Journal article
Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness
The New England journal of medicine, Vol.379(26), pp.2506-2516
12/27/2018
DOI: 10.1056/NEJMoa1808217
PMCID: PMC6364999
PMID: 30346242
Abstract
There are conflicting data on the effects of antipsychotic medications on delirium in patients in the intensive care unit (ICU).
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.
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.
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 .).
Details
- Title: Subtitle
- Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness
- Creators
- Timothy D Girard - University of PittsburghMatthew C Exline - The Ohio State UniversityShannon S Carson - University of North Carolina at Chapel HillCatherine L Hough - University of WashingtonPeter Rock - University of Maryland, BaltimoreMichelle N Gong - Albert Einstein College of MedicineIvor S Douglas - University of DenverAtul Malhotra - University of California, San DiegoRobert L Owens - University of California, San DiegoDaniel J Feinstein - Cone HealthBabar Khan - Indiana University BloomingtonMargaret A Pisani - Yale UniversityRobert C Hyzy - University of Michigan–Ann ArborGregory A Schmidt - University of IowaWilliam D Schweickert - University of PennsylvaniaR Duncan Hite - Cleveland ClinicDavid L Bowton - Wake Forest UniversityAndrew L Masica - Scott & White Memorial HospitalJennifer L Thompson - Vanderbilt UniversityRameela Chandrasekhar - Denver Health Medical CenterBrenda T Pun - Vanderbilt UniversityCayce Strength - Denver Health Medical CenterLeanne M Boehm - Vanderbilt UniversityJames C Jackson - Vanderbilt UniversityPratik P Pandharipande - Vanderbilt UniversityNathan E Brummel - Vanderbilt UniversityChristopher G Hughes - Vanderbilt UniversityMayur B Patel - Vanderbilt UniversityJoanna L Stollings - Vanderbilt UniversityGordon R Bernard - Vanderbilt UniversityRobert S Dittus - Vanderbilt UniversityE Wesley Ely - Geriatric Research Education and Clinical CenterMIND-USA Investigators
- Resource Type
- Journal article
- Publication Details
- The New England journal of medicine, Vol.379(26), pp.2506-2516
- DOI
- 10.1056/NEJMoa1808217
- PMID
- 30346242
- PMCID
- PMC6364999
- ISSN
- 0028-4793
- eISSN
- 1533-4406
- Grant note
- K24 HL132105 / NHLBI NIH HHS T32 HL134632 / NHLBI NIH HHS K24 HL132093 / NHLBI NIH HHS R01 AG035117 / NIA NIH HHS UL1 TR000445 / NCATS NIH HHS K12 HL137943 / NHLBI NIH HHS R01 HL085188 / NHLBI NIH HHS
- Language
- English
- Date published
- 12/27/2018
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984359934302771
Metrics
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