Anesthesiology Clin N Am

23 (2005) 573 – 595

Pediatric Anesthesia Historical Perspective

Andrew T. Costarino, Jr, MDa,b,T, John J. Downes, MDc,d
a
Department of Anesthesiology and Critical Care Medicine,
the Alfred I. duPont Hospital for Children, 1600 Rockland Road, PO Box 269,
Wilmington, DE 19899, USA
b
Jefferson Medical College, 1025 Walnut Street, Philadelphia, PA 19107, USA
c
Department of Anesthesiology and Critical Care Medicine, The Children’s Hospital of Philadelphia,
Philadelphia, PA 19104, USA
d
University of Pennsylvania School of Medicine, Philadelphia, PA, USA

The pain and anxiety experienced with all but the most minimal operation
without the benefits of anesthesia for us or for our children is incomprehensible
today. Anesthesia developed in the nineteenth century allowed many of the
advances that occurred in the twentieth century that make up what we currently
take for granted. Figs. 1 and 2 are images of two important paintings by the
American artist Thomas Eakins, of Philadelphia. His ‘‘Gross Clinic’’ (Fig. 1) was
painted in 1875 and currently hangs in the Thomas Jefferson Medical College.
The picture shows Dr. Gross performing an operation at the Thomas Jefferson
Hospital. The physicians and nurses are dressed in street clothes; Dr. Gross wears
no gloves or mask, and there are no barriers to reduce contamination of the
wound. The patient undergoing surgery, however, is receiving a general anes-
thetic, provided by an open-drop technique using a gauze cloth over her face [1].
Fig. 2 is Eakins’ ‘‘Agnew Clinic,’’ painted in 1889, currently hanging in the
Hospital of the University of Pennsylvania. This picture, painted only 14 years
later, shows some significant technological advances. Dr. Agnew in his surgical
amphitheater wears gloves and a gown, and his assistant, Dr. J. William White, is
gloved, and he and the other attendants are clothed in a way that indicates that
asepsis techniques had entered clinical practice. Dr. Agnew’s patient is receiving
an anesthetic provided by the intern Dr. Ellwood Kirby, holding a canister of
ether in his right hand [2]. Eakins’ two paintings illustrate the clinical application

T Corresponding author. Department of Anesthesiology and Critical Care Medicine, the Alfred I.
duPont Hospital for Children, 1600 Rockland Road, PO Box 269, Wilmington, DE 19899.
E-mail address: acostari@nemours.org (A.T. Costarino, Jr).

0889-8537/05/$ – see front matter D 2005 Elsevier Inc. All rights reserved.
doi:10.1016/j.atc.2005.08.005 anesthesiology.theclinics.com
574 costarino & downes

Fig. 1. ‘‘The Gross Clinic’’ painted in 1875 by Thomas Eakins (American 1844–1916), Thomas
Jefferson Medical College. The picture shows Dr. Gross operating in street clothes and the patient
receiving a general anesthetic provided by an open-drop technique, using a gauze cloth over her face.

Fig. 2. ‘‘The Agnew Clinic’’ painted in 1889 by Thomas Eakins (American 1844–1916), Hospital of
the University of Pennsylvania. Technologic advances are evident, compared with the earlier painting
of the Gross clinic. Dr. Agnew wears gloves and a gown, and the patient breaths anesthesia through
some type of ether inhaler.
 pediatric anesthesia historical perspective 575

of what are arguably the two most important medical advances of the nineteenth
century. The first, the discovery of surgical anesthesia, an American discovery,
allowed aggressive surgical management of disease. The second, the elucidation
of the germ theory of disease, a European discovery, allowed the control of
acquired infections and reduced the incidence of infectious complications to
surgery. Looking beyond the nineteenth century to the present day, these two
advances must be considered the key components that allowed the development
of modern medicine.
This article examines how anesthesia evolved to serve the needs of children
[3–5]. Discussion includes milestones in technologic advancement related to
pediatric anesthetic care and how collaboration among pediatric surgeons,
neonatologists, and pediatric anesthesiologists has helped our specialty to
progress [6–12]. Conversely, the significant contributions of pediatric anesthesi-
ology to pediatric critical care medicine, pain management, and pediatric public
health care are also presented [12–16].

The nineteenth century

On March 30, 1842, Crawford W. Long, MD, a graduate of the University of

Pennsylvania School of Medicine, while practicing medicine in rural Georgia,
provided diethyl ether (‘‘ether’’) to a patient named James Venable to incise a cyst
on the patient’s neck [17]. Long had observed that the occasional bruises
encountered by participants in ‘‘ether frolics’’ caused no pain when they occurred
during the ‘‘exhilarating’’ effects induced by the inhalation of ether vapor. The
practice of inhaling ‘‘sulfuric ether’’ or nitrous oxide for its hallucinatory effects
was not unusual in the United States at that time. Dr. Long correctly concluded
that he might perform painless minor invasive procedures while patients were in
this state of apparent anesthesia.
Describing his therapeutic trial with the patient James Venable, Long
recorded: ‘‘The patient continued to inhale ether during the time of the operation;
when informed it was over, seemed incredulous, until the tumor was shown to
him’’ [17]. This first recorded experience with surgical anesthesia preceded by
more than 4 years the highly publicized demonstration of ether anesthesia by the
dentist William T.G. Morton at the Massachusetts General Hospital on October
16, 1846. Dr. Long waited until 1849 to report his ‘‘experiments’’ because of his
desire to have a large series. Nonetheless, Long’s primacy has been confirmed
through published eyewitness accounts and the scrutiny of historic scholars.
The public demonstration of anesthesia by Morton, in 1846, was more widely
publicized, and its news spread rapidly. Within 2 months of Morton’s work, ether
had been used for patients in Paris, France, and in Scotland. In the United States,
in the year after the Morton demonstration, the Massachusetts General Hospital
case records list 83 surgeries in which 45 (54%) patients received anesthesia.
Children received anesthesia from the start of these earliest clinical appli-
cations. Long’s third patient was an 8-year-old child, about whom he recorded,
576 costarino & downes

