functional outcome. At present, however, there
are few outcome studies of sufficient quality to support the general use of regional analgesia for trauma as a
standard of practice. Consequently, this chapter provides more questions than answers. Numerous investigators have
focused on the superior analgesia provided by regional anesthesia. However, the most compelling rationale for the
use of regional anesthesia is provided by the prompt restoration of physical functioning, the reduction in morbidity,
and the prevention of delayed post-traumatic sequelae that have been observed in subjects treated with regional
anesthesia in the few available studies. Additional well-controlled clinical trials using prospective, randomized,
double-blinded designs to examine specific outcomes are needed.
REFERENCES
1. APS Bulletin. American Pain Society, 7, 1997.
2. Agency for Health Care Policy and Research: Acute pain management: Operative or medical procedures and trauma, Rockville, Maryland,
1989.
3. The necessity for early evaluation and treatment of the chronic pain patient: A consensus statement from the American Academy of Pain
Medicine. Clin J Pain 13, 1997.
4. International Association for the Study of Pain: Management of Acute Pain: A Practical Guide. Seattle, IASP Publications, 1992.
5. Myles PS, Bain DL, Johnson F, et al: Is anaesthesia evidence-based? A survey of anaesthetic practice. Br J Anaesth 82:591–595, 1999.
6. DeLeo JA, Yezierski RP: The role of neuroinflammation an neuroimmune activation in persistent pain. Pain 90:1–6, 2001.
7. Moller IW, Rem J, Brandt MR, et al: Effect of posttraumatic epidural analgesia on the cortisol and hyperglycemic response to surgery. Acta
8. Brandt MR, Fernades A, Mordhorst R, et al: Epidural analgesia improves postoperative nitrogen balance. Br Med J 1:1106–1108, 1978.
9. Yokoyama M, Natatsuka H, Itano Y, Hirakawa M: Stellate ganglion block modifies the distribution of lymphocyte subsets and natural-killer
cell activity. Anesthesiology 92:109–115, 2000.
10. Coggeshall RE, Carlton SM: Evidence for an inflammation-induced change in the local glutamatergic regulation of postganglionic sympathetic
efferents. Pain 83:163–168, 1999.
11. Liu
T, van Rooijen N, Tracey DJ: Depletion of macrophages reduces axonal degeneration and hyperalgesia following nerve injury. Pain
86:25–32, 2000.
12. Cui
J-G, Holmin S, Mathiesen T, et al: Possible role of inflammatory mediators in tactile hypersensitivity in rat models of mononeuropathy.
Pain 88:239–248, 2000.
13. Hartrick CT: www.neuropathic_pain.yourmd.com [unpublished data].
14. Moriwaki K, Yuge O, Tanaka H, et al: Neuropathic pain and prolonged regional inflammation as two distinct symptomatological components
in complex regional pain syndrome with patchy osteoporosis—a pilot study. Pain 72:277–282, 1997.
15. Johnson WC: Postoperative ventilatory performance: Dependence upon surgical incision. Ann Surg 41:615–619, 1975.
16. Bulger EM, Arneson MA, Mock CN, et al: Rib fractures in the elderly. J Trauma 48:1040–1046, 2000.
17. O'Kelly E, Garry B: Continuous pain relief for multiple fractured ribs. Br J Anaesth 53:987–991, 1981.
18. Murphy DF: Intercostal nerve blockade for fractured ribs and postoperative analgesia. Reg Anesth 8:151–153, 1983.
19. RoccoA, Reiestad F, Gudman J, et al: Intrapleural administration of local anesthetics for pain relief in patients with multiple rib fractures. Reg
Anesth 12:10–14, 1987.
20. Lee VC, Abram SE: Interpleural administration of bupivacaine for post-thoracotomy analgesia. Anesthesiology 66:586, 1987.
1099
21. Dittman M, Keller R, Wolff G: A rationale for epidural analgesia in the treatment of multiple rib fractures. Intensive Care Med 4:193, 1976.
22. Johnson IR, McCaughey GJ: Epidural morphine: A method of management of multiple fractured ribs. Anaesthesia 35:155, 1980.
23. Dittman M, Steenblock G, Kranzlin M, et al: Epidural analgesia or mechanical ventilation for multiple fractures. Intensive Care Med 8:89–92,
1982.
24. Spence AA: Pulmonary changes after surgery. Reg Anesth 7(Suppl):S119–S121, 1982.
25. Bromage PR, Camporesi E, Chestnut D: Epidural narcotics for postoperative analgesia. Anesth Analg 59:473–480, 1980.
26. BenhamouD, Samii K, Noviant Y: Effect of analgesics on respiratory muscle function after upper abdominal surgery. Acta Anaesthesiol
Scand 27:22–25, 1983.
27. Rybro
L, Schurizer BA, Peterson TK, et al: Postoperative analgesia and lung function: A comparison of intramuscular with epidural morphine.
28. Rawal N, Sjostrand UH, Dahlstrom B, et al: Epidural morphine for postoperative pain relief: A comparative study with intramuscular narcotic
and intercostal nerve block. Anesth Analg 61:93–98, 1982.
29. MankikianB, Cantineau JP, Bertrand M, et al: Improvement of diaphragmatic function by a thoracic extradural block after upper abdominal
30. Ullman DA, Fortune JB, Greenhouse BB, et al: The treatment of patients with multiple rib fractures using continuous thoracic epidural
narcotic infusion. Reg Anesth 14:43–47, 1989.
31. RyanMoon M, Luchette FA, Gibson SW, et al: Prospective, randomized comparison of epidural versus parenteral opioid analgesia in thoracic
trauma. Ann Surg 229:684–692, 1999.
32. Ballantyne
meta-analysis of randomized, controlled trials. Anesth Analg 86:598–612, 1998.
33. Shinohara
K, Iwama H, Akama Y, et al: Interpleural block for patients with multiple rib fractures: Comparison with epidural block. J Emerg
Med 12:441–446, 1994.
34. Bridenbaugh PO: Anesthesia and influence on hospitalization time. Reg Anesth 7(Suppl):S151–S155, 1982.
35. Carrell ED, Eyring EJ: Intravenous regional anesthesia for childhood fractures. J Trauma 11:301, 1971.
36. Abbaszadegan H, Jonsson U: Regional anesthesia preferable for Colle's fracture. Acta Orthop Scand 61:348–349, 1990.
37. Kendall
JM, Allen P, Younge I, et al: Haematoma block or Bier's block for Colles' fracture reduction in the accident and emergency
department—which is best? J Accid Emerg Med 14:352–356, 1997.
38. Wardrope J, Flowers M, Wilson DH: Comparison of local anaesthetic techniques in the reduction of Colles' fracture. Arch Emerg Med 2:67–
72, 1985.
39. Heffington
CA, Thompson RC Jr: The use of interscalene block anesthesia for manipulative reduction of fractures and dislocations of the
upper extremities. J Bone Joint Surg Am 55:83–86, 1973.
40. Hughes TJ, Desgrand DA: Interscalene block for Colles' fracture. Anaesthesia 38:149–151, 1983.
42. Hartrick CT: Pain due to trauma including sports injuries. Pain Digest 8:237–259, 1998.
43. Nawal N, Hylander J, Allvin R, et al: Postoperative patient controlled regional anesthesia at home. Reg Anesth 22:S82, 1997.
44. Iskandar H, Rakotondriamihary S, Dixmerias F, et al: Analgesia using continuous axillary block after surgery of severe hand injuries: Self-
administration versus continuous injection. Ann Fr Anesth Reanim 17:1099–1103, 1998.
45. Berry FR: Analgesia in patients with fractured shaft of femur. Anaesthesia 32:576, 1977.
46. GrossbardGD, Love BRT: Femoral nerve block: A simple and safe method of instant analgesia for femur fractures in children. Aust N Z J
Surg 49:592, 1979.
47. Tondare AS: Femoral nerve block for fractured shaft of femur. Can Anaesth Soc J 53:1055–1058, 1982.
48. Rosenblatt RM: Continuous femoral anesthesia for lower extremity surgery. Anesth Analg 59:631–633, 1980.
1100
49. WinnieAP, Ramamurthy S, Durani Z: The inguinal perivascular technique of lumbar plexus anesthesia: The 3-in-1 block. Anesth Analg
52:989, 1973.
50. Schultz
P, Anker-Moller E, Dahl JB, et al: Postoperative pain treatment after open knee surgery: Continuous lumbar plexus block with
bupivacaine versus epidural morphine. Reg Anesth 16:34–37, 1991.
51. Dalens
B, Vanneuville G, Tanguy A: Comparison of the fascia iliaca compartment block with the 3-in-1 block in children. Anesth Analg
69:705–713, 1989.
52. Chayden D, Nathan H, Chayden M: The psoas compartment block. Anesthesiology 45:95, 1976.
53. Parker MJ, Griffiths R, Appadu BN: Nerve blocks (subcostal, lateral cutaneous, femoral, triple, psoas) for hip fractures. Cochrane Database
Syst Rev 1, 2001.
54. Parker
MJ, Unwin SC, Handoll HHG, et al: General versus spinal/epidural anaesthesia for surgery for hip fractures in adults. Cochrane
Database of Syst Rev 1, 2001.
55. TamsenA, Sjoestroem S, Hartvig P: The Uppsala experience of patient-controlled analgesia. In Foley KM, Inturrisi CE (eds): Advances in
Pain Research and Therapy, vol 8. New York, Raven Press, 1986.
56. RushDS, Frame SB, Bell RM, et al: Does open fasciotomy contribute to mortality after acute lower extremity ischemia and revascularization?
J Vasc Surg 10:343–350, 1989.
57. Hartrick CT: Managing the difficult pain patient. In Raj P, Erdine S, Niv D, Raja S (eds): Management of Pain—a World Perspective. Bologna,
Monduzzi Editore, 1995.
58. Montgomery CJ, Ready LB: Epidural opioid analgesia does not obscure diagnosis of compartment syndrome resulting from prolonged
lithotomy position. Anesthesiology 75:541–543, 1992.
59. Martin JT: Compartment syndromes: Concepts and perspectives for the anesthesiologist. Anesth Analg 75:275–283, 1992.
60. Beerle BJ, Rose RJ: Lower extremity compartment syndrome from prolonged lithotomy position not masked by epidural bupivacaine and
fentanyl. Reg Anesth 18:189–190, 1993.
61. Capdevila X, Barthelet Y, Biboulet P, et al: Effects of perioperative analgesic technique on the surgical outcome and duration of rehabilitation
after major knee surgery. Anesthesiology 91:8–15, 1999.
62. Hartrick CT, Green P, Kovan J: Preoperative sustained-release epidural morphine improves discharge ambulatory tolerance following total
knee arthroplasty. Reg Anesth Pain Med 26:S24, 2001.
63. Raj
PP, Knarr D, Vigdorth E, et al: Difference in analgesia following epidural blockade in patients with postoperative or chronic low back pain.
Pain 34:21–27, 1988.
64. Mogensen T, Scott NB, Lund C, et al: The roles of acute and chronic pain in regression of sensory analgesia during continuous epidural
bupivacaine infusion. Anesth Analg 67:737–740, 1988.
65. Inbal R, Devor M, Tuchendler O, et al: Autotomy following nerve injury: Genetic factors in the development of chronic pain. Pain 9:327–337,
1980.
66. Devor M, Raber P: Heritability of symptoms in an experimental model of neuropathic pain. Pain 42:51–67, 1990.
67. Wiesenfeld-Hallin
Z, Hao J-X, Xu X-J, et al: Genetic factors influence the development of mechanical hypersensitivity, motor deficits and
morphological damage after transient spinal cord ischemia in the rat. Pain 55:235–241, 1993.
68. Mailis
A, Wade J: Profile of Caucasian women with possible genetic predisposition to reflex sympathetic dystrophy: A pilot study. Clin J Pain
10:210–217, 1996.
69. Dworkin RH: Which individuals with acute pain are most likely to develop a chronic pain syndrome? Pain Forum 6:127–136, 1997.
70. Bach S, Noreng MF, Tjellden NU: Phantom limb pain in amputees during the first 12 months following limb amputation, after preoperative
lumbar epidural blockade. Pain 33:297–301, 1988.
71. Kroner K, Krebs B, Skov J, et al: Immediate and long-term phantom breast syndrome after mastectomy: Incidence, clinical characteristics and
relationship to premastectomy breast pain. Pain 36:327–334, 1989.
72. Jensen TS, Krebs B, Nielsen J, et al: Immediate and long-term phantom limb pain in amputees: Incidence, clinical characteristics and
relationship to preamputation limb pain. Pain 21:267–278, 1985.
73. Weiss SA, Lindell B: Phantom limb pain and etiology of amputation in unilateral lower extremity amputees. J Pain Symptom Manage 11:3–17,
1996.
74. Philips HC, Berkowitz J: The prevention of chronic pain and disability: A preliminary investigation. Behav Res Ther 29:443–450, 1991.
1101
75. GatchelRJ, Polatin PB, Kinney RK: Predicting outcome of chronic back pain using clinical predictors of psychopathology: A prospective
analysis. Health Psychol 14:415–420, 1995.
76. Gatchel RJ, Polatin PB, Mayer TG: The dominant role of psychosocial risk factors in the development of chronic low back pain disability.
Spine 20:2702–2709, 1995.
77. CoderreTJ, Katz J, Vaccarino AL, et al: Contribution of central neuroplasticity to pathological pain: Review of clinical and experimental
evidence. Pain 52:259–285, 1993.
78. Dannenberg
AL, Needle S, Mullady D, et al: Predictors of injury among 1638 riders in a recreational long-distance bicycle tour. Am J Sports
Med 24:747–753, 1996.
79. Heir
T, Glomsaker P: Epidemiology of musculoskeletal injuries among Norwegian conscripts undergoing basic military training. Scand J Med
Sci Sports 6:186–191, 1996.
80. Heir T, Eide G: Age, body composition, aerobic fitness and health condition as risk factors for musculoskeletal injuries in conscripts. Scand J
Med Sci Sports 6:222–227, 1996.
81. Cowan DN, Jones BH, Frykman PN, et al: Lower limb morphology and risk of overuse injury among male infantry trainees. Med Sci Sports
Exerc 28:945–952, 1996.
82. Bennell KL, Crossley K: Musculoskeletal injuries in track and field: Incidence, distribution and risk factors. Aust J Sci Med Sport 28:69–75,
1996.
83. Bennell
KL, Malcolm SA, Thomas SA, et al: Risk factors for stress fractures in track and field athletes: A twelve-month prospective study. Am
J Sports Med 24:810–818, 1996.
84. Inklaar H, Bol E, Schmikli SL, et al: Injuries in male soccer players: Team risk analysis. Int J Sports Med 17:229–234, 1996.
85. Lysens
RJ, Ostyn MS, Vanden Auweele Y, et al: The accident-prone and overuse-prone profiles of the young athlete. Am J Sports Med
17:612–619, 1989.
86. Sola A: Upper-extremity pain. In Wall PD, Melzack R, eds: Textbook of Pain. New York, Churchill-Livingstone, 1984.
87. Cooper DE, DeLee JC, Ramamurthy S: Reflex sympathetic dystrophy of the knee: Treatment using continuous epidural anesthesia. J Bone
Joint Surg 71:365–369, 1989.
88. Cousins MJ: Acute pain and the injury response: Immediate and prolonged effects. Reg Anesth 14:162–179, 1989.
89. Perkins FM, Kehlet H: Chronic pain as an outcome of surgery: A review of predictive factors. Anesthesiology 93:1123–1133, 2000.
90. Stulz
P, Pfieffer KM: Peripheral nerve injuries resulting from common surgical procedures in the lower portion of the abdomen. Arch Surg
117:324–327, 1982.
91. Hartrick CT: Thermographic evaluation of postsurgical groin pain. Mich Osteo J 52:20–24, 1987.
92. Hitchcock E, Alvarez RM: Incisional pain. Clin J Pain 4:205–208, 1988.
93. MelzackR, Abbott FV, Zackon W, et al: Pain on a surgical ward: A survey of the duration and intensity of pain and the effectiveness of
medication. Pain 29:67–72, 1987.
94. AidaS, Fujihara H, Taga K, et al: Involvement of presurgical pain in preemptive analgesia for orthopedic surgery: A randomized double blind
study. Pain 84:169–173, 2000.
95. Cousins MJ: Acute pain and the injury response: Immediate and prolonged effects. Reg Anesth 14:162–179, 1989.
96. Feldman DE: Inhibition and plasticity. Nat Neurosci 3:303–304, 2000.
97. Koch C, Segev I: The role of single neurons in information processing. Nat Neurosci 3S:1171–1177, 2000.
98. Crile GW: The kinetic theory of shock and its prevention through anoci-association (shockless operation). Lancet 185:7–16, 1913.
99. Woolf CJ: Evidence for a central component of postinjury pain hypersensitivity. Nature 308:686–688, 1983.
100. Jahangiri
M, Bradley JWP, Jayatunga AP, et al: Prevention of phantom limb pain after major lower limb amputation by epidural infusion of
diamorphine, clonidine and bupivacaine. Ann R Coll Surg Engl 76:324–326, 1994.
101. Schug SA, Burrell R, Payne J, et al: Pre-emptive epidural analgesia may prevent phantom limb pain. Reg Anesth 20:256, 1995.
102. Nikolajsen L, Ilkjaer S, Christensen JH, et al: Randomised trial of epidural bupivacaine and morphine in prevention of stump and phantom
1102
pain in lower-limb amputation. Lancet 350:1353–1357, 1997.
103. Davies SN, Lodge D: Evidence for involvement of N-methylaspartate receptors in `wind-up' of class 2 neurons in the dorsal horn of the rat.
Brain Res 424:402–406, 1987.
104. Devor M, Wall PD: Effect of peripheral nerve injury on receptive fields of cells in the cat spinal cord. J Comp Neurol 199:277–291, 1981.
105. Woolf
CJ, King AK: Dynamic alterations in the cutaneous mechanoreceptive fields of dorsal horn neurons in the rat spinal cord. J Neurosci
10:2717–2726, 1990.
106. Woolf CJ, Shortland P, Coggeshall RE: Peripheral nerve injury triggers central sprouting of myelinated afferents. Nature 355:75–78, 1992.
107. Okamoto M, Yoshimura M, Baba H, et al: Patch clamp analysis of synaptic plasticity in rat substantia gelatinosa neurons following sciatic
nerve transection. Anesthesiology 85:A720, 1996.
108. Iadarola MJ, Brady LS, Draisci G, et al: Enhancement of dynorphin gene expression in spinal cord following experimental inflammation:
Stimulus specificity, behaviour parameters and opioid receptor binding. Pain 35:313–326, 1988.
109. Nahlin RL, Ren K, DeLeon M, et al: Primary sensory neurons exhibit altered gene expression in a rat model of neuropathic pain. Pain 58:95–
108, 1994.
110. Dun NJ, Dun SL, Forstermann U, et al: Nitric oxide synthetase immunoreactivity in the rat spinal cord. Neurosci Lett 147:217–220, 1992.
111. Meller ST, Gebbart GF: Nitric oxide (NO) and nociceptive processing in the spinal cord. Pain 52:127–136, 1993.
112. Haley
JE, Sullivan AF, Dickenson AH: Evidence of N-methyl-D-aspartate receptor involvement in prolonged chemical nociception in the rat.
Brain Res 518:218–226, 1990.
113. Woolf CJ, Thompson SWN: The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor
activation: Implications for treatment of post-injury pain hypersensitivity states. Pain 44:293–299, 1991.
114. Seltzer
Z, Cohn S, Ginzburg R, et al: Modulation of neuropathic pain behavior in rats by spinal disinhibition and NMDA receptor blockade of
injury discharge. Pain 45:69–75, 1991.
115. Arendt-Nielsen L, Petersen-Felix S, Fischer M, et al: The effect of N-methyl-D-aspartate antagonist (ketamine) on single and repeated
nociceptive stimuli: A placebo-controlled experimental human study. Anesth Analg 81:63–68, 1995.
116. Elliot KJ, Brodsky M, Hynansky AD, et al: Dextromethorphan suppresses both formalin-induced nociceptive behavior and the formalin-
induced increase in spinal cord c-fos mRNA. Pain 61:401–409, 1995.
117. MunglaniR, Bond A, Smith GD, et al: Changes in neuronal markers in a mononeuropathic rat model: Relationship between neuropeptide Y,
preemptive drug treatment and long-term mechanical hyperalgesia. Pain 63:21–31, 1995.
118. Hartrick
CT, Wise JJ, Patterson JS: Preemptive intrathecal ketamine delays mechanical hyperalgesia in the neuropathic rat. Anesth Analg
86:557–560, 1998.
119. Woolf
CJ, Chong M-S: Preemptive analgesia—treating postoperative pain by preventing the establishment of central sensitization. Anesth
Analg 77:362–379, 1993.
120. LaMotte RH, Shaine CN, Simone DA, et al: Neurogenic hyperalgesia: Psychophysical studies of underlying mechanisms. J Neurophysiol
66:190–211, 1991.
121. Dickenson AH, Sullivan AF: Peripheral origins and central modulation of subcutaneous formalin-induced activity of rat dorsal horn neurones.
Neurosci Lett 83:207–211, 1987.
122. Abbadie C, Taylor BK, Peterson MA, Bausbaum AI: Differential contribution of the two phases of the formalin test to the pattern of c-fos
expression in the rat spinal cord: Studies with remifentanil and lidocaine. Pain 69:101–110, 1997.
123. Dickenson AH, Sullivan AF: Differential effects of excitatory amino acid antagonists on dorsal horn nociceptive neurons in the rat. Brain Res
506:31–39, 1990.
124. Dahl
BJ, Brennum J, Arendt-Nielsen L, et al: The effect of pre- versus postinjury infiltration with lidocaine on thermal and mechanical
hyperalgesia after heat injury to the skin. Pain 53:43–51, 1993.
125. Sotgiu ML, Castagna A, Lacerenza M, et al: Pre-injury lidocaine treatment prevents thermal hyperalgesia and cutaneous thermal
abnormalities in a rat model of peripheral mononeuropathy. Pain 61:3–10, 1995.
126. Tverskoy
M, Cozacov C, Ayache M, et al: Postoperative pain after inguinal herniorrhaphy with different types of anesthesia. Anesth Analg
70:29–35, 1990.
127. Shir Y, Raja SN, Frank SM: The effect of epidural versus general anesthesia requirements in patients undergoing radical prostatectomy.
1103
128. Ejlersen E, Andersen HB, Eliasen K, et al: A comparison between preincisional and postincisional lidocaine infiltration and postoperative
pain. Anesth Analg 74:495–498, 1992.
129. Bugedo GJ, Carcamo CR, Mertens RA, et al: Preoperative percutaneous ilioinguinal and iliohypogastric nerve block with 0.5% bupivacaine
for post-herniorrhaphy pain management in adults. Reg Anesth 15:130–133, 1990.
130. Pedersen JL, Crawford ME, Dahl JB, et al: Effect of preemptive nerve block on inflammation and hyperalgesia after human thermal injury.
131. Negre I, Gueneron JP, Jamali SJ, et al: Preoperative analgesia with epidural morphine. Anesth Analg 79:298–302, 1994.
132. Tverskoy
M, Oz Y, Isakson A, et al: Preemptive effect of fentanyl and ketamine on postoperative pain and wound hyperalgesia. Anesth Analg
78:205–209, 1994.
133. Hannibal K, Galatius H, Hansen A, et al: Preoperative wound infiltration with bupivacaine reduces early and late opioid requirement after
hysterectomy. Anesth Analg 83:376–381, 1996.
134. WangJ-J, Ho S-T, Lui H-S, et al: The effect of spinal versus general anesthesia on postoperative pain and analgesic requirements in patients
undergoing lower abdominal surgery. Reg Anesth 21:281–286, 1996.
135. Katz
J, Clairoux M, Kavanagh BP, et al: Pre-emptive lumbar epidural anaesthesia reduces postoperative pain and patient-controlled morphine
consumption after lower abdominal surgery. Pain 59:395–403, 1994.
136. Pasqualucci
A, De Angelis V, Contardo R, et al: Preemptive analgesia: Intraperitoneal local anesthetic in laparoscopic cholecystectomy: A
randomized, double-blind, placebo-controlled study. Anesthesiology 85:11–20, 1996.
137. Katz
J, Kavanagh BP, Sandler AN, et al: Preemptive analgesia: Clinical evidence of neuroplasticity contributing to postoperative pain.
138. HelmySAK, Bali A: The effect of the preemptive use of a the NMDA receptor antagonist dextromethorphan on postoperative analgesic
requirements. Anesth Analg 92:739–744, 2001.
139. Choe H, Choi Y-S, Kim Y-H, et al: Epidural morphine plus ketamine for upper abdominal surgery: Improved analgesia from preincisional
versus postincisional administration. Anesth Analg 84:560–563, 1997.
140. Rockermann MG, Seeling W, Bischof C, et al: Prophylactic use of epidural mepivacaine/morphine, systemic diclofenac, and metamizole
reduces postoperative morphine consumption after major abdominal surgery. Anesthesiology 84:1027–1034, 1996.
141. WuCT, Yeh CC, Yu JC, et al: Pre-incisional epidural ketamine, morphine and bupivacaine combined with epidural and general anesthesia
provides pre-emptive analgesia for upper abdominal surgery. Acta Anaesthesiol Scand 44:63–68, 2000.
142. Grunau VE, Whitfield MF, Petrie JH: Pain sensitivity and temperamentin extremely low-birth-weight premature toddlers and pre-term and
full-term controls. Pain 58:341–346, 1994.
143. Katz J, Jackson M, Kavanagh BP, et al: Acute pain after thoracic surgery predicts long-term post-thoracotomy pain. Clin J Pain 12:50–55,
1996.
144. Gwirtz KH, Beckes KA, Maddock RP, et al: Subarachnoid opioid analgesia reduces long-term postsurgical pain after nephrectomy. Reg
Anesth 19:98–103, 1994.
145. Gottschalk A, Smith DS, Kennedy S, et al: The role of preemptive analgesia in recovery from major lower abdominal surgery. Anesthesiology
85:A746, 1996.
146. Obata
H, Saito S, Fujita N, et al: Epidural block with mepivacaine before surgery reduces long-term post-thoracotomy pain. Can J Anaesth
46:1127–1132, 1999.
147. Coyle DE: Efficacy of animal models for neuropathic pain. Pain Digest 6:7–20, 1996.
148. Yashpal K, Katz J, Coderre TJ: Effects of preemptive or postinjury intrathecal local anesthesia on persistent nociceptive responses in rats:
Confounding influences of peripheral inflammation and the general anesthetic regimen. Anesthesiology 84:1119–1128, 1996.
149. Kissin I: Preemptive analgesia: Why its effect is not always obvious. Anesthesiology 84:1015–1019, 1996.
150. Mogil
JS, Wilson SG, Bon K, et al: Heritability of nociception II. “Types” of nociception revealed by genetic correlation analysis. Pain
80:83–93, 1999.
151. Iadarola MJ: Functional analysis of cloned genes and regulation of gene expression: Examples from pain related studies. In Campbell JN (ed):
Pain 1996—an Updated Review. Seattle, IASP Press, 1996.
152. Lord SM, Barnsley L, Wallis BJ, et al: Percutaneous radio-frequency neurotomy for chronic cervical zygapophyseal-joint pain. N Engl J Med
335:1721–1726, 1996.
1104
153. Hord AH, Rooks MD, Stephens BO, et al: Intravenous regional bretylium and lidocaine for treatment of reflex sympathetic dystrophy: A
randomized, double-blind study. Anesth Analg 74:818–821, 1992.
154. Kingery WS: A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndromes. Pain 72:123–
139, 1997.
155. Raja SN, Campbell JN: Risk-benefit ratio for surgical sympathectomy: Dilemmas in clinical decision making. J Pain 1:261–264, 2000.
156. Park SK, Chung K, Chung JM: Effects of purinergic and adrenergic antagonists in a rat model of painful peripheral neuropathy. Pain 87:171–
179, 2000.
1105
Section VII Chapter 48 - Efficacy and Outcome of Regional Anesthesia Techniques in Obstetrics
Chapter 48 - Efficacy and Outcome of Regional Anesthesia

Techniques in Obstetrics
BRANKO M. WEISS
ELI ALON
ROBERT S. F. McKAY
Outcome and “Seven Pillars of Quality”
Avedis Donabedian asserted that the “seven pillars,” or attributes, that define quality in healthcare are (1) efficacy
[1] [1]
(ability to bring improvements); (2) effectiveness (degree to which the care could attain the level of improvement
that studies of efficacy have established as attainable in the clinical practice); (3) efficiency (if two approaches are
equally efficacious or effective, the less costly one is the more efficient); (4) optimality (relationship between the
health benefit and the cost of care); (5) acceptability (care adapted to the wishes, expectations, and values of patients
and their families, who expect and deserve accessibility of care, an effective patient-practitioner relationship,
amenities, and individual preferences as to the effects and the costs of care); (6) legitimacy (conformity to the social
preferences or features that are important to individuals are of social concern; now, a road to conflicts of interest
opens widely); and (7) equity (fair distribution of care and its benefits from the individual and social points of view).
Donabedian’s conclusion was that the patient and the social preferences must be taken into account in assessing and
ensuring quality. In the real world, the seven pillars of quality may look like an endless conflict of interest. The
conflicts involve all components, ranging from patients and families, insurance companies, and medical institutions
to the industry, economists, politicians, and society as a whole. In this generation, the healthcare system may not
reach an efficacious, effective, efficient, optimal, and patient-acceptable (with all attributes) level that can
simultaneously fulfill both individual and social legitimacy and equity. Otherwise, the maternal mortality rate in the
United States, France, the Netherlands, and other developed countries would be a concern of the past, and the
relative death risk would not be higher for ethnic minorities than for the population of the local majority. [2] [3] [4]
Factors involved in the measurable differences in mortality rates among black, Hispanic, and white pregnant women
in the United States would be identified and eliminated. The proportion of cases of maternal death in which
[5]
substandard care is present would not remain constant at about 40% to 50% in the United Kingdom, a country with a
traditional triennial audit, known as the Confidential Enquiries into Maternal Death. An aspect of equity emerged [6]
from the report spanning 1994 to 1996. There was no evidence of any excess in substandard care for cases involving
death of the nonwhite women. In the United States, Australia, and, certainly, other countries, the rates of obstetric
[6]
and anesthetic intervention among women covered by private and public health insurance would not be, with similar
risk profiles, significantly higher in private hospitals. An editorial plea that begged, “Let’s not turn back the
[7] [8] [9]
clock to the dark ages of the leather wrists straps on the delivery beds, screaming women in pain, and various
intravenous or inhalational shots of analgesia,” would be unnecessary. The American College of Obstetricians and
[10]
Gynecologists (ACOG) would not need to repeat in a news release that “the last thing a woman needs to hear during
a painful labor is that her insurance company isn’t going to cover her epidural.” [11]
Evidence-Based Medicine: Epidemiologic Data versus Individual Healthcare
Measuring and improving the quality and outcome of healthcare have become high priorities. The collection and
interpretation of outcome in the healthcare system have been addressed from individual, institutional, and national
perspectives in both developed countries and less developed regions. The proper
[6] [9] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25]
identification and analysis of reliable evidence (evidence-searched and evidence-based medicine) became a complex
process, (over)loaded by methodological, statistical, and analytic difficulties, and unsolved controversies and
disagreements. The critical aspect of evidence-based medicine is the wide gap that exists between the
[22] [24] [26] [27] [28]
value of epidemiologic data for the population in general and applicability of these data to the healthcare
requirements of an individual patient. Some medical evidence may not be transferable (again, for various reasons
and without any trace of poor clinical practice) between the countries and institutions. Although the developed
countries have reached an almost uniform standard of healthcare, the cultural, social, religious, financial, traditional,
climatic, and political differences among them remain measurable and, occasionally, relevant.
Outcome is considered to denote favorable, adverse, or neutral changes of health status, integrating the physical,
psychological, emotional, and social consequences that occur after or during healthcare. Emphasizing positive
categories, outcome analysis looks for survival, longevity, activity, comfort, satisfaction, achievement and resilience,
and rapid, full restitution to productive business and social life. The medical, financial, political, and social
[12]
pressures are continually increasing, asking for real (or at least surrogate) improvements in healthcare. Not
1106
infrequently, a variety of soft, indirect, and biologically or chronologically remote variables (pseudo-outcome
variables) are presented as denoting outcome. Although it is easy to differentiate extremely poor from impeccably
excellent medical care, a variety of fine details make the definition of outcome rather complex. Frequently, financial,
performance, and clinical outcomes, or the patient’s perceived outcome, must be considered from the perspective of
the specific procedure, the medical institution, or the individual patient. The outcome variables may be [16] [17] [23] [24] [29]
divided, from the epidemiologic point of view, into traditional (morbidity, mortality rates) and nontraditional
(patient satisfaction, costs) categories and subcategories. The quality and outcome of healthcare in obstetrics
[24] [29]
look simple only at first sight; in an individual woman, and particularly in a larger number of subjects, the exact
definition may depend on the focus of interest, subjective interpretations and expectations, education, and previous
experience, as well as on the construction of questionnaires (called psychometric measurements, if multiple items
are included and properly analyzed). [29]
David Gaba claimed, following the school of thought of Arthur Keats, that traditional epidemiologic studies are
[30] [31]
insufficient for assessment of the incidence of adverse events related to anesthesia. The errors, mistakes, and [30]
system failures have continued to prevent reduction in negative outcomes related to anesthesia. For [30]
accomplishments in patient safety in anesthesiology, Gaba accentuated nontraditional investigation techniques that
analyze a small proportion of the events to glean the maximum amount of useful information, such as “critical
incident” analysis adapted from aviation, closed malpractice claims, and the Australian Incident Monitoring [14]
Study. Unfortunately, the trend in the quality assessment of anesthesia seems to be redirected (again) to the
[18]
collection of small and largely irrelevant incidents, errors, mishaps, short-term nonvital equipment failures, and
“abnormal” laboratory findings. The majority of such data are useless for conducting quality assessment at the
[18] [32]
institutional or national level. When reviewed individually, the collection and the data imply waste of time and
resources. Worse, they confuse the differentiation between “events without any relevance or consequences” (within
the bounds of reason) for the anesthesia practice and the critical incidents and near-miss events that constitute or
have real potential for anesthesia-related complications and negative outcomes.
Regional anesthesia and techniques of neural blockade present one of the most important aspects of modern clinical
anesthesiology and management of pain. Central neuraxial blockades for combatting the pain of labor, delivery, and
interventions postpartum became the single most important pillar of quality in obstetric anesthesia. The [33] [34] [35] [36]
regional anesthesia techniques in obstetrics (as elsewhere) are not free from complications, controversies, and
dissensions. The controversies originate from different sources and incentives, such as
[14] [24] [37] [38] [39] [40] [41] [42] [43] [44] [45]
improvements in medical knowledge, spread of new and reliable information (evidence), real or surrogate
technologic and pharmaceutical innovations, and increased or decreased financial and nonfinancial expenditure in
healthcare. They may reflect a changing quality of life or the fashionable trends involving both providers and
consumers in the healthcare system. Some attributes of quality and outcome in obstetric anesthesia have been
addressed repeatedly, but for many techniques and drugs, “hard” data are missing. The proper assessment of effects,
side effects, and complications, as well as their impact on the attributes of quality, remains frequently a matter of
subjective interpretation. Even if or when objective outcome studies address a specific topic, regional and national
interpretations keep the discussion open. Compared with regional anesthesia techniques, all other pharmacologic
and nonpharmacologic methods of pain relief in obstetrics are lagging far behind. Of course, all these alternative
avenues are a traditional part of obstetrics and obstetric anesthesia, involving certain attributes of quality. However,
they represent only compromises and alternatives to central neuraxial techniques. None are addressed here because
detailed reviews are available elsewhere. [35] [36] [46]
Maternal Outcome Related to Regional Anesthesia Techniques
MATERNAL MORTALITY
From the point of view of the modern healthcare system, it is relatively easy to consider anesthesia-related death as
just a marker or “sentinel event” (unusual, unexpected, and very rare outcome) and then assess the percentage of
“avoidable/preventable deaths” in a specific population or institution. Mortality data may be even dismissed as
highly problematic and unusable (distorted) indicators of outcome. Death “resulting” from anesthesia per se is [12] [31]
considered to have dropped dramatically over the past decades by a combination of various reasons and
“mechanisms.” Similar to the previous conclusions of Henrik Kehlet, the preliminary data from an overview of
[22] [42]
the randomized trials indicate—probably the best available outcome analysis for 2000 and beyond—that the use of
[24]
regional anesthesia techniques, compared with general anesthesia, was associated with risk of death reduced by 30%
and risk of severe complications reduced by 30% to 60%. Despite the inherent methodologic and statistical [24]
difficulties and the caution required to interpret and extrapolate epidemiologic conclusions to the clinical practice,
the outcome differences remain much too high to be ignored.
1107
Pregnant women and new mothers die in all countries, and the rate of maternal deaths (or, better, the maternal
survival rate) could be considered one of the best indicators of the “quality of life” in a country or a region. In both
underdeveloped and undeveloped countries, the mortality rates exceed 50 to 100 cases or even 500 to 1000 cases per
100,000 maternities. It is assumed (an educated guess from the historical perspectives) that the main factors
[25] [47] [48]
and critical remedies that could lead to decline of maternal deaths in poor countries are improvements in maternal
care (easier to accomplish) more than improvements in the standards of living. Currently, pregnant women die in [49]
developed countries at the rate of 3 to 25 cases per 100,000 maternities. One analysis concluded [4] [5] [6] [13] [21] [50] [51] [52] [53] [54]
that the maternal mortality rate did not change substantially in Canada and the United States between 1982 and
1997. Other developed countries are reaching a plateau, and, in some, increased mortality rates are expected in the
[20]
near future because of the more advanced age of the pregnant population; regional differences within one country;
national, international, and intercontinental migration of the population; omnipresent “human factors and
preventable cases”; and improved data collection. The risks of maternal complications and death are specifically
increased by women’s greater age and parity, multiple gestations, preeclampsia, emergent cesarean delivery,
coincidence of lower socioeconomic status in local minorities and recent immigrants, and by various aspects of
substandard care. The “final” major causes of death are thromboembolism, extrauterine pregnancy
[4] [6] [21] [51] [52] [54] [55] [56] [57]
and bleeding, hypertension, and diseases involving the cardiovascular system and the central nervous system.
[50] [51] [52] [53] [58] [59] [60]
[5] [6] [13] [21]
Anesthesia-Related Maternal Deaths
The maternal mortality rate is decreasing, but it is still associated with or attributed to anesthetic care. An increasing
number of pregnant women are “treated” in one form or another by anesthesiologists. The number of anesthetic
interventions (anesthesia denominator) is increasing (changing) over time. The standard calculations, expressing
mortality rate as “per 100,000” maternities, deliveries, or live births and using the number of “anesthetic” deaths as
a percentage of the total, could present the real or distorted (favorably or unfavorably) rate of anesthesia-related
deaths. At a very low number of total cases, 1% to 13% of all direct maternal deaths are considered anesthesia
related In Massachusetts, the maternal mortality rate decreased from 50 cases to 10 cases per
[3] [5] [6] [13] [21] [22] [50] [51] [52] [58] [61] [62]
100,000 live births between 1954 and 1985, accompanied by a threefold decrease in anesthesia-related deaths. The [2]
primary causes were pulmonary aspiration during general anesthesia administered by face mask in the first decade,
cardiovascular collapse associated with regional anesthesia in the second decade, and in the third decade, all deaths
were associated with general anesthesia and tracheal intubation. The pattern of change and the causes of [63]
anesthetic-related death were almost identical in other countries, and certain similarities persist up to the present
time. In the United States, England, and Wales, the mortality rate directly associated with
[6] [13] [14] [21] [50] [52] [54] [61] [62]
anesthesia decreased to 17 cases per 100,000 in the period from 1988 to 1990. In the United Kingdom, one [13] [52] [61]
case of anesthetic death was found in the 1994 to 1996 triennium, which made a negligent impact of anesthesia
(0.8%) on all direct maternal deaths. Hopkins and coworkers analyzed maternal mortality rates between 1979 and
[6] [5]
1992 in the United States. Pregnancy-induced hypertension explained, in part, the higher mortality rate in Hispanics
(10.3 per 100,000 live births) compared with non-Hispanic whites (6.0), but the highest mortality rate was found in
blacks (25.1). The rates of anesthesia-related death for pregnant white, Hispanic, and black women were 0.1 (3%),
0.3 (4%), and 0.7 (5%), respectively. A Swiss analysis from 1985 to 1994 showed a total maternal mortality rate
[5] [54]
of 6.7 per 100,000 live births. Four anesthesia-related deaths (all associated with general anesthesia and tracheal
intubation) represented a mortality rate of 0.5 per 100,000 or 9% of all direct deaths in the 10-year study period. [54]
Regional Anesthesia and Decreasing Anesthesia-Related Mortality Rate
Regional anesthesia techniques, by reducing the requirement for general anesthesia and tracheal intubation in
emergencies, have (combined with other, less visible factors) played a major role in decreasing anesthesia-
associated maternal deaths. In the analysis of anesthesia-related deaths during obstetric delivery, Hawkins
[52] [61] [62] [64]
and coworkers calculated that the maternal mortality rate decreased 2.5-fold (from 43 to
[61]
TABLE 48-1 -- ANESTHESIA-RELATED OBSTETRIC DEATHS IN THE UNITED STATES 1979-1990 *
General Anesthesia (n = 67) Regional Anesthesia (n = 33)

Cause of death (%)
Airway problems 73 0
Cardiac arrest 22 6
Local anesthetic toxicity 0 51
High spinal or epidural block 0 36
Overdosage 0 0
Anaphylaxis 0 0
1108
TABLE 48-1 -- ANESTHESIA-RELATED OBSTETRIC DEATHS IN THE UNITED STATES 1979-1990 *
General Anesthesia (n = 67) Regional Anesthesia (n = 33)

Unknown 5 6
†
Mortality risk of cesarean delivery
Case fatality rate
1979–1984 2.00 (1.77–2.27) 0.86 (0.19–0.94)
1985–1990 3.23 (2.59–4.93) 0.19 (0.18–0.20)
Risk ratio of general vs. regional anesthesia
1979–1984 0.23 (0.19–0.29) referent
1985–1990 1.67 (1.29–2.18) referent
Modified from Hawkins JL, Koonin LM, Palmer SK, Gibbs Cl’: Anesthesia-related deaths during obstetric delivery in the United States, 1979-
1990. Anesthesiology 86:277,1997. Reproduced with permission.
* Additional 29 cases occurred during "sedation" and unknown anesthetic technique.
†
Rate per 100,000 anesthetics (95% confidence interval).
17 cases per 100,000) in the United States between 1979 and 1990. The majority of deaths were related to cesarean
delivery (82%) and use of general anesthesia (52%). The predominant causes were airway/respiratory problems and
cardiac arrest with general anesthesia, and local anesthetic toxicity, high level of block, and cardiac arrest with
regional anesthesia ( Table 48-1 ). Deaths caused by local anesthetic toxicity decreased abruptly after 1984,
temporally related to the discontinuance of 0.75% bupivacaine from the obstetric anesthesia practice. The case
fatality rate for cesarean delivery with regional anesthesia was calculated to have decreased by a factor of 4.5
between 1979 to 1984 and 1985 to 1990. With general anesthesia, it increased by a factor of 1.6. The risk of death
has been 2.3-fold higher with general than with regional anesthesia until 1984 and almost 17-fold higher in the 1985
to 1990 period (see Table 48-1 ). These results, insufficient methodologic precision notwithstanding, became an
almost ironclad argument for regional and against general anesthesia in obstetrics. The authors attempted to define
the risk of death more precisely by including cesarean deliveries only to obtain the correct anesthesia denominators.
However, the combination of missing and incomplete data, estimates and extrapolations, based on surveys with 50%
returns, and underestimation of the number of general anesthetics exaggerated the risk between the two techniques. [61]
Hawkins and coworkers recognized the study limitations and suggested that the discrepancy in the mortality
[62] [61]
rates emerged from different indications and circumstances. General anesthesia may have been used primarily in
emergencies and in patients for whom regional block was difficult to administer (obesity) or was contraindicated
(coagulopathy, preeclampsia). After 1984, the abrupt decrease of mortality rate caused by local anesthetic toxicity
[61]
could be considered not only as temporally but also as causally related to the discontinuance of epidural 0.75%
bupivacaine from the obstetric anesthesia practice. “The high maternal mortality associated with unrecognized
intravenous injection of bupivacaine probably relates to the difficulties involved in resuscitating a parturient, not to
the greater intrinsic toxicity of bupivacaine in this population.” Because of the time delay, the cases entering the [65]
American Society of Anesthsiologists (ASA) closed claims project after 1995 might be expected to show a similar [14]
trend of decreased maternal mortality rate resulting from local anesthetic toxicity.
Risk Assessment of General versus Regional Anesthesia
The surveys of national and institutional obstetric anesthesia practice are showing an overall trend toward preferring
regional anesthesia techniques. However, the percentage of cases for elective, urgent, and emergent cesarean
delivery is varying widely among countries and among different-sized hospitals. The detailed [64] [66] [67] [68] [69] [70] [71] [72] [73]
analyses are missing and the absolute number of fatalities in the developed countries is very small. It seems that
anesthesia-associated maternal mortality could not be explicitly related to the proportion of deliveries managed with
general anesthesia. [4] [5] [6] [34] [50] [52] [61] [64] [66] [67] [68] [69] [71] [72] [73]
For various reasons, a direct comparison of obstetric regional and general anesthesia remains difficult or almost
impossible. The use of general anesthesia tends to be a priori associated with urgent or emergent conditions, failed
or refused regional anesthesia, and complicated pregnancy with coexisting diseases. These factors, either combined
or isolated, increase (even with experienced practitioners and institutions) the risk of complications and death. [61] [62] [74]
David Chestnut, in an editorial, analyzed the data of the Hawkins’ study and addressed a critical point in
[75] [76] [77] [78] [61]
obstetrics. “As long as obstetricians continue to ask anesthesiologists to provide anesthesia for emergency cesarean
section at a moment’s notice, it is unlikely we can reduce the general anesthesia-related mortality to zero.” In a [62]
retrospective study from Boston, the proportion of general anesthesia for cesarean delivery was found to have
[74]
decreased from 7% in 1990 to 4% in 1995, but the procedure was used in parturients with significantly more
1109
maternal diseases. The number of women who refused regional anesthesia increased slightly as did the rate of failed
regional (particularly, spinal) techniques. One maternal death resulting from failed intubation was documented
among 536 parturients who received general anesthetics. Human error, inexperience, and poor judgment are [74]
confounding factors that contribute to the maternal mortality rate. However, presuming that human error, [79]
inexperience, and poor judgment are evenly distributed in all obstetric cases, the core message of the Hawkins study
and other studies (higher risk of death from general anesthesia in obstetrics) must be taken into account. [6] [13] [14] [52] [61]
This risk assessment, cumulatively for the whole population, is a rough indicator of epidemiologic value only and
not an absolute parameter for the management of an individual case. Christopher Rout came to the conclusion that [64]
“there is epidemiologic evidence of an association between increased use of regional techniques and decreasing
maternal mortality.” In normal, healthy women undergoing elective cesarean delivery under the care of an
experienced anesthesiologist, “there is probably little difference between general and regional anesthesia in terms of
mortality risk. Nevertheless, collective experience suggests that the unpredictable complications of general
anesthesia are more likely to result in an adverse outcome compared with those occurring during regional
anesthesia.” Conversely, the practice of obstetric and anesthetic care is decisive. A combination of unfavorable
[64]
circumstances in the local process and structure of antenatal, medical, obstetric, anesthetic, and postanesthesia care,
without a specific focus on one or another anesthetic technique or drugs, may explain the vast majority of
anesthesia-associated maternal fatalities. In the 1994 to 1996 Confidential Enquiries in the United
[6] [13] [34] [52] [62] [64] [79] [80] [81]
Kingdom, the single maternal death directly attributed to anesthesia resulted from a massive overdose of several
drugs used for a combined spinal-epidural block. Indeed, to suggest that the regional technique per se was a factor
[6]
in this death would be absurd. The same report provided an analysis of “deaths associated with anaesthesia” in
[80]
women whose deaths were due to direct obstetric causes (such as eclampsia, amniotic fluid embolism, sepsis, or
bleeding) and preexisting concomitant diseases (such as severe cardiac failure, pulmonary hypertension, or
pheochromocytoma). Aspects of substandard care and lack of communication were identified and involved (in
[6]
various combinations) obstetric (dominant), medical, anesthetic, and peripartum intensive care. The “association
with anesthesia” was in some cases obvious, but in others it was poorly defined or even lacking ; at any rate, it [6]
would be absurd to blame or associate “general anesthesia” per se with these fatalities. The ASA task force
concluded that “the literature is insufficient to determine the relative risk of maternal death with general anesthesia
compared with other anesthetic techniques. However, the literature suggests that a greater number of maternal
deaths occur when general anesthesia is administered.” An additional insight on the topic is provided by the reports
[34]
describing maternal survival after amnio- or thromboembolism, massive postpartum bleeding, eclampsia, and [82] [83]
two cardiac arrests, cardiorespiratory arrest during cesarean delivery under epidural anesthesia or after combined
[84] [85]
spinal-epidural anesthesia. The reports highlight not only the specific management but also the core of the
[86]
prevention of anesthesia-related maternal deaths.
Maternal Mortality—Incident Reporting and Closed Claims Studies
Heathcliff Chadwick provided the 1985 to 1995 data from the ASA closed malpractice claims project, an ongoing
[14]
study of the United States insurance company liability files that are closed, and compared the obstetric and
nonobstetric files. Although the hard facts are lacking (insurance claims but not a total number of procedures and
complications are known), the study provided important data concerning the anesthetic outcome of pregnant women.
The most common injury in the files was death, which was found at a significantly lower rate in obstetric than in
nonobstetric files, in obstetric regional rather than obstetric general anesthesia cases ( Table 48-2 ), and after vaginal
(10%) more than cesarean (23%) delivery. It is of interest that maternal fatalities are completely missing in reports
[14]
from Australia and Canada. This absence of fatalities shows either an excellent standard of national anesthesia
[18] [87]
care, a different medicolegal system with different thresholds to trigger a malpractice claim, a different definition of
anesthesia-related and unrelated deaths, or an unreliable data collection and incomplete reporting. In a 1990 to 1997
review of closed claims involving Canadian anesthesiologists, no cause of death was identified among the files
involving regional anesthesia (13 in obstetrics), in contrast to the 17% mortality rate in other anesthetic files. [87]
TABLE 48-2 -- ASA CLOSED CLAIMS PROJECT 1985-l995: OBSTETRIC AND NONOBSTETRIC ANESTHESIA FILES
All Obstetric Files (II = Obstetric Regional (n = Obstetric General (n = Nonobstetric Files (n =
Maternal Injuries 434) 290) 133) 3099)
Maternal death 83 (19%) 31 (ll%) * 52 (39%) 1111 (36%) †
Headache 64 (15%) 61 (21%) * 2 (2%) 50 (2%) †
*
Nerve damage 43 (10%) 38 (13%) 5 (4%) 523 (17%) †
Pain 37 (9%) 36 (12%) 0 (0%) 27 (1%) †
Back pain 36 (8%) 36 (12%) * 0 (0%) 37 (l%) †
Brain damage 32 (7%) 17 (6%) 14 (11%) 403 (13%)
Emotional distress 31 (7%) 23 (8%) 8 (6%) 115 (4%) †
1110
TABLE 48-2 -- ASA CLOSED CLAIMS PROJECT 1985-l995: OBSTETRIC AND NONOBSTETRIC ANESTHESIA FILES
All Obstetric Files (II = Obstetric Regional (n = Obstetric General (n = Nonobstetric Files (n =
Maternal Injuries 434) 290) 133) 3099)
Pulmonary aspiration 20 (5%) 2 (1%) * 18 (14%) 58 (2%) †
From Chadwick HS: An analysis of obstetric anesthesia cases from the American Society of Anesthesiologists closed claim database. Int J Obstet
Anesth 5:258,1996. Reproduced with permission.
*P< 0.05 regional vs. general anesthesia in obstetric files.
†
P < 0.05 obstetric vs. nonobstetric files.
MATERNAL MORBIDITY
Complications Related to Regional Anesthesia Techniques in Nonobstetric Patients
A retrospective 1987 to 1990 review of 4767 consecutive spinal anesthetics, performed at the Mayo Clinic in the [88]
United States, for genitourinary and lower extremity orthopedic procedures, revealed a low incidence of paresthesias
during needle placement (6%) and postdural puncture headache (PDPH) (1%). Six patients reported pain after
resolution of the block, which slowly resolved 1 week to 24 months later, and, in two cases, spinal infectious
complications occurred. A combined retrospective and prospective study analyzed 18,000 central neuraxial blocks
[88]
performed between 1991 and 1994 at the Lund University Hospital in Sweden. Persistent lesions associated with [89]
regional anesthesia (some still involving other cofactors) were identified in 13 patients. Three patients had lesions
after a single-shot spinal block (rate 1:2834) and 10 after an epidural block (1:923). [89]
The most detailed data on the incidence and severity of complications related to regional anesthesia were provided
by a prospective survey of French anesthesiologists in 1994. Analyzing more than 100,000 spinal, epidural,
[90]
peripheral nerve, and intravenous regional blocks, Auroy and coworkers identified 89 cases (< 0.1%) of severe
complications fully or partially attributed to anesthesia ( Table 48-3 ). The incidence of cardiac arrest and neurologic
injury was significantly higher during spinal than during epidural block. The authors concluded that the higher risk
of cardiac arrest might be associated with factors other than regional anesthesia (age, procedure), whereas the risk of
neurologic injury might have been primarily associated with the type of regional block and the drug used. In most
but not all cases (21 of 34) of neurologic symptoms, paresthesias during puncture or pain during injection heralded
the complications. All except five patients recovered within 48 hours to 3 months. Nine of 12 patients with
neurologic deficit received hyperbaric lidocaine, and in 3 the deficit remained permanent; the neurotoxicity of local
anesthetic remained primarily suspected. Three patients after hyperbaric bupivacaine had only transient neurologic
symptoms. Seizures occurred in 14 of 23 patients after the use of bupivacaine, but in none did the event result in
cardiac arrest. Thus, the study documented a remarkable safety margin, because the risk of neurologic injury lasting
longer than 3 months and the risk of death were assessed to be 0.5 and 0.7 per 10,000, respectively, for all regional
anesthetic techniques. Even in experienced hands, the serious complications remain unavoidable, and cardiac arrest
[90]
is the major cause of fatality during regional anesthesia. [91]
An analysis of the patient insurance claims in Finland between 1987 and 1993 identified 86 (one obstetric) cases of [92]
serious neurologic complications associated with spinal or epidural anesthesia. The rates of complications after
spinal (0.45/10,000) and epidural (0.52/10,000) anesthesia, according to the insurance claims in Finland, were as [92]
low as those found prospectively in France. A survey of the reports from 1965 to 1994 in the Swedish adverse drug
[90]
reaction registry identified peripheral neurologic deficits in 21 cases after central neuraxial block. Intrathecal
application was involved in 17 and epidural in 4 (1 obstetric patient) cases. The number of cases was extremely [93]
low, but 15 of 21 cases were reported between 1992 and 1994. Hyperbaric lidocaine was associated with nine spinal
anesthetics, and other iso- or hyperbaric local anesthetics, plain or with epinephrine, in the remaining 12 cases. Pain
in the lower extremities and paresthesias were the most frequent symptoms, followed by low back pain, abdominal
pain, urinary and fecal incontinence, and erectile dysfunction. The patients with reversible deficit after 2 weeks had
no motor deficit, whereas in those with persistent symptoms, some motor dysfunction was present in 50% of cases.
TABLE 48-3 -- REGIONAL ANESTHESIA-RELATED COMPLICATIONS: PROSPECTIVE SURVEY IN FRANCE, 1994

