Greet Van den Berghe, M.D., Ph.D., Alexander Wilmer, M.D., Ph.D., Greet Hermans, M.D., Wouter Meersseman, M.D., Pieter J. Wouters, M.Sc., Ilse Milants, R.N., Eric Van Wijngaerden, M.D., Ph.D., Herman Bobbaers, M.D., Ph.D., and Roger Bouillon, M.D., Ph.D.
Background Intensive insulin therapy reduces morbidity and mortalityin patients in surgical intensive care units (ICUs), but itsrole in patients in medical ICUs is unknown.
Methods In a prospective, randomized, controlled study of adultpatients admitted to our medical ICU, we studied patients whowere considered to need intensive care for at least three days.On admission, patients were randomly assigned to strict normalizationof blood glucose levels (80 to 110 mg per deciliter [4.4 to6.1 mmol per liter]) with the use of insulin infusion or toconventional therapy (insulin administered when the blood glucoselevel exceeded 215 mg per deciliter [12 mmol per liter], withthe infusion tapered when the level fell below 180 mg per deciliter[10 mmol per liter]). There was a history of diabetes in 16.9percent of the patients.
Results In the intention-to-treat analysis of 1200 patients,intensive insulin therapy reduced blood glucose levels but didnot significantly reduce in-hospital mortality (40.0 percentin the conventional-treatment group vs. 37.3 percent in theintensive-treatment group, P=0.33). However, morbidity was significantlyreduced by the prevention of newly acquired kidney injury, acceleratedweaning from mechanical ventilation, and accelerated dischargefrom the ICU and the hospital. Although length of stay in theICU could not be predicted on admission, among 433 patientswho stayed in the ICU for less than three days, mortality wasgreater among those receiving intensive insulin therapy. Incontrast, among 767 patients who stayed in the ICU for threeor more days, in-hospital mortality in the 386 who receivedintensive insulin therapy was reduced from 52.5 to 43.0 percent(P=0.009) and morbidity was also reduced.
Conclusions Intensive insulin therapy significantly reducedmorbidity but not mortality among all patients in the medicalICU. Although the risk of subsequent death and disease was reducedin patients treated for three or more days, these patients couldnot be identified before therapy. Further studies are neededto confirm these preliminary data. (ClinicalTrials.gov number,NCT00115479
[ClinicalTrials.gov]
.)
Source Information
From the Departments of Intensive Care Medicine (G.V.B., P.J.W., I.M.) and Medical Intensive Care Medicine (A.W., G.H., W.M., E.V.W., H.B.) and the Laboratory for Experimental Medicine and Endocrinology (R.B.), Catholic University of Leuven, Leuven, Belgium.
Address reprint requests to Dr. Van den Berghe at the Department of Intensive Care Medicine, Catholic University of Leuven, B-3000 Leuven, Belgium, or at greta.vandenberghe{at}med.kuleuven.be.
Intensive Insulin Therapy in the Medical ICU
Hammer L., Dessertaine G., Timsit J.-F., Aberegg S. K., Tamler R., LeRoith D., Roth J., Van den Berghe G., Wilmer A., Bouillon R., Malhotra A.
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N Engl J Med 2006;
354:2069-2071, May 11, 2006.
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Lacherade, J.-C., Outin, H., De Jonghe, B., Bracco, D., Schricker, T., Carvalho, G., Muller, L., Jaber, S., Lefrant, J. Y., Van den Berghe, G., Wilmer, A., Bouillon, R., Ellger, B., van den Heuvel, I., Poelaert, J., Brunkhorst, F. M., Reinhart, K., Engel, C.
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