‘‘My third experiment in etherization was made on the 3rd July 1842, and was
on a Negro boy, the property of Mrs. S. Hemphill, who resides nine miles
from Jefferson. The boy had a disease of the toe, which rendered its amputation
necessary, and the operation was performed without the boy evincing the least
sign of pain’’ [18]. Anesthesia care of children also seemed to take priority;
for example, in the surgical records of the Massachusetts General Hospital from
1846 to 1947, four of the five pediatric cases (80%) received anesthesia.

Fig. 3. Illustration (A) and photograph (B) of Wilson and Pinson’s nickel-plated steel ether apparatus,
the ‘‘Bomb.’’ This early vaporizer was filled with ether and placed in a container of hot water. The
rubber tube (D) allows direction of the vapor to the patient. Dial (B) allows adjustment of the amount
of vapor. (C) Yankauer no. 75 and Dunkley no. 77 ether inhalers for open-drop technique. (A–C, Allen
and Hanburys, Ltd. A reference list of surgical instruments and medical appliances [catalogue].
London: Allen and Hansbury, Ltd; 1930.) (D) Ether inhalers. (Courtesy of Dr. Gary Enever, Northern
Schools of Anaesthesia. Copyright by Dr. Gary Enever. The Brian Welsh Memorial Museum of Anaes-
thesia. Available at: http://www.ncl.ac.uk/nsa/museum.html. Accessed July 31, 2005.) (E) Magill’s
1930 endotracheal ether apparatus. A heating chamber formed by the space between two metal
cylinders, the innermost of which must be kept filled with water at a temperature of not less than
1208F. The ether is driven into the heating chamber through a drop sight-feed by maintaining a slightly
increased pressure in the bottle with a hand bellows. The apparatus can be used with a motor blower,
compressed air, oxygen, or foot bellows. (Allen and Hanburys, Ltd. A reference list of surgical instru-
ments and medical appliances [catalogue]. London: Allen and Hansbury, Ltd; 1930.)
pediatric anesthesia historical perspective 577

Fig. 3 (continued).
578 costarino & downes

Similarly, from the beginning, children were observed to be at higher risk for
certain complications related to anesthesia. Morton himself noted that very
young subjects were more likely to have nausea and vomiting following surgery,
and he eventually refused to administer ether to children because of that problem.
Another example comes from a report in an issue of the London Gazette,
sometime in 1847, of an 11-year-old boy who received anesthesia to undergo
amputation of a leg. The paper reports that the anesthesia ‘‘was not totally
effective and in addition, death occurred shortly following the surgery.’’ In
the same year, in the Edinburgh Medical and Surgical Journal there is a case
report of a 15-year-old girl who underwent anesthesia with chloroform for the
removal of a toenail. She had a cardiac arrest, and the report concluded that
the death was secondary to the anesthetic. Thus, the first recorded anesthetic
deaths were in children!
John Snow of London, England, who famously provided anesthesia to Queen
Victoria during her labor for the delivery of her eighth child (Prince Leopold),
is considered the father of anesthesia practice [19]. His care of the Queen paved
the way for widespread acceptance of the value of the anesthesia practice. He had
begun providing anesthesia for adults and children in 1847, using diethyl ether
[20]. Soon, however, he switched to the more potent and rapidly acting
halogenated ether, chloroform. In 1857, one decade into his practice, Snow
reported his experience with chloroform anesthesia on several hundred children,
including 186 under that age of 1 year [19]. By skillful observation and analysis,
he concluded that in children ‘‘The effects of chloroform are more quickly
produced and also subside more quickly than in adults, owing no doubt to
quicker breathing and circulation’’ [19]. This statement would be proven correct
more than a century later with sophisticated gas analyzers and measurements of
ventilation and cardiac output in infants [10,21–23].
During Snow’s time and well into the twentieth century, thousands of new-
borns, infants, and children survived surgery and anesthesia in North America,
Europe, and elsewhere, but in the hands of those less skilled than Dr. Snow, the
use of chloroform led to an unacceptably high incidence of hypotension and
cardiac arrest. Diethyl ether proved to be by far the most effective and the safest
agent for widespread application. It was usually applied using an open-drop
method, until the invention and manufacture of reliable vaporizers and precision
flow meters for concomitant nitrous oxide and oxygen administrations in the
1920s (Fig. 3).

