Prophylactic haloperidol does not improve survival in critically ill patients


Clinical question: Does prophylactic use of haloperidol in critically ill patients at high risk of delirium improve survival at 28 days?

Background: Delirium occurs frequently in critically ill patients and can lead to increased ICU length of stay, hospital length of stay, duration of mechanical ventilation, and mortality. Prior research into the use of prophylactic antipsychotic administration has yielded inconsistent results.

Study design: Double-blind, randomized, controlled trial.

Setting: 21 ICUs in the Netherlands, from July 2013 to March 2017.

Dr. Kevin Winters, a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, Boston

Dr. Kevin Winters

Synopsis: A total of 1,789 critically ill adults with an anticipated ICU stay of at least 2 days were randomized to receive 1 mg of haloperidol, 2 mg of haloperidol, or a placebo three times daily. All study sites used “best practice” delirium prevention (for example, early mobilization, noise reduction, protocols aiming to prevent oversedation). The primary outcome was defined as the number of days patients survived in the 28 days following inclusion, and secondary outcome measures included number of days survived in 90 days, delirium incidence, number of delirium-free and coma-free days, duration of mechanical ventilation, and length of ICU and hospital stay. The 1-mg haloperidol group was stopped early because of futility. There was no significant difference between the 2-mg haloperidol group and the placebo group for the primary outcome (P = .93), or any of the secondary outcomes.Bottom line: In a population of critically ill patients at high risk of delirium, prophylactic haloperidol did not significantly improve 28-day survival, nor did it significantly reduce the incidence of delirium or length of stay.

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. Winters is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, Boston.

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