Pain Management

1. Pain Management Suzana Makowski, MD Palliative Medicine and Laura Lambert, MD Surgical Oncology

2. Key concepts • Pain assessment • Opioid pharmacology • Pain management • Side effects of pain medications

3. The 5th Vital Sign Pain

4. What do most surgical patients have in common? Pain Pre-op Post-op

5. How do you assess pain? • L the exact Location of the pain and whether it travels to other body partsO Other associated symptoms such as nausea, numbness, or weaknessC The Character of the pain, whether it's throbbing, sharp, dull or burningA Aggravating or Alleviating factors. What makes the pain better or worse?T the Timing of the pain, how long it lasts, is it constant or intermittent?E the Environment where the pain occurs, for example, while working or at home

6. How do you assess pain? • Intensity • Categories: Nociceptive (somatic and visceral), Neuropathic

7. Acute vs. Chronic Pain • Acute pain • Identified event (onset) • Resolves in days-weeks • Usually nociceptive • Chronic pain • Cause often not easily identified, multifactorial • Indeterminate duration • Nociceptive and/or neuropathic

8. Barriers to assessing and treating pain • Addiction: means a person has lost control over the use of the drug and they continue to use it despite harmful consequences. • Tolerance: the situation in which a drug becomes less effective over time and an increased dosage of the medication is required to maintain the same pain relief. • Dependence: a person will develop symptoms and signs of withdrawal (e.g., sweating, rapid heart rate, nausea, diarrhea, goosebumps, anxiety) if the drug is suddenly stopped or the dose is lowered too quickly. • Pseudo-addiction: refers to patient behaviors that may occur when pain is under-treated. This is different from true addiction because such behaviors can be resolved with effective pain management. • Substance-abusers

9. What is the easiest pain to bear? SOMEONE ELSE’S! • Don’t delay • Unmanaged pain leads to nervous system changes • Permanent damage • Amplification of pain • Development of chronic pain

10. WHO step-ladder 7-10 3severe 4-6 Morphine Hydromorphone Methadone Levorphanol Fentanyl Oxycodone ± Adjuvants 2moderate 1-3 A/Codeine A/Hydrocodone A/Oxycodone A/Dihydrocodeine Tramadol ± Adjuvants 1 mild ASA Acetaminophen NSAID’s ± Adjuvants WHO. Geneva, 1996.

11. Opioid Pharmacology • Conjugated in liver • First pass metabolism • Excreted by kidney (90-95%) • First order kinetics

12. Opioid kinetics IV SC/IM Cmax PO/PR Plasma Concentration 0 Time Half-life (t1/2) 15-20 min 6-7 min 45-60 min

13. Clearance Issues • Conjugated by liver • 90-95% excreted in urine • Dehydration, renal failure, severe hepatic failure • Decrease interval/dosing size • If oliguria/anuria • STOP routine dosing (basal rate) of morphine • Use ONLY PRN

14. Opioid pharmacology • What is the half life (range) for IV opioids? • 2-4 hours • How many half lives to get to steady state? • 4-5 • What do you base your scheduled dosing on: Cmax or T1/2? • T1/2 • What do you base your breakthrough dosing on:Cmax or T1/2? • Cmax

15. Routine oral dosing:immediate release formulations • Scheduled dosing based on t1/2 • Q4 hours • PRN dosing based on time to Cmax • Q1 hour PRN • Adjust scheduled dose daily based on prn use

16. Routine oral dosingExtended release preparations • Reason for use: • Improve compliance, adherence • Dose q8, q12, q24 hours (depending on product) • Don’t crush or chew • May use time-release granules (Kadian) • Adjust dose every 2-4 days (once steady state is reached.)

