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, according to research published in the February 20 issue of JAMA.
“These findings do not support the use of prophylactic haloperidol in critically ill adults,” said Mark van den Boogaard, PhD, Assistant Professor of Intensive Care Medicine at Radboud University Medical Center in Nijmegen, the Netherlands.
Haloperidol is used routinely in ICUs to treat and prevent delirium, which affects as many as half of ICU patients and is associated with prolonged mechanical ventilation, longer ICU and hospital stays, and increased mortality. Results of past studies of haloperidol in the ICU have been mixed.
For this study, eligible participants were expected to be in the ICU for at least two days and were not delirious at baseline. Patients were randomized to receive 1 mg of haloperidol (n = 350), 2 mg of haloperidol (n = 732), or placebo (n = 707) three times daily. The 1-mg haloperidol arm was stopped early because of futility. The ICUs also used nonpharmacologic interventions to prevent delirium, including early mobilization and noise reduction.
Patients had a mean age of 66.6; 61.4% were men. Most of the ICU admissions were urgent and for medical or surgical reasons. There was no statistically significant difference in survival at 28 days following entrance into the study, which was the study’s primary end point. At that point, 83.3% of the patients who received 2-mg doses of haloperidol and 82.7% of the subjects who received placebo had survived.
Prophylactic haloperidol had no effect on reducing the incidence of delirium, which was diagnosed in 33.3% of patients who received haloperidol and 33.0% of patients who received placebo. Likewise, there were no significant differences between the groups in the number of delirium-free and coma-free days, duration of mechanical ventilation, and ICU and hospital length of stay.
“The study population included severely ill ICU adults whose brains may have been too seriously affected for haloperidol to exert a prophylactic effect, since in non-ICU adults, prophylactic haloperidol may have beneficial effects. But the subgroup of patients with a low severity of illness score also demonstrated no beneficial effects,” the investigators said.
—M. Alexander Otto
Suggested Reading
van den Boogaard M, Slooter AJC, Brüggemann RJM, et al. Effect of haloperidol on survival among critically ill adults with a high risk of delirium: The REDUCE randomized clinical trial. JAMA. 2018;319(7):680-690.