Intensive Insulin Therapy, Pentastarch May Be Harmful for Patients With Severe Sepsis

Laurie Barclay
The use of intensive insulin therapy and pentastarch for critically ill patients with severe sepsis was harmful and increased the risk for serious adverse events, according to the results of a multicenter, 2 x 2-factorial trial reported in the January 10 issue of the New England Journal of Medicine.
"The role of intensive insulin therapy in patients with severe sepsis is uncertain," write Frank M. Brunkhorst, MD, and colleagues from the German Competence Network Sepsis. "Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids."
Patients with severe sepsis were randomized 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 main outcome measures were mortality rate at 28 days and mean score for organ failure.
For safety reasons, this study was terminated early. Of 537 patients who could be evaluated, mean morning blood glucose level was lower in the intensive-therapy group (112 mg/dL [6.2 mmol/L]) vs the conventional-therapy group (151 mg/dL [8.4 mmol/L]; P < .001).
At 28 days, the rate of death and the mean score for organ failure did not differ significantly between the 2 groups. Compared with the conventional-therapy group, the intensive-therapy group had a higher rate of severe hypoglycemia (blood glucose level ≤ 40 mg/dL [2.2 mmol/L]; 17.0% vs 4.1%; P < .001) and serious adverse events (10.9% vs 5.2%; P = .01).
Compared with Ringer's lactate, HES therapy was associated with higher rates of acute renal failure and renal replacement therapy.
"The use of intensive insulin therapy placed critically ill patients with sepsis at increased risk for serious adverse events related to hypoglycemia," the study authors write. "As used in this study, HES was harmful, and its toxicity increased with accumulating doses. . . . Since adverse effects have been attributed to various HES solutions, until long-term studies with adequate numbers of patients show that a particular HES solution is safe in critically ill patients, HES solutions should be avoided."
The German Federal Ministry of Education and Research, B. Braun, HemoCue, and Novo Nordisk (makers of insulin and glucometers used in the study) supported this study. Two of the study authors have received lecture and consulting fees from B. Braun. The remaining study authors have disclosed no relevant financial relationships.
N Engl J Med. 2008;358:125-139.