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Association of Cumulative Dose of Haloperidol With Next-Day Delirium in Older Medical ICU Patients*

Pisani, Margaret A. MD, MPH1; Araujo, Katy L. B. MPH2; Murphy, Terrence E. PhD2

doi: 10.1097/CCM.0000000000000863
Clinical Investigations
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Objectives: To evaluate the association between cumulative dose of haloperidol and next-day diagnosis of delirium in a cohort of older medical ICU patients, with adjustment for its time-dependent confounding with fentanyl and intubation.

Design: Prospective, observational study.

Setting: Medical ICU at an urban, academic medical center.

Patients: Age 60 years and older admitted to the medical ICU who received at least one dose of haloperidol (n = 93). Of these, 72 patients were intubated at some point in their medical ICU stay, whereas 21 were never intubated.

Interventions: None.

Measurements and Main Results: Detailed data were collected concerning time, dosage, route of administration of all medications, as well as for important clinical covariates, and daily status of intubation and delirium using the confusion assessment method for the ICU and a chart-based algorithm. Among nonintubated patients, and after adjustment for time-dependent confounding and important covariates, each additional cumulative milligram of haloperidol was associated with 5% higher odds of next-day delirium with odds ratio of 1.05 (credible interval [CI], 1.02–1.09). After adjustment for time-dependent confounding and covariates, intubation was associated with a five-fold increase in odds of next-day delirium with odds ratio of 5.66 (CI, 2.70–12.02). Cumulative dose of haloperidol among intubated patients did not change their already high likelihood of next-day delirium. After adjustment for time-dependent confounding, the positive associations between indicators of intubation and of cognitive impairment and next-day delirium became stronger.

Conclusions: These results emphasize the need for more studies regarding the efficacy of haloperidol for treatment of delirium among older medical ICU patients and demonstrate the value of assessing nonintubated patients.

1Department of Medicine, Pulmonary & Critical Care Section, and the Program on Aging, Yale University School of Medicine, New Haven, CT.

2Department of Medicine, Geriatrics Section, and the Program on Aging, Yale University School of Medicine, New Haven, CT.

*See also p. 1143.

Supported, in part, by the American Lung Association and Connecticut Thoracic Society (ID# CG-002-N), Claude D. Pepper Older Americans Independence Center at Yale University School of Medicine (grant 2P30AG021342-06), the T. Franklin Williams Geriatric Development Initiative through The CHEST Foundation, ASP, Hartford Foundation, and grants through the National Institute on Aging.

Dr. Pisani received grants (K23AG23023 and 1R21NR011066) from the National Institute on Aging. Dr. Murphy received grant (1R21AG033130-01A2) for article research from the National Institutes of Health (NIH). His institution received grant support from the National Institute of Aging. Dr. Araujo received support for article research from the NIH. Her institution received grant support from the National Institute of Aging.

For information regarding this article, E-mail: terrence.murphy@yale.edu

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