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Statins and Delirium During Critical Illness: A Multicenter, Prospective Cohort Study*

Morandi, Alessandro MD, MPH1,2,3; Hughes, Christopher G. MD4,5; Thompson, Jennifer L. MPH6; Pandharipande, Pratik P. MD, MSCI4,5; Shintani, Ayumi K. PhD, MPH6; Vasilevskis, Eduard E. MD, MPH7,8,9; Han, Jin H. MD, MSc10; Jackson, James C. PsyD7,11,12,13; Laskowitz, Daniel T. MD, MHS14; Bernard, Gordon R. MD11; Ely, E. Wesley MD, MPH3,7,9,11; Girard, Timothy D. MD, MSCI3,7,9,11

doi: 10.1097/CCM.0000000000000398
Neurologic Critical Care

Objective: Since statins have pleiotropic effects on inflammation and coagulation that may interrupt delirium pathogenesis, we tested the hypotheses that statin exposure is associated with reduced delirium during critical illness, whereas discontinuation of statin therapy is associated with increased delirium.

Design: Multicenter, prospective cohort study.

Setting: Medical and surgical ICUs in two large tertiary care hospitals in the United States.

Patients: Patients with acute respiratory failure or shock.

Interventions: None.

Measurements and Main Results: We measured statin exposure prior to hospitalization and daily during the ICU stay, and we assessed patients for delirium twice daily using the Confusion Assessment Method for the ICU. Of 763 patients included, whose median (interquartile range) age was 61 years (51–70 yr) and Acute Physiology and Chronic Health Evaluation II was 25 (19–31), 257 (34%) were prehospital statin users and 197 (26%) were ICU statin users. Overall, delirium developed in 588 patients (77%). After adjusting for covariates, ICU statin use was associated with reduced delirium (p < 0.01). This association was modified by sepsis and study day; for example, statin use was associated with reduced delirium among patients with sepsis on study day 1 (odds ratio, 0.22; 95% CI, 0.10–0.49) but not among patients without sepsis on day 1 (odds ratio, 0.92; 95% CI, 0.46–1.84) or among those with sepsis later, for example, on day 13 (odds ratio, 0.70; 95% CI, 0.35–1.41). Prehospital statin use was not associated with delirium (odds ratio, 0.86; 95% CI, 0.44–1.66; p = 0.18), yet the longer a prehospital statin user’s statin was held in the ICU, the higher the odds of delirium (overall p < 0.001 with the odds ratio depending on sepsis status and study day due to significant interactions).

Conclusions: In critically ill patients, ICU statin use was associated with reduced delirium, especially early during sepsis; discontinuation of a previously used statin was associated with increased delirium.

1Rehabilitation and Aged Care Unit, Hospital Ancelle, Cremona, Italy.

2Geriatric Research Group, Brescia, Italy.

3Center for Quality Aging, Vanderbilt University School of Medicine, Nashville, TN.

4Division of Critical Care, Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN.

5Anesthesia Service, Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN.

6Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN.

7Center for Health Services Research, Vanderbilt University School of Medicine, Nashville, TN.

8Division of General Internal Medicine and Public Health, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN.

9Geriatric Research, Education and Clinical Center Service, Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN.

10Department of Emergency Medicine, Vanderbilt University School of Medicine, Nashville, TN.

11Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN.

12Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN.

13Research Service, Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN.

14Division of Neurology, Department of Medicine, Department of Anesthesiology, and Department of Neurobiology, Duke University Medical Center, Durham, NC.

* See also p. 1955.

This investigation was supported, in part, by the National Institutes of Health (NIH) (AG027472). Dr. Morandi received support from the NIH (AG027472). Dr. Hughes received support from the Foundation for Anesthesia Education and Research (FAER). Ms. Thompson received support from the NIH (AG027472). Dr. Pandharipande received support from the NIH (HL111111) and the VA Clinical Science Research and Development Service (VA Career Development Award) and he received honoraria from Hospira and Orion Pharma. Dr. Shintani received support from the NIH (AG027472). Dr. Vasilevskis received support from the Veterans Affairs Clinical Research Training Center of Excellence, the Veterans Affairs Tennessee Valley Geriatric Research, Education and Clinical Center (GRECC), and the NIH (AG040157). Dr. Han received support from the NIH (AG032355). Dr. Jackson received support from the NIH (AG031322). Dr. Laskowitz received support from the NIH. Dr. Bernard received support from the NIH (TR000445). Dr. Ely received support from the NIH (AG027472 and AG035117), the VA Clinical Science Research and Development Service (VA Merit Review Award), and the Veterans Affairs Tennessee Valley GRECC; received honoraria from Pfizer, Eli Lilly and Company, Hospira, and Abbott Laboratories; and consulted for Cumberland and Masimo. Dr. Girard received support from the NIH (AG034257) and the Veterans Affairs Tennessee Valley GRECC and received honoraria from Hospira.

For information regarding this article, E-mail: timothy.girard@vanderbilt.edu

© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins