The use of intensive insulin therapy and pentastarch resuscitation in patients with severe sepsis

Prosanto Chaudhury, Jeffrey Barkun, John Marshall, Lena Napolitano, N. N. Baxter, K. J. Brasel, C. J. Brown, T. H. Cogbill, C. S. Cutter, E. Dixon, G. W.N. Fitzgerald, H. J.A. Henteleff, A. W. Kirkpatrick, S. Latosinsky, A. MacLean, T. M. Mastracci, R. S. McLeod, A. Morris, L. A. Neumayer, S. SmithL. R. Temple, M. E. McKenzie

Research output: Contribution to journalReview articlepeer-review


Question: Is the use of intensive insulin therapy compared with conventional therapy (on the basis of Leuven titration protocol) and hydroxyethyl starch (HES) compared with Ringer lactate effective and safe in patients with severe sepsis or septic shock? Design: Randomized open-label controlled trial. Setting: Multicentre (18 aca - demic tertiary hospitals in Germany). Patients: Six hundred patients with a diagnosis of severe sepsis or septic shock. Patients were deemed to be eligible if the onset of the syndrome was less than 24 hours before admission to the intensive care unit (ICU) or less than 24 hours after admission if the condition developed in the ICU. Interventions: Patients were randomly assigned in a 2 × 2 factorial design to receive either conventional (target blood glucose 180°C200 mg/dL; n = 326) or intensive insulin therapy (target blood glucose 80°C100 mg/dL; n = 274) or HES (n = 207) or Ringer lactate (n = 303). Main outcomes: Death from any cause at 28 days and morbidity measured by the mean score on the Sequential Organ Failure Assessment (SOFA) on a scale ranging from 0 to 4 for each of 6 organ systems with an aggregate score of 0°C24 and higher scores indicating more severe organ dysfunction. Results: The mean morning blood glucose level was lower in the intensive therapy group (112 mg/dL [6.2 mmol/L]) than in the conventional therapy group (151 mg/dL [8.4 mmol/L]; p ≤ 0.001). However, at 28 days there were no significant differences between the groups in the rate of death or mean score for organ failure. The rate of severe hypoglycemia (glucose level ≤ 40 mg/dL [2.2 mmol/L]) was higher in the intensive therapy group than in the conventional therapy group (17% v. 4.1%; p ≤ 0.001), as was the rate of serious adverse events (10.9% v. 5.2%, p = 0.010). Hydroxyethyl starch therapy was associated with higher rates of acute renal failure and renal replacement therapy than Ringer lactate. Conclusion: The use of the intensive insulin therapy placed critically ill patients with sepsis at an increased risk for serious adverse events related to hypoglycemia. As used in this study, HES was harmful and its toxicity increased with accumulating doses.

Original languageEnglish (US)
Pages (from-to)512-514
Number of pages3
JournalCanadian Journal of Surgery
Issue number6
StatePublished - Dec 1 2009

ASJC Scopus subject areas

  • Surgery


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