Advertisement
ADVANCED SEARCH

This Article Figures Only Full Text Full Text (PDF) Résumé Online Appendices All Versions of this Article: cmaj.090206v1 180/8/821    most recent Submit a response View responses Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Griesdale, D. E.G. Articles by Talmor, D. Search for Related Content PubMed PubMed Citation Articles by Griesdale, D. E.G. Articles by Talmor, D. Related Collections Related Articles

Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data

From the Departments of Medicine (Griesdale, Henderson, Chittock) and Anesthesiology, Pharmacology and Therapeutics (Griesdale), University of British Columbia; the Program of Critical Care Medicine (Griesdale, Henderson, Chittock) and the Department of Anesthesia (Griesdale), Vancouver General Hospital, Vancouver, BC; the Department of Nutrition (de Souza, van Dam), Harvard School of Public Health; the Channing Laboratory, Department of Medicine (van Dam), and the Divisions of Pulmonary, Critical Care and Sleep Medicine (Malhotra), Brigham and Women’s Hospital and Harvard Medical School; the Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School (Talmor), Boston, USA; the Department of Medicine (Heyland), Queen’s University; the Clinical Evaluation Research Unit (Dhaliwal), Kingston General Hospital, Kingston, Ont; the Departments of Medicine and of Clinical Epidemiology and Biostatistics (Cook), McMaster University, Hamilton, Ont.; and the Intensive Therapy Unit (Finfer), Royal North Shore Hospital, and the George Institute for International Health and the Faculty of Medicine (Finfer), University of Sydney, Sydney, Australia

Correspondence to: Dr. Donald E.G. Griesdale, Critical Care Medicine, Vancouver General Hospital, Rm. 2438, Jim Pattison Pavilion, 2nd Floor, 855 West 12th Ave., Vancouver BC V5Z 1M9; fax 604 875-5957; dgriesdale{at}post.harvard.edu

Background: Hyperglycemia is associated with increased mortality in critically ill patients. Randomized trials of intensive insulin therapy have reported inconsistent effects on mortality and increased rates of severe hypoglycemia. We conducted a meta-analysis to update the totality of evidence regarding the influence of intensive insulin therapy compared with conventional insulin therapy on mortality and severe hypoglycemia in the intensive care unit (ICU).

Methods: We conducted searches of electronic databases, abstracts from scientific conferences and bibliographies of relevant articles. We included published randomized controlled trials conducted in the ICU that directly compared intensive insulin therapy with conventional glucose management and that documented mortality. We included in our meta-analysis the data from the recent NICE-SUGAR (Normoglycemia in Intensive Care Evaluation — Survival Using Glucose Algorithm Regulation) study.

Results: We included 26 trials involving a total of 13 567 patients in our meta-analysis. Among the 26 trials that reported mortality, the pooled relative risk (RR) of death with intensive insulin therapy compared with conventional therapy was 0.93 (95% confidence interval [CI] 0.83–1.04). Among the 14 trials that reported hypoglycemia, the pooled RR with intensive insulin therapy was 6.0 (95% CI 4.5–8.0). The ICU setting was a contributing factor, with patients in surgical ICUs appearing to benefit from intensive insulin therapy (RR 0.63, 95% CI 0.44–0.91); patients in the other ICU settings did not (medical ICU: RR 1.0, 95% CI 0.78–1.28; mixed ICU: RR 0.99, 95% CI 0.86–1.12). The different targets of intensive insulin therapy (glucose level 6.1 mmol/L v. 8.3 mmol/L) did not influence either mortality or risk of hypoglycemia.

Interpretation: Intensive insulin therapy significantly increased the risk of hypoglycemia and conferred no overall mortality benefit among critically ill patients. However, this therapy may be beneficial to patients admitted to a surgical ICU.

This article has been cited by other articles:

				Respiratory Intensive Care Assembly contribution t, S. Nava, and P. Pelosi Pulmonologists and intensivists: "two hearts are better than one" Eur. Respir. J., March 1, 2010; 35(3): 463 - 466. [Full Text] [PDF]

				P. E. Marik and J.-C. Preiser Toward Understanding Tight Glycemic Control in the ICU: A Systematic Review and Metaanalysis Chest, March 1, 2010; 137(3): 544 - 551. [Abstract] [Full Text] [PDF]

				U. Holzinger, J. Warszawska, R. Kitzberger, M. Wewalka, W. Miehsler, H. Herkner, and C. Madl Real-Time Continuous Glucose Monitoring in Critically Ill Patients: A prospective randomized trial Diabetes Care, March 1, 2010; 33(3): 467 - 472. [Abstract] [Full Text] [PDF]

