Perioperative Pain Management Using a Multi-Modal 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 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 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)

“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%

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 GI ulceration Nephrotoxicity 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 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 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 % more effective Pain intensity lessened Analgesic supplementation lessened APAP+NSAID 64% 37.7% 31.3% NSAID APAP + NSAID 85% 35.0% 38.8% 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 Naproxen 500 2.7 Morphine 10mg IV 2.9 Ketorolac 30mg IV 3.4 Acetaminophen 500 3.5 Celecoxib 200 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 50mg-150mg of durations 24h – 2 weeks No influence on prevention of PONV

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

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

Questions and Comments. Thank you. Questions and Comments.