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KEY CONCEPTS IN ACUTE

PAIN MANAGEMENT

John Penning MD FRCPC


Director Acute Pain Service

Objectives

Why is acute pain management important?


Clinical concepts not readily found in texts
COX-inhibitors, the foundation of all acute
pain protocols
Opioid dose:response variability
Limitations of T#3
Role of NMDA antagonists

Consequences of poorly managed


acute post-operative/trauma pain

The Patient suffers

CVS: MI, dysrhythmias


Resp: atelectasis, pneumonia
GI: ileus, anastamosis failure
Endocrine: stress hormones
Hypercoagulable state: DVT, PE
Impaired immunological state
Infection, cancer, wound healing

Psychological:
Anxiety, Depression, Fatigue

Chronic Post-surgery/trauma Pain

Consequences of poorly managed


acute post-operative/trauma pain

The Hospital

Increased costs $$$


Poor staff morale
Reputation/Standing in the Community, Nationally
Accreditation
Litigation

The Healthcare professional


Morale
Complaints to College
Litigation

The New Challenges in Managing Acute


Pain after Surgery and Trauma

Patients/Society more aware of their rights


to have good pain control
We are being held accountable
JCAHCO standards, Pain is the Fifth Vital sign

Pressure from hospital to minimize length of


stay
Control pain, limit S/E and complications

The New Challenges in Managing Acute


Pain after Surgery and Trauma
The

Opioid Tolerant Patient

The greatest change in pain management


practice/attitudes in the last 10 years is the
now wide spread acceptance of the use of
opioids for CHRONIC NON-MALIGNANT
PAIN
Renders the usual standard box orders
totally inadequate in these patients

What is the Best Way to manage


acute post-operative/trauma pain?
FIRST,

DO NO HARM

Therefore, the best way is a BALANCE


Patient
Safety

Effective
Analgesic
Modalities

KEY POINTS

Emphasis is placed on the utilization of a


multimodal analgesic approach to maximize
analgesia while minimizing side-effects.
Transduction
Transmission
Modulation
Perception
There is as of yet no single silver bullet!!

Pain Pathways

Acute Pain Management Modalities


Cyclo-oxygenase inhibitors
Non-specific COX inhibitors(classical NSAIDs)
Selective COX-2 inhibitors, the coxibs
Acetaminophen is probably COX-3

Opioids

Local Anesthetics

NMDA antagonists
Ketamine, dextromethorphan

Tissue Trauma
Cell Membrane Phospholipids
Phospholipase
Arachidonic Acid
C
O
X

Cyclo-oxygenase

Endoperoxides
Thromboxane
Prostaglandins

Toxic Oxygen Radicals


Prostacyclin

Case Problem: Inadequate Analgesia with IV


PCA after Open Cholecystectomy

45 yr. female c/o severe pain at rest and difficulty


breathing due to incisional pain- 4 hrs. post-op
IV PCA morphine: 1mg bolus, 5 min. lock-out
150 demands : 28 good
has stopped using PCA because, it is making me sick(N/V)
and its not working
received 25 mg gravol X 2 one hour ago which helped just a
little with the N/V, but did make her quite groggy

Solution?
Between a rock and a hard place! as far as the
use of opioids goes.

Case Problem: Inadequate Analgesia with IV


PCA after Open Cholecystectomy

Problem: Patient unable to attain required morphine


blood level due to intolerable side-effects (N/V,
sedation)
Solution:
Administer COX-inhibitor
Toradol IV/IM or Naproxen 500 mg PR Q12H, this may
be changed to 250 mg PO TID with meals once eating
Control N/V
Stemetil, Ondansetron, Decadron
May need to consider changing opioid i.e. Demerol
Local Anesthetics: intercostals, paravertebral, epidural

Analgesia with Opioids alone

The harder we push with single mode analgesia,


the greater the degree of side-effects

Side-effects

Analgesia

Multi-modal Analgesia

With the multimodal analgesic approach there is


additive or even synergistic analgesia, while the sideeffects profiles are different and of small degree.

Side-effects
Analgesia

The rationale for COX-Inhibitors in


acute pain management

The problem with the Little Pain Little Gun,


Big Pain Big Gun Approach
With opioids, analgesic efficacy is limited by sideeffects
Optimal analgesia is often difficult to titrate
>10 fold variability in opioid dose:response for
analgesia in opioid nave patients!
factors add to the difficulty
Opioid tolerance, anxiety, obstructive sleep apnea, sleep
deprivation, concomitantly administered sedative drugs

The rationale for COX-Inhibitors in


acute pain management

The problem with the Little Pain Little


Big Pain Big Gun Approach

Gun,

Patient Safety!! If the Big Gun is failing due to


dose limiting sedation/respiratory depression, the
addition at that time of the Little Gun may kill the
patient.