First half of the twentieth century

Generally, between 1846 and the 1940s, anesthesia was a risky event for
children. The understanding of children’s physiology was crude in comparison
with adult cardiorespiratory physiology [18,24,25]. In addition, there was poor
anesthesia equipment, little ability to provide vascular access, and no under-
standing of resuscitation techniques; and surgical techniques were primitive, and
 pediatric anesthesia historical perspective 579

antibiotics did not exist. Few physicians devoted their clinical practice to
anesthesia, let alone to anesthesia for children. Any success that occurred before
the 1940s was the result of the dedicated work of a few practitioners who
contrived special pediatric anesthesia equipment for their own practice and
committed their energy and talents to anesthesia management of infants and
children and the training of others.
One individual of this early period who deserves recognition and praise for his
difficult pioneering work is Dr. Charles Robson [4,26]. He is likely the first
person who could be labeled a pediatric anesthesiologist. A McGill University
medical graduate, Robson had 1 year of formal training and 3 years’ practice as
the senior ranking anesthetist of the Canadian Expeditionary Force during World
War I. In 1919, he accepted a full-time position as Chief Anesthetist at Toronto’s
Hospital for Sick Children [27].
In Robson’s 1925 overview lecture [28] on the challenges confronting the
pediatric anesthesiologist, it is interesting to note the accuracy of his clinical
observations in the context of the limitations of his tools and his incomplete
scientific knowledge of developmental physiology—knowledge we now take for
granted. For example, Robson appreciated that children have different anesthetic
requirements than adults do, but concluded that this observation was related to
airway obstruction and an inadequate fit of the mask. The subsequent studies that
determined the variation of minimal alveolar concentration with age were then
unavailable [29,30], but his experience allowed him to appropriately emphasize
the need for age-appropriate airway equipment and the vital requirement to assure
a patent airway during induction.
Dr. Robson described, in a candid and yet alarming account [31], how open-
drop ether administration without tracheal intubation was his routine anesthetic
approach. This was the standard of practice at the time, although he acknowl-
edged that cyclopropane with tracheal intubation using a ‘‘soft rubber catheter
which fits gas tightly’’ proved preferable for complex procedures; he did not state
whether ventilation was assisted or controlled [31]. Like most anesthesiologists
of his time, he was ‘‘prepared to do, and able to do, a tracheostomy’’; however, he
also believed pediatric anesthesiologists ‘‘should be able to pass an endotracheal
catheter, by the sense of touch in any patient under anesthesia, whose mouth can
be opened’’ [28].
Some additional comments and observations Robson made of pediatric
anesthesia in the 1920s are also of interest [28]. He advocated preinduction
fasting, so that ‘‘the stomach is empty in from three to four hours after the taking
of food.’’ He observed that trauma victims have slower gastric emptying: ‘‘[W]e
must not consider ourselves safe in giving an anesthetic to accident cases, even of
a minor nature, believing the stomach to be empty in four hours.’’ He described a
trick to get his young patients to cooperate during induction; he would ask them
to blow through the mask, ‘‘This is a psychological trick, for the natural impulse
is to blow away a strange-smelling vapor. Obviously, the patient ventilates very
thoroughly.’’ He also disagreed vigorously with many of his colleagues who
believed neonates needed no anesthesia [4,28].
580 costarino & downes

One of the most important figures in the history of pediatric anesthesia is

Dr. Philip Ayre (Fig. 4). He was a visiting anesthetist at the Babies’ Hospital,
Newcastle-Upon-Tyne, England, when he developed an especially suitable pedi-
atric anesthesia breathing system for use with tracheal intubation during the re-
pair of cleft lip and palate deformities in infants, in 1938 [24,32]. The key
element was the T-shaped piece through which fresh gases were introduced at a
relatively high flow rate, through the side inflow tube (Figs. 5 and 6). It was a
valveless system that minimized dead space and resistance to breathing. This
innovation was one of the first important mechanical developments in anesthesia
practice. It allowed compensation for the special cardiorespiratory physiologic
needs of infants and small children during anesthesia. Ayre recommended that the
fresh gas flow should be twice the minute volume. Additionally, he advocated
that the reservoir tube volume should be one third that of the tidal volume.
He and later practitioners modified the use of the T piece and expanded its
application, for example, to control ventilation by the intermittent occlusion of
the open end of the reservoir tube. The Ayre T piece formed the basis for the
modern semi-open pediatric anesthesia systems as well as mechanical ventilator
circuits and modalities.
Many of the early twentieth century advances in anesthesia came in response
to challenges presented by the quest for surgical solutions to treating congenital
and acquired diseases. The primary surgical innovator whose work made
inevitable the evolution of pediatric anesthesia was William T. Ladd, an obste-
trician and pediatric surgeon. Dr. Ladd devoted his enormous talent as a clinician,
teacher, and author, from 1917 until his retirement in 1945 to the surgical care of

Fig. 4. Portrait of Philip Ayre. (Courtesy of Dr. Gary Enever, Northern Schools of Anaesthesia.
Copyright by Dr. Gary Enever. The Brian Welsh Memorial Museum of Anaesthesia. Available at:
http://www.ncl.ac.uk/nsa/museum.html. Accessed July 31, 2005.)
 pediatric anesthesia historical perspective 581

