Background The optimal target range for blood glucose in criticallyill patients remains unclear.
Methods Within 24 hours after admission to an intensive careunit (ICU), adults who were expected to require treatment inthe ICU on 3 or more consecutive days were randomly assignedto undergo either intensive glucose control, with a target bloodglucose range of 81 to 108 mg per deciliter (4.5 to 6.0 mmolper liter), or conventional glucose control, with a target of180 mg or less per deciliter (10.0 mmol or less per liter).We defined the primary end point as death from any cause within90 days after randomization.
Results Of the 6104 patients who underwent randomization, 3054were assigned to undergo intensive control and 3050 to undergoconventional control; data with regard to the primary outcomeat day 90 were available for 3010 and 3012 patients, respectively.The two groups had similar characteristics at baseline. A totalof 829 patients (27.5%) in the intensive-control group and 751(24.9%) in the conventional-control group died (odds ratio forintensive control, 1.14; 95% confidence interval, 1.02 to 1.28;P=0.02). The treatment effect did not differ significantly betweenoperative (surgical) patients and nonoperative (medical) patients(odds ratio for death in the intensive-control group, 1.31 and1.07, respectively; P=0.10). Severe hypoglycemia (blood glucoselevel, 40 mg per deciliter [2.2 mmol per liter]) was reportedin 206 of 3016 patients (6.8%) in the intensive-control groupand 15 of 3014 (0.5%) in the conventional-control group (P<0.001).There was no significant difference between the two treatmentgroups in the median number of days in the ICU (P=0.84) or hospital(P=0.86) or the median number of days of mechanical ventilation(P=0.56) or renal-replacement therapy (P=0.39).
Conclusions In this large, international, randomized trial,we found that intensive glucose control increased mortalityamong adults in the ICU: a blood glucose target of 180 mg orless per deciliter resulted in lower mortality than did a targetof 81 to 108 mg per deciliter. (ClinicalTrials.gov number, NCT00220987
[ClinicalTrials.gov]
.)
Source Information
The NICE-SUGAR study is a collaboration of the Australian and New Zealand Intensive Care Society Clinical Trials Group, the George Institute for International Health (University of Sydney), the Canadian Critical Care Trials Group, and the Vancouver Coastal Health Research Institute (University of British Columbia). The NICE-SUGAR study writing committee (Simon Finfer, F.R.C.P., F.J.F.I.C.M., Dean R. Chittock, F.R.C.P.C., Steve Yu-Shuo Su, Ph.D., Deborah Blair, R.N., Denise Foster, R.N., Vinay Dhingra, F.R.C.P.C., Rinaldo Bellomo, F.J.F.I.C.M., Deborah Cook, M.D., Peter Dodek, M.D., William R. Henderson, F.R.C.P.C., Paul C. Hébert, M.D., Stephane Heritier, Ph.D., Daren K. Heyland, M.D., Colin McArthur, F.J.F.I.C.M., Ellen McDonald, R.N., Imogen Mitchell, F.R.C.P., F.J.F.I.C.M., John A. Myburgh, Ph.D., F.J.F.I.C.M., Robyn Norton, Ph.D., M.P.H., Julie Potter, R.N., M.H.Sc.(Ed.), Bruce G. Robinson, F.R.A.C.P., and Juan J. Ronco, F.R.C.P.C.) assumes full responsibility for the overall content and integrity of the article. This article (10.1056/NEJMoa0810625) was published at NEJM.org on March 24, 2009. It will appear in the March 26 issue of the Journal.
Address reprint requests to Dr. Finfer at the George Institute for International Health, P.O. Box M201, Missenden Rd., Sydney NSW 2050, Australia, or at sfinfer{at}george.org.au.
Spray, T. L.
(2009). The quality conundrum.. J. Thorac. Cardiovasc. Surg.
138: 1053-1059
[Full Text]
MENEGHINI, L. F.
(2009). Perioperative management of diabetes: Translating evidence into practice. Cleveland Clinic Journal of Medicine
76: S53-S59
[Abstract][Full Text]
Ferrer, R., Artigas, A., Suarez, D., Palencia, E., Levy, M. M., Arenzana, A., Perez, X. L., Sirvent, J.-M., for the Edusepsis Study Group,
(2009). Effectiveness of Treatments for Severe Sepsis: A Prospective, Multicenter, Observational Study. Am. J. Respir. Crit. Care Med.
180: 861-866
[Abstract][Full Text]
Patel, G. W., Roderman, N., Lee, K. A, Charles, M. M, Nguyen, D., Beougher, P., Kleja, K., Casteneda, E.
(2009). Sliding Scale Versus Tight Glycemic Control in the Noncritically Ill at a Community Hospital. The Annals of Pharmacotherapy
43: 1774-1780
[Abstract][Full Text]
Opie, L. H., Knuuti, J.
(2009). The adrenergic-Fatty Acid load in heart failure.. J Am Coll Cardiol
54: 1637-1646
[Abstract][Full Text]
Baker, E. H, Bell, D.
(2009). Blood glucose: of emerging importance in COPD exacerbations. Thorax
64: 830-832
[Full Text]
Kosiborod, M., Inzucchi, S. E., Krumholz, H. M., Masoudi, F. A., Goyal, A., Spertus, J. A.
