Premedication With Midazolam or Haloperidol to Prevent Recovery Agitation in Adults Undergoing Procedural Sedation With Ketamine: A Randomized Double-Blind Clinical Trial

Abstract

Study objective: We evaluate the effect of midazolam and haloperidol premedication for reducing ketamine-induced recovery agitation in adult patients undergoing procedural sedation. We also compare physician satisfaction and recovery time.

Methods: We randomized emergency department patients older than 18 years who needed procedural sedation to receive 1 of the following 3 interventions in double-blind fashion 5 minutes before receiving intravenous ketamine at 1 mg/kg: intravenous distilled water, intravenous midazolam at 0.05 mg/kg, or intravenous haloperidol at 5 mg. Our main study outcomes were recovery agitation as assessed by the maximum observed Pittsburgh Agitation Scale score and by the Richmond Agitation-Sedation Scale score at 5, 15, and 30 minutes after ketamine administration. Our secondary outcomes were clinician satisfaction and recovery duration.

Results: We enrolled 185 subjects. The maximum Pittsburgh Agitation Scale score was significantly less with midazolam compared with placebo (difference 3; 95% confidence interval 1.27 to 4.72) and with haloperidol compared with placebo (difference 3; 95% confidence interval 1.25 to 4.75), and Richmond Agitation-Sedation Scale scores at 5, 15, and 30 minutes trended lower with the active agents. Midazolam and haloperidol significantly delayed recovery but did not alter overall clinician satisfaction.

Conclusion: For adult procedural sedation, premedication with either midazolam 0.05 mg/kg or haloperidol 5 mg intravenously significantly reduces ketamine-induced recovery agitation while delaying recovery.

Trial registration: ClinicalTrials.gov NCT02909465.