Intramuscular midazolam superior in sedating acutely agitated adults


Clinical question: How effective are intramuscular midazolam, olanzapine, ziprasidone, and haloperidol at sedating acutely agitated adults in the emergency department?

Background: Acute agitation is commonly seen in the ED and sometimes requires parenteral medications to keep patients and staff safe. Although many medications, including benzodiazepines and antipsychotics, are used, there is no consensus regarding which medications are most effective and safe for acute agitation.

Study design: Prospective observational study.

Setting: Emergency department of an inner-city Level 1 adult and pediatric trauma center.

Synopsis: This study enrolled 737 adults in the ED who presented with acute agitation and treated them with either haloperidol 5 mg, ziprasidone 20 mg, olanzapine 10 mg, midazolam 5 mg, or haloperidol 10 mg intramuscularly, based on predetermined 3-week blocks. The main outcome was the proportion of patients adequately sedated at 15 minutes, based on Altered Mental Status Scale score less than 1. A total of 650 patients (88%) were agitated from alcohol intoxication.

Dr. Stephen Jenkins, University of Utah, Salt Lake City

Dr. Stephen Jenkins

Midazolam resulted in a statistically higher proportion of patients adequately sedated, compared with ziprasidone (difference, 18%; 95% confidence interval, 6%-29%), haloperidol 5 mg (difference, 30%; 95% CI, 19%-41%), and haloperidol 10 mg (difference, 28%; 95% CI,17%-39%). Midazolam resulted in a higher proportion of patients adequately sedated, compared with olanzapine (difference 9%), but this difference was not statistically significant because the confidence interval crossed 1 (95% CI, –1%-20%). Olanzapine resulted in a statistically higher proportion of patients adequately sedated, compared with haloperidol 5 mg (difference 20%; 95% CI, 10%-31%) and 10 mg (difference 18%; 95% CI, 7%-29%). Adverse effects were rare.

Bottom line: Intramuscular midazolam is safe and may be more effective for treating acute agitation in the emergency department than standard antipsychotics.

Citation: Klein LR et al. Intramuscular midazolam, olanzapine, ziprasidone, or haloperidol for treating acute agitation in the emergency department. Ann Emerg Med. 2018 Jun 6. doi:

Dr. Jenkins is assistant professor of medicine and an academic hospitalist, University of Utah, Salt Lake City.

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