Key Point

In critically ill patients, intensive insulin therapy was shown to increase risk of severe hypoglycemia, compared with conventional insulin therapy. In the same study, 10% pentastarch was associated with higher rates of acute renal failure than was Ringer’s lactate.

In critically ill patients with sepsis, intensive insulin therapy and fluid resuscitation with 10% hydroxyethyl starch (HES) can be harmful, according to a report in the January 10 New England Journal of Medicine.

In a multicenter randomized trial—the Efficacy of Volume Substitution and Insulin Therapy in Severe Sepsis (VISEP) study—Frank M. Brunkhorst, MD, of Friedrich Schiller University, Jena, Germany, and colleagues compared the safety and efficacy of intensive insulin therapy with that of conventional insulin therapy. Whether intensive insulin therapy improves outcome in patients with severe sepsis had not been determined; however, such therapy has been advocated by some health care professionals, said the researchers. The group also examined the efficacy and safety of HES compared with that of Ringer’s lactate.

EARLY TERMINATION

Patients with severe sepsis or septic shock, age 18 or older, were eligible for participation in the study if the onset of the syndrome occurred less than 24 hours after admission to the ICU or less than 12 hours after admission if the condition developed in the ICU. Patients randomized to the conventional insulin therapy group received 50 mL of 0.9% saline solution delivered through a perfusion pump when their blood glucose level exceeded 200 mg/dL; thereafter, insulin level was adjusted to maintain a blood glucose level of 180 to 200 mg/dL. In the intensive insulin therapy group, insulin infusion was initiated when blood glucose levels exceeded 110 mg/mL. Patients had their insulin dose adjusted to whole-blood glucose levels, which were measured at intervals of one to four hours. Coprimary end points included the rate of death from any cause at 28 days and morbidity, as measured by the Sequential Organ Failure Assessment (SOFA) at the time of the intervention. The safety end point was the occurrence of severe hypoglycemia.

Intensive insulin therapy was terminated early after the first safety analysis. Severe hypoglycemia (ie, glucose level ≤ 40 mg/dL) was found in 17.0% and 4.1% of the intensive and conventional insulin therapy groups, respectively. There was no significant difference between the two groups in the rate of death at 28 days (24.7% vs 26.0%) or 90 days (39.7% vs 35.4%). In addition, there was no significant difference between the groups in mean SOFA scores (7.8 vs 7.7).

Comparison of HES and Ringer’s lactate was terminated at the time of the interim analysis, due to a greater incidence of renal failure and a trend toward higher 90-day mortality in patients who received HES (41.0%), compared with those who received Ringer’s lactate (33.9%). The rate of death at 28 days did not differ significantly between the HES and Ringer’s lactate groups (26.7% and 24.1%, respectively), the researchers observed.

NO CONSISTENT BENEFIT

Dr. Brunkhorst and his colleagues said their results are similar to those of prior research. “Taken together, our study and the medical ICU study by Van den Berghe et al [published in 2006] establish that intensive insulin therapy has no measurable, consistent benefit in critically ill patients in a medical ICU, regardless of whether the patients have severe sepsis, and that such therapy increases the risk of hypoglycemic episodes,” they said.

“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,” concluded the researchers.            

—Karen L. Spittler

Suggested Reading
Brunkhorst FM, Engel C, Bloos F, et al; German Competence Network Sepsis (SepNet). Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med. 2008;358(2):125-139.
Dellinger RP, Carlet JM, Masur H, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32(3):858-873.
Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med. 2006;354(5):449-461.
Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001;345(19):1359-1367.

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