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(Stroke. 2008;39:384.)
© 2008 American Heart Association, Inc.

Original Contributions

Treatment of Hyperglycemia In Ischemic Stroke (THIS)

A Randomized Pilot Trial

Askiel Bruno, MD; Thomas A. Kent, MD; Bruce M. Coull, MD; Ravi R. Shankar, MD; Chandan Saha, PhD; Kyra J. Becker, MD; Brett M. Kissela, MD Linda S. Williams, MD

From the Department of Neurology (A.B.), Division of Pediatric Endocrinology (R.R.S.), and Division of Biostatistics (C.S.), Indiana University School of Medicine, and the Roudebush Veterans Affairs Medical Center (L.S.W.), Indianapolis, Ind; the Department of Neurology (T.A.K.), Baylor College of Medicine, Houston, Tex; the Department of Neurology (B.M.C.), University of Arizona School of Medicine, Tucson, Ariz; the Department of Neurology (K.J.B.), University of Washington School of Medicine, Seattle, Wash; and the Department of Neurology (B.M.K.), University of Cincinnati School of Medicine, Cincinnati, Ohio.

Correspondence to Askiel Bruno, MD, Department of Neurology, Indiana University School of Medicine, 1050 Wishard Blvd, 6th Floor, Indianapolis, IN 46202. E-mail abruno{at}iupui.edu

Background and Purpose— Hyperglycemia may worsen brain injury during acute cerebral infarction. We tested the feasibility and tolerability of aggressive hyperglycemia correction with intravenous insulin compared with usual care during acute cerebral infarction.

Methods— We conducted a randomized, multicenter, blinded pilot trial for patients with cerebral infarction within 12 hours after onset, a baseline glucose value 8.3 mmol/L (150 mg/dL), and a National Institutes of Health Stroke Scale score of 3 to 22. Patients were randomized 2:1 to aggressive treatment with continuous intravenous insulin or subcutaneous insulin QID as needed (usual care). Target glucose levels were <7.2 mmol/L (<130 mg/dL) in the aggressive-treatment group and <11.1 mmol/L (<200 mg/dL) in the usual-care group. Glucose was monitored every 1 to 2 hours, and the protocol treatments continued for up to 72 hours. Final clinical outcomes were assessed at 3 months.

Results— We randomized 46 patients (31 to aggressive treatment and 15 to usual care). All patients in the aggressive-treatment group and 11 (73%) in the usual-care group had diabetes (P=0.008). Glucose levels were significantly lower in the aggressive-treatment group throughout protocol treatment (7.4 vs 10.5 mmol/L [133 vs 190 mg/dL], P<0.001). Hypoglycemia <3.3 mmol/L (<60 mg/dL) occurred only in the aggressive-treatment group (11 patients, 35%), 4 (13%) of whom had brief symptoms, including only 1 (3%) neurologic. Final clinical outcomes were nonsignificantly better in the aggressive-treatment group.

Conclusions— The intravenous insulin protocol corrected hyperglycemia during acute cerebral infarction significantly better than usual care without major adverse events and should be investigated in a clinical efficacy trial.

Key Words: brain infarction • diabetes mellitus • hyperglycemia • insulin

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