All Regional Techniques (n =
Serious Event * 103,730) Spinal Anesthesia (n = 40,640) Epidural Anesthesia (n = 30,413)
Cardiac arrest 32 (3.1) 26 (6.4) 3 (l.o) †
(3.9–8.9) (3.9–8.9) (0.2–2.9)
Death related to event 7 (0.9) 6 (1.5) 0
(0.2–1.2) (0.3–2.7) (0.0–1.2)
Seizures 23 (2.2) 0 4 (1.3)
(1.3–3.1) (0.0–0.9) (0.4–3.4)
Neurologic injury 34 (3.3) 24 (5.9) 6 (2.0) †
1111
TABLE 48-3 -- REGIONAL ANESTHESIA-RELATED COMPLICATIONS: PROSPECTIVE SURVEY IN FRANCE, 1994

All Regional Techniques (n =
Serious Event * 103,730) Spinal Anesthesia (n = 40,640) Epidural Anesthesia (n = 30,413)
(2.2–4.4) (3.5–8.3) (0.4–3.6)
Radiculopathy 28 (2.7) 19 (4.7) 5 (1.6) †
(1.7–3.7) (2.6–6.8) (0.5–3.8)
Cauda equina syndrome 5 (0.5) 5 (1.2) 0
(0.2–1.1) (0.1–2.3) (0.0–1.2)
Paraplegia 1 (0.1) 0 1 (0.3)
(0.0–0.5) (0.000.9) (0.0–1.8)
From Auroy Y, Narchi P, Messiah A, et al.: Serious complications related to regional anesthesia.
Results of a prospective survey in France. Anesthesiology 87:479486,1997. Reproduced with permission.
* Number of cases, (rate per 10,000) and (95% confidence interval).
†
P < 0.05 epidural vs. spinal anesthesia.
Pleym and Spigset concluded that the causal relationship between the neuraxial application of local anesthetic and
[93]
neurologic deficit remains uncertain, but the number of cases associated with hyberbaric 5% lidocaine (injected
through fine-bore needles) are consistent with the suspicion that lidocaine is neurotoxic.
The “safe” use of intrathecal lidocaine abruptly ended in the mid-1990s when numerous studies started to implicate
lidocaine as the cause of transient (48– 72 hr) neurologic symptoms (pain and dysesthesias with radiation to the
buttocks, thighs, or legs), found in up to one third of patients after an otherwise uneventful spinal anesthesia with
hyperbaric 5% lidocaine. Lithotomy position, caudal-oriented injection, outpatient status, and obesity
[90] [94] [95] [96] [97] [98] [99]
were found to increase the risk, whereas preexisting neurologic disorders, paresthesias during needle placement, or
lidocaine dose did not affect the risk. In a multicenter study of 1863 patients, the risk of neurologic symptoms
[100] [101]
after spinal lidocaine was calculated to be three to five times higher compared with risk after spinal tetracaine and
bupivacaine, respectively. The incidence of transient symptoms after spinal anesthesia with hyperbaric lidocaine
[100]
was significantly higher compared with hyperbaric bupivacaine in patients operated on in a supine position. The [102]
negative report of lidocaine escalated, because a suspicion was raised that hyperbaric 5% lidocaine could be the
cause of rare but permanent damage to the cauda equina, even after single-shot spinal anesthesia. After a review of
six cases of cauda equina syndrome reported in Sweden from 1993 to 1997, Loo and Irestedt repeated the [103]
recommendations that hyperbaric (or even isobaric) lidocaine should be administered intrathecally in a
concentration not greater than 2% (equipotency ratio of 4:1 to 0.5% bupivacaine) and at a total dose not exceeding
60 mg. Some editorialists questioned the relevance and etiology of transient neurologic symptoms. They requested
proof of neurotoxicity and claimed that lidocaine might still be an excellent drug. These investigators warned
against reaching any hasty conclusion. [104] [105]
Complications Related to Regional Anesthesia in Obstetrics
In obstetrics, the complications result from pregnancy, labor and delivery, preexisting diseases, and conditions
arising from or during pregnancy, concomitant medical treatment, obstetric interventions, regional anesthesia
techniques per se, or multifactorial combinations (as in other patient populations) of several factors or mechanisms. [37]
An objective assessment of the patient’s history; concomitant risks, triggers, and drug treatment;
[38] [39] [88] [89] [101] [103] [106] [107] [108]
details of obstetric and anesthetic procedure; positioning; course and management postpartum; and clinical and
radiologic presentation are required to treat and elucidate the predominant or primary cause and mechanism of
injury. A review of the 1988 to 1994 institutional consultations revealed 12 (6 obstetric patients)
[37] [38] [39] [101] [106] [108] [109] [110] [111]
cases of neurologic complications related to lumbar epidural technique. Yuen and coworkers concluded that [112] [112]
neurologic sequelae associated with epidural block are rare but potentially severe in the presence of spinal stenosis
or after inadvertent subarachnoidal injection. In another neurologic series, seven women attributed falsely their
symptoms to epidural analgesia administered during labor, and five were considering litigation. The example of [113]
three cases of severe neurologic damage after administration of general anesthesia is highly didactic. Philip
Bromage concluded that “the anesthetic technique was not incriminated in any of these three cases. However, there
is a high probability that a cause-and-effect relationship would have been imputed and medicolegal proceedings
instituted if spinal or epidural anesthesia had been used.” [37]
Improved Safety of General and Regional Anesthesia
The concept that the anesthesia-related maternal mortality rate is low and decreasing because of the widespread use
of regional anesthesia techniques has become implicitly established. The mechanisms and types of [14] [18] [52] [61] [62] [87]
complications associated with regional and general anesthesia are different. In a proportion of cases, however, both
techniques may have the same type and severity of complications. General anesthesia (in a majority of [14] [18] [87] [90]
1112
countries and institutions) remains reserved for high-risk pregnant women who are prone to or who have already had
complicated gestation. General anesthesia is predominantly used for cesarean delivery and less frequently for
vaginal delivery. Thus, the proportion of cases and indications for regional techniques and general anesthesia in
obstetrics remain, quantitatively and qualitatively, widely different. Multiple advantages have been attributed to
regional anesthesia techniques. Maintaining consciousness and allowing women to participate in delivery results in
high maternal satisfaction, reduced blood loss, lower incidence of minor complications, and prolonged postpartum
pain relief, which are all factors that are considered to contribute to a faster and smoother recovery with regard to
the use of regional anesthesia in obstetrics. [33] [34] [64] [65] [81] [114] [115] [116] [117]
With the remarkable popularity and safety of regional techniques in obstetrics, it remains neglected that general
anesthesia is undergoing a process of safety improvement as well. The following factors [34] [52] [62] [64] [79] [81] [121] [122] [123]
contribute to the safety and improved outcome of general anesthesia in obstetrics:
1. Routine use of prophylaxis against pulmonary aspiration

2. Increased recognition of risk factors associated with difficult intubation [118] [119] [120]
3. Widespread use of capnometry and pulse oximetry

4. A more favorable pharmacologic profile of new anesthetic drugs and muscle relaxants
5. Availability of laryngeal masks, fiberoptic instruments, and other tools for the management of failed
intubation or ventilation
In the United Kingdom, with decreased use of general anesthesia for cesarean delivery (from 66% to 83% in the
mid-1980s to 23% in the mid-1990s), the incidence of failed intubation remained stable. The majority of cases [71] [72] [124]
of failed intubation occurred during the night, over the weekend, in an emergency situation, and in women from
minority groups (a sign of nonequity) in whom general anesthesia was used with disproportionate frequency, but
none resulted in an adverse outcome. Data from the United Kingdom (1993 to 1998) show that a trend toward
[71]
more cesarean deliveries and fewer general anesthetics (14% for elective surgeries and 30% for emergency cesarean
deliveries) continues. The incidence of failed intubation (1:249 among 8790 obstetric general anesthetics)
[73] [125]
remained stable in a United Kingdom region. Of 36 cases of failed intubation, 26 were well documented, and none
[73]
resulted in negative outcome. Six cases were finally managed with an endotracheal tube, 12 were switched to
regional anesthesia, and for most other procedures a laryngeal mask was used. In the 24/26 cases, there was either
no recording of preoperative assessment, failure to follow an accepted protocol, or no follow-up. [73]
The risk of pulmonary aspiration is considered to be higher in pregnant women than in the nonobstetric population. [14]
However, the risk assessment of aspiration in obstetrics seems to be based more on past than on current practice
[126]
and options in obstetric anesthesia. Widely different practices prevail among and within hospitals
[14] [81] [126] [127] [128] [129] [130]
and countries for the following : [81] [132] [133]
1. Eating routines in wards, delivery units, and labor rooms [131]
2. Indications for cesarean delivery [132] [133]
3. Definition of elective, semielective, emergent, and urgent procedures [62] [132] [133]
4. The whole process and structure of obstetric and anesthesia care
A routine use of antacids, histamine-receptor antagonists, and other measures reduced the risk and the consequences
of pulmonary aspiration in obstetrics in a highly efficacious and cost-effective manner. The risk of aspiration is ill [81]
defined and needs revision. A mandatory use of endotracheal intubation if general anesthesia is induced intrapartum
should be considered, at the least, controversial. In a series of difficult or failed intubations (ideal conditions for
[134]
gastric regurgitation), no aspiration was reported. These data are rough indicators only and should not be
[18] [71] [72] [73]
transferred directly to the management of individual cases. A part of anesthesia-related morbidity and mortality
seems to be hidden in the inadequately defined risks of both regional and general anesthesia techniques. The quality
and outcome of obstetric anesthesia are continuously improving, but this may be true only for institutions that
succeeded to define the risks adequately, within their respective structure and process of anesthesia care.
Maternal Morbidity: Incident Reporting and Closed Claims Studies
The Australian Incident Monitoring Study is a collection of anonymous and voluntary reports of all anesthesia
incidents. In its first 5000 reports, the proportion of obstetric cases was 4% (203 per 5000). The obstetric incidents [18]
were over-represented with respect to accidental dural puncture and headache as well as drug incidents involving
wrong ampule or syringe swap. The rate of failed intubation was significantly higher in obstetric than in
nonobstetric cases, particularly in emergent procedures, but the analysis did not provide the outcome of 12 pregnant
women in whom intubation “failed.” Unexpectedly high spinal or epidural blockade was reported in 22 cases, and in
8 cases general anesthesia or ventilatory support was required. In the ASA closed malpractice claims project, [18] [14]
1113
nerve damage was more frequently found in the nonobstetric files, but the proportion of cases involving obstetric
regional techniques (the third most common maternal claim) was remarkable (see Table 48-2 ). Of 38 nerve injuries
after spinal or epidural anesthesia, 21 cases were judged to be caused by the regional block procedure. The most
frequent causes were needle or catheter trauma, neurotoxicity, and ischemia. Convulsion (predominantly associated
with epidural block resulting in neurologic injury or death to the mother, newborn, or both in 74% of cases),
headache, pain during anesthesia, and back pain were the most frequent injury/damaging event leading to claims in
obstetric regional cases. Brain damage was evenly distributed between obstetric and nonobstetric files and between
obstetric regional and general anesthesia. Difficult intubation and pulmonary aspiration were the leading causes of
claims and death in obstetric files. Damaging events related to the respiratory system were more common among
obese than nonobese parturients. A Canadian review of the 1990–1997 closed legal actions involving
[14]
anesthesiologists identified 42 claims (13 in obstetrics) related to the use of central neuraxial block. The outcome [87]
in the majority of obstetric cases resulted in no or minor disability, except for one case of paraplegia after cesarean
delivery (details of block not provided). The legal outcome was favorable for the patient in 10% of regional
anesthesia claims compared with 28% of all anesthesia-related claims. [87]
Neurologic Complications Associated with Epidural Anesthesia
In a 1975 to 1983 study from Winnipeg, Canada, the postpartum paresthesias and motor dysfunction were all of
transient duration (< 72 hr). The overall rate was 19 per 10,000 deliveries, but primiparas (27.9 vs. 11.7 in
[135]
multiparas), women who had prolonged labors and forceps/vacuum-assisted deliveries (28.5 vs. 11.0 in spontaneous
deliveries), and those who had any type of anesthesia (considered to be a priori at higher risk) were more likely to
experience a neurologic deficit. The rate of complications was low (2.4 per 10,000) in women who delivered
without analgesia in contrast to delivery under epidural (36.2 or 1 per 277 deliveries) and general anesthesia (34.7 or
1 per 288). Ong and coworkers concluded that neurologic deficits after labor and delivery are rare and that the
[135]
causal relationship with epidural analgesia is highly unlikely. An inquiry of more than 11,000 women in
Birmingham, England, 13 months to 9 years after delivery, from 1978 to 1985, found that women who delivered [136]
with epidural anesthesia (compared with those who delivered without) more commonly complained of backache
(19% vs. 11%), frequent headaches (5% vs. 3%), migraine (2% vs. 1%), and tingling in hands or fingers (3% versus
2%). Twenty-six women reported numbness or tingling in the lower back, buttocks, and legs, and 23 of them had
received epidural anesthesia. The high rate of long-term numbness or tingling postpartum (presumably) associated
[136]
with epidural analgesia (48 per 10,000) remained an isolated finding of the Birmingham study that was not
confirmed by later investigators. A 1982 to 1986 survey of United Kingdom obstetric units identified 108 nonfatal
events after 505,000 epidurals (2 per 10,000). The most frequent complications were single nerve neuropathy (rate
0.75 per 10,000; 37 of 38 women recovered), convulsions, prolonged headache after dural puncture, too high level
of block, urinary problems, severe backache, and cranial nerve palsy; permanent damage was considered to have
occurred in five cases. A United Kingdom 1990 to 1991 prospective survey confirmed that the incidence of
[44]
reversible neuropathy after obstetric epidural (3.5 per 10,000) and spinal anesthesia (5.4 per 10,000) is low. A [45]
series of seven obstetric cases of radiculopathy were encountered within a period of 1 year. A stiff (Teflon) epidural
catheter and a direct mechanical trauma were considered the most likely causes of injury. The symptoms remained
unresolved in two women from 2 to 9 months later. [137]
Holdcroft and coworkers addressed prospectively all neurologic complications associated with pregnancy in the
[38]
1991 to 1992 period. The study covered more than 40,000 deliveries in the Northwest Thames Region, England, and
an independent specialist panel analyzed the cases according to notifications from hospital and community
specialists. The majority of cases were only identified within the community; thus, an audit restricted to the hospital
data would provide a falsely low incidence of morbidity. The neurologic complications associated with pregnancy
and delivery and persisting for more than 6 weeks were identified in 19 women (1 per 2530 deliveries). Epidural
analgesia was used in 13 women who had neurologic complications. It was considered contributory to a disorder in
just one case of more than 13,000 epidurals. In other words, an epidural block was five times less likely to be of
cause of injury than pregnancy, labor, delivery, and preexisting diseases. The same proportion of cases involved the
upper and lower parts of the body. Higher prepregnant body index was found in 60% of women with pregnancy-
associated neurologic problems. The authors concluded that, in contrast to a dramatic decrease in maternal mortality
rate in the past decades, “neurological maternal morbidity has remained static, although it can cause serious distress
and disability.” Another eight women in the Holdcroft analysis had no identifiable lesion, but their symptoms,
[38]
suggestive of neurologic dysfunction, such as back pain, stress incontinence, or paresthesias, could not be excluded.
These injuries were considered by the panel to be “mechanical rather than neurological.” However, several [38]
factors/mechanisms, including regional anesthesia, could be simultaneously involved. Bladder and sphincter
disorders have been previously associated with obstetric epidural block. Severe bladder dysfunction (rarely,
[138]
complete atony) could be encountered after recovery from a central neuraxial block. An interview study revealed a
de novo stress incontinence after vaginal delivery in 27% of women who delivered under epidural analgesia,
compared with 13% in the control group. In those who had epidural block, the first stage of labor lasted significantly
longer. After 1 year, stress incontinence persisted in 7% of the epidural group and 3% of the control group. An [139]
1114
analysis of 3364 labors found a low incidence of significant but temporary urinary retention. Twenty-seven of 30
women delivered under epidural block. [140]
A prospective study (1989 to 1994) from an Australian referral obstetric unit and an audit (1987 to 1997) from a [141]
district hospital in the United Kingdom each analyzed more than 10,000 epidural cases. The incidence of
[142]
complications, such as inadvertent intravascular injection, subdural or extra-arachnoid injection resulting in an

asymmetrically high block, or inadvertent subarachnoid injection resulting in a rapid, dense, and high spread of local
anesthetic, was extremely low (< 0.1% – <0.01%). In two cases of each series, endotracheal intubation and assisted
ventilation were required. Just one case (per 10,995) of persisting traumatic mononeuropathy was identified in
[141] [142]
one series. Thus, the incidence of longer lasting neurologic complications related to epidural anesthesia reached in
[141]
the last decade (at least, in the United Kingdom and Australia) a level that seems to be lower in the obstetric than in
the nonobstetric population. [14] [38] [39] [44] [45] [87] [89] [90] [101] [108] [141] [142]
Continuous Spinal Anesthesia
The reinstitution of continuous spinal anesthesia (from the 1940s) into the clinical practice of the late 1980s was of
short duration. The invasiveness and technical difficulties, high incidence of complications (difficulties with
microcatheters, neurotoxicity or maldistribution of local anesthetics, as well as other mechanisms have been blamed,
but their roles remain controversial), and probably, above all, the lack of clear-cut advantages and indications soon
led to the fading popularity and virtual abandonment of the method. One prospective survey found no [37] [143] [144] [145] [146]
serious neurologic complications among 216 single-shot and 218 microcatheter-continuous spinal epidural blocks in
pregnant women. A 1987 to 1992 Mayo retrospective review reported that, among 603 continuous spinal
[147]
anesthetic procedures, 127 parturients were managed with a microcatheter technique. Five complications occurred in
the nonobstetric and one (reversible) complication occurred in the obstetric group. Continuous spinal block [143]
remains an option after unintentional dural puncture during attempted epidural block, in morbidly obese parturients,
and (possibly) for high-risk cardiovascular patients. [144] [148] [149] [150] [151] [152]
Neurologic Complications Associated with Combined Spinal-Epidural Technique
Starting from the mid-1980s, combined spinal-epidural anesthesia rapidly gained in popularity because of the
greater flexibility and reliability, compared with spinal or epidural block alone In a prospective study [114] [115] [117] [153] [154] [155]
of more than 1000 parturients, no major complications occurred either after combined spinal-epidural or epidural
technique, according to the phone interviews within 2 weeks after hospital discharge. Another prospective study of [153]
761 nulliparous women (not focused on anesthetic complications as it ended on postpartum day 1) reported no
serious complications. A 1994 to 1997 retrospective analysis of more than 6000 combined anesthetics (including
[154]
more than 4100 obstetric cases) found just one temporary (3 to 4 weeks) postpartum peripheral nerve injury. The [156]
consultants of the ASA Task Force took an equivocal position concerning the rate of complications after spinal or
epidural block compared with the combined spinal-epidural technique. [34]
Holloway and coworkers investigated whether, in obstetrics, the combined spinal-epidural approach is more likely
[43]
to result in neurologic complications than single-shot spinal anesthesia. They conducted a postal survey of 259
United Kingdom obstetric units in 1995; 222 (86%) replied. Forty units reported a total of 56 cases of prolonged
postpartum problems following two techniques. The study did not address the complications in women who
delivered without anesthesia. None of the differences were significant between the combined and single-shot spinal
anesthesia or between the pencil-point “atraumatic” Whitacre and Sprotte spinal needles ( Table 48-4 ). The
Quincke needle was used
TABLE 48-4 -- PROLONGED NEUROLOGIC COMPLICATIONS RELATED TO OBSTETRIC COMBINED SPINAL-

EPIDURAL AND SINGLE-SHOT SPINAL ANESTHESIA: RETROSPECTIVE U.K. SURVEY 1995
Combined Spinal- Epidural Single-Shot Spinal
Anesthesia (n = 12,254) Anesthesia (n = 29,698) Total n = 41,952)
*
Causes of Complications
Obstetric/nonanesthetic 5 (4.1) 4 (1.3) 9 (2.1)
Anesthetic 7 (5.7) 11 (3.7) 18 (4.3)
Uncertain 7 (5.7) 22 (7.4) 22 (5.2)
†
Spinal Needles
Whitacre 13/10,700 15/17,560 28/28,260
(12.1) (4.7–31.5) (8.7) (4.5–17.0) (10.0) (5.8–17.2)
1115
TABLE 48-4 -- PROLONGED NEUROLOGIC COMPLICATIONS RELATED TO OBSTETRIC COMBINED SPINAL-

EPIDURAL AND SINGLE-SHOT SPINAL ANESTHESIA: RETROSPECTIVE U.K. SURVEY 1995
Combined Spinal- Epidural Single-Shot Spinal
Anesthesia (n = 12,254) Anesthesia (n = 29,698) Total n = 41,952)
Sprotte l/1,554 18/12,138 19/13,692
(6.4) (0.80–49.7) (14.4) (6.2–33.8) (13.5) (6.0–30.3)
Both needles 14/12,254 33/29,698 47/41,9529
(11.4) (4.8–27.2) (11.1) (6.4–19.1) (11.2) (7.0–17.7)
From Halloway J, Seed PT, O’Sullivan G, Reynolds F: Paraesthesiae and nerve damage following combined spinal epidural
and spinal anaesthesia: A pilot survey. Int J Obstet Anesth 9:151-155,200O. Reproduced with permission.
* Number of cases, (rate per 10,000).
†
Number of cases, (rate per 10,000) and (95% confidence interval).
in a few cases (without complications), and any advantage or disadvantage of “atraumatic” needles could not be
verified. The rarely reported damage to the spinal cord should not be regarded as a fault of “atraumatic” needles but
rather of technique. Because of the unpredictable caudal extension of the spinal cord, it was recommended that a
[43]
space no higher than L3–L4 should be selected. The rate of neurologic complications (11.1 to 11.4 cases per
[43]
10,000 obstetric procedures) was nearly identical after the single-shot and combined technique. Notwithstanding [43]
the methodologic differences (retrospective in the United Kingdom and prospective in France), the rate of
complications of 11.1 to 11.4 per 10,000 obstetric spinal and combined anesthetics in the United Kingdom was [43]
similar to the rate of 11.8 per 10,000 nonobstetric spinal anesthetics in the French survey (see Tables 48-3 and 48- [90]
4 ). Thus, the studies indicate that a slightly higher rate of complications must be expected after spinal anesthesia
than after epidural technique in the obstetric as in the nonobstetric population. [38] [43] [89] [90] [141] [142]
Rare Neurologic Complications
Loo and coworkers reviewed the neurologic complications of obstetric regional anesthesia techniques according to
[39]
the published reports from 1966 to 1998. The most impressive finding of the review is an extremely low number of
neurologic injuries and diseases that have been caused, cotriggered, or suspected to be associated with regional
anesthesia over a period of time when millions of women received central neuraxial blockade for labor and delivery.
Of course, the publications reflect a selection of cases (possibly biased?) and not the exact incidence of
complications. Nevertheless, obstetric epidural abscess could be identified in only eight or, according to another [39]
1974 to 1996 review, in a total of nine cases. Loo and coworkers listed five spontaneous (anesthesia-unrelated)
[157]
obstetric epidural abscesses. Epidural abscess is more frequently associated with an endogenous infection than
[39]
with regional anesthesia. Bacterial meningitis after spinal, epidural, and combined spinal-epidural technique was
identified in 15 cases, and aseptic meningitis was seen in 5. The case reports of meningitis associated with [39]
combined spinal-epidural block started to appear more frequently in the 1994 to 2000 period. This [114] [158] [159] [160]
incidence could represent a coincidence of publishing the complications of a new technique, inadequate antiseptic
(technical, personal, pharmacologic) precautions, and a factually increased risk of infection of the combined
technique. Anyway, the incidence of spontaneous obstetric meningitis must be taken into account to assess properly
the risk of regional anesthesia per se. Loo and coworkers identified nine cases of arachnoiditis (we hope this
[161] [162] [163] [39]
complication is of historical relevance only), attributed to an inadvertent intrathecal injection of large doses of
procaine or chloroprocaine or the preservatives in the solution.
The review of the 1966 to 1998 period revealed only seven published cases of spinal hematoma in obstetrics, all
after epidural and none after spinal technique. Similar to the 1906 to 1994 review of Vandermeulen and
[39]
coworkers, a coexisting hemostatic disorder (spontaneous or iatrogenic) was found only in some reports.
[107] [39]
However, regional techniques still continue to contribute to spinal bleeding in patients with preeclampsia-induced or
drug-induced coagulopathy. As in the nonobstetric population, spontaneous spinal bleeding in pregnant women
[164] [165]
could be expected at the higher rate than spinal hematoma associated with regional anesthesia. A regional [39] [166] [167] [168]
technique was successfully used in few cases of documented or assumed hemostatic defect. The impact [169] [170] [171] [172] [173]
of these experiences on the recommendations and guidelines for obstetric anesthesia remains rather hidden, and the
specific management may be defined only on the case-to-case basis. Spinal anesthesia or inadvertent [34] [64] [101] [122] [174]
dural puncture (leading to cerebrospinal fluid loss and traction of the subdural veins) and preeclampsia per se may
cause cranial subdural hematoma. The critical point is that thromboembolism still remains one of the
[39] [175] [176] [177] [178]
leading causes of maternal mortality. A prophylactic use of antithrombotic drugs is indicated in some cases
[6] [13]
throughout the pregnancy and, preferably, in all women peripartum. The importance of the implementation of [60] [174]
the guidelines concerning the assessment of hemostasis, risk of bleeding, and use of anticoagulant drugs could not
be overemphasized, particularly concerning the exact timing and dosage before and after lumbar puncture and the
insertion and removal of epidural catheter. [34] [60] [101] [108] [174] [179] [180]
1116
If an ischemic injury to the spinal cord is suspected, unavoidably, the discussions are prone to focus on the role of
arterial hypotension, local anesthetic- and catheter-induced injury, or constriction of the spinal vessels due to
additional epinephrine. Even the epidural air, used for the loss-of-resistance technique to identify the epidural
[37] [39] [108]
space, has been incriminated as a (remotely) possible cause of ischemic spinal injury. A potential for ischemic [181]
injury seems to result primarily from the unfavorable spinal blood supply (present in 15% of humans), epidural and
spinal venous engorgement during gestation, unfavorable positioning, and compression of the spinal cord by the
fetus in prolonged and traumatic labor. Not a single obstetric case of cauda equina syndrome, unmistakably
[37] [39]
related to regional anesthesia, was identified by Loo and coworkers. A hypothetical explanation could be a rare [39] [109]
use of continuous spinal anesthesia or intrathecal 5% hyperbaric lidocaine in obstetrics. Transient neurologic
symptoms were reported rarely after lidocaine use in obstetrics, although pain and paresthesias postpartum could be
easily considered as being of “obstetric” rather than of “anesthetic” origin.
Extensive Cephalad Spread
A high cephalad spread of a lumbar neuraxial block is one of the most frequent side effects of epidural block or
unrecognized intrathecal injection, with a relevant potential for morbidity and negative outcome. It is less frequently
reported after intentional spinal and (probably, because technique is not so widely used) combined spinal-epidural
anesthesia. The real incidence of extensive cephalad spread is unknown, but the rate was
[18] [37] [45] [61] [64] [108] [114] [122] [141] [142] [156]
estimated at 1 in 500 to 1400 epidural blocks and 1 in 3000 spinal blocks. Not only is the cephalad spread [45] [64] [108] [141]
facilitated in pregnant women (a combined effect of epidural venous distention, reduced buffer capacity for local
anesthetic, suspected increase of nerve axon sensitivity, and lower volume and density of cerebrospinal fluid), [33] [182] [183]
but a significant difference in the maximal cephalad spread was found between parturients with singleton
[184] [185] [186]
(T8–T4) and twin (T6–T2) pregnancies. The clinical presentation of an extensive block may vary from mild
[187]
paresthesias and decreased sensations in the upper extremities and the face to difficulties with breathing, apnea,
severe arterial hypotension, fetal distress, maternal quadriplegia, and coma. It was reported with a meticulous
technique, low-dose epidural local anesthetics with or without opioids, combined spinal-epidural technique, or
single dose of intrathecal opioid with or without parenteral opioids. Proper [18] [86] [141] [142] [156] [188] [189] [190] [191] [192] [193] [194] [195]
monitoring of every regional block and prompt treatment of complications should result in a good maternal and
neonatal outcome. Severe maternal complications or death from an extensive cephalad spread of a regional
[34] [37] [122]
block have resulted not from an exotic mechanism, drug toxicity, or heart disease, but more often from an
inappropriate technique, drug overdose, or insufficient monitoring. [6] [37] [61] [196] [197] [198]
Horner’s Syndrome and Dysfunction of Cranial Nerves
Cephalad spread of a local anesthetic to thoracic and cervical segments may easily reach the fine fibers of
sympathetic nerve supply (C8–T4) to the eye and face. Resulting Horner’s syndrome (miosis, ptosis, enophthalmus,
ipsilateral facial anhidrosis, and, occasionally, eye pain) is a relatively frequent side effect of epidural and caudal
anesthesia in obstetrics. In one series, it occurred in 4% of cesarean deliveries and 1% of vaginal labors, but [199]
isolated pupillary constriction could be found in 75% to 80% of women receiving obstetric epidural blocks. [108]
Horner’s syndrome may involve one or both sides; may be isolated or combined with a high sensory level, arterial
hypotension, paresthesias and weakness in the arm, or cranial nerve palsy; and may occur even without detectable
sensory analgesia over the trunk. The mechanism involves the exaggerated spread of local anesthetic (it must not be
uniform in all cases) by epidural, subarachnoid, or subdural route. The course is benign and the symptoms disappear
without sequelae. [108] [200] [201] [202]
Different mechanisms are responsible for the dysfunction/palsy of cranial nerves associated with regional anesthesia
techniques. Anesthesia per se and high cephalad spread are involved only in part and only in some palsies. The
abducens nerve palsy is believed to result from a dural puncture, cerebrospinal fluid leakage, and stretching and
mechanical trauma to the nerve. Despite an instant blood patch, the recovery may last weeks to months. Abducens [203]
nerve palsy may occur spontaneously and as an isolated event during pregnancy or as an unusual manifestation of
preeclampsia. It has been reported (at a similar rate) in the nonobstetric and obstetric populations. Very few
[204] [205] [39]
obstetric cases of ischemic injury to the optic nerve have been published after bleeding-induced arterial
hypotension. The rate of optic nerve injury and visual loss in cardiovascular patients and procedures at
[39] [206] [207]
particular risk of ischemia are much higher compared with the few cases reported in pregnant women.
[208] [209] [210] [39]
Trigeminal nerve palsy associated with obstetric epidural anesthesia (in few reported cases) resulted from a high
spread of local anesthetic. Trigeminal and facial nerve palsy may occur simultaneously, combined with a
[39] [200] [201]
PDPH. A complete recovery from trigeminal palsy is usually rapid.

[211]
Idiopathic facial paralysis (Bell’s palsy) is more than three times more likely to develop in a pregnant woman than
in a nonpregnant women. A 1982 to 1992 institutional survey found 36 obstetric cases of Bell’s palsy; in 25, the
symptoms started during the third trimester, and in 11 in the first postpartum week. The use or no use of any
anesthetic technique was unrelated to the development of Bell’s palsy ; thus, a postanesthesia case of facial palsy [212]
1117
should be considered just a temporal coincidence without a causal relationship with anesthesia. Bell’s palsy is
frequently associated with gestational hypertension or preeclampsia. On the other hand, in three cases reported in [213]
the 1990s, the facial nerve palsy occurred after accidental dural puncture; the epidural blood patch itself was labeled
as the cause of increased intracranial pressure and neural ischemia. Recovery usually takes weeks to months, but [39]
prognosis is good in most cases.
Hearing loss due to vestibulocochlear nerve dysfunction is usually attributed to the dural puncture and decreased
liquor pressure, although general anesthesia and a variety of other factors may be involved. Hearing loss may or [214]
may not be associated with headache. The incidence in obstetrics seems to be lower than in nonobstetric spinal
anesthesia. In one series, reduced hearing was found in 14% of women who received spinal anesthetic for cesarean
delivery. Blood patch could resolve the hearing loss in some but not in all patients.
[39] [39] [101]
Postdural Puncture Headache
The incidence of PDPH, one of the most frequent complications of spinal anesthesia, decreased over the years to
less than 1% to 2% with the widespread use of fine-gauged noncutting spinal needles. A multifactorial [88] [215] [216] [217]
predisposition and a high incidence of headache in pregnancy and in the postpartum period, the clinical and
medicolegal (see Table 48-2 ) relevance, the differential diagnosis, the role of the needle design and size, and the
prevention and therapy of PDPH have been addressed in detail in the obstetric anesthesia literature. [14] [18] [37] [101] [114] [153] [218]
Norris and coworkers found no significant differences in the incidence and type of headaches within 2 weeks of
[219] [153]
childbirth after epidural, combined technique, and no neuraxial analgesia. Similar findings were reported by a
French survey of the incidence of postpartum headache without and with labor epidural analgesia. Several [220]
obstetric studies of single-shot spinal anesthesia showed in the 1990s that the fine-gauged needles (except for the
Quincke type) are associated with PDPH at a rate of 0% to 4%. In some studies, a requirement for blood patch
[101] [218]
was relatively high and the incidence of headache was 11% at discharge. A 1987 to 1999 review of the literature [218] [221]
showed that the risk of PDPH after combined spinal (pencil-point needles, 25-G to 27-G) and epidural technique for
vaginal and cesarean delivery decreased to 0% to 2.5%, or even to 0% to 1%. The major aspect of [114] [153] [154] [156] [218]
PDPH, concerning the incidence, intensity, difficulties to treat, and overall impact on the negative outcome, arises
from the unintentional dural puncture with larger epidural needles. Some analyses reported only a 0.4% to 2.7%
incidence of accidental dura perforation in attempting epidural block, but PDPH could be expected in up to 85% of
these cases. Schneider and Schmid strongly recommended a conservative therapy first; then,
[101] [141] [142] [153] [154] [156] [218] [222] [223]
for women with severe symptoms for more than 24 hours after dural puncture, epidural blood patch (despite
potential side effects and risks) would be a safe and highly effective treatment of PDPH. Some studies and surveys [218]
of the use and efficacy of the patch provided somewhat different and less enthusiastic conclusions. A survey [223] [224] [225]
of 38 tertiary obstetric units in North America, according to the reported rates of patch failures and persistent
headaches, concluded that the “optimism regarding the efficacy of epidural blood patch is not supported by the
evidence available and may be unwarranted.” An institutional retrospective (1993 to 1998) audit found no relief of
[224]
PDPH in 12% and 14% of patients after the first and second epidural blood patch, respectively. A 1991 to 1997 [223]
study reported a high total effectiveness (98%) of epidural blood patch in the treatment of PDPH. Despite such an
excellent success rate, the epidural blood patch was considered less successful than is commonly believed. [225]
Backache
On a short-term basis, posterior pelvic soreness with backache is a very common complaint, which may be
experienced in up to 70% of women during pregnancy and after childbirth. Various factors that occur during [226]
pregnancy, such as multiple pregnancy and preexisting or severe back pain, are strongly associated with the intensity
and persistence of pain for months after delivery. In rare cases, however, antepartum or postpartum back
[37] [226] [227] [228]
pain may be the first herald of an unrecognized spinal pathologic condition such as lumbar disc disease or spinal
tumor. Obviously, lumbar regional anesthesia should not be implicated as the cause of backache or other symptoms
after delivery; instead, a detailed clinical and radiologic investigation and, eventually, prompt surgical treatment are
recommended. A magnetic resonance imaging (MRI) investigation in London revealed lumbar disc
[39] [109] [110] [111] [229] [230]
abnormalities in 9 of 35 women studied postpartum. The soft tissue changes were found in the lumbar region in all
[231]
women, and in 12 (34%) of them the changes were rated as severe, with an average of five segments involved.
These changes were reversible and unrelated either to the mode of delivery, the use of epidural block, or the trauma
of epidural cannulation. Symphysis pubis separation, with or without involvement of sacroiliac joints, is
[231]
considered a rare complication, with an incidence of 1 case in 30,000 up to 1 case in 500 to 600 deliveries. The
episode of severe pain occurred during labor despite adequate epidural block, or epidural analgesia was used for [232]
the treatment and mobility antepartum in symphysis pubis separation. [233]
A controversy started in the early 1990s when several retrospective inquiries concluded that epidural anesthesia for
labor (but not for cesarean delivery) was associated with (1) a backache for months to years after delivery; (2) a [136]
new, long-term backache (although it tends to be “postural and not severe”) 12 to 15 months after childbirth; or (3) [234]
1118
a new back pain 1 year after delivery. The risk of low back pain was significantly increased on the first day after
[235]
epidural delivery, but otherwise, the association between epidural block and postpartum low back pain was found to
be inconsistent. The subsequent properly designed and prospective studies evaluated all factors associated with the
[236]
back pain and cleared the controversy. Breen and coworkers interviewed more than 1000 women and found that [237]
the incidence (44%) of back pain 1 to 2 months after delivery was identical in women who delivered with or without
epidural analgesia. The predisposing factors for new onset of back pain were greater weight and shorter stature.
Russell and coworkers and Macarthur and coworkers came to similar conclusions; namely, that epidural block
[238] [239]
for labor and delivery per se does not increase the incidence of back pain 3 and 12 months after delivery. The factor
associated with backache 3 months after delivery was the history of backache before and during pregnancy. A [238]
prospective study of epidural and combined spinal-epidural anesthesia for elective cesarean delivery documented
back pain in over half of the women (55% versus 62%, respectively) during the first 3 postpartum days. In 5 of 114
patients, a new backache occurred, but it was unrelated to the epidural site. A prospective study of 270 women [117]
after epidural anesthesia for labor found that the incidence of backache after delivery (31%) decreased (9%) 14 days
later. The history of back pain was confirmed to increase the likelihood of any back pain after delivery. Thus, the [240]
regional anesthesia techniques in obstetrics do not increase the risk of postpartum low back pain. However, [101] [108] [219]
according to the ASA study of malpractice closed claims (involving, unavoidably, the perspectives of patients and
many consultants and lawyers), a higher proportion of back pain is still found in obstetric (all after regional
anesthesia) than in nonobstetric files. Durbridge and Holdcroft concluded that although significant postpartum
[14] [219]
morbidity is found in the community, “its relationship to analgesia in labor is still to be proved.”
Efficacy and Other Attributes of Quality of Regional Anesthesia
All central neuraxial blockades are highly efficacious and effective in providing anesthesia and analgesia in
obstetrics. Together with safety, these attributes of quality have been most frequently studied and accentuated. [33] [34] [35]
Efficiency and optimality became important variables in the assessment of

[36] [37] [64] [79] [114] [116] [144] [153] [156] [241] [242] [243] [244] [245] [246]
quality of obstetric anesthesia, although, for good reasons, they are lagging behind safety and efficacy.
[246] [247] [248] [249]
Another attribute of quality, patient’s acceptability (healthcare adapted to the wishes and values of patient and their
family) is currently being addressed more vigorously. The conflict and confusion surrounding the influence [17] [23] [78] [250]
of regional anesthesia techniques on the (presumably higher) rate of instrumental vaginal delivery and cesarean
delivery involve all these attributes of quality in anesthesia and obstetrics, and eventually touch the legitimacy and
equity aspects as well. [40] [41] [245] [251] [252] [253]
Concerning legitimacy and equity, the data in many medical disciplines, including obstetrics and anesthesia, are
[1]
largely missing. Legitimacy and equity seem to be unpopular to address and difficult to explain within a given
medicosocial context; they remain strongly dependent on various local traditions and social and economic
circumstances. [2] [3] [5] [9] [11]
CENTRAL NEURAXIAL TECHNIQUES FOR LABOR AND VAGINAL DELIVERY
Epidural Analgesia for Labor
“Compared with other forms of pain relief, epidural analgesia is associated with the highest level of maternal
satisfaction.” The use of either an intermittent bolus or a continuous infusion of local anesthetic (with or without
[33]
an opioid) is considered to provide similar analgesic efficacy and no measurable outcome differences. The [33] [242] [243]
addition of an opioid to the local anesthetic epidural bolus or infusion has become a highly popular technique, and
the combination is believed to influence the duration and quality of labor analgesia. The efficacy and duration of
epidural opioid alone is considered inferior to epidural local anesthetic, but the benefits of an opioid should
outweigh the side effects such as nausea, pruritus, and sedation. An epidural opioid-local anesthetic [33] [254] [255]
combination may enhance the duration and quality of pain relief at less intense motor blockade and contribute to the
good progress of labor and vaginal delivery. [33]
Patient-controlled epidural analgesia has become popular as programmable pumps have become widely available.
The success of this method, however, depends strongly on the local structure and process of obstetric and anesthesia
care. The opinions, impressions, and study conclusions on its role range widely, from disappointment and
skepticism to full-blown enthusiasm. Parturient-controlled epidural analgesia may improve
[33] [242] [243] [244] [256] [257]
satisfaction, decrease the number of rescue analgesic interventions, reduce local anesthetic requirements, and
minimize motor block. It offers no significant advantage (over alternatives) concerning hypotensive episodes, high
block, and outcome of delivery. In a randomized double-blinded study, Bernard and coworkers found that a 12-
[244] [258]
mL bolus and 25-minute lockout interval, compared with 4 mL and 8-minute setting, improved the level of maternal
satisfaction. The requirements for rescue analgesia and for ephedrine to correct arterial hypotension were
comparable, as well as the course of delivery and Apgar scores in the two groups. Epidural bolus, continuous
infusion, and parturient-controlled-bolus techniques, compared in a randomized prospective fashion, provided
1119
analgesia of similar quality without differences in the outcome of delivery. A significantly larger number of
[259]
parturients required extra boluses with continuous infusion (32%) than those in the patient-controlled (13%) group.
The frequency of motor block was highest in the continuous infusion group (22%), intermediate in the patient-
controlled group (12%), and lowest with the intermittent bolus technique (4%). The use of this technique may
[259]
improve some aspects of outcome and may be of some help in the understaffed units (in a collateral way, this is
outcome as well). In addition to the financial expenses for pumps and their insufficient performance, which requires
more frequent staff engagement, this technique may not improve the outcome and efficacy in institutions with
different structure and processes of obstetric anesthesia.
The proportion of cases with inadequate epidural pain relief may vary widely for different reasons within a unit and
between hospitals. The timing of request for epidural analgesia and the individual or institutional threshold for
replacing a malfunctioning catheter are the relevant outcome variables in this respect. Le Coq and [114] [242] [243]
coworkers prospectively studied the institutional causes of failure of epidural analgesia during labor and delivery
[260]
during a 6-month period. Inadequate pain relief was found in 5% of cases during labor and in 20% during delivery.
Several factors were identified as significantly increasing the risk of epidural failure, notably the radicular pain
during catheter placement and inadequate efficacy of the first dose ( Tables 48-5 and 48-6 ). The efficacy of the first
local anesthetic dose, not the lack of combination with an opioid, was considered a major (nonpharmacologic) factor
of success. Despite the popularity of epidural
[260] [261]
TABLE 48-5 -- RISK OF EPIDURAL FAILURE DURING LABOR

