Ketamine administration for acute painful sickle cell crisis: A randomized controlled trial

Acad Emerg Med. 2022 Feb;29(2):150-158. doi: 10.1111/acem.14382. Epub 2021 Sep 21.


Objective: The objective was to evaluate the efficacy and safety of single-dose ketamine infusion in adults with sickle cell disease (SCD) who presented with acute sickle vasoocclusive crisis (VOC).

Methods: This study was a parallel-group, prospective, randomized, double-blind, pragmatic trial. Participants were randomized to receive a single dose of either ketamine or morphine, infused over 30 min. Primary outcome was mean difference in the numerical pain rating scale (NPRS) score over 2 h. NPRS was recorded every 30 min for a maximum of 180 min and secondary outcomes were cumulative dose of opioids, emergency department (ED) length of stay, hospital admission, change in vital signs, and drug-related side effects. Authors performed the analysis using intention-to-treat principle.

Result: A total of 278 adults with SCD and who presented with acute sickle VOC participated in this trial. A total of 138 were allocated to the ketamine group. Mean (±standard deviation [SD]) NPRS scores over 2 h were 5.7 (±2.13) and 5.6 (±1.90) in the ketamine and morphine groups. The ketamine group received significantly lower cumulative doses of morphine during their ED stay (mean ± SD = 4.5 ± 4.6 mg) than of the morphine group (mean ± SD = 8.5 ± 7.55 mg). Both groups had similar rates of hospital admission: 6.3% in the ketamine group had drug-related side effects compared to 2.2% in the morphine group.

Conclusion: Early use of ketamine in adults with VOC resulted in a meaningful reduction in pain scores over a 2-h period and reduced the cumulative morphine dose in the ED with no significant drug-related side effects in the ketamine-treated group.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acute Pain* / drug therapy
  • Acute Pain* / etiology
  • Analgesics / therapeutic use
  • Analgesics, Opioid / therapeutic use
  • Anemia, Sickle Cell* / complications
  • Anemia, Sickle Cell* / drug therapy
  • Double-Blind Method
  • Humans
  • Ketamine*
  • Morphine
  • Pain Measurement / methods
  • Prospective Studies


  • Analgesics
  • Analgesics, Opioid
  • Ketamine
  • Morphine