Comparison of Propofol and Dexmedetomidine Infused Overnight to Treat Hyperactive and Mixed ICU Delirium: A Prospective Randomised Controlled Clinical Trial.

backgroundDelirium is a frequent yet pathophysiologically still poorly understood complication in the intensive care unit (ICU) and is associated with adverse outcomes for the patients. Currently, guidelines give several recommendations for treating delirium in the ICU, but to date no sufficient drug treatment exists. Dexmedetomidine, primarily used for anesthesia and sedation in ICUs has shown a preventive effect of delirium compared to other sedatives, such as propofol. We hypothesize that overnight administration of dexmedetomidine may prevent and/or shorten the duration of delirium in ICU patients.

methodsThe Basel propofol dexmedetomidine (BaProDex) Study was a single-center, prospective, randomized controlled trial. We included adult ICU patients with hyperactive or mixed delirium. Patients with delirium prior to ICU admission, advanced heart block, uncontrolled hypotension, or status epilepticus were excluded. The participants were randomly assigned 1:1 to either receive dexmedetomidine (study group) or propofol (control group) as a continuous infusion overnight. The Intensive Care Delirium Screening Checklist (ICDSC) was applied at least three times per day. Delirium was defined as an ICDSC ≥ 4. The study drug was administered until the end of delirium or ICU discharge. The primary endpoint was the time to delirium episode end, which was analyzed using cumulative incidence curves and a cause specific Cox proportional hazards regression with death as a competing risk. Secondary endpoints included recurrence of delirium until 28 days after ICU discharge, death until day 28, severity of ICU delirium, number of ventilation days, ICU length of stay (LOS) in hours, hospital length of stay in days and survival after three and twelve months after ICU discharge. Due to insufficient recruitment the trial needed to be stopped prematurely.

resultsIn total, 38 patients were enrolled and randomized in the two groups. The median duration of delirium was shorter in the dexmedetomidine group as compared to the propofol group (ITT: 34 vs. 66 h; PP: 31 vs. 66 h), resulting in a hazard ratio of 1.92 (95% CI 0.89-4.15,

conclusionsDespite premature termination, BaProDex provides preliminary evidence for a reduction in the duration of delirium by nocturnal infusion of dexmedetomidine compared to propofol. Therefore, dexmedetomidine may be considered an option to treat hyperactive or mixed delirium in ICU patients. However, due to the small sample size, the study is rather of exploratory nature due to the premature termination, and we cannot rule out that the observed treatment effect is overly optimistic or by chance.