(2009). Is Insulin the Preferred Compound in Lowering Glucose Levels in Patients After a Myocardial Infarction?--Reply. Arch Intern Med
169: 1637-1638
[Full Text]
Ziegler, T. R.
(2009). Parenteral Nutrition in the Critically Ill Patient. NEJM
361: 1088-1097
[Full Text]
Joseph, J., Sinha, A., Paech, M., Walters, B. N J
(2009). Sepsis in pregnancy and early goal-directed therapy. Obstet Med
2: 93-99
[Abstract][Full Text]
Van den Berghe, G., Schetz, M., Vlasselaers, D., Hermans, G., Wilmer, A., Bouillon, R., Mesotten, D.
(2009). Intensive Insulin Therapy in Critically Ill Patients: NICE-SUGAR or Leuven Blood Glucose Target?. J. Clin. Endocrinol. Metab.
94: 3163-3170
[Abstract][Full Text]
Webster, N. R., Galley, H. F.
(2009). Does strict glucose control improve outcome?. Br J Anaesth
103: 331-334
[Full Text]
Sourij, H., Schmolzer, I., Kettler-Schmut, E., Eder, M., Pressl, H., deCampo, A., Wascher, T. C.
(2009). Efficacy of a Continuous GLP-1 Infusion Compared With a Structured Insulin Infusion Protocol to Reach Normoglycemia in Nonfasted Type 2 Diabetic Patients: A Clinical Pilot Trial. Diabetes Care
32: 1669-1671
[Abstract][Full Text]
Cyrus, R. M, Szumita, P. M, Greenwood, B. C, Pendergrass, M. L
(2009). Evaluation of Compliance with a Paper-based, Multiplication-factor, Intravenous Insulin Protocol. The Annals of Pharmacotherapy
43: 1413-1418
[Abstract][Full Text]
Weinrauch, L. A., Lewis, E. F.
(2009). Aiming for the best control of glycemia in patients with heart failure and type 2 diabetes the "sweet spot".. J Am Coll Cardiol
54: 429-431
[Full Text]
Van den Berghe, G., Bouillon, R., Mesotten, D., Braithwaite, S. S., Pei, J., Yi, D., Khoo, T. K., Olsen, K. A., Mohammedi, K., Roussel, R., Marre, M., Hallas, P., Finfer, S., Chittock, D., the NICE-SUGAR Study Investigators,
(2009). Glucose control in critically ill patients.. NEJM
361: 89-90
[Full Text]
Cefalu, W. T.
(2009). Mortality and Glycemic Targets in the Intensive Care Unit: Another Paradigm Shift?. Diabetes
58: 1469-1470
[Full Text]
Fuentes, B., Castillo, J., Cobo, E., Diez-Tejedor, E.
(2009). Response to Letter by O'Connell et al. Stroke
40: e512-e513
[Full Text]
Kellum, J. A., Uchino, S.
(2009). International Differences in the Treatment of Sepsis: Are They Justified?. JAMA
301: 2496-2497
[Full Text]
Comi, R. J.
(2009). Glucose Control in the Intensive Care Unit: A Roller Coaster Ride or a Swinging Pendulum?. ANN INTERN MED
150: 809-811
[Abstract][Full Text]
Moghissi, E. S., Korytkowski, M. T., DiNardo, M., Einhorn, D., Hellman, R., Hirsch, I. B., Inzucchi, S. E., Ismail-Beigi, F., Kirkman, M. S., Umpierrez, G. E.
(2009). American Association of Clinical Endocrinologists and American Diabetes Association Consensus Statement on Inpatient Glycemic Control. Diabetes Care
32: 1119-1131
[Full Text]
Bellomo, R., Egi, M.
(2009). What Is a NICE-SUGAR for Patients in the Intensive Care Unit?. Mayo Clin Proc.
84: 400-402
[Full Text]
Nathan, D. M.
(2009). Progress in Diabetes Research--What's Next. JAMA
301: 1599-1601
[Full Text]
Griesdale, D. E.G., de Souza, R. J., van Dam, R. M., Heyland, D. K., Cook, D. J., Malhotra, A., Dhaliwal, R., Henderson, W. R., Chittock, D. R., Finfer, S., Talmor, D.
(2009). Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data. CMAJ
180: 821-827
[Abstract][Full Text]
(2009). All you need to read in the other general journals. BMJ
338: b1296-b1296
[Full Text]
Inzucchi, S. E., Siegel, M. D.
(2009). Glucose Control in the ICU -- How Tight Is Too Tight?. NEJM
360: 1346-1349
[Full Text]
(2009). Intensive Glucose Control Harms Critically Ill Patients. JWatch General
2009: 1-1
[Full Text]
Elasy, T. A.
(2009). Diabetes Quality Improvement: Rigor and Ridicule. Clin. Diabetes
27: 49-51
[Full Text]
Gropper, M. A.
(2009). Issues in Postoperative Management: Postoperative Pain Management and Intensive Glycemic Control. ACCP Crit Care Med Brd Rev
20: 425-432
[Full Text]
40 mg per deciliter [2.2 mmol per liter]) was reported in 206 of 3016 patients (6.8%) in the intensive-control group and 15 of 3014 (0.5%) in the conventional-control group (P<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU (P=0.84) or hospital (P=0.86) or the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39). 
