From Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine (TDG, BTP, GRB, EWE) and Center for Health Services Research (TDG, RSD, EWE), Department of Anesthesiology, Division of Critical Care (PPP), Department of Biostatistics (JLT, AKS), and Department of Psychiatry (HYM), Vanderbilt University School of Medicine, Nashville, TN; Department of Medicine, Division of Pulmonary and Critical Care Medicine (SSC), University of North Carolina, Chapel Hill, NC; Department of Internal Medicine, Division of Pulmonary Diseases, Critical Care, and Occupational Medicine (GAS), University of Iowa Carver College of Medicine, Iowa City, IA; Moses H. Cone Memorial Hospital (PEW), Greensboro, NC; Department of Medicine (AEC), Saint Thomas Hospital, Nashville, TN; Geriatric Research, Education, and Clinical Center Service (TDG, RSD, EWE) and Anesthesia Service (PPP), Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN.
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Objective:To demonstrate the feasibility of a placebo-controlled trial of antipsychotics for delirium in the intensive 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.Patients: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 effects.Measurements and Main Outcomes:The primary end point was the number of days patients were alive without delirium or coma. 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 differences 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. Thus, a large trial is needed to determine whether use of antipsychotics for intensive care unit delirium is appropriate.Trial Registration:ClinicalTrials.gov, number NCT00096863.