Significant Variables Adequate Pain Relief (n= 432) Failure (n = 24, 5%) * Odds Ratio (95% CI) †
Weight before delivery, kg 58 ± 9 63± 9 —
Weight at delivery, kg 71 ± 10 77± 10 —
Abnormal fetal presentation, % 33 67 5.6 (2.2–1.44)
Twin pregnancy, % 3 14 —
Radicular pain, % 5 21 3.9 (1.1–13.7)
Visual analog pain score after 19 ± 21 30 ± 29 3.5(1.3–9.1) ‡
epidural analgesia, 100 mm scale
Interval of cervical dilatation 139 ± 82 197 ± 115 —
(from 5 to 10 cm), min
Rate of cervical dilatation, cm/h 2.3 ± 2.1 1.2 ± 0.5 —
Duration of labor, min 390 ± 145 489 ± 166 —
Duration of epidural analgesia, 227 ± 119 355 ± 138 9.1 (3.5–23.4) §
min
Bupivacaine dose, mg 100 ± 42 175 ± 52 —
From Le Coq G, Ducot B, Benhamou D: Risk factors of inadequate pain relief dung epidurial analgesia for labour and delivery. Can J Anaesth
45:719-723,1998. Reproduced with permission.
* Univariate analysis.
†
Multivariate analysis; CI, confidence
‡
More than 30/100 mm score 30 minutes after the first
§
6 hours during labor.
TABLE 48-6 -- RISK OF EPIDURAL FAILURE DURING LABOR

Significant Variables Adequate Pain Relief (n = 366) Failure (n = 90, 20%) * Odds Ratio (95% CI) †
Abnormal fetal presentation, % 26 39 3.0 (1.7–5.3)
Visual analog pain score after 16 ± 18 34 ± 29 4.1 (2.4–7.1) ‡
epidural analgesia, 100 mm scale
Duration of labor, min 403 ± 148 365 ± 142 —
Duration of epidural analgesia, 246 ± 119 184 ± 132 18.3 (4.8–70.3) §
min
Bupivacaine dose, mg 108 ± 44 87 ± 52 —
From Le Coq G, Ducot B, Benhamou D: Risk factors of inadequate pain relief during epidural analgesia for labour and delivery. Can J Anaesth
45:719-723,199s. Reproduced v&h permission.
* Univariate analysis.
†
Multivariate analysis; CI, confidence interval.
1120
‡
More than 30/100 mm score 30 minutes after the first dose.
§
Less than 1 hour during labor.
analgesia for labor, the technique has an inherent potential for negative outcome. It is poorly predictable whether the
spread of epidural analgesia could be converted, rapidly and urgently, to epidural anesthesia of sufficient potency
(involving high thoracic or low sacral segments) for cesarean delivery or postpartum interventions. A conversion to
spinal or general anesthesia was reported to be required in up to 50% of cases, although failure rates should not
exceed 5% to 10% in the experienced units. On the other hand, the course of labor and delivery
[33] [64] [65] [81] [108] [114] [156] [243] [262]
dictates in many cases (e.g., massive bleeding) an indication for general anesthesia, controlled ventilation, and other
life-saving measures, regardless of the initial method of analgesia.
Intrathecal and Combined Spinal-Epidural Labor Analgesia
Even if the dura is considered to be too vulnerable to be breached routinely, intrathecal drug application has [155]
become highly popular in obstetric anesthesia, particularly as a part of the combined spinal-epidural technique.
Intrathecal drugs are considered to be more rapid and effective than any other technique or method available to
relieve urgently severe pain of labor, instrumental vaginal or cesarean delivery, and postpartum interventions. [33] [108] [114]
Several studies using different protocols and drug combinations suggested that intrathecal
[153] [154] [156] [241] [263] [264] [265] [266] [267]
opioids may provide some advantages compared with the epidural local anesthetic-opioid technique. [268] [269] [270] [271] [272]
The time required to obtain satisfactory analgesia was found to be more rapid (mean difference of 6 minutes) and
the duration was prolonged for (mean) 31 minutes compared with epidural block in one study. Pruritus and PDPH
(despite using a 29-G needle) were the drawbacks of the intrathecal technique. Dunn and coworkers found both [270] [271]
analgesia techniques similarly efficacious, but again, itching was more pronounced with intrathecal than epidural
opioid. Intrathecal opioid caused a more rapid and prolonged duration of analgesia (mean difference 43 minutes), a
higher incidence of pruritus, and a lower incidence of motor weakness than epidural opioid-local anesthetic. With [272]
increasing popularity of intrathecal analgesia and the combined technique for labor, several difficulties and
problems started to emerge. They arose less from the dural perforation per se than from the variety of technical
aspects of the technique, the definition of the “safe” opioid dose, the double potential for drug overdose, and the
unpredictable spread of the combined spinal-epidural technique. [6] [33] [86] [114] [115] [153] [154] [156] [189] [192] [264] [266] [267]
Some experts strongly recommend the combined spinal-epidural technique, but others are more reserved and less
enthusiastic. The incidence and severity of maternal complications (such as pruritus, or potential for extensive
dermatomal spread, hypotension, or headache) should be considered of minor relevance (say the enthusiasts),
compared with the advantages, such as speed of analgesia, maternal satisfaction, lower failure rate, and lower
incidence of general anesthesia for cesarean delivery, of the combined spinal-epidural versus epidural technique. [33] [114]
In a retrospective review of 4000 obstetric cases, the likelihood of efficacious

[115] [156] [265] [266] [267] [268] [269] [270] [271] [272] [273] [274]
analgesia was increased if epidural block was initiated after intrathecal analgesia. Mark Norris, analyzing his [275] [265]
experiences with almost 1500 epidural catheters, found that the combined technique had a significantly higher
probability of efficacy than epidural technique without prior intrathecal analgesia. On the other hand, the arguments
from several prospective comparisons in a total of over 3000 parturients seem equally strong. The studies reported
no or only minor differences between the combined and epidural techniques, regarding analgesic efficacy, side
effects, course of delivery, and maternal and neonatal outcomes. Intrathecal opioids led to a [153] [154] [266] [267] [274] [276] [277] [278]
higher incidence of pruritus (41% vs. 1%), but nausea and vomiting and unintended dural puncture (4% vs. 2%)
were more frequent with epidural analgesia. Similarly, pruritus (47% vs. 8%) and requirement for an additional
[153]
epidural bolus (38% vs. 27%) were significantly higher in women receiving combined spinal-epidural block. The [154]
use of intrathecal opioid increased the number of emergency cesarean deliveries because of fetal bradycardia, but [278]
not in all studies. The only advantage of the combined versus the epidural technique was possibly more
[274] [279]
complete pain relief after 5 minutes. Compared with epidural analgesia, the combined block provided a similar
[277]
analgesic efficacy and maternal satisfaction (72% to 75%) but caused more technical difficulties. In one study, [266] [276]
the speed of onset of the combined and epidural block (10 ± 6 minutes and 12 ± 7 minutes, respectively), and the
incidence of failures and side effects were found to be comparable. [267]
CENTRAL NEURAXIAL TECHNIQUES FOR CESAREAN DELIVERY
“The literature suggests that spinal, epidural, or combined spinal-epidural techniques can be used effectively for
cesarean delivery. When compared to regional techniques, the literature indicates that general anesthetics can be
administered with shorter induction-to-delivery times.” The ASA Task Force concluded that “the literature is [34]
insufficient to examine the comparative merits of various regional anesthetic techniques, … but fewer complications
and improved maternal satisfaction result from regional than general anesthesia.” Thus, the outcome (at least, in [34]
some women and in some hospitals) may depend on the choice of anesthesia. The outcome and risk differences
between regional techniques are small or negligible in experienced hands. The critical [33] [64] [65] [79] [114] [115] [116] [117] [246] [249] [280]
difference between regional techniques may be the speed of onset, even if only a few minutes are involved. In many
1121
emergent cases, the amount of time available may be sufficient for a specific regional technique or the lack of time
is leading to general anesthesia. Of 212 emergent cesarean deliveries in a retrospective obstetric analysis
[62] [64] [71] [74] [81]
in Glasgow, 18% were considered urgent, requiring delivery within 20 minutes. The realized time interval from [281]
decision to delivery was (median) 25 minutes; in one third of cases, it exceeded 30 minutes; and the longest delay
was 56 minutes. Achievement of the 20- to 30-minute interval was considered possible with regional techniques, but
general anesthesia was indicated when delivery was required in less than 20 minutes. Another prospective study [281]
addressed the time interval from decision to delivery in emergency in Finland. Significant differences were found in
fetal/neonatal outcome between in-hospital versus on-call anesthesia teams; the critical decision-delivery interval
was set at 20 minutes. The troublesome aspect is that these and other investigators addressed (and the vast
[282]
majority of obstetricians consider) almost exclusively the consequences of fetal hypoxia and neonatal outcome. [132]
The fact that the maternal morbidity and mortality rates in urgent/emergent cesarean delivery are significantly
higher than in elective procedures or vaginal delivery remains too often neglected. [6] [13] [52] [61] [62] [79] [133] [283] [284]
Epidural versus Spinal Anesthesia
Almost the same proportion of cesarean deliveries was performed in 1992 in the United States under epidural (44%)
and spinal (40%) block. In the United Kingdom, in 1997, a single-shot spinal block was the most frequently
[116] [285]
used technique for elective cesarean delivery. A trend toward favoring regional anesthesia for cesarean delivery
[70]
started to emerge in the 1990s in Germany. Spinal block has reached a high level of popularity. It is
[68] [69]
recommended for elective and emergent cesarean delivery and even considered an alternative to general anesthesia
for urgent delivery. [33] [64] [79] [116]
The outcome advantages of regional anesthesia (vs. general anesthesia) originate from the presence of ongoing
epidural analgesia for labor, which could be rapidly switched to anesthesia for cesarean delivery on demand. On the
other hand, failure of epidural block may result in a negative outcome. The epidural failure rates have been assessed
to range between 4% and 25%, or between 1% and 6% for cases started in the operating room. The complete
[114] [115] [156]
and partial failure rates combined may, however, exceed 10% to 30%, depending on various clinical and
pharmacologic factors. The chances of success are seemingly better with a single-shot spinal
[64] [65] [156] [260] [286] [287] [288]
injection than with epidural block. The reported failure rates of spinal anesthesia ranged between 1% and 5%, and
could easily be higher in less experienced units. In obstetrics, the speed of onset apart, the differences (if
[33] [116] [156] [190] [289]
any) between the two techniques and their clinical significance are rather difficult to define in terms of outcome
parameters. Some investigators concluded that the quality and acceptance rate of spinal and epidural anesthesia are
identical. The differences seem to result more from pharmacologic reasons, variable sensitivity, and time invested to
evaluate “minor” differences and side effects, as well as local aspects of obstetric and anesthesia care than from the
choice of anesthesia technique per se. However, simplicity, more rapid onset and more complete spread, lower
incidence of analgesic supplementation and shivering, and higher maternal acceptance are the advantages most
frequently attributed to spinal anesthesia. [33] [64] [65] [116] [190] [246] [280] [290] [291] [292] [293] [294] [295] [296]
Riley and coworkers restrospectively compared spinal and epidural anesthesia for nonemergent cesarean delivery.
[246]
The time period from entering the operating room to incision and the total time spent in operating room (but not in
the recovery room) were significantly shorter with spinal anesthesia. The complications (dural puncture, misplaced
catheter, inadequate block in 6 of 47 cases) and higher charges and indirect costs characterized the epidural group. [246]
Although the time efficiency is a favorable attribute, it may be an outcome parameter only if it is “calculated” within
the whole practice of obstetric and anesthesia care. This measurement would probably be extremely difficult
because of too many confounding (primarily obstetric) variables. The higher charges and indirect costs, calculated [246]
from the difference in time efficiency, should not be, for obvious reasons, translated to other institutions and
different healthcare systems. The costs may be based not only on the fixed fee for anesthesia materials and
equipment but on the fixed (time-independent) operating room charges and professional fees, on the combined time
and the patient’s risk-dependent physician fee, or on some other formulas as well. A prospective and randomized
comparison showed that epidural and spinal block provided an adequate quality of anesthesia for women undergoing
elective cesarean delivery. The differences between the techniques emerged in the onset of postoperative pain. A [249]
small-scale, randomized, and double-blind comparison of epidural and spinal anesthesia found a more rapid onset [295]
of spinal block (mean of 6 vs. 14 minutes), similar time intervals in the operating room, no difference in pain scores,
and a significantly higher maternal satisfaction with epidural anesthesia. Minor side effects (mostly, pruritus due to
use of intrathecal morphine) contributed to a lower maternal satisfaction with spinal block. No outcome [295]
differences should be expected between spinal and epidural anesthesia for nonemergent cesarean delivery.
[247] [249] [289] [293] [295] [296] [297]
[33] [64] [65] [79] [116]
Combined Spinal-Epidural Anesthesia
Rawal and coworkers concluded that “for cesarean section the combined spinal-epidural technique can reduce or
[114]
eliminate most of the disadvantages of subarachnoid or epidural anesthesia alone, while preserving their respective
1122
advantages.” The accumulation of sufficient experience with the technique is still in progress. At this writing, no
investigator had yet provided convincing confirmation that the elimination of disadvantages and the preservation of
advantages of single-shot spinal and epidural anesthesia technique are possible and, particularly, that the use of
combined spinal-epidural technique improves the outcome of women undergoing cesarean delivery. In a [114] [115]
randomized study of 42 women, the intervals from induction of block to incision and delivery were shorter (mean
[298]
difference 11 and 12 minutes, respectively) with single-shot spinal than with the combined technique. A
significantly higher cephalad spread occurred with spinal (mean T4) than with combined anesthesia (mean T7). No
difference was found in the incidence of arterial hypotension (62%) (it occurred earlier after a more rapid onset of
single-shot spinal anesthesia) or other maternal and neonatal outcome parameters. A double-blind study [298]
randomized 114 parturients to receive epidural or combined spinal-epidural anesthesia for cesarean delivery. [117]
Several (called minor) advantages were found with combined anesthesia, such as earlier onset times, more intense
motor block, lower pain scores during block and at delivery, lower anxiety, and higher maternal satisfaction. Both
techniques were considered to be associated with low failure rate, good operative conditions, and high level of
maternal satisfaction. In contrast, another randomized, open comparison in 64 women found a greater efficacy
[117]
and fewer side effects with combined spinal-epidural than with epidural anesthesia for elective cesarean delivery. [287]
The combined technique was characterized by a shorter onset time (mean for T4 level, 10 vs. 18 minutes), an
excellent analgesia in all women (vs. 7 of 32 cases with pain under epidural block), a better muscle relaxation, less
shivering (3% vs. 34%), a more rapid sensory and motor recovery after procedure, and a shorter stay in the recovery
room. According to the vast majority of opinions, no outcome differences should be expected among epidural,
[287]
single-shot spinal, and combined techniques. An editorial and two in-depth reviews provide
[64] [65] [117] [156] [246] [291] [295] [299] [114] [115]
the details, controversies, opinions, and suggestions, but no consensus concerning the maternal risk-benefit of the
combined spinal-epidural technique in obstetrics. Despite the popularity and firm arguments in favor of spinal
anesthesia, a rhetorical question of whether “the dura is too vulnerable to be breached routinely in labour” is [155]
equally valid for cesarean delivery.
HEMODYNAMIC CHANGES AND PREVENTION OF ARTERIAL HYPOTENSION
The cardiovascular system undergoes a complex set of changes throughout pregnancy to provide “ideal conditions”
for fetal growth, labor, and delivery, and to cope with maternal postpartum adaptation. Individual cardiovascular
characteristics may range widely, and the adaptation should not be seen as uniform or (quantitatively, qualitatively,
or chronologically) sufficient. Healthy and less healthy parturients are exposed to different “degrees and qualities”
of cardiovascular adaptation, to the various forms of medical and obstetric treatments, and to nonuniform weight
gain, volume status, and cardiac output. The impact of these differences is difficult to assess on a
[60] [134] [300] [301] [302] [303] [304]
routine basis. Women in the last trimester, at term, and in the postpartum period are characterized more by
heterogeneity
than homogeneity, and, correspondingly, the hemodynamic effects of anesthesia, labor, and delivery show a wide
and nonuniform pattern.
Arterial hypotension is not an exclusive characteristic of single-shot spinal anesthesia. Pressure either remains stable
or falls with intrathecal analgesia, epidural or spinal-epidural technique, or general anesthesia. Appropriate
prophylactic measures are required, and drug dosages and speed of injection must be adapted to the individual
tolerance of the maternal cardiovascular system. Arterial pressure depends on too many
[33] [64] [65] [81] [114] [115] [116] [117] [122] [305]
variables, not least on the (un)reliability of the method of measurements. Hypotension may or may not represent a [306]
serious event. Almost as a rule, in prospective studies, the incidence and severity of arterial hypotension show no
correlation with outcome. Only occasionally (a characteristic of case reports), the cardiovascular changes provoked
by anesthesia and delivery lead to morbidity and negative outcome. A requirement for ephedrine, 0 or 50 mg; of and
by itself, is not an outcome variable. The consequences of profound arterial pressure decrease, however—such as
nausea and vomiting, use of additional drugs, maternal dissatisfaction, prolonged treatment and hospitalization,
maternal or neonatal short-term or permanent damages, or death—denote the minor, major, and final aspects of
outcome. [6] [14] [33] [61] [64] [65] [79] [80] [116] [122] [188] [196] [197] [198]
The number of studies focusing narrowly on arterial hypotension and its prevention by far outnumber the studies
addressing the cardiovascular changes induced by regional techniques or general anesthesia with appropriate
methodology. A prospective study enrolled 22 nonlaboring women at term who selected general
[146] [307] [308] [309] [310] [311] [312] [313]
or epidural anesthesia for cesarean delivery. Crystalloids, 10 mL/kg (general) or 15 mL/kg (epidural), were given
[307]
before anesthetic induction. Cardiac output was measured by Doppler echocardiography above the aortic valve in
the lateral position. Compared with baseline values, cardiac output increased (mean for the group) by 9% and 19%
after induction of general and epidural anesthesia, respectively. Stroke volume was the major factor in the epidural
group, and both stroke volume and heart rate contributed to the increase of cardiac output with general anesthesia.
Cardiac output peaked at 15 to 30 minutes after delivery with both techniques (37% to 26% with epidural and 28%
to 17% with general anesthesia), then slowly decreased and remained at the preoperative level for 24 hours after
1123
delivery ( Fig. 48-1 ). In a prospective randomized comparison, Robson and coworkers found few
[307] [311]
hemodynamic (but no outcome) differences between spinal and epidural blocks in 32 parturients undergoing
cesarean delivery. Preloading with crystalloids increased the cardiac output by (mean) 14% (spinal) to 20%
(epidural). Cardiac output returned within (mean) 3% to 6% of the baseline value (for 15 min) after spinal block,
whereas, with
Figure 48-1 Anesthesia and cardiac output changes before and

after cesarean delivery. Data are mean ± standard deviation.
(Modified from James CF, Banner T, Caton D: Cardiac output
in women undergoing cesarean section with epidural or general
anesthesia. Am J Obstet Gynecol 160:1178–1184, 1989.
Reproduced with permission.)
gepidural anesthesia, it remained (for 30 min) at 22% to 26% above the baseline. No significant changes were found
in heart rate and systemic vascular resistance with either technique. The volume of fluids, amount of ephedrine, and
incidence of arterial hypotension were significantly higher in the spinal group. The subsequent study by the same
investigators suggested that continuous spinal anesthesia may provide greater hemodynamic stability, although the
course of cardiac output and arterial pressure changes starkly resembled the effects of single-shot spinal block. [146] [311]
It could be argued that the increase of cardiac output of shorter duration (assuming that arterial pressure is
maintained within a “reasonable” range) with spinal and general anesthesia is more favorable for pregnant women
(certainly, for cardiovascular patients with limited reserves) than a longer lasting high cardiac performance
maintained by preload and epidural block. The slightly different findings of a Doppler echocardiographic study
[307] [311]
may be explained by the difference between epidural technique for cesarean and vaginal delivery. Fluid preload [310]
alone significantly increased heart rate (11%) and cardiac output (20%) and decreased systemic vascular resistance
(19%) without changing arterial pressure. After epidural analgesia, cardiac output returned to the baseline values,
heart rate remained elevated, and resistance decreased, without changes in arterial pressure. Epidural anesthesia in [310]
the left semirecumbent position and after prehydration increased the Doppler blood flow velocity in the femoral
artery and vein. No changes in the vessels’ diameter as well as stable (upper arm) arterial pressure indicated a higher
blood flow and decreased vascular resistance in the leg. Valli and coworkers conducted a prospective, [309] [312]
randomized study in 24 parturients. The femoral artery Doppler-derived flow velocity profiles and pulsatility index
(systolic peak end-diastolic velocity/mean velocity) were obtained in the lateral position after crystalloid
prehydration, 15 mL/kg, and when spinal, epidural, or combined spinal-epidural anesthesia reached the T7 sensory
level. Pulsatility index (a surrogate of vascular resistance distal to measurement) decreased similarly (by 26% to
[312]
28%) in all three groups after prehydration. The T7-sensory changes were obtained (mean) 13, 17, and 8 minutes
after the spinal, epidural, and combined techniques, respectively. The pulsatility index further decreased by (mean)
22% with spinal, 40% with epidural, and 26% with combined block. Etilephrine was used prophylactically only in
women receiving spinal and combined anesthesia. All three techniques provided a similar safety and positive
outcome in women with uncomplicated pregnancy undergoing cesarean delivery. [312]
Intrathecal opioids may result in some cases, independent of quality and duration of sensory changes, in arterial
pressure decrease. The mechanism seems to be mediated not by sympathetic vasodilation but by spinal cord
receptors and pain relief per se. Single-shot spinal anesthesia is considered not exclusively but more
[33] [241] [264] [305] [314]
frequently than epidural anesthesia to lead to a rapid and intense sensory and motor blockade associated with arterial
hypotension. Arterial hypotension may be attenuated but not eliminated by proper positioning of the parturient, use
of lower doses of intrathecal and epidural drugs, crystalloid or colloid fluid preloading, and vasoactive drugs. [33] [64] [65] [79]
In addition to lateral positioning, a fluid preloading (with crystalloids, colloids, or both) is

[116] [122] [146] [190] [311] [313] [315] [316] [317]
recommended unequivocally before spinal anesthesia in an amount sufficient to expand the blood
[79] [116] [122] [316] [318] [319] [320]
volume. The incidence of hypotension may be reduced from greater than 90% (no prevention) to 10% by fluid
[313]
preloading and use of left uterine displacement or to even less than 5% by using low-dose hyperbaric bupivacaine
[116]
and the head-down tilt. Ephedrine (most popular), phenylephrine, and infusion of angiotension II are equally
[315]
effective in maintaining arterial pressure within an acceptable range or in restoring it. “The [33] [64] [65] [79] [116] [122] [316] [317] [318] [321] [322]
1124
choice of vasopressor drug appears to be of minor importance compared with the avoidance of hypotension.” The [323]
combined technique may offer an advantage of using intrathecal low-dose local anesthetic and opioid, with the
epidural catheter as a backup in case of insufficient analgesia. Some investigators failed to prevent arterial
hypotension, but others reported that fluid preload, ephedrine, and low-dose combined technique reduced the
[116] [190]
incidence to less than 10%. An important aspect of management concerns the use of spinal anesthesia in women
[316] [324]
with insufficient epidural block. The reports of high cephalad spread and potential for complications by using spinal
anesthesia after a failed epidural block triggered a debate if such a procedure should be contraindicated. Obviously,
monitoring an epidural labor analgesia to replace the catheter on time and attending to clinical, pharmacologic, and
technical details are required when spinal block is performed after partially sufficient epidural anesthesia, or vice
versa. A maternal exposure to a new epidural attempt or to general anesthesia may increase similarly the risks
[64] [116] [325]
of hemodynamic complications, particularly under urgent conditions.
Given the difficulties in assessing individual cardiovascular tolerance, the option of a slow induction and a slow
spread of regional anesthesia led to a high level of popularity of epidural anesthesia (less frequently, intrathecal
techniques) for cesarean or vaginal delivery in pregnant cardiovascular patients. In a few reported cases, [60] [144] [149] [151] [152]
combined spinal-epidural analgesia for labor provided excellent hemodynamic stability in patients with complex
cardiovascular diseases. [326] [327]
PREECLAMPSIA
Hypertension in pregnancy is one of the leading causes of maternal complications and death in many countries. [5] [6] [13]
The detailed discussion on the diagnostic and therapeutic aspects of preeclampsia as well as the
[48] [51] [52] [59] [80] [328] [329]
anesthetic considerations are provided elsewhere in the anesthesia literature. Regional anesthesia could be [328] [329] [330] [331]
advantageous if its use is adapted to or avoided owing to specific risks associated with preeclampsia, such as
thrombocytopenia and distorted hemostasis, hypovolemia, poorly controlled hypertension, interaction with
antihypertensive drugs, and the potential for rapid deterioration of the cardiovascular, renal, and central nervous
functions. Bleeding, hypocoagulopathy, disseminated intravascular coagulation, liver dysfunction, and
[328] [329] [330] [331]
unstable cardiovascular and cerebral status signal a serious multiorgan deterioration and a contraindication for
regional anesthesia; under such conditions, an emergent cesarean delivery under general anesthesia is indicated. The
outcome generally seems to depend much more on the severity and course of the disease (highly variable) and the
local experiences than (taken in isolation) the choice of anesthetic technique. Using appropriate hemodynamic
monitoring and fluid therapy, at a narrow margin of safety between hypovolemia and overt pulmonary and cerebral
edema, early use of epidural analgesia may improve the control of arterial hypertension, in addition to providing an
effective and highly flexible peripartum analgesia and anesthesia. A large, retrospective study concluded [173] [328] [329] [330]
that in labor “epidural anesthesia use did not increase the frequencies of cesarean delivery, pulmonary edema, and
renal failure among women with severe hypertensive disease.” [332]
As in healthy women, the popularity of regional anesthetic techniques in preeclamptic patients has increased. A
prospective study randomized 80 women with severe preeclampsia undergoing cesarean delivery to receive general,
epidural, or combined spinal-epidural anesthesia. The outcome was similar and all three methods were considered
equally acceptable. A detailed study of preeclamptic women undergoing cesarean delivery with spinal anesthesia
[333]
after crystalloid preloading found in only 3 of 12 cases an arterial pressure decrease less than 70% to 80% of the
baseline. A rapid correction of hypotension resulted in good maternal and neonatal outcomes. In an observational [334]
study, a low-dose spinal anesthesia for cesarean delivery provoked, at a similar level of sensory block, a comparable
incidence and severity of arterial hypotension in healthy and preeclamptic women. An institutional retrospective [335]
(1989–1996) survey identified 138 preeclamptic patients receiving spinal (103) or epidural (35) anesthesia for
[336]
cesarean delivery. The reason for (and the risk of) a significantly higher amount of crystalloids used in patients
receiving spinal anesthesia rather than epidural anesthesia (mean 1780 vs. 1359 mL) remained unclear, but the
arterial pressure changes were found to be similar. No maternal and fetal outcome differences resulted from the use
of either spinal or epidural techniques. Another prospective study randomized 28 preeclamptic women to receive
[336]
epidural or spinal anesthesia for urgent cesarean delivery. A similar amount of ephedrine was required in both
[337]
groups. Inadequate analgesia was the “major complication” in the epidural group. The outcome was not different,
and it was concluded that spinal anesthesia is safe and efficacious for these patients. A warning that larger [337]
prospective studies are needed to properly assess the risks of spinal versus general anesthesia for cesarean delivery
in preeclamptic women, and that, currently, there is insufficient evidence to support the widespread use of spinal
block in preeclampsia, seems over rigorous. Many maternal and fetal arguments might be raised against the spinal
[338]
(or epidural or combined) technique. No negative anesthesia-related outcome data, whatsoever, are actually
available. General anesthesia in severe preeclampsia may be bound with numerous, poorly predictable, and
marginally treatable complications, even in experienced hands. Ahmed and coworker exposed the differences[328] [329] [339]
between spinal and general anesthesia in a series of preeclamptic women. The incidence of complications was not
only higher with the general (69%) than with the spinal (47%) technique, but the complications differed
qualitatively as well. Hypertension (69%), difficult intubation (25%), pulmonary edema (13%), delayed recovery
1125
(13%), and death (4%) showed a tendency to negative outcome with general anesthesia compared with management
of “minor” problems, such as hypotension (47%), technical difficulties with the block (29%), and vomiting (6%) in
the spinal group. The morbidity and mortality rates are (presumably) lower in other institutions and countries with
[339]
different structures and processes of antenatal, obstetric, and anesthetic care. Nevertheless, the outcome relationship
of spinal versus general anesthesia was remarkable. Spinal block was found suitable for postpartum tubal ligation
after normal pregnancy and after pregnancy complicated by preeclampsia. Hypertensive patients experienced more
profound hypotension, but the lowest pressure values and ephedrine requirements were similar in both groups. [340]
MATERNAL SATISFACTION
Maternal satisfaction results from many (subjective and objective) social and psychological variables, as well as
from the quality of obstetric and obstetric anesthesia care, maternal previous experience, expectations and concerns,
timing and quality of information provided before labor, individually adapted or less adapted treatment, and other
“human” factors on the healthcare provider site. Most probably, the attributes of care that lead to maternal
satisfaction are acceptability and equity ; meaning, the care adapted to individual wishes, expectations, and values;
[1]
and fair distribution of service and its benefits. In general, maternal satisfaction is considered a semireliable or
unreliable (nonhard, nonlinear, and non-technique-specific) indicator of outcome. Future studies,
[75] [76] [77] [78] [297] [341]
applying an improved methodology of measuring patient satisfaction, may convert it to a more specific indicator of
outcome. [29] [342]
Two studies showed that even a perfectly efficacious epidural analgesia for labor (taken as an isolated factor) may
not change parturients’ anxiety and because of more frequent use of forceps delivery and prolonged labor, may
result in a high rate of maternal dissatisfaction. A prospective, randomized study of 97 parturients showed that
[343] [344]
epidural analgesia was superior to parenteral pethidine in providing pain relief with fewer side effects. Significantly
more women (73% vs. 30%) decided to request epidural analgesia for a subsequent labor. A prospective Finnish [345]
survey of 1091 parturients found a low rate of dissatisfaction with the childbirth experience associated with
instrumental delivery but not with use of analgesia. However, 80% of women described their pain as severe to
intolerable and more than half of these women complained of inadequate pain relief. Similarly, other studies found
[346]
no direct relationship between satisfaction and pain management. Epidural analgesia was rated significantly
[347] [348]
better than no or intravenous pethidine analgesia, but 43% to 58% of women experienced severe to unbearable pain
during epidural labor analgesia. A European multicenter study that interviewed parturients before and after
[348]
delivery concluded that epidural analgesia was more effective than other methods of pain relief, and that the most
satisfied mothers were those who expected more pain but who instead received effective analgesia. A [341]
questionnaire survey of 520 women revealed that factors significantly associated with high levels of maternal
satisfaction were good analgesia during labor (particularly epidural), vaginal delivery, adequate preparation for labor,
and staff care-oriented to the individual. A prospective study of 447 low-risk parturients in early active labor
[349]
evaluated the factors that influence the recommendation of epidural analgesia by obstetricians and its acceptance by
women. Epidural technique was recommended more often to low-parity, younger women exhibiting more pain.
Women more likely to accept epidural analgesia for labor were those who perceived greater pain, were more secular,
and had low parity and a higher level of education. The interviews with women who refused regional anesthesia
[78]
for cesarean delivery revealed that the most frequent reasons were fear of backache, fear of the needle, and
apprehension of witnessing the operation. Holdcroft and coworkers identified 10 among 39 women undergoing
[75] [77] [76]
elective cesarean delivery who requested general anesthesia. These women had a similar level of anxiety but were
more depressed and had experienced more pregnancies overall and more without live babies. Maternal sense of
control was found to be the item most related to satisfaction in women who received regional anesthesia. [350]
The full complexity of “outcome” was shown in a pioneering, small-scale study in Leiden, the Netherlands. [250]
Pregnant women, mothers, and obstetricians participated in a “standard reference gamble” to determine the value of
12 different outcomes concerning the type of birth and infant outcome. The values attached to the birth process and
maternal and neonatal outcome were found to differ significantly among pregnant women, mothers, and
obstetricians. Obstetricians tended to view permanent neurologic handicap as a worse outcome than neonatal death
and overestimated the burden caused by cesarean delivery than did pregnant women and mothers. Obstetricians also
differed more among themselves in the values attached to specific outcomes than did pregnant women and
mothers.[250]
Local Anesthetics, Opioids, and Clonidine
LOCAL ANESTHETICS
Lidocaine and bupivacaine are the most frequently used local anesthetics in obstetrics. The popularity of
chloroprocaine (available only in some countries) and tetracaine seems to be sharply decreasing, and the new drugs,
1126
ropivacaine and levobupivacaine, still do not have a firm cost-benefit place in the clinical routine. [64] [114] [115] [116] [241] [242] [243] [351]
Local anesthetics, despite different pharmacodynamic and kinetic characteristics and different potential for
[352] [353] [354]
toxicity, may all provide a similar level of safety and efficacy in obstetric anesthesia. 2-Chloroprocaine is an
exception, although its pharmacokinetic and fetal/neonatal characteristics are nearly ideal. The toxic effects (owing
to preservatives in previous years) and peculiar side effects, such as analgesic interference with other drugs, limit the
use of 2-chloroprocaine in obstetric anesthesia. No negative maternal or neonatal outcome could be associated
[64] [242] [355]
with the choice of local anesthetic. The impact on outcome depended on other factors, such as concentration and
baricity, amount of drug, addition of opioids or adjuvant drugs, and other aspects of management (positioning,
fluids).
Lidocaine
Epidural lidocaine is characterized by fast onset and moderate duration of action. It is equipotent with bupivacaine
in a ratio of 4 to 1. For labor analgesia, lidocaine was previously found to be insufficiently potent in lower
[64] [242] [351]
(<1%) concentrations. A 1.5% solution without or with epinephrine (to improve the quality of block and limit
[242] [356]
the plasma concentration), provided sufficient analgesia without adversely affecting parturients, neonates, or
characteristics of labor. Epinephrine contributed to a significantly longer duration of pain relief (mean 107 vs. 66
min). In 1995, Columb and Lyons introduced a concept of minimum local analgesic concentration for epidural
[356] [357]
labor analgesia. The design was used in several studies to determine the effective concentration (EC) (actually, an
EC/dose in a 20-mL volume) of various local anesthetics, alone or combined with opioids for women in labor. [254] [255]
The minimum EC denotes a concentration of local anesthetic that provides an efficacious analgesia (< 10
[357] [358] [359] [360]
on a visual analogue scale of 100) for 50% (EC50 ) and 95% (EC95 ) of a studied population. The EC should not be
seen (for various local, demographic, and obstetric reasons) as an absolute value but as a reliable clinical starting
point. The minimum EC50 and EC95 of lidocaine in early labor (3- to 5-cm cervical dilation) was set at
[242] [351] [357] [359]
0.37% and 0.52%, respectively. With increasing intensity of pain in the later phase of labor, the effective
[242] [357]
concentration of lidocaine seems to be increasing threefold to 1.5%, which is identical to a threefold increase of [356]
the EC for bupivacaine. [358]
For epidural anesthesia lidocaine, 1% to 2%, is considered a drug of choice when rapid and intense anesthesia is
required for instrumental or operative delivery. For cesarean delivery, the maternal effects were similar
[33] [64] [242] [361]
after epidural bupivacaine, 0.75% (in the mean time pulled back from obstetrics), 2-chloroprocaine, 3% and 2%,
lidocaine, with or without epinephrine. In a randomized, double-blinded study of 60 women undergoing cesarean
[362]
delivery, Norton and coworkers compared epidural lidocaine, 2%, with epinephrine, 5 µg/mL, with plain
[363]
bupivacaine 0.5%. Significantly shorter time to establish the block above the T6 dermatome (mean 22 vs. 31 min), a
more intense motor block, and a more rapid regression of epidural anesthesia were found with lidocaine, at similar
quality of analgesia and incidence of complications with both drugs. In another study, epidural lidocaine, 2% and [363]
bupivacaine, 0.5% (both with epinephrine) resulted in an identical onset time of anesthesia at the T5 level (32–33
min). Bupivacaine was characterized by a longer duration of sensory (mean 253 vs. 351 min) and motor (mean 195
vs. 329 min) block, and lidocaine provoked a higher incidence of shivering (72% vs. 25%). The impact of motor [364]
involvement was evaluated by pulmonary function tests in healthy parturients undergoing cesarean delivery. Peak
expiratory pressure (largely dependent on abdominal musculature) showed a significantly greater decrease after
lidocaine, 2% with epinephrine than after plain bupivacaine, 0.5%. [365]
A prospective, randomized study of 20 parturients undergoing elective cesarean delivery found a more rapid onset [366]
(mean time to delivery 33 vs. 40 min) and a higher incidence of arterial hypotension after epidural 2% lidocaine
with epinephrine (7/10) than plain bupivacaine, 0.5% (1/10). The drug distribution among the mother, placenta, and
fetus was similar, attributed to the effect of hypotension on the kinetics of lidocaine. [366]
In a randomized study of women receiving epidural labor analgesia (maintained at T10) and undergoing urgent
cesarean delivery, Gaiser and coworkers compared lidocaine with epinephrine, 1.5%, and 2-chloroprocaine, 3%,
[367]
both mixed with sodium bicarbonate. The time to achieve the sensory changes at T4 was very rapid but slightly
shorter (mean 3.1 vs. 4.4 min) with 2-chloroprocaine. [367]
A double-blinded, randomized trial compared bupivacaine, 0.5%, lidocaine, 2% with epinephrine, and an equal
mixture of two drugs in a 20-mL volume to convert ongoing labor analgesia into epidural anesthesia for emergent
cesarean delivery. Lucas and coworkers found no difference in the onset time at T4, because it took 10 to 20
[369]
minutes with all three solutions for the median 50% of cases (interquartile range) ( Fig. 48-2 ). In the lidocaine-
epinephrine group, in 3 of 28 women, the spread of analgesia was insufficient, and a switch to general anesthesia
was required. Although epidural lidocaine-epinephrine is considered a rapid-acting drug, it may require less than 5
[368]
minutes or exceed 30 minutes in elective and even in top-up cases. Onset is a relative variable with [361] [363] [364] [367] [368]
several subjective components, such as acceptable sensory level for incision, methods of testing, individual
experience, and individual maternal satisfaction.
1127
Intrathecal lidocaine anesthetic, in a 5% hyperbaric solution, showed unpredictable spread, quality, and frequency of
side effects. On the other hand, in a 1.5% to 2% solution, hyperbaric lidocaine was considered to provide the ideal
[116]
conditions for most obstetric procedures. In a randomized, prospective double-blinded study, hyperbaric lidocaine
[33]
without or with fentanyl (15 µg) was compared in 28 women undergoing elective cesarean delivery. Palmer and [369]
coworkers found a similar quality of analgesia, but fentanyl increased (mean 71 vs. 101 minutes) the duration of
[369]
effective pain relief. Women receiving fentanyl were less likely to experience nausea and vomiting, but no
differences were noted in the incidence of pruritus or shivering. In a nonrandomized study, no radicular irritation [369]
was found in 67 parturients after intrathecal 5% hyperbaric lidocaine. When spinal anesthesia was used for oocyte [370]
retrieval for in vitro fertilization in a randomized, double-blinded fashion in 56 women, 60 mg of hyperbaric

lidocaine in a 1.5% or 5% solution
Figure 48-2 Onset of epidural anesthesia for cesarean delivery in

women with ongoing labor epidural analgesia. B, Bupivacaine;
BL, bupivacaine-lidocaine-epinephrine mixture; L, = lidocaine-
epinephrine. The range, interquartile range (box), and median
(vertical bar) values are shown at the top for the three groups.
(From Lucas DN, Ciccone GK, Yentis SM: Extending low-dose
epidural analgesia for emergency caesarean section. A
comparison of three solutions. Anesthesia 54:1173–1177, 1999.
Reproduced with permission.)
(both combined with fentanyl, 10 µg) did not cause any side effects. The recovery was significantly shorter with the
1.5% solution. The risk of transient neurologic symptoms (see earlier discussion) decreased the popularity of
[371]
hyperbaric lidocaine, 5%. Its current role (even at lower doses and in a less concentrated solution) is, at the least,
[116]
controversial.
Bupivacaine
Epidurally, bupivacaine is characterized by a slower onset and longer duration of action. It is equipotent with
lidocaine in a ratio of 1 to 4. Evaluating the minimum EC of lidocaine and bupivacaine for labor analgesia,
[64] [242] [351]
Columb and Lyons came to the conclusion that bupivacaine is actually 5.7 and 7 times more potent in weighted
[357]
and molar ratios, respectively, than lidocaine. Subsequently, the median values of minimum EC50 of bupivacaine
were found to range widely (heterogeneity of the patients’ and investigators’ population) between 0.065% and
0.104% ( Fig. 48-3 ). In the first stage of labor, the minimum EC95 of bupivacaine (without an opioid)
[254] [357] [359] [360] [372]
usually exceeds 0.125% and may be as high as 0.18%. The changing intensity of pain throughout labor
[242] [357] [359] [360] [373]
is changing the requirements for epidural drugs. Capogna and coworkers showed that the minimum EC50 of [358]
bupivacaine increased by a factor of 2.7 to 3.2 from the early to the late phase of labor (from 0.048% to 0.14%). [358]
By extrapolation, the minimum EC95 of bupivacaine in the late labor might be as high as 0.4%.
For cesarean delivery, the major disadvantage of epidural bupivacaine is a relatively slow onset of action. [64] [363] [364] [366]
The onset (to T4–T6) may be improved by increasing the initial dose. In the two studies, 30 mL of plain 0.5%
bupivacaine required only (mean) 17 minutes and 6 minutes. However, the onset of surgical anesthesia in the
[374] [354]
majority of cases of a new epidural block was reported to last 20 to 50 minutes, making bupivacaine a poor choice
for urgent cesarean delivery. However, for extending ongoing analgesia, bupivacaine showed
[64] [288] [363] [364] [366] [375]
characteristics similar to these of lidocaine-epinephrine. A longer duration of action of bupivacaine, although

[368]
favorable from the point of postpartum pain relief, involves a less desirable prolonged motor block. The [288] [354] [363] [364] [374]
duration of sensory block exceeds the duration of motor block with bupivacaine, a highly advantageous
characteristic and, actually, an outcome variable. The difference was found to range from (mean) 22 minutes, over [364]
3 hours at T12 level to greater than 2.5 hours for complete offset of block. With an epidural dose of 30 mL of
[374] [354]
0.5% bupivacaine, arterial hypotension could be expected in 90% to 100% of cases, but with a lower volume [354] [374]
the incidence of hypotension could be relevantly reduced. Because of the high epidural dose requirements,
bupivacaine is considered to possess a higher potential for cardio- and neurotoxicity compared with other local
anesthetics, particularly for
1128
Figure 48-3 Minimal effective concentration (EC50 ) of bupivacaine in labor: The

