Neurosurgical Unit, Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, UK.
J Neurosurg. 2010 Jun;112(6):1235-9. doi: 10.3171/2009.10.JNS09954.
In a previous randomized controlled trial, the authors demonstrated that acute erythropoietin (EPO) therapy reduced severe vasospasm and delayed ischemic deficits (DIDs) following aneurysmal subarachnoid hemorrhage. In this study, the authors aimed to investigate the potential interaction of neurovascular protection by EPO with age, sepsis, and concurrent statin therapy.
The clinical events of 80 adults older than 18 years and with < 72 hours of aneurysmal subarachnoid hemorrhage, who were randomized to receive 30,000 U of intravenous EPO-beta or placebo every 48 hours for a total of 3 doses, were analyzed by stratification according to age (< or > or = 60 years), sepsis, or concomitant statin therapy. End points in the trial included cerebral vasospasm and impaired autoregulation on transcranial Doppler ultrasonography, DIDs, and unfavorable outcome at discharge and at 6 months measured with the modified Rankin Scale and Glasgow Outcome Scale. Analyses were performed using the t-test and/or ANOVA for repeated measurements.
Younger patients (< 60 years old) or those without sepsis obtained benefits from EPO by a reduction in vasospasm, impaired autoregulation, and unfavorable outcome at discharge. Compared with nonseptic patients taking EPO, those with sepsis taking EPO had a lower absolute reticulocyte count (nonsepsis vs sepsis, 143.5 vs. 105.8 x 10(9)/L on Day 6; p = 0.01), suggesting sepsis impaired both hematopoiesis and neurovascular protection by EPO. In the EPO group, none of the statin users suffered DIDs (p = 0.078), implying statins may potentiate neuroprotection by EPO.
Erythropoietin-related neurovascular protection appears to be attenuated by old age and sepsis and enhanced by statins, an important finding for designing Phase III trials.
作者在先前的一项随机对照试验中证实，急性促红细胞生成素（EPO）治疗可减少蛛网膜下腔出血后严重血管痉挛和迟发性缺血性损伤（DID）。在这项研究中，作者旨在研究 EPO 的神经血管保护作用与年龄、脓毒症和同时使用他汀类药物治疗之间的潜在相互作用。
对 80 名年龄大于 18 岁且蛛网膜下腔出血时间小于 72 小时的成年人进行分析，他们被随机分为接受 30000U 静脉内 EPO-β或安慰剂，每 48 小时一次，共 3 个剂量。试验终点包括经颅多普勒超声检查的脑血管痉挛和自动调节受损、DID、出院和 6 个月时使用改良 Rankin 量表和格拉斯哥结局量表测量的不良结局。分析采用 t 检验和/或重复测量方差分析。
年轻患者（<60 岁）或无脓毒症患者通过减少血管痉挛、自动调节受损和出院时不良结局从 EPO 中获益。与接受 EPO 的非脓毒症患者相比，接受 EPO 的脓毒症患者的绝对网织红细胞计数较低（非脓毒症 vs 脓毒症，第 6 天分别为 143.5 和 105.8×109/L；p=0.01），这表明脓毒症既损害了造血功能，也损害了 EPO 的神经血管保护作用。在 EPO 组中，没有他汀类药物使用者发生 DID（p=0.078），这表明他汀类药物可能增强了 EPO 的神经保护作用。
EPO 相关的神经血管保护作用似乎被年龄和脓毒症减弱，被他汀类药物增强，这一发现对设计 III 期试验很重要。
