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IMPROVING THE

MANAGEMENT OF
POSTOPERATIVE PAIN:

MULTIMODAL APPROACHES
IN CLINICAL PRACTICE
ACUTE PAIN EPIDEMIOLOGY

Acute pain is very common


51.4 million surgical in-patient procedures were

performed in 2010 in the United States

Centers for Disease Control and Prevention. National Center for Health Statistics.
www.cdc.gov/nchs/faststats/inpatient-surgery. Accessed July 8, 2015.
ACUTE PAIN SCOPE OF THE
PROBLEM
Almost all patients experience pain after surgery,
procedure, or injury
Survey of 300 US adults undergoing surgery:
86% experienced pain post surgery
75% had moderate to extreme pain in the immediate
postsurgical period
74% still had pain post discharge

Gan TJ et al. Curr Med Res Opin. 2014;30(1):149-160.


ACUTE PAIN SCOPE OF THE
PROBLEM
Studies suggest that after orthopedic, general, or
cardiac surgery, 63% of patients experience pain
resolution within 6 days
That means that 37% of patients continued to
have pain problems beyond discharge from the
hospital
However, in 25% of patients, the pain did not

change, and in 12% the pain worsened in this


period of time

Chapman CR et al. J Pain. 2011;12(2):257-262.


Chapman CR et al. Pain Res Treat. 2012;2012:608359.
THE ASSESSMENT OF ACUTE
PAIN
Current taxonomies for postoperative pain
do not adequately describe an individual
patients pain profile

Harstall C, Ospina M. Pain: American Association for Marriage and Family Therapy Clinical Updates.
2003;11(2):1-4.
World Health Organization. WHO guidelines on the pharmacological treatment of persisting pain in children
with medical illnesses. http://www.who.int/medicines/areas/quality_safety/children_persisting_pain/en/.
Accessed July 8, 2015.
CURRENT PROBLEMS WITH THE
ASSESSMENT OF ACUTE PAIN
When used alone, these taxonomies do not capture the
multidimensionality of pain or the dynamics of pain
over the course of a 24-hour day in an individual
patient
This approach may result in inadequate
individualization of pharmacologic pain management
Somatic vs neuropathic
Pitfalls in the implementation of therapy to treat these patients:
Multimodal therapy
Opioid metabolism

Drug-drug interactions

Psychological issues: catastrophizing, anxiety, depression, etc

History of opioid use preoperatively

Preexisting pain

Genetics: gene polymorphism


MAKING THE DIFFERENTIAL
DIAGNOSIS
Is there an early neuropathic pain component present?
Suspect in individuals who are still receiving high doses of
opioids + adjuvants 4-5 days post surgery
Must rule out opioid tolerance from preoperative opioid use
or abuse
CHALLENGES IN THE
MANAGEMENT OF ACUTE PAIN
Variable response to analgesics
Older age = more sensitivity to opioids
Ethnicity
Psychological issues
Type of surgical procedure
The use of pre-emptive analgesic techniques
Intraoperative anesthetic techniques:
Regional anesthetic procedures vs general
Ketamine use

Genetics: gene polymorphism


MAKING THE DIFFERENTIAL
DIAGNOSIS
Is there an early neuropathic pain component present?
Suspect in individuals who are still receiving high doses of
opioids + adjuvants 4-5 days post surgery
Must rule out opioid tolerance from preoperative opioid use
or abuse
NEUROPATHIC PAIN (NP) DIAGNOSIS
LANSS PAIN SCALE
Leeds Assessment of Neuropathic Symptoms and Signs

A. PAIN QUESTIONNAIRE
5 Questions

B. SENSORY TESTING
2 Questions

Maximum score = 24. If < 12, NP unlikely

Bennett M. Pain. 2001;92(1-2):147-157.


