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Randomized Controlled Trial
. 2006 Feb 2;354(5):449-61.
doi: 10.1056/NEJMoa052521.

Intensive insulin therapy in the medical ICU

Greet Van den Berghe  1 , Alexander Wilmer, Greet Hermans, Wouter Meersseman, Pieter J Wouters, Ilse Milants, Eric Van Wijngaerden, Herman Bobbaers, Roger Bouillon
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Free article
Randomized Controlled Trial

Intensive insulin therapy in the medical ICU

Greet Van den Berghe et al. N Engl J Med. .
Free article

Abstract

Background: Intensive insulin therapy reduces morbidity and mortality in patients in surgical intensive care units (ICUs), but its role in patients in medical ICUs is unknown.

Methods: In a prospective, randomized, controlled study of adult patients admitted to our medical ICU, we studied patients who were considered to need intensive care for at least three days. On admission, patients were randomly assigned to strict normalization of blood glucose levels (80 to 110 mg per deciliter [4.4 to 6.1 mmol per liter]) with the use of insulin infusion or to conventional therapy (insulin administered when the blood glucose level exceeded 215 mg per deciliter [12 mmol per liter], with the infusion tapered when the level fell below 180 mg per deciliter [10 mmol per liter]). There was a history of diabetes in 16.9 percent of the patients.

Results: In the intention-to-treat analysis of 1200 patients, intensive insulin therapy reduced blood glucose levels but did not significantly reduce in-hospital mortality (40.0 percent in the conventional-treatment group vs. 37.3 percent in the intensive-treatment group, P=0.33). However, morbidity was significantly reduced by the prevention of newly acquired kidney injury, accelerated weaning from mechanical ventilation, and accelerated discharge from the ICU and the hospital. Although length of stay in the ICU could not be predicted on admission, among 433 patients who stayed in the ICU for less than three days, mortality was greater among those receiving intensive insulin therapy. In contrast, among 767 patients who stayed in the ICU for three or more days, in-hospital mortality in the 386 who received intensive insulin therapy was reduced from 52.5 to 43.0 percent (P=0.009) and morbidity was also reduced.

Conclusions: Intensive insulin therapy significantly reduced morbidity but not mortality among all patients in the medical ICU. Although the risk of subsequent death and disease was reduced in patients treated for three or more days, these patients could not be identified before therapy. Further studies are needed to confirm these preliminary data. (ClinicalTrials.gov number, NCT00115479.)

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