Ketamine with and without midazolam for emergency department sedation in adults: a randomized controlled trial.

Study Objective: We assess whether midazolam reduces recovery agitation after ketamine administration in adult emergency department (ED) patients and also compared the incidence of adverse events (recovery agitation, respiratory, and nausea/vomiting) by the intravenous (IV) versus intramuscular (IM) route.

Methods: This prospective, double-blind, placebo-controlled, 2×2 factorial trial randomized consecutive ED patients aged 18 to 50 years to 4 groups: receiving either 0.03 mg/kg IV midazolam or placebo, and with ketamine administered either 1.5 mg/kg IV or 4 mg/kg IM. Adverse events and sedation characteristics were recorded.

Results: Of the 182 subjects, recovery agitation was less common in the midazolam cohorts (8% versus 25%; difference 17%; 95% confidence interval [CI] 6% to 28%; number needed to treat 6). When IV versus IM routes were compared, the incidences of adverse events were similar (recovery agitation 13% versus 17%, difference 4%, 95% CI -8% to 16%; respiratory events 0% versus 0%, difference 0%, 95% CI -2% to 2%; nausea/vomiting 28% versus 34%, difference 6%, 95% CI -8% to 20%).

Conclusion: Coadministered midazolam significantly reduces the incidence of recovery agitation after ketamine procedural sedation and analgesia in ED adults (number needed to treat 6). Adverse events occur at similar frequency by the IV or IM routes.