Fig. 5. Assorted sizes of Ayre’s T piece. (Courtesy of Dr. Gary Enever, Northern Schools of Anaes-
thesia. Copyright by Dr. Gary Enever. The Brian Welsh Memorial Museum of Anaesthesia. Available
at: http://www.ncl.ac.uk/nsa/museum.html. Accessed July 31, 2005.)

children at The Children’s Hospital in Boston. For this work he is considered the
father of pediatric surgery [15,33]. He and his successor as Surgeon-in-Chief,
Robert Gross, MD, trained most of the next generation of leading pediatric
surgeons in North America. Their work and that of their trainees required
participation and innovation by anesthesiologists who were dedicated to a
pediatric focus [5,9,27,34].
Early developments in cardiovascular surgery similarly created demands met
with advancement in pediatric anesthesiology. In 1939, Robert Gross, at The
Children’s Hospital, Boston, inaugurated pediatric cardiovascular surgery when
he successfully ligated a patent ductus arteriosus in a 7-year-old girl [35]. This
event was the first repair of a congenital cardiovascular lesion. In 1945, Gross
added the repair of a pediatric aortic coarctation [36]. Dr. C. Craaford, in Sweden,
also independently developed this operation. At the same time as Gross’ efforts in

Fig. 6. Ayre’s T piece operation. During inspiration, the patient inspires fresh gas from the reservoir
tube. During expiration, the patient expires into the reservoir tube. Although fresh gas is still flowing
into the system at this time, it is wasted because it is contaminated by expired gas. In the expiratory
pause, fresh gas washes the expired gas out of the reservoir tube, filling it with fresh gas for the next
inspiration. In the reservoir tube, the volume must be greater than the patient’s tidal volume, other-
wise the inspired gas will be contaminated by the surrounding air. (From Ayre’s T-Piece. Anesthesia
Equipment Resources. http://asevet.com/resources/circuits/ayres.htm. Accessed November 1, 2005;
with permission.)
582 costarino & downes

Boston, Alfred Blalock and Helen Taussig at Johns Hopkins Hospital, Baltimore,
MD, invented the palliative procedure for the tetralogy of Fallot [37].
Johns Hopkins Hospital anesthesiologists Merel Harmel and Austin Lamont
[14] provided the pediatric anesthesia support that helped make Blalock and
Taussig’s surgery and postoperative patient care successful. They reported on
their anesthetic management and the postoperative care and complications of
Blalock’s first 100 patients who received the Blalock-Taussig shunt operation
[14]. The patients ranged in age from 10 weeks to 20 years, and the authors
provided details of the operative conditions and support with endotracheal
cyclopropane and ether [14]. Five children died during or immediately after the
operation, and another 17 patients died later during their postoperative course.
The authors contend that anesthetic management might have played a role in the
death of nine of the patients. The achievements of these physicians were
remarkable, nearly 60 years ago, at a time when cardiovascular diagnoses were
at most uncertain, and patients usually underwent operations late in the course
of their disease, when their physical condition had become desperate. The
postoperative cardiopulmonary monitoring they had available was so limited as
to be nonexistent. Harmel and Lamont’s work is another example of surgical
progress in the treatment of congenital disease in children that spurred the clinical
and academic development of pediatric anesthesia.

After World War II

The American Board of Anesthesiology had been formed in 1938, giving

anesthesiology a professional status that was distinct and equal to medicine and
surgery. Medical science and clinical care had been greatly influenced by the
experiences and technologic advances associated with the world war. Addition-
ally, anesthesiology had produced some influential role models and educators,
such as Ralph M. Waters, who established the first anesthesiology residency
program at the University of Wisconsin. The stage was set in the late 1940s and
1950 for significant development in anesthesia care of children.
In North America, M. Digby Leigh, MD (Fig. 7), another McGill University
medical graduate who trained in Wisconsin with Dr. Waters, became the first full-
time director of anesthesia at the Montreal Children’s Memorial Hospital [26]. He
developed an anesthesia training program for the Canadian military during World
War II, which, after the war, developed into a 3-year diploma course in 1945 [26].
His program has been the model for residency programs for the last 60 years. In
addition to training physicians in anesthesiology and pediatric anesthesiology, he
invented pediatric anesthesia devices and performed clinical studies (eg, defining
bradycardia following the administration of succinylcholine in children).
Importantly, he wrote, with his colleague, Dr. Kay Belton, ‘‘Pediatric Anesthe-
sia,’’ the first textbook in the new subspecialty [27].
Gordon Jackson-Rees was the director of pediatric anesthesia at the University
of Liverpool. He began his medical training in Liverpool in 1937 and served in
 pediatric anesthesia historical perspective 583

Fig. 7. Portrait of M. Digby Leigh (1904–1975). (From the Canadian Anesthesiologists Society.
Copyright by the Canadian Anesthesiologists’ Society, 2005. All Rights Reserved.)

