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      Diabetic status and the relation of the three domains of glycemic control to mortality in critically ill patients: an international multicenter cohort study

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          Abstract

          Introduction

          Hyperglycemia, hypoglycemia, and increased glycemic variability have each been independently associated with increased risk of mortality in critically ill patients. The role of diabetic status on modulating the relation of these three domains of glycemic control with mortality remains uncertain. The purpose of this investigation was to determine how diabetic status affects the relation of hyperglycemia, hypoglycemia, and increased glycemic variability with the risk of mortality in critically ill patients.

          Methods

          This is a retrospective analysis of prospectively collected data involving 44,964 patients admitted to 23 intensive care units (ICUs) from nine countries, between February 2001 and May 2012. We analyzed mean blood glucose concentration (BG), coefficient of variation (CV), and minimal BG and created multivariable models to analyze their independent association with mortality. Patients were stratified according to the diagnosis of diabetes.

          Results

          Among patients without diabetes, mean BG bands between 80 and 140 mg/dl were independently associated with decreased risk of mortality, and mean BG bands >140 mg/dl, with increased risk of mortality. Among patients with diabetes, mean BG from 80 to 110 mg/dl was associated with increased risk of mortality and mean BG from 110 to 180 mg/dl with decreased risk of mortality. An effect of center was noted on the relation between mean BG and mortality. Hypoglycemia, defined as minimum BG <70 mg/dl, was independently associated with increased risk of mortality among patients with and without diabetes and increased glycemic variability, defined as CV >20%, was independently associated with increased risk of mortality only among patients without diabetes. Derangements of more than one domain of glycemic control had a cumulative association with mortality, especially for patients without diabetes.

          Conclusions

          Although hyperglycemia, hypoglycemia, and increased glycemic variability is each independently associated with mortality in critically ill patients, diabetic status modulates these relations in clinically important ways. Our findings suggest that patients with diabetes may benefit from higher glucose target ranges than will those without diabetes. Additionally, hypoglycemia is independently associated with increased risk of mortality regardless of the patient's diabetic status, and increased glycemic variability is independently associated with increased risk of mortality among patients without diabetes.

          See related commentary by Krinsley, http://ccforum.com/content/17/2/131

          See related commentary by Finfer and Billot, http://ccforum.com/content/17/2/134

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          Most cited references39

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          Variability of blood glucose concentration and short-term mortality in critically ill patients.

          Moritoki Egi, Rinaldo Bellomo, Edward Stachowski … (2006)
          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. 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 databases; calculation of SD of glucose as a marker of variability and of several indices of glucose control in each patient; and statistical assessment of the relation between these variables and intensive care unit mortality. There were 168,337 blood glucose measurements in the study cohort of 7,049 critically ill patients (4.2 hourly measurements on average). The mean +/- SD of blood glucose concentration was 1.7 +/- 1.3 mM in survivors and 2.3 +/- 1.6 mM in nonsurvivors (P < 0.001). Using multiple variable logistic regression 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). The SD of glucose concentration is a significant independent predictor of intensive care unit and hospital mortality. Decreasing the variability of blood glucose concentration might be an important aspect of glucose management.
          Article 0 comments Cited 169 times – based on 0 reviews     Review now
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            Hyperglycemia-related mortality in critically ill patients varies with admission diagnosis.

            Mercedes Falciglia, Ron Freyberg, Peter Almenoff … (2009)
            Hyperglycemia during critical illness is common and is associated with increased mortality. Intensive insulin therapy has improved outcomes in some, but not all, intervention trials. It is unclear whether the benefits of treatment differ among specific patient populations. The purpose of the study was to determine the association between hyperglycemia and risk- adjusted mortality in critically ill patients and in separate groups stratified by admission diagnosis. A secondary purpose was to determine whether mortality risk from hyperglycemia varies with intensive care unit type, length of stay, or diagnosed diabetes. Retrospective cohort study. One hundred seventy-three U.S. medical, surgical, and cardiac intensive care units. Two hundred fifty-nine thousand and forty admissions from October 2002 to September 2005; unadjusted mortality rate, 11.2%. None. A two-level logistic regression model determined the relationship between glycemia and mortality. Age, diagnosis, comorbidities, and laboratory variables were used to calculate a predicted mortality rate, which was then analyzed with mean glucose to determine the association of hyperglycemia with hospital mortality. Hyperglycemia was associated with increased mortality independent of illness severity. Compared with normoglycemic individuals (70-110 mg/dL), adjusted odds of mortality (odds ratio, [95% confidence interval]) for mean glucose 111-145, 146-199, 200-300, and >300 mg/dL was 1.31 (1.26-1.36), 1.82 (1.74-1.90), 2.13 (2.03-2.25), and 2.85 (2.58-3.14), respectively. Furthermore, the adjusted odds of mortality related to hyperglycemia varied with admission diagnosis, demonstrating a clear association in some patients (acute myocardial infarction, arrhythmia, unstable angina, pulmonary embolism) and little or no association in others. Hyperglycemia was associated with increased mortality independent of intensive care unit type, length of stay, and diabetes. The association between hyperglycemia and mortality implicates hyperglycemia as a potentially harmful and correctable abnormality in critically ill patients. The finding that hyperglycemia-related risk varied with admission diagnosis suggests differences in the interaction between specific medical conditions and injury from hyperglycemia. The design and interpretation of future trials should consider the primary disease states of patients and the balance of medical conditions in the intensive care unit studied.
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              Glucose variability is associated with intensive care unit mortality.

