Aichner F T, Fazekas F, Brainin M, Pölz W, Mamoli B, Zeiler K
Department of Neurology and MR Institute, Leopold Franzens University Innsbruck, Austria.
Stroke. 1998 Apr;29(4):743-9. doi: 10.1161/01.str.29.4.743.
Experimental studies suggest a beneficial effect of hemodilution on acute ischemic stroke. This was not proven by previous multicenter trials in the clinical setting. Various reasons have been suggested for the failure of these studies, which we attempted to consider in the Multicenter Austrian Hemodilution Stroke Trial (MAHST).
MAHST is a randomized, double-blind, placebo-controlled study of hypervolemic hemodilution (HHD) within 6 hours of a clinically first ischemic stroke localized in the middle cerebral artery territory. The treatment consisted of 10% hydroxyethyl starch 200/0.5 (HES) and was tested against pure rehydration with Ringer's lactate over a period of 5 days. Our primary outcome measure was clinical improvement within 7 days as measured by the Graded Neurologic Scale (GNS). We performed an adaptive interim analysis to reevaluate the study goal after entering half of the projected number of patients (n = 200). At least 600 patients per group would have been required for significant results, and therefore we decided to terminate the trial.
Ninety-eight patients received HHD and 102 patients placebo. The baseline characteristics were comparable between both groups. In the HHD group the absolute reduction of the hematocrit was 2.5% on day 2 with a maximum of 3.7% on day 5, which compares with a reduction in the placebo group of 1% and 1.9%, respectively. Intention-to-treat analysis showed no significant difference of the change of the GNS scores between HHD-treated (median, -8.5; 95% confidence interval, -14.2 to -4.0) and placebo-treated patients (median, -6.0; 95% confidence interval, -11.0 to 0.0) on day 7, and GNS scores remained similar in both treatment groups throughout the trial. At 3 months, slightly more HHD patients showed complete independence on the Barthel Index (28 versus 24), and fewer HHD than placebo patients had died (13 versus 17), but these differences were not statistically significant. HHD treatment was not associated with any specific adverse event.
Mild HHD is safe but failed to demonstrate a significant beneficial effect over the pure rehydration regimen in patients with acute ischemic stroke.
实验研究表明血液稀释对急性缺血性卒中具有有益作用。但先前在临床环境中的多中心试验并未证实这一点。对于这些研究的失败提出了各种原因，我们试图在奥地利多中心血液稀释卒中试验（MAHST）中予以考虑。
MAHST是一项随机、双盲、安慰剂对照研究，针对首次临床诊断为大脑中动脉区域缺血性卒中且发病6小时内的患者进行高容量血液稀释（HHD）。治疗采用10%羟乙基淀粉200/0.5（HES），并与使用乳酸林格氏液单纯补液进行为期5天的对照试验。我们的主要结局指标是7天内通过神经功能分级量表（GNS）测量的临床改善情况。在纳入预计患者数量（n = 200）的一半后，我们进行了适应性中期分析以重新评估研究目标。为获得显著结果，每组至少需要600例患者，因此我们决定终止试验。
98例患者接受了HHD治疗，102例患者接受了安慰剂治疗。两组的基线特征具有可比性。在HHD组中，第2天血细胞比容的绝对降低为2.5%，第5天最大降低为3.7%，而安慰剂组第2天和第5天的降低分别为1%和1.9%。意向性分析显示，在第7天，接受HHD治疗的患者（中位数，-8.5；95%置信区间，-14.2至-4.0）与接受安慰剂治疗的患者（中位数，-6.0；95%置信区间，-11.0至0.0）的GNS评分变化无显著差异，且在整个试验过程中两个治疗组的GNS评分均保持相似。在3个月时，在巴氏指数上显示完全独立的HHD患者略多（28例对24例），且HHD组死亡患者少于安慰剂组（13例对17例），但这些差异无统计学意义。HHD治疗未伴有任何特定不良事件。
轻度HHD是安全的，但在急性缺血性卒中患者中，与单纯补液方案相比未能显示出显著的有益效果。
