1. Perioperative Pain Management Using a Multi-Modal Approach
Melanie MacInnis; PharmD, RPh
Clinical Pharmacist, HHS/McMaster
May 2012

2. 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

3. 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”.

4. 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

5. The Role of Pain Control in Postoperative Care
Prevent suffering
Hasten recovery
Influence perioperative morbidity
Decrease the development of chronic pain

7. Chronic Pain Medications
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)

8. 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

9. Can J Anesth 2006; 53 (12):

10. 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

11. 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

12. CNS Drugs 2007; 21(3):

13. 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

14. Acetaminophen Very weak COX inhibitor Liver metabolism
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)

15. “Tylenol” 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%

16. 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

18. Adverse effects Platelet dysfunction GI ulceration Nephrotoxicity
NSAIDs alone not a risk for spinal hematoma
GI ulceration
Nephrotoxicity
Headache, tinnitus, abdominal pain, rash, hyperkalemia, asthma

19. 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

20. SCr = (140-age)(kg) x 0.85 if female OR
(from calculators menu select CrCl multi-calc under C)

21. 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

22. 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

23. NSAIDs + Acetaminophen
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

24. NSAIDs + Acetaminophen
% more effective
Pain intensity lessened
Analgesic supplementation lessened
APAP+NSAID
64%
37.7%
31.3%
NSAID
APAP + NSAID
85%
35.0%
38.8%
APAP

25. NSAIDs + Acetaminophen
No evidence of increased side effects
If morphine rescue required; higher incidence of N/V

26. 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

27. Analgesic (mg)
NNT
Ibuprofen 600 or 800
1.7
Ibuprofen 400
2.5
Acetaminophen oxycodone 10 (2 Percocet)
2.6
Ketorolac 10
Naproxen 500
2.7
Morphine 10mg IV
2.9
Ketorolac 30mg IV
3.4
Acetaminophen 500
3.5
Celecoxib 200
Acetaminophen (2 Extra Strength Tylenol)
3.8
Acetaminophen codeine 60 (2 Tylenol #3)
4.2
Acetaminophen 650 (2 Tylenol Plain)
4.6
Acetaminophen oxycodone 5 (1 Percocet)
5.5
Acetaminophen codeine 30 (1 Tylenol #3)
5.7
Codeine 60mg
16.7

28. 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

29. Gabapentinoids Role in post-operative treatment is unclear
Can reduce pain intensity and opioid consumption
Optimal dose and duration unknown
Gabapentin: mg pre op, post op mg variety of dosing strategies
Pregabalin: mg pre-op, post op doses 50mg-150mg of durations 24h – 2 weeks
No influence on prevention of PONV

30. Gabapentinoids 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

31. 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)

32. 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

33. Questions and Comments.
Thank you.
Questions and Comments.