%0 Journal Article %1 Brunkhorst.2008 %A Brunkhorst, Frank M. %A Engel, Christoph %A Bloos, Frank %A Meier-Hellmann, Andreas %A Ragaller, Max %A Weiler, Norbert %A Moerer, Onnen %A Gruendling, Matthias %A Oppert, Michael %A Grond, Stefan %A Olthoff, Derk %A Jaschinski, Ulrich %A John, Stefan %A Rossaint, Rolf %A Welte, Tobias %A Schaefer, Martin %A Kern, Peter %A Kuhnt, Evelyn %A Kiehntopf, Michael %A Hartog, Christiane %A Natanson, Charles %A Loeffler, Markus %A Reinhart, Konrad %D 2008 %J The New England journal of medicine %K Acute_Kidney_Injury/etiology Aged Combined_Modality_Therapy Critical_Illness Dose-Response_Relationship,_Drug Female Fluid_Therapy Humans Hydroxyethyl_Starch_Derivatives/administration_&_dosage/adverse_effects/therapeutic_use Hypoglycemia/chemically_induced Hypoglycemic_Agents/administration_&_dosage/adverse_effects Infusions,_Intravenous Insulin/administration_&_dosage/adverse_effects Isotonic_Solutions/adverse_effects/therapeutic_use Kaplan-Meier_Estimate Male Middle_Aged Multivariate_Analysis Risk_Factors Sepsis/drug_therapy/mortality/therapy Treatment_Failure %N 2 %P 125–139 %T Intensive insulin therapy and pentastarch resuscitation in severe sepsis %V 358 %X BACKGROUND\r\nThe 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.\r\nMETHODS\r\nIn 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.\r\nRESULTS\r\nThe 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.\r\nCONCLUSIONS\r\nThe 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.)

@article{Brunkhorst.2008, abstract = {BACKGROUND\r\nThe 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.\r\nMETHODS\r\nIn 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.\r\nRESULTS\r\nThe 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.\r\nCONCLUSIONS\r\nThe 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.)}, added-at = {2014-10-15T15:03:42.000+0200}, author = {Brunkhorst, Frank M. and Engel, Christoph and Bloos, Frank and Meier-Hellmann, Andreas and Ragaller, Max and Weiler, Norbert and Moerer, Onnen and Gruendling, Matthias and Oppert, Michael and Grond, Stefan and Olthoff, Derk and Jaschinski, Ulrich and John, Stefan and Rossaint, Rolf and Welte, Tobias and Schaefer, Martin and Kern, Peter and Kuhnt, Evelyn and Kiehntopf, Michael and Hartog, Christiane and Natanson, Charles and Loeffler, Markus and Reinhart, Konrad}, biburl = {https://www.bibsonomy.org/bibtex/27ea0e40d118ef2267c29127156d72d7d/drtester}, interhash = {f3ba85ee9dd7e0ffae1de51825a6acb5}, intrahash = {7ea0e40d118ef2267c29127156d72d7d}, journal = {The New England journal of medicine}, keywords = {Acute_Kidney_Injury/etiology Aged Combined_Modality_Therapy Critical_Illness Dose-Response_Relationship,_Drug Female Fluid_Therapy Humans Hydroxyethyl_Starch_Derivatives/administration_&_dosage/adverse_effects/therapeutic_use Hypoglycemia/chemically_induced Hypoglycemic_Agents/administration_&_dosage/adverse_effects Infusions,_Intravenous Insulin/administration_&_dosage/adverse_effects Isotonic_Solutions/adverse_effects/therapeutic_use Kaplan-Meier_Estimate Male Middle_Aged Multivariate_Analysis Risk_Factors Sepsis/drug_therapy/mortality/therapy Treatment_Failure}, number = 2, pages = {125–139}, timestamp = {2014-10-15T15:03:42.000+0200}, title = {Intensive insulin therapy and pentastarch resuscitation in severe sepsis}, volume = 358, year = 2008 }