Management of hyperglycemia in patients with acute ischemic stroke: comparison of two strategies

Introduction

The 2001 study of Van den Berghe and colleagues demonstrating important benefits of intensive insulin therapy in critically ill patients [1] led to the hypothesis that aggressive control of hyperglycemia in patients with acute stroke could limit brain damage and improve clinical outcome. The best strategy to control hyperglycemia is open to discussion.

Objective

To compare the safety and efficacy of two different strategies for glycemic control in acute ischemic stroke patients, evaluating the outcome through the Glasgow Outcome Scale Extended [2], hospital mortality and NIHSS during the ICU stay.

Methods

Included in the study were all patients admitted to a general ICU with acute ischemic stroke. Patients randomized to Group 1 (intensive insulin therapy) received continuous intravenous insulin infusion adjusted to maintain blood glucose levels below 140 mg/dl. Group 2 patients (carbohydrate restrictive strategy) received intravenous hydration with a glucose-free solution (Ringer III) and enteral nutritional formula containing 33.3% carbohydrates. These patients received regular insulin subcutaneously according to a sliding scale, aiming to maintain blood glucose levels below 150 mg/dl. We evaluated glycemic variability (SD of blood glucose concentration × 100/mean blood glucose level), ΔNIHH (discharge – admittance NIHH), hospital mortality and the Glasgow Outcome Scale Extended.

Results

Thirty-four patients were submitted to randomization, 14 to Group 1 and 20 to Group 2. Both groups were comparable regarding age, gender, APACHE II score, prevalence of diabetes mellitus and systemic hypertension. There was also no difference between the two groups regarding admittance Glasgow Coma Score and NIHH. Patients in Group 1 received 35.7 (6.7 to 49.8) units of regular insulin per day, whereas patients in Group 2 received 0.0 (0 to 7.2) (P = 0.001). The mean blood glucose level in Group 1 was 139.2 ± 25.9 mg/dl and in Group 2 was 146.9 ± 39.3 mg/dl (P = 0.52). Hypoglycemia occurred in one patient in Group 1 and in two patients in Group 2 (P = 1.0). Glycemic variability was 27.0 in Group 1 and 20.1 in Group 2 (P = 0.075), and was significantly higher among patients who died during the hospital stay (29.6) compared with those discharged (20.3) (P = 0.02). Four (28.5%) patients in Group 1 and six (30%) patients in Group 2 died during the hospital stay (P = 1.0). The ΔNIHH was -2 in Group 1 and -4.3 in Group 2 (P = 0.3). The Extended Glasgow Outcome Scale, used to evaluate functional outcome after hospital discharge, showed that one (10%) patient in Group 1 and five (41.6%) patients in Group 2 had a favorable outcome (moderate disability and good recovery) (P = 0.1, relative difference of 76%).

Conclusion

The present study shows a trend toward better outcomes in the group of patients submitted to a more conservative approach of glycemic control, although without statistical significance. A glycemic variability significantly higher in the intensive insulin therapy group may explain, at least in part, our results.