NEUROPATHIC SYMPTOMS AND
SIGNS
Would you describe your pain as strange unpleasant sensations in your skin? (eg, pricking,
tingling, pins and needles)
Yes= 5/No= 0
Does the skin in the painful areas look different to normal? (eg, mottled, more red/pink than
usual)
Yes= 5 /No= 0
Is the skin in the affected area abnormally sensitive to touch? (eg, unpleasant sensations if
lightly stroked, painful to wear tight clothes)
Yes= 3/No= 0
Does your pain come on suddenly in bursts for no apparent reason when you are still?
(eg, like electric shocks, 'bursting' or 'jumping' sensations)
Yes= 2/No= 0
Do you feel that skin temperature in the painful area has changed (eg, hot, burning)

Yes= 1/No= 0
Does stroking the affected area of skin with a piece of cotton wool produce an unpleasant painful
sensation?
Yes= 5/No= 0
Does touching the affected area of skin with a sharp needle feel sharper or duller when compared
to an area of normal skin?
Yes= 3/No= 0
Bennett M. Pain. 2001;92(1-2):147-157.
CHALLENGES IN THE
MANAGEMENT OF ACUTE PAIN
Variable response to analgesics
Older age = more sensitivity to opioids
Ethnicity
Psychological issues
Type of surgical procedure
The use of pre-emptive analgesic techniques
Intraoperative anesthetic techniques:
Regional anesthetic procedures vs general
Ketamine use

Genetics: gene polymorphism


ACUTE PAIN IMPACTS
PATIENTS LIVES

Negative effects of inadequate acute pain management


include:
Increased hospital stay or more frequent
readmissions
Reduced quality of life (QOL)
Impaired physical function
Decreased functional recovery
Increased complications
Impaired sleep

McCarberg BH et al. Am J Ther. 2008;15(4):312-320.


Pavlin DJ et al. J Clin Anesth. 2004;16(3):200-206.
Sinatra R. Pain Med. 2010;11(12):1859-1871.
Morrison RS et al. J Am Geriatr Soc. 2009;57(1):1-10.
MANAGEMENT CAN HAVE
CONSEQUENCES

Chronic pain
Chronic pain Clinically
Clinically Up to
Up to 50%
50% Effectively
Effectively
may develop
may develop meaningful,
meaningful, of patients
of patients managing
managing
after surgery
after surgery severe acute
severe acute reportedly suffer
reportedly suffer acute pain
acute pain can
can
as aa result
as result postoperative
postoperative from chronic
from chronic reduce the
reduce the risk
risk
of complex
of complex pain may
pain may bebe aa pain following
pain following for pain
for pain
biochemical and
biochemical and risk factor
risk factor for
for the
the common surgery
common surgery progression
progression
pathophysiologica
pathophysiologica development of
development of
ll mechanisms
mechanisms chronic pain
chronic pain

Sinatra R. Pain Med. 2010;11(12):1859-1871.


Morrison RS et al. J Am Geriatr Soc. 2009;57(1):1-10.
Voscopoulos C, Lema M. Br J Anaesth. 2010;105(suppl 1):i69-i85.
IMPROVING POSTOPERATIVE
PAIN MANAGEMENT
Studies suggest that individualization of pain
evaluations are important to determine:
Preoperative risk factors
The pattern of resolution for each patient
The therapeutic approach to implement

Chapman CR et al. J Pain. 2011;12(2):257-262.


Chapman CR et al. Pain Res Treat. 2012;2012:608359.
MULTIMODAL THERAPY

Synchronous administration of 2 pharmacological


agents or approaches, each with a distinct
mechanism of action

American Society of Anesthesiologists Task Force on


Acute Pain Management. Practice Guidelines for Acute
Pain Management in the Perioperative Setting.
Anesthesiology. 2012;116:248-273.

American Society of Anesthesiologists Task Force on Acute Pain Management.


Anesthesiology. 2012;116(2):248-273.
MULTIMODAL THERAPY

Key Practice Guidelines Recommendations

Whenever possible, anesthesiologists


should use multimodal pain management
therapy.

American Society of Anesthesiologists Task Force on Acute Pain Management.