the Royal Air Force in Africa during World War II. He specialized in anesthesia
after returning to England in 1945, training with Robert Macintosh. He made two
related and important contributions to the care of anesthetized children. First, he
introduced the Jackson-Rees modification of Ayre’s T-shaped piece (Fig. 8)
[38,39]. His modification introduced an open-ended bag connected to the
expiratory limb, which allowed respiratory movements to be more easily moni-
tored when the patient was breathing spontaneously, and allowed intermittent
pressure ventilation when needed. Second, he helped to evaluate and safely
introduce curare and other relaxants into clinical practice [39], performing studies
to determine whether relaxant drugs had analgesic properties. He also performed
electromyography to determine the action of d-tubocurarine on muscle groups
[9,40]. Using his modified circuit and curare, he developed the so-called
Liverpool technique in the mid 1950s. The technique consisted of the tracheal
intubation of a neuromuscular blockade and controlled hyperventilation during
the surgery. Nitrous oxide and low concentrations of ether or other inhalation
agents provided amnesia and further anesthesia [39]. He found these methods
particularly suited to the newborn [40–42] or sick older infant, and this became
his standard approach for the management of children receiving anesthesia.
Robert M. Smith, MD, a Harvard Medical School graduate, also trained in
the military during World War II. Returning to Boston in 1946, he decided to
devote his entire career to pediatric anesthesiology. He joined the newly
appointed Ladd Professor of Pediatric Surgery, Robert Gross, as director of

Fig. 8. Jackson-Rees modification of the Ayre’s T piece. (From Ayre’s T-Piece. Anesthesia Equip-
ment Resources. http://asevet.com/resources/circuits/ayres.htm. Accessed November 1, 2005;
with permission.)
584 costarino & downes

anesthesia at The Children’s Hospital [33]. Dr. Smith contributed extensively

to the clinical appreciation of the unique anatomy and physiology of the new-
born and young infant as they apply to anesthetic care. Like Jackson-Rees in the
United Kingdom, Smith explored the safety and efficacy of tracheal intubation
and muscle relaxants in children. Maybe more importantly, he trained future
leaders in the subspecialty, and his textbook [43], the first truly comprehensive
textbook of pediatric anesthesia, remains current and is soon to be released in its
seventh edition.
In the period after WW II and into the 1960s, a small group of talented
and dedicated anesthesiologists concentrated their efforts in the care of children
and gradually developed pediatric anesthesia into a subspecialty. In addition
to Leigh, Jackson-Rees, and Smith, notable members of this group included
Dr. C. Ronald Stephen, Dr. Digby Leigh’s successor in Montreal, who invented
a pediatric breathing apparatus, trained numerous residents, and wrote an intro-
ductory textbook of pediatric anesthesia; Dr. Margot van Deming, who became
the first full-time director of anesthesia at the Children’s Hospital of Philadelphia
in 1950 and worked closely with the pediatric surgeon C. Everett Koop, MD,
where she demonstrated the relationship between anesthetic blood levels and the
anesthetic state in infants [25], as well as making other insightful observations;
and Dr. Robert Cope, who set new standards for British pediatric anesthesia
practice during his long tenure at London’s Great Ormond Street Hospital for
Sick Children.
Dr. Virginia Apgar (Fig. 9) deserves particular notice as a figure from
this period [44]. An obstetric and pediatric anesthesiologist at Columbia
Presbyterian Hospital and Babies’ Hospital in New York City, she is the second
anesthesiologist to be honored with a commemorative United States stamp
(1993), (the first was Dr. Crawford Long, in 1940). Her 1- and 5-minute Apgar
physical assessment scores for the newborn are the standard of care in hospitals
throughout the world [45]. She entered Columbia’s College of Physicians and

Fig. 9. Portrait of Virginia Apgar (1909–1974). (Courtesy of the National Library of Medicine,
National Institutes of Health, Washington, DC.)
 pediatric anesthesia historical perspective 585

Surgeons in 1929. After graduation, she began training in surgery but switched to
anesthesia after 2 years. She trained for 6 months with Ralph Waters at Wisconsin
and 6 months with Emory Rovenstine at Bellevue Hospital and returned to
Columbia as Director of the Division of Anesthesia in 1938. In 1949, in response
to a medical student’s question regarding the assessment of newborns, she jotted
down on a scrap of paper what became the Apgar score [45,46]. The system
was designed to determine which babies needed resuscitation. Later studies by
Apgar and colleagues demonstrated that hypoxia and acidosis were not normal at
birth, as had once been believed [46].
In addition, Apgar’s leadership at Babies’ Hospital helped pull together
pediatricians interested in newborn care, including L. Stanley James, Duncan A.
Holaday, Frank Moya, and Sol Schnider. Apgar and this group formed the
perinatal division, which helped spark the development of neonatology as a
subspecialty [44].