opioid effect. Data are median with 95% confidence interval. (Modified from
Riley ET: Neuroaxial analgesia for labor. Part III: Epidural drugs. In Norris
MC (ed): Obstetric Anesthesia, 2nd ed. Philadelphia, Lippincott Williams &
Wilkins, 1999, pp 333–342; Polley LS, Columb MO, Wagner DS, Naughton NN:
Dose-dependent reduction of the minimum local analgesic concentration of
bupivacaine by sufentanil for epidural analgesia in labor. Anesthesiology
89:626–632, 1998. Reproduced with permission.)
pregnant women. Given the advantage of an epidural catheter, a rapid injection of large volumes of local anesthetics
should be strongly discouraged. [64] [65] [122] [351] [355]
Intrathecal bupivacaine provides an excellent quality and sufficient duration of sensory block (compared with
lidocaine and tetracaine) and a lower duration of motor block (compared with tetracaine). It has become the most
popular drug for spinal anesthesia for cesarean delivery. One of the dominant factors governing the
[64] [116] [289] [290] [291]
spread of subarachnoid local anesthetics is the baricity of the solution. Other factors, such as position and
subsequent repositioning, dosage (and volume), combination of drugs, and the length and anatomic configuration of
vertebral column all contribute (individually and therefore less predictably) to the spread, quality, and side effects of
intrathecal anesthesia. In contrast to the equivocal opinions concerning the effects,
[116] [280] [315] [376] [377] [378] [379] [380] [381] [382] [383]
predictability, and side effects of plain versus hyperbaric intrathecal bupivacaine in nonobstetric populations, [384] [385] [386]
a hyperbaric bupivacaine solution is the preferred choice in obstetrics. It is considered a reliable and fast-acting
(onset 2–10 min) drug for cesarean delivery. The recommended dose to obtain an
[116] [190] [290] [315] [316] [324] [381] [387] [388] [389]
efficacious block ranges widely, from 7.5 to 15 mg in a 0.25% to 0.75% solution. The conflict among the quality of
surgical anesthesia, maternal satisfaction, sensory changes reaching but limited to the T4 level, and the incidence of
hypotension, nausea, and other side effects remains only partially solved. Despite high popularity and widespread
use, the “ideal margin of safety and efficacy” of spinal anesthesia for cesarean delivery remains narrow. When
0.25% hyperbaric bupivacaine was used in a prospective randomized study of 60 parturients undergoing cesarean
delivery, the 8- to 9-mg dose led to a lower spread, duration, and efficacy of sensory analgesia, almost no complete
motor block, and a lower incidence of arterial hypotension, compared with the 9- to 11-mg dose. In another [381]
prospective study, 0.75% (11.25 mg) and 1% (12.5 mg) of hyperbaric bupivacaine provided a similar onset (mean
[387]
4 minutes) and a similar duration of block (regression to T10 level, mean 89 to 94 minutes). The 0.75% solution
offered several significant benefits, and bupivacaine, 1% resulted in a shorter duration of analgesia and a slightly
higher incidence of PDPH and backache. Hyperbaric 0.75% bupivacaine, 15 mg, was recommended as an
[387]
approach to providing excellent operative conditions without intrathecal or intravenous supplements, although the
maximal spread may easily reach the cervical segments. [116]
A bupivacaine dose of 10 to 12.5 mg in a 0.5% to 0.75% hyperbaric solution offers a compromise between efficacy
and side effects for a majority of parturients undergoing cesarean delivery. [116] [249] [290] [315]
Plain isobaric (actually hypobaric) bupivacaine is considered, for unknown reason, to be a less reliable drug in
obstetrics. In a randomized, double-blinded trial, 12.5 mg of 0.5% hyperbaric and plain bupivacaine resulted in
equal effects and side effects in 40 parturients undergoing cesarean delivery. The maximum cephalad levels reached
the T4 to C1 level in both groups. More recently, in a double-blinded study of 76 parturients, the effects of 9 mg
[390] [190]
of 0.5% bupivacaine, combined with fentanyl in a plain or hyperbaric solution, were almost indistinguishable. The
onset time to reach T5 level for the median 80% of cases was 7 to 22 minutes and 10 to 30 minutes with the plain
and hyperbaric solution, respectively. Cervical spread in five of six cases occurred after hyperbaric bupivacaine. The
1129
motor block developed and diminished slightly but significantly faster (mean 92 vs. 110 min) after hyperbaric
solution. Plain and hyperbaric bupivacaine (both mixed with morphine, 0.2 mg) in a double-blinded, randomized
[190]
study of cesarean delivery in 30 women, resulted in a similar sensory and motor block, quality of intra- and
postoperative analgesia, incidence of side effects, psychometric scores, and no clinical outcome differences. [280]
Ropivacaine
Huge pharmaceutical, experimental, and clinical efforts have been invested to provide a substitute for bupivacaine.
The search for the new local anesthetics was governed seemingly by an assumption that anesthetic drugs
(resembling “weapons”), not the people within specific medical and social circumstances, are primarily responsible
for the anesthesia-associated complications and deaths. Simultaneously, however, the practice of regional
[14] [22] [30] [31]
anesthesia changed to the widespread use of epidural catheters, test doses, and smaller single doses of local
anesthetics, all factors that decreased (or, presumably, should have decreased) the potential for clinical manifestation
of toxicity of local anesthetics. The new drugs, ropivacaine and levobupivacaine, were soon labeling as offering no
relevant clinical advantage that might be translated into an improved outcome in obstetrics. “From the standpoint of
systemic toxicity, the expected benefit of these new drugs during routine labour analgesia is questionable. Their use,
in theory, may be more beneficial to patients having a caesarean section.” “Ropivacaine has not lived up to [352]
expectations in obstetric analgesia and anesthesia.” [353]
For epidural analgesia, according to the multicenter studies, the EC50 of ropivacaine in the first stage of labor ranged
from 0.111% to 0.156% (CI, 95%, 0.10–0.176), and the EC95 value may reach 0.24%. The analgesic potency of [359] [360]
ropivacaine was found to be 0.6 (95% CI, 0.49 to 0.75) relative to bupivacaine. Effective ropivacaine analgesia
lasted longer (mean 94 vs. 73 min) than that observed with bupivacaine. Nevertheless, the advantages of [359]
ropivacaine (lower toxicity and lower intensity of motor block, which should result in fewer instrumental and
cesarean deliveries and should denote an improved outcome) was questioned concerning the difference in analgesic
potency between ropivacaine and bupivacaine. Some concerns were expressed regarding the study design to
[359] [360]
determine the EC of local anesthetics, the size and characteristics (heterogeneity) of the population, and the real
potency relationship between the drugs. Other investigators studied a priori a higher concentration (0.10%–
[372] [391]
0.25%) of ropivacaine without or with an opioid. Epidural ropivacaine (0.125%–0.20%) provided a similarly
efficacious labor analgesia as bupivacaine. In Manchester, England, ropivacaine, 0.25%, compared with
[392] [393] [394] [395] [396]
bupivacaine, 0.25%, resulted in a higher incidence of spontaneous vaginal delivery. Two low-dose ropivacaine [397]
studies, of different sizes and from different countries, came to dissimilar conclusions. Ropivacaine, 0.08% mixed
with fentanyl resulted in highly effective epidural labor analgesia. Compared with bupivacaine, 0.08%, and fentanyl,
ropivacaine better preserved ambulation and spontaneous micturition during labor and reduced the incidence of
forceps delivery (10% vs. 35%) in a randomized trial of 40 parturients. In another randomized, double-blinded [398]
trial of 200 parturients, a patient-controlled epidural analgesia with ropivacaine 0.1%-sufentanil, compared with
[399]
bupivacaine 0.1%-sufentanil, resulted in less motor block but did not reduce the incidence of instrumental delivery.
Although pain scores changed similarly during labor and delivery, maternal satisfaction was higher with
bupivacaine. [399]
For cesarean delivery, epidural ropivacaine, 0.5% to 0.75%, provided very similar effects and side effects compared
to bupivacaine 0.5%. The significant differences (with a potential for an improved outcome) were a lower incidence
of nausea and a shorter duration of motor block (45 min–3 hr, depending on grade) with ropivacaine 0.5%
[375]
; [288] [374] [375]
the later advantage disappeared when ropivacaine, 0.75% was used. [400]
Levobupivacaine
For epidural labor analgesia, the EC50 of levobupivacaine, evaluated in a randomized, double-blinded fashion in 60
parturients, was found to be 0.083% (95% CI; 0.065–0.101). The median EC95 of levobupivacaine exceeded 0.14% [373]
compared with 0.125% to 0.180% of bupivacaine. The potency ratio of levobupivacaine to bupivacaine was
[357] [373]
calculated as 0.98 (95% CI 0.67 to 1.41), although in molar terms it was only 0.87 (0.60 to 1.25). The concentration-
response and the potency ratio curves indicate that levobupivacaine between the EC50 and EC95 values (relevant for
women with a lower pain threshold and, particularly, when intensity of pain starts to increase during labor) may be
more potent than bupivacaine. Although these findings remain to be confirmed, “any expected benefits to be
[373]
gained from lower cardiotoxicity of levobupivacaine do not appear to be at the expense of potency.” [352]
For cesarean delivery, epidural levobupivacaine was compared with bupivacaine in a randomized, double-blinded
study in 60 parturients. With a volume of 30 mL, the onset time of T4 to T6 sensory block (mean 8 vs. 6 min), the
[354]
time to offset of motor block (mean 241 vs. 265 min), the time to offset of sensory block (mean 451 vs. 428 min),
the incidence of hypotension (84% vs. 100%), and the overall quality of anesthesia did not differ between
levobupivacaine, 0.5%, and bupivacaine, 0.5%, respectively. [354]
1130
OPIOIDS
No firm arguments are available to suggest the optimal choice of an opioid, or the dosage, intervals, and mode of
application for women undergoing vaginal labor or cesarean delivery. [33] [64] [65] [116] [241] [242] [243] [264] [401] [402] [403]
Epidural Opioids for Labor Analgesia
Fentanyl and sufentanil alone, compared with a local anesthetic-opioid combination, possess an inferior efficacy for
labor analgesia in the majority of parturients. In a study of 46 women, fentanyl, 100 µg, and 0.25%
[255] [404] [405] [406] [407]
bupivacaine resulted in reliable labor analgesia with more rapid onset and longer duration (mean 140 min) than
either fentanyl (114 min) or bupivacaine (99 min) alone. Fentanyl, 100 µg with bupivacaine 0.068%, was found to
[408]
be equianalgesic to bupivacaine 0.25% for women in labor. Fentanyl potency was able to reduce the EC of [409]
bupivacaine 3.7-fold, as later described by other investigators (see Fig. 48-3 ). Epidural fentanyl, 60 µg, [255] [405]
compared with intravenous fentanyl, 60 µg, increased significantly the analgesic potency of bupivacaine (by a factor
of 1.09 to 3.67), the segmental spread of epidural block, and the incidence of pruritus. In a prospective, double- [255]
blinded trial involving 147 parturients, sufentanil, 0.5 to 1.5 µg/mL, in a dose-dependent fashion significantly
reduced the EC50 (95% CI) of epidural bupivacaine, from 0.104% (0.090–0.117) to 0.009% (0 to 0.023) (see Fig. 48-
3 ). No differences in efficacy and side effects were found in a double-blinded randomized comparison of epidural
[254]
fentanyl, 2.5 µg/mL, and sufentanil, 0.25 µg/mL, added to a 0.0625% bupivacaine infusion. However, at a [404]
different dose-potency ratio of fentanyl (2 µg/mL) to sufentanil (1 µg/mL), sufentanil resulted in lower pain scores
and less bupivacaine rescue. Bupivacaine added to sufentanil, 30 µg, enhanced and prolonged analgesia, but the
[409]
incidence of instrumental delivery significantly increased with a 0.25% versus a 0.125% solution. In a double- [410]
blinded randomized, prospective, multicenter study of 695 parturients, incremental doses of epidural sufentanil [411]
(10 to 30 µg) added to bupivacaine-epinephrine, 0.125%, improved the quality and duration of pain relief, reduced
the incidence of instrumental deliveries (significantly but not dramatically) from 36% to 24%, and caused pruritus in
26% of patients. A bicenter, randomized, and double-blinded trial established that fentanyl, 50 µg, and sufentanil,
[411] [406]
8 µg (mean equipotency ratio of 6.3:1) were the effective (pain score < 10) epidural doses for 95% of parturients
(ED95 ), when they were injected with bupivacaine, 0.125%. According to maternal assessments, bupivacaine alone
was rated as excellent in 80%, and the bupivacaine-opioid mixtures were rated excellent in 60% to 100% of cases
after 30 minutes. The incidence of side effects and the duration of analgesia (mean 101–188 min, with great
intragroup variability) were similar. An appropriate, outcome-oriented question of efficiency was raised concerning
the cost difference between the two opioids. In a double-blinded prospective study, fentanyl, 100 µg, and
[406]
sufentanil, 20 µg, after a lidocaine-epinephrine test dose, provided an equal duration of analgesia (mean 124 and 138
min, respectively). No motor block, no differences in the outcome of delivery, and (in a few and equally
[407]
distributed cases) mild sedation, mild pruritus, and nausea/vomiting were found after both opioids. Similar [407]
efficacy (at different efficiency, concerning the cost of ropivacaine) of labor analgesia was described by combining
a low-dose of epidural ropivacaine with sufentanil or fentanil. [395] [398] [399]
Meperidine (pethidine), 25 mg, added to bupivacaine, is an equally efficacious epidural opioid for labor analgesia.
However, repeating or increasing the dose to 50 to 100 mg is associated with a high incidence of nausea and
sedation and a potential for adverse neonatal effects. Shivering (at an incidence of 35% to 80%) is one of the
[33] [412]
major side effects of epidural analgesia and anesthesia. Owing to its specific pattern of action on thermoregulatory
impairment, meperidine, 50 mg intravenously or 25 mg epidurally, is considered (after delivery of the infant) the
[413]
drug of choice to reduce the incidence and intensity of shivering. However, a similar effect was obtained by [33] [414] [415]
warming the injectate, with small doses of epidural fentanyl or sufentanil, intravenous clonidine, 30 µg, or
intravenous tramadol, 0.25 to 0.5 mg/kg. [33] [65] [416] [417] [418]
Diamorphine (heroin), a lipophilic derivate of morphine available in the United Kingdom, provides a rapid and
effective epidural analgesia of 6 to 10 hours, with side effects similar to those of other opioids. In a [33] [402] [403]
retrospective institutional analysis, respiratory depression was found in 0.9% of 800 patients treated for
postoperative or traumatic pain. Epidural diamorphine alone was considered an alternative to bupivacaine in the
[419]
first stage of labor. Epidural infusion of diamorphine, 0.5 mg per hour, mixed with bupivacaine, 0.0625%,
[420]
provided a quality of analgesia similar to that of bupivacaine, 0.125%, alone, implicating a relevant (50%) reduction
of the bupivacaine EC in labor. [421]
Epidural Opioids for Anesthesia and Postcesarean Analgesia
Opioids combined with a local anesthetic improve the quality and extend the duration of postoperative analgesia. [33] [64]
The use of opioids is surrounded, despite its popularity, by a conflict (not only in obstetrics) between efficacy,
[65]
safety, and maternal satisfaction and side effects and complications that may lead to additional treatment, morbidity,
and maternal dissatisfaction. “Epidural and intrathecal opioids often produce analgesia of greater intensity than
similar doses administered parenterally.” However, the “degree of analgesia achieved, though a primary objective
[403]
1131
of each therapeutic modality, is less important to patients than overall satisfaction.” Two detailed reviews have [403]
addressed various pharamacologic options, combinations of opioids, and different modes of drug application,
accentuating the advantages of patient-controlled analgesia. Severity and duration of pain, side effects, and final
[402] [403]
maternal satisfaction or dissatisfaction (much less the use, timing, or amount of additional analgesic) should be
considered the primary outcome variables for postcesarean pain relief. A postcesarean analgesic that is efficacious,
cost-efficient, and acceptable for 95% of women in 95% of obstetric units (ECA95 ), remains to be found.
Epidural morphine provides, uniquely among all opioids, the longest duration of analgesia (24 hr after 3 to 5 mg,
with 4 to 5 mg recommended as the maximal single dose. Despite a high incidence of adverse effects
[64] [65] [403] [422]
(nausea, vomiting, and pruritus are more frequent after epidural than intramuscular or intravenous application),
epidural morphine did not lose its popularity. It has been claimed that morphine is the most widely used epidural
opioid for postcesarean analgesia. This claim is probably true for some but certainly not for all countries.
[402]
Previously, an oxyhemoglobin desaturation was found significantly more frequently and of longer duration after
epidural morphine compared with parenteral meperidine or morphine. A requirement for intensive monitoring [423] [424]
must be considered higher after epidural morphine, although the incidence of significant respiratory depression was
low (0.04%–0.3%) in large retrospective studies. In addition, the recommendations to use scopolamine,
[402] [403] [425]
metoclopramide, ondansetron, intravenous or epidural droperidol, or an additional systemic or epidural analgesic

drug indicate that epidural morphine (even at the so-called optimal dose of 3.0 to 3.75 mg) frequently
[33] [402] [403] [426] [427]
requires additional interventions that may all adversely influence various clinical, organizational, and cost-benefit
aspects of outcome.
Other opioids, of course, are not free of respiratory depressant and other side effects. Drowsiness, nausea, vomiting,
and pruritus do occur occasionally, at an incidence comparable with epidural morphine. However, the risk of
ventilatory depression with epidural fentanyl and sufentanil, at usual clinical doses, must be considered extremely
low. Compared with the delayed effect of morphine, lipophilic opioids lead to respiratory depression much earlier. [65]
The incidence of oxyhemoglobin desaturation (<94%) was found to be higher during epidural bupivacaine-
[264] [402] [403]
fentanyl infusion than with bupivacaine alone during vaginal delivery. In a randomized, double-blinded study of [428]
epidural anesthesia for cesarean delivery, Celleno and coworkers reported that a significantly higher number of [422]
women experienced pruritus and vomiting after epidural morphine, 3 mg, but somnolence dominated in women
receiving epidural fentanyl (75 µg) and sufentanil (50 µg). The ventilatory response to carbon dioxide and degree of
sedation was significantly different after epidural sufentanil, 30 or 50 µg, combined with bupivacaine for cesarean
delivery. Cohen and coworkers concluded that the lower sufentanil dose was preferable with regard to respiratory
[429]
and nonrespiratory side effects and recommended monitoring of ventilation for a minimum of 2 hours. A high
epidural dose, the technique (involving, unpredictably, systemic absorption or subdural or intrathecal penetration)
and the use of additional drugs were considered the causes of respiratory depression and severe complications after
epidural application of fentanyl, sufentanil, or meperidine. [6] [86] [430] [431] [432] [433]
Fentanyl, 50 to 100 µg, and sufentanil, 10 to 30 µg have been widely used to shorten the onset and prolong the
action of epidural bupivacaine anesthesia for cesarean delivery. Bupivacaine-fentanyl (75 µg) even reached onset
time equal to that of chloroprocaine. Both opioids may (this is controversial) improve the quality of intraoperative
[434]
anesthesia and duration (2–5 hr, dependent on the local anesthetic) of postcesarean analgesia without provoking
adverse neonatal effects. Olofsson and coworkers compared, in a randomized, prospective study,
[65] [247] [369] [422] [435] [249]
epidural and spinal bupivacaine, 100 and 12.5 mg, respectively, without or with fentanyl, 100 and 10 µg,
respectively in 100 women undergoing elective cesarean delivery. No differences were found in the quality of
intraoperative anesthesia, but the intensity of pain and requirement for analgesic treatment were significantly higher
in the first 6 hours after surgery in women receiving spinal anesthesia. A double-blinded, randomized study of 250 [249]
women after cesarean delivery compared epidural analgesia with fentanyl (2 µg/mL) or sufentanil (0.8 µg/mL). [436]
The opioids were mixed with bupivacaine-epinephrine, 0.01%, in a patient-controlled mode using a bolus (3 mL,
lockout interval 15 min) and a continuous infusion. Sufentanil resulted, at a higher dose-potency ratio, in fewer
pump requests, more frequent vomiting (12% vs. 5%), and dizziness after discontinuation of the infusion in 42 of
125 women. [436]
In general, a continuous epidural infusion of local anesthetics for postcesarean analgesia is rarely if ever indicated. [402]
When an epidural versus intravenous mode of patient-controlled analgesia was studied using fentanyl, 20 µg, with a
lockout interval of 10 minutes, the pain scores at rest and during coughing and the self-infused dose were lower with
the epidural mode. Nine women in the intravenous group versus none in the epidural group considered analgesia
inadequate. A double-blinded, dose-response epidural study confirmed that fentanyl and sufentanil are comparable
[437]
at onset and for the duration (117–138 min), as well as in effectiveness of postcesarean analgesia. The effective
doses (pain score < 10) of fentanyl and sufentanyl were set at 33 and 6.7 µg (ED50 ) and 92 and 17.5 µg (ED95 ),
respectively, suggesting that the mean analgesic potency ratio of epidural sufentanil to fentanyl is approximately 5
to 1. Patient-controlled epidural analgesia is considered superior (in terms of outcome) to patient-controlled
[438]
1132
intravenous mode regarding lower requirements of fentanyl or sufentanil, fewer side effects, earlier mobilization and
maternal-infant bonding, and a shorter duration of hospitalization. [402] [403]
Epidural meperidine, 25 to 50 mg, at a moderately fast onset, provides 2.5 to 3 hour of effective analgesia. [33] [402] [403] [439]
A randomized study compared intramuscular and mother-controlled epidural analgesia with meperidine after
[433]
cesarean delivery. The patient-controlled epidural group required less drug and had lower pain scores, ambulated
sooner, and cared for their infants earlier than the intramuscular group. In few reported cases, a respiratory
depression occurred early after a single epidural bolus of 75 mg. A randomized, double-blinded, cross-over
[432] [433]
study confirmed that patient-controlled epidural analgesia with meperidine is superior (high-quality pain relief at a
lower incidence of side effects) to the intravenous mode. Except for drowsiness, patient-controlled epidural
[440]
meperidine scored better in all side effects and in maternal satisfaction compared with fentanyl. In a prospective, [441]
randomized trial of 137 women, intrathecal morphine, 0.2 mg, resulted in significantly better pain relief after
cesarean delivery but but also caused more pruritus, nausea, and drowsiness. Unsurprisingly, the satisfaction was
highest with patient-controlled epidural meperidine. [442]
Epidural diamorphine, 3 mg, compared with intramuscular morphine, 10 mg, provided a longer duration of
analgesia (mean 11 vs. 6.5 hr) at a higher incidence of urinary retention and vomiting. In a double-blinded, [443]
randomized study of 45 women after cesarean delivery under spinal anesthesia, diamorphine, 2.5 mg, provided an
effective analgesia for 11 to 22 hours. Epidural diamorphine resulted in pain relief of significantly longer duration
[444]
after spinal than after epidural anesthesia for cesarean delivery. [445]
Intrathecal Opioids in Labor
Fentanyl and sufentanil, the lipophilic opioids, provide a rapid onset and reliable pain relief. Camann and
coworkers described a rapid effect, pruritus in three of nine women, and superior duration of labor analgesia with
[446]
10 µg of intrathecal sufentanil (median 84 min), compared with epidural (30 min) or intravenous (34 min) sufentanil
injection. Duration of labor analgesia after a single dose of sufentanil, 5 to 10 µg, or fentanyl, 25 to 50 µg, could
[446]
be expected to range from 60 to 180 minutes and 30 to 120 minutes, respectively. Therefore, sufentanil, 10 µg, [241] [264]
or fentanyl, 25 µg, with a small dose of bupivacaine, started to be used to prolong (for 30–60 min) the duration of
intrathecal analgesia. Viscomi and coworkers reported that the duration effect of sufentanil, 10 µg, and
[447] [448] [449]
bupivacaine, 2.5 mg, was significantly influenced by the progress of labor. On average, analgesia lasted 120 minutes
if the cervix was dilated more than 7 cm, and 167 minutes in women with less than 5 cm of dilation, resembling [449]
the described increase of epidural bupivacaine requirements throughout labor. Wong and coworkers tested [358]
intrathecal sufentanil, 2.5 to 10 µg, mixed with bupivacaine, 2.5 mg. Duration of action ranged similarly for all
groups (mean 93–97 min), but side effects occurred more frequently after higher 7.5 and 10 µg doses of sufentanil. [450]
Several groups of investigators, in a randomized and prospective fashion, studied the dose-response relationship for
intrathecal sufentanil in nulliparous parturients. The ED50 (95% confidence interval) ranged between 1.8 µg (0.6–3.0
µg) and 2.6 µg (1.8–3.2 µg). The ED95 (95% CI) was set at 8.9 µg (7.5–11.5 µg). The ED50 and ED95 (95%
[273] [451] [452] [451]
CI) of intrathecal fentanyl, investigated prospectively in a dose-randomized study of 90 women in early labor, were
found to be 5.5 µg (3.4–7.2 µg) and 17.4 µg (13.8–27.1 µg), respectively. The ED50 and ED95 values for nulliparous [453]
women (5.3 and 15.9 µg, respectively) and multiparous women (6.9 and 27.1 µg, respectively) were slightly but not
significantly different. Herman and coworkers concluded that intrathecal fentanyl induces rapid analgesia, pruritus
[453]
(overall incidence 66%), and decreased tidal volume (in the absence of overt somnolence or changes in the pulse
oximetric oxygen saturation), particularly at doses of 15 µg or more, in a dose-related fashion. The mean analgesic [453]
potency ratio of intrathecal sufentanil to fentanyl was set at approximately 2 to 1 (in contrast to 5:1 for [241] [451]
postcesarean epidural analgesia). [438]
Another prospective and randomized study concluded that the median ED (95% CI) of intrathecal fentanyl is 14 µg
(13–15 µg); little benefit may be obtained by increasing the dose beyond 25 µg. Thus, concerning the [454]
heterogeneity of the laboring women, intrathecal opioids alone at the extremes of the effective doses may not be
sufficiently potent in some cases or may exceed an effective dose threshold in others and potentially trigger serious
side effects.
In a retrospective institutional analysis of over 4100 obstetric cases, the combined spinal-epidural labor analgesia [156]
resulted in a lower failure rate compared with epidural block alone. However, the side effects were observed after
intrathecal sufentanil (in a dose-dependent fashion) in 1% of cases after 10 µg up to 6% after rather high dose of 20
µg or when systemic opioids were given 6 hours before intrathecal opioid. Immediate treatment with intravenous
naloxone for severe drowsiness and low oxygen saturation unresponsive to oxygen given by mask, clinical
observation, and pulse oximetric monitoring were strongly recommended to minimize the risk of apnea in
parturients managed with the combined technique. Barbara Leighton came to the point, concluding that “from
[156] [122]
1133
the respiratory standpoint, the maximum safe dose of intrathecal fentanyl or sufentanil in laboring women has yet to
be determined.”
Resembling the effect of epidural bupivacaine-opioid, epidural bupivacaine was found to provide
[254] [255] [405] [409]
anesthesia over more dermatomes when administered 1 to 2.5 hours after 10 µg of intrathecal sufentanil than when
injected alone. Camann and coworkers defined the dose response of intrathecal sufentanil 2, 5, or 10 µg and
[455] [273]
epidural bupivacaine, 5, 12.5, or 25 mg, given alone and in combination (intrathecal sufentanil [1, 2.5, or 5 µg] with
epidural bupivacaine [2.5, 6.25, or 12.5 mg]) in a randomized, double-blinded fashion. The ED50 (95% CI) of [273]
intrathecal sufentanil was 2.3 µg (1.7–3.2 µg) and 24 mg (12–50) for epidural bupivacaine. The sufentanil-
bupivacaine ED50 was approximately one third to one tenth of the single dose each, that is 0.85 µg for intrathecal
sufentanil and 2.2 mg for epidural bupivacaine 20 to 30 minutes after injection. Intrathecal sufentanil alone [273]
provided a similar duration of analgesia (83–102 min). The dose-response effect became apparent with epidural
bupivacaine alone (duration of analgesia increased from 35 to 42 and 74 min, respectively) and with the combined
technique (from 60 to 79 and 101 min, respectively). Thus, reduced doses of intrathecal opioids may provide an
[273]
efficacious and effective labor analgesia with a lower rate of side effects. The use of epidural local [241] [264] [273] [450] [456] [457]
anesthetics after an intrathecal opioid requires a careful dose selection and proper monitoring of the spread and side
effects. [33] [114] [156] [273] [455]
Intrathecal meperidine, 10 mg, fentanyl, 10 µg, and sufentanil, 5 µg, were found to be equally effective in the first
stage of labor, but meperidine provided lower pain scores when cervical dilation progressed beyond 6 cm. Nausea [458]
and vomiting are recognized complications of intrathecal meperidine, negating the advantages of efficacious [241]
analgesia. Recently Booth and coworkers discontinued a labor study of intrathecal meperidine, in rather high
[459]
doses of 15 and 25 mg, because of frequent nausea and vomiting. The duration of pain relief (1.5–2 hr) was found to
be comparable with that of bupivacaine-fentanyl. [459]
Intrathecal Opioids and Postcesarean Analgesia
The combination of an opioid with a lower dose of local anesthetic became highly popular in improving the quality
and prolonging the duration of postcesarean analgesia. Intrathecal opioids are considered to provide the most
efficient method of pain relief. However, the incidence and the impact of side effects on outcome were assessed
[402] [403]
variably by different investigators. [33] [247] [249] [264] [280] [293] [295] [316] [324] [389] [402] [403]
Dahl and coworkers performed a qualitative and quantitative systematic review of the 1966 to 1998 literature
[247]
regarding the intrathecal use of morphine, fentanyl, and sufentanil, and summarized in numerical terms (critically,
aware of limitations) some aspects of outcome of intrathecal opioid-local anesthetic anesthesia for cesarean delivery.
They found that intrathecal morphine reduced pain relevantly and prolonged time to first postoperative analgesic (at
least 11 hr after 0.1 mg). For every 100 women receiving 0.1 mg of morphine, it was calculated that 43 would
experience pruritus, 10 would have nausea, and 12 would vomit. Intrathecal fentanyl and sufentanil were found to be
virtually inefficacious postoperative analgesics. Only one study showed that intrathecal fentanyl, in a high dose of [460]
40 to 60 µg, may produce meaningful postoperative analgesia (11–13 hr) with few adverse effects. On average, only
24% of patients in the control group required supplemental analgesic intraoperatively; thus, a substantial number of
patients given opioids for intraoperative analgesia were exposed to unnecessary adverse effects. Pruritus, nausea,
and vomiting occurred significantly more often with intrathecal opioids than in control subjects. Only morphine
increased all three adverse effects (dose-dependent relative risk); the incidence of pruritus was very high, but similar
with morphine, fentanyl, and sufentanyl; and nausea and vomiting occurred less frequently with lipophilic opioids
than with morphine. In some studies, intrathecal sufentanil, 2.5 to 5 µg, and fentanil, 10 to 15 µg, actually
[293] [369]
decreased the incidence of nausea and vomiting compared with placebo. The most feared side effect of intrathecal
opioids, respiratory depression, was found in only 1 of 485 cases reviewed. Concerning respiratory depression, Dahl
and coworkers left open the meaning of the number-needed-to-harm of 476, as calculated in the analysis.
[247] [247]
Although different opioids and dosages have been used at different clinical conditions over time (the study period
was too long), the number implicates (in general, meta-analytical terms) that one of 476 patients receiving
intrathecal opioids may be expected to experience respiratory depression.
In a large-scale prospective study of spinal anesthesia with bupivacaine-morphine, 0.2 mg, for cesarean delivery,
reported in 1991, Abouleish and coworkers found only 6% of more than 800 women dissatisfied by pruritus,
[292]
nausea, and vomiting. In 1998, intrathecal morphine, 0.2 mg, with bupivacaine resulted in a high quality of intra-
and postoperative analgesia, low incidence of side effects, and no negative outcome. In 2000, intrathecal morphine, [280]
0.2 mg, with bupivacaine caused a high degree of maternal dissatisfaction, compared with epidural lidocaine-
fentanyl-morphine anesthesia. No explanations (except for the time factor) are available to clarify these
[295]
discrepancies. After Dahl’s overview, two studies provided the outcome data for intrathecal anesthesia in
[247]
obstetrics. Gerancher and coworkers, in a double-blinded study, used an updown method of dose allocation of spinal
morphine, combined with bupivacaine, 0.75%, and fentanyl, 20 µg, to provide effective postcesarean analgesia in 40
1134
women. Various postoperative rescue analgesics were included in the protocol. The ED50 of intrathecal morphine
[461]
was estimated to be only (mean ± SD) 22 ± 53 µg. Treatment for nausea was required in 20% of women, and 25% of
women required treatment for pruritus. Very small doses of intrathecal morphine combined with other analgesics
may provide adequate pain relief and patient satisfaction that is time- and cost-effective. In a randomized study, [461]
Manullang and coworkers found that intrathecal fentanyl, 20 µg, compared with intravenous ondansetron given
[462]
immediately after spinal block significantly decreased the perioperative nausea but not the vomiting score. A low-
dose intrathecal opioid and postoperative systemic analgesics, without requirement for other drugs (usually of higher
price) may improve efficiency of management.
Intrathecal diamorphine, 0.125 to 0.375 mg, influenced postoperative pain scores and the incidence of vomiting and
pruritus in a dose-related manner; all doses were considered safe for women undergoing cesarean delivery. [463]
Compared with intrathecal morphine, 0.2 mg, intrathecal diamorphine, 0.2 mg, showed similar efficacy but lower
incidence of itching and drowsiness. Subsequent correspondence addressed the selection of better drugs and
[464]
dosages, and the proper assessment of pain relief. A similar duration and quality of pain relief, with a high
[465]
incidence of pruritus characterized the study of intrathecal diamorphine 0.25 mg, and epidural diamorphine 5 mg.
Nausea and vomiting were significantly less frequent (4% vs. 24%) in the intrathecal group. Bloor and [466]
coworkers, using a different ratio of intrathecal (0.3 mg) to epidural (3 mg) diamorphine, reported a similar
[467]
incidence of nausea and vomiting (17% vs. 23%, respectively), but pruritus was more common and more severe
after intrathecal application. Skilton and coworkers randomized 40 parturients undergoing cesarean delivery to
[467] [468]
receive intrathecal bupivacaine alone or with diamorphine, 0.1 to 0.3 mg. The pain scores, requirements for [468]
intravenous morphine, and side effects (not requiring treatment and deemed acceptable) were dose-dependent. [468]
CLONIDINE
Epidural Application
Epidural clonidine, through a spinal site of action, provides significant and segmental labor analgesia, sedation, and
maternal blood pressure and heart rate decrease. The appropriate dose was set at 75 µg. Clonidine effect was
[469] [470]
found to prolong pain relief for (mean) 56 to 122 minutes and duration of labor for (mean) 113 minutes, compared
with local anesthetic alone. Fetal heart rates were normal and high Apgar scores were found with high plasma
[468] [471]
umbilical cord clonidine concentrations. A randomized trial of epidural clonidine, 50 µg, in 100 parturients found
[471]
a superior quality and duration of labor analgesia but a higher frequency of arterial hypotension and sedation (both
easily reversed), compared with bupivacaine-epinephrine-sufentanil alone. Another study, however, found a [472]
similar duration of analgesia (mean 153 vs. 178 min) comparing epidural sufentanil, 20 µg, and sufentanil-clonidine,
75 µg. In a double-blinded trial of patient-controlled epidural analgesia in 75 parturients, clonidine (mean 28 µg
[473]
per hour) improved pain relief, reduced shivering, and led to mild maternal sedation and moderately lowered blood
pressure compared with bupivacaine-fentanyl alone. [474]
Epidural clonidine, 150 µg, compared with parenteral morphine, 10 mg, provided a better and more prolonged
postcesarean analgesia in the first 3 to 4 hours. Higher clonidine doses induced sedation, respiratory depression, and,
in some studies, oxyhemoglobin desaturation. The incidence of moderately severe maternal hypotension was set
[470] [475]
at approximately 10%. When combined with fentanyl, the postoperative ED50 of epidural clonidine decreased 3.5-
fold, from 353 to 98 µg. In a randomized study of 60 women, the addition of epidural clonidine, 75 or 150 µg, to
[476]
morphine increased the duration of analgesia (mean 21.6 vs. 13.3 hr) and reduced the morphine requirements over
36 hours without an impact on side effects compared with epidural morphine alone. [477]
Intrathecal Application
Initial intrathecal doses of clonidine, 100 to 200 µg, alone or combined with sufentanil, increased significantly the
risk of hypotension in laboring women. In a randomized study of 98 parturients, intrathecal clonidine, 30 µg,
[470] [478]
combined with sufentanil, 2.5 or 5 µg, was found to increase the duration of labor analgesia for (mean) 41 minutes
compared with sufentanil, 5 µg, alone, without adverse effects. However, in a study of 53 parturients, Mercier and
[479]
coworkers obtained a sensory level not exceeding T2 and reported an extended duration of labor analgesia but
[480]
higher incidence of hypotension when intrathecal clonidine, 30 µg, was combined with sufentanil, 5 µg, followed by
epidural bupivacaine, 5 mg. D’Angelo and coworkers randomized 30 parturients early in labor to receive
[480] [481]
intrathecal sufentanil, 7.5 µg, and bupivacaine, 2.5 mg, with or without clonidine, 50 µg. At a sensory level of (mean)
T5 in both groups, clonidine prolonged the pain relief for (mean) 75 minutes without producing serious adverse
effects. Thus, the studies of clonidine-sufentanil led to an interesting hemodynamic difference between spinal and
[481]
epidural bupivacaine in labor.
For postcesarean analgesia, intrathecal clonidine, 150 γ, was compared with placebo in a double-blinded, clinical
trial in 20 women. Clonidine prolonged the time of first analgesic request for (mean) 3.9 hours, decreased the mean
1135
arterial pressure (mean) 18%, and increased the incidence of side effects such as sedation and dry mouth. A [470] [482]
multicenter study compared efficacy and side effects of spinal bupivacaine combined with clonidine or clonidine-
fentanyl in 78 women undergoing elective cesarean delivery. Clonidine, 75 µg, and clonidine-fentanyl, 12.5 µg
[294]
increased the spread of sensory block and decreased the intraoperative pain scores and the incidence of nausea and
vomiting compared with bupivacaine alone. Clonidine-fentanyl (moderately) prolonged the duration of
postoperative analgesia for (mean) 32 to 78 minutes but increased sedation and pruritus compared with two other
groups. [294]
The role of clonidine, its dosage, and its impact on outcome remain insufficiently defined in obstetric anesthesia. A
potentiation of analgesic effects of local anesthetic-opioid is certainly favorable, but the side effects (sedation and
hypotension) and a narrow margin of safety in a heterogenous population are rather unfavorable.
Progress of Labor and Mode of Delivery
OBSTETRIC AND NONOBSTETRIC FACTORS
Risks and Advantages of Cesarean Delivery
The practice of cesarean delivery is dominated by huge international, regional, and institutional differences,
conflicting indications, and a negative impact on the outcome. James Roberts addressed the changing
[133] [283] [284] [483] [484] [284]
attitudes toward cesarean delivery and questioned the safety of vaginal delivery for the woman or infant. As the age
of the pregnant population is increasing, trauma of labor and delivery (including forceps and episiotomy) is leading
to (previously unsuspected) loss of pelvic support, injury of pelvic structures, urinary and fecal incontinence, and
high incidence of anal sphincter injury after vaginal birth. “Even spontaneous delivery is associated with increased
risk.” Abnormal labor (regardless of management) was found to be associated with a two- to threefold increased
[284]
risk of serious neonatal complications, but “one certain way of preventing abnormal labor is by elective cesarean
delivery before the onset of labor.” On the other hand, according to the 1994 to 1996 United Kingdom Enquiry,
[284] [6]
the fatality rate for all cesarean deliveries was six times that for vaginal delivery, and even for elective cases the rate
was almost three times as great. Erskine and McGrady addressed the woman’s right to choose along with the
[283] [484]
risks and benefits of each mode of delivery, and came to opposite conclusions. A dramatic increase in cesarean
delivery rate has been mirrored (in Brazil and possibly other countries) by a rising maternal mortality rate. At first [484]
sight, these differences in the mortality rate speak for themselves. It could be assumed that the differences are even
[283]
wider in some countries and institutions or, presumably, are quite narrow when experienced obstetric and anesthetic
teams take care of a selected female population with a preference for cesarean delivery.
[7] [8] [9]
The Controversy—Impact of Regional Analgesia on Labor and Delivery
The controversy surrounding the impact of neuraxial techniques on normal labor and the rate of instrumental and
cesarean deliveries is rooted deeply in the awareness of morbidity, mortality, and costs associated with cesarean
delivery. The controversy started in the late 1960s and remained almost unresolved a generation later. “Resolving
[485]
the issue of whether obstetric outcome and epidural analgesia are causally related” was and remains difficult [486]
because of many confounding variables (local, regional, traditional, obstetric, anesthetic, social, financial, and
population heterogeneity) of different origins. Relevant disagreements divide practice and opinion in
[41] [245] [487]
obstetrics concerning the proper use of regional analgesia, management of labor, and contribution of different “risk
factors” to the incidence of instrumental and cesarean delivery. [40] [488] [489] [490] [491] [492] [493] [494]
James Thorp, keeping the flag of controversy flying high, complained of false methodology in studies with high
[40]
cross-over rates to the epidural group. Some conclusions, he said, were based on “academic centers with protocol-
driven, aggressive obstetric management.” Thorp claimed that the “best evidences” suggest that regional
[40]
analgesia/anesthesia may lead to hypotension or redistribution of cardiac output away from the uteroplacental unit
and fetal acidemia; therefore, it should be avoided in nonreassuring fetal heart rate tracings and pregnancy-induced
hypertension. (There is no evidence that regional techniques, arterial pressure and cardiac output changes, and
postnatal fetal acidemia—presumably of anesthetic origin— correlate with adverse outcome. (See earlier discussion
of Preeclampsia and subsequent discussion of Uteroplacental Circulation and Fetal Acidemia.) Thorp concluded that
the epidural technique has contributed to the cesarean epidemic in the United States. [40]
Segal and coworkers addressed the use of epidural analgesia and concomitant risk factors for cesarean delivery for
[495]
110 institutional obstetricians caring
1136
Figure 48-4 No controversy at the National Maternity Hospital in Dublin,

Ireland. At six-fold increase of the rate of epidural analgesia in labor, the rates of
instrumental and cesarean delivery remained low between 1987 and 1994. (From
Impey L, MacQuillan K, Robson M: Epidural analgesia need not increase
operative delivery rates. Am J Obstet Gynecol 182:358–363, 2000. Reproduced
with permission.)
for low-risk parturients in the 1990 to 1995 period. The frequency of use of epidural analgesia did not predict
obstetricians’ rates of cesarean delivery for dystocia, and a major determinant of cesarean delivery appeared to be
the individual practice style. The consequences of a new start or a sudden removal of the “epidural service” in a
[495]
hospital have been used to assess the local practice and outcome in obstetrics. Although the model, by definition,
used a noncontemporary comparison, all studies came to the same conclusions—the abruptly increased or decreased
rate of epidural analgesia did not significantly change the local instrumental and cesarean delivery rates—and
provided epidemiologic data of considerable value. A retrospective analysis of 1000 spontaneous
[41] [251] [487] [496] [497] [483]
nulliparous labors in the years 1987, 1992, and 1994 at the National Maternal Hospital in Dublin (the “pioneers of
active labor management”), showed remarkable and examplary results concerning the practice of obstetrics and
obstetric anesthesia. The rate of epidural analgesia increased sixfold, and the rates of instrumental vaginal and
cesarean delivery remained unchanged over the study period ( Fig. 48-4 ). [483]
REGIONAL ANESTHESIA TECHNIQUES AND PROGRESS OF LABOR
Parenteral opioids, as alternatives and surrogates, remain rooted in obstetric care despite low analgesic efficacy,
frequent overdose, side effects, and negative impact on fetal well-being and neonatal adaptation. [10] [35] [36] [46] [278] [498] [499]
Comparing intravenous analgesia—at disastrous to moderate (in) efficacy, (in) effectiveness, and (un) acceptability,
and at questionable efficiency and optimality—with the highly efficacious and acceptable but expensive neuraxial
analgesia techniques is an abnormality. Actually, it is a “pragmatic” well-recognized contradiction in obstetrics and
obstetric anaesthesia. There is no receipe for how to rate obstetric outcome when comparisons of intravenous and
neuraxial analgesia show, repeatedly and in all countries, the large to huge differences in pain scores and maternal
satisfaction. New concepts and designs are required in obstetrics, more in accordance with the
[78] [278] [341] [348] [349] [498] [499]
contemporary medical, ethical, and overall outcome goals. A cost model of analgesia for labor pain calculated the
cost differences between epidural analgesia and intravenous analgesia. If this assessment of parenteral analgesia is [248]
correct, the intravenous-to-epidural cost relationship is of no interest to anyone. On the other hand, Macario and
coworkers concluded in the interest of everyone that “patients, physicians, and society need to weigh the value of
[248]
improved pain relief from epidural analgesia versus the increased cost of epidural analgesia.”
Eberle and Norris addressed the effects of neuraxial analgesia on the progress and outcome of labor and
[487]
accentuated the difficulties surrounding the topic in general and the cause-and-effect relationships in particular. The
nonrandomized studies are considered distorted by selection bias, heterogeneity of maternal, fetal, and obstetric
characteristics, obstetric and anesthetic management (such as concentration and dosages of neuraxial drugs), [251] [500]
and socioeconomic factors on the maternal and care provider sides. Even some prospective randomized trials,
[7] [8]
because of the small size, cross-over rates, and ethical conflicts, are of only limited value. [487]
Neuraxial Analgesia and First Stage of Labor
Epidural analgesia may positively and negatively affect or not affect the rate of cervical dilation, uterine activity,
efficiency of contractions, and duration of first stage. Severe pain of very early labor is an independent predictor of
duration of labor, and “delaying effective analgesia will only result in more pain, not in shorter labor.” In a [487]
prospective study of more than 450 parturients, adequate (vs. failed) epidural pain relief significantly shortened the
duration of labor (see Table 48-5 ). In a retrospective analysis of over 4400 cases, the intensity of pain led to
[257]
higher epidural analgesia requirements and then, as a confounding variable, to a higher chance of cesarean
delivery. In an observational study of 1000 parturients, epidural analgesia prolonged the first stage, at different
[501]
managements of labor, for (mean) 89 to 182 minutes. Compared with the late start of epidural analgesia, early (at
[488]
3 cm of dilation) administration of epidural analgesia did not prolong labor or increase the incidence of operative
delivery in a prospective, randomized study of 150 nulliparous women receiving oxytocin. The low or high fetal [502]
head position at the start of epidural pain relief did not influence the duration of labor and mode of delivery in a
prospective study of 131 parturients. In another prospective study, the fundal dominance (pressure gradient
[503]
1137
between upper and lower uterine segments) was not only maintained with epidural bupivacaine (started at a dilation
of mean 5.6 cm), but the gradient increased during the next 50 minutes. Similarly, epidural analgesia administered
[504]
early (< 5 cm of dilation) attenuated some mediators (beta-endorphin, cortisol) of metabolic stress response of labor,
but plasma oxytocin concentration and frequency of uterine contraction remained unaffected. In a large-scale, [505]
randomized trial (with few crossovers), epidural analgesia was compared with patient-controlled intravenous
meperidine. Regional technique prolonged the first stage (mean difference 61 minutes, but the range was wide in
both groups), increased oxytocin augmentation and the incidence of fever (> 38°C) in labor, increased the rate of
forceps but not cesarean delivery, and resulted in fewer (< 1% vs. 3%) infants requiring naloxone for respiratory
depression. A double-blinded, randomized study suggested that combined spinal-epidural anesthesia is associated
[498]
with a more rapid cervical dilation (mean 3.8 vs. 5.1 hr) than epidural analgesia in early labor, but the second stage,
mode of delivery, and obstetric outcome were similar in both groups. In a randomized study of 761 parturients, no
[274]
statistical differences were found in cervical dilation and mode of delivery with epidural and combined analgesia. [154]
Several investigators tried to implicate the use of regional analgesia as the cause of malpresentation of the fetal head,
although other factors, such as pelvic capacity and concomitant severity of pain, influenced the request for epidural
analgesia and the incidence of malpresentation. Epidural pain relief may allow spontaneous correction of
[487] [506]
malpresentation, but the rates of instrumental delivery remain high in women with complicated labors. A [487]
randomized, controlled trial suggested that epidural analgesia may contribute to inadequate rotation because of
weakened pelvic floor muscles, but this is more likely to occur with a 0.125% dose than with a 0.0625% dose of
bupivacaine. [507]
Neuraxial Analagesia and the Second Stage of Labor
Neuraxial pain relief was found to prolong (on average, 10–30 min) the second stage in some series, but [278] [487] [488] [508] [509]
not in all studies and not with all types of obstetric management. When epidural infusion was stopped or
[488] [498]
replaced by saline solution and epidural block allowed to wear off, the pain scores increased and the duration of
labor decreased. An analysis of over 900 vaginal deliveries identified the factors (epidural analgesia,
[487] [488] [508] [509]
active-phase duration, parity, height, birth weight, and station at full dilation) which may predict independently the
duration of second stage. The sum of their effect, however, accounted for less than 25% of the variability, leaving
75% of the variance in second-stage length unexplained! [510]
In a randomized study of 36 nulliparous women, lumbar sympathetic block resulted in faster cervical dilation (mean
57 vs. 120 min/cm), shorter second stage (mean 105 vs. 270 min), a similar number of instrumental deliveries, and a
trend to a lower rate of cesarean delivery (6% vs. 28%) compared with epidural analgesia. Further studies are [511]
required to elucidate the advantages and disadvantages of this technique.
Walking During Labor
In a large-scale randomized trial, Bloom and coworkers concluded that walking neither enhanced nor impaired
[512]
active labor and was not harmful to mothers or infants. The flexibility of management, prevention and treatment of
dystocia, individual comfort, and quest for higher maternal satisfaction led many obstetricians and parturients to
[513] [514]
prefer walking (or at least, to provide an option of mobility) during labor. Walking raised the question of safety and
specific pharmacologic requirements for combining regional analgesia and maternal mobility. Collis and
coworkers used a combined technique—a small dose of intrathecal bupivacaine-fentanyl followed by a low
[515] [516]
concentrated infusion of the same drugs—with success and, despite some minor degree of neurologic impairment,
walking in labor in company of an adult became a clinical routine. A high percentage of abnormal
[515] [516]
proprioception, altered vibration sense, and subjective lack of confidence to walk alone was found in a study with
epidural bupivacaine-fentanyl 0.1%. Despite some criticism, Buggy and coworkers warned correctly that
[517] [517]
walking under epidural analgesia should not be considered a safe technique. Subsequently, a prospective [516] [517]
observational study, in addition to neurologic examination, used computed dynamic posturography (sensory and
motor coordination tests) to examine balance function in pregnant women after combined spinal-epidural
analgesia. All women received intrathecal bupivacaine, 2.5 mg, and fentanyl, 5 µg (4% were subsequently
[518]
excluded because of motor block), and 9 of 44 required epidural bolus of 0.1% bupivacaine and fentanyl, 2 µg/mL,
during testing. Compared with a control group, neuraxial analgesia (without evidence of motor block) resulted in a
small, significant reduction in one of six sensory tests without any functional impairment of balance function. In [518]
some institutions, 80% to 90% of laboring parturients were allowed to be ambulant after undergoing a refined
spinal-epidural technique, and the significant feature of success was considered the omission of the traditional
epidural test dose. A randomized study of 229 parturients confirmed the safety and high maternal satisfaction with
[519]
combined analgesia and ambulation; the duration of labor, analgesic requirements, and mode of delivery were not
influenced by mobility. [520]
1138
In a prospective, double-blinded, randomized trial of intrathecal analgesia and ambulation, significantly fewer
parturients were able to ambulate after bupivacaine, 2.5 mg, with sufentanil, 10 µg, (at higher sensory spread and
with more hypotension) than after sufentanil alone. The efficacy of epidural analgesia to allow ambulation was [521]
evaluated in a randomized, double-blinded study of 60 parturients. A high percentage (73% to 93%) of women [522]
walked at some stage during labor. Omitting the test dose and using 0.125% bupivacaine with sufentanil, 10 µg, as
an initial bolus followed by 0.0625% bupivacaine with sufentanil, 0.33 µg/mL, infusion permitted ambulation in
most cases. Only 33% of women were found to be mobile when 0.125% bupivacaine-sufentanil was used for labor
[522]
analgesia. Obviously, strict criteria for ambulation under neuraxial analgesia and a balanced risk-benefit approach
[500]
for an individual woman are required. [114] [514]
REGIONAL ANESTHESIA TECHNIQUES AND MODE OF DELIVERY
Epidural Analgesia and the Rate of Instrumental Vaginal Delivery
The effects of epidural analgesia on the frequency of instrumental delivery are difficult to determine, not least
because efficacious pain relief makes it easier to perform. Obstetric and anesthetic management and characteristics [487]
of the population are considered to be relevant risk cofactors.
Hawkins and coworkers addressed the topic retrospectively and prospectively. They compared the time periods
[497]
before and after implementation of an epidural service and found, at a 10-fold increase of the regional technique,
similar association between instrumental delivery and epidural analgesia. An independent association with
instrumental delivery was identified for each epidural analgesia, gestational age greater than 41 weeks, second stage
longer than 2 hours, fetal presentation, and previous cesarean delivery. Several studies showed that the lower [497]
concentrations (0.125%) of bupivacaine (by reducing motor block, improving ability to push, or improving fetal
head rotation) may decrease the incidence of instrumental delivery. Comparing 0.0625% bupivacaine (with [411] [487] [500] [507]
fentanyl) and 0.125% bupivacaine, however, revealed no differences in method of delivery and a similar rate of
good to excellent analgesia (59%–66%) with both concentrations. Obviously, increasing the bupivacaine [523]
concentration to reach the EC95 in late labor improves pain relief but at the expense of loss of pelvic muscle tone,
reduced pushing force, higher chance of forceps delivery, and, finally, less maternal satisfaction. The effect of [33]
ropivacaine-associated lower degree of motor block was assumed to be advantageous for the second stage and
spontaneous delivery. A meta-analysis of six randomized, double-blinded trials suggested in 1998 that epidural
ropivacaine resulted in more spontaneous deliveries and fewer instrumental vaginal deliveries, than bupivacaine. [524]
Ropivacaine, compared with bupivacaine, allowed more ambulation at a lower degree of motor block and a slightly
shortened second stage of labor. In two studies, however, the impact on the incidence of instrumental delivery
[398] [399]
differed. One study showed no benefit from ropivacaine, whereas in the other, ropivacaine significantly reduced [399]
(10% vs. 35%) the number of forceps deliveries. [398]
Delayed pushing may allow more spontaneous and fewer instrumental deliveries. A multicenter, randomized trial [487]
of nulliparous women receiving epidural analgesia concluded that delayed (vs. early) pushing is an effective [525]
strategy in reducing difficult deliveries. Abnormal umbilical cord blood pH (< 7.15; relative risk 2.5) was more
frequently found in the delayed group; the abnormality was obviously not an effect of epidural analgesia. The final
outcome (Neonatal Morbidity Index) was similar in early and delayed pushing. Although taken for granted [525]
(through repetition), it is far from self-evident that the difference in duration of labor (within the bounds of reason)
or the requirement for instrumental vaginal delivery should be considered a priori a negative outcome. The speed
and quality of maternal and neonatal recovery and adaptation and timing of discharge must be considered the “hard”
outcome variables of individual and social importance.
Epidural Analgesia and the Rate of Cesarean Delivery
Two meta-analyses provided a (global) assessment of the epidural analgesia-obstetric outcome relationship. Halpern
and coworkers extracted data from 10 randomized trials in the 1966 to 1998 (rather too long) period. They
[252] [252]
concluded that epidural analgesia had prolonged (mean 42 min) first stage and (mean 14 min) second stage of labor
with lower pain scores and a higher level of maternal satisfaction. The risk of cesarean delivery did not differ
between patients who received epidural or intravenous analgesia, but women with epidural technique were twice as
likely to have an instrumental delivery. Neonates after epidural labor were less likely to have a low 5-minute Apgar
score or to need naloxone. Another meta-analysis (again, the 1965–1997 period was too long) showed a twofold
[252]
increased risk of oxytocin augmentation with epidural analgesia. Randomized trials suggested that epidural block
did not increase the risk of instrumental and cesarean delivery, in contrast to a fourfold increased risk found in the
observational studies. Thorp’s critical position seems to stay almost isolated from other investigators, studies,
[253] [40]
and analyses with differing views on the confounding variables that (in various combinations) influence the rates of
cesarean delivery. The early (< 5-cm dilation) administration of epidural
[41] [245] [251] [483] [487] [488] [489] [490] [491] [492] [493] [494] [495] [496] [503]
analgesia did not increase the risk of dystocia and cesarean delivery. Epidural analgesia, compared with [251] [487] [502]
1139
intravenous meperidine, resulted in a similar rate of cesarean delivery. Combined spinal-epidural versus [498]
intravenous analgesia and combined versus epidural analgesia

