Perioperative Pain
Management Using a MultiModal Approach
Melanie MacInnis; PharmD, RPh
Clinical Pharmacist, HHS/McMaster
May 2012
Learning Objectives
• After this presentation, the learner should be
able to:
– Describe the rationale of multimodal analgesia
– Understand the role of acetaminophen, NSAIDs
and gabapentin in post-operative pain control
– Determine patient specific factors for prescribing a
multi modal pain control regimen
Pain Definitions
Pain is defined by IASP as “an unpleasant sensory
and emotional experience associated with actual
or potential tissue damage, or described in terms
of such damage”.
Analgesia Postop Pain
“The major difference between iatrogenic pain and
other types of pain is that iatrogenic pain is
anticipated. Therefore, the physician has an
excellent opportunity to deal with such pain in a
planned and expeditious manner.”
Brian Goldman, MD
The Role of Pain Control in
Postoperative Care
• Prevent suffering
• Hasten recovery
• Influence perioperative morbidity
• Decrease the development of chronic pain
Chronic Pain Medications
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Anti-inflammatories (NSAIDs, steroids)
Muscle relaxants
Benzodiazepines
TCAs and other anti-depressants (SSRIs, SNRIs)
Anticonvulsants (Gabapentin, Pregabalin, Carbamazepine)
Opioids
Tramadol
IV Anti-arrhythmics (lidocaine, bretylium)
Topical formulations (capsaicin, lidocaine, NSAIDs)
Alpha 2-agonists (clonidine, guanethedine)
Cannabinoids (Nabilone)
NMDA antagonists (ketamine, methadone, memantine)
Osteoclast inhibitors (calcitonin, alendronate)
Opioid Tolerance
• Shortened duration and decreased intensity of analgesia,
euphoria, sedation, and other CNS effects
• Predictable pharmacologic adaptation
• Rightward shift in the dose-response curve means increasing
amount of drug to maintain the same effects
• In general, the higher the daily dose, the greater the degree of
tolerance
• Individuals requiring >1 mg IV (3 mg PO) morphine per hour
for a period of > 1 month are considered to have high-grade
tolerance and withdrawal symptoms
World Institute of Pain 2005; 5(1): 18-32
Can J Anesth 2006; 53 (12): 1190-99
Problems of Equi-Analgesic Dose
Ratios of Opioids
• Incomplete cross tolerance occurs during
chronic opioid use
• Accumulation of active metabolites can
influence effect of opioids
• The ratios may change according to the
direction of opioid switch
Strategies for Pain Control
• Multimodal analgesia: balanced technique
• Determine and continue baseline opioid requirements, in
addition to acute pain requirements
• Treat contributing co-morbidities, such as anxiety, poor sleep,
nausea and constipation
• Order pain medications in the acute phase routinely, rather
than PRN
CNS Drugs 2007; 21(3): 185-211
Multi modal analgesia
• Different classes of drugs exert different side
effects
• Side effects can be dose related
• Additive/synergistic
• Combinations can provide superior analgesia
than either drug alone
• Opioid sparing
• Improved recovery, shorter hospital stay
Acetaminophen
• Very weak COX inhibitor
– No appreciable anti-inflammatory or NSAID side
effects
• Liver metabolism
• 4g/d in healthy adults
• Lower doses:
– Liver disease (2g/d)
– Alcoholism (2g/d)
– Frail elderly (3.2g/d)
“Tylenol”
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Always confirm with patients
Extra strength tylenol ≠ tylenol with codeine
PRN vs RTC
Acetaminophen as part of multi-modal
analgesia minimizes opioid requirements by
20%
NSAIDS
• Effective for post operative pain
• MOA:
– Inhibit cyclo-oxygenase (COX) in the periphery and
spinal column
– Several variants of COX enzyme
– Influence platelet function, GI mucosa, and renal
