Pain Management Suzana Makowski, MD Palliative Medicine and  Laura Lambert, MD Surgical Oncology
Key concepts <ul><li>Pain assessment </li></ul><ul><li>Opioid pharmacology </li></ul><ul><li>Pain management </li></ul><ul...
The 5 th  Vital Sign <ul><li>Pain </li></ul>
What do most surgical patients have in common? <ul><li>Pain </li></ul><ul><li>Pre-op </li></ul><ul><li>Post-op </li></ul>
How do you assess pain? <ul><li>L  the exact Location of the pain and whether it travels to other body parts O  Other asso...
How do you assess pain? <ul><li>Intensity </li></ul><ul><li>Categories:  </li></ul><ul><li>Nociceptive (somatic and viscer...
Acute vs. Chronic Pain <ul><li>Acute pain </li></ul><ul><ul><li>Identified event (onset) </li></ul></ul><ul><ul><li>Resolv...
Barriers to assessing and treating pain <ul><li>Addiction: </li></ul><ul><li>means a person has lost control over the use ...
What is the easiest pain to bear? <ul><li>SOMEONE ELSE’S! </li></ul><ul><li>Don’t delay </li></ul><ul><li>Unmanaged pain l...
WHO step-ladder 1 mild 2   moderate 3   severe Morphine Hydromorphone Methadone Levorphanol Fentanyl Oxycodone ± Adjuvants...
Opioid Pharmacology <ul><li>Conjugated in liver </li></ul><ul><li>First pass metabolism </li></ul><ul><li>Excreted by kidn...
Opioid kinetics Plasma Concentration 0 Half-life (t 1/2 ) Time IV PO/PR SC/IM C max 6-7 min 15-20 min 45-60 min
Clearance Issues <ul><li>Conjugated by liver </li></ul><ul><li>90-95% excreted in urine </li></ul><ul><li>Dehydration, ren...
Opioid pharmacology <ul><li>What is the half life (range) for IV opioids? </li></ul><ul><ul><li>2-4 hours </li></ul></ul><...
Routine oral dosing: immediate release formulations <ul><li>Scheduled dosing based on t 1/2 </li></ul><ul><ul><li>Q4 hours...
Routine oral dosing Extended release preparations <ul><li>Reason for use: </li></ul><ul><ul><li>Improve compliance, adhere...
 
Equation: To convert from one opioid to another using same route   FROM CHART: Opioid A dose (mg), route X  opioid B route...
Coverting <ul><li>Step 1: Calculate 24 hour dose of medication </li></ul><ul><li>Step 2: Choose 2nd medication </li></ul><...
Example: <ul><li>Mr. Jones is a 67 yo man with colon cancer, just had low anterior resection with diverting ileostomy. He ...
Example <ul><li>Step 1: calculate 24 hour dose –  </li></ul><ul><ul><li>Oxycontin 40mg bid  = 80mg  </li></ul></ul><ul><ul...
 
Example continued <ul><li>Step 3: select ratio from chart for formula </li></ul><ul><ul><li>Hydromorphone IV = 1 </li></ul...
 
Opioid Side Effects <ul><li>Common </li></ul><ul><li>Constipation </li></ul><ul><li>Dry mouth </li></ul><ul><li>Nausea/vom...
POP Quiz <ul><li>Pharmacologic tolerance develops to all of the following side effects of opioid analgesics  except : </li...
Constipation <ul><li>Common to all opioids </li></ul><ul><li>Due to effects on:  </li></ul><ul><ul><li>CNS, spinal cord, m...
Options to Treat Constipation <ul><li>Stimulant laxative: </li></ul><ul><ul><li>Senna, bisacodyl, glycerine, etc. </li></u...
Nausea/Vomiting <ul><li>Onset with start of opioids, tolerance may develop </li></ul><ul><li>Prevent or treat with dopamin...
Sedation <ul><li>Onset with start of opioids </li></ul><ul><ul><li>Distinguish from exhaustion due to pain* </li></ul></ul...
Delirium/Neuroexcitability <ul><li>Presentation </li></ul><ul><ul><li>Cognitive changes: CAM assessment  </li></ul></ul><u...
