#VisualAbstract: Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness

1. Among critically ill patients with delirium in the intensive care unit (ICU), there was no significant difference in the duration of delirium between patients treated with haloperidol, ziprasidone, or placebo.

2. At the time of randomization, 89% of patients in the trial had hypoactive delirium versus only 11% that had hyperactive delirium.

Evidence Rating Level: 1 (Excellent)      

Study Rundown: Though primarily based on observational studies and expert recommendation, haloperidol and atypical antipsychotics are a standard therapy for delirium; however, the literature is conflicting about whether these medications are of benefit. The authors thus conducted this randomized trial to assess the efficacy of haloperidol and ziprasidone, a common atypical antipsychotic used to treat delirium, for the treatment of delirium during critical illness. The results showed no significant difference in the primary endpoint – days alive without delirium or coma – between the haloperidol, ziprasidone, or placebo groups. There was also no significant difference in the secondary endpoints, including days with delirium or coma and time to freedom from mechanical ventilation, ICU discharge, ICU readmission, and hospital discharge. Besides the higher incidence of prolongation of the corrected QT interval with ziprasidone, no significant differences in safety were reported between the three groups. While the results challenge the widespread use of antipsychotics to treat delirium in clinical practice, more data is needed to assess efficacy in hyperactive versus hypoactive delirium.

This was a randomized, double-blinded, placebo-controlled trial that assessed two of the most commonly used medications to treat delirium. Validated tools to assess delirium were used and high adherence to the trial protocol was reported. However, the high percentage of patients with hypoactive delirium limits the generalizability of the results, as the trial medications are more commonly used to treated hyperactive delirium. Additional limitations include that the trial was only powered to detect a 2-day difference between groups (thus any smaller difference is unknown) and the common co-administration of sedatives during the trial.

Click to read the study in NEJM

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