Dexmedetomidine for treatment of hyperactive delirium in non-intubated ICU patients: the 4D randomized clinical trial

Whether dexmedetomidine improves the control of hyperactive delirium in non-intubated intensive care unit (ICU) patients as compared with placebo remains uncertain.

In a multicenter, double-blind, placebo-controlled, two-arm, investigator-initiated, randomized trial conducted in 9 ICUs, we randomly assigned non-intubated critically ill adults with hyperactive delirium to receive continuous intravenous infusion of dexmedetomidine or placebo for at least 36 h. The primary outcome was a joint modelling of multiple outcomes of agitation duration (score of + 1 or higher on the Richmond agitation-sedation scale), delirium duration, or the need for intubation and deep sedation. Key secondary outcomes included the occurrence of complications (such as bradycardia or hypotension), length of stay in ICU, or death.

Enrollment occurred from December 2017 to February 2022. Final follow-up was in February 2023. The study was stopped for efficacy at the time of the preplanned interim analysis. Among the 151 patients who were included in the final analysis, the between-group difference in the primary outcome was statistically significant (median difference, -30 points; 95% CI, - 49 to - 12, p = 0.001). Agitation duration was shorter in the dexmedetomidine group (1.0 (1.0-2.0) vs 2.0 (1.0-7.0) hours, absolute difference 95% CI - 1.0 (- 2.0 to - 0.1); ES, - 0.60; 95% CI, -0.92 to -0.27, p = 0.001). Other key secondary outcomes were similar between groups.

In non-intubated adult ICU patients with hyperactive delirium, the use of dexmedetomidine was associated with a greater clinical benefit than placebo for the joint modelling of multiple endpoints of agitation control, delirium resolution, and intubation with mechanical ventilation. Dexmedetomidine appears to be a valuable alternative that significantly reduced the median duration of agitation by approximately 1 h compared to placebo in hyperactive delirious non-intubated intensive care unit patients.

ClinicalTrial.gov Identifier: NCT03317067. Registration on October 17th, 2017 prior to first patient inclusion. https://clinicaltrials.gov/search?term=NCT03317067 .