Prehospital Use of Ketamine Versus Midazolam for Sedation in Acute Severe Agitation

Objective: Acute severe agitation often requires pharmacologic sedation. While benzodiazepines and antipsychotics are traditional first-line medications for this purpose, recent evidence has shown that prehospital intramuscular (IM) administration of ketamine results in rapid, effective sedation. However, ketamine may be associated with adverse clinical events including a higher intubation rate. The purpose of this study is to compare the efficacy and safety of IM ketamine versus IM midazolam as medications to achieve sedation in the prehospital setting. Methods: This is a retrospective cohort study of agitated patients with an initial Richmond Agitation-Sedation Scale (RASS) score of at least 3, who were sedated and transported by ambulance to Hartford Hospital. The primary endpoint was incidence of endotracheal intubation occurring during transportation and within one hour after arrival to the emergency department (ED). Secondary endpoints included the percentage of patients who achieved an improved RASS score post drug administration, the use of additional sedating agents and the need for airway and breathing support, and differences in adverse events. Results: 66 patients in the ketamine group and 68 patients in the midazolam group met inclusion criteria. While more patients in the midazolam group achieved target RASS score of -1, 0, or 1 post drug administration, patients in the ketamine group had a lower mean RASS score post drug administration. There was no difference in endotracheal intubation rates between the two groups (6.1% versus 2.9%, respectively; p = 0.383). However, upon arrival to the ED, more patients in the ketamine group required additional sedating agents as well as airway or respiratory support Conclusion: Both ketamine and midazolam are relatively safe and efficacious in the prehospital environment. IM ketamine resulted in deeper sedation without increasing intubation rate. However, ED providers receiving patients treated with IM ketamine should prepare for additional sedating agents and airway interventions.