1. A logical method for hospital- based pain treatment Bob Arnold MD Institute to Enhance Palliative Care

2. Objectives By the end of the session, participants should be able to: –Describe the various steps in determining opiate orders –Describe the principle of equianalgesia and perform the calculations

3. Objectives By the end of the session, participants should be able to: –Write initial PCA orders –Describe how to dose escalate in a patient with more severe pain –Describe the major side effects of opiates (if we have time!)

4. Objectives What do you want to learn?

5. Addiction fear Dependence Tolerance Addiction –Evidence for –Dealing with addiction in the hospital Pseudo addiction

6. Steps in Opiate dosing Calculate the previous days oral morphine equivalent Determine if the dose is adequate for the pain and dose adjust Determine the opiate that will be used and dose adjust for cross tolerance Determine the route the opiate will be given Determine the dosing schedule Determine breakthrough dose

7. Case 1 Mrs Jones is a 63 year woman with back pain due to ovariancancer. At home she has been taking percoset 1-2 every 4 hours (8 day)In the ER, She got 3 mg iv hydromorphine over 3 hours and on the floor her pain is a 8/10. WHAT OPIATE SHOULD YOU USE?

8. Opiates Opioids –All opioid analgesics produce pain relief via interaction with opioid receptors in the brain/spinal cord and perhaps via peripheral opioid receptors –The mu receptor is the dominant analgesic receptor, but other receptors play a role in analgesia for certain opioids –There is no dose ceiling for opioids, only for acetaminophen in combination products

9. Opioids are classified by their interaction with the opioid receptors –pure agonist (morphine, hydromorphone (Dilaudid ®) oxycodone, codeine, meperidine, fentanyl) –mixed agonist-antagonist (Stadol ®, Talwin ®, Nubain ®) –partial agonist (buprenorphine) –pure antagonist (naloxone, naltrexone) Opioids (cont)

10. Case 1 You admit a patient with cancer-related chest wall pain. She is on MS Contin 15 mg bid with 5 mg prn q 3 hr. Last week, she called up herPCP who gave her percoset 1-2 q 4 hrs (she took 10 day) as well as started her on Oxycontin 10 two times a day. What should you do?

11. Calculate the previous days OME Since all potent opioids produce analgesia by the same pharmacological mechanism, they will produce the same degree of analgesia if provided in equianalgesic doses. Thus, there is little basis to say, “morphine did not work, but hydromorphone did work”. Such a statement generally means that non- equianalgesic doses were used.

12. Equianalgesia Common Conversions SEE PAIN CARD – EVERYTHING ON THE CARD IS EQUIPOTENT 10 mg IV MS = 30 po MS 10 mg IV MS = 1.5 mg IV Dilaudid 30 mg po MS = 7.5 mg po Dilaudid ® 30 mg po MS = 30 mg po oxycodone ** Note: Conversions factors are only a rough guide to approximate the correct dose.

13.  PAUSE & Calculate Equianalgesic Problem Calculate: What is the patient’s OME (15 mg MS Contin bid; 10 mg oxycontin bid; 10 percoset day and 6 MSIR (5 mg))

14. Determine the “new” OME dose Determine if the dose is adequate for the pain –Assess pain using a 1-10 scale –Fudge factors Activities of daily living Adverse effect Previous pain score

15. Opioid Dose Escalation Always increase by a percentage of the present dose based upon patient’s pain rating and current assessment Mild pain 1-3/10 25% increase Moderate pain 4-6/10 25-50% increase Severe pain 7-10/10 50-100% increase

16. Determine the opiate that will be used Based largely on side effect profile Meperidine Morphine and renal failure Cross tolerance fudge factor –If changing opiate decrease OME 30-50% –BACK TO OUR CASE

17. Case 1 You admit a patient with cancer-related chest wall pain. She is on MS Contin 15 mg bid with 5 mg prn q 3 hr. Last week, she called up her PCP who gave her percoset 1-2 q 4 hrs (she took 10 day) as well as started her on Oxycontin 10 two times a day. What do you estimate her OME will be? What opiate would you use

18. Determine route and dosing schedule Ultra short Short Long

19. Short Acting Opioids Parenteral or Oral –morphine –hydromorphone (Dilaudid ®) –meperidine (Demerol ®) –codeine Oral only –Oxycodone/Acetam or NSAID –Hydrocodone/Acetam or NSAID –Note: hydrocodone is only available as a combination product.

