Clinical outcomes after single induction dose of etomidate versus ketamine for emergency department sepsis intubation: a randomized controlled trial

Abstract Background: Patients with sepsis often require emergency intubation. In emergency departments (EDs), rapid-sequence intubation with a single-dose induction agent is standard practice but the best choice of induction agent in sepsis remains controversy. High quality RCTs are needed to determine the optimal induction agents in sepsis. Methods: We conducted a randomized, controlled, single-blind trial in the ED. We included septic patients who were aged at least 18 years and required sedation for emergency intubation. Patients were randomly assigned by a blocked randomization to receive 0.2-0.3 mg/kg of etomidate or 1-2 mg/kg of ketamine for intubation. Outcomes were compared with intention-to-treat analysis. The primary objective was to compare the 28-day survival outcomes between etomidate and ketamine. The secondary objectives outcomes were to compare 24-hour and 7-day survival rates, and adverse events after intubation. Results: 260 septic patients were enrolled; 130 patients/ drug arm whose baseline characteristics were well balance at baseline. In the etomidate group, 105 patients (80.8%) were alive at 28 days, as compared with 95 patients (73.1%) in the ketamine group (risk difference [RD], 7.7%; 95% confidence interval [CI], -2.5% to 17.9%; P=0.092). There was no significant difference in the proportion of patients who survived at 24 hours (91.5% vs. 96.2%; P=0.097) and survived at 7 days (87.7% vs. 87.7%; P=0.574). A significantly higher proportion of the etomidate group needed a vasopressor within 24 hours after intubation: 43.9% vs. 17.7%, RD, 26.2% (95% CI, 15.4% to 36.9%; P<0.001). Conclusions: In patients with sepsis who needed emergency intubation in the ED, there were no differences in early and late survival rates between etomidate and ketamine. However, etomidate associated with higher risks of early vasopressor needed after intubation. Trial registration: The trial protocol was registered in Thai Clinical Trials Registry (identification number; TCTR20210213001). Registered 13 February 2021 – Retrospectively registered, https://www.thaiclinicaltrials.org/export/pdf/TCTR20210213001.