Anesthesiology. 2012;116(2):248-273.
MULTIMODAL THERAPY

Rationale:
Targeting of different pathways
Synergism of multiple agents
Allows for dose reduction of individual agents,
reducing the risk for adverse effects
MULTIMODAL THERAPY

Key Practice Guidelines Recommendations

Anesthesiologists who manage perioperative pain


should, after thoughtfully considering the risks and
benefits for the individual patient, use therapeutic
options such as:
Epidural or intrathecal opioids
Systemic opioid patient-controlled analgesia (PCA)
Regional techniques

American Society of Anesthesiologists Task Force on Acute Pain Management.


Anesthesiology. 2012;116(2):248-273.
MULTIMODAL THERAPY

Key Practice Guidelines Recommendations

Unless contraindicated, patients should receive an


around-the-clock regimen of nonsteroidal anti-
inflammatory drugs (NSAIDs), COX-2 inhibitors, or
acetaminophen.

Dosing regimens should be administered to optimize


efficacy while minimizing the risk for adverse events.

The choice of medication, dose, route, and duration of


therapy should be individualized.

American Society of Anesthesiologists Task Force on Acute Pain Management.


Anesthesiology. 2012;116(2):248-273.
PERIOPERATIVE
TECHNIQUES
IN PAIN MANAGEMENT
Technique Examples Advantages Disadvantages
Central Regional Intrathecal or Improved pain Increased
Analgesia epidural opioida relief frequency of
pruritus
Epidural opioida Improved pain Increased
+ local scores motor
anestheticb weakness

Epidural opioida None noted None noted


a
Examples of + clonidine
opioids include morphine, fentanyl, sufentanil
b
Examples of local anesthetics include bupivacaine, ropivacaine

American Society of Anesthesiologists Task Force on Acute Pain Management.


Anesthesiology. 2012;116(2):248-273.
PERIOPERATIVE
TECHNIQUES
IN PAIN MANAGEMENT
Technique Examples Advantages Disadvantages
Systemic Staff-administered None noted Pain on injection
opioidsa intramuscular (IM) Tissue damage
injections
Staff-administered Similar pain Peak / trough
intravenous control to PCA opioid adverse
injections drug reactions
(ADRs)
PCA without Improved pain None noted
background infusion scores vs IM
PCA with Improved pain Increased
a
Examples of opioids include
background infusion morphine,
scores fentanyl,
vs IM hydromorphone
analgesic use vs
American Society of Anesthesiologists Task Force on Acute Pain Management. no background
Anesthesiology. 2012;116(2):248-273.
PERIOPERATIVE
TECHNIQUES
IN PAIN MANAGEMENT
Technique Examples Advantages Disadvantages
Peripheral Peripheral Generally, improved None noted
Regional nerve blocksb pain relief and lower
Analgesia analgesic consumption
compared with saline
Intra-articular None noted compared None noted
blocksb or with saline
opioidsa
Infiltration of Generally, improved None noted
incisionsb pain relief and lower
analgesic consumption
a
Examples of opioids include morphine, fentanyl, sufentanil
b compared
Examples of local anesthetics with saline ropivacaine
include bupivacaine,

American Society of Anesthesiologists Task Force on Acute Pain Management.


Anesthesiology. 2012;116(2):248-273.
PERIOPERATIVE
TECHNIQUES
IN PAIN MANAGEMENT
Technique Examples Advantages Disadvantages
Nonopioid Acetaminophen Similar benefit to None noted
systemic (oral, rectal, intravenous (IV) PCA
analgesics injectable) opioid
Fewer ADRs
Injectable Improved pain scores NSAID risks /
NSAIDs Reduced analgesic ADRs
use
Oral NSAIDs None noted NSAID risks /
(both non- and ADRs
selective
Gabapentinoids When combined w/ None noted
(both gabapentin opioids
American Society of Anesthesiologists Task Force on Acute Pain Management.
and pregabalin)
Anesthesiology. 2012;116(2):248-273. Improved pain scores
Dual Ascending Pathways Limbic Cortex

