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Treatment of Refractory Pain: A Focus on IV Lidocaine and Ketamine

Emmeline Tran, PharmD , BCPS Medical University of South Carolina PGY2 Internal Medicine Resident. Treatment of Refractory Pain: A Focus on IV Lidocaine and Ketamine. Objective. Develop a therapeutic plan for the treatment of refractory pain using intravenous lidocaine or ketamine.

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Treatment of Refractory Pain: A Focus on IV Lidocaine and Ketamine

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  1. Emmeline Tran, PharmD, BCPS Medical University of South Carolina PGY2 Internal Medicine Resident Treatment of Refractory Pain: A Focus on IV Lidocaine and Ketamine

  2. Objective • Develop a therapeutic plan for the treatment of refractory pain using intravenous lidocaine or ketamine

  3. Background • Pain • Complex • Subjective Psychological Biological Social Institute of Medicine. 2011.

  4. Patient Case • 34 year old male • Past medical history • Sickle cell disease • Chronic pain • Pain medications • ibuprofen 800 mg PO TID • gabapentin 800 mg PO TID • hydromorphone PCA • Total daily dose = 300 mg

  5. WHO Pain Ladder Can Fam Physician. 2010 Jun;56(6):514-7, e202-5.

  6. WHO Pain Ladder Can Fam Physician. 2010 Jun;56(6):514-7, e202-5.

  7. Lidocaine • Adjunctive agent • High degree of opioid tolerance • Neuropathic pain Pain Physician. 2013 May-Jun;16(3):231-49.

  8. Lidocaine • Mechanism of Action perception cortex modulation transmission thalamus primary afferent neuron dorsal root Pain Physician. 2013 May-Jun;16(3):231-49.

  9. Lidocaine • Mechanism of Action perception cortex modulation transmission thalamus primary afferent neuron dorsal root Pain Physician. 2013 May-Jun;16(3):231-49.

  10. Lidocaine • Mechanism of Action • Non-selective sodium channel blocker sodium extracellular fluid sodium channel potassium channel intracellular fluid potassium Pain Physician. 2013 May-Jun;16(3):231-49.

  11. Lidocaine • Mechanism of Action • Non-selective sodium channel blocker sodium extracellular fluid sodium channel potassium channel intracellular fluid potassium Pain Physician. 2013 May-Jun;16(3):231-49.

  12. Lidocaine LexiComp. Accessed February 29, 2016. Micromedex. Accessed February 29, 2016. Pain Physician. 2013 May-Jun;16(3):231-49.

  13. Lidocaine LexiComp. Accessed February 29, 2016. Micromedex. Accessed February 29, 2016. Pain Physician. 2013 May-Jun;16(3):231-49.

  14. Lidocaine • Clinical Pearls • No formal renal or hepatic dose adjustments, use caution • Telemetry is not necessary for patients with no previous cardiac conditions • Cardiac arrhythmias and hemodynamic instability are possible, but not found in trials when used in pain management LexiComp. Accessed February 29, 2016. Micromedex. Accessed February 29, 2016. J Palliat Med. 2015 Apr;18(4):373-7.

  15. Ketamine • Adjunctive agent • High degree of opioid tolerance • Opioid-induced hyperalgesia • Neuropathic pain Pain Physician. 2013 May-Jun;16(3):231-49. J Palliat Med. 2012 Apr;15(4):474-83. Pain Physician. 2007 May;10(3):493-500. Biomed Pharmacother. 2006 Aug;60(7):341-8.

  16. Ketamine • Mechanism of Action perception cortex modulation transmission thalamus primary afferent neuron dorsal root Pain Physician. 2013 May-Jun;16(3):231-49. J Palliat Med. 2012 Apr;15(4):474-83.

  17. Ketamine • Mechanism of Action perception cortex modulation transmission thalamus primary afferent neuron dorsal root Pain Physician. 2013 May-Jun;16(3):231-49. J Palliat Med. 2012 Apr;15(4):474-83.

  18. Ketamine • Mechanism of Action • N-methyl-D-aspartate (NMDA) antagonist calcium extracellular fluid calcium NDMA receptor NMDA receptor intracellular fluid Pain Physician. 2013 May-Jun;16(3):231-49. J Palliat Med. 2012 Apr;15(4):474-83.