[278] [279]
showed no differences as well. Lower doses [154] [274]
of epidural drugs may favorably influence the course of spontaneous labor. A prospective, randomized trial of [251]
1000 parturients showed significant differences in the incidence of instrumental (35% vs. 20%) and cesarean (14%
vs. 10%) deliveries when bupivacaine, 0.125%, and sufentanil, instead of bupivacaine, 0.25%, and epinephrine were
used for epidural labor analgesia. [500]
Fetal and Neonatal Outcome
EFFECTS OF REGIONAL ANESTHESIA ON THE FETUS IN UTERO
Uteroplacental Circulation
Regional anesthesia techniques may affect the uteroplacental and fetal blood flow in several ways. Arterial [526]
hypotension, uncompensated aortocaval compression, and uteroplacental vasoconstriction, as a result of high plasma
concentrations of a local anesthetic, added epinephrine, or use of vasopressors with a predominant alpha-adrenergic
activity, are the mechanisms of adverse effects on the fetus of regional anesthesia. On the other hand, anxiety, stress,
and pain relief, the basic components of efficacy of neuraxial techniques, may increase the uteroplacental blood flow,
and result in salutary effects on the fetus. Obviously, the maternal, fetal, and obstetric characteristics, and various
[526]
details of management (positioning, fluids, choice of vasopressors, neuraxial technique, speed of action, drugs,
dosages) influence fetal well-being and final neonatal outcome. Many studies using Doppler flow velocimetry in [33] [526]
normal and preeclamptic women evaluated the effects of epidural, spinal, and combined analgesia for labor and
epidural and spinal anesthesia in cesarean delivery on the waveforms in the uterine, umbilical, and fetal vessels. No
harmful effect, no compromise of uteroplacental circulation, and no adverse neonatal outcome were found using
different techniques and drugs. Several investigators suggested that labor epidural analgesia and
[146] [309] [310] [311] [312] [323] [526]
epidural anesthesia for cesarean delivery in hypertensive women are able to reduce preeclamptic uteroplacental
vasoconstriction and (if epidural epinephrine is avoided) may improve or at least maintain the indices of blood flow
in chronic fetal asphyxia. Avoidance or prompt treatment of maternal arterial hypotension, a frequent
[334] [526]
consequence of regional (and general) anesthesia techniques, is the major determinant of uteroplacental blood flow,
fetal oxygenation, and neonatal outcome. [323] [334] [526]
Fetal Heart Rate Changes
A study of intrathecal labor analgesia, small series, and case reports [458]
warned that decelerations of the fetal
[527] [188] [189] [528]
heart rate or sudden uterine hyperactivity and fetal bradycardia (with or without maternal hypotension) may occur
after intrathecal administration of opioids. In a large-scale prospective, randomized study of intravenous meperidine
and combined spinal-epidural analgesia, fetal heart decelerations were detected in 21% and 18% of cases,
respectively. However, profound fetal bradycardia (without maternal hypotension) occurred within 1 hour of
[278]
intrathecal administration of sufentanil, 10 µg, in 8 to 400 parturients (vs. 0 of 352 in the meperidine group), and led
to emergency cesarean delivery. In the majority of emergently delivered neonates, umbilical artery pH was below
7.20, and in two it was less than 7.00. In the meperidine group 4% (vs. 0 in the combined group) required
resuscitation with naloxone. The incidence of umbilical artery pH below 7.20 and the final immediate neonatal
outcome were comparable in the two groups. [278]
Another large-scale, randomized study of epidural and combined spinal-epidural labor analgesia found an identical
rate (6%) of periodic fetal heart rate changes. Nielsen and coworkers addressed the incidence and significance
[154] [529]
of fetal heart rate changes during regional labor analgesia in a prospective observational study. Significant fetal
heart rate abnormalities occurred at a similar rate in women receiving intrathecal (22%) or epidural (23%) analgesia,
and presented a similar risk for cesarean delivery. Mark Norris concluded that any method of effective pain[529] [530]
relief results in a similar incidence of fetal heart rate abnormalities, associated in many cases with uterine
hyperactivity. Women in early labor are at lower risk than those in more active labor, and conservative management
(short-term tocolysis) is usually successful in stabilizing the fetal heart rate. [530]
EFFECTS OF REGIONAL ANESTHESIA TECHNIQUES ON THE NEONATE
General versus Regional Anesthesia and Neonatal Outcome
The comparisons of regional versus general anesthesia for cesarean delivery are typically focused on the fetal status
and neonatal outcome data, such as acid-base values, Apgar score, and ventilatory pattern, which may or may not
represent the outcome. The studies in the 1970s and 1980s reported, variably, some or no
[33] [64] [124] [132] [531] [532] [533] [534]
differences in the neonatal status regarding the type of anesthesia given. In a 1975 to 1983 retrospective analysis, [33]
Ong and coworkers found a better neonatal outcome after regional than general anesthesia for elective and
[531]
1140
nonelective cesarean deliveries. A 1980 to 1985 retrospective study concluded that general anesthesia was
responsible for postnatal depression after elective cesarean delivery. Using a neurobehavioral testing in 31 [124]
neonates, Kangas-Saarela and coworkers stated that infants born under general anesthesia were more depressed in
[535]
the first 24 hours than those born after epidural anesthesia. Several studies indicated the superiority of epidural
[535]
anesthesia, particularly if the uterine incision-delivery time interval increased during general anesthesia. An [33] [533]
observational study of 138 neonates born at a low (< 3 min) uterine incision-delivery interval found similar Apgar
scores and (clinically not relevant but) significantly more infants with an umbilical venous pH below 7.28 after
general than after spinal anesthesia. [536]
In a prospective, semirandomized comparison of general and spinal anesthesia, no differences were found in the
neonatal behavioral adaptive capacity score and other outcome variables. A prospective, observational analysis of [534]
cesarean deliveries in premature infants (≤ 32 weeks) revealed a significantly higher incidence of low Apgar scores
after general than after epidural anesthesia. When other confounding factors were controlled in the analysis, the
[537]
risk of low Apgar score remained almost three times higher after general anesthesia. The complex topic of
compromised fetus, difficulties with the definition of fetal distress, unreliable results of retrospective and
nonrandomized studies, obstetric resuscitative interventions and other relevant aspects of obstetric care, and the
advantages and adverse effects of various regional techniques have been addressed elsewhere. [64] [132] [281] [367] [368]
Neonatal Acid-Base Status after Regional Anesthesia
Shyken and coworkers collected the umbilical venous and arterial acid-base values of 142 women who delivered
[532]
at term after a noninduced labor. They found significant but small and outcome-irrelevant differences in some acid-
base data according to the type of anesthesia and mode of delivery. They claimed that epidural anesthesia for
vaginal delivery prolonged the labor and resulted in deteriorated acid-base values. If cesarean delivery was
performed in the active phase of labor, epidural anesthesia resulted in lower umbilical PO2 values than general
anesthesia. In women undergoing elective cesarean deliveries, general and epidural anesthesia resulted in similar
acid-base status. More precise studies came to different conclusions; namely, that the duration of second stage—
[532]
with or without epidural analgesia—is the single factor related to the umbilical cord blood acid-base status. [525] [538]
Another group analyzed the data of 1601 uncomplicated pregnancies and repeat cesarean deliveries. A much higher
incidence of acidemia was calculated under epidural (odds ratio 3.7), combined spinal-epidural (6.1), and spinal (8.6)
technique than general anesthesia. However, the infants after general anesthesia were characterized by
[539]
significantly lower Apgar scores and more frequent requirements for assisted ventilation at birth. Even as a
surrogate, the relevance of this “respiratory acidemia” disappeared completely, and an overall superior neonatal
outcome emerged from regional anesthesia techniques. In a 1985 to 1994 retrospective analysis of more than 5800
elective cesarean deliveries in healthy women after uncomplicated term pregnancies, again, fetal acidemia (pH <
7.10) was found to be significantly more frequent under spinal (odds ratio 4.7) and epidural (2.4) than with general
anesthesia. The incidence of low Apgar scores was significantly higher in infants born under general anesthesia
[540]
(“they were sleepy not depressed”). The rates of mask ventilation, intubation, and intensive care unit transfer were
identical in all groups, but the intensive postnatal monitoring was more frequently found after regional than after
general anesthesia. Mueller and coworkers pointed to the possible albeit unproved role of arterial hypotension of
[540]
regional anesthesia and acknowledged the disadvantages inherent in an epidemiologic study. [540]
Neurologic and Adaptive Capacity Score
Brockhurst and coworkers reviewed the use of the Neurologic and Adaptive Capacity Score, which was
[541]
developed to evaluate the neurobehavior of term (> 37 weeks), healthy neonates in obstetric anesthesia research.
They found a high rate of insufficiency and inadequate reporting concerning the design, implementation, and
exclusion criteria as originally intended, training and interrater reliability, validity of the scale, dose-response
relationship for medication and score, data reporting, and sensitivity of the studies. It was originally hoped that the
score could immediately identify a depressed or vigorous neonate, and a score of 35 to 40 was arbitrarily set to
indicate a vigorous neonate. It is unclear how the score may differentiate between a neonatal depression induced by
drugs and that induced by asphyxia, trauma, or disease. The normal range and the standardization with normal
neonates not exposed to any medication in utero are still lacking. Although the use of the score is widespread, the
[541]
authors found that few studies reported statistically significant differences. In some cases, umbilical concentrations
of central nervous system depressant drugs correlated negatively with the score, but in some it did not. Using a too-
small number of infants, incomplete reporting, and marginal statistical differences (with a large number of
comparisons) were found to limit the interpretation of opioid investigations. Although the subjects were not
randomized and the examiner not blinded, two studies found that 15 minutes and 2 hours after cesarean delivery, the
scores were significantly lower in infants born under general than under regional anesthesia. Neonates delivered [542] [543]
with epidural anesthesia scored lower than those delivered with spinal anesthesia. Other investigators attempted to [542]
validate the score using other indicators but (possibly, owing to much smaller effects, inadequate design, or
1141
insensitivity of the tool) the results were equivocal. Frequently, the comparison with other measures of neonatal
well-being (Apgar score, fetal heart rate, acid-base values) were lacking. [541]
The neurobehavioral testing of the newborn requires a high level of expertise to provide clinically meaningful
results. The testing was used in some but not all studies and analyses of the effects of regional anesthesia techniques.
No differences in neonatal outcome could be expected when various regional techniques, local anesthetics, opioids,
and adjuvant drugs were used by experienced hands. In a meta-
[64] [65] [116] [122] [146] [242] [249] [293] [298] [311] [356] [362] [366] [367] [368] [471] [479] [480] [526] [534]
analysis of six randomized, double-blind studies of labor, epidural ropivacaine versus bupivacaine, Writer and
coworkers found that the Neurologic and Adaptive Capacity Scores were approximately equal at 2 hours, but at 24
[524]
hours the incidence of a score below 35 was significantly lower (3% vs. 8%) in infants born under ropivacaine. [524]
The paper triggered a discussion and appropriate criticism, with regard to the general problems with the meta-
[544]
analysis, the results of other ropivacaine studies, and, in particular, the (un)reliability of the score when used by
[374]
different investigators and in different institutions. Some investigators claimed that epidural analgesia may
[541] [545]
affect (reduce) the efficacy of breastfeeding, or that sufentanil may be superior to fentanyl in this respect. No [541]
studies examined this topic specifically “as an outcome correlated with intrapartum analgesia.” [545]
Conclusions
Outcome is influenced by different objective and subjective, individual, local, and regional characteristics at the care
consumer and care provider site. Regional anesthesia techniques are the pillar of quality in obstetric anesthesia.
Some data indicate that the increased use of neuraxial analgesia and anesthesia has contributed to decreased
maternal morbidity and mortality rates. Severe complications of regional anesthesia occur at a low to very low
incidence in obstetrics and, possibly, less frequently than in the nonobstetric population. The adverse effects found
at a higher rate are extensive cephalad spread and postdural postural headache. Backache, although a usual
postpartum complaint, is caused by other risk factors and not by regional anesthesia techniques. Epidural, spinal,
and combined epidural-spinal analgesia/anesthesia, and all local anesthetics and opioids (in appropriate doses) may
provide efficacious pain relief for labor for either vaginal or cesarean delivery. Maternal satisfaction, a nonlinear
indicator of outcome, depends not only on the effectiveness of pain relief but on the acceptability (individual wishes
and expectations) and equal distribution of the benefits of healthcare. The progress of labor and mode of delivery are
influenced by numerous maternal, fetal, obstetric, and anesthetic characteristics. With a complex interplay of
different confounding variables, regional anesthesia techniques do not increase the rates of instrumental and
cesarean delivery. Lower doses of local anesthetics contribute favorably to an uneventful, spontaneous delivery. The
fetal/neonatal outcome is not adversely affected by regional analgesia/anesthesia. The neonates born under neuraxial
block recover more rapidly and vigorously than those born under general anesthesia.
REFERENCES
1. Donabedian A: The seven pillars of quality. Arch Pathol Lab Med 114:1115–1158, 1990.
2. Sachs BP, Brown DAJ, Driscoll SG, et al: Hemorrhage, infection, toxemia, and cardiac diseases, 1954–85: Causes for their declining role in
maternal mortality. Am J Public Health 78:671–675, 1988.
3. Atrash HK, Alexander S, Berg CJ: Maternal mortality in developed countries: Not just a concern of the past. Obstet Gynecol 86:700–705, 1995.
4. Razum
O, Jahn A, Blettner M, Reitmaier P: Trends in maternal mortality ratio among women of German and non-German nationality in West
Germany, 1980–1996. Int J Epidemiol 28:919–924, 1999.
5. Hopkins FW, McKay AP, Koonin LM, et al: Pregnancy-related mortality in hispanic women in the United States. Obstet Gynecol 94:747–752,
1999.
6. Lewis G, Drife J, Botting B, et al: Why Mothers Die. Report on Confidential Enquiries into Maternal Deaths in the United Kingdom 1994–1996.
London, Department of Health and Her Majesty’s Stationery Office, 1998.
7. Wagner CL, Metts AG: Rates of successful vaginal delivery after cesarean for patients with private versus public insurance. J Perinatol 19:14–
18, 1999.
8. AronDC, Gordon HS, DiGiuseppe DL, et al: Variations in risk-adjusted cesarean delivery rates according to race and health insurance. Med
Care 38:35–44, 2000.
9. Roberts CL, Tracy S, Peat B: Rates for obstetric intervention among private and public patients in Australia: Population based descriptive study.
BMJ 321:137–141, 2000.
10. Cohen SE: Labor epidural analgesia: Back to the dark ages or a potential win-win situation (editorial). Int J Obstet Anesth 8:223–225, 1999.
11. ACOG: Women should not be denied pain relief during labor says ACOG. News Release January 31, 2000.
1142
12. Tuman KJ: Outcome studies in patients with heart disease: Cardiac and noncardiac surgery. In Kaplan JA (ed): Cardiac Anesthesia, 3rd ed.
13. Hibbard
BM, Anderson MM, Drife JO, et al: Report on Confidential Enquiries into Maternal Deaths in the United Kingdom 1988–1990.
London, Her Majesty’s Stationary Office, 1994.
14. ChadwickHS: An analysis of obstetric anesthesia cases from the American Society of Anesthesiologists closed claim project database. Int J
Obstet Anesth 5:258–263, 1996.
15. Richardson
DK, Gray JE, Gortmaker SL, et al: Declining severity adjusted mortality: Evidence of improving neonatal intensive care. Pediatrics
102:893–899, 1998.
16. Macario A, Weinger M, Truong P, Lee M: Which clinical anesthesia outcomes are both common and important to avoid? The perspective of a
panel of expert anesthesiologists. Anesth Analg 88:1085–1091, 1999.
17. Macario
A, Weinger M, Carney S, Kim A: Which clinical anesthesia outcomes are important to avoid? The perspective of patients. Anesth
Analg 89:652–658, 1999.
18. Sinclair
M, Simmons S, Cyna A: Incidents in obstetric anesthesia and analgesia: An analysis of 5000 AIMS reports. Anaesth Intensive Care
27:275–281, 1999.
19. Smith A, Pedersen T, Moller A: The Cochrane Anaesthesia Review Group. Eur J Anaesthesiol 17:279–283, 2000.
20. Hoyert DL, Danel I, Tully P: Maternal mortality, United States and Canada, 1982–1997. Birth 27:4–11, 2000.
21. Nagaya K, Fetters MD, Ishikawa M, et al: Causes of maternal mortality in Japan. JAMA 283:2661–2667, 2000.
22. Fleisher LA: Risk of anesthesia. In Miller RD (ed): Anesthesia, 5th ed. Philadelphia, Churchill Livingstone, 2000, pp 795–823.
23. Dodson
BA: Quality assurance/quality improvement. In Miller RD (ed): Anesthesia, 5th ed. Philadelphia, Churchill Livingstone, 2000, pp
2597–2612.
24. Wu CL, Fleisher LA: Outcomes research in regional anesthesia and analgesia. Anesth Analg 91:1232–1242, 2000.
25. de Bernis L, Dumont A, Bouillin D, et al: Maternal morbidity and mortality in two different populations of Senegal: A prospective study
(MOMA survey). Br J Obstet Gynecol 107:68–74, 2000.
26. LiebermanD, Sachs BP: Essentials in biostatistics and perinatal epidemiology. In Reece EA, Hobbins JC (eds): Medicine of the Fetus and
Mother, 2nd ed. Philadelphia, Lippincott-Raven, 1999, pp 1439–1449.
27. Goodman
N: Evidence based medicine: Cautions before use. In Tramer M (ed): Evidence Based Resource in Anaesthesia and Analgesia.
London, BMJ Books, 2000, pp 3–25.
28. Egger
M, Smith GD: Under the meta-scope: Potentials and limitations of meta-analysis. In Tramer M (ed): Evidence Based Resource in
Anesthesia and Analgesia. London, BMJ Books, 2000, pp 45–65.
29. Fung D, Cohen MM: Measuring patient satisfaction with anesthesia care: A review of current methodology. Anesth Analg 87:1098–1098,
1998.
30. Gaba DM: Anesthesiology as model for patient safety in health care. BMJ 320:785–788, 2000.
31. Keats AS: Anesthesia mortality in perspective. Anesth Analg 71:113–119, 1990.
32. Bothner U, Georgieff M, Schwilk B: Building a large-scale perioperative anaesthesia outcome-tracking database: Methodology,
implementation, and experiences from one provider within the German quality project. Br J Anaesth 85:271–280, 2000.
33. BrownridgeP, Cohen SE, Ward ME: Neural blockade for obstetrics and gynecologic surgery. In Cousins MJ, Bridenbaugh PO (eds): Neural
34. ASA:Practice Guidelines for Obstetrical Anesthesia. A Report by the American Society of Anesthesiologists Task Force on Obstetrical
Anesthesia. Anesthesiology 90:600–611, 1999.
35. Norris MC (ed): Obstetric Anesthesia, 2nd ed. Philadelphia, Lippincott Williams & Wilkins, 1999.
36. Birnbach DJ, Gatt SP, Datta S (eds): Textbook of Obstetric Anesthesia. New York, Churchill Livingstone, 2000.
37. Bromage PR: Neurologic complications of labor, delivery, and regional anesthesia. In Chestnut DH (ed): Obstetric Anesthesia. Principles and
Practice. St. Louis, Mosby, 1994, pp 621–639.
38. Holdcroft A, Gibberd FB, Hargrove RL, et al: Neurological complications associated with pregnancy. Br J Anaesth 75:522–526, 1995.
1143
39. Loo CC, Dahlgren G, Irestedt L: Neurological complications in obstetric regional anaesthesia. Int J Obstet Anesth 9:99–124, 2000.
40. Thorp JA: Epidural analgesia during labor. Clinic Obstet Gynecol 42:785–801, 1999.
41. Beilin Y, Leibowitz AB, Bernstein HH, Abramovitz SE: Controversies of labor epidural analgesia. Anesth Analg 89:969–978, 2000.
42. Kehlet
H: Modification of responses to surgery by neural blockade: Clinical implications. In Cousins MJ, Bridenbaugh PO (eds): Neural
43. Holloway J, Seed PT, O’Sullivan G, Reynolds F: Paraesthesiae and nerve damage following combined spinal epidural and spinal anaesthesia:
A pilot survey. Int J Obstet Anesth 9:151–155, 2000.
44. Scott DB, Hibbard BM: Serious non-fatal complications associated with extradural block in obstetric practice. Br J Anaesth 64:537–541, 1990.
45. Scott
DB, Tunstall ME: Serious complications associated with epidural/spinal blockade in obstetrics: A two-year prospective study. Int J
46. Olofsson C, Irestedt L: Traditional analgesic agents: Are parenteral narcotics passe and do inhalational agents still have a place in labour?
Baillière’s Clin Obstet Gynaecol 12:409–422, 1998.
47. McKenzie AG: Operative obstetric mortality at Harare Central Hospital 1992–1994: An anesthetic view. Int J Obstet Anesth 7:237–241, 1998.
48. Angulo-VazquezJ, Alcantar JO, Rodriguez-Arias EA, et al: Maternal mortality at the Gynecologic-Obstetric Hospital of the Western National
Medical Center, Mexico. A 12-year review. Ginecol Obstet Mex 67:419–424, 1999.
49. Loudon I: Maternal mortality in the past and its relevance to developing countries today. Am J Clin Nutrition 72(suppl):241S–246S, 2000.
50. Bouvier-Colle MH, Varnoux N, Breart G: Les Morts Maternelles en France. Paris, Editions INSERM, 1994.
51. Jacob S, Bloebaum L, Shah G, Varner MW: Maternal mortality in Utah. Obstet Gynecol 91:187–191, 1998.
52. Thomas TA: Maternal mortality. In Birnbach DJ, Gatt SP, Datta S (eds): Textbook of Obstetric Anesthesia. New York, Churchill Livingstone,
2000, pp 733–753.
53. Gherman RB, Macri CJ, Gerstenfeld T, Goodwin TM: Maternal mortality at LAC/USC Women’s Hospital: A 17-year review. Obstet Gynecol
95(suppl):44S–45S, 2000.
54. Meili-AntonG: Mütterliche Sterblichkeit in der Schweiz 1985–1994 [Inaugural Dissertation]. Zurich, Switzerland, Medical Faculty,
University of Zurich, 2000, 69 pp.
55. Coeuret-Pellicer
M, Bouvier-Colle MH, Salanave B: Do obstetric causes of death explain the differences in maternal mortality between France
and Europe? J Gynecol Obstet Biol Reprod (Paris) 28:62–68, 1999.
56. Salanave B, Bouvier-Colle MH: The likely increase in maternal mortality rates in the United Kingdom and in France until 2005. Paediatr
Perinat Epidemiol 10:418–422, 1996.
57. Scholz HS, Haas J, Petru E: Do primiparas aged 40 years or older carry an increased obstetric risk? Prev Med 29:263–266, 1999.
58. Berg CJ, Atrash HK, Koonin LM, Tucker M: Pregnancy-related mortality in the United States, 1987–1990. Obstet Gynecol 88:161–167, 1996.
59. Conde-Agudelo A, Belizan JM, Lindmark G: Maternal morbidity and mortality associated with multiple gestations. Obstet Gynecol 95:899–
904, 2000.
60. Weiss
BM, Hess OM: Pulmonary vascular disease and pregnancy: Current controversies, management strategies, and perspectives. Eur Heart J
21:104–115, 2000.
61. HawkinsJL, Koonin LM, Palmer SK, Gibbs CP: Anesthesia-related deaths during obstetric delivery in the United States, 1979–1990.
62. Chestnut DH: Anesthesia and maternal mortality. [editorial]. Anesthesiology 86:273–276, 1997.
63. Sachs BP, Oriol NE, Ostheimer GW, et al: Anesthetic-related maternal mortality, 1954 to 1985. J Clin Anesth 1:333–338, 1989.
64. Rout CC: Regional anesthesia for cesarean section. In Birnbach DJ, Gatt SP, Datta S (eds): Textbook of Obstetric Anesthesia. New York,
65. Gaiser
RR: Epidural anesthesia for cesarean delivery. In Norris MC (ed): Obstetric Anesthesia, 2nd ed. Philadelphia, Lippincott Williams &
Wilkins, 1999, pp 397–413.
66. Schneider MC: General anaesthesia for caesarean section revisited. Baillière’s Clin Anaesthesiol 9:649–673, 1995.
1144
67. Palot
M, Chale JJ, Colladon B, et al: Anesthesia and analgesia practice patterns in French obstetrical patients. Ann Fr Anesth Reanim 17:210–
219, 1998.
68. Stamer UM, Messerschmidt A, Wulf H: Anaesthesia for caesarean section—A German survey. Acta Anaesthesiol Scand 42:678–684, 1998.
69. StandlT, Wilhelm S, Gnirke A, Huneke B: Recent developments in obstetric anesthesia. A review of experiences at the Eppendorf University
Hospital. Anaesthesiol Intensivmed Notfallmed Schmerzther 34:648–658, 1999.
70. Shibli KU, Russell IF: A survey of anaesthetic techniques used for caesarean section in the UK in 1997. Int J Obstet Anesth 9:160–167, 2000.
71. Hawthorne L, Wilson R, Lyons G, Dresner M: Failed intubation revisited: 17-yr experience in a teaching maternity unit. Br J Anaesth 76:680–
684, 1996.
72. Jenkins JG: Failed intubation during obstetric anaesthesia [correspondence]. Br J Anaesth 77:698, 1996.
73. Barnardo PD, Jenkins JG: Failed tracheal intubation in obstetrics: A 6-year review in a UK region. Anaesthesia 55:690–694, 2000.
74. TsenLC, Pitner R, Camann WR: General anesthesia for cesarean section at a tertiary care hospital 1990–1995: Indications and implications.
Int J Obstet Anesth 7:147–152, 1998.
75. Gajraj NM, Sharma SK, Souter AJ, et al: A survey of obstetric patients who refuse regional anaesthesia. Anaesthesia 50:740–741, 1995.
76. Holdcroft A, Parshall AM, Knowles MG, et al: Factors associated with mothers selecting general anesthesia for lower segment caesarean
section. J Psychosom Obstet Gynaecol 16:167–170, 1995.
77. ChanY, Wong K, Lin C, et al: Views of obstetric patients who refuse regional anesthesia in cesarean section. Acta Anaesthesiol Sin 36:99–
102, 1998.
78. Sheiner
EE, Sheiner EK, Shoham-Vardi I, et al: Predictors of recommendation and acceptance of intrapartum epidural analgesia. Anesth Analg
90:109–113, 2000.
79. Richardson MG: Regional anesthesia in obstetrics. Anesth Clin North Am 18:383–406, 2000.
80. CrowhurstJA, Plaat F: Why mothers die—Report on Confidential Enquiries into Maternal Deaths in the United Kingdom 1994–96 (editorial).
Anaesthesia 54:207–209, 1999.
81. MalinowAM: General anesthesia for cesarean delivery. In Norris MC (ed): Obstetric Anesthesia, 2nd ed. Philadelphia, Lippincott Williams &
Wilkins, 1999, pp 375–395.
82. Alon E, Atanassoff PG: Successful cardiopulmonary resuscitation of a parturient with amniotic fluid embolism. Int J Obstet Anesth 1:205–207,
1992.
83. Ilsaas
C, Husby P, Koller ME, et al: Cardiac arrest due to massive pulmonary embolism following caesarean section. Successful resuscitation
and pulmonary embolectomy. Acta Anaesthesiol Scand 42:264–246, 1998.
84. Milne S: A pregnancy complicated by haemorrhage, cardiac arrest and eclampsia [correspondence]. Int J Obstet Anesth 7:140, 1998.
85. EppsSN, Robbins AJ, Marx GF: Complete recovery after near-fatal venous air embolism during cesarean section. Int J Obstet Anesth 7:131–
133, 1998.
86. Myint
Y, Bailey PR, Milne BR: Cardiorespiratory arrest following combined spinal epidural anaesthesia for caesarean section. Anaesthesia
48:684–686, 1993.
87. Peng
PW, Smedstad KG: Litigation in Canada against anesthesiologists practicing regional anesthesia. A review of closed claims. Can J
Anesth 47:105–112, 2000.
88. Horlocker
TT, McGregor DG, Matsushige DK, et al: A retrospective review of 4767 consecutive spinal anesthetics: Central nervous system
89. Dahlgren N, Törnerbrandt K: Neurological complications after anaesthesia. A follow-up of 18,000 spinal and epidural anaesthetics performed
over three years. Acta Anaesthesiol Scand 39:872–880, 1995.
90. AuroyY, Narchi P, Messiah A, et al: Serious complications related to regional anesthesia. Results of a prospective survey in France.
91. Eisenach JC: Regional anesthesia: Vintage Bordeaux (and Napa Valley) (editorial). Anesthesiology 87:467–469, 1997.
92. Aromaa U, Lahdensuu M, Cozanitis DA: Severe complications associated with epidural and spinal anaesthesias in Finland 1987–1993. A
study based on patient insurance claims. Acta Anaesthesiol Scand 41:445–452, 1997.
93. PleymH, Spigset O: Peripheral neurologic deficits in relation to subarachnoid or epidural administration of local anesthetics for surgery. A
survey of 21 cases. Acta Anaesthesiol Scand 41:453–460, 1997.
1145
94. Hampl KF, Schneider MC, Ummenhofer W, Drewe J: Transient neurologic symptoms after spinal anesthesia. Anesth Analg 81:1148–1153,
1995.
95. Hampl KF, Schneider MC, Pargger H, et al: A similar incidence of transient neurologic symptoms after spinal anesthesia with 2% and 5%
lidocaine. Anesth Analg 83:1051–1054, 1996.
96. PollockJE, Neal JM, Stephenson CA, Wiley CE: Prospective study of the incidence of transient radicular irritation in patients undergoing
spinal anesthesia. Anesthesiology 84:1361–1367, 1996.
97. Martinez-Bourio
R, Arzuaga M, Quintana JM, et al: Incidence of transient neurologic symptoms after hyperbaric subarachnoid anesthesia with
5% lidocaine and 5% prilocaine. Anesthesiology 88:624–628, 1998.
98. Liguori GA, Zayas VM, Chisholm MF: Transient neurologic symptoms after spinal anesthesia with mepivacaine and lidocaine.
99. Hampl KF, Heinzmann-Wiedmer S, Luginbuehl I, et al: Transient neurologic symptoms after spinal anesthesia. A lower incidence with
prilocaine and bupivacaine than with lidocaine. Anesthesiology 88:629–633, 1998.
101. Zakowski MI: Postoperative complications associated with regional anesthesia in the parturient. In Norris MC (ed): Obstetric Anesthesia, 2nd
ed. Philadelphia, Lippincott Williams & Wilkins, 1999, pp 723–748.
102. KeldDB, Hein L, Dalgaard M, et al: The incidence of transient neurologic symptoms (TNS) after spinal anesthesia in patients undergoing
surgery in the supine position. Hyperbaric lidocaine 5% versus hyperbaric bupivacaine 0.5%. Acta Anaesthesiol Scand 44:285–290, 2000.
103. Loo CC, Irestedt L: Cauda equina syndrome after spinal anaesthesia with hyperbaric 5% lignocaine: A review of six cases of cauda equina
syndrome reported to the Swedish Pharmaceutical Insurance 1993–1997. Acta Anaesthesiol Scand 43:371–379, 1999.
104. Gisvold SE: Lidocaine may still be an excellent drug for spinal anaesthesia (editorial). Acta Anaesthesiol Scand 43:369–370, 1999.
105. Rowlingson J: To avoid “transient neurologic symptoms”—The search continues (editorial). Reg Anesth Pain Med 25:215–217, 2000.
106. Reynolds F: Maternal sequelae of childbirth (editorial). Br J Anaesth 75:515–517, 1995.
107. Vandermuelen EP, Van Aken H, Vermyelen J: Anticoagulants and spinal-epidural anesthesia. Anesth Analg 79:1165–1177, 1994.
108. Collier CB: Complications of regional anesthesia. In Birnbach DJ, Gatt SP, Datta S (eds): Textbook of Obstetric Anesthesia. New York,
109. Ackerman WE 3rd, Andrews PJ, Juneja MM, Rigor BM: Cauda equina syndrome: A consequence of lumbar disk protrusion or continuous
subarachnoid analgesia? Anesth Analg 76:898–901, 1993.
110. Forster MR, Nimmo GR, Brown AG: Prolapsed intervertebral disc after epidural analgesia in labour. Anaesthesia 51:773–775, 1996.
111. Kawasaki K, Hoshino K, Takahashi M, et al: Complications of spinal anesthesia as the initial symptom in patients with spinal tumor—A
report of two cases. Masui 48:1340–1342, 1999.
112. Yuen EC, Layzer RB, Weitz SR, Olney RK: Neurologic complications of lumbar epidural anesthesia and analgesia. Neurology 45:1795–1801,
1995.
113. Tubridy N, Redmond JM: Neurological symptoms attributed to epidural analgesia in labor: An observational study of seven cases. Br J Obstet
Gynaecol 103:832–833, 1996.
114. Rawal N, Holmström B, Zundert AV, Crowhurst JA: The combined spinal-epidural technique. In Birnbach DJ, Gatt SP, Datta S (eds):
Textbook of Obstetric Anesthesia. New York, Churchill Livingstone, 2000, pp 157–182.
115. Cook TM: Combined spinal-epidural techniques. Anaesthesia 55:42–64, 2000.
116. Norris MC: Spinal anesthesia for cesarean delivery. In Norris MC (ed): Obstetric Anesthesia, 2nd ed. Philadelphia, Lippincott Williams &
Wilkins, 1999, pp 415–439.
117. DaviesSJ, Peach MJ, Welch H, et al: Maternal experience during epidural or combined spinal-epidural anesthesia for cesarean section: A
prospective, randomized trial. Anesth Analg 85:607–613, 1997.
118. Rocke DA, Murray WB, Rout CC, Gouws E: Relative risk analysis of factors associated with difficult intubation in obstetric anesthesia.
119. el-Ganzouri AR, McCarthy RJ, Tuman KJ, et al: Preoperative airway assessment: Predictive value of a multivariate risk index. Anesth Analg
82:1197–1204, 1996.
1146
120. Karkouti K, Rose DK, Wigglesworth D, Cohen MM: Predicting difficult intubation: A multivariable analysis. Can J Anaesth 47:730–739,
2000.
121. Stackhouse RA, Hughes SC: Cesarean section. Curr Opin Anaesthesiol 7:231–239, 1994.
122. Leighton BL: Intraoperative anesthetic complication. In Norris MC (ed): Obstetric Anesthesia, 2nd ed. Philadelphia, Lippincott, Williams &
Wilkins, 1999, pp 593–618.
123. Watanabe S, Handa F: Difficult and failed intubation. In Birnbach DJ, Gatt SP, Datta S (eds): Textbook of Obstetric Anesthesia. New York,
124. EvansCM, Murphy JF, Gray OP, Rosen M: Epidural versus general anesthesia for elective caesarean section. Effect on Apgar score and acid-
base status of the newborn. Anaesthesia 44:778–782, 1989.
125. Khor LJ, Cooper GM, Paterson-Brown S: National obstetric anaesthetic practice in the UK 1997/1998. Anaesthesia 55:1168–1172, 2000.
126. Soreide E, Bjornestad E, Steen PA: An audit of perioperative aspiration pneumonitis in gynaecological and obstetric patients. Acta
127. McIntyre JW: Evolution of the 20th century attitudes to prophylaxis of pulmonary aspiration during anaesthesia. Can J Anaesth 45:1024–1030,
1998.
128. Ezri T, Szmuk P, Stein A, et al: Peripartum general anaesthesia without tracheal intubation: Incidence of aspiration pneumonia. Anaesthesia
55:421–426, 2000.
129. Macfie AG, Magides AD, Richmond MN, Reilly CS: Gastric emptying in pregnancy. Br J Anaesth 67:54–57, 1991.
130. Zimmermann DL, Breen TW, Fick G: Adding fentanyl 0.0002% to epidural bupivacaine 0.125% does not delay gastric emptying in laboring
parturients. Anesth Analg 82:612–616, 1996.
131. Scrutton MJ, Metcalfe GA, Lowy C, et al: Eating in labour. A randomized controlled trial assessing the risks and benefits. Anaesthesia
54:329–334, 1999.
132. Frölich MA: Anesthesia for presumed fetal jeopardy. In Birnbach DJ, Gatt SP, Datta S (eds): Textbook of Obstetric Anesthesia. New York,
133. Shyken JM: Indications for cesarean delivery. In Norris MC (ed): Obstetric Anesthesia, 2nd ed. Philadelphia, Lippincott Williams & Wilkins,
1999, pp 363–374.
134. Ross A: Physiologic changes of pregnancy. In Birnbach DJ, Gatt SP, Datta S (eds): Textbook of Obstetric Anesthesia. New York, Churchill
135. Ong BY, Cohen MM, Esmail A, et al: Paresthesia and motor dysfunction after labor and delivery. Anesth Analg 66:18–22, 1987.
136. MacArthur C, Lewis M, Knox EG: Investigation of long term problems after obstetric epidural anaesthesia. BMJ 304:1279–1282, 1992.
137. Yoshii WJ, Rottman RL, Rosenblatt RA, et al: Epidural catheter-induced traumatic radicolopathy in obstetrics. Reg Anesth 19:132–135, 1994.
138. Kerdraon J, Amarenco G, Denys P: Vesico-sphincteric complications of spinal anesthesia. Eight cases. Press Med 22:410–412, 1993.
139. Viktrup L, Lose G: Epidural anesthesia during labor and stress incontinence after delivery. Obstet Gynecol 82:984–986, 1993.
140. Olofsson C, Ekblom A, Ekman-Ordeberg G, Irestedt L: Post-partum urinary retention: A comparison between two methods of epidural
analgesia. Eur J Obstet Gynecol Reprod Biol 71:31–34, 1997.
141. Peach MJ, Godkin R, Webster S: Complications of obstetric analgesia and anesthesia: A prospective analysis of 10,995 cases. Int J Obstet
Anesth 7:5–11, 1998.
142. Jenkins J: Complications of obstetric epidurals: An audit of 10,817 cases [correspondence]. Int J Obstet Anesth 7:280–281, 1998.
143. Horlocker TT, McGregor DG, Matsushige DK, et al: Neurologic complications of 603 consecutive continuous spinal anesthetics using
macrocatheter and microcatheter techniques. Perioperative Outcome Groups. Anesth Analg 84:1063–1070, 1997.
144. Hurley
RJ: Continuous spinal anesthesia techniques for labor and delivery. In Birnbach DJ, Gatt SP, Datta S (eds): Textbook of Obstetric
Anesthesia. New York, Churchill Livingstone, 2000, pp 183–188.
145. Huckaby T, Skerman JH, Hurley RJ, Lambert DH: Sensory analgesia for vaginal deliveries: A preliminary report of continuous spinal
anesthesia with a 32-gauge catheter. Reg Anesth 16:150–153, 1991.
146. Robson SC, Samsoon G, Boys RJ, et al: Incremental spinal anaesthesia for elective caesarean section: Maternal and fetal haemodynamic
1147
effects. Br J Anaesth 70:634–638, 1993.
147. Bayhi D, Cork RC, Heaton JF, Nolan TE: Prospective survey of continuous versus single-injection spinal anesthesia in obstetrics. South Med
J 88:1043–1048, 1995.
148. Standl
T, Celik L, Weyland C, et al: Microcatheter CSA in a young woman with Fontan repair undergoing elective sterilization. Acta
149. Honig
O, Winter H, Baum KR, et al: Cesarean section with continuous spinal anesthesia in a cardiopulmonary high-risk patient. Anaesthesist
47:685–689, 1998.
150. Overdyk FJ, Harvey SC: Continuous spinal anesthesia for cesarean section in a parturient with severe preeclampsia. J Clin Anesth 10:510–
513, 1998.
151. Lockhart
EM, Penning DH, Olufolabi AJ, et al: SVO2 monitoring during spinal anesthesia and cesarean section in a parturient with severe
cyanotic congential heart disease. Anesthesiology 90:1213–1215, 1999.
152. Pittard A, Vucevic M: Regional anaesthesia with a subarachnoid microcatheter for caesarean section in a parturient with aortic stenosis.
Anaesthesia 53:169–173, 1998.
153. Norris
MC, Grieco WM, Borkowski M, et al: Complications of labor analgesia: Epidural versus combined spinal epidural techniques. Anesth
Analg 79:529–537, 1994.
154. Nageotte MP, Larson D, Rumney PJ, et al: Epidural analgesia compared with combined spinal-epidural analgesia during labor in nulliparous
women. N Engl J Med 337:1715–1719, 1997.
155. Russell R, Plaat F: Controversies. The dura is too vulnerable to be breached routinely in labour. Int J Obstet Anesth 8:56–61, 1999.
156. Albright
GA, Forster RM: The safety and efficacy of combined spinal and epidural analgesia/anesthesia (6,002 blocks) in a community
hospital. Reg Anesth Pain Med 24:117–125, 1999.
157. Kindler
CH, Seeberger MD, Staender SE: Epidural abscess complicating epidural anesthesia and analgesia. An analysis of the literature. Acta
Anaesthsiol Scand 42:614–620, 1998.
158. Harding SA, Collis RE, Morgan BM: Meningitis after combined spinal-extradural anaesthesia in obstetrics. Br J Anaesth 73:545–547, 1994.
159. Bouhemad B, Dounas M, Mercier FJ, Benhamou D: Bacterial meningitis following combined spinal-epidural analgesia for labour.
Anaesthesia 53:292–295, 1998.
160. Duflo
F, Allaouchiche B, Mathon L, Chassard D: Bacterial meningitis following combined obstetric spinal and peridural anesthesia. Ann Fr
Anesth Reanim 17:1286, 1998.
161. Vives A, Carmona F, Zabala E, et al: Maternal brain death during pregnancy. Int J Obstet Gynecol 52:67–69, 1996.
162. Chen C, Wang K: Cryptococcal meningitis in pregnancy. Am J Perinatol 13:35–36, 1996.
163. Wolfe PR Jr, Norwick ML, Bofill JA: Fatal maternal beta-hemolytic group B streptococcal meningitis: A case report. Am J Perinatol 15:597–
600, 1998.
164. Wysowski
DK, Talrico L, Bacsanyi J, Botstein P: Spinal and epidural hematoma and low-molecular-weight heparin [letter]. N Engl J Med
338:1774–1775, 1998.
165. Yuen T, Kuan J, Tan T: Spinal haematoma following epidural anaesthesia in a patient with eclampsia. Anaesthesia 54:350–354, 1999.
166. Checketts MR, Wildsmith JA: Central nerve block and thromboprophylaxis—Is there a problem? (editorial). Br J Anaesth 82:164–167, 1999.
167. Hack
I, Cademartori MS, Mamani RS, et al: Spontaneous spinal epidural hematoma during pregnancy: Report of a case. Arq Neuropsiquiatr
42:41–44, 1984.
168. Mahieu X, Kridelka F, Pintiaux A, et al: Spontaneous cervical extradural hematoma in a pregnant woman. J Gynecol Obstet Biol Reprod
23:99–102, 1994.
169. Milaskiewicz RM, Holdcroft A, Letsky E: Epidural anaesthesia and Von Willebrand’s disease. Anaesthesia 45:462–464, 1990.
170. Fragneto
RY, Datta S: Epidural analgesia in a preeclamptic parturient after normalization of a prolonged bleeding time with DDAVP. Reg
Anesth 20:448–451, 1995.
171. Bailey AR, Wolmarans M, Rhodes S: Spinal anaesthesia for caesarean section in a patient with systemic sclerosis. Anaesthesia 54:350–371,
1999.
172. Beilin Y, Zahn J, Comerford M: Safe epidural analgesia in thirty parturients with platelet counts between 69,000 and 98,000 (mm−3 ). Anesth
1148
Analg 85:385–388, 1997.
173. Jones
BP, Bell EA, Maroof M: Epidural labor analgesia in a parturient with von Willebrand’s disease type IIA and severe preeclampsia.
174. Orlikowski
CE, Rocke DA: Anesthesia and hematologic diseases. In Norris MC (ed): Obstetric Anesthesia, 2nd ed. Philadelphia, Lippincott
Williams & Wilkins, 1999, pp 453–465.
175. Diemunsch P, Balabaud VP, Petau C, et al: Bilateral subdural hematoma following epidural anesthesia. Can J Anaesth 45:328–331, 1998.
176. Vaughan DJ, Stirrup CA, Robinson PN: Cranial subdural haematoma associated with dural puncture in labour. Br J Anaesth 84:518–520,
2000.
177. Cantais E, Benhamou D, Petit D, Palmier B: Acute subdural hematoma following spinal anesthesia with a very small spinal needle.
178. Giannina G, Smith D, Belfort MA, Moise KJ Jr: Atraumatic subdural hematoma associated with pre-eclampsia. J Matern Fetal Med 6:93–95,
1997.
179. Horlocker
Reg Anesth Pain Med 23 (Suppl 2):164–177, 1998.
180. Tryba M: European Practice Guidelines: Thromboembolism prophylaxis and regional anesthesia. Reg Anesth Pain Med 23 (Suppl 2):178–182,
1998.
181. Saberski
L, Kondamuri S, Osinubi O: Comment on severe lumbar back pain following epidural anesthesia (correspondence). Reg Anesth
20:550, 1995.
182. Hirabayashi Y, Shimizu R, Fukuda H, et al: Soft tissue anatomy within the vertebral canal in pregnant women. Br J Anaesth 77:153–156,
1996.
183. Hirabayashi Y, Shimizu R, Fukuda H, et al: Effects of pregnant uterus on the extradural venous plexus in the supine and lateral positions, as
determined by magnetic resonance imaging. Br J Anaesth 78:317–319, 1997.
184. Carpenter RL, Hogan QH, Liu SS, et al: Lumbosacral cerebrospinal fluid volume is the primary determinant of sensory block extent and
duration during spinal anesthesia. Anesthesiology 89:24–29, 1998.
185. Richardson MG, Wissler RN: Density of lumbar cerebrospinal fluid in pregnant and nonpregnant humans. Anesthesiology 85:326–330, 1996.
186. Igarashi T, Hirabayashi Y, Shimizu R, et al: The fiberscopic findings of the epidural space in pregnant women. Anesthesiology 92:1631–1636,
2000.
187. Jawan
B, Lee JH, Chong ZK, Chang CS: Spread of spinal anesthesia for caesarean section in singleton and twin pregnancies. Br J Anaesth
70:639–641, 1993.
188. Lu JK, Manullang TR, Staples MH, et al: Maternal respiratory arrest, severe hypotension, and fetal distress after administration of intrathecal
sufentanil, and bupivacaine after intravenous fentanyl. Anesthesiology 87:170–172, 1997.
189. D’Agnelo R, Eisenach JC: Severe maternal hypotension and fetal bradycardia after combined spinal epidural anesthetic. Anesthesiology
87:166–168, 1997.
190. Sarvela PJ, Halonen PM, Korttila KT: Comparison of 9 mg of intrathecal plain and hyperbaric bupivacaine both with fentanyl for cesarean
delivery. Anesth Analg 89:1257–1262, 1999.
191. Forrester DJ, Mukherji SK, Mayer DC, Speilman FJ: Dilute infusion for labor, obscure subdural catheter, and life-threatening block at
cesarean delivery. Anesth Analg 89:1267–1268, 1999.
192. AbuAbdou W, Avekine C, Bonnet F: Two additional cases of excessive extension of sensory blockade after intrathecal sufentanil for labor
analgesia. Int J Obstet Anesth 9:48–50, 2000.
193. Evron S, Krumholtz S, Wiener Y, et al: Prolonged coma and quadriplegia after accidental subarachnoid injection of a local anesthetic with an
opiate. Anesth Analg 90:116–118, 2000.
194. Ferouz F, Norris MC, Leighton BL: Risk of respiratory arrest after intrathecal sufentanil. Anesth Analg 85:1088–1090, 1997.
195. Katsiris
S, Williams S, Leighton BL, Halpern S: Respiratory arrest following intrathecal injection of sufentanil and bupivacaine in a parturient.
Can J Anaesth 45:880–883, 1998.
196. Alderson
JD: Cardiovascular collapse following epidural anaesthesia for Caesarean section in a patient with aortic incompetence. Anaesthesia
42:643–645, 1987.
197. Kimura T, Komatsu T, Hirabayashi A, et al: Autonomic imbalance of the heart during total spinal anesthesia evaluated by spectral analysis of
1149
heart rate variability. Anesthesiology 80:694–698, 1994.
198. Hawthorne L, Lyons G: Cardiac arrest complicating spinal anaesthesia for Caesarean section. Int J Obstet Anesth 6:126–129, 1997.
199. Clayton KC: The incidence of Horner’s syndrome during lumbar extradural for elective Caesarean section and provision of analgesia during
labour. Anaesthesia 38:583–585, 1983.
200. Sprung
J, Haddox JD, Maitra-D’Cruze AD: Horner’s syndrome and trigeminal nerve palsy following epidural anaesthesia for obstetrics. Can J
Anaesth 38:767–771, 1991.
201. DayDJ, Shutt LE: Auditory, ocular, and facial complications of central neural block. A review of possible mechanisms. Reg Anesth 21:197–
201, 1996.
202. Paw HG: Horner’s syndrome following low-dose epidural infusion for labour: A cautionary tale. Eur J Anaesthesiol 15:110–111, 1998.
203. Szokol JW, Falleroni MJ: Lack of efficacy of an epidural blood patch in treating abducens nerve palsy after an unintentional dural puncture.
204. Barry-Kinsella C, Milner M, McCarthy N, Walshe J: Sixth nerve palsy: An unusual manifestation of preeclampsia. Obstet Gynecol 83:849–
851, 1994.
205. Fung TY, Chung TK: Abducens nerve palsy complicating pregnancy: A case report. Eur J Obstet Gynecol Reprod Biol 83:223–224, 1999.
206. Chun DM, Levin DK: Ischemic optic neuropathy after hemorrhage from a cornual ectopic pregnancy. Am J Obstet Gynecol 177:1550–1552,
1997.
207. Sharma R, Desai S: Postpartum hemorrhage producing acute ischemic optic neuropathy. Asia Oceania J Obstet Gynaecol 19:249–251, 1993.
208. Shapira OM, Kimmel WA, Lindsey PS, Shahian DM: Anterior ischemic optic neuropathy after open heart operations. Ann Thorac Surg
61:660–666, 1996.
209. Busch T, Sirbu H, Aleksic I, et al: Anterior ischemic optic neuropathy: A complication after extracorporal circulation. Ann Thorac Cardiovasc
Surg 4:354–358, 1998.
210. Eggenberger ER, Desai NP, Kaufman DI, Pless M: Internuclear ophthalmoplegia after coronary artery catheterization and percutaneous
transluminal coronary balloon angioplasty. J Neuroophthalmol 20:123–126, 2000.
211. Carrero EJ, Agusti M, Fabregas N, et al: Unilateral trigeminal and facial nerve palsies associated with epidural analgesia in labour. Can J
Anaesth 45:893–897, 1998.
212. Dorsey DL, Camann WR: Obstetric anesthesia in patients with idiopathic facial paralysis (Bell’s palsy): A 10-year survey. Anesth Analg
77:81–83, 1993.
213. Shapiro JL, Yudin MH, Ray JG: Bell’s palsy and tinnitus during pregnancy: Predictors of preeclampsia? Three cases and a detailed review of
the literature. Acta Otolaryngol 119:647–651, 1999.
214. Schaffartzik W, Hirsch J, Frickmann F, et al: Hearing loss after spinal and general anesthesia: A comparative study. Anesth Analg 91:1466–
1472, 2000.
215. Jeanjean
P, Montpellier D, Carnec J, et al: Headaches after spinal anesthesia: Prospective multicenter study of a young adult population. Ann
Fr Anesth Reanim 16:350–353, 1997.
216. Eriksson AL, Hallen B, Lagerkranser M, et al: Whitacre or Quincke needles—does it really matter? Acta Anaesthesiol Scand 113 (Suppl):17–
20, 1998.
217. Liu SS: Why are postdural puncture headaches still a problem [editorial]? Reg Anesth Pain Med 25:347–349, 2000.
218. Schneider MC, Schmid M: Post-dural puncture headache. In Birnbach DJ, Gatt SP, Datta S (eds): Textbook of Obstetric Anesthesia. New
York, Churchill Livingstone, 2000, pp 487–503.
219. Durbridge J, Holdcroft A: The long-term effects of analgesia in labour. Baillière’s Clin Obstet Gynaecol 12(3):485–498, 1998.
220. Benhamou D, Hamza J, Ducot B: Post-partum headache after epidural analgesia without dural puncture. Int J Obstet Anesth 4:17–20, 1995.
221. Hopkinson JM, Samaan AK, Russell IF, et al: A comparative multicentre trial of spinal needles for cesarean section. Anaesthesia 52:1005–
1011, 1997.
222. Gleeson CM, Reynolds F: Accidental dural puncture rates in the UK obstetric practice. Int J Obstet Anesth 7:242–246, 1998.
223. Williams EJ, Beaulieu P, Fawcett WJ, Jenkins JG: Efficacy of peridural blood patch in the obstetric population. Int J Obstet Anesth 8:105–
109, 1999.
1150
224. Berger CW, Crosby ET, Grodecki W: North American survey of the management of dural puncture occurring during labour epidural
analgesia. Can J Anaesth 45:110–114, 1998.
225. Vercauteren MP, Hoffmann VH, Martens E, et al: Seven-year review of requests for epidural blood patches for headache after dural puncture:
Referral patterns and the effectiveness of blood patches. Eur J Anaesthesiol 16:298–303, 1999.
226. Östgaard HC, Roos-Hansson E, Zetherström G: Regression of back and posterior pelvic pain after pregnancy. Spine 21:2777–2780, 1996.
227. Kristiansson P, Svärdsudd K, Von Schoultz B: Back pain during pregnancy. A prospective study. Spine 21:702–709, 1996.
228. Brynhildsen J, Hansson A, Persson A, Hammar M: Follow-up of patients with low back pain during pregnancy. Obstet Gynecol 91:182–186,
1998.
229. Martin HB, Gibbons JJ, Bucholz RD: An unusual presentation of spinal cord tumor after epidural anesthesia. Anesth Analg 75:844–846, 1992.
230. Garmel SH, Guzelian GA, D’Alton JG, D’Alton ME: Lumbar disk disease in pregnancy. Obstet Gynecol 89:821–822, 1997.
231. HoldcroftA, Badouin C, Fernando R, et al: Post partum magnetic resonance imaging: Lumbar tissue changes are unrelated to epidural
analgesia or mode of delivery. Int J Obstet Anesth 4:201–206, 1995.
232. Musumeci R, Villa E: Symphysis pubis separation during vaginal delivery with epidural anesthesia. Case report. Reg Anesth 19:289–291,
1994.
233. Fuller JG, Janzen J, Gambling DR: Epidural analgesia in the management of symptomatic symphysis pubis diastasis. Obstet Gynecol 73:855–
857, 1989.
234. Russell R, Groves P, Taub N, et al: Assessing long term backache after childbirth. BMJ 306:299–303, 1993.
235. MacLeod J, Macintyre C, McClure JH, Whitfield A: Backache and epidural analgesia. A retrospective survey of mothers 1 year after child
birth. Int J Obstet Anesth 4:21–25, 1995.
236. Macarthur AJ, Macarthur C, Weeks SK: Epidural anaesthesia and low back pain after delivery: A prospective cohort study. BMJ 311:1336–
1339, 1995.
237. Breen TW, Ransil BJ, Groves PA, Oriol NE: Factors associated with back pain after childbirth. Anesthesiology 81:29–34, 1994.
238. Russell R, Dundas R, Reynolds F: Long term backache after childbirth: Prospective search for causative factors. BMJ 312:1384–1388, 1996.
239. Macarthur
AJ, Macarthur C, Weeks SK: Is epidural anesthesia in labor associated with chronic low back pain? A prospective cohort study.
Anesth Analg 85:1066–1070, 1997.
240. Butler R, Fuller J: Back pain following epidural anaesthesia in labor. Can J Anaesth 45:724–728, 1998.
241. ArkooshVA: Neuroaxial analgesia for labor. Part II: Intrathecal drugs. In Norris MC (ed): Obstetric Anesthesia, 2nd ed. Philadelphia,
Lippincott Williams & Wilkins, 1999, pp 317–331.
242. Riley
ET: Neuroaxial analgesia for labor. Part III: Epidural drugs. In Norris MC (ed): Obstetric Anesthesia, 2nd ed. Philadelphia, Lippincott
Williams & Wilkins, 1999, pp 333–342.
243. Paull
J: Epidural anesthesia for labor. In Birnbach DJ, Gatt SP, Datta S (eds): Textbook of Obstetric Anesthesia. New York, Churchill
244. Peach MJ: Patient-controlled epidural analgesia. In Birnbach DJ, Gatt SP, Datta S (eds): Textbook of Obstetric Anesthesia. New York,
245. Finster M, Santos AC: The effects of epidural analgesia on the course and outcome of labour. Baillière’s Clin Obstet Gynaecol 12(3):473–484,
1998.
246. Riley
ET, Cohen SE, Macario A, et al: Spinal versus epidural anesthesia for cesarean section: A comparison of time efficiency, costs, charges,
and complications. Anesth Analg 80:709–712, 1995.
247. Dahl JB, Jeppesen IS, Jorgensen H, et al: Intraoperative and postoperative analgesic efficacy and adverse effects of intrathecal opioids in
patients undergoing cesarean section with spinal anesthesia. A qualitative and quantitative systematic review of randomized controlled trials.
248. Macario A, Scibetta WC, Navarro J, Riley E: Analgesia for labor pain. A cost model. Anesthesiology 92:841–850, 2000.
249. Olofsson
C, Ekblom A, Skoldefors E, et al: Anesthetic quality during cesarean section following subarachnoid or epidural administration of
bupivacaine with or without fentanyl. Acta Anaesthesiol Scand 41:332–338, 1997.
1151
250. Vandenbussche FP, de Jong-Potjer LC, Stiggelbout AM, et al: Differences in the valuation of birth outcomes among pregnant women,
mothers, and obstetricians. Birth 26:178–183, 1999.
251. Chestnut DH: Epidural analgesia and the incidence of cesarean section. Time for another close look [editorial]. Anesthesiology 87:472–476,
1997.
252. Halpern
SH, Leighton BL, Ohlsson A, et al: Effect of epidural vs parenteral opiod analgesia on the progress of labor. A meta-analysis. JAMA
280:2150–2110, 1998.
253. Zhang J, Klebanoff MA, DerSimonian R: Epidural analgesia in association with duration of labor and mode of delivery: A quantitative review.
Am J Obstet Gynecol 180:970–977, 1999.
254. Polley
LS, Columb MO, Wagner DS, Naughton NN: Dose-dependent reduction of the minimum local analgesic concentration of bupivacaine
by sufentanil for epidural analgesia in labor. Anesthesiology 89:626–632, 1998.
255. Polley
LS, Columb MO, Naughton NN, et al: Effect of intravenous versus epidural fentanyl on the minimum local analgesic concentration of
epidural bupivacaine in labor. Anesthesiology 93:122–128, 2000.
256. Wissler
RN, Norris MC: Neuroaxial analgesia for labor. Part I: Techniques. In Norris MC (ed): Obstetric Anesthesia, 2nd ed. Philadelphia,
257. Vandermeulen EP, Van Aken H, Vertommen JD: Labor pain relief using bupivacaine and sufentanil: Patient controlled epidural analgesia
versus intermittent injections. Eur J Obstet Gynecol Reprod Biol 59 (Suppl):S47–S54, 1995.
258. BernardJM, Le Roux D, Vizquel L, et al: Patient-controlled epidural analgesia during labor: The effects of the increase in bolus and lockout
interval. Anesth Analg 90:328–332, 2000.
259. Boutros A, Blary S, Bronchard R, Bonnet F: Comparison of intermittent epidural bolus, continuous epidural infusion and patient controlled-
analgesia during labor. Int J Obstet Anesth 8:236–241, 1999.
260. Le Coq G, Ducot B, Benhamou D: Risk factors of inadequate pain relief during epidural analgesia for labour and delivery. Can J Anaesth
45:719–723, 1998.
261. Russell R, Quinlan J, Reynolds F: Motor block during epidural infusions for nulliparous women in labour. Int J Obstet Anesth 4:82–88, 1995.
262. TanakaK, Watanabe R, Harada T, Dan K: Extensive application of epidural anesthesia and analgesia in a university hospital: Incidence of
complications related to technique. Reg Anesth 18:34–38, 1994.
263. Vande Velde M, Mignolet K, Vandermeersch E, Van Assche A: Prospective, randomized comparison of epidural and combined spinal
epidural analgesia during labor. Acta Anaesthesiol Belg 50:129–136, 1999.
264. Wilson DJ, Douglas MJ: Neuroaxial opioids in labour. Baillière’s Clin Obstet Gynaecol 12:363–376, 1998.
265. Norris MC: Are combined spinal-epidural catheters reliable? Int J Obstet Anesth 9:3–6, 2000.
266. Dresner
M, Bamber J, Calow C, et al: Comparison of low-dose epidural with combined spinal-epidural analgesia for labour. Br J Anaesth
83:756–760, 1999.
267. Nickells JS, Vaughan DJ, Lillywhite NK, et al: Speed of onset of regional analgesia for labour: A comparison of the epidural and spinal routes.
Anaesthesia 55:17–20, 2000.
268. D’Angelo R, Anderson MT, Philip J, Eisenach JC: Intrathecal sufentanil compared to epidural bupivacaine for labor analgesia.
269. Collis
RE, Davies DW, Aveling W: Randomised comparison of combined spinal-epidural and standard epidural analgesia in labour. Lancet
345:1413–1416, 1995.
270. Kartawiadi L, Vercauteren MP, Van Steenberge AL, Adriaensen AH: Spinal analgesia during labor with low-dose bupivacaine, sufentanil,
and epinephrine. A comparison with epidural analgesia. Reg Anesth 21:191–196, 1996.
271. Dunn SM, Connelly NR, Steinberg RB, et al: Intrathecal sufentanil versus epidural lidocaine with epinephrine and sufentanil for early labor
analgesia. Anesth Analg 87:331–335, 1998.
272. Breen TW, Giesinger CM, Halpern SH: Comparison of epidural lidocaine and fentanyl to intrathecal sufentanil for analgesia in early labor. Int
J Obstet Anesth 8:226–230, 1999.
273. Camann W, Abouleish A, Eisenach J, et al: Intrathecal sufentanil and epidural bupivacaine for labor analgesia: Dose-response of individual
agents and in combination. Reg Anesth Pain Med 23:457–462, 1998.
274. Tsen LC, Thue B, Datta S, Segal S: Is combined spinal-epidural analgesia associated with more rapid cervical dilation in nulliparous patients
when compared with conventional epidural analgesia? Anesthesiology 91:920–925, 1999.
1152
275. Eappen
S, Blinn A, Segal S: Incidence of epidural catheter replacement in parturients: A retrospective chart review. Int J Obstet Anesth
7:220–225, 1998.
276. Roux M, Wattrisse G, Tai RB, et al: Obstetric analgesia: Peridural analgesia versus combined spinal and epidural analgesia. Ann Fr Anesth
Reanim 18:487–498, 1999.
277. Hepner
DL, Gaiser RR, Cheek TG, Gutsche BB: Comparison of combined spinal-epidural and low dose epidural for labour analgesia. Can J
Anaesth 47:232–236, 2000.
278. Gambling DR, Sharma SK, Ramin SM, et al: A randomized study of combined spinal-epidural analgesia versus intravenous meperidine
during labor. Impact on cesarean delivery rate. Anesthesiology 89:1336–1344, 1998.
279. Albright GA, Forster RM: Does combined spinal epidural analgesia with subarachnoid sufentanil increase the incidence of emergency
cesarean delivery? Reg Anesth 22:400–405, 1997.
280. Richardson MG, Collins HV, Wissler RN: Intrathecal hypobaric versus hyperbaric bupivacaine with morphine for cesarean section. Anesth
Analg 87:336–340, 1998.
281. Quinn AJ, Kilpatrick A: Emergency caesaren section during labour: Response times and type of anaesthesia. Eur J Obstet Gynecol Reprod
Biol 54:25–29, 1994.
282. Korhonen J, Kariniemi V: Emergency cesarean section: The effect of delay on umbilical arterial gas balance and Apgar scores. Acta Obstet
Gynecol Scand 73:782–786, 1994.
283. Hall MH, Bewley S: Maternal mortality and mode of delivery. Lancet 354:776, 1999.
284. Roberts JM: Recent advances. Obstetrics. BMJ 321:33–35, 2000.
285. Hawkins JL, Gibbs CP, Orleans M, et al: Obstetric anesthesia work force survey, 1981 versus 1992. Anesthesiology 87:135–143, 1997.
286. Stacey
RGW, Gass CWJ, Garry M, et al: Epidural failure rate. Switching to saline may decrease epidural failure rate (correspondence). Int J
287. Choi DH, Kim JA, Chung IS: Comparison of combined spinal epidural anesthesia and epidural anesthesia for cesarean section. Acta
288. Griffin RP, Reynolds F: Extradural anaesthesia for caesarean section: A double-blind comparison of 0.5% ropivacaine with 0.5% bupivacaine.
Br J Anaesth 74:512–516, 1995.
289. Juhani TP, Hannele H: Complications during spinal anesthesia for cesarean delivery: A clinical report of one year’s experience. Reg Anesth
18:128–131, 1993.
290. Pedersen H, Santos AC, Steinberg ES, et al: Incidence of visceral pain during cesarean section: The effect of varying doses of spinal
bupivacaine. Anesth Analg 69:46–49, 1989.
291. AlahuhtaS, Kangas-Saarela T, Hollmen A, Edstrom H: Visceral pain during caesarean section under spinal and epidural anaesthesia with
bupivacaine. Acta Anaesthesiol Scand 34:95–98, 1990.
292. Abouleish E, Rawal N, Rashad MN: The addition of 0.2 mg subarachnoid morphine to hyperbaric bupivacaine for cesarean delivery: A
prospective study of 856 cases. Reg Anesth 16:137–140, 1991.
293. Dahlgren
G, Hultstrand C, Jakobsson J, et al: Intrathecal sufentanil, fentanyl, or placebo added to bupivacaine for cesarean section. Anesth
Analg 85:1288–1293, 1997.
294. Benhamou D, Thorin D, Brichant JF, et al: Intrathecal clonidine and fentanyl with hyperbaric bupivacaine improves analgesia during cesarean
section. Anesth Analg 87:609–613, 1998.
295. MorganPJ, Halpern SH, Lam-McCulloch J: Comparison of maternal satisfaction between epidural and spinal anesthesia for elective
Caesarean section. Can J Anaesth 47:956–961, 2000.
296. Russell IF: Levels of anaesthesia and intraoperative pain at caesarean section under regional block. Int J Obstet Anesth 4:71–77, 1995.
297. Caba
F, Echevarria M, Gomez-Reja P, et al: Satisfaction with locoregional anesthesia in women who had undergone cesarean section. Rev
Esp Anesthesiol Reanim 45:172–178, 1998.
298. Thorén T, Holmström B, Rawal N, et al: Sequential combined spinal epidural block versus spinal block for cesarean section: Effects on
maternale hypotension and neurobehavioral function of the newborn. Anesth Analg 78:1087–1092, 1994.
299. Eisenach JC: Obstetric anesthesia. What have you done for us lately (editorial)? Anesthesiology 91:907–908, 1999.
300. Bonica JJ: Maternal anatomic and physiologic alterations during pregnancy and parturition. In Bonica JJ, McDonald JS (eds): Practice of
Obstetric Anesthesia and Analgesia, 2nd ed. Baltimore, Williams & Wilkins, 1995, pp 45–82.
1153
301. van Oppen ACC, Stigert RH, Bruinse HW: Cardiac output changes in normal pregnancy: A critical review. Obstet Gynecol 87:310–318, 1996.
302. Mone SM, Sanders SP, Colan SD: Control mechanisms for physiological hypertrophy of pregnancy. Circulation 94:667–672, 1996.
303. Koffel
B: Physiologic adaptation to pregnancy. The healthy parturient. In Norris MC (ed): Obstetric Anesthesia, 2nd ed. Philadelphia,
304. Gershon RY, Alleyne AS: Preoperative evaluation of the parturient with coexisting diseases. Part I: Diseases of the cardiac, renal, and
hematologic systems. In Norris MC (ed): Obstetric Anesthesia, 2nd ed. Philadelphia, Lippincott Williams & Wilkins, 1999, pp 29–62.
305. Riley ET, Ratner EF, Cohen SE: Intrathecal sufentanil for labor analgesia: Do sensory changes predict better analgesia and greater
hypotension? Anesth Analg 84:346–351, 1997.
306. Weiss BM, Pasch T: Measurement of systemic arterial pressure. Curr Opin Anaesthesiol 10:459–466, 1997.
307. James
CF, Banner T, Caton D: Cardiac output in women undergoing cesarean section with epidural or general anesthesia. Am J Obstet
Gynecol 160:1178–1184, 1989.
308. Robson SC, Dunlop W, Hunter S, et al: Haemodynamic changes associated with caesarean section under epidural anaesthesia. Br J Obstet
Gynaecol 96:642–647, 1989.
309. Baumann H, Alon E, Atatanassoff P, et al: Effect of epidural anesthesia for cesarean delivery on maternal femoral arterial and venous,
uteroplacental, and umbilical blood flow velocities and waveforms. Obstet Gynecol 75:194–198, 1990.
310. Patton DE, Lee W, Miller J, Jones M: Maternal, uteroplacental, and fetoplacental hemodynamic and Doppler velocimetric changes during
epidural anesthesia in normal labor. Obstet Gynecol 77:17–19, 1991.
311. Robson SC, Boys RJ, Rodeck C, Morgan B: Maternal and fetal haemodynamic effects of spinal and extradural anaesthesia for elective
caesarean section. Br J Anaesth 68:54–59, 1992.
312. Valli J, Pirhonen J, Aantaa R, et al: The effects of regional anaesthesia for caesarean section on maternal and fetal blood flow velocities
measured by Doppler ultrasound. Acta Anaesthesiol Scand 38:165–169, 1994.
313. Ueyama H, He YL, Tanigami H, et al: Effects of crystalloid and colloid preload on blood volume in the parturient undergoing spinal
anesthesia for elective cesarean section. Anesthesiology 91:1571–1576, 1999.
314. Riley ET, Walker D, Hamilton CL, Cohen SE: Intrathecal sufentanil for labor analgesia does not cause a sympathectomy. Anesthesiology
87:874–878, 1997.
315. Santos AC, Pedersen H, Finster M, Edstrom H: Hyperbaric bupivacaine for spinal anesthesia in cesarean section. Anesth Analg 63:1009–1013,
1984.
316. Vercauteren MP, Coppejans HC, Hoffmann VH, et al: Small-dose hyperbaric versus plain bupivacaine during spinal anesthesia for cesarean
section. Anesth Analg 86:989–993, 1998.
317. Stoneham M, Eldridge J, Popat M, Russell R: Oxford positioning technique improves haemodynamic stability and predictability of block
height of spinal anaesthesia for elective caesarean section. Int J Obstet Anesth 8:242–248, 1999.
318. Rout CC, Rocke DA, Levin J, et al: A reevaluation of the role of crystalloid preload in the prevention of hypotension associated with spinal
anesthesia for elective cesarean section. Anesthesiology 79:262–269, 1993.
319. Birnbach DJ, Datta S, Bassell GM, et al: Intravenous fluid preload in the prevention of spinal block-induced hypotension in parturients
(correspondence). Anesthesiology 80:701–704, 1994.
320. Sharma SK, Gajraj NM, Sidawi JE: Prevention of hypotension during spinal anesthesia: A comparison of intravascular administration of
hetastarch versus lactated Ringer’s solution. Anesth Analg 84:111–114, 1997.
321. Vincent RD Jr, Werhan CF, Norman PF, et al: Prophylactic angiotensin II infusion during spinal anesthesia for elective cesarean delivery.
322. LaPortaRF, Arthur GR, Datta S: Phenylephrine in treating maternal hypotension due to spinal anaesthesia for cesarean delivery: Effects on
neonatal catecholamine concentrations, acid base status and Apgar score. Acta Anaesthesiol Scand 39:901–905, 1995.
323. WrightPM, Iftikhar M, Fitzpatrick KT, et al: Vasopressor therapy for hypotension during epidural anesthesia for cesarean section: Effects on
maternal and fetal flow velocity ratios. Anesth Analg 75:56–63, 1992.
324. Vercauteren MP, Coppejans HC, Hoffmann VH, et al: Prevention of hypotension by a single 5-mg dose of ephedrine during small-dose spinal
anesthesia in prehydrated cesarean delivery patients. Anesth Analg 90:324–327, 2000.
325. Watkins EJ, Dresner M, Calow CE: Severe vasovagal attack during regional anaesthesia for cesarean section. Br J Anaesth 84:118–120, 2000.
326. Ammar T, Beilin Y, Bernstein HH: Successful regional anesthesia for a woman with a single ventricle presenting for labor and delivery. J
1154
Cardiothor Vasc Anesth 10:640–642, 1996.
327. Yarrow S, Russell R: Transposition of the great vessels: A series of three cases with a review of the literature. Int J Obstet Anesth 9:179–185,
2000.
328. HawkinsJ: Anesthesia and preeclampsia/eclampsia. In Norris MC (ed): Obstetric Anesthesia, 2nd ed. Philadelphia, Lippincott Williams &
Wilkins, 1999, pp 501–523.
329. Gatt
SP: Hypertensive disorders and renal disease in pregnancy and labor. In Birnbach DJ, Gatt SP, Datta S (eds): Textbook of Obstetric
Anesthesia. New York, Churchill Livingstone, 2000, pp 541–552.
330. Brodie H, Malinow AM: Anesthetic management of preeclampsia/eclampsia. Int J Obstet Anesth 8:110–124, 1998.
331. Mörtl MG, Schneider MC: Key issues in assessing, managing and treating patients presenting with severe preeclampsia. Int J Obstet Anesth
9:39–44, 2000.
332. Hogg
B, Hauth JC, Caritis SN, et al: Safety of labor epidural anesthesia for women with severe hypertensive disease. National Institute of
Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol 181:1096–1101, 1999.
333. WallaceDH, Levano KJ, Cunningham FG, et al: Randomized comparison of general and regional anesthesia for cesarean delivery in
pregnancies complicated by severe preeclampsia. Obstet Gynecol 86:193–199, 1995.
334. Karinen J, Rasanen J, Alahuhta S, et al: Maternal and uteroplacental haemodynamic state in pre-eclamptic patients during spinal anaesthesia
for Caesarean section. Br J Anaesth 76:616–620, 1996.
335. Bogaert LV: Spinal block caesarean section in parturients with pregnancy-induced hypertension. East Afr Med J 75:227–231, 1998.
336. HoodDD, Curry R: Spinal versus epidural anesthesia for cesarean section in severely preeclamptic patients: A retrospective survey.
337. Sharwood-Smith G, Clark V, Watson E: Regional anaesthesia for caesarean section in severe preeclampsia: Spinal anesthesia is the preferred
choice. Int J Obstet Anesth 8:85–89, 1999.
338. Howell P: Spinal anaesthesia in severe preeclampsia: Time for reappraisal, or time for caution [editorial]? Int J Obstet Anesth 7:217–219,
1998.
339. Ahmed SM, Khan RM, Bano S, et al: Is spinal anaesthesia safe in pre-eclamptic toxaemia patients? J Indian Med Assoc 97:165–168, 1999.
340. Suelto MD, Vincent RD Jr, Larmon JE, et al: Spinal anesthesia for postpartum tubal ligation after pregnancy complicated by preeclampsia or
gestational hypertension. Reg Anesth Pain Med 25:170–173, 2000.
341. Capogna G, Alahuhta S, Celleno D, et al: Maternal expectations and experiences of labour pain and analgesia: A multicentre study of
nulliparous women. Int J Obstet Anesth 5:229–235, 1996.
342. Ross A: Maternal satisfaction with labour analgesia. Baillière’s Clin Obstet Gynaecol 12:499–512, 1998.
343. MorganBM, Bulpitt CJ, Clifton P, Lewis PJ: Analgesia and satisfaction in childbirth (the Queen Charlotte’s 1000 mothers survey). Lancet
2:808–810, 1982.
344. Garel M, Crost M: Epidural analgesia. Women’s viewpoint. J Gynecol Obstet Biol Reprod (Paris) 11:523–533, 1982.
345. Philipsen
T, Jensen NH: Maternal opinion about analgesia in labour and delivery. A comparison of epidural blockade and intramuscular
pethidine. Eur J Obstet Gynecol Reprod Biol 34:205–210, 1990.
346. Ranta
P, Spalding M, Kangas-Saarela T, et al: Maternal expectations and experiences of labor pain—Options of 1091 Finnish parturients.
347. Heitman
DE, Birdwell SW, Bennett DL: Patient satisfaction as an outcome indicator of pain management during labor and delivery. Hosp
Pharm 30:589–595, 1995.
348. Shapiro A, Fredman B, Zohar E, et al: Delivery room analgesia: An analysis of maternal satisfaction. Int J Obstet Anesth 7:226–230, 1998.
349. Geary M, Fanagan M, Boylan P: Maternal satisfaction with management in labour and preference for mode of delivery. J Perinat Med
25:433–439, 1997.
350. Morgan PJ, Halpern S, Lo J: The development of a maternal satisfaction scale for caesarean section. Int J Obstet Anesth 8:165–170, 1999.
351. Lyons G: Pharmacology of local anesthetics. In Birnbach DJ, Gatt SP, Datta S (eds): Textbook of Obstetric Anesthesia. New York, Churchill
352. Yun EM, Meadows W, Santos AC: New amide local anaesthetics for obstetric use. Baillière’s Clin Obstet Gynaecol 12:461–472, 1998.
1155
353. Hill
D, Scrutton M: Controversies. Ropivacaine has not lived up to expectations in obstetric analgesia and anaesthesia. Int J Obstet Anesth
9:246–254, 2000.
354. Bader AM, Tsen LC, Camann WR, et al: Clinical effects and maternal and fetal plasma concentrations of 0.5% epidural levobupivacaine
versus bupivacaine for cesarean delivery. Anesthesiology 90:1596–1601, 1999.
355. Covino BC, Wildsmith JAW: Clinical pharmacology of local anesthetic agents. In Cousins MJ, Bridenbaugh PO (eds): Neural Blockade in
Clinical Anesthesia and Management of Pain, 3rd ed. Philadelphia, Lippincott-Raven Publishers, 1998, pp 97–128.
356. Abboud TK, David S, Nagappala S, et al: Maternal, fetal, and neonatal effects of lidocaine with and without epinephrine for epidural
anesthesia in obstetrics. Anesth Analg 63:973–979, 1984.
357. Columb MO, Lyons G: Determination of the minimum local anesthetic concentrations of epidural bupivacaine and lidocaine in labor. Anesth
Analg 81:833–837, 1995.
358. Capogna G, Celleno D, Lyons G, et al: Minimum local anesthetic concentration of extradural bupivacaine increases with progression of
labour. Br J Anaesth 80:11–13, 1998.
359. Polley L, Columb MO, Naughton NN, et al: Relative analgesic potencies of ropivacaine and bupivacaine for epidural analgesia in labor:
Implications for therapeutic indexes. Anesthesiology 90:944–950, 1999.
360. Capogna G, Celleno D, Fusco P, et al: Relative potencies of bupivacaine and ropivacaine for analgesia in labour. Br J Anaesth 82:371–373,
1999.
361. Clark V, McGrady E, Sugden C, et al: Speed of onset of sensory block for elective extradural caesarean section: Choice of agent and
temperature of injectate. Br J Anaesth 72:221–223, 1994.
362. Abboud TK, Kim KC, Noueihed R, et al: Epidural bupivacaine, chloroprocaine, or lidocaine for cesarean section—Maternal and neonatal
effects. Anesth Analg 62:914–919, 1983.
363. Norton
AC, Davis AG, Spicer RJ: Lignocaine 2% with adrenaline for epidural caesarean section. A comparison with 0.5% bupivacaine.
Anaesthesia 43:844–849, 1988.
364. Peach MJ: Epidural anaesthesia for caesarean section: A comparison of 0.5% bupivacaine and 2% lignocaine both with adrenaline. Anaesth
Intens Care 16:187–196, 1988.
365. Yun E, Topulos GP, Body SC, et al: Pulmonary function changes during epidural anesthesia for cesarean delivery. Anesth Analg 82:750–753,
1996.
366. Ala-KokkoTI, Alahuhta S, Arvela P, Vähäkangas K: Maternal, fetal, and placental distribution of lidocaine-epinephrine and bupivacaine after
epidural administration for cesarean section. Int J Obstet Anesth 7:82–87, 1998.
367. Gaiser RR, Cheek TG, Adams HK, Gutsche BB: Epidural lidocaine for cesarean delivery of the distressed fetus. Int J Obstet Anesth 7:27–31,
1998.
368. Lucas DN, Ciccone GK, Yentis SM: Extending low-dose epidural analgesia for emergency caesarean section. A comparison of three solutions.
Anaesthesia 54:1173–1177, 1999.
369. Palmer CM, Voulgaropoulos D, Alves D: Subarachnoid fentanyl augments lidocaine spinal anesthesia for cesarean delivery. Reg Anesth
20:389–394, 1995.
370. Wong CA, Slavenas P: The incidence of transient radicular irritation after spinal anesthesia in obstetric patients. Reg Anesth Pain Med 24:55–
58, 1999.
371. ManicaVS, Bader AM, Fragneto R, et al: Anesthesia for in vitro fertilization: A comparison of 1.5% and 5% spinal lidocaine for
unltrasonically guided oocyte retrieval. Anesth Analg 77:453–456, 1993.
372. D’Angelo R, Eisenach JC: Is ropivacaine less potent than bupivacaine (editorial)? Anesthesiology 90:941–943, 1999.
373. Lyons G, Columb M, Wilson RC, Johnson RV: Epidural pain relief in labour: Potencies of levobupivacaine and racemic bupivacaine. Br J
Anaesth 81:899–901, 1998.
374. Datta
S, Camann W, Bader A, VanderBurgh L: Clinical effects and maternal and fetal plasma concentrations of epidural ropivacaine versus
bupivacaine for cesarean section. Anesthesiology 82:1346–1352, 1995.
375. Crosby E, Sandler A, Finucane B, et al: Comparison of epidural anaesthesia with ropivacaine 0.5% and bupivacaine 0.5% for caesarean
section. Can J Anaesth 45:1066–1071, 1998.
376. Bridenbaugh PO, Green NM, Brull SJ: Spinal (subarachnoid) neural blockade. In Cousins MJ, Bridenbaugh PO (eds): Neural Blockade in
Clinical Anesthesia and Management of Pain, 3rd ed. Philadelphia, Lippincott-Raven Publishers, 1998, pp 203–241.
1156
377. HartwellBL, Aglio LS, Hauch MA, Datta S: Vertebral column length and spread of hyperbaric subarachnoid bupivacaine in the term
parturient. Reg Anesth 16:17–19, 1991.
378. Patel
M, Samsoon G, Swami A, Morgan B: Posture and the spread of hyperbaric bupivacaine in parturients using the combined spinal
epidural technique. Can J Anaesth 40:943–946, 1993.
379. Yun EM, Marx GF, Santos AC: The effects of maternal position during induction of combined spinal-epidural anesthesia for cesarean
delivery. Anesth Analg 87:614–618, 1998.
380. Hirabayashi
Y, Shimizu R, Fukuda H, et al: Anatomical configuration of the spinal cord in the supine position. I. A study using magnetic
resonance imaging. Br J Anaesth 75:3–5, 1995.
381. ChungCJ, Bae SH, Chae KY, Chin YJ: Spinal anaesthesia with 0.25% hyperbaric bupivacaine for Caesarean section: Effects of volume. Br J
Anaesth 77:145–149, 1996.
382. Bell
R, Fernando R, Parry MG, Chung CJ: Spinal anaesthesia with 0.25% hyperbaric bupivacaine for caesarean section: Effects of volume
(correspondence). Br J Anaesth 78:339–340, 1997.
383. King HK: Effects of volume on spinal anaesthesia with 0.25% hyperbaric bupivacaine [correspondence]. Br J Anaesth 79:262, 1997.
384. Logan MR, McClure JH, Wildsmith JA: Plain bupivacaine: An unpredictable spinal anesthetic agent. Br J Anaesth 58:292–296, 1986.
385. Van Gessel EF, Forster A, Schweizer A, Gamulin Z: Comparison of hypobaric, hyperbaric, and isobaric solutions of bupivacaine during
continuous spinal anesthesia. Anesth Analg 72:779–784, 1991.
386. Malinovsky JM, Renaud G, Le Corre P, et al: Intrathecal bupivacaine in humans: Influence of volume and baricity of solutions.
387. Runza
M, Albani A, Tagliabue M, et al: Spinal anesthesia using hyperbaric 0.75% versus hyperbaric 1% bupivacaine for cesarean section.
Anesth Analg 87:1099–1103, 1998.
388. Aveling W, Howell P: Controversies. Heavy bupivacaine has no advantage over plain bupivacaine in spinal anaesthesia for caesarean section.
Int J Obstet Anesth 8:260–265, 1999.
389. Choi DH, Ahn HJ, Kim MH: Bupivacaine-sparing effect of fentanyl in spinal anesthesia for cesarean delivery. Reg Anesth Pain Med 25:240–
245, 2000.
390. Russell IF, Holmqvist EL: Subarachnoid analgesia for caesarean section. A double-blind comparison of plain and hyperbaric 0.5%
bupivacaine. Br J Anaesth 59:347–353, 1987.
391. Pinder AJ, Dresner M, D’Angelo R, et al: Ropivacaine and bupivacaine with fentanyl for labor epidural anesthesia (correspondence). Anesth
Analg 91:1310–1311, 2000.
392. Stienstra R, Jonker TA, Bourdrez P, et al: Ropivacaine 0.25% versus bupivacaine 0.25% for continuous epidural analgesia in labor: A double-
blind comparison. Anesth Analg 80:285–289, 1995.
393. Cascio MG, Gaiser RR, Camann WR, et al: Comparative evaluation of four different infusion rates of ropivacaine (2 mg/mL) for epidural
labor analgesia. Reg Anesth Pain Med 23:548–553, 1998.
394. Owen MD, D’Angelo R, Gerancher JC, et al: 0.125% ropivacaine is similar to 0.125% bupivacaine for labor analgesia using patient-
controlled epidural infusion. Anesth Analg 86:527–531, 1998.
395. Meister
GC, D’Angelo R, Owen M, et al: A comparison of epidural analgesia with 0.125% ropivacaine with fentanyl versus 0.125%
bupivacaine with fentanyl during labor. Anesth Analg 90:632–637, 2000.
396. Beilin Y, Galea M, Zahn J, Bodian CA: Epidural ropivacaine for the initiation of labor epidural analgesia: A dose finding study. Anesth Analg
88:1340–1345, 1999.
397. Eddleston JM, Holland JJ, Griffin RP, et al: A double-blind comparison of 0.25% ropivacaine and 0.25% bupivacaine for extradural analgesia
in labour. Br J Anaesth 76:66–71, 1996.
398. Cambell DC, Zwack RM, Crone LL, Yip RW: Ambulatory labor epidural analgesia: Bupivacaine versus ropivacaine. Anesth Analg 90:1384–
1389, 2000.
399. Fischer C, Blanié P, Jaouën E, et al: Ropivacaine, 0.1%, plus sufentanil, 0.5 mcg/ml, versus bupivacaine, 0.1%, plus sufentanil, 0.5 mcg/ml,
using patient-controlled epidural analgesia for labor. Anesthesiology 92:1588–1593, 2000.
400. BjørnestadE, Smedvig JP, Bjerkreim T, et al: Epidural ropivacaine 7.5 mg/ml for elective Caesarean section: A double-blind comparison of
efficacy and tolerability with bupivacaine 5 m/ml. Acta Anaesthesiol Scand 43:603–608, 1999.
401. Cohen S, Amar D, Pantuck CB, et al: Epidural analgesia for labour and delivery: Fentanyl or sufentanil? Can J Anaesth 43:341–346, 1996.
1157
402. Palmer CM: Postoperative analgesia. In Norris MC (ed): Obstetric Anesthesia, 2nd ed. Philadelphia, Lippincott Williams & Wilkins, 1999, pp
697–721.
403. Sinatra RS, Ayoub CM, Sevarino FB: Postcesarean analgesia: Patient-controlled analgesia and neuroaxial techniques. In Birnbach DJ, Gatt SP,
Datta S (eds): Textbook of Obstetric Anesthesia. New York, Churchill Livingstone, 2000, pp 320–341.
404. Russell R, Reynolds F: Epidural infusions for nulliparous women in labour. A randomised double-blind comparison of fentanyl/bupivacaine
and sufentanil/bupivacaine. Anaesthesia 48:856–861, 1993.
405. Lyons G, Columb M, Hawthorne L, Dresner M: Extradural pain relief in labour: Bupivacaine sparing by extradural fentanyl is dose dependent.
Br J Anaesth 78:493–497, 1997.
406. HermanNL, Sheu KL, Van Decar TK, et al: Determination of the analgesic dose-relationship for epidural fentanyl and sufentanil with
bupivacaine 0.125% in laboring patients. J Clin Anesth 10:670–677, 1998.
407. Connelly NR, Parker RK, Vallurupalli V, et al: Comparison of epidural fentanyl versus epidural sufentanil for analgesia in ambulatory
patients in early labor. Anesth Analg 91:374–378, 2000.
408. Reynolds F, O’Sullivan G: Epidural fentanyl and perineal pain in labour. Anaesthesia 44:341–344, 1989.
409. Cohen SE, Tan S, Albright GA, Halpern J: Epidural fentanyl/bupivacaine mixtures for obstetric analgesia. Anesthesiology 67:403–407, 1987.
410. Steinberg
RB, Dunn SM, Dixon DE, et al: Comparison of sufentanil, bupivacaine, and their combination for epidural analgesia in obstetrics.
Reg Anesth 17:131–138, 1992.
411. Vertommen JD, Vandermeulen E, Van Aken H, et al: The effects of the addition of sufentanil to 0.125% bupivacaine on the quality of
analgesia during labor and on the incidence of instrumental deliveries. Anesthesiology 74:809–814, 1991.
412. Ngan Kee WD: Epidural pethidine: Pharmacology and clinical experience. Anaesth Intensive Care 26:247–255, 1998.
413. Kurz A, Ikeda T, Sessler DI, et al: Meperidine decreases the shivering threshold twice as much as the vasoconstriction threshold.
414. Casey WF, Smith CE, Katz JM, et al: Intravenous meperidine for control of shivering during caesarean section under epidural anaesthesia.
Can J Anaesth 35:128–133, 1988.
415. Sutherland J, Seaton H, Lowry C: The influence of epidural pethidine on shivering during lower segment caesarean section under epidural
anaesthesia. Anaesth Intensive Care 19:228–232, 1991.
416. Matthews NC, Corser G: Epidural fentanyl for shaking in obstetrics. Anaesthesia 43:783–785, 1988.
417. Capogna G, Celleno D: IV clonidine for post-extradural shivering in parturients: A preliminary study. Br J Anaesth 71:294–295, 1993.
418. Chan AM, Ng KF, Tong EW, Jan GS: Control of shivering under regional anesthesia in obstetric patients with tramadol. Can J Anaesth
46:253–258, 1999.
419. Stuart-TaylorME, Billingham IS, Barrett RF, Church JJ: Extradural morphine for postoperative analgesia: Audit of a nurse-administered
service to 800 patients in a district general hospital. Br J Anaesth 68:429–432, 1992.
420. Keenan
GM, Munishankarappa S, Elphinstone ME, Milne MK: Extradural diamorphine with adrenaline in labour: Comparison with
diamorphine and bupivacaine. Br J Anaesth 66:242–246, 1991.
421. Bailey CR, Ruggier R, Findley IL: Diamorphine-bupivacaine mixture compared with plain bupivacaine for analgesia. Br J Anaesth 72:58–61,
1994.
422. Celleno
D, Capogna G, Sebastiani M, et al: Epidural analgesia during and after cesarean delivery. Comparison of five opioids. Reg Anesth
16:79–83, 1991.
423. BroseWG, Cohen SE: Oxyhemoglobin saturation following cesarean section in patients receiving epidural morphine, PCA, or im meperidine
analgesia. Anesthesiology 70:948–953, 1989.
424. Pan PH, James CF: Anesthetic-postoperative morphine regimens for cesarean section and postoperative oxygen saturation monitored by a
telemetric pulse oximetry network for 24 continuous hours. J Clin Anesth 6:124–128, 1994.
425. Fuller JG, McMorland GH, Douglas MJ, Palmer L: Epidural morphine for analgesia after caesarean section: A report of 4880 patients. Can J
Anaesth 37:636–640, 1990.
426. Palmer CM, Nogami WM, Van Maren G, Alves D: Postcesarean epidural morphine: A dose response study. Anesth Analg 90:887–891, 2000.
427. Horta ML, Ramos L, Goncalves ZR: The inhibition of epidural morphine-induced pruritus by epidural droperidol. Anesth Analg 90:638–641,
2000.
1158
428. Griffin
RP, Reynolds F: Maternal hypoxaemia during labour and delivery: The influence of analgesia and effect on neonatal outcome.
Anaesthesia 50:151–156, 1995.
429. Cohen SE, Labaille T, Benhamou D, Levron JC: Respiratory effects of epidural sufentanil after cesarean section. Anesth Analg 74:677–682,
1992.
430. Brockway MS, Noble DW, Sharwood-Smith GH, McClure JH: Profound respiratory depression after extradural fentanyl. Br J Anaesth
64:243–245, 1990.
431. Noble DW, Morrison LM, Brockway MS, McClure JH: Adrenaline, fentanyl or adrenaline and fentanyl as adjuncts to bupivacaine for
extradural anaesthesia in elective caesarean section. Br J Anaesth 66:645–650, 1991.
432. Rosaeg OP, Suderman V, Yarnell RW: Early respiratory depression during caesarean section following epidural meperidine. Can J Anaesth
39:71–74, 1992.
433. Yarnell
RW, Polis T, Reid GN, et al: Patient-controlled analgesia with epidural meperidine after elective cesarean section. Reg Anesth
17:329–333, 1992.
434. Johnson C, Ransil B, Oriol N: Comparison of onset time between 0.5% bupivacaine and 3% 2-chloroprocaine with and without 75
micrograms fentanyl. Reg Anesth 16:228–231, 1991.
435. Vertommen JD, Van Aken H, Vandermeulen E, et al: Maternal and neonatal effects of adding epidural sufentanil to 0.5% bupivacaine for
cesarean delivery. J Clin Anesth 3:371–376, 1991.
436. Cohen SE, Amar D, Pantuck CB, et al:. Postcesarean delivery epidural patient-controlled analgesia. Fentanyl or sufentanil? Anesthesiology
78:486–491, 1993.
437. Cooper
DW, Ryall DM, Desira WR: Extradural fentanyl for postoperative analgesia: Predominant spinal or systemic action? Br J Anaesth
74:184–187, 1995.
438. Grass JA, Sakima NT, Schmidt R, et al: A randomized, double-blind, dose-response comparison of epidural fentanyl versus sufentanil
analgesia after cesarean section. Anesth Analg 85:365–371, 1997.
439. Ngan Kee WD, Lam KK, Chen PP, Gin T: Epidural meperidine after cesarean section. A dose-response study. Anesthesiology 85:289–294,
1996.
440. Peach MJ, Moore JS, Evans SF: Meperidine for patient-controlled analgesia after cesarean section. Intravenous versus epidural administration.
441. Goh
JL, Evans SF, Pavy TJ: Patient-controlled epidural analgesia following caesarean delivery: A comparison of pethidine and fentanyl.
Anaesth Intens Care 24:45–50, 1996.
442. Peach
MJ, Pavy TJG, Orlikowski CEP, et al: Postoperative intraspinal opioid analgesia after caesarean section: A randomized comparison of
subarachnoid morphine and epidural pethidine. Int J Obstet Anesth 9:238–245, 2000.
443. Stevens JD, Braithwate P, Corke CF, et al: Double-blind comparison of epidural diamorphine and intramuscular morphine after elective
cesarean section, with computerised analysis of continuous pulse oximetry. Anaesthesia 46:256–259, 1991.
444. Roulson CJ, Benett J, Shaw M, Carli F: Effect of extradural diamorphine on analgesia after caesarean section under subarachnoid block. Br J
Anaesth 71:810–813, 1993.
445. Norman BJ, Yentis S: Analgesia produced by epidural diamorphine is better following caesarean section under spinal anaesthesia than under
epidural anaesthesia. Int J Obstet Anesth 7:98–102, 1998.
446. Camann WR, Denney RA, Holby ED, Datta S: A comparison of intrathecal, epidural, and intravenous sufentanil for labor analgesia.
447. Cambell DC, Camann WR, Datta S: The addition of bupivacaine to intrathecal sufentanil for labor analgesia. Anesth Analg 81:305–309, 1995.
448. Palmer CM, Van Maren G, Nogami WM, Alves D: Bupivacaine augments intrathecal fentanyl for labor analgesia. Anesthesiology 91:84–89,
1999.
449. Viscomi CM, Rathmell JP, Pace NL: Duration of intrathecal labor analgesia: Early versus advanced labor. Anesth Analg 84:1108–1112, 1997.
450. Wong CA, Scavone BM, Loffredi M, et al: The dose response of intrathecal sufentanil added to bupivacaine for labor analgesia.
1159
Section VII Chapter 49 - Outcomes Using Procedures for Nociceptive Pain
Chapter 49 - Outcomes Using Procedures for Nociceptive Pain
JAY B. BENDER
EDWARD A. R. LORD
ALLEN W. BURTON
As is the case in many areas of medicine, in pain management, objective documentation of outcome has been
lacking. Using evidence-based practice, pain medicine must introspectively examine the available procedural
armamentarium with this critical viewpoint. Our procedures must not only be safe and effective, but they must also
be supported by scientifically valid literature.
Randomized controlled trials (RCTs) are held up as the gold standard in evidence-based medicine literature, but
there are few RCTs in pain medicine literature. Still, in this chapter the authors have attempted to make a
conscientious use of the current best evidence available regarding interventional procedures for nociceptive pain.
Traditional Pain Management Procedures
EPIDURAL STEROID INJECTIONS
Epidural steroid injections (ESIs) have been used for low back and radicular pain for almost 50 years. Today they
[1]
rank as one of the most common interventional procedures performed by pain management specialists. ESIs are
primarily indicated as part of a nonoperative approach to the treatment of spinal and radicular pain.
Pages first described his technique for accessing the epidural space via a paramedian approach in 1921. The [2]
technique involved the use of “loss of resistance” to the needle as it entered the epidural space, and needle
placement was confirmed by the lack of free-flowing spinal fluid. This was a technique that was obviously fraught
with complications. Several modifications to this technique were proposed over the years, including the use of a
fluid-filled syringe attached directly to the spinal needle as it was being introduced and the “hanging drop”
[3]
technique, which relied on the theory that the epidural space was under negative pressure at all times. Not until
[4]
1933, when Dogliotti developed the “loss-of-resistance” technique that used a syringe filled with air to identify the
[5]
epidural space, did the technique become reasonably reliable. The introduction of the Tuohy needle later became the
most significant breakthrough with regard to the clinical application of this procedure, because it greatly reduced the
incidence of iatrogenic dural punctures (and, thus, the associated morbidity) and also allowed the placement of
indwelling catheters for relatively long-term analgesia.
The list of indications is quite extensive and includes several well-described conditions such as lumbar-cervical
radiculopathy, spinal stenosis, postlaminectomy syndrome, failed back syndrome, postherpetic neuralgia, complex
regional pain syndrome, pelvic pain syndromes, phantom limb pain, and periaxial malignancies. Conversely, the
[6]
list of contraindications is relatively short and includes sepsis, local infection, anticoagulation or coagulopathy, and
hypovolemia (relative contraindication). White and coworkers, in a study of 304 patients, found that the response to
[6]
epidural steroid injections was most closely related to onset of symptoms, presence of nerve root compression, and
the lack of any associated psychological issues. Many others
[7]
have identified some of the primary positive
[8] [9] [10] [11] [12]
and negative predictive factors of the response to epidural steroid injections. Factors associated with the patient's
history that correlate with a favorable response to the procedure include the presence of radicular pain and numbness,
relatively short duration of symptoms (<6 mo), advanced educational background, absence of previous back surgery,
and young age. Findings on the physical examination or in diagnostic studies that correlate well with a positive
response to ESI include the presence of dermatomal sensory loss, motor loss correlating with the involved nerve root,
positive straight leg raise test, positive findings on electromyography involving the affected nerve root, and
radiographic confirmation of a herniated disc affecting the suspected nerve root. Negative predictive factors that
have been identified include pain duration of greater than 6 to 24 months, occupational injuries, previous back
surgery, primarily axial pain, injury-related litigation, history and examination consistent with myofascial pain
syndrome, and the so-called “nonorganic” physical signs (Waddell's signs).
The mechanism of action of epidural steroids also remains somewhat controversial. It is known, however, that the
enzyme phospholipase A2 is contained in relatively high concentrations within the nucleus pulposus of the
intervertebral discs. This enzyme initiates the release of arachidonic acid from cell membranes, initiating an
[13]
enzymatic cascade that—in the presence of annular tears or severe degenerative disc disease—can cause a chemical
irritation (or radiculitis) of an adjacent nerve root. Steroids induce the synthesis of a phospholipase A2 inhibitor,
1160
which inhibits arachidonic acid metabolism one step earlier in the pathway compared with nonsteroidal anti-
inflammatory drugs (NSAIDs). In addition, steroids have been shown to have an effect on local membrane
depolarization. Johansson and associates demonstrated that local administration of methylprednisolone blocks the
[14]
transmission of C fibers but not A beta fibers. The effect was noted to be reversible, suggesting that there is a direct
membrane action of the steroid.
The efficacy of epidural steroid injections for back pain, neck pain, and radicular pain remains a fairly controversial
issue. This is partly because the majority of the literature published to date has been hindered by poor study designs
or inconclusive data. Kepes and Duncalf concluded in 1985 that the role of steroids in this subgroup of patients
[15]
was not warranted. However, their study included patients who were treated with both epidural and systemic
steroids. Benzon concluded, in a study of patients with lumbosacral radiculopathy who were treated only with ESIs,
[16]
that epidural steroids were effective in the treatment of those with acute radiculopathy. In 1995, Koes and
associates concluded that epidural steroids were not effective in patients with chronic back pain without evidence
[17]
of ongoing radiculopathy, but that those with ongoing radiculopathy showed a positive response in 50% of the cases.
They reviewed all available randomized, controlled trials published up to 1994 and determined that only four studies
adhered to acceptable standards of quality, and that of these four only two supported the use of epidural steroids in
the treatment of radicular pain. In 1995, Watts and Silagy performed a meta-analysis of the same data using odds
[18]
ratios, with the goal of answering the question, Do epidural steroids work? In their meta-analysis, they defined
efficacy as at least 75% improvement for short-term (60 days) and long-term (1 year) outcomes. With an odds ratio
of more than 1 suggestive of efficacy and of more than 2 suggestive of significant efficacy, they determined that
ESIs had an odds ratio of 2.61 for short-term outcomes and 1.87 for long-term outcomes. This meta-analysis
provided quantitative evidence of the efficacy of epidural steroids in the management of radicular pain. In 1998,
McQuay and Moore sought the answer to the question, How well do epidural steroids work? They used the same
[19]
data as Watts and Silagy, in addition to the work of Carette and coworkers and used the number needed to treat
[20]
(NNT) as the measure of clinical benefit. In the short-term outcomes group, the NNT was 7. In other words, to
achieve a goal of 75% improvement in pain relief in one patient, one would have to treat 7 patients with ESI.
However, if a more reasonable goal of 50% improvement in pain relief were the standard, the NNT would be just
under 3. In the long-term group, the NNT corresponding to 50% improvement at 12 months was 13. It was also
noted that there was no difference in the functional level or the need for subsequent surgery in the patients who
received the injections. These data seem to indicate a significant short-term decrease in leg pain, but a minimal
decrease in back pain and minimal improvement in function after ESI for radiculopathy.
There are relatively few long-term follow-up studies in the literature with regard to ESIs. Most patients report a
diminished effect after 120 days. However, Dilke and associates reported 36% of patients with complete relief and
[21]
55% with partial relief at 3 months. Ridley and associates noted that 65% of their patients reported sustained relief
[22]
at 6 months. At 1 year, Green and associates reported that 41% of their patients experienced sustained relief. White
[23]
and associates reported persistent improvement after 6 months in 34% of patients with acute pain and in only 12%
[7]
of patients with chronic pain. In this study, White also concluded that ESIs were most appropriately used in the
presence of root compression, root irritation, or annular tears. ESIs were least effective when given for chronic
degenerative disc disease, herniated discs without neurologic deficit, spinal stenosis, and functional low back pain.
The response time to epidural steroids is between 4 and 6 days in most patients (59%), but many others (37%)
experience an earlier effect, and a small percentage of patients (4%) respond after 6 days. It is, therefore, advisable
[23]
to allow at least 7 days between each injection. The decision to proceed with another ESI after the initial one is
usually based on the results of the first. A positive response to the initial injection— usually measured by a
subjective claim on the part of the patient of a 50% reduction in pain—is considered a good indication that the
patient will receive further benefit from additional injections. Brown demonstrated that there was generally no
[24]
further benefit to the patient after three injections. Duration of pain or onset of symptoms has also been positively
correlated with the response to epidural steroid injections. Patients with symptoms lasting less than 3 months
[23] [25] [26] [27]
have response rates of 83% to 100%. Symptoms for pain lasting up to 6 months correspond to a response rate of
67% to 81%, and 44% to 69% in those with symptoms lasting longer than 6 months.
The bulk of the literature supports the use of ESIs as another treatment modality to be used in the comprehensive
management of patients with chronic back and neck pain. There is some controversy concerning the mandatory use
of fluoroscopy. The major issue is that there is less than 100% certainty of epidural steroid placement because of
intravascular or other extraepidural location of the needle or catheter tip. The absolute efficacy depends on the
[28] [29]
diagnosis and the amount of pain relief deemed to be successful. ESIs are particularly beneficial in patients with
signs of acute or ongoing radiculopathy. They play a vital role in the armamentarium of the pain management
specialist. Appropriate patient selection can help to improve the success rate of the procedure.
FACET BLOCKS
1161
In some individuals with cervical, thoracic, or lumbar back pain, the anatomic source of the pain may be the facet
joints. In 1933, Ghormley made the first description of the “facet syndrome.” He defined this syndrome as low
[29A]
back pain with or without sciatic pain, which occurred after a twisting or rotating strain on the low back. The
therapeutic benefit of facet injections remains controversial. Much of this controversy stems from difficulty in
diagnosing the facet syndrome. Facet syndrome pain may account for up to 30% of so-called mechanical back pain
[30]
in the cervical, thoracic, and lumbar spine. The pattern of pain in individuals with facet joint problems may radiate
from the area affected to the shoulder and the upper arm in the case of a cervical facet joint or to the buttock and the
thigh in the case of lumbar facet syndrome. Injections of local anesthetic and steroids into the facet joint
(intrarticular injection) or median branch blocks (of the dorsal ramus to the facet joint) may be beneficial for both
diagnosis and treatment of facet syndrome. [31]
Randomized, controlled studies of the effectiveness of injection therapy have yielded conflicting results. With
respect to intraarticular corticosteroid facet injections in the cervical and lumbar areas, evidence for both short- and
long-term effectiveness is lacking. [32] [33]
Injections into the facet joints do not have proven efficacy, but some favorable outcomes have been seen with
radiofrequency (RF) rhizotomy in the cervical and lumbar spine. In a randomized, double-blinded trial, Lord and
Barnsley performed RF facet rhizotomy in patients with mechanical neck pain. Of the 24 patients studied, 12
[34]
underwent facet rhizotomy after obtaining pain relief with local anesthetic facet block. The median time before the
pain returned to 50% of baseline levels was 263 days in the rhizotomy group versus 8 days in the control group. [34]
McDonald and coworkers noted a 71% success rate using RF rhizotomy for cervical mechanical pain, with the
[35]
mean duration of relief being 422 days. Further evidence of this procedure's efficacy was shown by Wallis and
coworkers, who showed that patients experienced significant improvement in psychological well-being (as well as
[36]
improvement in pain control) after cervical RF rhizotomy.
Lumbar facet blocks seem to follow this same pattern, with RF median branch blocks demonstrating better efficacy
than intraarticular steroid injections. Dreyfuss and coworkers prospectively followed 15 patients with chronic low
[40]
back pain who experienced temporary relief after median branch blocks. These 15 patients underwent detailed
[40A]
evaluation before and after RF neurotomy. The results revealed that 60% of the patients obtained a 90% or greater
level of pain relief, which was sustained up to 12 months.
In summary, there is a lack of evidence for sustained pain relief from intra-articular corticosteroid facet injections.
On the other hand, the technique of diagnostic median branch block followed by RF lesioning shows strong
evidence of long-term efficacy.
SACROILIAC INJECTIONS
The sacroiliac (SI) joint is a synovial (diarthrodial) joint that is formed from the union of the sacrum with the iliac
bones in the pelvis. The pathologic state of this joint is becoming a more common source of discussion among
specialists after years of being virtually ignored as a cause of low back pain. When Mixter and Barr published their
[37]
article in the New England Journal of Medicine in 1934, describing the intervertebral disc as a source of back pain,
the SI joint was suddenly relegated to the background in the search for the cause of low back pain. However, it has
since been shown that disc pathology fails to fully explain many pain syndromes. As a result, consideration is once
[38]
again being given to pathology of the SI joint as a possible source of both acute and chronic low back pain.
The anatomy of the SI joint is fairly complex and highly variable from person to person and from side to side. It has
a double-S orientation that helps to maintain stability of the pelvic ring, allowing very limited movement. Further
motion of the joint is also limited by the irregular shape of the articulating surfaces of the two ilia and the sacrum,
which allow the sacrum to slide securely into the pelvic ring. The joint is more mobile in youth and during
pregnancy in women; it becomes more fibrotic with age. The joint is stabilized by thin anterior ligaments and very
thick, strong posterior ligaments. The fibers of the joint capsule are interwoven with the interosseus and posterior SI
ligaments, thus providing protection against separation. The sacrospinous ligament resists rotational motion of the
pelvis around the axial spine, and the sacrotuberous ligament resists flexion of the ilia on the axial spine. Together,
the sacrospinous and sacrotuberous ligaments buttress the posterior ligaments of the SI joint to prevent any
backward movement of the sacrum on the ilia. The two iliolumbar ligaments also serve an important role in pelvic
stabilization by resisting motion between the distal lumbar segments and the sacrum. Innervation of the joint is
highly variable but occurs predominantly via the posterior primary divisions of L3 to S2.
There are multiple muscle attachments across the SI joint that also contribute to pelvic stability. The thoracolumbar
fascia includes attachments to the twelfth rib, the lumbar spinous processes, and the iliac crest. The gluteus maximus
and minimus, latissimus dorsi, multifidus, biceps femoris, psoas, piriformis, obliquus, and transverse abdominis
1162
muscles all attach near the SI joint and function to confer stability for loading and unloading forces during walking
and running.
Dysfunction of the SI joint in the absence of direct trauma is usually the result of the often injurious combination of
rotation with axial loading. Patients often give a history of pain onset after falling, lifting and turning, pushing and
[39]
turning, or bracing with a leg in an automobile collision. Pain related to SI joint dysfunction is exacerbated with
bending and with prolonged sitting or standing. It is often worse in the morning and improves with daily activities.
Driving for long periods of time is often difficult.
Pain origin for the SI joint does seem to have a somewhat distinct referral pattern. Fortin and associates studied
[41]
both normal and symptomatic patients in order to generate a pain referral map of the SI joint. The most common
discomfort was described as aching or hypersensitivity along the joint line to the ipsilateral hip and trochanter. Other
pains, reported less frequently, included groin pain, testicular pain, and periumbilical pain.
Physical examination must include evaluation for pelvic obliquity as well as scapular/shoulder obliquity and range
of motion of the spine in all planes. The back is examined for points of tenderness at the lumbosacral junctions, the
iliolumbar ligaments, the posterior superior iliac spine, the hips, the buttocks, and the trochanteric bursa. A full
[41] [42]
neurologic examination is performed as well. There should not be evidence of motor weakness or reflex
asymmetries from SI joint dysfunction. Provocative maneuvers may appear during the straight leg raising test,
Gaenslen's test, Patrick's test, the SI compression test, or the one-legged stork test in a majority of patients with SI
dysfunction. However, many of these maneuvers also yield positive results in patients with facet dysfunction or
degenerative disc disease of the lumbar spine. Thus, one of the difficulties encountered in interpretation of SI joint
injection literature is that of accurately diagnosing SI joint pain. In other words, no pain relief after an SI joint
injection may represent a misdiagnosis rather than a failure of the procedure itself.
SI joint injection, either by computed tomographic or fluoroscopic guidance, serves as both the definitive diagnostic
and the therapeutic tool for SI joint dysfunction. The technique for this procedure involves placing the patient in the
prone position on a fluoroscopy table. The fluoroscopy tube is rotated laterally to a plane parallel to the ipsilateral
iliac wing. This view allows the operator to view the posterior third of the SI joint. A 22- or 25-gauge (G), 3.5-inch
spinal needle is then directed into the inferior-most aspect of the joint. An arthrogram is then performed using
radiographic contrast medium to confirm needle placement with the joint. Often, this injection is performed without
imaging, but we caution against this practice. On many occasions, it is challenging to place the needle accurately,
even with fluoroscopic guidance. About 2 mL of a solution of local anesthetic (usually 0.25% bupivicaine), with or
without a long-acting steroid (methylprednisolone or triamcinalone) is then injected into the joint. Other treatment
modalities include the use of superficial and deep heat, manual therapy via osteopathic or chiropractic techniques,
transcutaneous electrical nerve stimulation, and an exercise program consisting of isometric exercises designed to
improve strength and range of motion of the muscles of the abdomen and pelvis.
Maugars and associates demonstrated very encouraging results in a series of 42 SI joint injections in 22 patients
[43]
with seronegative spondylarthropathies. At one month follow-up, 16 of the 22 described very good (80% to 100%)
improvement, and another 3 patients obtained good results (70% to 80% improvement). Of these 19 patients with
very good or good responses, all but 2 experienced relief within 2 to 3 days of the procedure. Eighteen of the 19
patients were taking nonsteroidal anti-inflammatory drugs (NSAIDs) before the injections. After the injections, 8
stopped taking NSAIDs, and 6 were able to reduce the dosage by at least 50%. The mean duration of improvement
was 8.4 months, and 14 of the 19 patients (74%) still showed improvement after a mean follow-up time of 9.6
months. Only 5 of the 19 (26%) experienced a relapse within a mean follow-up time of 5.6 months.
Thus, the literature provides some support for diagnostic and therapeutic SI injections. Again, the reader must be
cautioned regarding the difficulty in accurately diagnosing (and therefore treating) sacroiliac pain.
Implantable Devices
NEURAL STIMULATION
Spinal cord stimulation (SCS) has been used for more than 30 years in the treatment of chronic pain ( Fig. 49–1 ). [44]
The literature is difficult to interpret regarding efficacy. Reported success rates for SCS implants vary widely (18%–
86%), with earlier work showing much poorer outcomes, probably owing to the evolution of SCS hardware and
refinements in patient selection. [45] [46] [47]
1163
SCS should be considered with respect to efficacy and complications. It is important to note that technical problems
(and many complications) with SCS, including lead migration, progress in many cases to total failure of pain relief.
Rarely, in our experience, do patients have a “partially successful” SCS implant. Most SCS implants are performed
for failed back surgery syndrome (FBSS), with an increasing number being done for complex regional pain
syndrome (CRPS) and ischemia. The bulk of the available literature deals with FBSS.
One prospective study was done by Burchiel and colleagues to evaluate SCS in a cohort of patients with back and
extremity pain, with respect to pain measurements (McGill) and functional parameters (Oswestry disability
questionnaire, Sickness Impact Profile, and the Beck Depression Inventory). They began with a cohort of 219
[48]
patients who met criteria for trial stimulation. Of 219 patients, 182 (83%) obtained enough relief (≥50%) to go to
implant. Only 70 patients completed the 1-year follow-up. However, in that cohort of patients, 56% of patients
reported at least 50% or greater pain relief (mean percentage of pain relief was 47% ± 27%). Also, the Oswestry
questionnaire, the Sickness Impact Profile, and the Beck scale all showed significant improvement. Medication
usage and work status, although not specifically quantitated in the study, were essentially unchanged. During the
year, 17% of patients required some surgical intervention. The reasons were varied, including lead migration (No. =
3), and infection (No. = 3), and lead fracture (No. = 2), as well as other, less common causes. Twenty of the 182
patients who received implants (11%) discontinued therapy during the year for lack of efficacy, and 15 of these
patients had the implants removed.
A prospective, randomized, clinical trial evaluated SCS in patients with CRPS refractory to conventional
treatments. The authors enrolled 54 patients randomly, assigning them into two groups—SCS plus physical
[49]
therapy (PT) or PT alone. They followed the patients carefully for 6 months with a series of evaluations, including
pain scales, functional assessment, health-related quality of life measures, and complications. Of the 36 patients
assigned to the SCS group, 24 received 50% relief or more with a trial, thereby going on to receive implants.
Comparison of the SCS plus PT group with the PT group alone revealed significant improvement in pain scores,
functional status, and health-related quality of life status for the SCS plus PT group. Of the 24 patients implanted, 6
(25%) had complications, including one explant for infection and five lead migrations. Four of the five lead
migrations were successfully replaced with one procedure, and
Figure 49-1 A, Percutaneous dual lead spinal

