Serum Glucose Level and Diabetes Predict Tissue Plasminogen Activator–Related Intracerebral Hemorrhage in Acute Ischemic Stroke

Abstract

Background and Purpose —Five pretreatment variables ( P <0.1 univariate analysis), including serum glucose (>300 mg/dL), predicted symptomatic intracerebral hemorrhage (ICH) in the National Institute of Neurological Disorders and Stroke rtPA trial. We retrospectively studied stroke patients treated <3 hours from onset with intravenous rtPA at 2 institutions to evaluate the role of these variables in predicting ICH. Methods —Baseline characteristics, including 5 prespecified variables (age, baseline glucose, smoking status, National Institutes of Health Stroke Scale [NIHSS] score, and CT changes [>33% middle cerebral artery territory hypodensity]), were reviewed in 138 consecutive patients. Variables were evaluated by logistic regression as predictors of all hemorrhage (including hemorrhagic transformation) and symptomatic hemorrhage on follow-up CT scan. Variables significant at P <0.25 level were included in a multivariate analysis. Diabetes was substituted for glucose in a repeat analysis. Results —Symptomatic hemorrhage rate was 9% (13 of 138). Any hemorrhage rate was 30% (42 of 138). Baseline serum glucose (5.5-mmol/L increments) was the only independent predictor of both symptomatic hemorrhage [OR, 2.26 (CI, 1.05 to 4.83), P =0.03] and all hemorrhage [OR, 2.26 (CI, 1.07 to 4.69), P =0.04]. Serum glucose >11.1 mmol/L was associated with a 25% symptomatic hemorrhage rate. Baseline NIHSS (5-point increments) was an independent predictor of all hemorrhage only [OR, 12.42 (CI, 1.64 to 94.3), P =0.01]. Univariate analysis demonstrated a trend for nonsmoking as a predictor of all hemorrhage [OR, 0.45 (CI, 0.19 to 1.08), P =0.07]. Diabetes was also an independent predictor of ICH when substituted for glucose in repeat analysis. Conclusions —Serum glucose and diabetes were predictors of ICH in rtPA-treated patients. This novel association requires confirmation in a larger cohort.

Blood Biomarkers of Ischemic Stroke

“…t-PA itself activates MMP-9 and thus may promote hemorrhagic transformation. Hyperglycemia and diabetes have also been associated with elevated MMP-9 and the development of hemorrhagic transformation [81]. {Uemura, 2001 #2927 BBB disruption independently correlates with serum MMP9 levels [82].…”

Management of blood glucose in patients with stroke

“…Nevertheless, hyperglycaemia has a particularly potent adverse effect after thrombolysis, also in patients with diabetes [23]. Hyperglycaemic patients more commonly develop intracerebral hemorrhage after thrombolysis and have overall poorer clinical and radiological outcome [24]. Hyperglycaemic patients are also less likely to recanalise with thrombolysis.…”

Association of Acute and Chronic Hyperglycemia With Acute Ischemic Stroke Outcomes Post‐Thrombolysis: Findings From Get With The Guidelines‐Stroke

“…Some studies have reported an increased risk of symptomatic intracranial hemorrhage (sICH) after tPA treatment in patients with diabetes or hyperglycemia,8, 9, 10 and admission glucose has been used in prognostic models to identify patients at risk of sICH after tPA 11. Even though studies did not find overall reduced benefit of tPA in diabetic patients,12 decreased rates of tPA administrations are observed in diabetic patients 13.…”