• David Barbic, Gary Andolfatto, Brian Grunau, Frank X Scheuermeyer, Bill Macewan, Hong Qian, Hubert Wong, Skye P Barbic, and William G Honer.
• Department of Emergency Medicine, University of British Columbia, Vancouver, BC, Canada; Centre for Health Evaluation & Outcomes Sciences, St. Paul's Hospital, Vancouver, BC, Canada. Electronic address: david.barbic@ubc.ca.
• Ann Emerg Med. 2021 Dec 1; 78 (6): 788-795.

Study ObjectiveWe hypothesized that the use of intramuscular ketamine would result in a clinically relevant shorter time to target sedation.MethodsWe conducted a randomized clinical trial comparing the rapidity of onset, level of sedation, and adverse effect profile of ketamine compared to a combination of midazolam and haloperidol for behavioral control of emergency department patients with severe psychomotor agitation. We included patients with severe psychomotor agitation measured by a Richmond Agitation Score (RASS) ≥+3. Patients in the ketamine group were treated with a 5 mg/kg intramuscular injection. Patients in the midazolam and haloperidol group were treated with a single intramuscular injection of 5 mg midazolam and 5 mg haloperidol. The primary outcome was the time, in minutes, from study medication administration to adequate sedation, defined as RASS ≤-1. Secondary outcomes included the need for rescue medications and serious adverse events.ResultsBetween June 30, 2018, and March 13, 2020, we screened 308 patients and enrolled 80. The median time to sedation was 14.7 minutes for midazolam and haloperidol versus 5.8 minutes for ketamine (difference 8.8 minutes [95% confidence interval (CI) 3.0 to 14.5]). Adjusted Cox proportional model analysis favored the ketamine arm (hazard ratio 2.43, 95% CI 1.43 to 4.12). Five (12.5%) patients in the ketamine arm and 2 (5.0%) patients in the midazolam and haloperidol arm experienced serious adverse events (difference 7.5% [95% CI -4.8% to 19.8%]).ConclusionIn ED patients with severe agitation, intramuscular ketamine provided significantly shorter time to adequate sedation than a combination of intramuscular midazolam and haloperidol.Copyright © 2021 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

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