Treatment of hyperglycemia in ischemic stroke (THIS): a randomized pilot trial.
OBJECTIVE
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 >or=8.3 mmol/L (>or=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.
Bruno
Askiel
A
Department of Neurology, Indiana University School of Medicine, Roudebush Veterans Affairs Medical Center, Indianapolis, IN 46202, USA. abruno@iupui.edu
Kent
Thomas A
TA
Coull
Bruce M
BM
Shankar
Ravi R
RR
Saha
Chandan
C
Becker
Kyra J
KJ
Kissela
Brett M
BM
Williams
Linda S
LS
D000208:Acute Disease; D000328:Adult; D000368:Aged; D001786:Blood Glucose; D002545:Brain Ischemia / Q000150:complications*; D003920:Diabetes Mellitus / Q000188:drug therapy; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000150:complications* / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D020127:Recovery of Function / Q000187:drug effects; D020521:Stroke / Q000150:complications*; D016896:Treatment Outcome
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin