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Delirium duration and mortality in lightly sedated, mechanically ventilated intensive care patients*

Shehabi, Yahya FCICM, EMBA; Riker, Richard R. MD; Bokesch, Paula M. MD; Wisemandle, Wayne MA; Shintani, Ayumi PhD, MPH; Ely, E. Wesley MD, MPH

doi: 10.1097/CCM.0b013e3181f85759
Clinical Investigations

Objectives: To determine the relationship between the number of delirium days experienced by intensive care patients and mortality, ventilation time, and intensive care unit stay.

Design: Prospective cohort analysis.

Setting: Patients from 68 intensive care units in five countries.

Patients: Three hundred fifty-four medical and surgical intensive care patients enrolled in the SEDCOM (Safety and Efficacy of Dexmedetomidine Compared with Midazolam) trial received a sedative study drug and completed at least one delirium assessment.

Interventions: Sedative drug interruption and/or titration to maintain light sedation with daily arousal and delirium assessments up to 30 days of mechanical ventilation.

Measurements and Main Results: The primary outcome was all-cause 30-day mortality. Multivariable analysis using Cox regression incorporating delirium duration as a time-dependent variable and adjusting for eight relevant baseline covariates was conducted to quantify the relationship between number of delirium days and the three main outcomes. Overall, delirium was diagnosed in 228 of 354 patients (64.4%). Mortality was significantly lower in patients without delirium compared to those with delirium (15 of 126 [11.9%] vs. 69 of 228 [30.3%]; p < .001). Similarly, the median time to extubation and intensive care unit discharge were significantly shorter among nondelirious patients (3.6 vs. 10.7 days [p < .001] and 4 vs. 16 days [p < .001], respectively). In multivariable analysis, the duration of delirium exhibited a nonlinear relationship with mortality (p = .02), with the strongest association observed in the early days of delirium. In comparison to 0 days of delirium, an independent dose-response increase in mortality was observed, which increased from 1 day of delirium (hazard ratio, 1.70; 95% confidence interval, 1.27–2.29; p < .001), 2 days of delirium (hazard ratio, 2.69; confidence interval, 1.58–4.57; p < .001), and ≥3 days of delirium (hazard ratio, 3.37; confidence interval, 1.92–7.23; p < .001). Similar independent relationships were observed between delirium duration and ventilation time and intensive care length of stay.

Conclusions: In ventilated and lightly sedated intensive care unit patients, the duration of delirium was the strongest independent predictor of death, ventilation time, and intensive care unit stay after adjusting for relevant covariates.

From the University of New South Wales Clinical School (YS), The Prince of Wales Hospital Campus, Randwick, New South Wales, Australia; University of Vermont College of Medicine (RRR), Burlington, VT, and Maine Medical Center, Portland, ME; Cubist Pharmaceuticals (PMB), Lexington, MA; Hospira (WW), Lake Forest, IL; Department of Biostatistics (AS), Vanderbilt University, Nashville, TN; Department of Medicine (SEW), Division of Pulmonary and Critical Care, Vanderbilt University, Nashville, TN, and Veteran's Affairs Geriatric Research Education Clinical Center for the Tennessee Valley Healthcare System VA, the VA GRECC, Nashville, TN.

The original SEDCOM trial was funded by Hospira, Lake Forest, IL. This investigation was initiated and led by Drs. Shehabi, Riker, and Ely with assistance from Drs. Bokesch and Wisemandle) and an independent biostatistician (Dr. Shintani). Drs. Shehabi, Riker, and Ely all declare having received research grants from Hospira. Drs. Bokesch and Wisemandle were employees of Hospira.

Study concept and design: Drs. Shehabi, Riker, Ely, and Bokesch and Mr. Wisemandle. Acquisition of data: Drs. Shehabi and Riker. Analysis and interpretation of data: Drs. Shehabi, Riker, Ely, and Shintani. Drafting of the manuscript: Drs. Shehabi, Riker, Bokesch, and Ely. Critical revision of the manuscript for important intellectual content: Drs. Shehabi, Riker, and Bokesch, Mr. Wisemandle, and Drs. Shintani and Ely. Statistical analysis: Dr. Shintani. Dr. Shintani had access to all the data used in the study and performed a full and independent analysis of all primary and secondary end points reported in this article. The results of Dr. Shintani's analysis are reported in this article.

Dr. Shehabi consulted for Hospira, Fisher-Paykel, Theravance; received honoraria/speaking fees from Hospira, Edward Lifesciences, Fisher-Paykel, and Eli-Lilly; and has received grant support from the Intensive Foundation, Melborne, Australia. Dr. Riker receives funding from Hospira. Dr. Bokesch is a past employee (as of May 2009) and has received honoraria/speaking fees from Hospira. Dr. Wisemandle is employed by Hospira, Inc, Chicago; and receives funding and has stock options from Hospira. Dr. Ely has consulted for, received grant support, and received speaking fees/honoraria from Pfizer, Hospira, GSK, and Aspect. Dr. Shintani has not disclosed any potential conflicts of interest.

For information regarding this article, E-mail: y.shehabi@unsw.edu.au

© 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins