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Using Opioids for Pain

Using Opioids for Pain. A continuous infusion of knowledge with intermittent doses of pain Nicole L. Artz, MD. You are the intern on call. You admit a 70 year old woman with severe pain from a compression fracture of her lumbar spine.

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Using Opioids for Pain

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  1. Using Opioids for Pain A continuous infusion of knowledge with intermittent doses of pain Nicole L. Artz, MD

  2. You are the intern on call. You admit a 70 year old woman with severe pain from a compression fracture of her lumbar spine. • She has not had adequate relief from tylenol or ibuprofen at home. Her son has accompanied her to the hospital and mentions that he is a malpractice attorney. • Recognizing that pain is the 5th vital sign, you vow to control her pain and, since the Duragesic drug rep bought your lunch yesterday, you apply a 25 mcg fentanyl patch immediately.

  3. You are busy with other patients and don’t have a chance to check on her again for around 5 hours. • You find her moaning in pain. • You start a dilaudid PCA with a basal infusion rate of 1.0 mg/hr and rescue doses of 0.5 mg q 15 minutes. You ask the nurse to call you if she is still in pain once the PCA is started. • You get busy again with more admissions but assume that her pain must be better controlled because you haven’t heard anything from the nurses.

  4. Just at that moment you hear a “Dr. Cart” called to her room. • On arriving you are horrified to find that she is unarousable, hypotensive, and only breathing 4 times/minute. • What happened?

  5. Outline • Misperceptions about Addiction • Opioids to Avoid • General Principles • PCA’s • Special Populations • Methadone • Practice Cases

  6. Tolerance • Diminished drug effect over time due to ongoing drug exposure- i.e. takes higher dose to get relief. • Desireable in the case of side effects. • * Which side effect do patients NOT develop tolerance to? • Tolerance does NOT cause addiction.

  7. Physical Dependence • Physiologic changes expected to occur with ongoing exposure to opioids. • Similar changes occur w/ other medications (beta blockers, anti-depressants, alpha-2 agonists….). • Abrupt opioid withdrawal results in withdrawal syndrome.

  8. Physical Dependence Cont. • Signs/symptoms of opioid withdrawal: • Tachycardia, nausea, vomiting, diarrhea, rhinorrhea, lacrimation, yawning, anxiety. • Avoid by tapering dose by 50% every 2-3 days. • Does NOT imply or cause addiction.

  9. Pseudoaddiction • Aberrant behaviors occurring as a result of under-treated pain. • “clock-watching” • Aggressive complaining • Requesting specific drugs • Unsanctioned dose escalation • *Behaviors decrease or resolve with improved pain control.

  10. Addiction • Psychological dependence on a drug. • Fundamental features include: • Loss of control • Compulsive use • Use despite harm

  11. Addiction, Cont. • Behaviors more likely to be related to addiction: • Prescription forgery • Stealing or “borrowing” drugs • Multiple episodes of prescription “loss” • Concurrent abuse of related illicit drugs • Selling prescription drugs

  12. Are there opioids to avoid? • Demerol • Poorly absorbed orally, short half-life (3 hrs) • Normeperidine- • non-analgesic metabolite • long half-life • renally excreted • Toxic-- CNS excitation (tremors, anxiety, dysphoria, myoclonus, seizures) with accumulation • Frequent dosing required leads to inevitable accumulation of metabolite, esp. in setting of renal insufficiency.

  13. Indications for Demerol: • If patient has a history of 1 or more of the following: • Unmanageable adverse reactions to other 1st line opioids. • Tx failure to other 1st line opioids given in adequate doses. • Prevention/tx of drug/ blood product induced rigors • Single injection conscious sedation for procedures • Should not be used >48 hrs. or >600 mg/day

  14. Propoxyphene (Darvon, Darvocet) • Not any more effective than tylenol or aspirin. • Toxic metabolite with a half-life of 30-36 hrs(!) also renally excreted– repeat dosing may lead to accumulation of metabolite esp in setting of renal insuff– results in seizures, cardiac toxicity, pulmonary edema…general badness.

  15. Which drug should I start with? • Morphine is the gold standard but can use any opioid- just make sure to dose correctly. • Keep cost in mind. • In general, reserve fentanyl patches for patients who are unable to swallow pills or are on a stable dose of opioid since it is difficult to titrate and is very expensive.

  16. What about patients with hepatic or renal disease? • Opioids 90-95% renally cleared • Renal Disease • Morphine - 2 metabolites: M6G is active and has a longer half-life than morphine. As a result– decrease the dose, widen the interval, use PRN or not at all. • Safer to use dilaudid, methadone, fentanyl but still consider starting w/ half the usual dose and/or increasing the interval. • Less of an issue w/ liver disease but with severe hepatic dysfunction increase the dosing interval or decrease the dose.

