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