• Frank M Brunkhorst, Christoph Engel, Frank Bloos, Andreas Meier-Hellmann, Max Ragaller, Norbert Weiler, Onnen Moerer, Matthias Gruendling, Michael Oppert, Stefan Grond, Derk Olthoff, Ulrich Jaschinski, Stefan John, Rolf Rossaint, Tobias Welte, Martin Schaefer, Peter Kern, Evelyn Kuhnt, Michael Kiehntopf, Christiane Hartog, Charles Natanson, Markus Loeffler, Konrad Reinhart, and German Competence Network Sepsis (SepNet).
• Department of Anesthesiology and Intensive Care Medicine, Friedrich Schiller University, Jena, Germany.
• N. Engl. J. Med. 2008 Jan 10; 358 (2): 125139125-39.

BackgroundThe role of intensive insulin therapy in patients with severe sepsis is uncertain. Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids.MethodsIn a multicenter, two-by-two factorial trial, we randomly assigned patients with severe sepsis to receive either intensive insulin therapy to maintain euglycemia or conventional insulin therapy and either 10% pentastarch, a low-molecular-weight hydroxyethyl starch (HES 200/0.5), or modified Ringer's lactate for fluid resuscitation. The rate of death at 28 days and the mean score for organ failure were coprimary end points.ResultsThe trial was stopped early for safety reasons. Among 537 patients who could be evaluated, the mean morning blood glucose level was lower in the intensive-therapy group (112 mg per deciliter [6.2 mmol per liter]) than in the conventional-therapy group (151 mg per deciliter [8.4 mmol per liter], P<0.001). However, at 28 days, there was no significant difference between the two groups in the rate of death or the mean score for organ failure. The rate of severe hypoglycemia (glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was higher in the intensive-therapy group than in the conventional-therapy group (17.0% vs. 4.1%, P<0.001), as was the rate of serious adverse events (10.9% vs. 5.2%, P=0.01). HES therapy was associated with higher rates of acute renal failure and renal-replacement therapy than was Ringer's lactate.ConclusionsThe use of intensive insulin therapy placed critically ill patients with sepsis at increased risk for serious adverse events related to hypoglycemia. As used in this study, HES was harmful, and its toxicity increased with accumulating doses. (ClinicalTrials.gov number, NCT00135473.)2008 Massachusetts Medical Society

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