The 1960s and 1970s

The landmark studies of Geoffrey Dawes and colleagues at Oxford University

defined mammalian fetal transitional circulation and metabolism [9] and provided
new scientific evidence that helped clinicians interested in the care of sick
newborn. The work of these clinicians complimented that of their contemporaries
such as Drs. L. Stanley James of the Columbia neonatal group, who examined
birth asphyxia; McCance and Widdowson, who studied neonatal metabolism;
Cross and Dejour, who studied respiratory control; Hill, who defined thermo-
regulation; Friis-Hansen, who measured body fluid volumes and their redis-
tribution after birth; and Avery and Mead, who identified pulmonary surfactant
and its absence in the premature infant. These efforts established the scientific
impetus for modern neonatology and neonatal intensive care [3]. From 1960
onward, pediatricians in several major North American centers, such as Clement
Smith in Boston, William Silverman in New York City, and Paul R. Swyer in
Toronto, as well as pediatric surgeons and anesthesiologists such as C. Everett
Koop and Leonard Bachman in Philadelphia [6,34], studied cohorts of infants
suffering from asphyxia, respiratory distress syndrome, and other life-threatening
anomalies, and organized them into special neonatal units. In these settings,
the emphasis on care was no longer limited to nutrition and environmental sup-
port with minimal intervention. Vital system monitoring such as serial mea-
surement of arterial pH level and blood gas tensions and direct therapeutic
interventions, including mechanical ventilation [11,47], the administration of
buffers [21], and infusion of vasoactive medications to support the circulation
[11] became standards of care. The anesthesiologists working with these pedia-
tricians, surgeons, and researchers played a central role in successfully imple-
menting these treatments and other interventions suggested by new physiologic
discoveries [6,11,24,47].
586 costarino & downes

Nowhere was this collaboration more successful than in the management of

respiratory failure caused by prematurity. In 1963, President John F. Kennedy’s
son Patrick was born prematurely at 34 weeks gestational age and suffered from
hyaline membrane disease (or respiratory distress syndrome [RDS]). In a
desperate attempt to save him, the attending physician treated the infant with
experimental hyperbaric oxygen. Tragically, however, Patrick died at 2 days of
age. By the end of the decade, the clinical and research efforts described above
significantly altered such outcomes [11,13]. Particularly important for this
breakthrough was the work of the pediatric anesthesiologist Dr. George Gregory
and his mentor William K. Hamilton, MD, Chairmen of Anesthesia at the Uni-
versity of California, San Francisco [13]. Gregory, at the suggestion of Hamilton,
applied continuous positive airway pressure to infants who had RDS. Using an
endotracheal tube and a circuit based on Jackson-Rees’ modification of Ayre’s
T piece, he demonstrated a dramatic improvement in survival. This innova-
tion was the first of many strategies in pulmonary care of infants, developed
by pediatric anesthesiologists, which started to make neonatal respiratory failure
manageable [13,18,48].
Advances in neonatology provided essential information and techniques to
pediatric anesthesiologists and surgeons, enabling them to expand the scope of
surgical procedures, including cardiovascular surgery, and the surgical treatment
of smaller and sicker infants. Pediatric anesthesiologists regularly were the
providers of respiratory care and other support to these patients for days or weeks
after surgery and until the infant achieved cardiopulmonary stability [5,34].
Among the leaders who integrated neonatology, anesthesiology, and intensive
care were Drs. Alan Conn of Toronto, Leonard Bachman and Charles Richards
of Philadelphia [6], Ernest Salanitre and Herbert Rackow of New York, and
George Gregory in San Francisco.
As an outgrowth of these developments, pediatric anesthesiologists applied
the knowledge and techniques gained in caring for neonates to older infants
and children with a wide variety of life-threatening conditions [5]. Dr. Goran
Haglund, a pediatric anesthesiologist, established, in 1955, the first multidisci-
plinary pediatric intensive care unit, a 12-bed complex at the Children’s Hospital
of Goteburg, Sweden. In Europe and Australia during the mid 1960s, pediatric
anesthesiologists established similar units in Stockholm (Dr. Hans Feychting),
Liverpool (Dr. G. Jackson-Rees), and Melbourne (Drs. L.H. McDonald and John
Stocks) [5]. In North America, the first multidisciplinary physician-directed
pediatric intensive care unit (PICU) was established at the Children’s Hospital
of Philadelphia in 1967, a 7-bed facility with a full-time nursing staff [6]. One
of the present authors (J.J.D.) served as the medical director of this facility and
along with partners in anesthesiology and pediatrics developed a training pro-
gram in pediatric anesthesiology and critical care medicine (1968). Within a few
years pediatric anesthesiologists and their pediatrician colleagues established
similar PICUs at the Children’s Hospital of Pittsburgh (Dr. Stefan Kampschulte),
the Yale-New Haven Medical Center (Drs. Gilman and Talner), the Massachu-
setts General Hospital (Drs. Todres and Shannon), and the Hospital for Sick
 pediatric anesthesia historical perspective 587

Children in Toronto (Dr. Conn) [5]. A further extension of the pediatric anes-
thesiologists’ involvement in a life support outside the operating room was the
pioneering work of Dr. Alvin Hackel, a Stanford University pediatric anes-
thesiologist, in developing a highly coordinated regional emergency transport
system for infants and children in Northern California in the early 1970s that has
continued to the present time [49].

