From the Journals

Haloperidol does not prevent delirium in ICU patients


Key clinical point: Prophylactic haloperidol did not prevent delirium or improve survival in a large, placebo-controlled trial at 21 ICUs in the Netherlands.

Major finding: Delirium was diagnosed in 33.3% of haloperidol subjects versus 33.0% of placebo patients.

Study details: The trial enrolled 1,789 critically ill adults.

Disclosures: This work was supported by ZonMw, the Netherlands Organization for Health Research and Development. The lead investigator had no disclosures.

Source: van den Boogaard M et al. JAMA. 2018 Feb 20;319(7):680-90.

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Nondrug options may be the key

The study has demonstrated that in critically ill patients currently receiving best-practice nonpharmacological interventions to prevent delirium, the addition of haloperidol does not improve survival nor reduce the incidence of delirium or the harms associated with delirium. The findings challenge the current model that the addition of psychoactive medication to patients who are already receiving multiple interventions may be beneficial. Prophylactic haloperidol is not the solution for the complex problem of delirium in critically ill patients. It may be that no single pharmacological intervention can provide a solution.

Future research is warranted into nonpharmacological interventions. They generally involve either doing less for patients (avoiding excessive sedation, benzodiazepines, nocturnal noise, and stimulation) or ensuring the continued provision of relatively simple therapies (mobilization, maintaining a day-night schedule, and noise reduction). Although some of these interventions may require planning and cooperation of a multidisciplinary team, a strength of ICU care in general, other interventions may be as simple as providing earplugs and eye patches to improve sleep.

Anthony Delaney, MD, PhD, is associate professor of intensive care medicine at the University of Sydney. Naomi Hammond, PhD, is a research fellow and senior lecturer at the University of New South Wales, Sydney. Edward Litton, MD, PhD, is an intensive care specialist in Perth, Australia. They made their comments in a JAMA editorial, and had no disclosures ( JAMA. 2018 Feb 20;319[7]:659-60 ).



Prophylactic haloperidol did not prevent delirium or improve survival in a placebo-controlled trial of 1,789 critically ill adults at 21 ICUs in the Netherlands.

Haloperidol is used routinely in ICUs to both treat and prevent delirium, which strikes up to half of ICU patients and is associated with prolonged mechanical ventilation, longer ICU and hospital stays, and increased mortality. Results of past studies have been mixed, with some showing a benefit for haloperidol in the ICU and others not.

“These findings do not support the use of prophylactic haloperidol in critically ill adults,” said the authors of a new study, led by Mark van den Boogaard, PhD, of Radboud University Medical Center, Nijmegen, the Netherlands (JAMA. 2018 Feb 20;319[7]:680-90).

The subjects were all expected to be in the ICU for at least 2 days, and were not delirious at baseline. The patients were randomly assigned to receive one of two treatments or a placebo three times daily, with 350 receiving 1 mg of haloperidol; 732 receiving 2 mg of haloperidol; and 707 receiving a 0.9% sodium chloride placebo. The 1-mg haloperidol arm was stopped early because of futility.

A doctor tends to a patient in the ICU XiXinXing/ThinkStock
The ICUs also used nonpharmacologic interventions to prevent delirium, including early mobilization and noise reduction.

There was no statistically significant difference in survival at the primary endpoint of 28 days following entrance into the study. At that point, 83.3% of the patients who received 2-mg does of haloperidol and 82.7% of the of the subjects who received the placebo were alive (absolute difference 0.6%, 95% confidence interval –3.4% to 4.6%).

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