Ketamine versus propofol for sedation in acute psychiatric emergencies during aeromedical retrieval: a randomized clinical trial

OBJECTIVES: The prevalence of psychiatric disease is increasing globally. Regional Australian communities are disproportionately affected and uniquely lacking mental health resources. Those needing inpatient psychiatric care often require aeromedical retrieval, creating safety and operational challenges. The optimal medication regimen for sedation of non-intubated patients experiencing psychiatric agitation is unclear. METHODS: We performed a prospective, single-center, open-label, phase IV randomized clinical trial (RCT) of ketamine versus propofol for the sedation of acutely agitated patients undergoing aeromedical transport. Our primary outcome of interest was a composite adverse event endpoint including airway complications (need for adjuncts, manipulation, suctioning), breathing complications (hypoxemia, hypoventilation, need for bag-valve-mask ventilation or stimulation), circulatory compromise (hypotension, need for intravenous fluid bolus), and aspiration. We evaluated clinician satisfaction as a secondary outcome, and medication efficacy as an exploratory analysis. RESULTS: Of 1,078 referrals screened for inclusion, 170 were enrolled after requiring sedation - 52% randomized to receive propofol and 48% ketamine. Most patients were young (median age 30 years), First Nations (75.9%), male (66.5%), and diagnosed with psychosis (82.4%). Adverse events were more common in the propofol group (12.4% vs. 24.7%; RR = 0.50, 95% CI (0.25-0.99); x2(1) = 4.25, p = 0.039), yet clinicians preferred propofol to ketamine (median Likert rating 4 (IQR 4,5) vs. 4 (IQR 2,4), p = 0.0007). Both medications exhibited similar efficacy at reaching the target Richmond Agitation Sedation Scale score (OR 0.73 (95%CI 0.50-1.07)). The study was stopped early due to low enrollment. CONCLUSIONS: In this RCT of 170 patients, ketamine was associated with fewer adverse events compared to propofol when used for sedation during aeromedical retrieval of patients experiencing acute psychiatric agitation. There was no significant difference in achieving the goal RASS between the two agents, however clinicians reported higher satisfaction scores with propofol.