				T. Duning, I. van den Heuvel, A. Dickmann, T. Volkert, C. Wempe, J. Reinholz, H. Lohmann, H. Freise, and B. Ellger Hypoglycemia Aggravates Critical Illness-Induced Neurocognitive Dysfunction Diabetes Care, March 1, 2010; 33(3): 639 - 644. [Abstract] [Full Text] [PDF]

				M. Egi, R. Bellomo, E. Stachowski, C. J. French, G. K. Hart, G. Taori, C. Hegarty, and M. Bailey Hypoglycemia and Outcome in Critically Ill Patients Mayo Clin. Proc., March 1, 2010; 85(3): 217 - 224. [Abstract] [Full Text] [PDF]

				J. S. Krinsley and M. T. Keegan Hypoglycemia in the Critically Ill: How Low Is Too Low? Mayo Clin. Proc., March 1, 2010; 85(3): 215 - 216. [Full Text] [PDF]

				M. T. Keegan and D. B. Coursin Breathe Deeply the Sweet Air: Ruminations on Glycemic Control Anesth. Analg., February 1, 2010; 110(2): 296 - 298. [Full Text] [PDF]

				S. Akhtar, P. G. Barash, and S. E. Inzucchi Scientific Principles and Clinical Implications of Perioperative Glucose Regulation and Control Anesth. Analg., February 1, 2010; 110(2): 478 - 497. [Abstract] [Full Text] [PDF]

				A. J Graveling and B. M Frier Review: Does hypoglycaemia cause cardiovascular events? The British Journal of Diabetes & Vascular Disease, January 1, 2010; 10(1): 5 - 13. [Abstract] [PDF]

				B. Taylor and J. Krenitsky Nutrition in the Intensive Care Unit: Year in Review 2008-2009 JPEN J Parenter Enteral Nutr, January 1, 2010; 34(1): 21 - 31. [Full Text] [PDF]

				American Diabetes Association Standards of Medical Care in Diabetes--2010 Diabetes Care, January 1, 2010; 33(Supplement_1): S11 - S61. [Full Text] [PDF]

				L. H. Opie and J. Knuuti The adrenergic-Fatty Acid load in heart failure. J. Am. Coll. Cardiol., October 27, 2009; 54(18): 1637 - 1646. [Abstract] [Full Text] [PDF]

				E. H Baker and D. Bell Blood glucose: of emerging importance in COPD exacerbations Thorax, October 1, 2009; 64(10): 830 - 832. [Full Text] [PDF]

				J. Joseph, A. Sinha, M. Paech, and B. N J Walters Sepsis in pregnancy and early goal-directed therapy Obstet Med, September 1, 2009; 2(3): 93 - 99. [Abstract] [Full Text] [PDF]

				G. Van den Berghe, M. Schetz, D. Vlasselaers, G. Hermans, A. Wilmer, R. Bouillon, and D. Mesotten Intensive Insulin Therapy in Critically Ill Patients: NICE-SUGAR or Leuven Blood Glucose Target? J. Clin. Endocrinol. Metab., September 1, 2009; 94(9): 3163 - 3170. [Abstract] [Full Text] [PDF]

				N. R. Webster and H. F. Galley Does strict glucose control improve outcome? Br. J. Anaesth., September 1, 2009; 103(3): 331 - 334. [Full Text] [PDF]

				R. M Cyrus, P. M Szumita, B. C Greenwood, and M. L Pendergrass Evaluation of Compliance with a Paper-based, Multiplication-factor, Intravenous Insulin Protocol Ann. Pharmacother., September 1, 2009; 43(9): 1413 - 1418. [Abstract] [Full Text] [PDF]

				W. T. Cefalu Mortality and Glycemic Targets in the Intensive Care Unit: Another Paradigm Shift? Diabetes, July 1, 2009; 58(7): 1469 - 1470. [Full Text] [PDF]

				G. Van den Berghe, D. Mesotten, and I. Vanhorebeek Intensive insulin therapy in the intensive care unit Can. Med. Assoc. J., April 14, 2009; 180(8): 799 - 800. [Full Text] [PDF]

eLetters:

HOME	CURRENT ISSUE	PAST ISSUES	COLLECTIONS	HELP	SEARCH
Copyright 1995-2009, Canadian Medical Association. All rights reserved. ISSN 1488-2329 (e) 0820-3946 (p) All editorial matter in CMAJ represents the opinions of the authors and not necessarily those of the Canadian Medical Association.