Background: Although volume of intracerebral hemorrhage (ICH) is a predictor of mortality, it is unknown whether subsequent hematoma growth further increases the risk of death or poor functional outcome. Methods: To d...Background: Although volume of intracerebral hemorrhage (ICH) is a predictor of mortality, it is unknown whether subsequent hematoma growth further increases the risk of death or poor functional outcome. Methods: To determine if hematoma growth independently predicts poor outcome, the authors performed an individual meta-analysis of patients with spontaneous ICH who had CT within 3 hours of onset and 24-hour follow-up. Placebo patients were pooled from three trials investigating dosing, safety, and efficacy of rFVIIa (n = 115), and 103 patients from the Cincinnati study (total 218). Other baseline factors included age, gender, blood glucose, blood pressure, Glasgow Coma Score (GCS), intraventricular hemorrhage (IVH), and location. Results: Overall, 72.9%of patients exhibited some degree of hematoma growth. Percentage hematoma growth (hazard ratio [HR] 1.05 per 10%increase [95%CI: 1.03, 1.08; p < 0.0001]), initial ICH volume (HR 1.01 per mL [95%CI: 1.00, 1.02; p = 0.003]), GCS (HR 0.88 [95%CI: 0.81, 0.96; p = 0.003]), and IVH (HR 2.23 [95%CI: 1.25, 3.98; p = 0.007]) were all associated with increased mortality. Percentage growth (cumulative OR 0.84 [95%CI: 0.75, 0.92; p < 0.0001]), initial ICH volume (cumulative OR 0.94 [95%CI: 0.91, 0.97; p < 0.0001]), GCS (cumulative OR 1.46 [95%CI: 1.21, 1.82; p < 0.0001]), and age (cumulative OR 0.95 [95%CI: 0.92, 0.98; p= 0.0009]) predicted outcome modified Rankin Scale. Gender, location, blood glucose, and blood pressure did not predict outcomes. Conclusions: Hematoma growth is an independent determinant of both mortality and functional outcome after intracerebral hemorrhage. Attenuation of growth is an important therapeutic strategy.展开更多
Background and Purpose - Hematoma growth occurs in 38% of intracerebral hemorrhage (ICH) patients scanned by computed tomography (CT) within 3 hours of onset. Activated recombinant factor VII (rFVIIa) promotes hemosta...Background and Purpose - Hematoma growth occurs in 38% of intracerebral hemorrhage (ICH) patients scanned by computed tomography (CT) within 3 hours of onset. Activated recombinant factor VII (rFVIIa) promotes hemostasis at sites of vascular injury and may minimize hematoma growth after ICH. Methods - In this randomized, double- blind, placebo- controlled, dose- escalation trial, 48 subjects with ICH diagnosed within 3 hours of onset were treated with placebo (n= 12) or rFVIIa (10, 20, 40, 80, 120, or 160 μ g/kg; n=6 per group). The primary endpoint was the frequency of adverse events (AEs). Safety assessments included serial electrocardiography (ECG), troponin I and coagulation testing, lower extremity Doppler ultrasonography, and calculation of edema:ICH volume ratios. Results - Mean age was 61 years (range, 30 to 93) and 57% were male. At admission, mean National Institutes of Health Stroke Scale (NIHSS) score was 14 (range, 1 to 26), median Glasgow Coma Scale score was 14 (range, 6 to 15), and mean ICH volume was 21 mL (range, 1 to 151). Mean time from onset to treatment was 181 minutes (range, 120 to 265). Twelve serious AEs occurred, including 5 deaths (mortality 11% ). Six AEs were considered possibly treatment- related, including rash, vomiting, fever, ECG T- wave inversion, and 2 cases of deep vein thrombosis (placebo and 20- μ g/kg groups). No myocardial ischemia, consumption coagulopathy, or dose- related increase in edema:ICH volume occurred. Conclusion - This small phase II trial evaluated a wide range of rFVIIa doses in acute ICH and raised no major safety concerns. Larger studies are justified to determine whether rFVIIa can safely and effectively limit ICH growth.展开更多
文摘Background: Although volume of intracerebral hemorrhage (ICH) is a predictor of mortality, it is unknown whether subsequent hematoma growth further increases the risk of death or poor functional outcome. Methods: To determine if hematoma growth independently predicts poor outcome, the authors performed an individual meta-analysis of patients with spontaneous ICH who had CT within 3 hours of onset and 24-hour follow-up. Placebo patients were pooled from three trials investigating dosing, safety, and efficacy of rFVIIa (n = 115), and 103 patients from the Cincinnati study (total 218). Other baseline factors included age, gender, blood glucose, blood pressure, Glasgow Coma Score (GCS), intraventricular hemorrhage (IVH), and location. Results: Overall, 72.9%of patients exhibited some degree of hematoma growth. Percentage hematoma growth (hazard ratio [HR] 1.05 per 10%increase [95%CI: 1.03, 1.08; p < 0.0001]), initial ICH volume (HR 1.01 per mL [95%CI: 1.00, 1.02; p = 0.003]), GCS (HR 0.88 [95%CI: 0.81, 0.96; p = 0.003]), and IVH (HR 2.23 [95%CI: 1.25, 3.98; p = 0.007]) were all associated with increased mortality. Percentage growth (cumulative OR 0.84 [95%CI: 0.75, 0.92; p < 0.0001]), initial ICH volume (cumulative OR 0.94 [95%CI: 0.91, 0.97; p < 0.0001]), GCS (cumulative OR 1.46 [95%CI: 1.21, 1.82; p < 0.0001]), and age (cumulative OR 0.95 [95%CI: 0.92, 0.98; p= 0.0009]) predicted outcome modified Rankin Scale. Gender, location, blood glucose, and blood pressure did not predict outcomes. Conclusions: Hematoma growth is an independent determinant of both mortality and functional outcome after intracerebral hemorrhage. Attenuation of growth is an important therapeutic strategy.
文摘Background and Purpose - Hematoma growth occurs in 38% of intracerebral hemorrhage (ICH) patients scanned by computed tomography (CT) within 3 hours of onset. Activated recombinant factor VII (rFVIIa) promotes hemostasis at sites of vascular injury and may minimize hematoma growth after ICH. Methods - In this randomized, double- blind, placebo- controlled, dose- escalation trial, 48 subjects with ICH diagnosed within 3 hours of onset were treated with placebo (n= 12) or rFVIIa (10, 20, 40, 80, 120, or 160 μ g/kg; n=6 per group). The primary endpoint was the frequency of adverse events (AEs). Safety assessments included serial electrocardiography (ECG), troponin I and coagulation testing, lower extremity Doppler ultrasonography, and calculation of edema:ICH volume ratios. Results - Mean age was 61 years (range, 30 to 93) and 57% were male. At admission, mean National Institutes of Health Stroke Scale (NIHSS) score was 14 (range, 1 to 26), median Glasgow Coma Scale score was 14 (range, 6 to 15), and mean ICH volume was 21 mL (range, 1 to 151). Mean time from onset to treatment was 181 minutes (range, 120 to 265). Twelve serious AEs occurred, including 5 deaths (mortality 11% ). Six AEs were considered possibly treatment- related, including rash, vomiting, fever, ECG T- wave inversion, and 2 cases of deep vein thrombosis (placebo and 20- μ g/kg groups). No myocardial ischemia, consumption coagulopathy, or dose- related increase in edema:ICH volume occurred. Conclusion - This small phase II trial evaluated a wide range of rFVIIa doses in acute ICH and raised no major safety concerns. Larger studies are justified to determine whether rFVIIa can safely and effectively limit ICH growth.