18. FROM CHART: Opioid A dose (mg), route X opioid B route = opioid B dose (mg), route opioid A route () Equation: To convert from one opioid to another using same route

19. Coverting • Step 1: Calculate 24 hour dose of medication • Step 2: Choose 2nd medication • Step 3: Choose numbers from chart for ratio • Step 4: Calculate 24 hour dose of new opioid • Step 5: Divide 24 hour dose by new rate

20. Example: • Mr. Jones is a 67 yo man with colon cancer, just had low anterior resection with diverting ileostomy. He is now NPO. • His home regimen is Oxycontin 40mg bid and oxycodone IR 10 mg q1 hour prn, which he uses twice a day. • The chief resident writes for a Dilaudid PCA with no basal and 0.1mg q6 minutes demand. • Within one hour after the surgery, you are called by the nurse in the PACU about the pain because the CR is back in the OR.

21. Example • Step 1: calculate 24 hour dose – • Oxycontin 40mg bid = 80mg • Oxycodone 10mg 2x = 20 mg • Total 24 hour dose = 100 mg • Step 2: choose new opioid = hydromorphone • Step 3: look at the chart

23. Example continued • Step 3: select ratio from chart for formula Hydromorphone IV = 1 Oxycodone PO = 10 • Step 4: Calculate 24 hour dose of new opioid 100mg oxy (PO/24 hrs) x (1/10) = 10 mg hydromorphine IV/ 24 hrs • Step 5: Calculate new rate • 10mg/24hrs = 0.4 mg hydromorphone IV per hour At least!

25. Common Constipation Dry mouth Nausea/vomiting Sedation Sweats Less Common Bad dreams or hallucinations Delirium Myoclonus Seizures Pruritus, urticaria Respiratory depression Urinary retention Opioid Side Effects

26. POP Quiz Pharmacologic tolerance develops to all of the following side effects of opioid analgesics except: • constipation • nausea • respiratory depression • sedation

27. Constipation • Common to all opioids • Due to effects on: • CNS, spinal cord, myenteric plexus of gut • Easier to prevent than to treat • Diet insufficient • Bulk forming agents not recommended • Always order bowel regimen with opioid: • Colace and senna if able to tolerate po

28. Options to Treat Constipation • Stimulant laxative: • Senna, bisacodyl, glycerine, etc. • Stool softener • Docusate • Prokinetic agent • Metoclopramide • Osmotic laxative (from above or below) • Specific to peripheral opioid receptors • methylnatrexone

29. Nausea/Vomiting • Onset with start of opioids, tolerance may develop • Prevent or treat with dopamine-blocking anti-emetics (avoid with long-QT): • Haloperidol 0.5-1mg every 6 hours • Droperidol 0.625 mg (PACU order set) • Metoclopramide 10mg every 6 hours • Alternative opioid if refractory

30. Sedation • Onset with start of opioids • Distinguish from exhaustion due to pain* • Tolerance develops within days • Complex assessment in advanced disease • If persistent, may consider alternative opioid or route of administration • Psychostimulants may play a role as well • Methylphenidate 5mg qAM and 1 noon

31. Delirium/Neuroexcitability • Presentation • Cognitive changes: CAM assessment • acute onset or fluctuating course, • inattention, • disorganized thinking/altered level of consciousness • Restlessness, agitation • Myoclonic jerks, seizures (may be repressed if on benzodiazepines) • More common in renal failure

32. Respiratory Depression • Opioid effects differ among patients • Change in LOC occurs before respiratory suppression • Pharmacologic tolerance develops rapidly • Most studies of respiratory depression in opioids looked at patients with drug overdose • Management: • Identify and treat contributing causes • Reduce opioid dose and observe • If unstable vital signs: • Naloxone 0.1-0.2 mg IV q 1-2 min

33. Opioid “allergies” • Nausea/vomiting, constipation, drowsiness, confusion • Adverse effects, not allergic reactions • Anticipated and managed • Anaphylactic reactions are only true allergies • Bronchospasms • Urticaria, pruritus – need careful assessment • Mast cell destabilization • Treat with routine long-acting, non-sedating antihistamines

34. Adjunctive Analgesics • Supplement primary analgesics • May be primary analgesics • Use at any step of WHO ladder

35. Adjunctive Analgesics: • NSAIDS • Local anesthetics - Topical - Regional - Systemic • Steroids • Radiation • Physical therapy • Psychological approaches • Complementary therapies