Case Problem:

Severe Respiratory
Depression after Toradol?

Healthy 34 yr. patient c/o severe incisional pain in


PACU after ovarian cystecomy
Received 200 g fentanyl with induction and 10 mg
morphine during case
PCA morphine started in PACU, plus nurse
supplements totaled 26 mg in 90 minutes
Still c/o pain, 30 mg Toradol IM given with some relief
after 15 minutes, so patient sent to ward
60 minutes later found unresponsive, cyanotic, RR
4/min.

Case Problem:

Severe Respiratory
Depression after Toradol?

Pharmacodynamic drug interaction between


morphine and COX-inhibitor
morphines respiratory depressant effect opposed
by the stimulatory effects of pain, busy PACU
environment
COX-inh. decreases pain, morphines effect
unappossed
Gain control of acute pain with fast onset, short acting
opioid(fentanyl)
Add COX-inhibitor adjunct early
Monitor closely for sedation and respiratory
depression after pain is alleviated by any means

Analgesia with Opioids alone

The harder we push with single mode analgesia,


the greater the degree of side-effects

Pain
Opioid
Side-effects

Resp Depression
Analgesia

Opioid

The rationale for COX-Inhibitors in


acute pain management
CONCEPT # 1
The foundation of all acute pain Rx
protocols.

First on : last off

sole agent in mild /moderate pain


Analgesic efficacy is limited inherently
ceiling effect for analgesia exists, but toxicity
may continue to increase with increasing dosage

The rationale for COX-Inhibitors


in acute pain management
Opioid

dose sparing of 30 50%

Less c/o opioid S/E


Dose:response

is quite uniform from


patient to patient
S/E and contra-indications well described

The rationale for COX-Inhibitors


in acute pain management
Improved pain scores, especially with
activity
Greater patient satisfaction

Safer for the patient

The rationale for pre-operative


administration of COX-inh.

The benefits of Pre-emptive Analgesia


Goal: prevent the establishment of peripheral and
central sensitization (wind-up), conditions that
lead to an augmented response to pain stimuli
i.e. prevention of hyper-algesic state

Requirements: the analgesic must be


pharmacologically active at the time of surgical
incision and its activity must be maintained perioperatively. ( > 1 hr. pre-op for PO/PR COX-inh)

Why a Selective COX-2 inhibitor?

Equivalent analgesic efficacy with nonselective COX-inhibitors

No

effects on platelets! 0, ZIPPO


Much reduced incidence of upper GI
S/E compared to non-selective
Duration of action about 24 hr.

Cyclo-oxygenase inhibitors
Concept # 2
All patient having surgical procedures
associated with post-operative pain should
receive a pre-emptive COX inhibitor,
provided there are no patient contraindications.
COX-2 for everyone probably the safest
and easiest to organize.

The Opioids
We

have to stop trying to put every


patient in the analgesic dose box

Meperidine
75 mg
IM Q4H
prn

Tylenol #3
1 2 PO
Q4H
prn

Opioids
What are the factors that determine the
dose of opioid we choose?

Opioids
The dose of opioid administered is
dependant upon multiple factors
Pharmacological tolerance to opioids?
Route of administration
PO, IM/SC, IV bolus, intrathecal

Age
Weight
Severity of pain

Opioids

A dose of opioid that is inadequate for


patient A can lead to significant S/E
or even death in patient B.

Opioids
Pharmacokinetic + Pharmacodynamic
patient to patient variability results in1000 %
variability in opioid dose requirements

Concept # 1
opioid dosage must be individualized

therefore, if parenteral therapy indicated, IV


PCA much better suited to individual patient
needs than IM/SC

Patient Controlled Analgesia with


Intravenous Opioids

IV PCA:
morphine
golden standard, pruritus a common problem

meperidine
a little faster onset than morphine
normeperidine a toxic metabolite is a problem for
patients with decreased renal function or using large
dosages for more than a few days

hydromorphone
less confusion in elderly patients?