Respiratory Depression <ul><li>Opioid effects differ among patients </li></ul><ul><ul><li>Change in LOC occurs before resp...
Opioid “allergies” <ul><li>Nausea/vomiting, constipation, drowsiness, confusion </li></ul><ul><ul><li>Adverse effects, not...
Adjunctive Analgesics <ul><li>Supplement primary analgesics </li></ul><ul><li>May be primary analgesics </li></ul><ul><li>...
Adjunctive Analgesics:  <ul><li>NSAIDS </li></ul><ul><li>Local anesthetics - Topical - Regional - Systemic </li></ul><ul><...
Routes of Delivery <ul><li>PO/enteral feeding tubes </li></ul><ul><li>Transmucosal </li></ul><ul><li>Rectal </li></ul><ul>...
Contacts <ul><li>Acute Pain service at University:  </li></ul><ul><ul><li>Perioperative pain, interventional pain </li></u...
Take home messages <ul><li>Treat the pain like it was your own </li></ul><ul><li>Remember to take into account pain medica...
Questions?
Corticosteroids <ul><li>May have a role in patients with advanced illness: when? </li></ul><ul><li>Dexamethasone </li></ul...
Interventional Pain Management <ul><li>14% cancer patients have pain unrelieved despite aggressive medical management. </l...
Radiation Therapy <ul><li>Studies show that high dose/fraction, low number of fractions is as effective as low fraction an...
Non-pharmacologic interventions <ul><li>Neurostimulation </li></ul><ul><li>Surgical </li></ul><ul><li>Physical therapy </l...
Fentanyl patch (Duragesic) <ul><li>Black box warning: why? </li></ul><ul><li>Not for opioid naïve patients </li></ul><ul><...
To start Fentanyl Patch <ul><li>From oral morphine to patch: </li></ul><ul><li>Oral morphine 50-100 mg in 24 hours =  </li...
Adjunctive Analgesics: Anticonvulsants <ul><li>Gabapentin (Neurontin) </li></ul><ul><ul><li>100 mg PO daily to tid, titrat...
Adjunctive Analgesics: Tricyclic Antidepressants <ul><li>Amitriptyline </li></ul><ul><ul><li>Most extensively studied - NM...
Adjunctive Analgesics: SSNRI <ul><li>Duloxetine (Cymbalta) </li></ul><ul><li>Venlafaxine (Effexor) </li></ul>
Adjunctive Analgesics:  NMDA Receptor Antagonists <ul><li>Dextromethorphan </li></ul><ul><li>Ketamine </li></ul><ul><li>Me...
<ul><li>Dose interval for methadone is variable (q 6 h or q 8 h is usually adequate) </li></ul><ul><li>Biphasic pharmacolo...
Changing opioids… <ul><li>Adjusting for cross-tolerance </li></ul><ul><ul><li>Start with 50-75% of published equianalgesic...
Adjusting for cross-tolerance
Breakthrough dosing <ul><li>Based on time to Cmax </li></ul><ul><ul><li>PO/PR – q1 hour </li></ul></ul><ul><ul><li>SQ/IM –...
Relative strengths of routes <ul><li>Significant first-pass metabolism of PO/PR dose </li></ul>PO/PR to SC, IV, IM 2-3 ~ 1
Using a PCA <ul><li>Basal rate </li></ul><ul><li>Bolus dose (PCA dose) </li></ul><ul><li>Lock-out </li></ul><ul><ul><ul><u...
