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Intensive Insulin Beneficial For Those With Long ICU Stays

Posted: Thursday, April 27, 2006

Intensive insulin therapy administered from admission onwards in patients in the medical intensive care unit reduced morbidity among all patients and mortality among those who remained in the ICU for at least a third day.
 Current data support careful maintenance of normoglycemia in most ICU patients, from admission onwards. 

“Hyperglycemia and insulin resistance are common in severe illness and are associated with adverse outcomes,” investigators wrote in the New England Journal of Medicine. Greet Van den Berghe, MD, PhD, and colleagues conducted a randomized, controlled study of intensive insulin therapy for patients in the medical ICU, targeting those requiring intensive care for at least a third day. Van den Berghe is a professor of medicine at the Catholic Unversity of Leuven in Belgium.

A previous study found that patients in the surgical ICU had a pronounced mortality benefit from intensive insulin therapy if treatment lasted into the the third day and beyond.

“Several potential mechanisms may explain these benefits – prevention of immune dysfunction, reduction of systemic inflammation, and protection of the endothelium and of mitochondrial ultrastructure and function,” the researchers wrote.
Between March 2002 and May 2005, 1,200 adult patients admitted to the medical ICU were enrolled in the study. Patients were randomized to either intensive insulin treatment (n=595) or conventional insulin treatment (n=605). Conventional therapy consisted of continuous insulin infusion starting when the blood glucose level exceeded 215 mg/dL.

The dose was then adjusted to maintain a glucose level between 180 mg/dL and 200 mg/dL, and the infusion was tapered and stopped when the glucose level dropped below 180 mg/dL. Intensive therapy began with insulin infusion when glucose levels exceeded 110 mg/dL; normoglycemia (80 mg/dL to 110 mg/dL) was maintained.

“ It was clear that three days or more of intensive insulin therapy, started upon ICU admission, are needed to reduce hospital mortality,” —Greet Van den Berghe, MD, PhD

There were no significant differences in baseline characteristics between the two groups, including medications other than insulin. Morbidity was reduced in the intensive treatment group, with a reduction in newly acquired kidney injury (8.9% in the conventional group vs. 5.9% in the intensive group, P=.04), earlier weaning from mechanical ventilation (HR 1.21, 95% CI, 1.02-1.44) and earlier discharge from the ICU (HR 1.15, 95% CI, 1.01-1.32).

There were no significant effects on bacteremia, prolonged requirement of antibiotics, hyperbilirubinemia or hyperinflammation. More patients had hypoglycemia in the intensive treatment group, but there were no detectable adverse effects as the hypoglycemia was always detected and treated promptly.

Among all patients, there were nodifferences in mortality between the two treatment groups (26.8% in the conventional group vs. 24.2% in the intensive group, P=.31). However, a decrease in mortality was seen among the 767 patients who stayed in the ICU for at least three days (38.1% vs. 31.3%, P=.05). Investigators wrote that “death from all causes in the ICU appeared to be reduced.” In-hospital deaths among patients with longer stays were also reduced (52.5% vs. 43%, P=.009).

“Looking back at the data from our previous surgical study, it was clear that three days or more of intensive insulin therapy, started upon ICU admission, are needed to reduce hospital mortality,” stated, Van den Berghe. “It’s like giving antibiotics; if you do not continue them long enough, they don’t work either. Three days of blood glucose control in ICU appears the minimum you need.”

Van den Berghe, however, said that the current study’s results offer enough clear evidence to warrant intensive insulin therapy in most patients in the medical ICU upon admission. “Sustained blood glucose control in patients with diabetes or critical illness prevents cellular damage inflicted by hyperglycemia and this benefit outweighs the risk of hypoglycemia.” .

“Current data support careful maintenance of normoglycemia in most ICU patients, from admission onwards.” Because this study was designed to start treatment upon admission, she said, there is currently no evidence to support waiting until the third day to begin intensive therapy

Source: Diabetes In Control: Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med. 2006;354:449-461

 
 
 
 
 
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