Girard TD, et al. - Researchers assessed the effects of antipsychotic medications on delirium in patients in the intensive care unit (ICU) in this randomized, double-blind, placebo-controlled trial. Outcomes suggested that, in patients with acute respiratory failure or shock and hypoactive or hyperactive delirium, the use of haloperidol or ziprasidone did not significantly alter the duration of delirium compared with placebo.

Methods

• Patients with acute respiratory failure or shock and hypoactive or hyperactive delirium were assigned to receive intravenous boluses of haloperidol (maximum dose, 20 mg daily), ziprasidone (maximum dose, 40 mg daily), or placebo.
• At 12-hour intervals, researchers halved or doubled the volume and dose of a trial drug or placebo based on the presence/absence of delirium, as detected with the use of the Confusion Assessment Method for the ICU, and of side effects of the intervention.
• The number of days alive without delirium or coma during the 14-day intervention period was assessed as the primary end point.
• Secondary end points included 30- and 90-day survival, time to freedom from mechanical ventilation, and time to ICU, and hospital discharge.
• Extrapyramidal symptoms and excessive sedation were included as safety end points.

Results

• They obtained written informed consent from 1,183 patients or their authorized representatives.
• A total of 566 (48%) patients developed delirium; 89% had hypoactive delirium and 11% had hyperactive delirium.
• Among the 566 patients, placebo was given to 184, haloperidol to 192, and ziprasidone to 190.
• Patients were exposed to the trial drug or placebo for a median duration of 4 days (IQR: 3-7).
• In the placebo group, the median number of days alive without delirium or coma was 8.5 (95% CI: 5.6-9.9) vs 7.9 (95% CI: 4.4-9.6) and 8.7 (95% CI: 5.9-10.0) in the haloperidol group and the ziprasidone group, respectively (P=0.26, for overall effect across trial groups).
• The use of haloperidol or ziprasidone led to no significant effect on the primary end point compared with placebo (OR: 0.88 [95% CI: 0.64-1.21] and 1.04 [95% CI: 0.73-1.48], respectively).
• Groups showed no significant differences with respect to the secondary end points or the frequency of extrapyramidal symptoms.