20. Oral dosing: –onset in 20-30 min –peak effect in 60-90 minutes –duration of effect 2-4 hours –Start with this for opiate naive –Can be dose escalated or re-administered every 2-4 hours for poorly controlled pain as long as the daily Acetaminophen dose stays < 4 grams Short Acting Opioids

21. Be careful with tylanol Current recommendations is less than 3 gm/day Vicodan ES has 750 mg

22. Parenteral Opioids IV is the route of choice if access is available –There is no indication for IM opioids –All standard opioids can be given SQ, by either bolus dose or by continuous infusion More potent due to lack of first pass effect –Dose adjustment controversial

23. IV or SQ bolus doses have a shorter duration of action that oral doses; typically 1-3 hours The peak effect from an IV bolus dose is 5-15 minutes –Fentanyl >Morphine Parenteral Opioids

24. Dosing options PCA Long acting in concert with Breakthrough dosages Short acting “around the clock” PRN

25. PCA Theory –Patient controlled results in less opiate delivered with same pain relief –Allows for a constant level of opiate rather than peaks and valleys –ALL PCA’s ARE CONSTANT INFUSIONS

26. PCA Bolus –Morphine or Dilaudid –Q 15 minutes –Get a high drug level before start the pca –The amount it takes to control pain is more than the amount it takes to keep one out of pain

27. PCA Patient controlled dosing –Remember that 10mg of morphine =1.5 hydromorphine –Constant infusions –Time interval –Hour lockout –Relative contraindications

28. Case 2 You admit a 72 year old man with acute pancreatitis. His pain is 9/10. What should you do? (He can not take po)

29. Converting to oral dose Case 3- A patient with chronic low back pain is admitted with an exacerbation and put on a PCA. Over the next 48 hours, the patient used an average of 6 mg hour morphine and this controlled her pain. What is the patient’s OME? Is the pain well controlled?

30. Long act with BKT Long acting opiates allows a constant opiate with fewer doses. Long Acting - 2/3-3/4 of total daily dose All provide 8-12 hours of analgesia All provide onset of analgesia within 2 hours All can be dose escalated every 24 hours

31. Long Acting Opioids Oral –MS Contin ® –Kadian ® –Avinza ® –Oramorph SR ® –Oxycontin ® –Opana (oxymorphine) –methadone Transdermal –Fentanyl Patch (Duragesic ®)

32. Long act Morphine-oxycodone No clear benefit of one product over another –MS Contin/Avinza/Kadian/Oramorph contain morphine –Oxycontin contains oxycodone (70/30) –No difference in toxicity; No difference in addiction potential Oxycotin/Oramorph/MS Contin must be taken intact—they cannot be crushed; they do not fit down GI tubes. Kadian/Avinza pellets can go down large bore feeding tubes

33. Transdermal Fentanyl Slow onset of action: 13-24 hours –Duration of action: 48-72 hours Should only dose escalate q 3 days –Fentanyl stays in circulation for up to 24 hours after patch removal Place on hairless, non-irradiated skin No ceiling dose

34. Conversions from/to Transdermal Fentanyl (Duragesic ®) Equianalgesic conversion formula –24 hour total dose of oral morphine, divided by 2 = dose in micrograms of transdermal fentanyl –Iv/hr dose= dose in mcg of transdermal fentanyl; –Example: MS Contin ® 30 mg q 12 = 60 mg MS/24 hours 60 divided by 2 = 30; rounded to one 25 ug Fentanyl Patch SO IN OUR PATIENT WHAT FENTANYL DOSE WOULD YOU USE

35. Breakthrough Pain Patients on any long-acting med always need a second, short-acting med, available for breakthrough pain something they can take at least every 4 hours, preferably less Guideline, dose of breakthrough opioid should be: 10-20% of 24 hour dose of analgesics and made available q2 hours FOR OUR PATIENT ABOVE WHAT BKT DOSE WOULD YOU USE

36. Other dosing schedules Short acting “around the clock” PRN

37. Case examples 50 year old woman who comes in with severe pain due to a metastatic compression fracture At home she is on oxycontin 10 mg bid, a 25 mcg fentanyl patch and 9 oxycodone 10mg/day. Her pain is a 8/10 What would you do?

38. Steps in Opiate dosing Calculate the previous days oral morphine equivalent Determine if the dose is adequate for the pain and dose adjust Determine the opiate that will be used and dose adjust for cross tolerance Determine the route the opiate will be given Determine the dosing schedule Determine breakthrough dose

39. Case examples You are admitting a 75 year old woman with increasing pain because of breast cancer with invasion into the pleural wall. She has been on oxycotin 30 mg bid and percoset 1-2 every 4 hours for two days (taking roughly 10 a day). Her pain is a 8/10. What should you do?

40. Steps in Opiate dosing Calculate the previous days oral morphine equivalent Determine if the dose is adequate for the pain and dose adjust Determine the opiate that will be used and dose adjust for cross tolerance Determine the route the opiate will be given Determine the dosing schedule Determine breakthrough dose

41. Case examples You are asked to see a post-surgical patient due to “pain.” She is a 63 year old man who has cervical cancer. She was admitted for a SBO and had a venting gastrostomy. Shee says that his pain control is fair as long as they give him his medicine.

42. Case examples In the last 24 hours she has gotten 50 mcg fentanyl patch, 8 percoset, 10mg iv morphine and 2 mg iv hydromorphine. Her pain is his chronic mid-abd pain, although there is also some post- operative pain.

43. Steps in Opiate dosing Calculate the previous days oral morphine equivalent Determine if the dose is adequate for the pain and dose adjust Determine the opiate that will be used and dose adjust for cross tolerance Determine the route the opiate will be given Determine the dosing schedule Determine breakthrough dose

44. Dosing opiates in the actively dying patients You are asked to see a patient admitted from the ER who is actively dying and CMO. He was not on any opiates at home. He seems to be moaning and has a respiratory rate of 45. What should you do? –Bolusing every 15 minutes –Using a drip based on bolus amount

45. Opioid Adverse Effects CommonUncommon Constipation Bad dreams / hallucinations Dry mouth Dysphoria / delirium Nausea / vomiting Myoclonus /seizures Sedation Pruritus / urticaria Sweats Respiratory depression Urinary retention

46. Constipation Common to all opioids Opioid effects on CNS, spinal cord, myenteric plexus of gut Easier to prevent than treat

47. Constipation.. Diet usually insufficient Bulk forming agents not recommended Stimulant laxative –senna, bisacodyl, glycerine, casanthranol, etc. Combine with a stool softener –senna + docusate sodium

48. .. Constipation Prokinetic agent –metoclopramide, cisapride Osmotic laxative –MOM, lactulose, sorbitol Other measures

49. Nausea / Vomiting... Onset with start of opioids –tolerance develops within days Prevent or treat with dopamine-blocking antiemetics –prochlorperazine 10 mg q 6h –haloperidol 1 mg 6h –metoclopramide 10 mg q 6h

50. .. Nausea / Vomiting Serotonergic agents also are effective Alternative opioid if refractory

51. Sedation.. Onset with start of opioids –distinguish from exhaustion due to pain –tolerance develops within days Complex in advanced disease

52. .. Sedation If persistent, alternative opioid or route of administration Psychostimulants may be useful –methylphenidate 5 mg q am and q noon, titrate –Less common-Aricept/Modafinil

53. Delirium... Presentation –confusion, bad dreams, hallucinations –restlessness, agitation –myoclonic jerks, seizures –depressed level of consciousness Disorder of attention –CAM

54. .. Delirium Rare, unless multiple factors contributing, if –opioid dosing guidelines followed –renal clearance normal Treat –Rotate opiate –Look at other medicines –Haldol

55. Respiratory Depression... Opioid effects differ for patients treated for pain –pain is a potent stimulus to breathe –loss of consciousness precedes respiratory depression –pharmacological tolerance rapid

56. Questions Call Palliative care with questions –Magee -8510 –Winnie Teuteberg –Elizabeth Weinstein’s clinic-641-4530