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Postoperative Delirium in a Substudy of Cardiothoracic Surgical Patients in the BAG-RECALL Clinical Trial

Whitlock, Elizabeth L. MD, MSc*; Torres, Brian A. CRNA*; Lin, Nan PhD; Helsten, Daniel L. MD*; Nadelson, Molly R. MD*; Mashour, George A. MD, PhD; Avidan, Michael S. MB, BCh, FCASA*

doi: 10.1213/ANE.0000000000000028
Neuroscience in Anesthesiology and Perioperative Medicine: Research Report

BACKGROUND: Postoperative delirium in the intensive care unit (ICU) is a frequent complication after cardiac or thoracic surgery and is associated with increased morbidity and mortality.

METHODS: In this single-center substudy of the BAG-RECALL trial (NCT00682825), we screened patients after cardiac or thoracic surgery in the ICU twice daily for delirium using the Confusion Assessment Method for the ICU. The primary outcome was the incidence of delirium in patients who had been randomized to intraoperative Bispectral Index (BIS)-guided and end-tidal anesthetic concentration-guided depth of anesthesia protocols. As a secondary analysis, a Bayesian stochastic search variable selection strategy was used to rank a field of candidate risk factors for delirium, followed by binary logistic regression.

RESULTS: Of 310 patients assessed, 28 of 149 (18.8%) in the BIS group and 45 of 161 (28.0%) in the end-tidal anesthetic concentration group developed postoperative delirium in the ICU (odds ratio 0.60, 95% confidence interval, 0.35–1.02, P= 0.058). Low average volatile anesthetic dose, intraoperative transfusion, ASA physical status, and European System for Cardiac Operative Risk Evaluation were identified as independent predictors of delirium.

CONCLUSIONS: A larger randomized study should determine whether brain monitoring with BIS or an alternative method decreases delirium after cardiac or thoracic surgery. The association between low anesthetic concentration and delirium is a surprising finding and could reflect that patients with poor health are both more sensitive to the effects of volatile anesthetic drugs and are also more likely to develop postoperative delirium. Investigation of candidate methods to prevent delirium should be prioritized in view of the established association between postoperative delirium and adverse patient outcomes.

Published ahead of print January 1, 2014

From the *Department of Anesthesiology, Washington University School of Medicine; Department of Mathematics, Washington University in Saint Louis, Saint Louis, Missouri; and Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan.

Elizabeth L. Whitlock, MD, MSc, is currently affiliated with the Department of Anesthesiology and Perioperative Care, University of California, San Francisco, San Francisco, California.

Accepted for publication October 1, 2013.

Published ahead of print January 1, 2014

Funding: The BAG-RECALL trial was supported by grants from the Foundation for Anesthesia Education and Research and the American Society of Anesthesiologists (CFM-08/15/2007 to M. Avidan). The funding agencies had no role in the design, conduct, or reporting of the study. E. Whitlock was a predoctoral research trainee under grant number UL1 RR024992 and subaward number TL1 RR024995 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and the NIH Roadmap for Medical Research. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH.

This report was previously presented, in part, at the Association of University Anesthesiologists’ Annual Meeting, May 2011, Philadelphia, PA.

The authors declare no conflicts of interest.

Reprints will not be available from the authors.

Address correspondence to Elizabeth L. Whitlock, MD, MSc, Department of Anesthesia and Perioperative Care University of California, 513 Parnassus Ave., Room S436, San Francisco, CA 94143. Address e-mail to

© 2014 International Anesthesia Research Society