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Opioid pain surgery2010

  1. 1. Pain Management Suzana Makowski, MD Palliative Medicine and Laura Lambert, MD Surgical Oncology
  2. 2. Key concepts <ul><li>Pain assessment </li></ul><ul><li>Opioid pharmacology </li></ul><ul><li>Pain management </li></ul><ul><li>Side effects of pain medications </li></ul>
  3. 3. The 5 th Vital Sign <ul><li>Pain </li></ul>
  4. 4. What do most surgical patients have in common? <ul><li>Pain </li></ul><ul><li>Pre-op </li></ul><ul><li>Post-op </li></ul>
  5. 5. How do you assess pain? <ul><li>L the exact Location of the pain and whether it travels to other body parts O Other associated symptoms such as nausea, numbness, or weakness C The Character of the pain, whether it's throbbing, sharp, dull or burning A 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 </li></ul>
  6. 6. How do you assess pain? <ul><li>Intensity </li></ul><ul><li>Categories: </li></ul><ul><li>Nociceptive (somatic and visceral), Neuropathic </li></ul>
  7. 7. Acute vs. Chronic Pain <ul><li>Acute pain </li></ul><ul><ul><li>Identified event (onset) </li></ul></ul><ul><ul><li>Resolves in days-weeks </li></ul></ul><ul><ul><li>Usually nociceptive </li></ul></ul><ul><li>Chronic pain </li></ul><ul><ul><li>Cause often not easily identified, multifactorial </li></ul></ul><ul><ul><li>Indeterminate duration </li></ul></ul><ul><ul><li>Nociceptive and/or neuropathic </li></ul></ul>
  8. 8. Barriers to assessing and treating pain <ul><li>Addiction: </li></ul><ul><li>means a person has lost control over the use of the drug and they continue to use it despite harmful consequences. </li></ul><ul><li>Tolerance: </li></ul><ul><li>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. </li></ul><ul><li>Dependence: </li></ul><ul><li>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. </li></ul><ul><li>Pseudo-addiction: </li></ul><ul><li>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 . </li></ul><ul><li>Substance-abusers </li></ul>
  9. 9. What is the easiest pain to bear? <ul><li>SOMEONE ELSE’S! </li></ul><ul><li>Don’t delay </li></ul><ul><li>Unmanaged pain leads to nervous system changes </li></ul><ul><ul><li>Permanent damage </li></ul></ul><ul><ul><li>Amplification of pain </li></ul></ul><ul><ul><li>Development of chronic pain </li></ul></ul>
  10. 10. WHO step-ladder 1 mild 2 moderate 3 severe Morphine Hydromorphone Methadone Levorphanol Fentanyl Oxycodone ± Adjuvants A/Codeine A/Hydrocodone A/Oxycodone A/Dihydrocodeine Tramadol ± Adjuvants ASA Acetaminophen NSAID’s ± Adjuvants WHO. Geneva, 1996 . 1-3 4-6 7-10
  11. 11. Opioid Pharmacology <ul><li>Conjugated in liver </li></ul><ul><li>First pass metabolism </li></ul><ul><li>Excreted by kidney (90-95%) </li></ul><ul><li>First order kinetics </li></ul>
  12. 12. Opioid kinetics Plasma Concentration 0 Half-life (t 1/2 ) Time IV PO/PR SC/IM C max 6-7 min 15-20 min 45-60 min
  13. 13. Clearance Issues <ul><li>Conjugated by liver </li></ul><ul><li>90-95% excreted in urine </li></ul><ul><li>Dehydration, renal failure, severe hepatic failure </li></ul><ul><ul><li>Decrease interval/dosing size </li></ul></ul><ul><ul><li>If oliguria/anuria </li></ul></ul><ul><ul><ul><li>STOP routine dosing (basal rate) of morphine </li></ul></ul></ul><ul><ul><ul><li>Use ONLY PRN </li></ul></ul></ul>
  14. 14. Opioid pharmacology <ul><li>What is the half life (range) for IV opioids? </li></ul><ul><ul><li>2-4 hours </li></ul></ul><ul><li>How many half lives to get to steady state? </li></ul><ul><ul><li>4-5 </li></ul></ul><ul><li>What do you base your scheduled dosing on: C max or T 1/2 ? </li></ul><ul><ul><li>T 1/2 </li></ul></ul><ul><li>What do you base your breakthrough dosing on: C max or T 1/2 ? </li></ul><ul><ul><li>C max </li></ul></ul>
  15. 15. Routine oral dosing: immediate release formulations <ul><li>Scheduled dosing based on t 1/2 </li></ul><ul><ul><li>Q4 hours </li></ul></ul><ul><li>PRN dosing based on time to Cmax </li></ul><ul><ul><li>Q1 hour PRN </li></ul></ul><ul><li>Adjust scheduled dose daily based on prn use </li></ul>
  16. 16. Routine oral dosing Extended release preparations <ul><li>Reason for use: </li></ul><ul><ul><li>Improve compliance, adherence </li></ul></ul><ul><li>Dose q8, q12, q24 hours (depending on product) </li></ul><ul><ul><li>Don’t crush or chew </li></ul></ul><ul><ul><li>May use time-release granules (Kadian) </li></ul></ul><ul><li>Adjust dose every 2-4 days (once steady state is reached.) </li></ul>
  17. 18. Equation: To convert from one opioid to another using same route FROM CHART: Opioid A dose (mg), route X opioid B route = opioid B dose (mg), route opioid A route ( )
  18. 19. Coverting <ul><li>Step 1: Calculate 24 hour dose of medication </li></ul><ul><li>Step 2: Choose 2nd medication </li></ul><ul><li>Step 3: Choose numbers from chart for ratio </li></ul><ul><li>Step 4: Calculate 24 hour dose of new opioid </li></ul><ul><li>Step 5: Divide 24 hour dose by new rate </li></ul>
  19. 20. Example: <ul><li>Mr. Jones is a 67 yo man with colon cancer, just had low anterior resection with diverting ileostomy. He is now NPO. </li></ul><ul><li>His home regimen is Oxycontin 40mg bid and oxycodone IR 10 mg q1 hour prn, which he uses twice a day. </li></ul><ul><li>The chief resident writes for a Dilaudid PCA with no basal and 0.1mg q6 minutes demand. </li></ul><ul><li>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. </li></ul>
  20. 21. Example <ul><li>Step 1: calculate 24 hour dose – </li></ul><ul><ul><li>Oxycontin 40mg bid = 80mg </li></ul></ul><ul><ul><li>Oxycodone 10mg 2x = 20 mg </li></ul></ul><ul><ul><li>Total 24 hour dose = 100 mg </li></ul></ul><ul><li>Step 2: choose new opioid = hydromorphone </li></ul><ul><li>Step 3: look at the chart </li></ul>
  21. 23. Example continued <ul><li>Step 3: select ratio from chart for formula </li></ul><ul><ul><li>Hydromorphone IV = 1 </li></ul></ul><ul><ul><li>Oxycodone PO = 10 </li></ul></ul><ul><li>Step 4: Calculate 24 hour dose of new opioid </li></ul><ul><li>100mg oxy (PO/24 hrs) x (1/10) = 10 mg hydromorphine IV/ 24 hrs </li></ul><ul><li>Step 5: Calculate new rate </li></ul><ul><ul><li>10mg/24hrs = 0.4 mg hydromorphone IV per hour </li></ul></ul><ul><ul><li>At least! </li></ul></ul>
  22. 25. Opioid Side Effects <ul><li>Common </li></ul><ul><li>Constipation </li></ul><ul><li>Dry mouth </li></ul><ul><li>Nausea/vomiting </li></ul><ul><li>Sedation </li></ul><ul><li>Sweats </li></ul><ul><li>Less Common </li></ul><ul><li>Bad dreams or hallucinations </li></ul><ul><li>Delirium </li></ul><ul><li>Myoclonus </li></ul><ul><li>Seizures </li></ul><ul><li>Pruritus, urticaria </li></ul><ul><li>Respiratory depression </li></ul><ul><li>Urinary retention </li></ul>
  23. 26. POP Quiz <ul><li>Pharmacologic tolerance develops to all of the following side effects of opioid analgesics except : </li></ul><ul><li>constipation </li></ul><ul><li>nausea </li></ul><ul><li>respiratory depression </li></ul><ul><li>sedation </li></ul>
