Clearing up the confusion: The results of two pilot studies of antipsychotics for ICU delirium

Feasibility, effi cacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebo-controlled trial. Background Given the lack of compelling evidence supporting the use of antipsychotics for delirium in critically ill patients and the potential adverse eff ects associated with these medica tions, placebo-controlled clinical trials are greatly needed. Methods Objective: To demonstrate the feasibility of a placebo-controlled trial of antipsychotics for delirium in the inten sive care unit and to test the hypothesis that antipsychotics would improve days alive without delirium or coma. Design: Randomized, double-blind, placebo-controlled trial. Setting: Six tertiary care medical centers in the US. Subjects: One hundred one mechanically ventilated medical and surgical intensive care unit patients. Intervention: Patients were randomly assigned to receive haloperidol or ziprasidone or placebo every 6 hrs for up to 14 days. Twice each day, frequency of study drug administration was adjusted according to delirium status, level of sedation, and side eff ects. Outcomes: Th e primary end point was the number of days patients were alive without delirium or coma. Secondary effi cacy end points included daily delirium risk, duration of delirium, duration of coma, the number of days patients were alive and breathing without assistance during the 21-day study period (ventilator-free days), time to ICU and hospital discharge, and all-cause 21-day survival. Results During the 21-day study period, patients in the haloperidol group spent a similar number days alive without delirium or coma (median [interquartile range], 14.0 [6.0–18.0] days) as did patients in the ziprasidone (15.0 [9.1–18.0] days) and placebo groups (12.5 [1.2– 17.2] days; p = 0.66). No diff erences were found in secondary clinical outcomes, including ventilator-free days (p = .25), hospital length of stay (p = .68), and mortality (p = .81). Ten (29%) patients in the haloperidol group reported symptoms consistent with akathisia, compared with six (20%) patients in the ziprasidone group and seven (19%) patients in the placebo group (p = .60), and a global measure of extrapyramidal symptoms was similar between treatment groups (p = .46). Conclusions A randomized, placebo-controlled trial of antipsychotics for delirium in mechanically ventilated intensive care unit patients is feasible. Treatment with antipsychotics in this limited pilot trial did not improve the number of days alive without delirium or coma, nor did it increase adverse outcomes. Th us, a large trial is needed to determine whether use of antipsychotics for intensive care unit delirium is appropriate. …