A Comparison of Ketamine to Midazolam for the Management of Acute Behavioral Disturbance in the Out-of-Hospital Setting

Study objective: Acute behavioral disturbance is characterized by altered mental status and psychomotor agitation. Pharmacological sedation may be required, risking potential respiratory compromise. We compared the need for emergent airway support following administration of midazolam or ketamine to treat acute behavioral disturbance in the out-of-hospital setting.

Methods: In this retrospective cohort study of patients with acute behavioral disturbance in an urban emergency medical service system between 2017 and 2021, we compared the likelihood of out-of-hospital advanced airway management following administration of midazolam or ketamine. Advanced airway management was defined as out-of-hospital endotracheal intubation or supraglottic airway insertion.

Results: Among 376 eligible patients, the median age was 35, and 78% were men. The most common etiologies of acute behavioral disturbance were substance use (51%), trauma (18%), and presumed postictal agitation (11%). In all, 162 patients (43%) initially received midazolam and 214 (57%) ketamine. The frequency of advanced airway management was similar between these respective groups (12% [n=19] versus 11% [n=24], difference 0.5%, 95% CI -6.0% to 7.0%). Adjusted for potential confounders, the odds of receiving advanced airway management did not differ between midazolam and ketamine (aOR 1.02, 95% CI 0.44 to 2.38), and no differences were observed in emergency department intubation rates (14% in midazolam recipients, 11% for ketamine) or overall mortality (2% in midazolam recipients, 1% for ketamine).

Conclusion: In this cohort study of patients with acute behavioral disturbance, emergent airway support and other outcomes did not differ following out-of-hospital treatment with midazolam or ketamine.