  24. 27. Constipation <ul><li>Common to all opioids </li></ul><ul><li>Due to effects on: </li></ul><ul><ul><li>CNS, spinal cord, myenteric plexus of gut </li></ul></ul><ul><li>Easier to prevent than to treat </li></ul><ul><ul><li>Diet insufficient </li></ul></ul><ul><ul><li>Bulk forming agents not recommended </li></ul></ul><ul><li>Always order bowel regimen with opioid: </li></ul><ul><ul><li>Colace and senna if able to tolerate po </li></ul></ul>
  25. 28. Options to Treat Constipation <ul><li>Stimulant laxative: </li></ul><ul><ul><li>Senna, bisacodyl, glycerine, etc. </li></ul></ul><ul><li>Stool softener </li></ul><ul><ul><li>Docusate </li></ul></ul><ul><li>Prokinetic agent </li></ul><ul><ul><li>Metoclopramide </li></ul></ul><ul><li>Osmotic laxative (from above or below) </li></ul><ul><li>Specific to peripheral opioid receptors </li></ul><ul><ul><li>methylnatrexone </li></ul></ul>
  26. 29. Nausea/Vomiting <ul><li>Onset with start of opioids, tolerance may develop </li></ul><ul><li>Prevent or treat with dopamine-blocking anti-emetics (avoid with long-QT): </li></ul><ul><ul><li>Haloperidol 0.5-1mg every 6 hours </li></ul></ul><ul><ul><li>Droperidol 0.625 mg (PACU order set) </li></ul></ul><ul><ul><li>Metoclopramide 10mg every 6 hours </li></ul></ul><ul><li>Alternative opioid if refractory </li></ul>
  27. 30. Sedation <ul><li>Onset with start of opioids </li></ul><ul><ul><li>Distinguish from exhaustion due to pain* </li></ul></ul><ul><ul><li>Tolerance develops within days </li></ul></ul><ul><li>Complex assessment in advanced disease </li></ul><ul><li>If persistent, may consider alternative opioid or route of administration </li></ul><ul><li>Psychostimulants may play a role as well </li></ul><ul><ul><li>Methylphenidate 5mg qAM and 1 noon </li></ul></ul>
  28. 31. Delirium/Neuroexcitability <ul><li>Presentation </li></ul><ul><ul><li>Cognitive changes: CAM assessment </li></ul></ul><ul><ul><ul><li>acute onset or fluctuating course, </li></ul></ul></ul><ul><ul><ul><li>inattention, </li></ul></ul></ul><ul><ul><ul><li>disorganized thinking/altered level of consciousness </li></ul></ul></ul><ul><ul><li>Restlessness, agitation </li></ul></ul><ul><ul><li>Myoclonic jerks, seizures (may be repressed if on benzodiazepines) </li></ul></ul><ul><ul><li>More common in renal failure </li></ul></ul>
  29. 32. Respiratory Depression <ul><li>Opioid effects differ among patients </li></ul><ul><ul><li>Change in LOC occurs before respiratory suppression </li></ul></ul><ul><ul><li>Pharmacologic tolerance develops rapidly </li></ul></ul><ul><ul><li>Most studies of respiratory depression in opioids looked at patients with drug overdose </li></ul></ul><ul><li>Management: </li></ul><ul><ul><li>Identify and treat contributing causes </li></ul></ul><ul><ul><ul><li>Reduce opioid dose and observe </li></ul></ul></ul><ul><ul><li>If unstable vital signs: </li></ul></ul><ul><ul><ul><li>Naloxone 0.1-0.2 mg IV q 1-2 min </li></ul></ul></ul>
  30. 33. Opioid “allergies” <ul><li>Nausea/vomiting, constipation, drowsiness, confusion </li></ul><ul><ul><li>Adverse effects, not allergic reactions </li></ul></ul><ul><ul><li>Anticipated and managed </li></ul></ul><ul><li>Anaphylactic reactions are only true allergies </li></ul><ul><ul><li>Bronchospasms </li></ul></ul><ul><li>Urticaria, pruritus – need careful assessment </li></ul><ul><ul><li>Mast cell destabilization </li></ul></ul><ul><ul><li>Treat with routine long-acting, non-sedating antihistamines </li></ul></ul>
  31. 34. Adjunctive Analgesics <ul><li>Supplement primary analgesics </li></ul><ul><li>May be primary analgesics </li></ul><ul><li>Use at any step of WHO ladder </li></ul>
  32. 35. Adjunctive Analgesics: <ul><li>NSAIDS </li></ul><ul><li>Local anesthetics - Topical - Regional - Systemic </li></ul><ul><li>Steroids </li></ul><ul><li>Radiation </li></ul><ul><li>Physical therapy </li></ul><ul><li>Psychological approaches </li></ul><ul><li>Complementary therapies </li></ul>
  33. 36. Routes of Delivery <ul><li>PO/enteral feeding tubes </li></ul><ul><li>Transmucosal </li></ul><ul><li>Rectal </li></ul><ul><li>Transdermal (fentanyl) </li></ul><ul><li>Parenteral: SC, IV, IM </li></ul><ul><li>Intraspinal: Epidural, Intrathecal </li></ul>
  34. 37. Contacts <ul><li>Acute Pain service at University: </li></ul><ul><ul><li>Perioperative pain, interventional pain </li></ul></ul><ul><ul><li>OUCH pager </li></ul></ul><ul><li>Interventional Pain service at Memorial: </li></ul><ul><ul><li>Perioperative pain, back pain crisis, cancer pain requiring intervention </li></ul></ul><ul><ul><li>Christian Gonzalez, MD </li></ul></ul><ul><li>Palliative Medicine Service: </li></ul><ul><ul><li>Pain related to severe/life-limiting illness (cancer, cardiac, etc.) </li></ul></ul><ul><ul><li>Office: 334-8630; see call schedule for pager </li></ul></ul>
  35. 38. Take home messages <ul><li>Treat the pain like it was your own </li></ul><ul><li>Remember to take into account pain medications being taken before surgery </li></ul><ul><li>Take an active approach to avoiding constipation! </li></ul><ul><li>Decrease dose/frequency in renal and hepatic failure – and just use PRN doses </li></ul><ul><li>Think of adjuncts (NSAIDS, steroids, topicals etc) </li></ul>
  36. 39. Questions?
  37. 40. Corticosteroids <ul><li>May have a role in patients with advanced illness: when? </li></ul><ul><li>Dexamethasone </li></ul><ul><ul><li>Long half-life (>35 hours), dose once / day </li></ul></ul><ul><ul><li>Minimal mineralocorticoid effect </li></ul></ul><ul><ul><li>Doses 2-20+ mg/day </li></ul></ul><ul><li>Adverse effects </li></ul><ul><ul><li>Steroid psychosis </li></ul></ul><ul><ul><li>Proximal myopathy </li></ul></ul><ul><ul><li>Other long-term adverse effects </li></ul></ul>
  38. 41. Interventional Pain Management <ul><li>14% cancer patients have pain unrelieved despite aggressive medical management. </li></ul><ul><li>Intraspinal therapies </li></ul><ul><li>Plexus nerve blocks: celiac, etc. </li></ul><ul><li>Nerve stimulation, ablation </li></ul><ul><li>Vertebral cementing </li></ul><ul><li>Memorial : Interventional Pain – Christian Gonzalez, MD </li></ul><ul><li>University : Acute Pain Service – OUCH pager </li></ul>
  39. 42. Radiation Therapy <ul><li>Studies show that high dose/fraction, low number of fractions is as effective as low fraction and high number of treatments in palliative settings. </li></ul>
  40. 43. Non-pharmacologic interventions <ul><li>Neurostimulation </li></ul><ul><li>Surgical </li></ul><ul><li>Physical therapy </li></ul><ul><li>Psychological approaches </li></ul><ul><ul><li>Cognitive therapies </li></ul></ul><ul><ul><li>Biofeedback </li></ul></ul><ul><ul><li>Behavior therapy </li></ul></ul><ul><li>Complementary therapies </li></ul><ul><ul><li>Acupuncture </li></ul></ul><ul><ul><li>Massage </li></ul></ul><ul><ul><li>Meditation/relaxation: Refer to Center for Mindfulness </li></ul></ul>
  41. 44. Fentanyl patch (Duragesic) <ul><li>Black box warning: why? </li></ul><ul><li>Not for opioid naïve patients </li></ul><ul><li>Not good for acute pain </li></ul><ul><li>Takes 24 hours to reach peak effect </li></ul><ul><li>Held in subcutaneous fat, thus takes >12 hours after patch is removed to leave system </li></ul><ul><li>Must not cut patch </li></ul>
