1. Principles of Surgery PERI-OPERATIVE ANALGESIA Joseph Kay, MD FRCPC Sunnybrook & Women’s College HSC Assistant Professor, University of Toronto

2. Why should we treat peri-operative pain?  pain and suffering  complications  likelihood of chronic pain  patient satisfaction  speed of recovery  LOS  cost  productivity and quality of life

3. Adverse effects of poor pain management Cardiovascular Respiratory Gastrointestinal\Genitourinary Neuroendocrine\Metabolic Musculoskeletal Immunological Psychological

4. Current pain management Pain can virtually be eliminated with minimal side effects BUT 70% inpatients still have moderate or severe pain 40% outpatients have significant pain in 1 st 24 h WARFIELD Anesthesiol 1995 83:1090 BEAUREGARD Can J Anesth 1998 45:304

5. Barriers to effective pain management I ANESTHESIOLOGIST Inadequate pain education Underestimation analgesic requirements Failure to recognize patient variability Inadequate use local\regional techniques Complications from side effects

6. Barriers to effective pain management II PATIENT Expectation of severe pain Inadequate pain education Analgesic side effects Fear of addiction

7. Barriers to effective pain management III NURSE Expectation of severe pain Inadequate pain education Fear of causing analgesic side effects e.g respiratory depression, addiction Insufficient time for assessment/ treatment

8. Barriers to effective pain management IV SURGEON Belief that pain is ‘normal’ and not harmful Concern that pain may mask injury Inadequate pain education ‘Don’t ask don’t tell’ Complications from side effects\addiction

9. Barriers to effective pain management V HOSPITAL Inadequate funding & resources with pain as low priority Inadequate commitment Lack of accountability

10. Traditional opioid analgesia Parenteral prn

11. Traditional opioid analgesia Sedation Respiratory depression Nausea & Vomiting Urinary retention Ileus Constipation Pruritus

12. Multimodal Analgesia Using more than one drug, acting at a different place or with a different mechanism, each with a lower dose than if used alone, thus providing better analgesia with less side effects.

13. Multimodal Analgesia Opioid NSAID (COXIB) Acetaminophen Local anesthetic block Other adjuncts

14. Multimodal Analgesia

15. Better analgesia Less side effects Can decrease hospital stay May improve surgical outcome May decrease chronic pain KEHLET Br J Surg 1999 86:227 CAPDEVILLA Anesthesiol 1999 91:8 REUBEN Anesthesiol 2001 95:390

16. Multimodal Analgesia Opioids Systemic - oral/parenteral/transdermal Neuraxial - spinal/epidural Peripheral - intra-articular, periosteal

17. Multimodal Analgesia Opioids Sites of action Central: dorsal horn spinal cord Peripheral: synovium periosteum

18. Multimodal Analgesia Opioids Systemic Oral - contin + b/t Parenteral - iv PCA sc infusion + b/t

19. Multimodal Analgesia Opioids Neuraxial Spinal - single shot Epidural - continuous infusion (+local anesthetic)

20. Multimodal Analgesia Opioids Peripheral Intra-articular Iliac crest bone graft

21. Opioid Intraoperative vs Postoperative THA 40 pts Intra-operative group: achieved VAS<3 42 vs 76 min  morphine PACU 7 vs 15 mg  respiratory depression PICO Can J Anesth 2000 47:309

22. Opioid Oral Controlled Release Oxycontin TKA 59 pts 29 oxycontin vs 30 placebo Oxycodone q4h prn Oxycontin group:  pain  LOS 2.3 days  ROM CHEVILLE J Bone Jt Surg Am 2001 83A6:915

23. Opioid Iliac Crest Infiltration Spine fusion 60 pts Group I: saline into donor site Group II: 5 mg i.m morphine Group III: 5 mg morphine into donor site

24. Opioid Iliac Crest Infiltration Gp III 50% less morphine 24h lower pain scores > 2h  pain at 1 yr 5% vs 33% REUBEN Anesthesiol 2001 95:390

25. Multimodal Analgesia NSAID / COXIBS potent analgesics for mild-moderate pain adjunct to opioid for moderate-severe pain  VAS 2/10  opioid consumption 30-50%  opioid related side effects

26. NSAID Spinal fusion 70 pts Morphine PCA ketorolac 0-30 mg iv q6h Ketorolac 7.5-30 mg:  morphine use  pain VAS  sedation  nausea REUBEN Anesth Analg 1998 87:98

27. NSAID side effects GI ulceration mild platelet dysfunction inhibition bone fusion mild Na + retention / hypertension  renal function in low flow states

28. NSAID side effects CAN WE MAKE A BETTER NSAID? Keep analgesic potency Reduce side effects

29. NSAID mechanism of action inhibits cyclo-oxygenases (COX-1&2) which convert arachidonic acid to prostaglandins (PG)  PGE 2 to sensitize nociceptors  PGE 2, PGI 2, TXA 2 for homeostasis

30. COX 2 isoforms COX-1 constitutive – everywhere ‘housekeeping’ PGE 2, PGI 2, TXA 2 COX-2 constitutive in kidney, CNS induced by trauma / pain main source PGE 2 for sens.

31. PGE 2 production EP receptor BK receptor Tissue Injury IL-1  Peripheral induction of COX-2 Central induction of COX-2

32. PGE 2 sensitization EP receptor Bradykinin BK receptor PGE 2 Tissue Injury PGE 2

33. YES Can we make a selective COX-2 inhibitor with excellent analgesia and less side effects than a conventional NSAID?

34. COX-2 COX-1 Active site Arachidonic acid Active site Arachidonic acid NSAID

35. COX-2 COX-1 Active site COX-2 Inhibitor Active site Arachidonic acid COX-2 Inhibitor PGE 2 PGI 2 TXA 2 Arachidonic acid

36. COX-2 inhibitors Celecoxib Rofecoxib Valdecoxib

37. COXIB analgesic potency similar to or more potent than NSAIDs valdecoxib 40 mg = ketorolac 30 mg = 2 percocets! 24h duration DANIELS J Am Dent Assoc 2002 133:611 MEHLISCH J Oral Maxillofac Surg 2003 61:1030

38. COXIB pre-emptive effect rofecoxib 50 mg given 1 h pre-incision vs post  pain  opioid consumption prevents PGE 2 sensitization from up- regulated COX-2 REUBEN Anesth Analg 2002 94:55

39. COXIB side effects: GI  incidence ulcers or bleeding compared to conventional NSAIDs BOMBARDIER NEJM 2000 343:1520

40. COXIB side effects: renal function COX-2 constitutive in kidney same effect as conventional NSAID mild Na + retention, blood pressure   renal blood flow in hypovolemia or  CO Avoid in hypovolemia, CHF, renal dysfunction, uncontrolled  BP,DM BRATER J Pain Symptom Management 2002 23:S15

41. COXIB side effects: bone fusion conventional NSAIDs inhibit bone growth & fusion coxibs do not appear to clinically affect bone fusion rofecoxib/celecoxib vs control vs ketorolac in spinal fusion patients 9/132 vs 6/90 vs 23/120 GLASSMAN Spine 1998 23:834 REUBEN ASRA Annual mtg 2002 Abstract PD-16 LEWIS Proc NA Spine mtg 2000 64

42. COXIB side effects:allergy Can use in asthmatics May use rofecoxib with caution in ASA allergy Avoid celecoxib/valdecoxib with sulfa allergy GLASSER Pharmacotherapy 2003 23:551 STEVENSON J Allergy Clin Immun 2001 108 :47

43. COXIB side effects: platelet function NO effect on platelets NO effect on bleeding Patients on warfarin may have  INR (need to adjust dose for cel/rof) LEESE Am J Emerg Med 2002 20:275 HOMONCIK Clin Exp Rheumatol 2003 21 :229

44. Summary COXIBS compared to NSAIDs more potent analgesic avoid opioid longer duration once a day pre-emptive effect use pre-op no effect on platelets use pre-op less or no GI S/E use in risk no effect on bone fusion use in ortho

45. Multimodal Analgesia Acetaminophen Central COX 3 inhibitor  opioid use by 30%  opioid related side effects SHUG Anesth Analg 1998

46. Multimodal Analgesia Acetaminophen Avoid with: hepatic insufficiency alcoholism malnutrition P450 inducers

47. Multimodal Analgesia Acetaminophen + NSAID usual adjunct for PCA opioid combination better than either alone VAS  rest & dynamic FLETCHER Can J Anesth 1997 44:479

48. Multimodal Analgesia Local anesthetic Infiltration Intraperitoneal Nerve block Neuraxial

49. Local anesthetic Local anesthetic Movement assoc pain reduces function Local anesthetic blocks A  & c fibres

50. Incisional local infiltration Lap chole 157 pts periportal & intraperitoneal bupivacaine pre-incision or at end  pain first three hours with pre-incisional periportal bupivacaine (+/- intraperitoneal) LEE Can J Anesth 2001 48:545

51. Peritoneal local infiltration Appendectomy Peritoneal infiltration 0.5% bupivacaine  pain scores  analgesic consumption COLBERT Can J Anesth 1998 45:734

52. Local infiltration Bupivacaine is BACTERICIDAL AYDIN Eur J Anesth 2001 18:687

53. Nerve Block Single shot ankle block interscalene 0.5% bupivacaine 6-24h postop analgesia

54. Nerve Block Continuous Continuous Femoral Nerve Blk post total knee arthroplasty compared to PCA or epidural

55. Nerve Block Continuous femoral Better analgesia Less morphine use Less opioid related side effects Better ambulation & hemodynamic stability CAPDEVILLA Anesthesiol 1999 91:8 SINGELYN Anesth Analg 1998 87:88 CHELLY J Arthroplasty 2001 16:436

56. Nerve Block Continuous femoral Better surgical outcome Less perioperative bleeding Increased flexion with CPM Earlier hospital discharge Less time in rehabilitation CAPDEVILLA Anesthesiol 1999 91:8 SINGELYN Anesth Analg 1998 87:88 CHELLY J Arthroplasty 2001 16:436

57. Nerve Block Single shot femoral 40 ml 0.25% bupivacaine vs saline post TKA  pain VAS  1-2 50%  morphine use 50%  morphine related side effects Better ambulation LOS 3 vs 4 days WANG Reg Anesth Pain Med 2002 27:139

58. Nerve Block Continuous interscalene /popliteal Disposable pumps Major shoulder /leg surgery can be done as an outpatient  $

59. Nerve Block Continuous popliteal nerve block at home 30 pts randomized to local anesthetic or saline Rescue oral opioids VRS 0 vs 4/10 Sleep disturbances 10x less O opioid pills vs 8 ILFIELD Anesthesiology 2002 97:208

60. Epidural Analgesia

61. LOCAL /OPIOID superior analgesia better cardiopulmonary function earlier return bowel function

62. Epidural Analgesia LOCAL /OPIOID better ambulation decreased hospital stay safe to use on wards

63. Epidural Analgesia Sigmoidectomy Early ambulation & feeding 2 day median hospital stay KEHLET Br J Surg 1999 86:227

64. Summary Pre-op Coxib Local infiltration / block Acetaminophen / Coxib post-op Controlled release opioid Thoracic epidural for major abdominal & thoracic surgery Continuous nerve blocks for extremity surgery