Ketamine infusion for sickle cell pain crisis refractory to opioids: a case report and review of literature

Abstract

This article reports a rare case of the use of low-dose ketamine infusion as an adjuvant to opioids to treat pain in sickle cell disease. A 31-year-old African-American male with history of sickle cell disease presented to the emergency department with complaints of chest tightness, multiple joint pain, and headache for 1 week. His vital signs and physical examination were unremarkable. His admission lab included hemoglobin of 8.4 g/dl, reticulocyte count of 16.3%, bilirubin of 1.7 mg/dl, and LDH of 1,267 U/l. Chest X-ray showed middle and lower lobe opacity and interstitial thickening. He was treated for acute pain crisis and community-acquired pneumonia with intravenous fluids, supplemental oxygen, and intravenous levofloxacin. He was placed on fentanyl patient-controlled analgesia (PCA), oxycodone, ketorolac, and methadone with co-analgesic gabapentin and venlafaxine. Over the course of his hospitalization, his chest pain resolved, but the joint pains continued. He was then transferred to the ICU and was discharged a day later after 7 days of ketamine infusion. Ketamine is a noncompetitive antagonist at the N-methyl-D-aspartate (NMDA) receptor. This property has been shown to modulate opioid tolerance and opioid-induced hyperalgesia. There have been a very few published reports on the use of low-dose ketamine in sickle cell pain management. A PubMed search revealed four published articles (Table 1). Fourteen out of the 17 cases (82.35%) who received ketamine infusion showed improvement in self-reported pain intensity and significant reduction in opioid dosage. Only one patient (5.9%) developed serious side effect leading to discontinuation of the drug. A low-dose ketamine can be an option for pain control in sickle cell disease. Randomized trial is required to establish this benefit of ketamine over currently available therapies.

An Evaluation of Central Sensitization in Patients With Sickle Cell Disease

“…This important iatrogenic effect of opioids is a particularly challenging topic to study in sickle cell, as complications of the disease typically require early, and sometimes extensive, exposure to opioid therapy intermittently over years. The use of ketamine, the noncompetitive NMDA receptor antagonist, in recent case reports of acute pain management of sickle cell crises [52] that have successfully reduced opioid dosing while enhancing pain management support the potential importance of OIH in sickle cell patients.…”

Low‐dose Ketamine Improves Pain Relief in Patients Receiving Intravenous Opioids for Acute Pain in the Emergency Department: Results of a Randomized, Double‐blind, Clinical Trial

“…In addition, we postulate that low-dose ketamine would be useful among patients for whom the use of opioids is problematic, such as severe polytrauma, chronic pain, suspected opioid induced-hyperalgesia, and tolerance to opioids (i.e., sickle cell pain crises). 19,20 These specific subpopulations have challenging issues when it comes to pain management and approaches to assist them are interesting areas of future study.…”

Sickle cell disease: a natural model of acute and chronic pain

“…[74] SCD patients often require large opioid doses due to increased opioid metabolism and clearance, as well as tolerance from receiving life-long opioid therapy[14] such that their pain becomes increasingly refractory to opioids. [65] Further, some SCD patients display opioid-induced hyperalgesia. [63]…”

“…Expressed on mast cells and CB1 and CB2 receptor agonists alleviate cutaneous and deep tissue pain behavior in SCD mice[65]…”