The role of a low-dose ketamine-midazolam regimen in the management of severe painful crisis in patients with sickle cell disease

J Pain Symptom Manage. 2014 Feb;47(2):334-40. doi: 10.1016/j.jpainsymman.2013.03.012. Epub 2013 Jul 12.


Context: Acute pain is one of the main causes of hospital admission in sickle cell disease, with variable intensity and unpredictable onset and duration.

Objectives: We studied the role of a low-dose intravenous (IV) ketamine-midazolam combination in the management of severe painful sickle cell crisis.

Methods: A retrospective analysis was performed with data from nine adult patients who were admitted to the intensive care unit with severe painful sickle cell crises not responding to high doses of IV morphine and other adjuvant analgesics. A ketamine-midazolam regimen was added to the ongoing opioids as an initial bolus of ketamine 0.25mg/kg, followed by infusion of 0.2-0.25mg/kg/h. A midazolam bolus of 1mg followed by infusion of 0.5-1mg/h was added to reduce ketamine emergence reactions. Reduction in morphine daily requirements and improvement in pain scores were the determinants of ketamine-midazolam effect. The t-tests were used for statistical analysis.

Results: Nine patients were assessed, with mean age of 27±11 years. Morphine requirement was significantly lower after adding the IV ketamine-midazolam regimen. The mean±SD IV morphine requirement (milligram/day) in the pre-ketamine day (D0) was 145.6±16.5, and it was 112±12.2 on Day 1 (D1) of ketamine treatment (P=0.007). The Numeric Rating Scale scores on D0 ranged from eight to ten (mean 9.1), but improved to range from five to seven (mean 5.7) on D1. There was a significant improvement in pain scores after adding ketamine-midazolam regimen (P=0.01).

Conclusion: Low-dose ketamine-midazolam IV infusion might be effective in reducing pain and opioid requirements in patients with sickle cell disease with severe painful crisis. Further controlled studies are required to prove this effect.

Keywords: Sickle cell disease; ketamine; midazolam; pain management; painful crisis.

MeSH terms

  • Administration, Intravenous
  • Adolescent
  • Adult
  • Analgesics / administration & dosage*
  • Analgesics, Opioid / administration & dosage
  • Anemia, Sickle Cell / physiopathology*
  • Critical Care / methods
  • Drug Combinations
  • Female
  • Humans
  • Hypnotics and Sedatives / administration & dosage*
  • Ketamine / administration & dosage*
  • Male
  • Midazolam / administration & dosage*
  • Morphine / administration & dosage
  • Pain / drug therapy*
  • Pain / physiopathology
  • Pain Management / methods
  • Pain Measurement
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult


  • Analgesics
  • Analgesics, Opioid
  • Drug Combinations
  • Hypnotics and Sedatives
  • Ketamine
  • Morphine
  • Midazolam