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Diurnal sedative changes during intensive care: Impact on liberation from mechanical ventilation and delirium*

Seymour, Christopher W. MD, MSc; Pandharipande, Pratik P. MD, MSCI; Koestner, Tyler BS; Hudson, Leonard D. MD; Thompson, Jennifer L. MPH; Shintani, Ayumi K. PhD, MPH; Ely, E. Wesley MD, MPH; Girard, Timothy D. MD, MSCI

doi: 10.1097/CCM.0b013e31825b8ade
Clinical Investigations

Objective: To determine whether benzodiazepine and propofol doses are increased at night and whether daytime and nighttime sedative doses are associated with delirium, coma, and delayed liberation from mechanical ventilation.

Design: Single-center, prospective cohort study nested within the Awakening and Breathing Controlled randomized trial.

Setting: Saint Thomas Hospital in Nashville, TN, from 2004 to 2006.

Patients: Adult patients receiving mechanical ventilation for >12 hrs with continuous recording of hourly sedation dosing.

Interventions: We measured hourly doses of benzodiazepine and propofol exposure during the daytime (7 AM to 11 PM) and nighttime (11 PM to 7 AM) for 5 days. We quantified nighttime dose increases by subtracting the average hourly daytime dose on the preceding day from subsequent average hourly nighttime dose. We used multivariable logistic regression to determine whether daytime and nighttime dose increases were independently associated with delirium, coma, and delayed liberation from mechanical ventilation.

Measurements and Main Results: Among 140 patients, the median Acute Physiology and Chronic Health Evaluation II score was 27 (interquartile range 22–33). Among those receiving the sedatives, benzodiazepine and propofol doses were increased at night on 40% and 41% of patient-days, respectively. Of 485 patient-days, delirium was present on 160 (33%) and coma on 206 (42%). In adjusted models, greater daytime benzodiazepine dose was independently associated with failed spontaneous breathing trial and extubation, and subsequent delirium (p < .02 for all). Nighttime increase in benzodiazepine dose was associated with failed spontaneous breathing trial (p < .01) and delirium (p = .05). Daytime propofol dose was marginally associated with subsequent delirium (p = .06).

Conclusions: Nearly half of mechanically ventilated intensive care unit patients received greater doses of sedation at night, a practice associated with failed spontaneous breathing trials, coma, and delirium. Over the first 5 days in our study, patients spent 75% of their time in coma or delirium, outcomes that may be reduced by efforts to decrease sedative exposure during both daytime and nighttime hours in the intensive care unit.

Supplemental Digital Content is available in the text.

From the Departments of Critical Care and Emergency Medicine (CWS) and The CRISMA (Clinical Research, Investigation, and Systems Modeling of Acute illness) Center, Department of Critical Care Medicine (CWS), University of Pittsburgh School of Medicine, Pittsburgh, PA; Anesthesia Service, Department of Veterans Affairs Medical Center (PPP) and Geriatric Research, Education and Clinical Center (GRECC) Service, Department of Veterans Affairs Medical Center (WE, TDG), Tennessee Valley Healthcare System, Nashville, TN; Division of Critical Care, Department of Anesthesiology (PPP), Department of Biostatistics (JLT, AKS), and Division of Allergy, Pulmonary, and Critical Care Medicine and Center for Health Service Research, Department of Medicine (WE, TDG), Vanderbilt University School of Medicine, Nashville, TN; University of Tennessee College of Medicine, Memphis, TN (TK); and Division of Pulmonary and Critical Care Medicine, University of Washington School of Medicine, Seattle, Washington (LDH).

*See also p. 2905.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (

Dr. Pandharipande received honoraria from Hospira, Inc. and Orion Pharmaceuticals. Dr. Ely consulted for Masimo and Aspect. He received honoraria from Hospira and the France Foundation. Dr. Girard received honoraria from Hospira. The remainingauthors have not disclosed any potential conflicts of interest.

This study was funded by the Saint Thomas Foundation (Nashville, TN) and the National Institutes of Health (NIH) (AG001023 and HL007123). In addition, Dr. Seymour is supported, in part, by a National Center for Research Resources grant from the National Institutes of Health (KL2 RR025015), Dr. Pandharipande is supported by the VA Clinical Science Research and Development Service (VA Career Development Award), Dr. Ely is supported by the NIH (AG027472) and the Veterans Affairs (VA) Tennessee Valley Geriatric Research, Education, and Clinical Center (GRECC), and Dr. Girard is supported by the NIH (AG034257) and the VA Tennessee Valley GRECC.

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© 2012 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins