Insulin for Glycemic Control in Acute Ischemic Stroke
Hyperglycemia predicts increased stroke mortality independently of age, stroke severity, or stroke type. The next step is to ascertain whether treating hyperglycemia reduces mortality and improves functional outcome.
The objective of this review was to determine whether maintaining serum glucose within a specific normal range (4–7.5 mmol/L or 72–135 mg/dL) in the first 24 hours of acute ischemic stroke influences outcome.
We searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, EMBASE, CINAHL, Science Citation Index, Web of Science, ongoing trials registers, and SCOPUS. Eligible studies were randomized controlled trials comparing intensively monitored insulin therapy versus usual care in adult patients with acute ischemic stroke.
We obtained a total of 191 studies through the literature search. A total of 7 trials involving 1296 participants (639 patients in the intervention group and 657 in the control group) were eligible. All 7 studies were randomized with parallel design and the intervention was intravenous insulin infusion.
The mean glycemic level during treatment was significantly lower in the intervention group than in the control group with a mean difference of −0.46 (95% CI, −0.67 to −0.25).
Dependence or Death
Modified Rankin and Barthel scores were used. Meta-analysis found no significant difference between the treatment and control groups with an OR of 1.00 (95% CI, 0.78–1.28).
Meta-analysis found no significant difference between the treatment and control groups with an OR of 1.15 (95% CI, 0.88–1.51).
Final Neurological Deficit
The National Institutes of Health Stroke Scale and European Stroke Scale were used. Meta-analysis found no significant difference between the treatment and control groups, with a pooled standardized mean difference of −0.12 (95% CI, −0.23 to 0.00). When using the dichotomized outcome of dependency on others for functional activities, the OR was 1.02 (95% CI, 0.77–1.36).
Meta-analysis found a significant difference in the incidence of hypoglycemia between the treatment and control groups with an OR of 25.9 (95% CI, 9.2–72.7) for symptomatic hypoglycemia and an OR of 31.4 (95% CI, 11.9–83.2) in patients with or without symptoms of hypoglycemia.
With the current evidence, we found that the administration of intravenous insulin with the objective of maintaining serum glucose within a specific range in the first hours of acute ischemic stroke does not provide benefit in terms of functional outcome, death, or improvement in final neurological deficit and significantly increased the number of hypoglycemic episodes.
Implications for Research and Practice
Although early studies showed a potential benefit to aggressive maintenance of glucose in the normal range, we have shown that there is no benefit and an increased risk of adverse events. There are further trials currently ongoing like the Stroke Hyperglycemia Insulin Network Effort (SHINE) study for which we will have to wait for final data. We do not however recommend and further research in this area and believe that the risks of tight glycemic control outweigh the benefits.
This review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 2011, Issue 9 (see www.thecochranelibrary.com for information). Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and The Cochrane Library should be consulted for the most recent version of the review.
Note: The full text of this review is available in the Cochrane Library (for subscribers http://dx.doi.org/10.1002/14651858.CD005346). The full article should be cited as: Bellolio MF, Gilmore RM, Stead LG. Insulin for glycaemic control in acute ischaemic stroke. Cochrane Database Syst Rev 2011. Issue 9.
- Received September 8, 2011.
- Revision received December 2, 2011.
- Accepted December 5, 2011.
- © 2012 American Heart Association, Inc.