cord stimulator trial. B, Fluoroscopic view of
appropriate positioning of spinal cord
stimulator leads. (Courtesy of Medtronic, Inc.)
the fifth patient required three procedures to replace the lead. All these patients continued to benefit from
stimulation after repositioning.
These two studies were conducted well and represent the best estimates known today of efficacy and complications
in SCS. SCS has efficacy in treating resistant pain syndromes, including FBSS and CRPS, and probably has efficacy
in treating patients with ischemic pain, angina, and other forms of neuropathic pain. It is an expensive technique,
although no more so than repeated back surgery. The difficulty with SCS remains the relatively high rate of
“nuisance” complications, such as lead migration. These complications are expensive, time-consuming for patients
and providers, and can interrupt the patient's recovery period (with CRPS, for example). It is important to remember
that this is a nondestructive technique. In the worst case, the system is explanted and the patient is basically left with
a nervous system no worse than before the implant. With careful patient selection and successful test stimulation,
SCS is safe, reduces pain, and improves the quality of life in the majority of patients treated.
1164
INTRATHECAL MEDICATION
Intrathecal medication delivery in humans was first reported in the late 1970s and has gradually taken hold as a
clinical option for patients with difficult to treat pain syndromes. Initially, much of this work was focused on
[50]
cancer pain syndromes, but as safety became established, intrathecal medications have been used increasingly in the
setting of nonmalignant chronic pain ( Fig. 49–2 ).
The interpretation of data regarding the safety and efficacy of intrathecal therapy is difficult owing to variation in
inclusion criteria, outcome parameters, and duration of follow-up. There are a number of reports showing good to
[51]
excellent pain relief in more than 50% of patients with cancer pain syndromes. Two of these reports are examined in
more detail. Sallerin-Caute and colleagues retrospectively examined the data regarding 159 patients with refractory
[52]
cancer pain syndromes who received intrathecal morphine therapy for a mean of 11 months (range of 1 to 90
months). More than 80% of these patients had good to excellent pain relief until death. Hassenbusch and
[52]
colleagues also reported the efficacy of intrathecal opioids in intractable cancer pain. Their report, although
[53]
retrospective, is quite interesting because of quantification of visual analogue pain scale scores (VAS) over time to
assess efficacy. They reported on 41 patients having implanted intrathecal medication pumps over 8 years. The
mean survival time of patients was 7.1 months (range of 1 to 27 months). The mean VAS scores at implant time
were 8.6, which decreased to 3.8 at 1 month after implant. This improvement was basically sustained until death,
with a small increase in VAS seen in the terminal phase.
Figure 49-2 Schematic view of an implanted intrathecal pump.(Courtesy of Medtronic, Inc.)
An important as yet unanswered question involves the efficacy and economics of intrathecal opioids versus optimal
medical management that uses the wide array of oral, transdermal, rectal, and parenteral medications available. An
ongoing multicenter, prospective, randomized trial will address this question (for cancer pain syndromes) by
comparing implanted intrathecal pump plus maximal medical therapy with maximal medical management alone. [54]
Use of intrathecal therapy for chronic nonmalignant pain is growing coincident with the increasing use of opioids
for nonmalignant pain syndromes. There are few prospective reports showing clinical efficacy in treatment of
chronic pain. It must be remembered that other options for these patients are limited. Anderson and colleagues [55]
reported prospectively on the implantation of intrathecal pumps into 22 patients with FBSS. Of their patients, 50%
reported a 25% decrease in pain at 24 months after implant, and 36% reported a 50% or greater decrease in pain at
24 months after implant. Nearly all patients experienced improvement in the functional parameters evaluated.
Complications included five necessary reoperations for kinking of catheters, seroma, and catheter migration.
Incidence of medication side effects was less than 20%. Retrospective reports confirming clinical efficacy in
nonmalignant pain are more common. Paice reported in a large, multicenter, retrospective survey type of study on
[56]
the outcome of 289 patients with nonmalignant pain. Good to excellent pain relief was noted in 95% of patients,
with improvement in functional abilities observed in 57% of patients. These data must be cautiously interpreted
because of the retrospective nature of the study. Pump-related complications were experienced by 22% of these
patients, and medication side effects were reported by 25%. More than 85% of the patients were satisfied with this
therapy.
1165
Much work over the past few years has focused on the intrathecal administration of nonopioid medications or
combinations of opioids and nonopioids for chronic pain. Baclofen certainly has efficacy and safety for intrathecal
[51]
use in spasticity. A report published in 2000 shows some efficacy in patients with nociceptive pain. Newer agents,
[57] [58]
including clonidine, bupivacaine, and ziconotide (pending approval by the United States Food and Drug
Administration), with analgesic efficacy are available. The controlled use of these mixtures may improve the
efficacy of intrathecal therapy. More research is needed on the efficacy and safety of these mixtures. [59]
In severe pain syndrome refractory to oral medications, with careful selection and after successful intrathecal or
epidural testing, intrathecal medication delivery is reasonably safe, reduces pain, and improves the quality of life in
the majority of patients treated.
Newer Procedures for Pain
VERTEBROPLASTY AND KYPHOPLASTY
More than 200,000 symptomatic osteoporotic vertebral compression fractures (VCFs), primarily in elderly women,
occur annually in the United States. These fractures, which are associated with substantial pain and disability,
typically lead to more than 100,000 hospital admissions for extended rehabilitation stays. After the first compression
fracture, the average risk increases fivefold for the second. The pain lasts on average 4 to 6 weeks; it typically
localizes one or two levels below the level of the fracture and radiates axially. It is increased with weight bearing
and decreased by lying down.
Vertebroplasty in the United States was virtually nonexistent until 1993. Jensen and Dion at the University of
[59A]
Virginia introduced it in the United States after hearing about the European experience presented by Depriester at
the American Society of Neuroradiologists (ASNR) in May 1993. The European experience was largely related to
[59B]
the treatment of vertebral bodies infiltrated by cancer or hemangiomas and, to a lesser extent, compression fractures.
Bench testing was performed with different types of commercially available polymethylmethacrylate (PMMA). [60]
(PMMA was used first in contact lenses and had been used for more than 15 years in hip prostheses.) Jensen and
Dion tested injectability of PMMA types through a variety of needles and with different types and combinations of
radiographic opacifying additives. A cadaveric pilot study was conducted and then initial clinical trials were begun
in patients. The first patient had a lung metastasis to a midthoracic vertebra, and the procedure was done with CT
guidance and a paravertebral approach. Encouraged by the positive experience with this patient, they performed
vertebroplasty on three patients with osteoporotic compression fractures who had undergone transplantation. For
these patients, a transpedicular approach was used under fluoroscopy, and all three experienced significant pain
relief. From these initial steps, vertebroplasty has become a commonly used technique to treat compression fractures.
Jensen and Dion created the following treatment criteria for vertebroplasty: pain unrelieved by narcotics,
[59A]
decreased mobility, radiographic evidence of VCF, pain localized to the fracture level, nonfocal neurologic
examination, and a negative computed tomography or magnetic resonance imaging scan for herniated nucleus
pulposus or retropulsed fragment.
Jensen and associates proposed the following pain mechanisms in VCF: (1) Because the cortex and marrow are
without nociceptive fibers, nociceptors in the periosteum and joint capsule are stimulated directly from micromotion
or compression or indirectly by the release of chemical mediators associated with tissue injury; (2) mechanical
changes in the vertebral body affect the posterior elements, causing stress on the adjacent facet joints. PMMA [61]
theoretically decreases pain in VCF by immobilization of microfractures, relieving stress on the remaining bone by
improving tensile strength and destroying nociceptive fibers by causing necrosis (heat created by polymerization as
seen in hip prostheses).
The procedure is done under local infiltration and conscious sedation using a C-arm fluoroscopy unit or biplane
fluoroscopy. An 11-G biopsy needle (Cook or Parallax) is directed via a careful transpedicular approach into the
vertebral body. PMMA is prepared with an opacifier such as barium sulfate powder and tobramycin powder as a
prophylaxis and then injected slowly, with continuous checking for venous uptake or posterior spread. For a concise
review of the technical aspects of the procedure, see the journal article by Jensen and coworkers ( Fig. 49–3 ). [61]
The safety margin is increased by using slow injection techniques (controlled injection apparatus such as from
Parallax) and stopping the injection of monomer when preferential flow into veins or across fractures or posterior
migration to the junction of the posterior quarter of the vertebral body is seen. Careful injection and attention to the
direction of the monomer can prevent the two biggest problems: pulmonary embolization and direct spread to
contiguous neural structures. Of course, the transpedicular needle placement is also potentially a complication point,
especially if
1166
Figure 49-3 A, Vertebroplasty needle placement,