The 1980s and 1990s

One of the most significant developments for pediatric anesthesia during

the decade of the 1970s was the expansion of formal training programs of the
type that began in 1968 at the Children’s Hospital of Philadelphia. During this
period in many of the major children’s hospitals and leading university medical
centers, full-time pediatric anesthesiology departments or services, including
organized training programs and research, were established [15,18]. Physicians
have come from all over the world to train in the United States and Canada and
selected centers in England. In addition, junior residents in core anesthesia
programs have had the opportunity to train in high-quality pediatric programs for
2 to 3 months. This training fueled the growth of the pediatric anesthesia as a
specialty in the 1980s and helped to set the high standard for care and safety of
the surgical and critical care that currently exists for children in Western society.
The perioperative survival of all but the most moribund infants and children,
including preterm infants weighing under 1000 g and those with complex
structural heart disease, has become a general expectation of anesthesiologists,
surgeons, and pediatricians [50].
During the last two decades of the twentieth century, the stature of pediatric
anesthesia as a unique specialty and the workforce marshaled by the formal
training have facilitated several advances. One of these advances has been the
introduction and safety and effectiveness evaluation of new anesthetic agents
for children. Anesthesia with diethyl ether posed significant hazards and side
effects. Induction was prolonged, patients became combative, laryngospasm
occurred with regularity, and there was a high incidence of postoperative nausea
and vomiting. Despite these problems, diethyl ether was an anesthetic mainstay
for children well into the 1960s because of an absence of alternatives. The more
potent chloroform preferred by Snow was dangerously toxic [19,20]. Cyclo-
propane was for a time popular, but its explosive nature made it too dangerous.
Other agents had limited popularity until the introduction of halothane in 1956.
This agent was potent, well tolerated when inhaled, and relatively insoluble
compared with ether. Halothane represented a major advance, and coupled with
the improved anesthesia machines and other equipment that came available at the
same time, the safety of anesthesia induction and maintenance improved
dramatically. Long after halothane was abandoned in adult anesthetic manage-
ment care because of its hepatotoxicity, it remained a central component of
pediatric anesthesia [51].
588 costarino & downes

Halothane did have significant hemodynamic toxicity, but even though

subsequent agents (eg, enflurane and isoflurane) introduced in the 1970s
and 1980s had a better toxicity profile than halothane, these other agents
did not completely replace halothane because of its value during inhalation
induction of infants and young children. In the last 10 years, however, a replace-
ment has been introduced. Sevoflurane (fluoromethyl) has recently supplanted
halothane. This agent is well tolerated when delivered by inhalation and has a
much better circulatory toxicity profile compared with halothane [51,52].
Preliminary data from the Pediatric Perioperative Cardiac Arrest Registry [53]
suggest that a significant reduction in anesthetic-related cardiac arrests is at-
tributable to the replacement of sevoflurane with halothane (J.P. Morray, per-
sonal communication, 2005).
Another area of significant progress relates to patient preoperative prepara-
tion. Preanesthesia sedation of children had been a problematic component of
care since the start of the anesthesia era. Anesthesia induction by the mask
administration of ether was a difficult and dangerous experience for the patient
and the anesthesiologist. In the 1930s, progress was made in reducing the
preoperative level of anxiety and fear related to induction by the use of age- and
size-adjusted doses of ‘‘hypodermic’’ morphine and scopolamine [54–56]. This
practice also provided some postoperative analgesia after short procedures.
Pentobarbital also was added when its safety was demonstrated [55].
Eckenoff and colleagues [57], in 1953, made the first large assessment of
the effects of preanesthesia sedation and the perioperative experience of children
using a questionnaire administered to the parents of 612 children undergoing
otolaryngologic procedures. The authors conclude, ominously, ‘‘that 17% of the
children had personality changes that might be attributed in part to inadequate
preanesthesia or anesthetic management; that the younger the child, the more
likely the development of personality changes’’ [57]. The study found, however,
that preanesthesia sedation with pentobarbital clearly was associated with fewer
postoperative psychologic difficulties. In response to the findings of Eckenhoff
and colleagues, Bachman and Freeman [7] conducted a landmark study of
preanesthesia sedation of children in 1959. They demonstrated the efficacy of
intramuscular morphine, pentobarbital, and scopolamine in achieving a high
incidence of satisfactory preanesthesia sedation and postoperative analgesia. This
type of regimen dominated premedication practice for children for the next 15 to
20 years [58].
In the 1980s and 1990s, effective regimens for oral and nasal administration of
sedatives were introduced [58]. At the same time, preoperative teaching and
anticipatory guidance tailored to children’s needs came as the result of attention
by pediatric anesthesiologists. Some practitioners found benefit in having the
patient’s parents be present during induction. The recent landmark studies of Kain
and colleagues [59–61] have helped sort out the relative value and the
implications each of these techniques (discussed elsewhere in this issue).
There have been many other influential developments in pediatric anesthesia
during the last decades of the twentieth century (Table 1) [62–103], but a few
 pediatric anesthesia historical perspective 589

Table 1
Important developments in pediatric anesthesia, 1980–2000
Selected developments References
Better understanding of the use of narcotics in small infants [62–65]
Growth of outpatient surgery [11,57,66–68]
Awareness and management of post anesthetic apnea in premature infants [69–72]
Addressing the pain response in neonates [73–78]
Inauguration of the Society of Pediatric Anesthesia [79]
Pediatric pain management [55,75,80–85]
Anesthesia education —
Pediatric cardiac anesthesia as subspecialty [86–98]
Pediatric Perioperative Cardiac Arrest Registry outcome research [49,52,95–97]
Evidence to help better define preoperative fasting practice. [79,98–100]
Defining safe procedural sedation practice for nonanesthesiologists [86,101–103]

