Year: 2018
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: BACKGROUND: There are conflicting data on the effects of antipsychotic medications on delirium in patients in the intensive care unit (ICU). METHODS: In a randomized, double-blind, placebo-controlled trial, we assigned patients with acute respiratory failure or shock and hypoactive or hyperactive delirium to receive intravenous boluses of haloperidol (maximum dose, 20 mg daily), ziprasidone (maximum dose, 40 mg daily), or placebo. The volume and dose of a trial drug or placebo was halved or doubled at 12-hour intervals on the basis of the presence or absence of delirium, as detected with the use of the Confusion Assessment Method for the ICU, and of side effects of the intervention. The primary end point was the number of days alive without delirium or coma during the 14-day intervention period. Secondary end points included 30-day and 90-day survival, time to freedom from mechanical ventilation, and time to ICU and hospital discharge. Safety end points included extrapyramidal symptoms and excessive sedation. RESULTS: Written informed consent was obtained from 1183 patients or their authorized representatives. Delirium developed in 566 patients (48%), of whom 89% had hypoactive delirium and 11% had hyperactive delirium. Of the 566 patients, 184 were randomly assigned to receive placebo, 192 to receive haloperidol, and 190 to receive ziprasidone. The median duration of exposure to a trial drug or placebo was 4 days (interquartile range, 3 to 7). The median number of days alive without delirium or coma was 8.5 (95% confidence interval [CI], 5.6 to 9.9) in the placebo group, 7.9 (95% CI, 4.4 to 9.6) in the haloperidol group, and 8.7 (95% CI, 5.9 to 10.0) in the ziprasidone group (P=0.26 for overall effect across trial groups). The use of haloperidol or ziprasidone, as compared with placebo, had no significant effect on the primary end point (odds ratios, 0.88 [95% CI, 0.64 to 1.21] and 1.04 [95% CI, 0.73 to 1.48], respectively). There were no significant between-group differences with respect to the secondary end points or the frequency of extrapyramidal symptoms. CONCLUSIONS: The use of haloperidol or ziprasidone, as compared with placebo, in patients with acute respiratory failure or shock and hypoactive or hyperactive delirium in the ICU did not significantly alter the duration of delirium. (Funded by the National Institutes of Health and the VA Geriatric Research Education and Clinical Center; MIND-USA ClinicalTrials.gov number, NCT01211522 .).
Source: New England Journal of Medicine
Authors: Timothy D. Girard, Matthew C. Exline, Shannon S. Carson, Catherine L. Hough, Peter Rock, Michelle N. Gong, Ivor S. Douglas, Atul Malhotra, Robert L. Owens, Daniel J. Feinstein, Babar Khan, Margaret A. Pisani, Robert C. Hyzy, Gregory A. Schmidt, William D. Schweickert, R. Duncan Hite, David L. Bowton, Andrew L. Masica, Jennifer L. Thompson, Rameela Chandrasekhar, Brenda T. Pun, Cayce Strength, Leanne M. Boehm, James C. Jackson, Pratik P. Pandharipande, Nathan E. Brummel, Christopher G. Hughes, Mayur B. Patel, Joanna L. Stollings, Gordon R. Bernard, Robert S. Dittus, E. Wesley Ely
Institutions: Cleveland Clinic, University of Pittsburgh, The Ohio State University Wexner Medical Center, The Ohio State University, University of North Carolina at Chapel Hill, University of Washington, University of Maryland, Baltimore, Albert Einstein College of Medicine, Montefiore Medical Center, Denver Health Medical Center, University of California San Diego, Cone Health, Indiana University Indianapolis, Indiana University School of Medicine, Indiana University – Purdue University Indianapolis, Yale University, University of Michigan, Michigan Medicine, University of Iowa, University of Iowa Hospitals and Clinics, University of Iowa Health Care, University of Pennsylvania, Atrium Health Wake Forest Baptist, Baylor Scott & White Health, Vanderbilt University, Geriatric Research Education and Clinical Center
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2896197442