Best evidence in anesthetic practice 0Recombinant activated factor VII for acute intracerebral hemorrhage: a promising therapy for a devastating problem?

摘要

Question: In patients with acute intracerebral hemorrhage (ICH), can recombinant factor VIIa (rFVIIa) reduce hematoma growth and improve clinical outcomes?Design: Multicentre, randomized, double-blind, placebo-controlled trial of three different doses of rFVIIa.Setting: Seventy-three hospitals in 20 countries.Patients: Three hundred and ninety-nine patients with computed tomographic (CT) scan-documented ICH within three hours of the onset of symptoms. Exclusion criteria included pregnancy; Glasgow Coma Scale score > 2; planned surgical evacuation within 24 hr; hemorrhage secondary to aneurysm, arteriovenous malformation, or trauma; use of oral anticoagulants; thrombocytopenia; preexisting coagulopathy or disseminated intravascular coagulation; crush injury; acute sepsis; a preexisting neurologic disability; or any history of symptomatic thrombotic or vaso-occlusive disease. Baseline characteristics were similar between groups.Intervention: One hundred and eight, 92, and 103 patients were allocated to receive a single dose of 40 mug centre kg~(-1), 80 mug centre kg~(-1), or 160 mug centre kg~(-1) rFVIIa respectively. Ninety-six patients were allocated to receive a placebo equivalent. The intervention was given within one hour of baseline CT, and no later than four hours after the onset of symptoms.Main outcomes: The primary outcome was the percentage change in the volume of ICH from baseline to 24 hr on CT scan as analyzed by two neuroradiologistsblinded to allocation. Secondary outcomes included the percentage change in volume of ICH from baseline to 72 hr, and scores from the Glasgow Coma Scale, the National Institutes of Health StrokeScale, the modified Rankin Scale, the Extended Glasgow Outcome Scale, and the Barthel Index based on clinical assessments performed on days one, two, three, 15 and 90.Main results: The mean increase in the hematoma volume was 29% in the placebo group, as compared to 16%, 14%, and 11% in the groups given 40, 80, and 160 mug centre kg~(-1) rFVIIa, respectively. Growth in the volume of intracerebral hemorrhage was reduced by 3.3 mL, 4.5 mL, and 5.8 mL in the three treatment groups, as compared with that in the placebo group (P = 0.01). Sixty-nine percent of placebo-treated patients died or were severely disabled (modified Rankin Scale score of 4-6), as compared to 55%, 49%, and 54% of the patients who received 40, 80, and 160 mug centre kg~(-1) rFVIIa, respectively. There was a trend towards higher rates of serious thromboembolic adverse events (mainly myocardial or cerebral infarction) in the three treatment groups when compared to the placebo group (7% vs 2%, P = 0.12). Mortality at 90 days was 29% for patients who received placebo, as compared with 18% in the three rFVIIa groups combined (P = 0.02).Conclusion: Treatment with rFVIIa within four hours after the onset of intracerebral hemorrhage limits the growth of the hematoma, reduces mortality, and improves functional outcomes at 90 days.