Stabilizing Glucose Didn't Help in Acute Stroke Trial


SAN FRANCISCO — Stabilizing glucose levels in acute stroke patients failed to reduce mortality or influence survival with severe disability at 90 days in a large randomized controlled trial presented at the 32nd International Stroke Conference.

Patients treated with a continuous infusion of glucose, insulin, and potassium (GIK) had significant reductions in glucose levels and blood pressure but received no benefit in outcomes, compared with a control group given a saline solution, Dr. Christopher Gray reported.

The reduction in blood pressure surprised investigators of the United Kingdom Glucose Insulin in Stroke (GIST-UK) study. The finding suggests that tight glucose control might be harmful to stroke patients, said Dr. Gray of the Newcastle University School of Clinical Medical Sciences in Sunderland, England.

“We may have inadvertently explained why lower glucose levels confer benefit in [acute myocardial infarction],” he said at a press briefing prior to his presentation at the meeting, which was sponsored by the American Stroke Association.

Reduced blood pressure “was not something we expected,” said Dr. Gray, chief investigator of GIST-UK. Other studies of glucose levels in myocardial infarction have not reported changes in blood pressure.

Although hyperglycemia is associated with greater mortality in stroke patients, he emphasized that tight glucose control has not been shown to be safe in stroke patients who are not diabetic. “It may be intensive glucose lowering is not associated with benefit,” he said. “It may be associated with risk.”

Regarding stepped-up efforts to control glucose in intensive care units, Dr. Gray added in an interview that “for stroke patients with mild to moderate elevations in glucose, we should leave well enough alone.”

GIST-UK randomized 933 acute stroke patients presenting with cerebral infarction or intracerebral hemorrhage at 21 centers from 1998 to 2006. It enrolled less than half of the intended trial population, but Dr. Gray said the results were statistically valid.

All patients had mild to moderate elevations in plasma glucose levels (6.1–17.0 mmol/L). Insulin-dependent diabetics were excluded, he said, because assigning them to a control arm would have been unethical.

The trial randomized 464 patients to a variable continuous infusion (100 mL/hr for 24 hours) of a 10% glucose solution supplemented with insulin and potassium chloride. They were monitored every 2 hours in an effort to maintain capillary glucose at 4–7 mmol/L. Another 469 patients were randomized to a saline solution with no attempt to stabilize glucose levels.

The GIK treatment resulted in a significant overall reduction in mean blood glucose of 0.57 mmol/L over 24 hours. It also produced a significant overall reduction in mean blood pressure of 9.03 mm Hg over 24 hours. With the saline solution, glucose levels fell spontaneously but by a smaller amount, Dr. Gray reported.

At 90 days post treatment, 139 patients (30%) in the GIK arm and 128 patients (27.3%) in the control arm had died. The difference was not significant, but it favored the saline solution. The impact on survival without severe disability also was not significantly different between the two groups.

The investigators looked at patients who had the greatest reductions in glucose levels to see whether reductions greater than the modest improvements in the study would have been beneficial. “Those patients who died had the greatest reduction in glucose level,” Dr. Gray said.

In an interview, press briefing moderator Dr. Philip Gorelick said the results of study—the first to test tight glycemic control in acute stroke patients—departed from findings in other recent trials showing benefits for critical care patients in intensive care units. “I don't think we can leave this issue yet. I think we need more studies,” said Dr. Gorelick, the John S. Garvin professor and head of neurology and rehabilitation at the University of Illinois at Chicago.

'For stroke patients with mild to moderate elevations in glucose, we should leave well enough alone.' DR. GRAY

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