Multimodal Approaches in Clinical Practice Acute Pain Epidemiology Acute pain is very common 514 million surgical inpatient procedures were performed in 2010 in the United States ID: 525593
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Slide1
Improving the Management of Postoperative Pain
:
Multimodal
Approaches
in
Clinical PracticeSlide2
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.Slide3
Acute Pain – Scope of the
Problem
Almost all patients experience pain after surgery, procedure, or injurySurvey of 300 US adults undergoing surgery:86% experienced pain post surgery75% had moderate to extreme pain in the immediate postsurgical period74% still had pain post discharge
Gan
TJ et al.
Curr
Med Res
Opin
. 2014;30(1):149-160.Slide4
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
.Slide5
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.Slide6
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 patientThis 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 metabolismDrug-drug interactions
Psychological issues: catastrophizing, anxiety, depression,
etc
History of opioid use preoperatively
Preexisting pain
Genetics: gene polymorphismSlide7
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 surgeryMust rule out opioid tolerance from preoperative opioid use
or abuseSlide8
Challenges in the Management of Acute Pain
Variable response to analgesics
Older age = more sensitivity to opioidsEthnicityPsychological issuesType of surgical procedureThe use of pre-emptive analgesic techniques
Intraoperative anesthetic techniques:
Regional anesthetic procedures vs general
Ketamine use
Genetics: gene polymorphismSlide9
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
abuseSlide10
Neuropathic Pain (NP) Diagnosis
LANSS PAIN SCALE
Leeds Assessment of Neuropathic Symptoms
and
Signs
Bennett M.
Pain
. 2001;92(1-2):147-157.
PAIN QUESTIONNAIRE
5 Questions
SENSORY TESTING
2 Questions
Maximum
score = 24. If
< 12
, NP unlikelySlide11
Leeds Assessment of
Neuropathic
Symptoms and SignsWould 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= 0Do 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.Slide12
Challenges in the Management of Acute Pain
Variable response to analgesics
Older age = more sensitivity to opioidsEthnicityPsychological issuesType of surgical procedureThe use of pre-emptive analgesic techniques
Intraoperative anesthetic techniques:
Regional anesthetic procedures vs general
Ketamine use
Genetics: gene polymorphismSlide13
Acute Pain Impacts
Patients’ Lives
Negative effects of inadequate acute pain management include:Increased hospital stay or more frequent readmissionsReduced 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
.Slide14
Chronic pain
may
develop
after
surgery
as a result
of complex biochemical and pathophysiological
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
Effectively managing
acute
pain can reduce the risk for pain
progression
Inadequate Acute
Pain Management
Can
Have
Consequences
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(
s
uppl
1
):i69-i85.Slide15
S
tudies suggest that individualization
of pain evaluations are important to determine:Preoperative risk factorsThe pattern of resolution for each patientThe 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
.
Improving postoperative pain managementSlide16
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.
Anesthesiology
. 2012;116(2):248-273.
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.Slide17
Multimodal Therapy
Key Practice Guidelines Recommendations
American Society of Anesthesiologists Task Force on Acute Pain Management.
Anesthesiology
. 2012;116(2):248-273.
Whenever possible, anesthesiologists should use
multimodal
pain management therapy.Slide18
Multimodal Therapy
Rationale:
Targeting of different pathwaysSynergism of multiple agentsAllows for dose reduction of individual agents, reducing the risk for adverse effectsSlide19
Multimodal Therapy
Key Practice Guidelines Recommendations
American Society of Anesthesiologists Task Force on Acute Pain Management.
Anesthesiology
. 2012;116(2):248-273.
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 techniquesSlide20
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.
Multimodal TherapySlide21
Perioperative Techniques
in Pain Management
Technique
Examples
Advantages
Disadvantages
Central
Regional Analgesia
Intrathecal or epidural
opioid
a
Improved pain relief
Increased
frequency of pruritus
Epidural
opioid
a
+ local
anesthetic
b
Improved
pain scores
Increased motor weakness
Epidural
opioid
a
+ clonidine
None noted
None noted
a
Examples of opioids include morphine, fentanyl,
sufentanil
b
Examples of local anesthetics include bupivacaine,
ropivacaineAmerican Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012;116(2):248-273.Slide22
Technique
Examples
Advantages
Disadvantages
Systemic
opioids
a
Staff
-administered intramuscular (IM) injections
None noted
Pain on injection
Tissue
damage
Staff
-administered intravenous injections
Similar pain control to PCA
Peak
/ trough opioid adverse drug reactions (ADRs)
PCA without
background infusion
Improved
pain scores vs IM
None noted
PCA with background infusion
Improved pain scores vs IM
Increased 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 ManagementSlide23
Technique
Examples
Advantages
Disadvantages
Peripheral
Regional Analgesia
Peripheral nerve
blocks
b
Generally, improved pain relief
and l
ower analgesic
consumption compared with saline
None noted
Intra-articular
blocks
b
or
opioids
a
None noted compared
with saline
None noted
Infiltration of
incisions
b
Generally, improved pain relief
and l
ower analgesic
consumption compared with saline
None noted
a
Examples of opioids include morphine, fentanyl,
sufentanil
b
Examples of local anesthetics include bupivacaine, ropivacaineAmerican Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012;116(2):248-273.Perioperative Techniques in Pain ManagementSlide24
Technique
Examples
Advantages
Disadvantages
Nonopioid
systemic
analgesics
Acetaminophen
(oral, rectal, injectable)
Similar benefit to
intravenous (IV) PCA opioid
Fewer ADRs
None noted
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
Improved pain scores
Reduced
analgesic use
None
noted
American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012;116(2):248-273.
