3180 Crit Care Med 2012 Vol. 40, No. 12 I n recent years, goals for glyce- mic control in the intensive care unit (ICU) have been vacillat- ing between lax and tight targets because of conficting reports. Tradition- ally, efforts were made to keep glucose concentrations <200 mg/dL, but following publication of the study by Van den Berghe et al (1) demonstrating the benefts of tight glucose control (TGC) between 80 and 110 mg/dL (4.4–6.1 mmol/L), many ICUs adopted this strategy (2). However, these results have been diffcult to reproduce and the widespread applicability of TGC has come into question. The glycemic con- trol pendulum has recently swung back to higher glycemic targets following the pub- lication of several trials and meta-analyses, which demonstrated the signifcant risk associated with TGC and resulting hypo- glycemia (3–5). Currently, the American Copyright © 2012 by the Society of Critical Care Medicine and Lippincott Williams and Wilkins DOI: 10.1097/CCM.0b013e3182656ae5 Objective: Our objective was to quantify the association between intensive care unit–acquired dysglycemia (hyperglyce- mia, hypoglycemia, and high variability) and in-hospital mortality. Design: Retrospective, observational study. Setting: eICU Research Institute participating hospitals with an active tele-ICU program between January 1, 2008, and September 30, 2010, representing 784,392 adult intensive care unit patients. Patients: A total of 194,772 patients met inclusion criteria with an intensive care unit length of stay >48 hrs. Interventions: None. Measurements and Main Results: Acute Physiology and Chronic Health Evaluation IV standardized mortality ratios were calculated for dysglycemia present at admission and acquired in the intensive care unit. Intensive care unit–acquired dysglycemia was modeled using multivariable modified Poisson regression to account for con- founding not incorporated in Acute Physiology and Chronic Health Evaluation. Dysglycemia severity was assessed by the relative risk of in-hospital mortality associated with the maximum, time- weighted average daily glucose; lowest glucose value throughout the intensive care unit stay; and quintiles of variability (coefficient of variation). The association of duration beyond thresholds of dys- glycemia on mortality was also modeled. The adjusted relative risk (95% confidence interval) of mortality for the maximum intensive care unit average daily glucose was 1.13 (1.04–1.58), 1.43 (1.30– 1.58), 1.63 (1.47–1.81), 1.76 (1.55–1.99), and 1.89 (1.62–2.19) for 110–150 mg/dL, 151–180 mg/dL, 180–240 mg/dL, 240–300 mg/dL, and >300 mg/dL, respectively, compared to patients whose high- est average daily glucose was 80–110 mg/dL. The relative risk of mortality for the lowest glucose value was 1.67 (1.37–2.03), 1.53 (1.37–1.70), 1.12 (1.04–1.21), and 1.06 (1.01–1.11) for <20 mg/dL, 20–40 mg/dL, 40–60 mg/dL, and 60–80 mg/dL, respectively, com- pared to patients whose lowest value was 80–110 mg/dL. The relative risk of mortality increased with greater duration of hyper- glycemia and with increased variability. The relative risk for the highest compared to lowest quintile of variability was 1.61 (1.47– 1.78). The association of duration of hyperglycemia on mortality was more pronounced with more severe hyperglycemia. Conclusions: The risk of mortality progressively increased with severity and duration of deviation from euglycemia and with increased variability. These data suggest that severe intensive care unit–acquired hyperglycemia, hypoglycemia, and variability are associated with similar risks of mortality. (Crit Care Med 2012; 40:3180–3188) KEY WORDS: critical care; glycemic control; hypoglycemia; hyper- glycemia; insulin; intensive care unit Association between intensive care unit–acquired dysglycemia and in-hospital mortality* Omar Badawi, PharmD, MPH, BCPS; Michael D. Waite, MD; Steven A. Fuhrman, MD; Ilene H. Zuckerman, PharmD, PhD *See also p. 3315. From the Department of Research and Product Marketing (OB), Philips Healthcare, Baltimore, MD; Department of Pharmacy Practice and Science (OB), University of Maryland School of Pharmacy, Baltimore, MD; Riverside Methodist Hospital (MDW), OhioHealth, Columbus, OH; Sentara Healthcare System (SAF), Norfolk, VA; Department of Pharmaceutical Health Services Research (IHZ), Pharmaceutical Research Computing Center, University of Maryland School of Pharmacy, Baltimore, MD. This was a collaborative (Drs. Badawi, Fuhrman, and Waite), investigator-initiated study selected for funding by the eICU Research Institute (eRI) Publications Committee. Philips Healthcare sponsors eICU customer-initiated research selected by the eRI Publications Committee through a competitive review of all submitted proposals on a semiannual basis. Only one voting member of the Publications Committee can be a Philips Healthcare employee. All data analyses were conducted by an inde- pendent academic research organization, the University of Maryland School of Pharmacy’s Pharmaceutical Research Computing Center. All decisions regarding the study design, analysis, and publication are made by consensus between primary investigators, a Philips Healthcare clinical project lead and the academic re- search organization. Further detail regarding the struc- ture and process of the eRI are presented elsewhere (17). Dr. Badawi is an employee of Philips Healthcare. Dr. Zuckerman is principal investigator on a contract funded by Philips Healthcare. The remaining authors have not disclosed any potential conflicts of interest. This work was performed at the University of Maryland School of Pharmacy, Baltimore, MD. 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 (http://journals.lww. com/ccmjournal). This article has been reviewed and approved by Craig M. Lilly, MD; Richard R. Riker, MD; Teresa Rincon, RN, BSN, CCRN-E; Gary Ripple, MD; Theresa Davis, RN, MSN, PhDc; Michael Witte, DO; and Michael Breslow, MD, of the eICU Research Institute Publications Committee. For information regarding this article, Email: omar. badawi@philips.com