• DOI:10.1056/NEJMoa070716
• Corpus ID: 8441982

Intensive insulin therapy and pentastarch resuscitation in severe sepsis.

@article{Brunkhorst2008IntensiveIT,
  title={Intensive insulin therapy and pentastarch resuscitation in severe sepsis.},
  author={Frank Brunkhorst and Christoph Engel and Frank Bloos and Andreas Meier‑Hellmann and Maximilian Ragaller and Norbert Weiler and Onnen Moerer and Matthias Gruendling and Michael Oppert and Stefan Grond and Derk Olthoff and Ulrich Jaschinski and Stefan John and Rolf Rossaint and Tobias Welte and Martin Schaefer and P Kern and Evelyn Kuhnt and Michael Kiehntopf and Christiane S. Hartog and Charles Natanson and Markus W. Loeffler and Konrad Reinhart},
  journal={The New England journal of medicine},
  year={2008},
  volume={358 2},
  pages={
          125-39
        }
}

• F. Brunkhorst, C. Engel, +20 authors K. Reinhart
• Published 10 January 2008
• Medicine
• The New England journal of medicine

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.)