The correlation between admission blood glucose and intravenous rt-PA-induced arterial recanalization in acute ischemic stroke: a multi-centre TCD study.
BACKGROUND
The relationship between hyperglycemia and arterial recanalization following intravenous recombinant tissue-plasminogen activator treatment in acute ischemic stroke is not well understood.


OBJECTIVE
We aimed to evaluate the effects of hyperglycemia in thrombolysed ischemic stroke patients on recanalization rate and clinical outcome.


METHODS
We studied 348 (231 subjects from the CLOTBUST databank and 117 subjects from the CLOTBUST trial phase II) with documented intracranial artery occlusion treated with intravenous recombinant tissue-plasminogen activator. Serum glucose was determined at baseline before intravenous recombinant tissue-plasminogen activator administration. Hyperglycemia was defined as a glucose level ≥140 mg/dl (7·7 mmol/l). Transcranial Doppler findings were interpreted using the thrombolysis in brain ischemia flow grading system as persistent arterial occlusion, re-occlusion or complete recanalization. Poor clinical outcome was defined by modified Rankin score > 2 at three-months.


RESULTS
At baseline, 138 patients (37·4%) were hyperglycemic and 210 patients (56·9%) normoglycemic. Baseline characteristics based on glucose ≥ 140 (7·7 mmol/l) or less 140: age (70·0 ± 12·4 vs. 67·3 ± 14·1, P = 0·065), baseline National Institutes of Health Stroke Scale (17·0 ± 5·5 vs. 15·8 ± 5·5, P = 0·054), time to recombinant tissue-plasminogen activator (141·4 ± 69·1 vs. 145·3 ± 48·4 mins, P = 0·56), and history of diabetes mellitus [60/138 (43·5%) vs. 22/210 (10·5%), P < 0·001]). Patients with hyperglycemia have a higher rate of persisting occlusion [72/138 (52·2%) vs. 66/210 (31·4%)] and less rate of complete recanalization [34/138 (24·6%) vs. 82/210 (39%), P < 0·001]. Median time to recanalization in patients with severe hyperglycemia (glucose ≥ 200) (11 mmol/l) and glucose <200 was 163 ± 79 and 131 ± 90 mins, respectively (P = 0·045). Sixteen patients (11·6%) in the hyperglycemic group and 12 (5·7%) in the normoglycemic group had symptomatic intracerebral hemorrhage (P = 0·049). Seventy-eight patients (69%) in the hyperglycemia group and 72 patients (41·6%) in the normoglycemic group had poor clinical outcome (three-month modified Rankin score > 2) (P ≤ 0·001). After adjusting for stroke risk factors, patients with hyperglycemia were more likely to have poor clinical outcome (three-month modified Rankin score > 2) (adjusted odds ratio = 2·22, 95% confidence interval: 1·2-4·11, P = 0·011) and low complete recanalization rate (adjusted odds ratio: 0·5, confidence interval: 0·3-0·92, P = 0·025) with trend of increase risk of symptomatic intracerebral hemorrhage (adjusted odds ratio: 2·07, confidence interval:0·8-5·1, P = 0·114). There was no association between baseline glucose as a continuous variable and poor clinical outcome, but there was with the complete recanalization's rate.


CONCLUSIONS
Hyperglycemia is associated with low rate of complete recanalization and poor clinical outcome in intravenous recombinant tissue-plasminogen activator-treated patients. Further studies are needed to evaluate whether lowering hyperglycemia is beneficial in the management of acute stroke patients.
Department of Medicine (Neurology), University of Alberta, Edmonton, AB, Canada.
Maher
M
Saqqur
Department of Medicine (Neurology), University of Alberta, Edmonton, AB, Canada.
Ashfaq
A
Shuaib
Department of Neurology and Semmes-Murphey, University of Tennessee Health Science Center, Memphis, TN, USA.
Andrei V
AV
Alexandrov
Department of Medicine (Neurology), University of Alberta, Edmonton, AB, Canada.
Joseph
J
Sebastian
Department of Medicine (Neurology), University of Alberta, Edmonton, AB, Canada.
Khurshid
K
Khan
Cerebrovascular Center, Cleveland Clinic Main Campus, Cleveland, OH, USA.
Ken
K
Uchino
D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications*; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D006943:Hyperglycemia / Q000150:complications*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012189:Retrospective Studies; D013223:Statistics as Topic; D020521:Stroke / Q000000981:diagnostic imaging* / Q000209:etiology / Q000628:therapy; D015912:Thrombolytic Therapy / Q000379:methods*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000009:adverse effects*; D016896:Treatment Outcome; D017585:Ultrasonography, Doppler, Transcranial
D001786:Blood Glucose; D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
acute stroke therapy; ischemic stroke; rt-PA; thrombolysis; treatment; ultrasound