              Carlie deVries, Durk Zandstra, Titia M Vriesendorp … (2010)
              Mounting evidence suggests a role for glucose variability in predicting intensive care unit (ICU) mortality. We investigated the association between glucose variability and intensive care unit and in-hospital deaths across several ranges of mean glucose. Retrospective cohort study. An 18-bed medical/surgical ICU in a teaching hospital. All patients admitted to the ICU from January 2004 through December 2007. None. Two measures of variability, mean absolute glucose change per hour and sd, were calculated as measures of glucose variability from 5728 patients and were related to ICU and in-hospital death using logistic regression analysis. Mortality rates and adjusted odds ratios for ICU death per mean absolute glucose change per hour quartile across quartiles of mean glucose were calculated. Patients were treated with a computerized insulin algorithm (target glucose 72-126 mg/dL). Mean age was 65 +/- 13 yrs, 34% were female, and 6.3% of patients died in the ICU. The odds ratios for ICU death were higher for quartiles of mean absolute glucose change per hour compared with quartiles of mean glucose or sd. The highest odds ratio for ICU death was found in patients with the highest mean absolute glucose change per hour in the upper glucose quartile: odds ratio 12.4 (95% confidence interval, 3.2-47.9; p < .001). Mortality rates were lowest in the lowest mean absolute glucose change per hour quartiles. High glucose variability is firmly associated with ICU and in-hospital death. High glucose variability combined with high mean glucose values is associated with highest ICU mortality. In patients treated with strict glycemic control, low glucose variability seemed protective, even when mean glucose levels remained elevated.
              Article 0 comments Cited 116 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                James S Krinsley
                Moritoki Egi
                Alex Kiss
                Amin N Devendra
                Philipp Schuetz
                Paula M Maurer
                Marcus J Schultz
                Roosmarijn TM van Hooijdonk
                Morita Kiyoshi
                Iain MJ Mackenzie
                Djillali Annane
                Peter Stow
                Stanley A Nasraway
                Sharon Holewinski
                Ulrike Holzinger
                Jean-Charles Preiser
                Jean-Louis Vincent
                Rinaldo Bellomo
                Journal
                Journal ID (nlm-ta): Crit Care
                Journal ID (iso-abbrev): Crit Care
                Title: Critical Care
                Publisher: BioMed Central
                ISSN (Print): 1364-8535
                ISSN (Electronic): 1466-609X
                Publication date (Print): 2013
                Publication date (Electronic): 1 March 2013
                Volume: 17
                Issue: 2
                Page: R37
                Affiliations
                [1 ]Division of Critical Care, Stamford Hospital and Columbia University College of Physicians and Surgeons, 190 West Broad Street, Stamford, CT, 06902, USA
                [2 ]Department of Anesthesiology and Resuscitology, Okayama University Hospital, 2-5-1 Shikatachou, Okayama, 700-8525, Japan
                [3 ]Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street, Toronto, M5T 3M6, Ontario, Canada
                [4 ]Medical/Surgical Intensive Care Unit, Morton Plant Hospital, 300 Pinellas Street, Clearwater, FL 33756, USA
                [5 ]Privat Dozent for Endocrinology and Internal Medicine, Medical University Department, Kantonsspital Aarau, Tellstrasse CH -5001 Aarau, Switzerland
                [6 ]BayCare Health Systems, 300 Pinellas Street, Clearwater, FL 33756, USA
                [7 ]Department of Intensive Care, Academic Medical Center, Meibergrdeef 9, 1105AZ, Amsterdam, The Netherlands
                [8 ]Department of Anesthesia and Critical Care Medicine, University Hospital Birmingham NHS, Mindelsohn Way, Edgbaston, B15 2WB, Birmingham, UK
                [9 ]Critical Care Department, Service de Réanimation, Hopital Raymond Poincaré, Université de Versailles SQY, 104 Boulevard Raymond Poincare, 92830, Garches, France
                [10 ]Intensive Care Unit, The Geelong Hospital, Barwon Health, Ryrie Street, Geelong, Victoria, 3220, Australia
                [11 ]Surgical Intensive Care Units, Tufts Medical Center, 800 Washington Street, NEMC 4360, Boston, MA 02111, USA
                [12 ]Medical Intensive Care Unit, Department of Medicine III, Division of Gastroenterology and Hepatology, ICU 13H1, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, 1090, Austria
                [13 ]Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Route de Lennik 808, Brussels, 1070, Belgium
                [14 ]Department of Intensive Care, Austin Hospital and Monash University, Studley Road, Heidelberg, Victoria, 3084, Australia
                Article
                Publisher ID: cc12547
                DOI: 10.1186/cc12547
                PMC ID: 3733432
                PubMed ID: 23452622
                SO-VID: 758baef7-1472-4a03-b9ae-c71fc392eb72
                Copyright © Copyright © 2013 Krinsley et al.; licensee BioMed Central Ltd.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 27 October 2012
                Date revision received : 18 February 2013
                Date accepted : 1 March 2013
                Categories
                Subject: Research

                ScienceOpen disciplines: Emergency medicine & Trauma
                Data availability:
                ScienceOpen disciplines: Emergency medicine & Trauma

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