The role of short-term, low dose intravenous ketamine infusion in Calciphylaxis


Calciphylaxis is a small vessel vasculopathy causing subcutaneous ischemic necrosis. This condition is a recognized complication of end stage renal disease and is associated with severe pain. The mechanism of the pain generated by calciphylaxis is thought to be partly related to tissue ischemia, with a significant neuropathic component associated with neuronal hypoxic injury. The pain can be further exacerbated by the inflammatory process ensuing as a result of calciphylactic lesion infections which are commonly associated with this condition. Obtaining adequate pain relief is a challenging aspect of symptom control in calciphylaxis, and historically, patients suffering from calciphylaxis required high dose opioid medications to achieve satisfactory analgesia.

This case report presents a multimodal pain management approach utilizing low dose ketamine infusion in an opioid-tolerant patient suffering from severe calciphylaxis-related pain. Ketamine is an anesthetic agent well established for its efficacy in the management of neuropathic pain in opioid-tolerant patients, and has been shown to prevent opioid-induced hyperalgesia and decrease opioid requirements. Prior published data studying pain control in calciphylaxis have mainly focused on subcutaneous ketamine administration which as noted in the literature, can be associated with infusion site complications. To the best of our knowledge, this report is first of its kind to describe successful use of ketamine infusion in treatment of acute calciphylaxis-related pain.

Dose modification of ketamine is not required for patients with impaired renal function, and low dose intravenous ketamine infusion was associated with no reported adverse effects in our patient.

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  1. 1.

    Gipstein RM, et al. Calciphylaxis in man. A syndrome of tissue necrosis and vascular calcification in 11 patients with chronic renal failure. Arch Intern Med. 1976;136(11):1273–80.

    CAS  Article  Google Scholar 

  2. 2.

    Oh DH, et al. Five cases of calciphylaxis and a review of the literature. J Am Acad Dermatol. 1999;40(6 Pt 1):979–87.

    CAS  Article  Google Scholar 

  3. 3.

    Polizzotto MN, et al. Symptomatic management of calciphylaxis: a case series and review of the literature. J Pain Symptom Manage. 2006;32(2):186–90.

    Article  Google Scholar 

  4. 4.

    Udomkarnjananun S, et al. Treatment of calciphylaxis in CKD: a systematic review and meta-analysis. Kidney Int Rep. 2019;4(2):231–44.

    Article  Google Scholar 

  5. 5.

    King S, et al. A systematic review of the use of opioid medication for those with moderate to severe cancer pain and renal impairment: a European Palliative Care Research Collaborative opioid guidelines project. Palliat Med. 2011;25(5):525–52.

    CAS  Article  Google Scholar 

  6. 6.

    Raina R, Krishnappa V, Gupta M. Management of pain in end-stage renal disease patients: short review. Hemodial Int. 2018;22(3):290–6.

    Article  Google Scholar 

  7. 7.

    Trujillo KA, Akil H. Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801. Science. 1991;251(4989):85–7.

    CAS  Article  Google Scholar 

  8. 8.

    Zhou HY, Chen SR, Pan HL. Targeting N-methyl-d-aspartate receptors for treatment of neuropathic pain. Expert Rev Clin Pharmacol. 2011;4(3):379–88.

    CAS  Article  Google Scholar 

  9. 9.

    Clark JL, Kalan GE. Effective treatment of severe cancer pain of the head using low-dose ketamine in an opioid-tolerant patient. J Pain Symptom Manage. 1995;10(4):310–4.

    CAS  Article  Google Scholar 

  10. 10.

    Mitra S, Sinatra RS. Perioperative management of acute pain in the opioid-dependent patient. Anesthesiology. 2004;101(1):212–27.

    Article  Google Scholar 

  11. 11.

    Mitra S. Opioid-induced hyperalgesia: pathophysiology and clinical implications. J Opioid Manag. 2008;4(3):123–30.

    Article  Google Scholar 

  12. 12.

    Aroni F, et al. Pharmacological aspects and potential new clinical applications of ketamine: reevaluation of an old drug. J Clin Pharmacol. 2009;49(8):957–64.

    CAS  Article  Google Scholar 

  13. 13.

    Capel MM, et al. Use of ketamine for ischemic pain in end-stage renal failure. J Pain Symptom Manage. 2009;35:232–4.

    Article  Google Scholar 

  14. 14.

    Kudoh A, et al. Small-dose ketamine improves the postoperative state of depressed patients. Anesth Analg. 2002;95(1):114–8.

    CAS  Article  Google Scholar 

  15. 15.

    Javery KB, et al. Comparison of morphine and morphine with ketamine for postoperative analgesia. Can J Anaesth. 1996;43(3):212–5.

    CAS  Article  Google Scholar 

  16. 16.

    Trivedi S, et al. A comparative study of dexmedetomidine and midazolam in reducing delirium caused by ketamine. J Clin Diagn Res. 2016;10(8):UC01-4.

    CAS  PubMed  Google Scholar 

  17. 17.

    Orhurhu, VJ., et al. Ketamine Toxicity, in StatPearls. 2020: Treasure Island (FL).

  18. 18.

    Fitzgibbon EJ, et al. Low dose ketamine as an analgesic adjuvant in difficult pain syndromes: a strategy for conversion from parenteral to oral ketamine. J Pain Symptom Manage. 2002;23(2):165–70.

    Article  Google Scholar 

  19. 19.

    Elia N, Tramer MR. Ketamine and postoperative pain–a quantitative systematic review of randomised trials. Pain. 2005;113(1–2):61–70.

    CAS  Article  Google Scholar 

  20. 20.

    Honarmand A, Safavi M, Karaky H. Preincisional administration of intravenous or subcutaneous infiltration of low-dose ketamine suppresses postoperative pain after appendectomy. J Pain Res. 2012;5:1–6.

    CAS  PubMed  Google Scholar 

  21. 21.

    Maher J, et al. Balloon cell melanoma: a case report with polarized and non-polarized dermatoscopy and dermatopathology. Dermatol Pract Concept. 2014;4(1):69–73.

    PubMed  Google Scholar 

  22. 22.

    Mitchell AC, Fallon MT. A single infusion of intravenous ketamine improves pain relief in patients with critical limb ischaemia: results of a double blind randomised controlled trial. Pain. 2002;97(3):275–81.

    CAS  Article  Google Scholar 

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Research idea and study design: SG, DLJ, JSS. Data acquisition: SG. Data analysis/interpretation: SG, DLJ, JSS. Supervision: DLJ, JSS. Each author contributed important intellectual content during manuscript drafting and revision, accepts personal accountability for the author’s own contributions, and agrees to ensure that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. This manuscript has been read and approved by all co-authors.

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Correspondence to Shirin Ghanavatian.

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Ghanavatian, S., James, D.L. & Sadolf, J.S. The role of short-term, low dose intravenous ketamine infusion in Calciphylaxis. CEN Case Rep (2021).

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  • Calciphylaxis
  • End stage renal disease
  • Ketamine