Emergency endotracheal intubation in critically ill patients are dangerous procedures with a greater risk of severe hypotension The efficacy and safety of esketamine with sympathoexcitatory effects for rapid sequence induction in critically ill patients remain unclear. In this prospective double-blinded randomized controlled trial, adult patients were randomly assigned to receive either esketamine or midazolam/sufentanil admixture for induction. The primary outcomes were the effects of induction with esketamine or midazolam/sufentanil admixture on hemodynamic responses (heart rate (HR) and mean arterial pressure (MAP) during and after induction). Secondary outcomes were the duration of ventilation support, length of intensive care unit (ICU) stay, 28-day mortality. We enrolled 80 patients, of whom 38 were assigned to the esketamine group and 42 to the midazolam/sufentanil admixture group. The MAP in group esketamine was significantly higher than that in group midazolam/sufentanil admixture during the induction, and at 1 min, 5 min and 10 min after intubation. No significant differences in HR between groups were observed. The duration of ventilation support [105.3 (interquartile range (IQR) 40.9 - 248.3) hours vs. 211.5 (IQR 122.1 - 542.1) hours, P = 0.002] and the length of ICU stay [7.0 (IQR 4.0 - 16.3) days vs. 15.0 (IQR 8.0 - 26.0) days, P = 0.002] were significantly decreased in group esketamine, compared to that in group midazolam/sufentanil admixture. In group esketamine, less norepinephrine [0.00 (IQR 0.00 - 0.10) µg/kg/min vs. 0.09 (IQR 0.00 - 0.29) µg/kg/min, P = 0.016] was needed. There was no significant difference in 28-day mortality between the two groups. No serious adverse events occurred. In conclusion, esketamine is a hemodynamically stable induction agent in critically ill patients, which could reduce the length of ICU stay and the duration of ventilation support.Trial registration: clinicaltrials.gov (19/07/2022
NCT05464979).