Sensory Cortex

Thalamus

Peripheral
Nociceptor
Ascending
Descending
Pathways
Pathways

Mid Brain

Sensory
Fiber Dorsal
Horn

Spinal Cord

Efferent
Fiber

Slide courtesy of Raymond Sinatra, MD


Limbic Cortex
Physiological Pain
Sensory Cortex

Thalamus

Ascending
Nociceptor
Pathways

Mid Brain

Sensory
Fiber Dorsal
Horn

Spinal Cord

Efferent
Fiber

Slide courtesy of Raymond Sinatra, MD


Postoperative Pain Opioids
Treatment 2-Agonists
Acetaminophen

Multimodal N-methyl-D-aspartate
(NMDA) antagonists

Therapy

Local anesthetics (LA)


infiltration
Acetaminophen
Anti-inflammatory agents,
COX-2 inhibitor

LA via peripheral
nerve catheters
Local anesthetics
Opioids
2-Agonists
NMDA antagonists
COX-2 Inhibitors

Slide courtesy of Raymond Sinatra, MD and modified for educational


MULTIMODAL APPROACHES:
EVIDENCE-BASED SUMMARY
Acetaminophen (APAP) oral, single dose
Cochrane review1
51 studies, 5762 patients, 3277 active, 2425 placebo
50% in pain with 50% APAP group, 20% placebo group

for 4 hours
Number needed to treat (NNT) based on dose:

APAP 500 mg: 3.5


APAP 650 mg: 4.6

APAP 1000 mg: 3.6

50% of APAP and 70% of placebo needed additional analgesia


A systematic review2 identified 21 studies comparing APAP
alone or in combination with NSAIDs and reported
increased efficacy with the combination of 2 agents than
with either alone

Toms L et al. Cochrane Database Syst Rev. 2008;(4):CD004602.


1

Ong CK et al. Anesth Analg. 2010;110(4):1170-1179.


2
MULTIMODAL APPROACHES:
EVIDENCE-BASED SUMMARY
Acetaminophen Parenteral
Studied single dose, multiple dose over 24 hours compared
with placebo
Orthopedic surgery, laminectomy, abdominal, gynecological,
cardiac, and thyroidectomy
Dosing: 1 gram IV, either single dose or every 6 hours
Summary APAP patients:
Statistically significant shortened time to meaningful pain relief
and in total relief compared with placebo
Improved patient satisfaction with pain control, lower morphine

consumption (up to 61%) and decreased incidence of vomiting


No statistical significant difference in the rates of adverse events

including liver function abnormalities compared with placebo


Wininger SJ et al. Clin Ther. 2010;32(14):2348-2369.
Cakan T et al. J Neurosurg Anesthesiol. 2008;20(3):169-173.
Memis D et al. J Crit Care. 2010;25(3):458-462.
Macario A, Royal MA. Pain Pract. 2011;11(3):290-296.
ACETAMINOPHEN
(PARACETAMOL OR APAP)
Produces a central analgesic effect, but unknown mechanism of
action (MoA) for years
New evidence for MoA from extensive research
MoA evidence now suggests that the analgesic effect of APAP is partly
due to the indirect activation of cannabinoid CB(1) receptors
APAP primary amine (p-aminophenol) is conjugated to form
N-arachidonoylphenolamine, an endogenous cannabinoid
N-arachidonoylphenolamine is an agonist at TrpV-1 receptors and an inhibitor

of cellular anandamide uptake, increased levels of endogenous cannabinoids


APAP may also work through inhibition of prostaglandin (PG) synthesis
via prostaglandin H(2) synthetase, particularly in areas of the brain with
high concentrations of fatty acid amide hydrolase
Thus, acetaminophen may have multiple MoAs, one of which
ultimately acts as a pro-drug, the active one being a cannabinoid
Dual effect may be both a direct analgesic effect and modulation effect
Bertolini A et al. CNS Drug Rev. 2006;12(3-4):250-275.
Graham GG et al. Inflammopharmacology. 2013;21(3):201-232.
Anderson BJ. Paediatr Anaesth. 2008;18(10):915-921.
MULTIMODAL APPROACHES:
EVIDENCE-BASED SUMMARY
Nonselective NSAIDs
Single dose oral ibuprofen1 Summary 72 randomized clinical
trials (RCTs), 9168 patients
50% pain relief in approximately half of patients with moderate to
severe postoperative pain, and adverse events were similar to placebo
Single dose oral aspirin2 Summary
50% or greater reduction in pain in 39% of those with moderate to
severe pain, compared with 15% of those in the placebo group
The efficacy of aspirin was considered equivalent to that of