lateral view. B, Vertebroplasty image after
methylmethacrylate injection. (Courtesy of Mike
Royal, M.D.)
the medial cortex of the pedicle is violated and the needle enters the spinal canal. There have also been reports of
needles being inserted through the conus (unpublished data).
Cyteval and associates reported on their series of 20 patients with VCF. They used computed tomography guidance
[62]
for percutaneous vertebroplasties via a parapedicular approach. In 15 patients, pain relief was complete within 24
hours of injection. Mild pain persisted in three, one had pain recur after being lifted (the next level collapsed!), and
one had crural pain with cement leakage into the psoas muscle along the needle track. At 6-month follow-up, four
patients had new vertebral body collapse at other levels. No significant complications were noted.
Jensen and associates reported on 47 vertebroplasties (17 thoracic, 30 lumbar) in 29 patients with VCF; they used
[61]
a fluoroscopically directed transpedicular approach. The procedure was technically successful in all patients, with an
average injection amount of 7.1 mL of PMMA per vertebral body. Four vertebral bodies were seen to fill from a
single unipedicular approach, but the remaining ones had to be filled via a bipedicular approach with two needles.
Two patients sustained rib fractures during the procedure from pressure during needle placement. Twenty-six (90%)
reported significant pain relief immediately (24 hr) after treatment. No significant complications occurred. Only
three patients did not have significant relief of their pain in this series.
A review of all available clinical literature on vertebroplasty concluded that although patient selection criteria have
not been definitely established, percutaneous vertebroplasty is considered appropriate treatment for patients with
vertebral lesions resulting from osteolytic metastasis and myeloma, hemangioma, and painful compression fractures
if certain criteria are met. Those selection criteria include the following:
1. The patient has severe, debilitating pain or loss of mobility that cannot be relieved by correct medical
management.
2. Other causes of pain, including herniated disc, have been ruled out.
3. The involved vertebra is not extensively destroyed and retains at least 30% of its original height.
4. Radiotherapy and surgery may also be required to treat some of these lesions. [63]
Kyphoplasty is a related procedure for the treatment of vertebral compression fractures. The difference involves
insertion of a tamp or balloon-type device through the needle and inflation of the balloon to (1) restore as much
vertebral height as possible and (2) create a cavity for the PMMA. In animal models of vertebral compression
fracture, kyphoplasty restores vertebral body height and, in comparison with vertebroplasty, creates a relatively
stiffer or stronger vertebral body after the procedure. Not much clinical data on kyphoplasty is available, especially
[64]
in comparison with vertebroplasty. One abstract was published concerning a retrospective look at the first 26 cases
of kyphoplasty. Significant pain relief and improved functioning were reported in 23 of 26 patients, with no
significant complications. These procedures clearly have a role to play in the management of painful vertebral
[65]
compression fracture, although more outcome data will be necessary to recommend one over the other.
INTRADISCAL ELECTROTHERMAL COAGULATION
Intradiscal electrothermal annuloplasty (IDET) is a minimally invasive technique developed for the treatment of
discogenic, nonradicular pain ( Fig. 49–4 ). Chronic unremitting low back pain caused by internal disc disruption
[66]
is a very frustrating problem for the clinician. Treatment options have been limited to physical therapy and
analgesics or surgical fusion, and both have marginal beneficial results. [67]
The IDET procedure involves introducing a flexible electrode into the painful disc. This electrode is threaded from
within the nucleus to pass circumferentially around the lateral and posterior anulus. The electrode is heated,
probably to coagulate the collagen or destroy the nociceptive fibers in this area.
1167
Figure 49-4 Intraoperative view of dual-level lumbar intradiscal electrothermal

(IDET) catheter placement.(Courtesy of Mike Royal, M.D.)
Two interesting prospective studies have provided validation for the use of this procedure. Saal and Saal [68]
prospectively studied patients with chronic low back pain who underwent the IDET procedure. These authors used
very strict selection criteria including unremitting back pain for 6 months or longer, no improvement with a
rehabilitation program, at least one epidural steroid injection, and the use of NSAIDs. Additionally, the patients had
to have a negative straight leg raising maneuver, normal neurologic examination, and no evidence of neural
compression on MRI scan. The authors studied 1117 patients for 12 months. Only 62 patients met their criteria to
have the IDET procedure. Patients demonstrated sustained (for at least 1 yr) improvement in pain and functional
status. The mean follow-up period was 16 months. Mean VAS decreased by 3.0, and significant improvement was
noted on the SF-36 scale. Of the 62 patients, 12 (19%) showed no improvement.
Another interesting study of IDET was reported by Karasek and Bogduk. This study was less carefully controlled
[69]
than the aforementioned report but is of interest because of a comparison group. The authors looked at 53 patients
with pain caused by internal disc disruption. They evaluated approximately 150 patients to obtain this group of 53
patients who did not have radiating pain or encroachment on neural structures. These authors were much less
rigorous in terms of their rehabilitation protocols and waiting periods. Of the 53 patients with internal disc
disruption, 36 received insurance authorization for IDET, and the other 17 served as a convenience control group.
There are many obvious difficulties with this method, but the results remain interesting. Outcome measures were
VAS, analgesic use, and return to work. In the IDET group 23 of 36 (63%) had significant pain relief at 3 months
after the procedure, whereas only 1 of 17 (5%) had significant improvement in VAS with a rehabilitation protocol.
Of note, 23% of the IDET group had complete pain relief. About 50% of the responders maintained pain relief for
up to 1 year, and 50% slowly lost their initial pain relief. Also, 53% of the IDET group returned to work.
These preliminary studies show IDET to be a valid option for patients with internal disc disruption. The initial
results are probably better than those with rehabilitation alone and may be as good as those seen with lumbar fusion.
More research needs to be done, but morbidity is low, and with careful selection, many patients show significant
benefit from IDET.
ENDOSCOPIC DISCECTOMY AND NUCLEOPLASTY
Endoscopic laser discectomy was approved by the Food and Drug Administration in 1992 for use in the treatment of
contained subligamentous disc herniations, the so-called contained disc. The idea behind this technique is to create
[70]
a central vacuum in a herniated disc and allow the disc to retract inward, thereby reducing the herniation. This
technique has not gained widespread acceptance, most probably due to the detailed technical nature of the
equipment involved (laser, endoscope, irrigation equipment). There is some literature supporting the clinical
efficacy and safety of this procedure. Casper and associates performed a retrospective review of 100 patients who
[71]
underwent laser-assisted decompression and found a success rate of 86% (excellent or good symptom resolution)
with no complications. This technique is increasing in popularity because it has been adopted by industry and
because the equipment has been packaged for ease of use on the part of the clinician. The technique is marketed by
Clarus under the trade name of LASE. More clinical studies will be forthcoming.
Nucleoplasty is a related technique based on the same idea of central decompression of a herniated disc to allow the
disc to draw in and thus reduce herniation. The equipment for this procedure is adapted from that used in other
1168
orthopedic procedures on the shoulder and knee, where heat remodels cartilage. This technique may have efficacy
[72]
similar to that of the laser technique, but it is technically much less difficult. Some clinical studies are under way.
REFERENCES
1. Lieve JA, Block-Michel H, Attali P: L'injection transsacrée. Étude clinique et radiologigue. Bull Soc Med Paris 73:1110–1118, 1957.
2. Pages E: Anestesia metamerica. Rev Sanid Mil Madr 11:351–385, 1921.
3. Bromage PR: Identification of the epidural space. In Bromage PR (ed): Epidural Analgesia. Philadelphia, WB Saunders, 1978, p 178.
4. Gutierrez A: Valor de la aspiracion liquada en al espacio peridural en la anestesia peridural. Rev Circ 12:225, 1933.
5. Dogliotti AM: Segmental periductal anesthesia. Am J Surg 20:107, 1933.
6. Waldman, SD: Epidural nerve block. In RS Weiner (ed): Innovations in Pain Management. Orlando, PMD Press, 1990, pp 4–5.
7. White AH, Derby R, Wynne G: Epidural injections for the diagnosis and treatment of low back pain. Spine 5:78–86, 1980.
8. AbramS, Hopwood MB: What factors contribute to outcome with lumbar epidural steroids? In Bond MR, Charlton JE, Woolf CJ (eds):
Proceedings of the Sixth World Congress on Pain. Amsterdam, Elsevier, 1991, p 495.
9. Jamison RN, VadeBoncouer T, Ferrante FM: Low back pain patients unresponsive to an epidural steroid injection: Identifying predictive
factors. Clin J Pain 7:311, 1991.
10. Abram SE, Anderson RA: Using a pain questionnaire to predict response to steroid epidurals. Regional Anesth 5:11, 1980.
11. Sandrock
NJG, Warfield CA: Epidural steroids and facet injections. In Warfield CA (ed): Principles and Practice of Pain Management. New
York, McGraw-Hill, 1993, p 401.
12. Hopwood MB, Abram SE: Factors associated with failure of lumbar epidural steroids. Regional Anesth 18:238, 1993.
13. Saal JS, Franson RC, Dovrow R, et al: High levels of inflammatory phospholipase A2 activity in lumbar disc herniations. Spine 15:674, 1990.
14. Johansson
A, Hao J, Sjolund B: Local corticosteroid application block transmission in normal nociceptive C-fibers. Acta Anaesth Scand
34:335, 1990.
15. Kepes ER, Duncalf D: Treatment of backache with spinal injections of local anesthetics, spinal and systemic steroids. Pain 22:33, 1985.
16. Benzon HT: Epidural steroid injections for low back pain and lumbosacral radiculopathy. Pain 24:277, 1986.
17. Koes
BW, Scholten RJPM, Mens JMA, et al: Efficacy of epidural steroid injections for low back pain and sciatica: A systemic review of
randomized clinical trials. Pain 63:279, 1995.
18. Watts RW, Silagy CA: A meta-analysis on the efficacy of epidural steroids in the treatment of sciatica. Anaesth Intensive Care, 23:564, 1995.
19. McQuay HJ, Moore RA: Epidural Corticosteroids for Sciatica: An Evidence-Based Resource for Pain Relief. New York, Oxford University
Press, 1998, p 216.
20. Carette
S, Leclaire R, Marcoux S, et al: Epidural corticosteroid injection for sciatica due to herniated nucleus pulposus. N Engl J Med
336:1634–1640, 1997.
21. Dilke TFW, Burry HC, Grahame R: Extradural corticosteroid injection in management of lumbar nerve root compression. Br Med J 2:635,
1973.
22. Ridley
MG, Kingsley GH, Gibson T, et al: Outpatient lumbar epidural corticosteroid injection in the management of sciatica. Br J Rheumatol
27:295, 1988.
23. Green PWB, Burke AJ, Weiss CA, et al: The role of epidural cortisone injection in treatment of diskogenic pain. Clin Orthop 153:121–125,
1980.
24. Brown FW: Protocol for management of acute low back pain with or without radiculopathy, including the use of epidural and intrathecal
steroids. In Brown FW (ed): American Academy of Orthopaedic Surgeons Symposium on the Lumbar Spine. St. Louis, Mosby, 1981.
25. Harley C: Extradural corticosteroid infiltration. A follow-up study of 50 cases. Ann Phys Med 9:22–28, 1967.
26. Brown FW: Management of discogenic pain using epidural and intrathecal steroids. Clin Orthop 129:72–78, 1977.
27. Warr AC, Wilkinson JA, Burn JM, et al: Chronic lumbosciatic syndrome treated by epidural steroid injection and manipulation. Practitioner
1169
209:53–59, 1972.
28. Liu
SS, Melmed AP, Klos JW, et al: Prospective experience with a 20-gauge Tuohy needle for lumbar epidural steroid injections: Is
confirmation with fluoroscopy necessary? Reg Anesth Pain Med 26:143–146, 2001.
29. FurmanMB, O'Brien EM, Zgleszewski TM: Incidence of intravascular penetration in transforaminal lumbosacral epidural steroid injections.
Spine 25(20):2628–2632, 2000.
29A. Ghormley RK: Low back pain with special reference to the articular facets, with presentation of an operative procedure. JAMA 101:1773–
1777, 1933.
30. Schwarzer AC, Aprill CN, Derby R, et al: Clinical features of patients with pain stemming from the lumbar zygapophyseal joints: Is the
31. Schwarzer AC, Derby R, Aprill CN, et al: The value of the provocation response in lumbar zygapophyseal joint injections. Clin J Pain 10:309–
313, 1994.
32. Barnsley L, Lord SM, Wallis BJ, Bogduk N: Lack of effect of intraarticular corticosteroids for chronic pain in the cervical zygapophyseal
joints. New Engl J Med 330(15):1047–1050, 1994.
33. Careete
S, Marcoux S, Trunchon R, et al: A controlled trial of corticosteroid injection into facet joints for chronic low back pain. N Engl J Med
325:1002–1007, 1992.
34. Lord
SM, Barnsley L: Percutaneous radiofrequency neurotomy in the treatment of cervical zygapophyseal joint pain. Neurosurgery 36:732–
738, 1995.
35. McDonaldGJ, Lord SM, Bogduk N: Long-term follow-up of patients treated with cervical radiofrequency neurotomy for chronic neck pain.
36. Wallis BJ, Lord SM, Bogduk N: Resolution of psychological distress of whiplash patients following treatment by radiofrequency neurotomy:
A randomized, double blind, placebo-controlled trial. Pain 73:15–22, 1997.
37. Mixter WJ, Barr JS: Rupture of the intervertebral disc with involvement of the spinal canal. N Engl J Med 211:210–215, 1934.
38. Burton CV, Kirkaldy-Willis WH, Yong-Hing K, Heithoff K: Causes of failure of surgery on the lumbar spine. Clin Orthop 157:191–199, 1981.
39. Beal MC: The sacroiliac problem: Review of anatomy, mechanics and diagnosis. J Am Osteopath Assoc 81:667–679, 1982.
40. Dreyfuss P, Cole AJ, Pauza K: Sacroiliac joint injection techniques. Phys Med Rehab Clin North Am 6:785–813, 1995.
40A. Dreyfuss P, Halbrook B, Pauza K, et al: Efficacy and validity of radiofrequency neurotomy for chronic lumbar zygapophysical joint pain.
Spine 25:1270–1277, 2000.
41. Fortin
JD, Dwyer AP, West S, Pier J: Sacroiliac joint: Pain referral maps upon applying a new injection/arthrograph technique. Part I:
Asymptomatic volunteers. Spine 19:1475–1482, 1994.
42. FortinJD, April CN, Ponthieux B, Pier J: Sacroiliac joint: Pain referral maps upon applying a new injection/arthrography technique. Part II:
Clinical evaluation. Spine 19:1483–1489, 1994.
43. Maugars Y, Mathis C, Vilon P, Prost A: Corticosteroid injection of the sacroiliac joint in patients with seronegative spondylarthropathy.
44. Shealy
CN, Mortimer JT, Reswick JB: Electrical inhibition of pain by stimulation of the dorsal columns: A preliminary clinical report. Anesth
Analg 46:489–491, 1967.
45. Daniel
MS, Long C, Hutcherson WL, et al: Psychological factorsand outcome of electrode implantation for chronic pain. Neurosurgery
36:1101–1111, 1985.
46. Nielson
KD, Adams JE, Hosobuchi Y: Experience with dorsal column stimulation for relief of chronic intractable pain: 1968–1973. Surg
Neurol 4:148–152, 1975.
47. North
RB, Ewend M, Lawton MT, et al: Failed back surgery syndrome: 5-year follow-up after spinal cord stimulator implantation.
pain. Spine 21:2786–2794, 1996.
49. Kemler MA, Barendse MD, van Kleef M, et al: Spinal cord stimulation in patients with reflex sympathetic dystrophy. N Engl J Med 343:618–
624, 2000.
50. Wang JK, Nauss LA, Thomas TE: Pain relief by intrathecally applied morphine in man. Anesthesiology 50:149–151, 1979.
1170
51. Bennett G, Serafini M, Burchiel K, et al: Evidence based review of the literature on intrathecal drug delivery of pain medication. J Pain Symp
Manage 20:S12–S36, 2000.
52. Sallerin-Caute
B, Lazorthes Y, Deguine O, et al: Does intrathecal morphine in the treatment of cancer pain induce the development of
tolerance? Neurosurgery 42:44–50, 1998.
53. Hassenbusch SJ, Pillay PK, Magdinec M, et al: Constant infusion of morphine for intractable cancer pain using an implanted pump. J
Neurosurg 73:405–409, 1990.
54. Staats P, Smith T, Deer T, et al: Randomized comparison of medtronic intrathecal drug delivery system plus comprehensive medical
management (CMM) versus CMM for unrelieved cancer pain [abstract]. Am Acad Pain Med 228:48, 2001.
55. Anderson VC, Burchiel KJ: A prospective study of long-term intrathecal morphine in the management of chronic non-malignant pain.
56. Paice JA, Penn RD, Shott S: Intraspinal morphine for chronic pain: A retrospective, multicenter study. J Pain Symp Manage 11:71–80, 1996.
57. Penn RD, Kroin JS: Intrathecal baclofen in the long-term management of severe spasticity. J Neurosurg 4:325–332, 1989.
58. Zuniga RE, Schlict CR, Abram SE: Intrathecal baclofen is analgesic in patients with chronic pain. Anesthesiology 92:876–880, 2000.
59. Bennett G, Burchiel K, Buchser E, et al: Clinical guidelines for intraspinal infusion: Report of an expert panel. J Pain Symp Manage 20:S37–
43, 2000.
59A. Jensen ME, Dion JE: Percutaneous vertebroplasty in the treatment of osteoporotic compression fractures. Neuroimaging Clin N Am 10:547–
568, 2000.
59B. American Society of Neuroradiologists, Deramond H, Depriester C, et al: Vertebroplasty and percutaneous interventional radiolgy in bone
metastasis. Bull Cancer Radiother 83:277–282, 1996.
60. Convery FR, Gunn DR, Hughes JE, et al: The relative safety of polymethylmethacrylate. J Bone Joint Surg 57A:57–64, 1975.
61. Jensen
ME, Evans AJ, Mathis JM, et al: Percutaneous polymethylmethacrylate vertebroplasty in the treatment of osteoporotic vertebral body
compression fractures: Technical aspects. Am J Neuroradiol 18:1897–1904, 1997.
62. Cyteval
C, Sarrabere MPB, Roux JO, et al: Acute osteoporotic vertebral collapse: Open study on percutaneous injection of acrylic surgical
cement in 20 patients. Am J Roentgenol 173:1685–1690, 1999.
63. Levine SA, Perin LA, Hayes D, Hayes WS: An evidence based evaluation of percutaneous vertebroplasty. Manag Care 9:56–60, 2000.
64. Belkoff
SM, Mathis JM, Fenton DC, et al: An ex vivo biomechanical evaluation of an inflatable bone tamp used in the treatment of
compression fracture. Spine 26:151–156, 2001.
65. Yuan HA, Garfin SR, Lieberman IH, et al: Early clinical outcomes with kyphoplasty, the minimally invasive reduction and fixation of painful
osteoporotic vertebral compression fracture. Presented at the American Academy of Neurosurgery (AANS/CNS), Section on Disorders of the
Spine and Peripheral Nervous System. Annual meeting, Palm Springs, CA, Feb. 2000.
66. Saal JS, Saal JA: Management of chronic discogenic low back pain with a thermal intradiscal catheter: A preliminary report. Spine 25:382–388,
2000.
67. Kostuik J: Failures after spinal fusion. In Frymoyer JW (ed): The Adult Spine. Philadelphia, Lippincott-Raven, 1997, pp 2277–2328.
68. Saal JA, Saal JS: Intradiscal electrothermal treatment for chronic discogenic low back pain: A prospective outcome study with minimum 1-
year follow-up. Spine 25(20):2622–2627, 2000.
69. Karasek M, Bogduk N: Twelve-month follow-up of a controlled trial of intradiscal thermal annuloplasty for back pain due to internal disc
disruption. Spine 20:2601–2607, 2000.
70. Choy DSJ, Asher PW, Saddekni S, et al: Percutaneous laser decompression. Spine 17:949–956, 1992.
71. Casper
GD, Hartman VL, Mullins LL: Results of a clinical trial of the holmium: YAG laser in disc decompression utilizing a side firing fiber:
A two year follow-up. Lasers Surg Med 19:90–96, 1996.
72. Barber FA, Click SD, Weideman CA: Arthroscopic or open Bankhart procedures: What are the costs? Arthroscopy 14:671–674, 1998.
1171
Section VII Chapter 50 - Neuropathic Pain: Outcome Studies on the Role of Nerve Blocks
Chapter 50 - Neuropathic Pain: Outcome Studies on the Role of

Nerve Blocks
Louis M. Panlilio
Prabhav Tella
Srinivasa N. Raja
Pain is primarily a subjective phenomenon. Often, it is a complex perceptual experience of an individual that defies
easy description and quantification. Tissue injury and inflammation lead to increased excitability in both the
peripheral and central nervous systems. These reversible sensory changes serve a protective role against further
injury during the healing process. Neuropathic pain, in contrast to inflammatory pain, is characterized by pain that
persists longer than the expected healing period after a neurologic injury and serves no useful function. The [1]
International Association for the Study of Pain (IASP) defines neuropathic pain as pain that results from a lesion or
dysfunction of neurologic structures. An extensive array of neurologic injuries can lead to a neuropathic pain state.
The site of injury can involve peripheral nerves, dorsal root ganglia, spinal cord, brainstem, or thalamocortical
structures.
Neuropathic pain can be classified based on the following:
• Etiology (e.g., traumatic injury, diabetic neuropathy, postherpetic neuralgia (PHN) [ Table 50–1 ])
• Anatomy: Specific nerve or anatomic site involved (e.g., trigeminal neuralgia, intercostal neuralgia,
sciatica)
• Symptom complex: if the etiology is unclear, a syndrome is described based on clinical features (e.g.,
complex regional pain syndrome)
• Mechanism: if the neural mechanism is understood (e.g., deafferentation pain)
Neuropathic syndromes may be manifested by a complex host of symptoms such as dysesthesias, paresthesias,
hypesthesia, and constant or paroxysmal pain. Paresthesias are spontaneous or evoked abnormal sensations that are
not unpleasant, whereas dysesthesias are spontaneous or evoked sensations that are both abnormal and unpleasant.
Hypesthesia is reduced sensitivity to a stimulus. Patients generally describe a lancinating or burning pain, often
associated with allodynia and hyperalgesia. Allodynia refers to pain induced by a stimulus that is normally not
painful (e.g., light stroking of the skin). Hyperalgesia is increased pain to a stimulus that is normally painful.
Spontaneous resolution may occur, as in some cases of PHN, but often symptoms persist indefinitely. The
relationship among etiology, mechanisms, and clinical features of neuropathic pain is complex and not well
understood ( Fig. 50–1 ).
Diagnosis of neuropathic pain is based on symptomatology, clinical examination, and history of possible nerve
injury. Electromyographic studies and nerve conduction studies can help provide additional information about the
nerve(s) involved. Neuropathic pain is associated with a heterogeneous group of disorders and presentations, making
controlled research, generalizations, and extrapolations of clinical findings difficult. For example, focal peripheral
entrapment neuropathies are similar to metabolic polyneuropathies, but treatment and outcomes may be dissimilar.
Also, neuropathic pain may coexist with other types of pain. For example, pain associated with an invasive tumor
may have components of nociceptive, neuropathic, and visceral pains.
Pathophysiology of Neuropathic Pain
Normally, pain results after a noxious stimulus from activation of specific peripheral sensory neurons called
TABLE 50-1 -- ETIOLOGICAL CLASSIFICATION OF NEUROPATHIC PAIN SYNDROMES