36. Routes of Delivery • PO/enteral feeding tubes • Transmucosal • Rectal • Transdermal (fentanyl) • Parenteral: SC, IV, IM • Intraspinal: Epidural, Intrathecal

37. Contacts • Acute Pain service at University: • Perioperative pain, interventional pain • OUCH pager • Interventional Pain service at Memorial: • Perioperative pain, back pain crisis, cancer pain requiring intervention • Christian Gonzalez, MD • Palliative Medicine Service: • Pain related to severe/life-limiting illness (cancer, cardiac, etc.) • Office: 334-8630; see call schedule for pager

38. Take home messages • Treat the pain like it was your own • Remember to take into account pain medications being taken before surgery • Take an active approach to avoiding constipation! • Decrease dose/frequency in renal and hepatic failure – and just use PRN doses • Think of adjuncts (NSAIDS, steroids, topicals etc)

39. Questions?

40. Corticosteroids • May have a role in patients with advanced illness: when? • Dexamethasone • Long half-life (>35 hours), dose once / day • Minimal mineralocorticoid effect • Doses 2-20+ mg/day • Adverse effects • Steroid psychosis • Proximal myopathy • Other long-term adverse effects

41. Interventional Pain Management • 14% cancer patients have pain unrelieved despite aggressive medical management. • Intraspinal therapies • Plexus nerve blocks: celiac, etc. • Nerve stimulation, ablation • Vertebral cementing Memorial: Interventional Pain – Christian Gonzalez, MD University: Acute Pain Service – OUCH pager

42. Radiation Therapy • Studies show that high dose/fraction, low number of fractions is as effective as low fraction and high number of treatments in palliative settings.

43. Non-pharmacologic interventions • Neurostimulation • Surgical • Physical therapy • Psychological approaches • Cognitive therapies • Biofeedback • Behavior therapy • Complementary therapies • Acupuncture • Massage • Meditation/relaxation: Refer to Center for Mindfulness

44. Fentanyl patch (Duragesic) • Black box warning: why? • Not for opioid naïve patients • Not good for acute pain • Takes 24 hours to reach peak effect • Held in subcutaneous fat, thus takes >12 hours after patch is removed to leave system • Must not cut patch

45. To start Fentanyl Patch From oral morphine to patch: Oral morphine 50-100 mg in 24 hours = Fentanyl 25 mcg/hour transdermal patch From IV Fentanyl to patch 1:1 conversion 25 mcg/hour = 25 mcg/hour patch

46. Adjunctive Analgesics: Anticonvulsants • Gabapentin (Neurontin) • 100 mg PO daily to tid, titrate • Increase dose q 1-3 days - Usual effective dose 900-1800 mg/day • Max may be > 3600 mg/day • Minimal adverse effects • Drowsiness, tolerance develops within days • Pregabalin (Lyrica) • Start 50 mg tid, titrate over 7 days up to 600mg/day in divided doses • Carbamazepine • 100mg bid, titrate • Valproic acid – monitor drug levels

47. Adjunctive Analgesics:Tricyclic Antidepressants • Amitriptyline • Most extensively studied - NMDA receptor • 10-25 mg po nightly, titrate ever 4-7 days • Analgesia in days to weeks • Monitor plasma levels • Adverse effects prominent (anticholinergic) • Desipramine • Fewer anticholinergic side effects • 10-25 mg po qhs, titrate • Tricyclic of choice in the seriously ill • Nortriptyline is an alternative

48. Adjunctive Analgesics: SSNRI • Duloxetine (Cymbalta) • Venlafaxine (Effexor)

49. Adjunctive Analgesics: NMDA Receptor Antagonists • Dextromethorphan • Ketamine • Methadone – opioid + NMDA r-antagonist

50. Methadone • Dose interval for methadone is variable (q 6 h or q 8 h is usually adequate) • Biphasic pharmacology makes it more complex: • side effects may only show up day 3 • Adjust methadone dose q 4-7 days • Do not use PRN dosing of methadone.