  19. Ketamine • Mechanism of Action • N-methyl-D-aspartate (NMDA) antagonist calcium extracellular fluid calcium NDMA receptor NMDA receptor intracellular fluid Pain Physician. 2013 May-Jun;16(3):231-49. J Palliat Med. 2012 Apr;15(4):474-83.

  20. Ketamine Pain Physician. 2013 May-Jun;16(3):231-49. J Palliat Med. 2012 Apr;15(4):474-83. Pain Physician. 2007 May;10(3):493-500. Biomed Pharmacother. 2006 Aug;60(7):341-8.

  21. Ketamine • Clinical Pearls • IV: PO conversion = 1:1 • IV product is used orally • No consensus on a uniform ketamine protocol or dose • Reduce the long acting opioid dose by ~25 to 50% Pain Physician. 2013 May-Jun;16(3):231-49. J Palliat Med. 2012 Apr;15(4):474-83. Pain Physician. 2007 May;10(3):493-500. Biomed Pharmacother. 2006 Aug;60(7):341-8.

  22. Ketamine • Clinical Pearls • No formal renal or hepatic dose adjustments, use caution • Elderly patients may warrant dose reductions Pain Physician. 2013 May-Jun;16(3):231-49. J Palliat Med. 2012 Apr;15(4):474-83. Pain Physician. 2007 May;10(3):493-500. Biomed Pharmacother. 2006 Aug;60(7):341-8.

  23. Ketamine Pain Physician. 2013 May-Jun;16(3):231-49. J Palliat Med. 2012 Apr;15(4):474-83. Pain Physician. 2007 May;10(3):493-500. Biomed Pharmacother. 2006 Aug;60(7):341-8. LexiComp. Accessed February 29, 2016. Micromedex. Accessed February 29, 2016.

  24. Ketamine • Clinical Pearls • Not well-studied for breakthrough pain • Give one-tenth to one-sixth of oral dose or 5 to 10 mg IV for breakthrough pain • Discontinuation can be done safely without concerns for withdrawal Pain Physician. 2013 May-Jun;16(3):231-49. J Palliat Med. 2012 Apr;15(4):474-83. Pain Physician. 2007 May;10(3):493-500. Biomed Pharmacother. 2006 Aug;60(7):341-8.

  25. Ketamine Pain Physician. 2013 May-Jun;16(3):231-49. J Palliat Med. 2012 Apr;15(4):474-83. Pain Physician. 2007 May;10(3):493-500. Biomed Pharmacother. 2006 Aug;60(7):341-8.

  26. Ketamine • Clinical Pearls • Most common side effects are psychomimetic • Test dose of 5 mg IV or 20 mg PO • Use benzodiazepine or butyrophenone to help prevent or manage • Cardiovascular side effects and respiratory depression are rare Pain Physician. 2013 May-Jun;16(3):231-49. J Palliat Med. 2012 Apr;15(4):474-83. Pain Physician. 2007 May;10(3):493-500. Biomed Pharmacother. 2006 Aug;60(7):341-8.

  27. Patient Case • 34 year old male • Past medical history • Sickle cell disease • Chronic pain • Pain medications • ibuprofen 800 mg PO TID • gabapentin 800 mg PO TID • hydromorphone PCA • Total daily dose = 300 mg Which of the following would you try next? a. Lidocaine IV b. Ketamine PO c. Ketamine IV d. None of the above

  28. Patient Case • 34 year old male • Past medical history • Sickle cell disease • Chronic pain • Pain medications • ibuprofen 800 mg PO TID • gabapentin 800 mg PO TID • hydromorphone PCA • Total daily dose = 300 mg Which of the following would you try next? a. Lidocaine IV b. Ketamine PO c. Ketamine IV d. None of the above

  29. Conclusions • Pain is difficult to treat • Utilize medications with unique mechanisms of action in the treatment of refractory pain

  30. Good Resources • Institute of Medicine (US) Committee on Advancing Pain Research, Care, and Education. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Washington (DC): National Academies Press (US); 2011. • KosharskyyB, Almonte W, Shaparin N, Pappagallo M, Smith H. Intravenous infusions in chronic pain management. Pain Physician. 2013 May-Jun;16(3):231-49. • OkonT. Ketamine: an introduction for the pain and palliative medicine physician. Pain Physician. 2007 May;10(3):493-500. • PrommerEE. Ketamine for pain: an update of uses in palliative care. J Palliat Med. 2012 Apr;15(4):474-83.

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