deserve special mention. First, the dramatic improvement in noninvasive

cardiopulmonary monitoring capability has greatly reduced the risk of anesthesia
and perioperative care [104]. Pulse oximetry, capnometry, and automated
oscillometric monitoring of systemic arterial pressure, all introduced in the
1980s, are now considered standards of care [105]. Similarly, invasive techniques
for cardiovascular monitoring and vascular access have benefited from the
miniaturization of improved reliability. The evaluation and treatment of the
circulation, nutritional support, and other important therapies are possible even in
the smallest of infants. Other monitoring techniques such as intraoperative
neurologic monitoring (discussed elsewhere) are now improving the care that
pediatric anesthesiologists can provide to children.
Pediatric anesthesiologists’ use of noninvasive cardiorespiratory monitors,
particularly pulse oximetry, has in turn allowed a better understanding of
developmental physiology and the clinical response to anesthetics. An example
or this is the phenomenon of postanesthesia apnea in infants, first noted in the
early 1980s [64]. Concern about this complication has had a significant influence
on anesthesia practice during the last two decades. Former preterm infants
younger than 50 to 55 weeks postconceptual age are at greater risk than are term
infants for incurring postoperative apnea, which can lead to bradycardia and
hypoxemia [62,65]. A meta-analysis performed in the mid 1990s has helped
better define the patients at risk for trouble (Fig. 10) [71]. Former premature
infants under 50 to 55 weeks postconceptual age should undergo cardiopulmo-
nary monitoring following anesthesia. Patients who are anemic and those
observed to have events in the postanesthesia care unit deserve longer periods
(18–24 hours) of observation.
An important controversy arose in the 1980s related to advances in anesthesia
care of children and the public’s impatience for more progress. This greatly
influenced subsequent pediatric anesthetic practice. In the middle of the decade, a
critically ill premature infant underwent a surgical repair of a patent ductus
arteriosus at a major pediatric center with a well-regarded department of pediatric
590 costarino & downes

Fig. 10. Risk of postanesthetic apnea. Former premature infants under 50 to 55 weeks postconceptual
age should undergo cardiopulmonary monitoring following anesthesia. Infants who have anemia and
those observed to have events in the postanesthesia care unit deserve longer periods because they
are at a greater risk. (From Coté CJ, Zaslavsky A, Downes JJ, et al. Postoperative apnea in former
preterm infants after inguinal herniorrhaphy. A combined analysis. Anesthesiology 1995;82:809–22;
with permission.)

anesthesia. Like many such children, this patient received a ‘‘light’’ anesthetic. At
the time pulse oximetry and capnometry were not available, and automated
oscillometric monitoring of systemic arterial pressure was just being introduced
[75]. When the parents of this infant understood that their child received only a
neuromuscular blockade and little else during the surgery, they were outraged.
Their story was published in the popular magazine RedBook [106].
At about the same time, a British physician, K.J.S. Anand, sought to evaluate
the neonatal endocrine response to stress. His study design compared two
routinely used anesthetic techniques for premature infants undergoing surgical
repair of patent ductus arteriosus [73]. In one group, the anesthetic used was the
classic Liverpool technique of Jackson-Rees [41]; in the other group, Anand
provided high-dose fentanyl. His findings indicated that the signs of stress (high
steroid metabolites and catecholamines and protein metabolism products) were
greater in the group of infants who did not get the narcotic [73]. When the study
was published, both the medical community and the lay public misunderstood his
study design, and Anand was accused of withholding anesthesia from premature
infants [74]. Anand’s experimental intervention did in fact provide a dose of
narcotic that was larger than routinely used in his experimental group.
The public controversy that surrounded these cases triggered a soul-searching
dialogue in the pediatric anesthesiology community. The frequently stated expla-
nation for the use of light or minimal anesthesia in infants was because they
did not feel pain, which never really correlated with clinical observations. Even
in the 1920s, Dr. Charles Robson recognized that this was inappropriate [4].
However, in the previous decades with the available anesthetic agents, vascular
access techniques, and cardiorespiratory monitoring tools at hand, patient safety
concerns demanded ‘‘light’’ anesthesia. A deeper technique might have resulted
in unrecognized cardiorespiratory collapse. The Liverpool technique was an
innovation that improved safe practice appropriate to the level of knowledge,
 pediatric anesthesia historical perspective 591

skill, and equipment of the 1950s through the 1970s [41]. By the 1980s, the
pediatric anesthesia experience, medications, and monitoring tools made it
appropriate to move forward, and the public was demanding that we do so more
aggressively. In the fall of 1987, editorials in the Journal of Pediatrics [71],
Anesthesiology [75], Pediatrics [77], and the New England Journal of Medicine
[107] advocated the provision of adequate anesthesia to young infants.

The twenty-first century

Only distance allows a historical perspective, so is difficult to identify the

important historical events of the last 5 years. It seems, however, that the defining
issue of this decade will be the way in which pediatric anesthesia responds to the
workforce shortfall in the face of the increasing demand for anesthesia services.
The mid-1980s dialogue about proper anesthesia management of our youngest
citizens continues today among pediatric anesthesiologists, surgeons, pediatri-
cians, and the public. Its current variation influences our efforts and planning
for operating room anesthesia and pediatric pain management. It also influences
the discussion related to the regulation of procedural sedation practice in children
and has a great influence on discussions of how to correct the current deficiency
in the number of skilled pediatric anesthesiologists. We will have to wait a few
years to see how this part of the story develops.

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