title: Intensive insulin therapy and pentastarch resuscitation in severe sepsis.
abstract: 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.)
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Friedrich Schiller University, Jena, Germany.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Brunkhorst
authors.forename: Christoph
authors.initials: C
authors.lastname: Engel
authors.forename: Frank
authors.initials: F
authors.lastname: Bloos
authors.forename: Andreas
authors.initials: A
authors.lastname: Meier-Hellmann
authors.forename: Max
authors.initials: M
authors.lastname: Ragaller
authors.forename: Norbert
authors.initials: N
authors.lastname: Weiler
authors.forename: Onnen
authors.initials: O
authors.lastname: Moerer
authors.forename: Matthias
authors.initials: M
authors.lastname: Gruendling
authors.forename: Michael
authors.initials: M
authors.lastname: Oppert
authors.forename: Stefan
authors.initials: S
authors.lastname: Grond
authors.forename: Derk
authors.initials: D
authors.lastname: Olthoff
authors.forename: Ulrich
authors.initials: U
authors.lastname: Jaschinski
authors.forename: Stefan
authors.initials: S
authors.lastname: John
authors.forename: Rolf
authors.initials: R
authors.lastname: Rossaint
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
authors.forename: Martin
authors.initials: M
authors.lastname: Schaefer
authors.forename: Peter
authors.initials: P
authors.lastname: Kern
authors.forename: Evelyn
authors.initials: E
authors.lastname: Kuhnt
authors.forename: Michael
authors.initials: M
authors.lastname: Kiehntopf
authors.forename: Christiane
authors.initials: C
authors.lastname: Hartog
authors.forename: Charles
authors.initials: C
authors.lastname: Natanson
authors.forename: Markus
authors.initials: M
authors.lastname: Loeffler
authors.forename: Konrad
authors.initials: K
authors.lastname: Reinhart
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology*; D000368:Aged; D003131:Combined Modality Therapy; D016638:Critical Illness; D004305:Dose-Response Relationship, Drug; D005260:Female; D005440:Fluid Therapy; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D007003:Hypoglycemia / Q000139:chemically induced*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects; D007552:Isotonic Solutions / Q000009:adverse effects / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000077331:Ringer's Solution; D012307:Risk Factors; D018805:Sepsis / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D017211:Treatment Failure
chemical_list: D006895:Hydroxyethyl Starch Derivatives; D007004:Hypoglycemic Agents; D007328:Insulin; D007552:Isotonic Solutions; D000077331:Ringer's Solution