Efficacy Endpoints: Death, disability
Harm Endpoints: Symptomatic hypoglycemia
Narrative: Hyperglycemia is common after acute ischemic stroke and occurs in up to two-thirds of patients. Clinical trials have concluded that hyperglycemia predicts increased mortality. It is uncertain whether this contributes to brain injury or is merely a physiologic response to acute stroke, and animal studies have suggested that insulin may reduce stroke size by reducing glucose levels, acidosis, and cell injury.
In this 2011 Cochrane review of randomized trials ‘dependence’, a primary outcome, was defined as being severely dependent on others in activities of daily living. Three treatment comparisons were investigated: insulin vs. placebo, low dose insulin vs. high dose insulin, or tight versus liberal glycemic control, all for glucose levels greater >110 mg/dl. This review found no benefit in any comparison.
Seven trials involving 1296 participants were included. Maintaining blood sugar level between 72 and 135 mg/dl immediately after a stroke did not improve outcomes (i.e. did not reduce death or dependence). It did however significantly increase symptomatic hypoglycemic events (confusion, visual disturbances, seizures, sweating, or hunger in a patient with a glucose level lower than 54 mg/dl). The NNH for symptomatic hypoglycemia in the experimental group was 7.
Caveats: The Cochrane authors report two major subgroup analyses. The first is a comparison of diabetic and non-diabetic stroke patients that also showed no benefit. In the second analysis the authors note that studies reporting only 30-day final outcomes appeared to show more favorable results for insulin treatment than studies reporting 90-day outcomes. The latter studies were larger and accounted for 82% of all subjects, and because the natural history of ischemic stroke is improvement and stabilization through three months this appears to be a more reliable and patient-oriented outcome measure. Notably, however, stroke scores did show nearly significant differences favoring insulin treatment in the overall group. However, this did not translate into a death or dependency advantage, statistically or otherwise.
Author: Jason Bell, MD
Published/Updated: January 30, 2012
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