acetaminophen
Adverse events were statistically similar for those taking a lower

aspirin dose, 600 mg to 650 mg, compared with placebo. However,


patients who took 900 mg to 1000 mg experienced adverse events at
more than twice the rate of patients receiving placebo (26% vs 12%).
The most common events in the aspirin group were drowsiness,
dizziness, nausea, vomiting, and gastric irritation
1
Derry C et al. Cochrane Database Syst Rev. 2009;(1):CD004234.
2
Derry C et al. Cochrane Database Syst Rev. Published Online Jan 2012
MULTIMODAL APPROACHES:
EVIDENCE-BASED SUMMARY
Selective NSAIDs Single dose Celecoxib
Cochrane review - 10 studies, 1785 patients
NNT for 50% decrease in pain over 4 to 6 hours:
Celecoxib 200 mg: 4.8

Celecoxib 400 mg: 3.5

Median time for rescue medication use:

Celecoxib 200 mg: 6.6 hours

Celecoxib 400 mg: 8.4 hours

Placebo: 2.3 hours

Proportion of patients requiring rescue medications:

Celecoxib 200 mg: 74%

Celecoxib 400 mg: 63%

Placebo: 91%

Adverse events mild to moderate in all groups with no difference

in frequency
Derry S et al. Cochrane Database Syst Rev. Published Online: 22 OCT 2013
MULTIMODAL APPROACHES:
EVIDENCE-BASED SUMMARY
Injectable NSAIDs
Ketorolac and ibuprofen studied in United States
Indicated for short-term moderate to severe acute pain
that requires analgesia at the opioid level
Studies (variety of surgery types) with ketorolac1,2 compared with
placebo suggest patients who received ketorolac:
Significant reduction in pain

Reduction in opioid consumption (~30%)

Facilitation of quicker recovery and rehabilitation

Studies with ibuprofen in orthopedic and abdominal surgery3

At 800-mg dose, reduced morphine use by 22% in first 24 hours

Significant reductions in pain at rest and with movement

No significant increases compared with placebo in ADRs

1. Cassinelli EH et al. Spine (Phila Pa 1976). 2008;33(12):1313-1317.


2. Wong HY et al. Anesthesiology. 1993;78(1):6-14.
3. Southworth S et al. Clin Ther. 2009;31(9):1922-1935.
MULTIMODAL APPROACHES:
EVIDENCE-BASED SUMMARY
Parenteral Opioids Patient-controlled Analgesia
Cochrane review
55 studies with 2023 patients receiving PCA and 1838 patients
assigned to a control group (nurse-administered opioid)
PCA provided better pain control and greater patient

satisfaction than conventional parenteral 'as-needed' analgesia


Patients using PCA:

Consumed higher amounts of opioids than the controls


Had higher incidence of pruritus (itching), but similar incidence of

other adverse effects


There was no difference in the length of hospital stay

Hudcova et al. Cochrane Database Syst Rev. 2006;(4):CD003348.


MULTIMODAL APPROACHES:
EVIDENCE-BASED SUMMARY
Parenteral Opioids Patient-controlled Analgesia
PCA vs nurse-controlled (NCA) after cardiac surgery
10 randomized trials, 666 patients
Compared with NCA:

PCA significantly reduced visual analogue scale (VAS) at 48 hours,


not at 24 hours
PCA groups showed significantly increased cumulative morphine

equivalents consumed at 24 hours


No difference with ventilation times, length of ICU stay, length of

hospital stay, patient satisfaction scores, sedation scores, incidence


of postoperative nausea and vomiting (PONV), respiratory
depression, severe pain, discontinuations, and death

Bainbridge D et al. Can J Anaesth. 2006;53(5):492-499.


