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

Abstract

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. 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. 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. 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.