function, CV risk
– Selecting the COX variant to avoid side effects
Adverse effects
• Platelet dysfunction
– NSAIDs alone not a risk for spinal hematoma
• GI ulceration
• Nephrotoxicity
• Headache, tinnitus, abdominal pain, rash,
hyperkalemia, asthma
Renal function
• Serum creatinine is used as a surrogate
• NB: extremes of body weight and
nourishment
• Baseline SCr and while on NSAID
• Also urea nitrogen, I/O
• Cockroft Gault
• eGFR
• SCr = (140-age)(kg) x 0.85 if female
(SCr)(72)
http://nephron.com/cgi-bin/CGSI.cgi
OR
www.globalrph.com (from calculators menu
select CrCl multi-calc under C)
Monitoring for NSAIDs
• CBC (plts), SCr, BUN, lytes
• Absolute contra-indication
– GI ulcer, hx of PUD/GUD; CHF; low platelets; CrCl
less than 30ml/min
• Relative contraindication
– Fracture, GERD, age
• Celecoxib: sulfa allergy; only COX-2 selective,
200mg/d max
• Ketorolac: only IV product, po
• Ibuprofen: suspension, OTC or rx, po
• Naproxen: OTC or rx, po or pr
NSAIDs + Acetaminophen
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21 studies
1909 patients
Ibuprofen, diclofenac, ketorolac, aspirin
Lower pain scores
Lower supplemental analgesic requirements
Better global pain relief
Anesth Analg 2010; 110:1170-9
NSAIDs + Acetaminophen
APAP+NSAID
% more effective
Pain intensity
lessened
Analgesic
supplementation
lessened
64%
37.7%
31.3%
85%
35.0%
38.8%
NSAID
APAP + NSAID
APAP
NSAIDs + Acetaminophen
• No evidence of increased side effects
• If morphine rescue required; higher incidence
of N/V
Analgesic Efficacy
• NNT calculated for at least 50% pain relief
over 4-6h compared to placebo
• Oral, single dose
• Moderate to Severe pain
• All are oral unless otherwise specified
• Doses in mg
Analgesic (mg)
NNT
Ibuprofen 600 or 800
1.7
Ibuprofen 400
2.5
Acetaminophen 650 + oxycodone 10 (2 Percocet)
2.6
Ketorolac 10
2.6
Naproxen 500
2.7
Morphine 10mg IV
2.9
Ketorolac 30mg IV
3.4
Acetaminophen 500
3.5
Celecoxib 200
3.5
Acetaminophen 1000 (2 Extra Strength Tylenol)
3.8
Acetaminophen 650 + codeine 60 (2 Tylenol #3)
4.2
Acetaminophen 650 (2 Tylenol Plain)
4.6
Acetaminophen 325 + oxycodone 5 (1 Percocet)
5.5
Acetaminophen 325 + codeine 30 (1 Tylenol #3)
5.7
Codeine 60mg
16.7
Gabapentinoids
• Gabapentin (Neurontin) and pregabalin (Lyrica)
• Enhance the inhibitory pain pathway long term
• Impact sodium gated channels of nerves in the
periphery
• Prevent hyperalgesia postoperatively
• Modify transmission of nerve impulses
• Can prevent persistent post surgical pain at 3-6
months
Gabapentinoids
• Role in post-operative treatment is unclear
• Can reduce pain intensity and opioid
consumption
• Optimal dose and duration unknown
– Gabapentin: 300-1200mg pre op, post op 100-300mg
variety of dosing strategies
– Pregabalin: 150-300mg pre-op, post op doses 50mg150mg of durations 24h – 2 weeks
• No influence on prevention of PONV
Gabapentinoids
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Renally eliminated
SCr needed baseline and after initiation
Dose reduction in renal impairment
After long term use needs to be tapered to DC
(seizure risk)
• In elderly can cause confusion, sedation,
dysphoria
Take Home Points
• Multimodal analgesia can help improve pain control
and minimize side effects
• Persistent postsurgical pain may be influenced by
improved acute pain control
• Order routine pain medications initially for moderate
to severe pain (rather than PRN)
Take Home Points
• Patient specific factors need to be considered
in prescribing the best post-operative
analgesic regimen
• Around the clock NSAIDS + acetaminophen
are effective and minimize opioid use
• The role of gabapentinoids is unclear in post
operative pain control
Thank you.
Questions and Comments.