Ginsberg Myron D, Hill Michael D, Palesch Yuko Y, Ryckborst Karla J, Tamariz Diego
Department of Neurology (D4-5), University of Miami Miller School of Medicine, PO Box 016960, Miami, Florida 33101, USA.
Stroke. 2006 Aug;37(8):2100-6. doi: 10.1161/01.STR.0000231388.72646.05. Epub 2006 Jun 29.
In preclinical stroke models, high-dose human albumin confers robust neuroprotection. We investigated the safety and tolerability of this therapy in patients with acute ischemic stroke.
The ALIAS (Albumin in Acute Stroke) Pilot Clinical Trial used a multiple-tier, open-label, dose-escalation design. Subjects with acute ischemic stroke (NIH Stroke Scale [NIHSS] of 6 or above) received a 2-hour infusion of 25% human albumin (ALB) beginning within 16 hours of stroke onset. Six successive ALB dose tiers were assessed ranging from 0.34 to 2.05 g/kg. Neurologic and cardiac function was sequentially monitored. At 3 months, the NIHSS, modified Rankin Scale, and Barthel Index were measured.
Eighty-two subjects (mean age, 65 years) received ALB at 7.8+/-3.4 hours after stroke onset (mean+/-standard deviation). Forty-two patients also received standard-of-care intravenous tissue plasminogen activator (tPA). Vital signs were unaltered by ALB treatment. Dose-related increases in plasma albumin and mild hemodilution were maximal at 4 to 12 hours. Age-related plasma brain natriuretic peptide levels increased at 24 hours after ALB but did not predict cardiac adverse events. The sole ALB-related adverse event was mild or moderate pulmonary edema in 13.4% of subjects, which was readily managed with diuretics. In the tPA-treated subgroup, symptomatic intracranial hemorrhage occurred in only one of 42 subjects.
Twenty-five percent human albumin in doses ranging up to 2.05 g/kg was tolerated by patients with acute ischemic stroke without major dose-limiting complications. tPA therapy did not affect the safety profile of ALB. The companion article presents neurologic outcome data and efficacy analysis in these subjects.
在临床前卒中模型中，高剂量人白蛋白具有强大的神经保护作用。我们研究了该疗法在急性缺血性卒中患者中的安全性和耐受性。
ALIAS（急性卒中白蛋白）试点临床试验采用多层、开放标签、剂量递增设计。急性缺血性卒中患者（美国国立卫生研究院卒中量表[NIHSS]评分为6分及以上）在卒中发作后16小时内接受25%人白蛋白（ALB）2小时输注。评估了6个连续的ALB剂量层级，范围从0.34至2.05 g/kg。对神经和心脏功能进行了连续监测。在3个月时，测量NIHSS、改良Rankin量表和Barthel指数。
82名受试者（平均年龄65岁）在卒中发作后7.8±3.4小时接受了ALB治疗（平均值±标准差）。42名患者还接受了标准治疗的静脉注射组织型纤溶酶原激活剂（tPA）。ALB治疗未改变生命体征。血浆白蛋白与剂量相关的增加和轻度血液稀释在4至12小时时最大。与年龄相关的血浆脑钠肽水平在ALB治疗后24小时升高，但未预测心脏不良事件。唯一与ALB相关的不良事件是13.4%的受试者出现轻度或中度肺水肿，使用利尿剂可轻松处理。在接受tPA治疗的亚组中，42名受试者中只有1人发生了症状性颅内出血。
急性缺血性卒中患者能够耐受高达2.05 g/kg剂量的25%人白蛋白，且无主要的剂量限制并发症。tPA治疗不影响ALB的安全性。配套文章介绍了这些受试者的神经学结局数据和疗效分析。