  17. What if the patient has a morphine allergy? • Most “allergies” are actually unexpected adverse effects. • If evidence of a true allergy- hives, bronchospasm, anaphylaxis or can’t be sure, can safely use: • Fentanyl • Methadone • ?Dilaudid

  18. What is the maximum dose? • There is no “ceiling effect” with the pure opioids (exception of codeine). Keep titrating until the pain is controlled or the dose is limited by adverse effects.

  19. How fast can I titrate? • Great question! • Some lack of consensus– • Short acting oral opioids can be titrated quickly- dose by dose. • Sustained release oral opioids can be dose-escalated every 24-72 hrs. • Transdermal fentanyl should not be dose escalated more often than every 72 hrs. • Methadone should not be titrated more often than every 5-7 days.

  20. How much should I increase the dose? • Mild Pain- increase by 25% • Moderate Pain- increase by 50% • Severe Pain- increase by 100% • Example- Pt receiving 5 mg morphine IV q3hrs with severe pain can go up to 10 mg IV q 3 hrs. • Don’t go from 5 mg morphine q 3 hrs to 6 mg morphine q 3hrs.

  21. How should I treat breakthrough pain? • Offer an immediate release opioid. • Give 10-15% of the 24 hour dose. • Peak analgesic effect correlates with the peak plasma concentration. • Extra breakthrough doses: • Q 1-2 hrs for po route • Q 30 minutes for SC or IM route • Q 15 minutes for IV route.

  22. How do I convert from one opioid to another? • Everyone needs an equianalgesic chart. • Used to convert opioids and also routes (IV – PO). • Provides a guide– in general, start a new opioid at 50-75% of the calculated equianalgesic dose to allow for incomplete cross-tolerance between different opioids.

  23. PCA’s…. • Loading dose • Basal rate • Demand dose • Lockout

  24. PCA’s- Basal Rate • Do not use a basal rate in patients who are opioid naiive. This undermines the safety mechanism of the PCA. • If not opioid naiive, calculate the 24hr dose of currently used opioids and convert to an equianalgesic basal rate.

  25. PCA’s Bolus Dose • May use a loading dose when initiating a continuous infusion or when increasing the basal rate. • Rescue dose usually 50-150% of basal rate. Example– Pt on morphine basal rate 2mg/hr. Could set rescue (demand dose) anywhere from 1-3 mg available Q15 minutes.

  26. PCA’s cont. • Reassess frequently!!! • May adjust the bolus dose every 30 minutes until desired effect. • May adjust the basal rate every 8 hrs. • Consider the number of bolus doses as guide. • Never increase the basal rate more than 100% at any one time.

  27. Loading Dose Range (Opioid naïve pt) <65/70 kg>65 y/o7-12/<50 kg>12/>50 kg (dose per kg) Morphine 1-3 mg 0.5-2 mg 0.01-0.03 mg 0.5-2 mg Dilaudid 0.2-0.6 mg 0.1-0.4 mg 0.002-0.004 mg 0.1-0.4mg Demerol 10-30 mg 5-20 mg 0.1-0.2 mg 5-20 mg Size of the loading dose is influenced by: Age Physical status Lean body weight Opioid tolerance

  28. Maintenance Dose Range <65/70 kg>65 y/o7-12/<50 kg>12/>50 kg (dose per kg) Morphine 0.5-1.5 mg 0.5-1 mg 0.01-0.03 mg 0.5-1 mg Dilaudid 0.1-0.3 mg 0.1-0.2 mg 0.002-0.006 mg 0.1-0.2 mg Demerol 5-15 mg 5-10 mg 0.1-0.2 mg 5-10 mg

  29. Sedation Scale 0 = Awake and alert 1 = Occasionally drowsy, but easy to arouse - - needs verbal stimulus only to become awake and stay alert. 2 = Frequently drowsy, arousable but may close eyes during conversation - - needs verbal & brief light tactile stimulus to become awake and stay alert. 3 = Somnolent, difficult to arouse - - needs repeated verbal & tactile stimulus to rouse; minimal to no response to stimulation.

  30. PCA’s • Do not start a PCA and then disappear for 24 hrs. • Reassess frequently! • Trust the patient’s report of pain.

  31. Methadone • Great drug for use in chronic pain • The LEAST expensive of all opioids (by far) • Safe even with ESRD • Dosed q 6-12 hrs • Extremely long and variable half-life (up to 190 hours!) • Do not titrate more often than once every 5-7 days

  32. Methadone Cont… • Racemic mix: one stereoisomer is a mu opioid receptor agonist, the other a NMDA receptor antagonist. • NMDA mechanism results in lower opioid tolerance, and may be the reason for increased efficacy with neuropathic pain. • Methadone behaves as a much more potent opioid the higher the dose of the prior opioid.