MULTIMODAL APPROACHES:
EVIDENCE-BASED SUMMARY
Epidural Opioids
Cochrane Review
Abdominal aortic surgery
15 trials with 1297 patients (633 received epidural analgesia and

664 received systemic opioid analgesia)


The epidural analgesia group showed significantly lower visual analogue
scale scores for pain on movement (up to postoperative day 3)
Conclusions: Compared with systemic opioids:
Regardless of the site of the epidural catheter and epidural

formulation, epidural analgesia provides better pain relief (especially


during movement) in the period up to 3 postoperative days
Duration of postoperative tracheal intubation is reduced by roughly

half with epidural


The occurrence of prolonged postoperative mechanical ventilation,

myocardial infarction, gastric complications, and renal complications


was reduced by epidural analgesia

Nishimori M et al. Cochrane Database Syst Rev. 2012;(7):CD005059.


MULTIMODAL APPROACHES:
EVIDENCE-BASED SUMMARY
Epidural Local Anesthetics vs Opioid-based Regimens
(systemic or epidural)
Cochrane Review
Abdominal surgery, 8 studies, small numbers of patients
Key outcome analysis:

Postoperative: Gastrointestinal (GI) function, pain, PONV,

and complications
Conclusions: Epidural local anesthetics:

Reduced time of GI functioning, slight reduction in VAS pain

scores on the first postoperative day


No significant differences in PONV or complications

Jorgensen H et al. Cochrane Database Syst Rev. Published Online: 22 JAN 2001
MULTIMODAL APPROACHES:
EVIDENCE-BASED SUMMARY
Continuous Epidural Analgesia
Cochrane database review1: 9 RCT comparing IV PCA and
continuous epidural analgesia (CEA)
CEA had better pain control in the first 72 hours after abdominal
surgery
There was no difference in length of hospital stay and adverse

events between the 2 routes


Patients with CEA had a higher incidence of pruritus related to

opioids
Comparing PCA vs CEA in colorectal surgery2 showed that CEA

significantly reduced postoperative pain and ileus, but was


associated with pruritus, hypotension, and urinary retention

1
Werawatganon T, Charuluxanun S. Cochrane Database Syst Rev. 2005;(1):CD004088.
Marret E et al; Postoperative Pain Forum Group. Br J Surg. 2007;94(6):665-673.
2
MULTIMODAL APPROACHES:
EVIDENCE-BASED SUMMARY
Intrathecal (IT) Morphine + PCA Morphine vs PCA
Morphine Alone
Major
abdominal surgery, 60 patients
Summary
Analgesia at rest and while coughing was significantly better in the
IT+PCA morphine group on the first postoperative day only
Morphine consumption was lower in the IT+PCA morphine group

during first postoperative day


No difference was found in pain relief and morphine consumption

between the groups on the second postoperative day


Nausea and vomiting were more frequent with IT+PCA morphine

on the first postoperative day


No respiratory depression occurred in either group

Satisfaction was high in both groups

Devys JM et al. Can J Anaesth. 2003;50(4):355-361.


MULTIMODAL APPROACHES:
EVIDENCE-BASED SUMMARY
Local Anesthetics Wound Infiltration
Useful in a variety of surgeries
Cardiothoracic, abdominal, gynecological, colorectal, head and
neck, orthopedic
General conclusions from studies:

Effective in a variety of surgical sites

Neither infection nor toxicity appears to be a significant clinical

issue
Preoperative blockage superior to postoperative

Pain is reduced both at rest and on mobilization

Opioid requirements are less

Decreased occurrence of acute and chronic pain 3 and 6 months

after surgery shown in 1 study with breast cancer surgery

Scott NB. Anaesthesia. 2010;65(suppl 1):67-75.