PCA order parameters


Bolus

dose
Lock-out Interval
Continuous infusion
One hour max. limit

Opioids
Issue
With parenteral opioids the patient may experience intolerable side
effects before adequate analgesia is attained

Opioids
CONCEPT # 2
Targeted regional
administration of opioid
results in enhancement of
the therapeutic index (ratio
of analgesia/side effects)

The proper use of oral opioids


The

limitations of combination drugs


Codeine is a pro-drug
Potent oral opioids are under-utilized
Offer around the clock not prn
In stable situations long acting, slow
release formulations may be indicated

The Limitations of Tylenol # 3


Codeine

is a pro-drug

codeine is methylated morphine and needs to


be de-methylated to active morphine (up to
10% of patients may not be able to convert
codeine to morphine), on the other hand,
some patients may overconvert and be
sensitive
Net result is unpredictability

The Limitations of Tylenol # 3


The

problem with combination drugs

The codeine dose is limited by the maximum


allowed dose for acetaminophen

4 grams/day = 12 tabs/day
12 X 30 mg = 360 mg codeine = 60 mg morphine
60 mg PO = 15 30 parenteral morphine
Equals about 1 mg/hr IV/s.c.
Adequate for moderate pain in average patient?

Net result is limited efficacy

The Limitations of Tylenol # 3


The

problem with combination drugs

Acetaminophen therapy may be limited by


intolerance to codeine
Patient sensitive to codeine may only want to
take 1 T#3 or even 1/2. If all they can tolerate
is 15 mg of codeine Q4H, the patient is not
receiving the benefit of optimum dose of
acetaminophen

The Limitations of Tylenol # 3

The constipation problem


Codeine may be more constipating than other
opioids

The codeine allergy problem


True immunological allergy is extremely rare
> 99% of allergy are sensitivities
N/V, excessive sedation, confusion
Need to perform adequate drug history,
otherwise problems may arise when an even
more potent opioid, such as Percocet is
substituted for T#3.

The Limitations of Tylenol # 3


1/ Codeine is a pro-drug
2/ The problem with combination drugs
a. The codeine dose is limited by the maximum allowed
dose for acetaminophen

b. Acetaminophen therapy may be limited by intolerance to


codeine

3/ The constipation problem


4/ The codeine allergy problem

Solution to the T #3 limitations


Provided codeine works in your Patient
The oral analgesic ladder
T#3
T#3
T#3
T

T#3

T#3

Oxy
5 mg

Solution to the T #3 limitations


Every 12 hours
COX-2
inhibitor

Long Acting
Opioid

For breakthough pain


Regular opioid PO Q4h prn
Acetaminophen 650 mg PO Q4h prn

Opioids

*Cancer Pain Monograph (H&W, 1984)

CONCEPT # 3
Under utilization of high efficacy PO opioids

PO opioid equivalence of 10 mg morphine IM/SC *

morphine 20 mg
hydromorphone 4 mg
oxycodone 10 mg

codeine 120 mg
meperidine 200 mg

Opioids
Dilaudid 1 4 mg PO/IM/IV Q4H prn

NOT!
This represents up to 30 fold range in
peak effect in any given patient
1 mg PO ---- 4 mg IV bolus
homeopathic dose ---- potentially lethal

Opioids: Rational multi-route


orders?

Foundation of Acetaminophen/COX-inh.

Morphine 5 - 10 mg PO Q4h prn


Morphine 2.5 - 5 mg s.c. Q4h prn
Morphine 1-2 mg IV bolus Q1h prn

Hydromorphone 1 - 2 mg PO Q4h prn


Hydromorphone 0.5 1 mg s.c Q4h prn
Hydromorphone 0.25 0.5 mg IV Q1h prn

NMDA Receptor Antagonists To prevent or reverse pathological acute pain


Ketamine,

Dextromethorphan

Ketamine is widely known as a dissociative


general anesthetic - 3 mg/Kg IV bolus
Ketamine 0.15 - 0.3 mg/kg IV with induction of
general anesthesia has pre-emptive analgesic
effects - less pain and less opioid use post-op
Ketamine 2.5 - 5.0 mg IV bolus for analgesia in
post-surgery/ trauma patient Ketamine as co-analgesic - combined 1:1 with
morphine IV PCA. Better analgesia, less S/E
Dextromethorphan 45 mg PO Q12H

Concluding Remarks
The foundation of all acute pain Rx
protocols is a COX-Inhibitor

First on : last off


Opioid dosage must be individualized
A dose of opioid that is inadequate for patient
A can lead to significant S/E or even death
in patient B.

Limitations of Tylenol # 3

Texts
Managing

Pain. The Canadian Healthcare

Professionals Reference
Edited by Roman Jovey MD
Endorsed by the CPS
Available free from Purdue Pharma

Medical Pharmacology by Katzung (Lange


Series)