Perioperative Techniques in Pain ManagementSlide25
Dual Ascending Pathways
Spinal Cord
Mid Brain
Thalamus
Sensory Cortex
Limbic Cortex
Ascending
Pathways
Peripheral
Nociceptor
Dorsal
Horn
Sensory
Fiber
Efferent
Fiber
Descending
Pathways
Slide courtesy of Raymond Sinatra, MDSlide26
Physiological Pain
Spinal Cord
Mid Brain
Thalamus
Sensory Cortex
Limbic Cortex
Ascending
Pathways
Nociceptor
Dorsal
Horn
Sensory
Fiber
Efferent
Fiber
Slide courtesy of Raymond Sinatra, MDSlide27
Postoperative Pain
Treatment
Multi
m
odal
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
Opioids
2
-Agonists
Acetaminophen
N
-methyl-
d
-aspartate
(NMDA) antagonists
Slide courtesy of Raymond Sinatra, MD and modified for educational purposes Slide28
Multimodal Approaches:
Evidence-based Summary
Acetaminophen (APAP) – oral, single doseCochrane review151 studies, 5762 patients, 3277 active, 2425 placebo50%
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
review
2
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
1
Toms L et al.
Cochrane Database
Syst
Rev
. 2008;(4):CD004602.
2
Ong CK et al.
Anesth
Analg
.
2010;110(4):
1170-1179.Slide29
Acetaminophen – Parenteral
Studied single dose, multiple dose over 24 hours compared with placebo
Orthopedic surgery, laminectomy, abdominal, gynecological, cardiac, and thyroidectomyDosing: 1 gram IV, either single dose or every 6 hoursSummary APAP patients:Statistically significant shortened time to meaningful pain relief and in total relief compared with placeboImproved patient satisfaction with pain control, lower morphine consumption (up to 61%) and decreased incidence of vomitingNo 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.
Multimodal Approaches:
Evidence-based SummarySlide30
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 cannabinoidsAPAP 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 effectBertolini
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.Slide31
Nonselective NSAIDs
Single dose oral ibuprofen
1 – 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 acetaminophenAdverse
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 2012Multimodal Approaches: Evidence-based SummarySlide32
S
elective NSAIDs – Single dose Celecoxib
Cochrane review - 10 studies, 1785 patientsNNT for 50% decrease in pain over 4 to 6 hours:Celecoxib 200 mg: 4.8Celecoxib 400 mg: 3.5Median 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 SummarySlide33
Injectable NSAIDs
Ketorolac and ibuprofen studied in United States
Indicated for short-term moderate to severe acute pain that requires analgesia at the opioid levelStudies (variety of surgery types) with ketorolac1,2 compared with placebo suggest patients who received ketorolac:Significant reduction in painReduction in opioid consumption (~30%)Facilitation of quicker recovery and rehabilitation
Studies with ibuprofen in orthopedic and abdominal surgery
3
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
SummarySlide34
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' analgesiaPatients 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 SummarySlide35
Parenteral Opioids – Patient-
c
ontrolled AnalgesiaPCA vs nurse-controlled (NCA) after cardiac surgery10 randomized trials, 666 patientsCompared with NCA:PCA significantly reduced visual analogue scale (VAS) at 48 hours, not at 24 hoursPCA groups showed significantly increased cumulative morphine equivalents consumed at 24 hoursNo 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 SummarySlide36
Epidural Opioids
Cochrane Review
Abdominal aortic surgery15 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
D
uration
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 SummarySlide37
Epidural Local Anesthetics vs
O
pioid-based Regimens (systemic or epidural)Cochrane ReviewAbdominal surgery, 8 studies, small numbers of patientsKey outcome analysis: Postoperative: Gastrointestinal (GI) function, pain, PONV, and complicationsConclusions:
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 SummarySlide38
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 surgeryThere 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 opioidsC
omparing PCA vs CEA in colorectal surgery
2
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.
2
Marret E
et
al; Postoperative Pain Forum Group.
Br J
Surg.
2007;94(6):665-673.
