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Intensive insulin therapy and pentastarch resuscitation in severe sepsis.
N Engl J Med. 2008 Jan 10;358(2):125-39.
Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, Moerer O, Gruendling M, Oppert M, Grond S, Olthoff D, Jaschinski U, John S, Rossaint R, Welte T, Schaefer M, Kern P, Kuhnt E, Kiehntopf M, Hartog C, Natanson C, Loeffler M, Reinhart K; German Competence Network Sepsis (SepNet).
Department of Anesthesiology and Intensive Care Medicine, Friedrich Schiller University, Jena, Germany.
BACKGROUND:
The 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. METHODS: In 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.
RESULTS: The 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. CONCLUSIONS: The
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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