Peripheral nerve injury
Trauma
Surgical
Postamputation
1172
Retractor injury
Nerve ligation
Compression or traction injuries
Nonsurgical
Nerve entrapment
Carpal tunnel syndrome
Tarsal tunnel syndrome
Cubital tunnel syndrome
Radial tunnel syndrome
Meralgia paresthetica (lateral femoral cutaneous nerve)
Thoracic outlet syndrome
Metabolic diseases
Diabetic neuropathy
Uremia
Amyloidosis
Multiple myeloma
Hypothyroidism
Alcoholism
Beri-beri
Fabry's disease
Infectious
Postherpetic neuralgia
HIV
Lyme disease
Guillain-Barre syndrome
Autoimmune
Polyarteritis
Systemic lupus erythematosus
Ischemic injury
Peripheral vascular disease
CNS infarct
Toxicity related
Isoniazid
Cisplatin
Thallium
Mercury
Other
Radiation injury
Idiopathic
CNS, Central nervous system.
nociceptors. These signals are transmitted to the central nervous system where they undergo modulation by local
and descending control systems and finally reach the level of perception at the sensory cortex. In contrast to this
physiologic pain, neuropathic pain can be associated with spontaneous pain in the absence of an external stimulus,
with pain evoked by a normally innocuous stimulus, or with both. The plastic changes in the nervous system that
result in the neuropathic pain state have been an area of considerable interest for researchers. Neuronal plasticity
refers to the process by which neurons involved in pain transmission are altered from a state of normal sensitivity to
a hypersensitive state. [2]
1173
A number of peripheral and central mechanisms contribute to the development of the neuropathic pain state. These [1]
mechanisms include the following:
1. The development of stimulus-independent ectopic activity resulting from an increased expression of

sodium channels at the nerve injury site. Spontaneous activity in C fiber nociceptors is thought to be
responsible for stimulus-independent pain (see Fig. 50–2 ). In addition, activity in large myelinated fibers
may lead to paresthesias. Neuromas also develop exquisite mechanosensitivity. Pressure on or stretching of
the neuroma results in a burst of action potentials, the neurophysiological correlate of Tinel's sign.
2. Phenotypic changes in functions of sensory neurons resulting from alterations in ion channels (e.g., sodium
and potassium), receptors (e.g., adrenoceptors), and transmitters (e.g., substance P, VIP, galanin).
3. Abnormal contacts between sympathetic efferent fibers and sensory neurons (e.g., sympathetic sprouting in
the dorsal root ganglion).
4. Abnormal sprouting and contacts between low-threshold myelinated A-beta afferent fibers in the
superficial layers of the dorsal horn and neurons that would normally be innervated by unmyelinated C
fibers.
5. Central disinhibition or loss of inhibitory mechanisms in the dorsal horn.
Figure 50-1 Etiology, mechanisms and symptoms of neuropathic pain(From Woolf CJ, Mannion RJ: Neuropathic pain: Aetiology, symptoms,
mechanisms, and management. Lancet 353:1959–1964, 1999. Reprinted with permission from Elsevier Science.)
A nerve injury often results in the formation of a neuroma. Neuromas become a site of hyperexcitability and act as
generators of ectopic action potentials. Studies suggest that sodium channels accumulate at the neuroma site, and the
repetitive burstlike firing from neuromas results from this increased sodium current. In particular, a tetrodotoxin-
[3]
insensitive sodium channel found only in nociceptive sensory neurons has been implicated in the neuropathic pain
state. Some studies have suggested that a subtype of an embryonic sodium channel is re-expressed at high levels in
[4]
injured neurons. [5]
Modulation of nociceptor signals from the periphery occurs at multiple levels starting from the dorsal horn, the site
of the first synapse in the pain pathway. Plasticity in the dorsal horn neurons is considered to be the primary
mechanism responsible for the development of hyperalgesia and allodynia. The hyperexcitability of dorsal horn
neurons, a mechanism that involves N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-
isoxazolepropionic acid (AMPA) receptors, results in more intense and/or sustained activity in dorsal horn neurons,
leading to the phenomenon of wind-up and central sensitization. Central sensitization can manifest as an
exaggerated response to a noxious stimulus (i.e., hyperalgesia), initiation of action potentials by normally
subthreshold stimuli (i.e., allodynia), and enlargement of the receptive field of dorsal horn cells (spread of
hyperalgesia to regions beyond those innervated by the injured nerve).
1174
Figure 50-2 Mechanism of ongoing, spontaneous pain after nerve injury(From Woolf CJ, Mannion RJ: Neuropathic pain: Aetiology, symptoms,
mechanisms, and management. Lancet 353:1959–1964, 1999. Reprinted with permission from Elsevier Science.)
Persistent or prolonged noxious input can also lead to transcriptional changes in the dorsal root ganglion and dorsal
horn cells. These changes can result in alterations in central synaptic transmitter levels and the number of receptors
on dorsal horn neurons. Sprouting of A-beta fibers into the superficial lamina may be the anatomic correlate for
allodynia, whereby activation of low threshold mechanoreceptors results in the sensation of pain. This phenomenon
may explain the brush-evoked allodynia seen in patients with PHN who have denervated skin. Disinhibition may [1]
result either from death of dorsal horn inhibitory intraneurons as a result of afferent activity from the periphery
inducing excitotoxicity or secondary to downregulation of inhibitory neurotransmitter mechanisms such as those
involving gamma aminobutyric acid (GABA) or glycine receptors.
To understand the mechanisms of neuropathic pain, two aspects deserve consideration. The first relates to the
initiation of central sensitization. It has been postulated that an injury in the periphery results in activation of
nociceptor fibers, and a barrage of input along these fibers serves as a trigger for central sensitization. Subsequently,
further peripheral nociceptor input may be required for maintenance of hypersensitive central neurons. Thus, the
rationale for performing peripheral nerve or sympathetic blocks is an attempt to interrupt the peripheral inputs along
nociceptive fibers that help maintain the central pain state. It is postulated that blocking the nociceptive drive may
help revert the central neurons from their sensitized state to a more normal state. What is unclear, however, is the
[6] [7]
optimal duration of blockade of the afferent signals that is required to allow the central neurons to return to their
normal state of excitability. The understanding of the reversibility of the plastic changes in the central nervous
system is likely to lead to a more rational approach to pain therapies.
Therapeutic Strategies
Although a wide variety of treatment techniques for neuropathic pain are available, successful treatment is often
difficult ( Table 50–2 ).
Pain associated with relatively discrete nerve lesions such as neuromas, nerve entrapment, spinal nerve root
compression, and space-occupying masses may respond to treatment of the underlying cause. Neuropathic pain,
1175
however, may persist after successful decompression or removal of the involved structure. When a direct therapy
targeted at the underlying mechanism is not available, management goals consist of reducing symptoms and
assisting patients in coping with chronic pain and associated suffering. Improvement
TABLE 50-1 -- THERAPEUTIC STRATEGICS FOR NEUROPATHIC PAIN

Surgical interventions directed at etiology
Peripheral nerve decompression (e.g., carpal tunnel release)
Nerve root decompression (e.g., intervertebral discectomy)
Systemic pharmacotherapy
Tricyclic antidepressants (e.g., amitriptyline)
Antiseizure medications (e.g., gabapentin)
Sympatholytics (e.g., guanethidine, phentolamine)
Non-narcotic analgesics (e.g., acetaminophen)
Opiates (e.g., morphine)
Sodium channel blockers (e.g., lidocaine, mexiletine)
NMDA antagonists (e.g., ketamine)
Regional pharmacotherapy
Topical medications (e.g., capsaicin, lidocaine)
Peripheral conduction blockade
Peripheral nerve steroid injection
Peripheral sympathectomy
Neuraxial conduction blockade
Neuraxial steroid injection
Neuraxial sympatholytics
Neuraxial opiates
Electrical stimulation
Transcutaneous nerve stimulation
Direct peripheral nerve stimulation
Spinal cord stimulation
Brain stimulation
Functional therapies
Physiotherapy
Occupational therapy
Behavioral modifications/psychotherapies
Biofeedback
Relaxation techniques
Destructive nervous system techniques
Peripheral neurolysis
Peripheral neurectomy
Chemical and surgical rhizotomy
Cordotomy
Stereotactic brain lesions
in functional ability and quality of life may be as important as analgesia in the comprehensive care of the chronic
pain patient.
Ongoing laboratory and clinical research has provided advances in pharmacotherapies for neuropathic pain. The
efficacy of pharmacologic treatments has been reviewed by Sindrup and Jensen. In general, tricyclic
[8]
1176
antidepressants are considered first-line medical therapy, and the efficacy of anticonvulsants such as gabapentin is
being established by a growing number of controlled trials. The role of opiate narcotics, once regarded as ineffective
in neuropathic pain, is being reevaluated. These and numerous other drug classes and delivery routes, such as
[9] [10] [11]
intrathecal clonidine and oral ketamine, are being studied; however, complete pain relief with medical therapy is
rarely achieved.
Nonpharmacologic interventions include both nondestructive and destructive techniques. Transcutaneous electrical
nerve stimulation, direct peripheral nerve stimulation, and dorsal column stimulation have demonstrated success in
some cases. These techniques are reversible, whereas neurolysis, rhizotomy, dorsal root entry zone lesions, and
cordotomy are not. Treatment of neuropathic pain with deep brain stimulation and stereotactic lesions remains
controversial.
When the number of pain clinics was increasing in the 1950s, peripheral nerve blocks with local anesthetics, often in
combination with corticosteroids, became standard treatment in managing neuropathic pain syndromes.
Interventional pain specialists have also employed nerve root, nerve plexus, sympathetic, epidural, and spinal
blockade techniques to help in the diagnosis, treatment, or prognosis of pain states. Neural blockade usually does not
result in permanent resolution of pain, but observation in some patients of pain relief lasting longer than the duration
of action of the drug suggests that the transient interruption of afferent signals from the periphery may provide long-
lasting benefit. Systemic absorption or centripetal intraneuronal transport of local anesthetic also may play a role in
pain modulation after neural blockade. In general, regional anesthetic procedures in the management of
[12]
neuropathic pain lack extensive long-term, randomized, controlled outcome studies that clearly define their role.
Similarly, the efficacy of neuroablative techniques using phenol, alcohol, radiofrequency, cryolysis, and surgical
neurectomy have not been critically evaluated with regard to long-term therapeutic outcomes.
Outcomes Research in Pain Management
Rational practice of medicine aims at elimination or maximal relief of the elusive and subjective phenomenon of
pain. Evidence-based pain management relies on the application of appropriate intervention strategies that possess
established reliability, validity, and effectiveness. The process of validation and selection of the most effective
treatment option demands objective assessment and monitoring of the multiple attributes of pain in relation to the
several available therapeutic alternatives. Because pain is multifaceted in nature, it follows that outcomes in pain
medicine are correspondingly numerous and varied. Outcomes serve as yardsticks for evaluating chronic pain in its
physical, cognitive, behavioral, social, and functional dimensions. When assessed and compared with regard to
specific treatments, outcomes aid in the selection of the most effective intervention. In the absence of such
systematic evaluation, it is difficult to establish the usefulness of the multitude of existing empiric treatment options.
The cardinal distinction between acute and chronic pain merits mention before any further discussion of outcomes in
the management of pain. Acute pain can often be linked to a preceding condition and usually lasts for a few minutes
or hours or sometimes can persist for a few months depending on the injury or the disease that caused it (e.g.,
postoperative pain). However, chronic pain is a more lasting condition that persists for several months and not
infrequently becomes a stable entity in the patient's life (e.g., neuropathic pain). The element of chronicity
invariably affects other aspects of life such as behavior and function, leading to a complex state of suffering that
often involves physical limitation and psychosocial derangement. Although the same tools and techniques may be
used for assessment of any type of pain, the aforementioned distinction between acute and chronic states needs to be
considered when interpreting outcomes and establishing goals for treatment. The objectives of quantifying pain in a
given acute pain setting such as intensive care, postoperative care, and invasive procedures are to prevent and
minimize suffering and to provide maximum relief of distress from acute pain. Thus, the measurement of pain
intensity and duration may suffice. However, the objectives of measuring pain in a chronic setting extend to
assessing the effects of the previous treatments and selecting the best of them to avert the dangers of overmedication
and repeated surgery as well as to devise an appropriate rehabilitative plan for the particular chronic pain patient. [13]
CHARACTERISTICS OF OUTCOMES
A brief account of the desirable characteristics of outcome measures is presented before outcomes specific to pain
are discussed. As mentioned earlier, outcome is a tool that enables assessment of the results of an intervention. Thus,
it follows that the outcome variable should be of real importance and be validly linked to the intervention. An [14]
outcome may be an objective measure or a subjective self-report. Regardless of the nature of the outcome, a set of
attributes determines the quality of the measure and indicates the ability of the outcome to reflect what it purports to
measure. Reliability and validity are the key criteria for qualifying an outcome measure.
1177
Reliability
Also referred to as repeatability or reproducibility, reliability is a measure of consistency in obtaining results.

Depending on the requirements of the particular clinical setting, it can be assessed in at least three different ways : [15]
1. Internal Consistency: Typically examined in assessing reliability of questionnaires, this quality refers to the
extent to which answers to individual questions are correlated with the total score or with each of the other
questions. Internal consistency provides an estimate of whether the items in the questionnaire are
[16]
measuring the same or related entities and helps determine whether the possible responses are compatible
to the real issue under question.
2. Test-retest Reliability: All the testing conditions kept constant; this measure expresses the degree to which
similar results are obtained on repetition of the test. An implicit assumption is that the condition being
tested remains unchanged over time. Intrarater reliability is a special case in which the consistency of
obtaining similar results on repeat testing by a single examiner is assessed.
3. Inter-rater Reliability: It refers to the degree of consistency in results obtained by different examiners
measuring the same attribute or outcome.
Validity
Validity refers to the ability of actually measuring what the outcome variable purports to measure. It can be assessed
in at least five different ways:
1. Face Validity: It describes whether the outcome measure seems to be a reasonable option to gain
information about the entity under question (e.g., the use of Beck's Depression Inventory [BDI] to
determine the presence of depression).
2. Content Validity: It refers to the extent to which the outcome measure assesses the constituent components
of the phenomenon being investigated. With reference to BDI, this reflects the ability of BDI to capture the
component attributes that constitute depression.
3. Concurrent Validity: Also known as criterion validity, this quality shows how the outcome compares with
other existing and accepted outcomes that are being used to measure the same attribute. This is considered
to be the easiest and most commonly used form of validity. For example, the comparative performance of
[15]
the BDI with the Zung Depression Index or other psychometric tests can provide an estimate of the
concurrent validity of the BDI.
4. Construct Validity: This form of validity assessment is done when numerous related factors are being
simultaneously measured to assess an attribute. It is the most intricate but also most important form of
validity. Complex correlation and factor analysis are required to assess this quality.
[15]
5. Discriminant Validity: This is the ability of an outcome to correctly discriminate the measures of an
attribute into discrete categories such as “Positive” and “Negative” or “Normal” and “Abnormal.”
Typically applied to testing procedures, this may take the form of sensitivity, specificity, or positive or
negative predictive value:
• Sensitivity: The ability of a test to correctly identify those who truly have the condition.
• Specificity: The ability of a test to correctly identify those who truly do not have the condition.
In general, outcome studies are directed towards establishing three important characteristics of an intervention:
1. Efficacy: It is defined as the effect of an intervention in well-controlled, essentially ideal circumstances.

Typically, efficacy studies involve a select group of subjects monitored by skilled personnel and are often
designed to answer the fundamental question: “Does the intervention have any effect at all?”
2. Effectiveness: It is described as the effect of an intervention in ordinary circumstances that may involve all
types of patients and personnel who are not specially trained. This provides an estimate of how well the
particular intervention works in “real-world” conditions. Many therapeutic procedures with proven efficacy
may not have substantial effectiveness to be chosen as optimal treatments.
3. Efficiency: The comparative estimate of value versus cost for each intervention is called efficiency. Thus,
high efficiency is characteristic of procedures that provide high value for a lesser input of money and time.
ASSESSMENT OF CHRONIC PAIN
In the early 1970s, chronic pain began to gain special attention as a discrete clinical syndrome that required
[17]
diagnosis and treatment in special clinics involving interdisciplinary teams. The need for robust measurement tools
1178
and techniques led investigators to research and develop reliable and valid instruments for assessing chronic pain.
For instance, an “algometer” was one of the many devices invented to measure chronic pain by comparing it with
acute pain induced by a brief electric current applied to an arm tourniquet or tooth pulp. However, these early[18]
attempts of “objectifying” a complex, subjective experience such as pain in a single dimension failed to gain
acceptance in the assessment of chronic pain. With time, as the multidimensional nature of chronic pain states was
recognized, the need for the multitude of descriptors to capture the complex pain experience began to be fulfilled.
Accordingly, several outcome measures emerged, although only a few of them have proven reliability and validity.
A simple classification of outcomes that are routinely used in evaluation of chronic pain is discussed in the
following paragraph.
Physical Outcomes
Location and distribution of pain are ascertained by marking on the relevant part of the body indicated verbally by
the patient. Intensity of pain is frequently measured by verbal descriptor scales such as mild, discomforting,
distressing, horrible, or excruciating, as suggested by Melzack and Torgerson. A numerical rating scale (NRS)
[19]
which may range from 0 to 10 or 0 to 100, representing “no pain at all” to “the worst imaginable pain,” may be used,
or a visual analogue scale (VAS), which also has a range similar to that of NRS may also be used to assess the
severity of pain. Although the reliability and validity of the VAS continues to be debated, it is commonly used in
[20] [21]
clinical studies. Duration and frequency of pain can be better assessed through pain diaries maintained by patients
rather than self-reports based on patient recall. Apart from these, questionnaires such as SF-36/SF-12, the Symptom
Checklist-90, and the Wisconsin Brief Pain Questionnaire are often used to assess physical symptoms in chronic
[22] [23]
pain patients. Muscle strength, endurance, flexibility, and range of motion at affected joints are routinely evaluated
physical measures. Electromyelographic activity and pressure algometers are also used in chronic pain patients to
measure tension in muscle groups and detect myofascial tender points, respectively.
[24] [25]
Functional Outcomes
A measure of the proportion of time in a day during which a pain patient is functionally active is called “uptime.”
Questionnaires that evaluate and electronic devices that monitor uptime are available. To assess disability in a
reliable and valid manner, a few standard tools are available: The Sickness Impact Profile, the Chronic Illness [26]
Problem Inventory (CIPI), and the Health Assessment Questionnaire. Activities of daily living, ambulation,
[27] [28]
productivity, and self-care are other routinely assessed functional outcomes.
Behavioral/Cognitive Outcomes
Drug usage, number of physician visits, hospitalizations, and surgeries, along with nonverbal pain behaviors such as
grimacing, sighing, and limping are a part of the behavioral evaluation of chronic pain.
Illness Behavior Questionnaire (IBQ) is frequently used to sketch the patient's behavioral pattern. Evaluation of
sleep patterns and coping skills are important components in the behavioral outcome assessment of chronic pain
patients. The Cognitive Errors Questionnaire (CEQ) is being increasingly used in the management of chronic pain
[29]
patients. The McGill Pain Questionnaire (MPQ) is a popular tool for assessing verbal pain behavior and has
[30] [31]
acceptable reliability and validity. It helps in evaluating the sensory and affective components of chronic pain.
Emotion-Related Outcomes
Depression and anxiety are important emotional factors that have a bearing on the management of chronic pain.
Minnesota Multiphasic Personality Inventory (MPI), Waddell's Non-organic LBP Signs, the BDI, and the State-
Trait Anxiety Inventory (STAI) are a few of the tools that may be used to ascertain depression and anxiety in
patients with chronic pain.
Other pertinent outcomes include social outcomes such as family involvement, living arrangements (especially for
older patients), quality of life, and outcomes related to economic factors such as costs of treatment procedures,
physician visits, medications, and lost workdays. Goal Attainment Scaling (GAS) provides an avenue to evaluate
[32]
the success in achieving goals set by the patient.
In summary, consistent with the multidimensional nature of chronic pain, it is imperative to use standard techniques
to collect, compare, analyze, and interpret data on all relevant outcomes. Furthermore, such comprehensive
assessment in routine clinical practice would aid not only in better management of individual patients but also in
establishing the effectiveness of the available treatment options.
1179
METHODOLOGY ISSUES IN EVALUATING CHRONIC PAIN
The primary problem in evaluating chronic pain is to define relevant outcome measures that can provide an estimate
of “success of treatment” consistent with the therapeutic procedure. Caution needs to be exercised in collecting,
analyzing, and interpreting outcome data because of two important conceptual concerns. First, there are no
satisfactory objective indicators of pain that are universally applicable and acceptable. Second, every outcome is
prone to some degree of error during design, collection, analysis, or interpretation. An attempt to define and apply
quality control helps in obtaining dependable data. Other factors that need to be considered when evaluating
outcomes include the demographic makeup, inpatient/outpatient status, and the credibility of the treatment
procedures in the patient population. Issues related to referral patterns, adherence to treatment, and attrition of the
[33]
initial study group need attention. “Reactivity,” which is a measure of inherent subjectivity of the outcome measures
also needs to be taken into account when drawing conclusions from outcome analysis. For instance, in one meta-
analytic review, it was found that only 3% of the 65 pain clinic treatment outcome studies included measures of
[34]
low reactivity and that only 29% of them assessed outcomes with acceptable levels of reliability and validity.
Additional criteria of importance include efficiency, consumer evaluation such as patient satisfaction, and the
distinction between statistical and clinical significance. Furthermore, moderately efficacious but inexpensive
strategies may be applied more efficiently to a larger patient population than highly efficacious interventions that
may be more expensive. There is increasing speculation that group interventions, home self-care, and service
through nonprofessionals may be highly cost-effective options. Despite all the efforts to minimize
[35]
misinterpretation of the results of outcomes, there remains a potential for overestimating the effects of treatment
procedures. Placebo effects, regression to the mean, and natural history of disease may falsely result in good
outcomes. Therefore, care needs to be exercised when inferences are drawn from studies that are not well-controlled,
randomized trials. [36]
PLACEBO
Any discussion of outcomes in pain therapies must acknowledge the possible significance of placebo effects of
medical and interventional therapies. Turner and colleagues described three possible reasons for improvements in
[36]
painful conditions after treatment. Observed changes may be the result of the natural history of the condition or
regression to the mean, a result of the specific effects of the treatment, or a result of nonspecific or placebo effects of
the treatment. In the absence of placebo-controlled trials, caution must be used in ascribing therapeutic effects to the
specific treatment being examined. Although wide variation has been noted, a desirable response attributed to a
placebo effect is often quoted to be roughly 30%, with response rates as high as 70%. [37]
In conclusion, it should be emphasized that the fundamental step toward a rational management of chronic pain is
multidimensional assessment of pain. Outcome evaluation should always consider the characteristics of the patient
population, the goals of treatment as defined by the patient and provider, and the reliability and validity of outcome
measures that are used. Finally, it is imperative to develop a consensus about refining and standardizing existing
outcome measures and to continually search for scientifically sound alternative outcomes, study designs, and
statistical methods that can capture the multidimensional nature of chronic pain in a better way.
Evaluating Risk-Benefit Ratio of Pain Therapies
Clinicians have long been confronted with the challenge of weighing the benefits and risks of a given therapy and
assessing whether the risk-benefit ratio is favorable to the patient. Changes in the healthcare industry have dictated
that the risk-benefit ratio to the physician and society also need to be considered. In managing patients with chronic
pain, benefits should include not only the efficacy of the therapy in attenuating the symptoms but also improvement
in quality of life. In assessing the overall risk of a procedure, several factors need to be considered. These include (1)
the incidence of complications, (2) the severity of the complications, (3) the time course and reversibility of the
problem when it occurs, and (4) the additive impact on the patient given that the complications are accompanied by
beneficial effects.
Surveys of experienced clinicians including anesthesiologists, neurologists, and neurosurgeons have revealed
disparate views and sometimes lack of opinion on the value of specific treatments of neuropathic pain conditions. [38]
Much of this disagreement is likely a result of the absence of critically appraised evidence and outcomes
information as well as inadequate dissemination of available information. Most studies on the role of nerve blocks in
chronic pain management have failed to quantitate the benefits and risks carefully. Typical inadequacies of many of
the studies include biased sampling, inadequate evaluation of outcome, and lack of long-term follow-up. The
inadequacies of the available data in the literature and the lack of data on the potential beneficial effects of nerve
blocks present significant barriers to making informed decisions for the physician and patient.
1180
PERIPHERAL NERVE BLOCKS
In a nonrandomized prospective study of regional anesthetic blocks reported by Arner and associates, 38 [12]
consecutive patients with neuralgias were treated with various local anesthetic peripheral nerve blocks. Etiologies
included entrapment syndromes as well as surgical and traumatic nerve damage, and all patients had demonstrable
sensory dysfunction. The peripheral nerves blocked included ilioinguinal, iliohypogastric, saphenous, superficial
peroneal, intercostal, suprascapular, and lateral femoral cutaneous nerves. Each patient underwent a series of blocks
(median number of 5) with 0.5% bupivacaine. The outcomes assessed included the magnitude of pain relief and its
time course. All patients reported complete pain remission immediately after the blocks were performed. After a
single block, 18 patients (47%) reported complete relief lasting from 12 hours to 6 days, which were durations
longer than the period of conduction block. Twenty patients (53%) reported initial complete relief lasting 4 to 12
hours; seven of these patients also reported a second phase of complete relief lasting 4 hours to 6 days, beginning
within 12 hours of the initial phase.
With regard to long-term results, 16 of 38 patients (42%) reported subjective improvement with reduction in pain for
weeks to months after the blocks were performed. Of these, 7 patients reported benefit after a second series of
blocks. Four of these 7 patients experienced improvement for an additional 1 to 4 years.
These results indicate that although pain relief after a series of nerve blocks in patients with neuralgias is usually
transient, a proportion of patients do experience prolonged relief. A significant number of patients had analgesia
longer than the expected duration of pharmacologic conduction blockade. This study lacked placebo control, and no
other outcome measurements, such as functional ability, quality of life, or additional medication, were reported.
In a similar study, Johansson and Sjolind reported retrospectively the long-term results in all patients treated with
[39]
local anesthesia and corticosteroid blocks over a 4-year period. Twenty-nine patients were identified as having
neurogenic pain. Nerve blocks were performed with 0.5% bupivacaine and methylprednisolone and included
intercostal, trigeminal branches, occipital, sacral plexus, ilioinguinal, and paravertebral blocks. The series consisted
of a median of 5 blocks. Assessments were made from clinical records and by questionnaire at varying intervals
within 1 to 5 years after treatment. Responses were categorized as complete, partial, or no pain relief. Additional
data on the duration of pain relief, medication use, activities of daily living (ADL), and occupational function were
collected. Sixty-six percent of patients with neurogenic pain experienced partial pain relief, and 28% experienced
initial complete relief. One half of those reporting complete relief benefited for less than 1 week, and most often
only the day the block was performed. One patient had complete relief of occipital neuralgia pain for more than a
year. Although oral analgesic use was reduced in 28% of patients, improvement in occupational function was noted
in only 3 patients (10%). Significantly, 41% showed improvement in ADLs. No references were made to any
rehabilitation or physical therapy regimens that the patients underwent during the study period.
These findings suggest that although effective for short-term analgesia, it is unlikely that peripheral nerve blocks as
a sole treatment modality will produce long-lasting relief of neuropathic pain. Improvement in function, reflected by
improvement in ADL or other functional measure, however, may possibly be a more attainable positive outcome.
When used in conjunction with physical and occupational therapies, even transient analgesia may help these
physical modalities become more tolerable. Rapid onset of analgesia may also ease suffering as pharmacologic
therapies are initiated and coping skills are acquired. Elucidating the efficacy of peripheral nerve blockade as a
component in a multidisciplinary approach will require subsequent well-designed trials. Inclusion of functional
outcome measures in addition to pain scores may provide greater sensitivity in evaluating their effects. The
aforementioned studies evaluated the use of a heterogeneous assortment of peripheral nerve block procedures. In the
next section, we explore the available further evidence with regard to the effectiveness of individual neural blockade
techniques.
Occipital Nerve
Greater occipital nerve blocks are performed for the diagnosis and treatment of cervicogenic headache based on a
presumed relationship to occipital neuralgia in some patients. Although several theories exist regarding the etiology
of this condition, the pathophysiology is not well established. The pain usually spreads anteriorly from the posterior
part of the head to the frontal region. Other associated features include reproduction of pain by palpation of the
[40]
greater occipital nerve and, possibly, hypesthesia in its cutaneous distribution. Gawel and Rothbart extensively
[41]
reviewed the role of occipital nerve blocks in the treatment of headache and cervical pain, which included their own
retrospective findings in patients with migraine. Of note, 72% of post-traumatic headache patients (63 of 87) and
54% of all patients reported to be “significantly better” for up to 6 months after greater occipital nerve block.
Occipital nerve block is considered a promising technique that is technically straightforward, relatively safe, and
deserving of further prospective trials.
1181
Caputi and Firetto postulated that central nervous system hyperexcitability may result from sensitization of
[42]
epicranial perivascular nociceptors and may lead to headaches. Trials were conducted using series of greater
occipital nerve and supraorbital nerve blocks to determine the analgesic effects of repeated epicranial neural
blockade, possibly by reducing peripheral sensitization. Twenty-seven patients with chronic headache were included
and underwent 5 to 10 greater occipital and supraorbital nerve blocks with 0.5 to 1 mL of 0.5% bupivacaine on
alternating days. Patients kept daily records of the frequency and severity of headaches, analgesic use, severity of
occurrences, and associated functional restrictions for a total of 7 months, beginning 1 month before treatment.
Within the first month, 85% of patients reported at least a 50% reduction of a pain index (calculated using numeric
frequency and severity scores). This favorable response was observed to continue for the entire 6-month follow-up
period.
A similar trial by Vincent found a mean reduction in pain scores of 41% in a 7-day follow-up compared with the 7
[40]
days before treatment. A better response was noted in patients with more severe initial symptoms. Conflicting
reports of prolonged relief of cervicogenic head pain with perineural steroid injection have been published. [43] [44]
There are no published reports of placebo-controlled trials of greater occipital nerve blocks, with or without steroid.
However, one study demonstrated no response in a randomized trial of intracutaneous saline compared with sterile
water for treating cervicogenic headache and has been referred to as a control of sorts. Although controversy
[45]
remains regarding the etiologic mechanisms of this type of pain, greater occipital neural blockade continues to show
promise in alleviating head pain associated with occipital neuralgias and awaits well-designed trials to clearly define
its potential.
Intercostal Nerve and Poststernotomy Neuroma
Defalque and Bromley examined the use of repeated local anesthetic injection as well as neurolysis in the
[46]
treatment of 54 patients with poststernotomy intercostal neuralgia. On an average of 6 weeks after surgery, this
group of patients developed pain described as constant, severe, and burning at one or both sternal borders. All
patients reported worsening of pain with Valsalva maneuvers and use of the arms, and some had radiation of pain to
other regions of the chest wall. Patients also had reproduction of pain and concomitant radiation with palpation of
discrete points along the sternal border and upper interchondral spaces, which was thought to represent neuroma
formation involving anterior branches of intercostal nerves. A few days apart, two injections were performed at
these points with 0.75% bupivacaine and epinephrine 1:200,000. All patients reported complete relief for at least 8
hours after injection. These injections were then repeated up to four times if pain recurred. Recurrence beyond this
point was treated again to a maximum of 4 times with 6% phenol neurolysis, and beyond this with 100% alcohol.
Fifty-seven percent of patients reported at least 6 months of relief following two to four injections with local
anesthetic, with an additional 31% after neurolysis. Of note, these blocks were not true intercostal nerve blocks and
do not provide information regarding effects thereof. Nevertheless, this study provides useful information for further
studies in treating intercostal neuralgia. No controlled trials of intercostal nerve blockade have been reported in the
treatment of neuropathic pain.
UPPER EXTREMITY BLOCKS

Median Nerve
Studies of perineural steroid injection, generally combined with local anesthetic, for the treatment of carpal tunnel
syndrome were examined by Abram. Initial efficacy was found in multiple studies to range from 77% to 92%.
[47]
However, many studies that followed patients for at least 1 year found continued benefit in only 13% to 22%.
A prospective, randomized, double-blinded, placebo-controlled study measuring the short-term efficacy of steroid
versus saline injection into the carpal tunnel was performed by Girlanda and associates. Thirty-two patients whose
[48]
clinical diagnosis of carpal tunnel syndrome was supported by electromyographic and nerve conduction findings
were included. Half of the affected nerves were randomly assigned to receive 15 mg methylprednisolone and half to
receive saline. A scoring system was devised, incorporating symptoms such as pain and paresthesias and signs such
as weakness and atrophy. Repeat electrophysiologic data were also gathered at routine intervals lasting for 2 months
after treatment. Ninety-three percent of the individual nerves treated with steroid were found to show significant
symptomatic improvement. Placebo effect was negligible, and there was little effect compared to baseline signs and
electrophysiologic profiles in either group. A nonplacebo-controlled trial of steroid injection performed with follow-
up intervals lasting through 2 years after treatment was also reported in the same publication. Fifty-three patients
were included, and results at 2 months were comparable with those of the placebo-controlled trial. Symptomatic
improvements persisted in 50% at 6 months, and in only 8% at 24 months. [48]
1182
With regard to the use of local anesthetic versus local anesthetic plus steroid injection for carpal tunnel syndrome,
Dammers and colleagues compared 10 mg lidocaine with 10 mg lidocaine plus 40 mg methylprednisolone in a
[49]
randomized, double-blinded trial. Sixty patients were included, and treatment success was defined as symptomatic
resolution or reduction to minor symptoms not requiring further treatment. After 1 month, improvement was noted
in 20% of the local anesthetic alone group and 77% of the local plus steroid group. After 1 year, 7% of the local
anesthetic group and 50% of the combination group continued to show improvement.
Findings such as these suggest that, although many may not, some patients may achieve prolonged benefit after
steroid and local anesthetic carpal tunnel injection, possibly preventing the need for surgery.
Radial Nerve
True radial tunnel syndrome is a relatively uncommon condition that is somewhat analogous to carpal tunnel
syndrome in its association with nerve entrapment and subsequent electrophysiologic findings, motor deficit, and
pain. Treatment by radial tunnel decompression has had unpredictable results.
[50] [51]
Sarhadi and coworkers reported retrospectively on 26 patients with suspected radial tunnel syndrome treated with
[52]
steroid injection. Patients were included who had reproduction of pain with palpation over a point along the course
of the radial tunnel, pain with resisted supination or extension of the middle finger, and temporary complete
resolution of pain after local anesthetic injection of the tunnel at the tender site. All patients were treated with
corticosteroid injection of the radial tunnel, and one patient underwent physical therapy as well. Almost two thirds
of the patients experienced long-term pain relief. Nine patients who did not report benefit underwent surgery, after
which 7 reported complete relief.
Ulnar Nerve
Management of ulnar neuropathy resulting from cubital tunnel syndrome, the second-most common nerve
entrapment condition of the upper extremity, has been reviewed in a meta-analysis by Mowlavi and associates. [53]
Operative and nonoperative treatments (five studies, 54 patients) were compared. Nonoperative treatment of mild
cases consisting of pain, intermittent paresthesias, and subjective (but not measurable) weakness showed total relief
in 65% of patients. However, too few studies included in the meta-analysis provided sufficient detail to draw
conclusions regarding specific nonsurgical techniques.
Treatment of ulnar neuropathy comparing elbow splinting with ulnar perineural injection of 40 mg triamcinolone
with 10 mg lidocaine at the elbow in addition to splinting was reported by Hong and colleagues. Twelve nerves in
[54]
10 patients were randomized to one or the other treatment. Assessment of symptoms and signs, including nerve
conduction studies, was made before treatment, 1 month after treatment, and 6 months after treatment. At 6 months,
both groups demonstrated symptomatic as well as electrophysiologic improvement. Another randomized trial
involving 57 ulnar nerves in 39 patients compared medial epicondylectomy or external decompression with
perineural steroid injection. Results showed significant and similar improvement that was sustained in both groups
[55]
for 2 years after treatment.
ILIOINGUINAL, ILIOHYPOGASTRIC, OBTURATOR, AND GENITOFEMORAL NERVES
Neuralgias have been noted to occur after surgery of the abdomen and pelvis, including, but not limited to, inguinal
herniorraphy, cesarean section, and appendectomy. They may also occur after blunt and penetrating injuries. These
patients may have a clinical presentation associated with neuropathic symptoms within the distributions of the
ilioinguinal, iliohypogastric, and/or genitofemoral nerves. There are no published, controlled clinical trials of
peripheral blockade of these nerves in the treatment of neuropathic pain. Limited numbers of case reports and a
small number of clinical trials of neurectomy are found in the surgical literature, generally with brief reference to
neural blockade as a diagnostic test.
Harms and colleagues described two case reports of genitofemoral neuralgia in which neural blockade was used
[56]
for diagnosis. One patient with persistent groin pain and hyperalgesia after inguinal hernia repair underwent three
unsuccessful repeat operations for diagnosis and treatment. Ilioinguinal nerve block with 0.125% bupivacaine
provided minimal relief, but genitofemoral block via L1 and L2 paravertebral blocks with 0.5% bupivacaine and
0.75% lidocaine with epinephrine 1:200,000 resulted in complete but transient pain resolution. Based on this
information, the patient underwent genitofemoral nerve excision and remained free of pain for the 18-month follow-
up period. A second similar patient, who obtained significant but incomplete relief after ilioinguinal block with
1183
bupivacaine, was eventually treated successfully with surgical excision of sections of both ilioinguinal and
genitofemoral nerves. No follow-up interval was reported for this patient.
In a retrospective look at 30 patients treated over 7 years, Starling and associates reported successful pain relief
[57]
with neurectomy after diagnosis with nerve block in genitofemoral and ilioinguinal neuralgia. No controlled studies
of the use of nerve block series in the treatment of these neuralgias are available.
Obturator neuropathy has been observed after surgical manipulation and in association with retroperitoneal
hemorrhage. Obturator neuralgia associated with forceps delivery has been discussed in a case report in which [58]
obturator nerve block with lidocaine and methylprednisolone resulted in 2 months of relief, followed by a second
block providing at least 2 years of relief.
Development of neuralgia after abdominopelvic surgery, which occurs with an unknown overall incidence, may be
more common than available published reports would suggest. Most studies have used local anesthetics primarily
for diagnostic purposes. There is insufficient evidence to draw conclusions about the use of local anesthetic and/or
steroid perineural injections in the treatment of these specific neuropathic pain syndromes.
Pudendal Nerve
Pudendal neuralgia has been implicated in certain chronic perineal pain syndromes by anatomic and
electrophysiologic studies. Although the technique of computed tomography (CT)-guided pudendal nerve
[59] [60] [61]
block has been described, no controlled trials of any pudendal perineural injection techniques have been reported
[62]
in the treatment of neuropathic pain.
Mauillon and coworkers studied the use of pudendal nerve block as a predictor of the efficacy of surgical
[63]
decompression. Their subjects were 12 consecutive patients who complained of pain, burning, or pinching in the
distribution of the pudendal nerve, their symptoms were exacerbated by sitting. Evidence of pudendal neuropathy
was reinforced with EMG and nerve conduction findings. CT-guided pudendal nerve block was performed with use
of 5 mL of 1% lidocaine and 3.75 mg cortivazol, a long-acting glucocorticoid. If two consecutive blocks at the
ischial spine were unsuccessful, a third was performed at the pudendal canal. Absence of long-term relief thereafter
was used as an indication for surgery. Results showed that 1 of 12 patients obtained no relief with blocks; 1 patient
reported relief of several hours; 4 had relief for days; 3 had relief for weeks but less than 1 month, and 3 had relief
for greater than 1 month. Two patients had extended analgesia for 14 weeks or longer. All patients subsequently
underwent surgery. Complete relief for any duration after the block seemed predictive of operative success.
Interestingly, one half of these patients had known depression, and only one depressed patient had a successful
outcome with surgery. Despite the high incidence of depression, which may hinder results after interventional pain
treatment techniques, 83% of patients demonstrated analgesia beyond the expected duration of the local anesthetic.
This again raises the issue of whether nerve blocks with local anesthetic and steroid may provide a window of
opportunity during which adjuvant therapies may be added and effective combination therapy realized.
LOWER EXTREMITY BLOCKS

Lateral Femoral Cutaneous Nerve
Injury to the lateral femoral cutaneous nerve can result in a neuropathic pain syndrome known as meralgia
paresthetica. Multiple etiologies have been reported, including surgical trauma, sports-related injuries,
[64] [65]
compressive tumors, limb length discrepancy, degeneration of the symphysis pubis, and nerve entrapment by the
[66] [67] [68]
inguinal ligament. In most cases, no underlying cause can be determined. Characteristic features are pain, sensory
loss, allodynia, and paresthesias in the anterolateral aspect of the thigh. Patients often report worsening pain with
standing and walking and relief with sitting.
Spontaneous improvement is the usual natural history of meralgia paresthetica. When pain persists despite
[69]
conservative management with oral analgesics, neural blockade with or without a perineural steroid has been
employed as well as neurolysis and decompressive surgery for refractory cases. Despite a large body of literature
describing the condition and case reports of prolonged relief after nerve blocks with local anesthetic and steroids, [70] [71]
no controlled trials of perineural injection techniques have been reported.
Ivins reported a series of 14 patients with meralgia paresthetica (one patient had bilateral symptoms) who
[72]
underwent injection of “a small amount of bupivacaine and epinephrine” adjacent to the lateral femoral cutaneous
nerve as it passed near the anterosuperior iliac spine. A second injection consisting of a mixture of bupivacaine and
1184
methylprednisolone followed. Pain was completely relieved in each case for several hours after both injections. Five
patients experienced complete resolution with follow-up that ranged from 28 to 60 months. Nine patients reported
recurrence of pain within 2 to 4 weeks after the second injection. Seven patients subsequently underwent surgery.
An earlier retrospective report included more subjects (277 patients over a 25-year period) and evaluated results
after conservative management and surgery for meralgia paresthetica. Conservative management consisted of
[73]
removal of any inciting factors such as tight undergarments and belts around the waist, avoidance of hip extension,
application of ice to the area of presumed nerve constriction, nonsteroidal anti-inflammatory medications, and
perineural injection of local anesthetic with steroid. Overall, 50% of patients received one to four blocks over a 6- to
12-month period, and 91% of all patients demonstrated satisfactory relief of symptoms. Relief occurred in 23 of 24
patients who went on to surgery.
The efficacy of percutaneous neurolytic techniques for meralgia paresthetica is not known. Van Eerten and
colleagues compared open neurolysis (10 patients) with transection of the lateral femoral cutaneous nerve (11
[74]
patients). Complete relief of symptoms was noted in 3 of 10 patients undergoing neurolysis and 9 of 11 for
transection.
Retrospective studies support the use of injection techniques in conjunction with other conservative therapies in the
treatment of meralgia paresthetica. However, controlled trials are lacking that would provide definitive evidence for
the utility of nerve blocks.
Sciatic and Common Peroneal Nerves
The use of sciatic nerve blocks in patients with sciatica has received attention primarily because of observations of
pain reduction in patients in whom the likely pain generator is a lesion proximal to the site of the block. Case reports
describe transient relief of sciatic pain after sciatic nerve block in patients who likely had nerve root pathology. [75]
Five patients are described, all of whom had radicular pain and EMG findings consistent with L5 or L5 to S1
radiculopathy. Two of these patients also had extradural defects seen on a myelogram and, in one case, on a lumbar
CT scan. All of these patients experienced relief of sciatic pain as measured by VAS pain scores, some for only
hours or days, but more than 1 week in one patient. Equal doses of local anesthetic used in trigger point injections in
these patients did not produce similar analgesia, which suggests that systemic absorption was not the likely
mechanism. Proximal spread of injected drug at the sciatic nerve to nerve roots is feasible but not completely
supported by results of radiolabeling techniques. These observations are contradictory to the concept that nerve root
compression or inflammation is solely responsible for the generation of afferent information that can be perceived as
peripheral pain in a nerve's distribution. The implication that input originating distal to a nerve tissue lesion may
play a significant role in the pain associated with the lesion has led to reassessment of the diagnostic meaning of
nerve blocks in general.
A prospective, randomized, double-blinded, placebo-controlled trial of common peroneal nerve blocks was
performed by Tajiri and associates. This trial sheds light on the nonspecificity of peripheral neural blockade
[76]
techniques. Twenty-two patients, diagnosed with sciatica on physical examination, who had intervertebral disc
herniations at L4 to L5 or L5 to S1 identified by subsequent myelography or magnetic resonance imaging were
randomized to receive common peroneal injections of either lidocaine or saline. Injections were made at the fibular
head, a location chosen for its anatomic distance from the nerve roots, with either 6 mL of 2% lidocaine or 6 mL of
saline. Pain scores were assessed 15 minutes after the blocks were performed, and the lidocaine group alone showed
significant relief. Without long-term follow-up, this study provides little information regarding therapeutic effect.
However, it does suggest that neural blockade distal to the presumed site of origin can produce reductions in
neuropathic pain.
Tibial Nerve
Tibial nerve entrapment syndromes, of which tarsal tunnel syndrome is most common, may result from metabolic,
vascular, injury-related, and idiopathic factors. Reports suggest that patients with carpal tunnel

Textbook of Regional Anesthesia PDF

Hochgeladen von

Dokumentinformationen

Originaltitel

Copyright

Verfügbare Formate

Dieses Dokument teilen

Dokument teilen oder einbetten

Freigabeoptionen

Stufen Sie dieses Dokument als nützlich ein?

Sind diese Inhalte unangemessen?

Copyright:

Verfügbare Formate

Textbook of Regional Anesthesia PDF

Hochgeladen von

Copyright:

Verfügbare Formate

Textbook of Regional Anesthesia

Anesthesiology is an ever-changing field. Standard safety precautions must be followed, but as

Library of Congress Cataloging-in-Publication Data

Acquisitions Editor: Allan Ross

TEXTBOOK OF REGIONAL ANESTHESIA ISBN 0–443–06569–1

Copyright © 2002 Elsevier Science (USA). All rights reserved.

Printed in the United States of America.

Last digit is the print number: 9 8 7 6 5 4 3 2 1

Associate Professor of Anesthesia,

Associate Professor of Anesthesiology,

SHAUNA BAUGHCUM CPC

Head, Department of Anesthesia and Resuscitation,

Assistant Professor of Anesthesiology,

Associate Professor of Anesthesiology,

Associate Professor of Anesthesia,

MILES DAY MD, DAPBM

Assistant Professor of Pain Management/Anesthesiology,

Perth Pain Management Centre,

Progressive Pain Management

Associate Professor of Anesthesiology,

Associate Professor of Anesthesiology;

JAMES E. HEAVNER DVM, PhD

Professor of Anesthesiology and Physiology,

Assistant Professor of Anesthesiology,

Texas Wesleyan University,

ALAN D. KAYE MD, PhD

Professor and Chairman,

Assistant Professor of Anesthesiology,

Assistant Professor of Anesthesiology,

DONALD H. LAMBERT MD, PhD

Assistant Professor of Anesthesiology,

Pharmaceutical Licensing Group,

Assistant Clinical Professor of Anesthesiology,

LELAND LOU MD, MPH, DABPM

Assistant Professor of Pain Management,

Assistant Professor of Anesthesiology,

Assistant Professor of Anesthesiology,

Clinical Instructor (Voluntary),

Associate Professor of Anesthesiology and Obstetrics/Gynecology,

Assistant Professor of Anesthesiology,

Servizio di Anestesia e Rianimazione,

Assistant Professor of Anesthesiology,

Professor Sackler Faculty of Medicine,

Comprehensive Pain Care,

Regional Hospital “S. Salvatore”

Assistant Professor of Anesthesiology and Critical Care Medicine,

Professor of Postgraduate Medical Especiality in Anesthesia,

Grober and Murray Professor,

P. PRITHVI RAJ MD, DABPM

MIGUEL ANGEL REINA MD

Department of Anesthesiology and Critical Care,

Assistant Professor of Postgraduate Medical Course in Pain Clinic,

Clinica del Dolor de Barcelona,

ROBERT P. SANDS JR. MD

Clinical Assistant Professor of Anesthesiology,

PHILLIP S. SIZER JR. MEd, PT, MOMT, PhD(c)

Texas Tech University Health Sciences Center,

Associate Professor of Anesthesiology,

PRABHAV TELLA MPH

Research Program Coordinator,

Assistant Professor of Anesthesia,

Associate Professor of Clinical Anesthesiology,

Assistant Professor of Anesthesiology,