Springborg J B, Møller C, Gideon P, Jørgensen O S, Juhler M, Olsen N V
Department of Neuroanaesthesia, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.
Acta Neurochir (Wien). 2007 Nov;149(11):1089-101; discussion 1101. doi: 10.1007/s00701-007-1284-z. Epub 2007 Sep 17.
Erythropoietin (EPO) is neuroprotective in experimental models of stroke and subarachnoid haemorrhage (SAH) and possibly in patients with thromboembolic stroke. We studied the efficacy and safety of EPO in patients with SAH.
A larger scale clinical trial was planned but preliminarily terminated because of a lower than expected inclusion rate. However, 73 patients were randomised to treatment with EPO (500 IU/kg/day for three days) or placebo. The primary endpoint was Glasgow Outcome Score at six months. We further studied surrogate measures of secondary ischaemia, i.e. transcranial Doppler (TCD) flow velocity, symptomatic vasospasm, cerebral metabolism (microdialysis) and jugular venous oximetry, biochemical markers of brain damage (S-100beta and neuron specific enolase) and blood-brain barrier integrity.
The limited sample size precluded our primary hypotheses being verified and refuted. However, data from this study are important for any other study of SAH and as much raw data as possible are presented and can be included in future meta analyses. On admission the proportion of patients in a poor condition was higher in the EPO group compared with the placebo group but the difference was statistically insignificant. In the EPO-treated patients the CSF concentration of EPO increased 600-fold. Except for a higher extracelullar concentration of glycerol in the EPO group probably caused by the poorer clinical condition of these patients, there were no statistically significant group differences in the primary or secondary outcome measures. EPO was well tolerated.
Beneficial effects of EPO in patients with SAH cannot be excluded or concluded on the basis of this study and larger scale trials are warranted.
促红细胞生成素（EPO）在中风和蛛网膜下腔出血（SAH）的实验模型中具有神经保护作用，在血栓栓塞性中风患者中可能也有作用。我们研究了EPO对SAH患者的疗效和安全性。
计划进行一项更大规模的临床试验，但由于纳入率低于预期而提前终止。然而，73例患者被随机分为接受EPO治疗组（500 IU/kg/天，共三天）或安慰剂组。主要终点是六个月时的格拉斯哥预后评分。我们进一步研究了继发性缺血的替代指标，即经颅多普勒（TCD）血流速度、症状性血管痉挛、脑代谢（微透析）和颈静脉血氧饱和度、脑损伤的生化标志物（S-100β和神经元特异性烯醇化酶）以及血脑屏障完整性。
样本量有限使我们无法证实或反驳主要假设。然而，本研究的数据对任何其他SAH研究都很重要，并且我们呈现了尽可能多的原始数据，这些数据可纳入未来的荟萃分析。入院时，EPO组病情较差的患者比例高于安慰剂组，但差异无统计学意义。接受EPO治疗的患者脑脊液中EPO浓度增加了600倍。除了EPO组细胞外甘油浓度较高（可能是由于这些患者临床状况较差所致）外，主要和次要结局指标在两组间无统计学显著差异。EPO耐受性良好。
基于本研究既不能排除也不能得出EPO对SAH患者有益的结论，因此有必要进行更大规模的试验。