MULTIMODAL APPROACHES:
EVIDENCE-BASED SUMMARY
Intravenous Lidocaine
Meta-analysis after abdominal surgery
8 trials, 161 patients received lidocaine (active arm),
159 saline (placebo arm)
Both arms could receive as-needed opioids

Lidocaine IV groups showed:

Decreased duration of ileus

Length of hospital stay

Postoperative pain intensity

Incidence of PONV

30%50% reduction in opioid consumption

Marret E et al. Br J Surg. 2008;95(11):1331-1338.


MULTIMODAL APPROACHES:
EVIDENCE-BASED SUMMARY
Intravenous Lidocaine
Systematic review (various surgeries, including:
abdominal, tonsillectomy, total hip, coronary bypass)
16 trials, 395 patients received lidocaine (active arm), 369 saline
(placebo arm)
All could receive as-needed opioids
In patients who received IV lidocaine IV:
Pain scores were reduced at rest and with cough or movement for
up to 48 hours postoperatively in abdominal surgery patients
No impact on postoperative analgesia in patients undergoing
tonsillectomy, total hip arthroplasty, or coronary artery bypass surgery
Decreased duration of ileus
Length of hospital stay shortened
Postoperative pain intensity lessened
Incidence of PONV decreased
Up to 85% reduction in opioid consumption

McCarthy GC et al. Drugs. 2010;70(9):1149-1163.


MULTIMODAL APPROACHES:
EVIDENCE-BASED SUMMARY
Ketamine Intravenous Systematic Review
70 studies, 4701 patients (2652 ketamine, 2049 placebo)
Summary
Patients receiving ketamine reported a reduction in total opioid
consumption and an increase in the time to first analgesic dose needed
across all studies
(P < .001).
o The greatest efficacy of ketamine was found for thoracic, upper abdominal,
and major orthopedic surgical subgroups
Despite using less opioid, 25 out of 32 treatment groups (78%) experienced
less pain than the placebo groups
Hallucinations and nightmares were more common with patients receiving
ketamine, but there was no association with increased sedation
In patients in whom ketamine was reported as efficacious for pain,
postoperative nausea and vomiting was less frequent in those patients who
received ketamine
The analgesic effect of ketamine was independent of the type of
intraoperative opioid administered, the timing of ketamine administration,
and the ketamine dose administered
Laskowski K et al. Can J Anaesth. 2011;58(10):911-23.
MULTIMODAL APPROACHES:
EVIDENCE-BASED SUMMARY
Gabapentinoids - Systematic Review of RCTs
Gabapentin: 22 trials, 1640 patients
Pregabalin: 8 trials, 707 patients
Summary:
Gabapentin provided better postoperative analgesia and in
sparing rescue analgesics than placebo in the 6/10 RCTs that
administered gabapentin as preemptive analgesia only
14 RCTs suggested that gabapentin did not reduce PONV when

compared with placebo


Pregabalin provided better postoperative analgesia and in

sparing rescue analgesics than placebo in 2/3 RCTs that


evaluated the effects of pregabalin alone vs placebo
4 studies reported no pregabalin effects on preventing PONV

Both agents reduced opioid consumption by ~30%

Dauri M et al. Curr Drug Targets. 2009;10(8):71633.26


MULTIMODAL APPROACHES:
EVIDENCE-BASED SUMMARY
Systemic 2 Agonist Meta-analysis of RCTs
Summary
Moderate analgesic benefitprobably better than paracetamol,
but less than that of ketamine and NSAIDs as inferred from
nonsystematic indirect comparison
Adverse reactions may be significant (hypotension and bradycardia)

Provides extra analgesic benefits such as sedation, anxiolysis,

analgesia, postoperative shivering, decreased PONV, agitation,


mitigation of stress response to surgery and tracheal intubation,
anaesthetic-sparing effect, and as supplement to neuraxial and
peripheral nerve blocks
Decreased perioperative mortality and myocardial infarction,

especially in high-risk vascular surgeries

Blaudszun G et al. Anesthesiology. 2012;116(6):1312-1322.


