Saito I, Asano T, Sano K, Takakura K, Abe H, Yoshimoto T, Kikuchi H, Ohta T, Ishibashi S
Department of Neurosurgery, School of Medicine, Kyorin University, Tokyo, Japan.
Neurosurgery. 1998 Feb;42(2):269-77; discussion 277-8. doi: 10.1097/00006123-199802000-00038.
The effect of ebselen, a seleno-organic compound with antioxidant activity through a glutathione peroxidase-like action, on the outcome of subarachnoid hemorrhage was evaluated in a multicenter placebo-controlled double-blind clinical trial.
Patients who suffered aneurysmal subarachnoid hemorrhages of Hunt and Kosnik Grades II through IV at admission and were able to start drug treatment within 96 hours of the ictus were enrolled. Early surgery was performed whenever possible. Oral administration of ebselen granules suspended in water (150 mg, twice a day) or placebo was started immediately after admission and continued for 2 weeks. The major end points were the Glasgow Outcome Scale at 2 weeks, 1 month, and 3 months after the start of treatment. The incidence of delayed ischemic neurological deficits clinically diagnosed as resulting from vasospasm and the incidence and extent of low-density areas on postoperative computed tomographic scans were also studied as secondary outcome measures.
Intent-to-treat analysis of the 286 patients enrolled in the trial (145 patients administered ebselen and 141 administered placebo) revealed that the incidence of clinically diagnosed delayed ischemic neurological deficits was unaltered. There were 52 (receiving ebselen) and 58 (receiving placebo) patients with delayed deficits; however, a significantly better outcome was observed after ebselen treatment than after placebo (P = 0.005, chi2 test). There was a corresponding decrease in the incidence and extent of low-density areas (P = 0.032, Wilcoxon rank sum test).
Ebselen reduced brain damage in patients with delayed neurological deficits after subarachnoid hemorrhage and may be a promising neuroprotective agent.
在一项多中心、安慰剂对照、双盲临床试验中，评估具有抗氧化活性的有机硒化合物依布硒啉（通过类谷胱甘肽过氧化物酶作用）对蛛网膜下腔出血预后的影响。
纳入入院时Hunt和Kosnik分级为Ⅱ至Ⅳ级的动脉瘤性蛛网膜下腔出血患者，且能够在发病96小时内开始药物治疗。尽可能早期进行手术。入院后立即开始口服悬浮于水中的依布硒啉颗粒（150毫克，每日两次）或安慰剂，并持续2周。主要终点为治疗开始后2周、1个月和3个月时的格拉斯哥预后量表评分。还研究了临床诊断为血管痉挛导致的迟发性缺血性神经功能缺损的发生率，以及术后计算机断层扫描低密度区的发生率和范围作为次要结局指标。
对试验中纳入的286例患者（145例服用依布硒啉，141例服用安慰剂）进行意向性分析显示，临床诊断的迟发性缺血性神经功能缺损的发生率未改变。有52例（服用依布硒啉）和58例（服用安慰剂）患者出现迟发性缺损；然而，依布硒啉治疗后的结局明显优于安慰剂（P = 0.005，卡方检验）。低密度区的发生率和范围相应降低（P = 0.032，Wilcoxon秩和检验）。
依布硒啉可减轻蛛网膜下腔出血后迟发性神经功能缺损患者的脑损伤，可能是一种有前景的神经保护剂。