Multimodal Approaches:
Evidence-based SummarySlide39
Intrathecal (IT) Morphine + PCA Morphine vs PCA Morphine Alone
Major abdominal surgery, 60 patients
SummaryAnalgesia 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 dayNo 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 SummarySlide40
Local Anesthetics – Wound Infiltration
Useful in a variety of surgeries
Cardiothoracic, abdominal, gynecological, colorectal, head and neck, orthopedicGeneral conclusions from studies:Effective in a variety of surgical sitesNeither infection nor toxicity appears to be a significant clinical issuePreoperative blockage superior to postoperativePain is reduced both at rest and on mobilizationOpioid 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 SummarySlide41
Intravenous
Lidocaine
Meta-analysis after abdominal surgery8 trials, 161 patients received lidocaine (active arm), 159 saline (placebo arm) Both arms could receive as-needed opioidsLidocaine IV groups showed:Decreased duration of ileusLength 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 SummarySlide42
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 opioidsIn 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
N
o
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 SummarySlide43
Ketamine Intravenous – Systematic Review
70 studies, 4701 patients (2652 ketamine, 2049 placebo)
SummaryPatients 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
).
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 SummarySlide44
Gabapentinoids
- Systematic Review of RCTs
Gabapentin: 22 trials, 1640 patientsPregabalin: 8 trials, 707 patientsSummary:
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 placebo4 studies
reported no
pregabalin
effects on preventing PONVBoth agents reduced opioid consumption by ~30%
Dauri
M et al.
Curr
Drug Targets
. 2009;10(8):71633.26
Multimodal Approaches:
Evidence-based SummarySlide45
Systemic
2 Agonist – Meta-analysis of RCTsSummaryModerate 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.
Multimodal Approaches:
Evidence-based SummarySlide46
Perioperative Pain –
Analgesic Adjuvants
Drug
Pain Intensity
Analgesic Opioid Consumption
Opioid-related Side Effects
Prevention
of Chronic
Postsurgical
Pain
Side Effects
Ketamine
Inconsistent
Psychomimetic
(hallucinations, dreams)
Pregabalin
Yes
Sedation,
dizziness
Gabapentin
Yes
Sedation, dizziness
IV
Lidocaine
Possible
None noted,
but monitorSystemic α2 agonistNo dataHypotension, bradycardia
Shankar R et al.
Anaesth
Crit
Care
Pain
.
2013;13(5):152-157. Slide47
Systemic Multimodal Medications – Common Adverse Drug Reactions
Class
Examples
ADR Risks
Comments
Opioids
Morphine
Hydromorphone
Fentanyl
Sedation
Constipation
Nausea / Vomiting
Dizziness
Sedation
may impair postoperative rehabilitation
Constipation may affect time to discharge
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 / VomitingMay affect wound / bone healingAcetaminophenAcetaminophen(oral and injectable)
Hepatotoxicity at high dosesNo effect on bleeding timesWell toleratedGabapentinoidsGabapentin PregabalinDizzinessSedation
Helpful with neuropathic painSlide48
Multimodal Analgesia
The state-of-the-art is multimodal therapy with:
Opioids IV Intraspinal
(IS)
O
ral 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. Slide49
Temporal Pain Intensity
Differences Between Acute and
Chronic Pain
Step 4 (interventional
)
Step 3 (potent
opioids
)
Increasing Pain Intensity
Step 2 (weak
opioids
)
Step 1 (
nonopioids
)
Decreasing Pain Intensity
No
analgesics
Chronic Pain “Ladder”
Acute Surgical PainSlide50
Transition From Acute Surgical Pain and the Development of Chronic Pain
interventional
potent opioids
weak opioids
non-
opioids
Decreasing
Pain Intensity
Surgery
Increasing Pain
Intensity
no medications
Time
Nerve Injury
v
s Central
Sensitization
interventional
potent opioids
adjuvantsSlide51
Transition From Acute Surgical Pain to Subacute (Persistent) Pain
interventional
potent opioids
weak opioids
non-
opioids
Decreasing
Pain Intensity
Surgery
Pain Intensity Remains High
no medications
Time 1 to 12 weeks
potent opioids
adjuvantsSlide52
Multimodal Pain Management:
Step Therapy
Crews JC.
JAMA.
2002;288(5):629-632.
Severe Postoperative Pain
Step 1 and Step 2 Strategies
AND
Local Anesthetic Peripheral Neural Blockade
(with or without catheter)
AND
Use of Sustained-release Opioid Analgesics
Nonopioid
Analgesic
Acetaminophen, NSAIDs, or COX-2 Selective Inhibitors
AND
Local Anesthetic Infiltration
Moderate Postoperative Pain
Mild Postoperative Pain
Step 1 Strategy
AND
Intermittent Doses of Opioid Analgesics
Step 3
Step 2
Step 1
Reprinted with permission. Copyright © 2002
American Medical Association. All rights reserved.Slide53
Pharmacoeconomics
Consequences of side effects
Consequences of inadequate pain control
Consequences of postoperative complications
ReadmissionsSlide54
Transition From Acute Surgical Pain to Subacute (Persistent) Pain
interventional
potent opioids
weak opioids
non-
opioids
Decreasing
Pain Intensity
Surgery
Pain Intensity Remains High
no medications
Time 1 to 12 weeks
potent opioids
adjuvantsSlide55
Clinical PearlsSlide56
Thank you!