  33. Important to use MEDD table • MS daily dose Morphine/Methadone • < 30 2:1 • 30-99 4:1 • 100-299 8:1 • 300-499 12:1 • 500-999 15:1 • >1000 20:1

  34. Let’s Practice…

  35. Case 1 • 55 y/o woman with ovarian cancer on MS Contin 60 mg po q 12 at home. She needs hospitalization for nausea/vomiting following chemo. You are the intern on call. Calculate the equivalent IV dose. • 60 mg po q 12= 120 mg/d • 120 mg po MSO4/d = 30 mg po MSO4 X mg IV MSO4/d 10 mg IV MSO4

  36. Case Cont… • X = 40 mg IV MSO4/d = 1.5-2.0 mg/hr • Demand dose? • Loading dose?

  37. Case Cont.. • The PCA machine will not be available for a few hours. • You give her Phenergan for nausea. How much IV morphine will you give her as a one time dose? • 15 minutes later her pain score has decreased from 10 to 8. Should you redose? How much should you give?

  38. Case 2 • 45 year old woman with breast cancer metastatic to bone. She is comfortable on a continuous infusion of morphine at 6 mg/hr. You need to change her to oral medication before discharge home. • 6 mg/hr X 24 hrs = 144 mg/day IV morphine 144 mg/d IV MSO4 = 10 mg IV MSO4 X mg/d po MSO4 30 mg po MSO4

  39. Case Cont… • X = 432 mg morphine po/day • Sig: 200 mg extended release morphine po bid • Prescribe a breakthrough dose of 10-15% of the total daily dose. • Sig: 45-60 mg immediate-release mophine po q 1 hr prn.

  40. Case 3 • 45 y/o man with chronic pancreatitis, transferred from an OSH. He has been receiving 100 mg Demerol IV q 3 hrs for pain and is now tolerating po with adequate pain control. You want to calculate an equivalent dose of a fentanyl patch. • 100 mg X 8 = 800 mg IV Demerol/24 hrs 800 mg IV Demerol/d = 100 mg IV Demerol X mg po Morphine/d 30 mg po Morphine

  41. Case 3 Cont… • X = 240 mg morphine/24 hrs • Reduce dose by 25-50% to account for incomplete cross-tolerance. • 120-180 mg morphine/day • Use 2:1 rule: (50 mg morphine/d = 25mcg fentanyl patch • 150 mg po morphine = 75mcg duragesic patch • Don’t forget a breakthrough dose. • 10% of 150 mg morphine= 15 mg po IR MSO4 q 2 hrs prn pain.

  42. Case 4 • 45 y/o man with chronic pancreatitis, transferred from an osh. He has been receiving 200 mg Demerol IV q 2 hrs for pain. You want to put him on a Dilaudid PCA. • 75 mg X 12 = 2400 mg IV Demerol/24 hrs 2400 mg IV Dem./24hrs = 100 mg IV Demerol X mg IV Dilaud./24hrs 1.5 mg IV Dilaudid

  43. Case 4 Cont… • X = 36 mg IV Dilaudid/day • Adjust for incomplete cross-tolerance 0.50(36)= 18 mg/day • Basal rate = 0.75 mg/hr • Order a rescue dose: 0.75 mg available Q 10 minutes on demand

  44. Case 4 Cont… • 2 hours after the PCA is started you reassess the patient and find that he is hitting his demand button 3 times/hour and is still moderately uncomfortable. • What should you do? • How much should you increase the demand dose? • How could we have avoided this situation?

  45. Back to our Patient • What went wrong? • The fentanyl patch is a poor choice in an opioid naiive patient. (Equivalent to approx 50 mg morphine/day!) • No effect for 6-12 hrs- no wonder she was still in the same amount of pain 5 hrs later! *Remember to always prescribe IR breakthrough pain medication with a fentanyl patch. • Never use two long-acting (basal) opioids at once. Fentanyl patch likely started to work at the same time she was started on the PCA with basal rate.

  46. Use great caution when starting a basal rate in an opioid naiive patient. • Always underestimate opioid needs in the elderly and titrate up as needed.

  47. References: • National Comprehensive Cancer Network: Practice Guidelines in Oncology- v.2.2005 • Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain, American Pain Society, Fifth edition, 2003. • Education for Physicians on End-of-Life Care (EPEC), Pain Management Module, RWJF, 1999.

  48. Resources • Hopkins Opioid Program- amazing, free downloadable program for your palm pilot that automatically does the calculations for you. • Fast Facts, National Residency End-of-Life Curriculum Project Download at www.eperc.mcw.edu

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