N Engl J Med. 2006 Feb 2;354(5):449-61.
Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, Van
Wijngaerden E, Bobbaers H, Bouillon R.
Department of Intensive Care Medicine, Catholic University of Leuven, Leuven,
Belgium. greta.vandenberghe@med.kuleuven.be
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.) Copyright 2006 Massachusetts Medical Society.