 CLINICAL INVESTIGATIONS Anesthesiology 2006; 105:244 –52 © 2006 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Variability of Blood Glucose Concentration and Short-term Mortality in Critically Ill Patients Moritoki Egi, M.D.,* Rinaldo Bellomo, M.D., F.J.F.I.C.M.,† Edward Stachowski, M.D.,‡ Craig J. French, M.D.,§ Graeme Hart, M.D. Background: Intensive insulin therapy may reduce mortality and morbidity in selected surgical patients. Intensive insulin therapy also reduced the SD of blood glucose concentration, an accepted measure of variability. There is no information on the possible significance of variability in glucose concentration. Methods: The methods included extraction of blood glucose values from electronically stored biochemical databases and of data on patient’s characteristics, clinical features, and outcome from electronically stored prospectively collected patient data- bases; calculation of SD of glucose as a marker of variability and of several indices of glucose control in each patient; and statis- tical assessment of the relation between these variables and intensive care unit mortality. Results: There were 168,337 blood glucose measurements in the study cohort of 7,049 critically ill patients (4.2 hourly mea- surements on average). The mean  SD of blood glucose con- centration was 1.7  1.3 mM in survivors and 2.3  1.6 mM in nonsurvivors (P < 0.001). Using multiple variable logistic re- gression analysis, both mean and SD of blood glucose were significantly associated with intensive care unit mortality (P < 0.001; odds ratios [per 1 mM] 1.23 and 1.27, respectively) and hospital mortality (P < 0.001 and P  0.013; odds ratios [per 1 mM] 1.21 and 1.18, respectively). Conclusions: The SD of glucose concentration is a significant independent predictor of intensive care unit and hospital mor- tality. Decreasing the variability of blood glucose concentration might be an important aspect of glucose management. ACUTE hyperglycemia associated with insulin resistance is common in critically ill patients. 1,2 Acute control of blood glucose is considered important. 3–8 Recently, in- tensive insulin therapy (target glucose concentration of 4.4 – 6.1 mM) was reported to reduce mortality and mor- bidity in selected surgical patients. 9 Therefore, decreas- ing mean blood glucose concentration may improve patient outcome in the critical care setting. Intensive insulin therapy was also associated with a reduction in the SD of blood glucose concentration, an accepted measure of variability (1.05 mM in intensive insulin ther- apy group vs. 1.83 mM in conventional control group; relative reduction of 42%). However, the benefit of in- tensive insulin therapy was ascribed to a reduction in the mean glucose concentration rather than minimization of its variability. Currently, there is no information on the possible significance of variability in glucose concentra- tion. This is unfortunate, because fluctuations in glucose concentration might be pathophysiologically important, especially from a neurologic perspective, 10 and possibly as important as sustained hyperglycemia. We hypothe- sized that the SD (a parameter commonly used to de- scribe variability of measurement) of blood glucose con- centration would independently predict mortality in a population of critically ill patients. We tested this hypothesis in patients admitted to the intensive care units (ICUs) of four hospitals and com- pared the predictive ability of SD with other indices of blood glucose control: mean glucose concentration (Glu Ave ), maximum blood glucose concentration during ICU stay (Glu Max ), 11,12 and blood glucose concentration on admission (Glu Adm ). 13,14 We further compared the mean and SD of blood glucose concentration during the first 24 h (Glu1 Ave and Glu1 SD ), because glucose concen- tration on the day of admission has been shown to be an accurate predictor of ICU patient outcome. 15,16 Materials and Methods The data collection for this study was part of a preex- isting quality assurance activity, approved by local insti- tutional ethics committees. The Austin Hospital Ethics Committee (Heidelberg, Victoria, Australia) approved this investigation. Study Population and Data Sources The current study was conducted as a multicenter retrospective observational study. Hospitals A and B are tertiary public hospitals in Melbourne, Australia. Hospi- tal C is a large private hospital in Melbourne. Hospital D is a tertiary public hospital in Sydney. All patients admit- ted to these ICUs from January 2000 to October 2004 were included. Time frames in each hospital were fixed according to time periods within which reliable and This article is accompanied by an Editorial View. Please see: Ouattara A, Grimaldi A, Riou B: Blood glucose variability: A new paradigm in critical care? ANESTHESIOLOGY 2006; 105:233– 4.  * Research Fellow, † Director of Research,  Staff Specialist, Department of Intensive Care, Austin Hospital. ‡ Staff Specialist, Department of Intensive Care, Westmead Hospital. § Director, Department of Intensive Care, Western Hospital. Received from the Department of Intensive Care, Western Hospital, Footscray, Victoria, Australia; the Department of Intensive Care, Westmead Hospital, West- mead, New South Wales, Australia; the Department of Intensive Care and De- partment of Medicine, Austin Hospital, Heidelberg, Victoria, Australia; and War- ringal Private Hospital, Heidelberg, Victoria, Australia. Submitted for publication June 9, 2005. Accepted for publication March 18, 2006. Supported by the Austin Hospital Anaesthesia and Intensive Care Trust Fund, Heidelberg, Victoria, Aus- tralia. Address correspondence to Dr. Bellomo: Department of Intensive Care, Austin & Repatriation Medical Centre, Heidelberg 3084, Victoria, Australia. rinaldo.bellomo@austin.org.au. Individual article reprints may be purchased through the Journal Web site, www.anesthesiology.org. Anesthesiology, V 105, No 2, Aug 2006 244