The EPEC-O Project Education in Palliative and End-of-life Care - Oncology

1. TM The EPEC-O Project Education in Palliative and End-of-life Care - Oncology The EPEC™-O Curriculum is produced by the EPECTM Project with major funding provided by NCI, with supplemental funding provided by the Lance Armstrong Foundation.

2. EPEC - Oncology Education in Palliative and End-of-life Care - Oncology Module 2: Cancer Pain Management

3. Overall message Pain management is an essential component of comprehensive cancer care.

4. Objectives . . . • Compare, contrast nociceptive, neuropathic pain • Understand steps of analgesic management • Demonstrate ability to convert between opioids while maintaining analgesia

5. . . . Objectives • Know use of adjuvant analgesic agents • Understand adverse effects of analgesics, their management • List barriers to pain management

6. Video

7. General principles . . . • Assessment • Management • Pharmacologic • Nonpharmacologic

8. . . . General principles • Education – patient, family, all caregivers • Ongoing assessment of outcomes, regular review of plan of care • Interdisciplinary care, consultative expertise

9. Pain pathophysiology • Acute pain • Identified event, resolves days–weeks • Usually nociceptive • Chronic pain • Cause often not easily identified, multifactorial • Indeterminate duration • Nociceptive and/or neuropathic • Wolf CJ. Ann Intern Med. 2004 .

10. Nociceptive pain . . . • Direct stimulation of intact nociceptors • Transmission along normal nerves • Somatic • Easy to describe, localize • Visceral • Difficult to describe, localize • Wolf CJ. Ann Intern Med. 2004.

11. …Nociceptive pain • Tissue injury apparent • Management • Opioids • Adjuvant/coanalgesics

12. Neuropathic pain . . . • Disordered peripheral or central nerves • Compression, transection, infiltration, ischemia, metabolic injury • Varied types • Peripheral, deafferentation, complex regional syndromes • Wolf CJ. Ann Intern Med. 2004.

13. . . . Neuropathic pain • Pain may exceed observable injury • Described as burning, tingling, shooting, stabbing, electrical • Management • Opioids • Adjuvant/coanalgesics often required

14. Pain management • Don’t delay for investigations or disease treatment • Unmanaged pain = > nervous system changes • Permanent damage, • amplified pain • Treat underlying cause (e.g., radiation for a neoplasm)

15. Placebos • No role for placebos to assess or treat pain

16. WHO 3-stepLadder WHO. Geneva, 1996.

17. Acetaminophen • Step 1 analgesic, coanalgesic • Site, mechanism of action unknown • Minimal anti-inflammatory effect • Hepatic toxicity if >4 grams/24 hours • Increased risk Hepatic disease, heavy alcohol use Mitchell JR, Potter WZ. Med Clin North Am. 1975.

18. NSAIDs . . . • Step 1 analgesic, coanalgesic • Inhibit cyclooxygenase (COX) • Vary in COX-2 selectivity • All have analgesic ceiling effects • Effective for bone, inflammatory pain • Individual variation, serial trials Carson LJ, Willett LR. Drugs.1993.

19. . . . NSAIDs • Highest incidence of adverse events • Gastropathy • Gastric cytoprotection • COX-2-selective inhibitors • Renal insufficiency • Maintain adequate hydration • COX-2-selective inhibitors • Inhibition of platelet aggregation • Assess for coagulopathy Peura DA. Cleve Clin J Med. 2002.

20. Opioid pharmacology . . . • Conjugated in liver • Excreted via kidney (90-95%) • First-order kinetics Collins SL, et al. J Pain Symptom Manage. 1998.

21. IV SC/IM PO/PR Plasma Concentration Pharmacologic Dosing Curves After a Single Opioid Dose 0 Time Half-life (t1/2)

22. . . . Opioidpharmacology . . . • Cmaxafter • PO about 1 hr • SC, IM about 30 min • IV about 6 min • Half-life at steady-state • PO/PR/SC/IV about 3-4 hrs

23. . . . Opioid pharmacology • Steady state after 4-5 half-lives • Steady state after 1 day (24 hours) • Duration of effect of “immediate-release” formulations (except methadone) • 3-5 hours PO/PR • Shorter with parenteral bolus

24. Routine oral dosingImmediate-release preparations • Codeine, hydrocodone, morphine, hydromorphone, oxycodone • Dose q 4 h • Adjust dose daily • Mild/moderate pain : increase by 25-50% • Severe/uncontrolled pain: increase by 50-100% • Adjust more quickly for severe, uncontrolled pain

25. . . . Routine oral dosingExtended-release preparations • Improve compliance, adherence • Dose q 8, 12, or 24 h (product specific) • Don’t crush or chew tablets • May flush time-release granules down feeding tubes • Adjust dose q 2-4 days (once steady state is reached)

26. Routine oral dosingLong half-life opioids • Dose interval for methadone is variable (q 6 h or q 8 h is usually adequate) • Adjust methadone dose q 4-7 days

27. Breakthrough dosing • Use immediate-release opioids • 5-15% of 24 hr dose • offer after Cmax reached • PO/PR  q 1 h • SC, IM  q 30min • IV  q 10–15min • Do NOT use extended-release opioids

28. Clearance concerns • Conjugated by liver • 90-95% excreted in urine • Dehydration, renal failure, severe hepatic failure • dosing interval, dosage size • If oliguria or anuria • STOP routine dosing of morphine use ONLY PRN Mercadante S, Arcuri E. J Pain. 2004.

29. Not recommended . . . • Meperidine • Poor oral absorption • Normeperidine is a toxic metabolite • Longer half-life (6 hrs), no analgesia • Psychotomimetic adverse effects, myoclonus, seizures • If dosing q 3 h for analgesia, normeperidine builds up • Accumulates with renal failure

30. . . . Not recommended . . . • Propoxyphene • No better than placebo • Low efficacy at commercially available doses • Toxic metabolite at high doses

31. . . . Not recommended • Mixed agonist-antagonists • Pentazocine, butorphanol, nalbuphine, dezocine • Compete with agonists  withdrawal • Analgesic ceiling effect • High risk of psychotomimetic adverse effects with pentazocine, butorphanol

32. Addiction . . . • Psychological dependence • Compulsive use • Loss of control over drugs • Loss of interest in pleasurable activities

33. . . . Addiction • Continued use of drugs in spite of harm • Rare outcome of pain management • Particularly if no history of substance abuse

34. . . . Addiction • Consider: • Substance use (true addiction) • Pseudoaddiction (undertreatment of pain) • Behavioral/family/psychological disorder • Drug diversion

35. Tolerance • Reduced effectiveness to a given dose over time • Not clinically significant with chronic dosing • If dose is increasing, suspect disease progression

36. Physical dependence • A process of neuro-adaptation • Abrupt withdrawal may cause abstinence syndrome • If dose reduction required, reduce by 50% every 2-3 days • Avoid antagonists

37. Substance users • Can have pain too • Treat with compassion • Protocols, contracting • Consultation with pain or addiction specialists

38. Pain that is poorly responsive to opioids • If dose escalation leads to adverse effects: • Try more sophisticated therapy to counteract adverse effect • Try alternative: • Route of administration • Opioid (“opioid rotation”) • Try using a coanalgesic • Use a nonpharmacologic approach

39. Ongoing assessment • Increase analgesics until pain relieved or adverse effects unacceptable • Be prepared for sudden changes in pain • Driving is safe if: • Pain is controlled, dose is stable, no adverse effects are present

40. Alternative routesof administration • Enteral feeding tubes • Transmucosal • Rectal • Transdermal • Parenteral • Intraspinal

41. Transdermal patch • Fentanyl • Peak effect after application  24 hrs • Patch lasts 48-72 hrs • Ensure adherence to skin Gourlay GK, et al. Pain. 1989.

42. Parenteral • Subcutaneous or Intravenous opioids may be administered by: • Bolus dosing q 3-4 h • Continuous infusion • Easier to administer • More even pain control

43. Intraspinal • Epidural • Intrathecal • Morphine, hydromorphone, fentanyl • Consultation

44. Bolus effect • Swings in plasma concentration can lead to: • Drowsiness ½ –1 hr post ingestion • Pain before next dose • Must move to : • Extended-release preparation • Continuous SC, IV infusion

45. Changing routesof administration • Equianalgesic table • Guide to initial dose selection • Significant first-pass metabolism of PO or PR doses with codeine, hydromorphone, morphine • Requires 2 to 3 times the dose PO or PR compared with SC or IV

46. Equianalgesic dosesof opioid analgesics

47. Changing opioids . . . • Equianalgesic table • Transdermalfentanyl • 25 microgram patch is about 45-135 (likely 50-60) mg morphine/24 hrs

48. . . . Changing opioids • Cross-tolerance must be taken into account: • Start with 50-75% of published equianalgesic dose • More if patient in severe pain, less if patient experiencing adverse effects • Methadone is a special case: • Start with 10-25% of published equianalgesic dose • Ripamonti C, Zecca E, Bruera E. Pain. 1997.

49. Adjuvant analgesics • Medications that supplement primary analgesics • May themselves be primary analgesics • Use at any step of WHO ladder

50. Gabapentin • Anticonvulsant • 100 mg PO daily to tid, titrate • Increase dose q 1-3 d • Usual effective dose 900-1,800 mg/day; max may be >3,600 mg/day • Minimal adverse effects: • Drowsiness; tolerance develops within days Backonja, et al. JAMA. 1998.