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Haloperidol and delirium in critically ill patients

Clinical question: Does prophylactic use of haloperidol increase survival in critically ill adults with high risk of delirium?

Background: Delirium is common and associated with high mortality. Studies evaluating prophylactic use of haloperidol have been inconclusive.

Study design: Randomized, double-blind, placebo-controlled, multicenter, investigator-driven study.

Setting: ICUs at university hospitals and teaching and nonteaching hospitals in the Netherlands.

Synopsis: 1,789 adults with mean age 66.6 years were randomized to receive either 1 or 2 mg of haloperidol or placebo. The 1-mg haloperidol group was prematurely stopped because of futility.

There was no difference in the primary outcome of survival days within a 28-day period between the 2-mg haloperidol group and the placebo group (hazard ratio, 1.003; 95% confidence interval, 0.78-1.30; P = .93).

Secondary outcome of survival was also the same at 90 days. No significant difference was seen in the delirium incidence, delirium- and coma-free days, and the delirium-related outcome measures.

Patients were already undergoing nonpharmacologic interventions for delirium prevention, and this likely attenuated the effects of haloperidol. The dose and duration of haloperidol used might have also been too low and short to have an effect on the outcomes considering the severity of patient illness.

Bottom line: Haloperidol has no role in prophylactic use to increase survival among critically ill patients with a high risk of delirium.

Citation: van den Boogaard M et al. Effect of haloperidol on survival among critically ill adults with a high risk of delirium: The REDUCE randomized clinical trial. JAMA. 2018 Feb 20;319(7):680-90.

Dr. Chikkanna is an assistant professor in the division of hospital medicine at the University of Kentucky, Lexington.

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