PERIOPERATIVE PAIN
ANALGESIC ADJUVANTS
Opioid- Prevention
Analgesic related of Chronic
Pain Opioid Side Postsurgical
Drug Intensity Consumption Effects Pain Side Effects

Ketamine Inconsistent Psychomimetic


(hallucinations,
dreams)
Pregabalin Yes Sedation,
dizziness
Gabapentin Yes Sedation,
dizziness
IV Possible None noted,
Lidocaine but monitor
Systemic No data Hypotension,
Shankar R et al. Anaesth Crit Care Pain. 2013;13(5):152-157.
2 agonist bradycardia
MEDICATIONS COMMON ADVERSE
DRUG REACTIONS
Class Examples ADR Risks Comments
Opioids Morphine Sedation Sedation may impair
Hydromorphone Constipation postoperative
Fentanyl Nausea / Vomiting rehabilitation
Dizziness Constipation may
affect time to
discharge

NSAIDs Ketorolac GI bleeds May affect wound /


(injectable) Ibuprofen Nephrotoxicity bone healing

NSAIDs Ibuprofen GI bleeds May affect wound /


(oral, Naproxen Nephrotoxicity bone healing
Diclofenac Nausea / Vomiting
nonselective)
NSAIDs Celecoxib Nephrotoxicity May affect wound /
(oral, selective) Nausea / Vomiting bone healing

Acetaminophen Acetaminophen Hepatotoxicity No effect on


(oral and at high doses bleeding times
MULTIMODAL ANALGESIA

The state-of-the-art is multimodal therapy with:


Opioids
IV
Intraspinal (IS)

Oral route

NSAIDs
APAP
Local anesthetics
Wound site infiltration or perfusion
Peripheral nerve infusions via catheters

Epidural

IV

Preperitoneal catheters

American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology.


2012;116(2):248-273.
DIFFERENCES BETWEEN ACUTE AN

CHRONIC PAIN
Chronic Pain Acute Surgical
Ladder Pain
De
it y cr
e ns ea
s
t in
In g
a in Step 4 (interventional)
Pa
P i n
i n g Step 3 (potent opioids) In
a s te
re n sit
c
In Step 2 (weak opioids) y

Step 1 (nonopioids)

No analgesics
TRANSITION FROM ACUTE SURGICAL PAIN
AND THE DEVELOPMENT OF CHRONIC PAIN
Decreasing
Surgery Pain Intensity Increasing Pain
Intensity
interventional

potent opioids
interventional
weak opioids
potent opioids
non-opioids
Nerve Injury
vs Central
Sensitization adjuvants
no medications

Time
TRANSITION FROM ACUTE SURGICAL
PAIN TO SUBACUTE (PERSISTENT) PAIN

Decreasing
Surgery Pain Intensity

Pain Intensity
Remains High
interventional

potent opioids

weak opioids potent opioids

non-opioids adjuvants

no medications

Time 1 to 12 weeks
MULTIMODAL PAIN
MANAGEMENT:
STEP THERAPY
Severe Postoperative Pain
Step 3 Step 1 and Step 2 Strategies
AND
Local Anesthetic Peripheral Neural
Blockade
(with or without catheter)
AND
Use of Sustained-release Opioid
Analgesics
Step 2 Moderate Postoperative Pain
Step 1 Strategy
AND
Intermittent Doses of Opioid
Analgesics
Mild Postoperative Pain
Step 1 Nonopioid Analgesic
Acetaminophen, NSAIDs, or COX-2 Selective
Inhibitors
AND
Local Anesthetic Infiltration
Reprinted with permission. Copyright 2002
American Medical Association. All rights reserved.

Crews JC. JAMA. 2002;288(5):629-632.


PHARMACOECONOMICS

Consequences of side effects


Consequences of inadequate pain control

Consequences of postoperative complications

Readmissions
TRANSITION FROM ACUTE SURGICAL
PAIN TO SUBACUTE (PERSISTENT) PAIN

Decreasing
Surgery Pain Intensity

Pain Intensity
Remains High
interventional

potent opioids

weak opioids potent opioids

non-opioids adjuvants

no medications

Time 1 to 12 weeks
CLINICAL PEARLS
THANK YOU!