Transcript Improving the Management of Postoperative Pain

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.
CURRENT PROBLEMS WITH THE
ASSESSMENT OF ACUTE PAIN
 Current
taxonomies for postoperative pain
do not adequately describe an individual
patient’s 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.
LEEDS ASSESSMENT OF
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.
INADEQUATE ACUTE PAIN MANAGEMENT
CAN HAVE CONSEQUENCES
Chronic pain
may develop
after surgery
as a result
of complex
biochemical and
pathophysiologic
al mechanisms
Clinically
meaningful,
severe acute
postoperative
pain may be a
risk factor for the
development of
chronic pain
Up to 50%
of patients
reportedly suffer
from chronic
pain following
common surgery
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.
Effectively
managing
acute pain can
reduce the risk
for pain
progression
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 antiinflammatory 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
Analgesia
Intrathecal or
epidural opioida
• Improved pain • Increased
relief
frequency of
pruritus
Epidural opioida
+ local
anestheticb
• Improved pain • Increased
scores
motor
weakness
Epidural opioida
+ clonidine
• None noted
• None noted
Examples of opioids include morphine, fentanyl, sufentanil
b Examples of local anesthetics include bupivacaine, ropivacaine
a
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
opioidsa
Staff-administered
intramuscular (IM)
injections
• None noted
• Pain on injection
• Tissue damage
Staff-administered
intravenous
injections
• Similar pain
• Peak / trough
control to PCA
opioid adverse
drug reactions
(ADRs)
PCA without
background infusion
• Improved pain • None noted
scores vs IM
PCA with
background infusion
• Improved pain • Increased
scores vs IM
analgesic use vs
no background
a
Examples of opioids include morphine, fentanyl, hydromorphone
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
Peripheral
Regional
Analgesia
Peripheral
nerve blocksb
• Generally, improved
• None noted
pain relief and lower
analgesic consumption
compared with saline
Intra-articular
blocksb or
opioidsa
• None noted compared
with saline
Infiltration of
incisionsb
• Generally, improved
• None noted
pain relief and lower
analgesic consumption
compared with saline
• None noted
Examples of opioids include morphine, fentanyl, sufentanil
b Examples of local anesthetics include bupivacaine, ropivacaine
a
American Society of Anesthesiologists Task Force on Acute Pain Management.
Anesthesiology. 2012;116(2):248-273.
PERIOPERATIVE TECHNIQUES
IN PAIN MANAGEMENT
Technique Examples
Advantages
Nonopioid
systemic
analgesics
Acetaminophen
(oral, rectal,
injectable)
• Similar benefit to
• None noted
intravenous (IV) PCA
opioid
• Fewer ADRs
Injectable
NSAIDs
• Improved pain scores
• Reduced analgesic
use
• NSAID risks /
ADRs
Oral NSAIDs
(both non- and
selective
• None noted
• NSAID risks /
ADRs
Gabapentinoids
(both gabapentin
and pregabalin)
When combined w/
opioids
• None noted
• Improved pain scores
• Reduced analgesic use
American Society of Anesthesiologists Task Force on Acute Pain Management.
Anesthesiology. 2012;116(2):248-273.
Disadvantages
Dual Ascending Pathways
Limbic Cortex
Sensory Cortex
Thalamus
Peripheral
Nociceptor
Descending
Pathways
Ascending
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
Pathways
Nociceptor
Mid Brain
Sensory
Fiber
Dorsal
Horn
Spinal Cord
Efferent
Fiber
Slide courtesy of Raymond Sinatra, MD
Postoperative Pain
Treatment
Multimodal
Therapy
Opioids
2-Agonists
Acetaminophen
N-methyl-D-aspartate
(NMDA) antagonists
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 purposes
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:





1Toms
2Ong
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
L et al. Cochrane Database Syst Rev. 2008;(4):CD004602.
CK et al. Anesth Analg. 2010;110(4):1170-1179.
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

1Derry
2Derry
C et al. Cochrane Database Syst Rev. 2009;(1):CD004234.
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

1Werawatganon
2Marret
T, Charuluxanun S. Cochrane Database Syst Rev. 2005;(1):CD004088.
E et al; Postoperative Pain Forum Group. Br J Surg. 2007;94(6):665-673.
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 benefit—probably 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
Pain
Intensity
Analgesic
Opioid
Consumption
Opioidrelated
Side
Effects
Prevention
of Chronic
Postsurgical
Pain
Ketamine



Inconsistent
Pregabalin



Yes
Sedation,
dizziness
Gabapentin



Yes
Sedation,
dizziness
IV
Lidocaine



Possible
None noted,
but monitor
Systemic
α2 agonist



No data
Hypotension,
bradycardia
Drug
Shankar R et al. Anaesth Crit Care Pain. 2013;13(5):152-157.
Side Effects
Psychomimetic
(hallucinations,
dreams)
SYSTEMIC MULTIMODAL MEDICATIONS –
COMMON ADVERSE DRUG REACTIONS
Class
Examples
Opioids
Morphine
Hydromorphone
Fentanyl
•
•
•
•
NSAIDs
(injectable)
Ketorolac
Ibuprofen
• GI bleeds
• Nephrotoxicity
• May affect wound /
bone healing
NSAIDs
(oral,
nonselective)
Ibuprofen
Naproxen
Diclofenac
• GI bleeds
• Nephrotoxicity
• Nausea / Vomiting
• May affect wound /
bone healing
NSAIDs
(oral, selective)
Celecoxib
• Nephrotoxicity
• Nausea / Vomiting
• May affect wound /
bone healing
Acetaminophen Acetaminophen
• Hepatotoxicity
at high doses
• No effect on
bleeding times
• Well tolerated
Gabapentinoids Gabapentin
• Dizziness
• Sedation
• Helpful with
neuropathic pain
(oral and
injectable)
Pregabalin
ADR Risks
Sedation
Constipation
Nausea / Vomiting
Dizziness
Comments
• Sedation may impair
postoperative
rehabilitation
• Constipation may
affect time to
discharge
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.
TEMPORAL PAIN INTENSITY
DIFFERENCES BETWEEN ACUTE AND
CHRONIC PAIN
Acute Surgical
Pain
Chronic Pain
“Ladder”
Step 4 (interventional)
Step 3 (potent opioids)
Step 2 (weak opioids)
Step 1 (nonopioids)
No analgesics
TRANSITION FROM ACUTE SURGICAL
PAIN AND THE DEVELOPMENT OF
CHRONIC PAIN
Surgery
Decreasing
Pain Intensity
Increasing Pain
Intensity
interventional
potent opioids
interventional
weak opioids
non-opioids
no medications
Time
Nerve Injury
vs Central
Sensitization
potent opioids
adjuvants
TRANSITION FROM ACUTE SURGICAL
PAIN TO SUBACUTE (PERSISTENT) PAIN
Surgery
Decreasing
Pain Intensity
interventional
Pain Intensity
Remains High
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
Surgery
Decreasing
Pain Intensity
interventional
Pain Intensity
Remains High
potent opioids
weak opioids
potent opioids
non-opioids
adjuvants
no medications
Time 1 to 12 weeks
CLINICAL PEARLS
THANK YOU!