  42. 45. To start Fentanyl Patch <ul><li>From oral morphine to patch: </li></ul><ul><li>Oral morphine 50-100 mg in 24 hours = </li></ul><ul><ul><li>Fentanyl 25 mcg/hour transdermal patch </li></ul></ul><ul><li>From IV Fentanyl to patch </li></ul><ul><li>1:1 conversion </li></ul><ul><li>25 mcg/hour = 25 mcg/hour patch </li></ul>
  43. 46. Adjunctive Analgesics: Anticonvulsants <ul><li>Gabapentin (Neurontin) </li></ul><ul><ul><li>100 mg PO daily to tid, titrate </li></ul></ul><ul><ul><li>Increase dose q 1-3 days - Usual effective dose 900-1800 mg/day </li></ul></ul><ul><ul><ul><li>Max may be > 3600 mg/day </li></ul></ul></ul><ul><ul><li>Minimal adverse effects </li></ul></ul><ul><ul><ul><li>Drowsiness, tolerance develops within days </li></ul></ul></ul><ul><li>Pregabalin (Lyrica) </li></ul><ul><ul><li>Start 50 mg tid, titrate over 7 days up to 600mg/day in divided doses </li></ul></ul><ul><li>Carbamazepine </li></ul><ul><ul><li>100mg bid, titrate </li></ul></ul><ul><li>Valproic acid – monitor drug levels </li></ul>
  44. 47. Adjunctive Analgesics: Tricyclic Antidepressants <ul><li>Amitriptyline </li></ul><ul><ul><li>Most extensively studied - NMDA receptor </li></ul></ul><ul><ul><li>10-25 mg po nightly, titrate ever 4-7 days </li></ul></ul><ul><ul><li>Analgesia in days to weeks </li></ul></ul><ul><ul><li>Monitor plasma levels </li></ul></ul><ul><ul><li>Adverse effects prominent (anticholinergic) </li></ul></ul><ul><li>Desipramine </li></ul><ul><ul><li>Fewer anticholinergic side effects </li></ul></ul><ul><ul><li>10-25 mg po qhs, titrate </li></ul></ul><ul><ul><li>Tricyclic of choice in the seriously ill </li></ul></ul><ul><ul><li>Nortriptyline is an alternative </li></ul></ul>
  45. 48. Adjunctive Analgesics: SSNRI <ul><li>Duloxetine (Cymbalta) </li></ul><ul><li>Venlafaxine (Effexor) </li></ul>
  46. 49. Adjunctive Analgesics: NMDA Receptor Antagonists <ul><li>Dextromethorphan </li></ul><ul><li>Ketamine </li></ul><ul><li>Methadone – opioid + NMDA r-antagonist </li></ul>
  47. 50. <ul><li>Dose interval for methadone is variable (q 6 h or q 8 h is usually adequate) </li></ul><ul><li>Biphasic pharmacology makes it more complex: </li></ul><ul><ul><li>side effects may only show up day 3 </li></ul></ul><ul><li>Adjust methadone dose q 4-7 days </li></ul><ul><li>Do not use PRN dosing of methadone. </li></ul>Methadone
  48. 51. Changing opioids… <ul><li>Adjusting for cross-tolerance </li></ul><ul><ul><li>Start with 50-75% of published equianalgesic dose </li></ul></ul><ul><ul><ul><li>More if pain is uncontrolled </li></ul></ul></ul><ul><ul><ul><li>Less if there are adverse side effects of current opioid. </li></ul></ul></ul><ul><li>Methadone </li></ul><ul><ul><li>Start with 10-25% of published equianalgesic dose and </li></ul></ul><ul><ul><li>Consult pain service for assistance. </li></ul></ul>Ripamonti C, Zecca E, Bruera E. Pain . 1997.
  49. 52. Adjusting for cross-tolerance
  50. 53. Breakthrough dosing <ul><li>Based on time to Cmax </li></ul><ul><ul><li>PO/PR – q1 hour </li></ul></ul><ul><ul><li>SQ/IM – q20-30 min </li></ul></ul><ul><ul><li>IV – q 6-15 min </li></ul></ul><ul><li>Use immediate release opioids 5-15% of 24 hour dose </li></ul>
  51. 54. Relative strengths of routes <ul><li>Significant first-pass metabolism of PO/PR dose </li></ul>PO/PR to SC, IV, IM 2-3 ~ 1
  52. 55. Using a PCA <ul><li>Basal rate </li></ul><ul><li>Bolus dose (PCA dose) </li></ul><ul><li>Lock-out </li></ul><ul><ul><ul><ul><ul><li>(See PCA form) </li></ul></ul></ul></ul></ul>
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