Etminan Nima, Vergouwen Mervyn D I, Macdonald R Loch
Department of Neurosurgery, Heinrich-Heine University, Duesseldorf, Germany.
Acta Neurochir Suppl. 2013;115:33-40. doi: 10.1007/978-3-7091-1192-5_8.
Despite a significant reduction of angiographic vasospasm, the reduction of poor functional outcome in clinical trials on aneurysmal subarachnoid hemorrhage (SAH) remains challenging. While there is general consensus that vasospasm is associated with delayed cerebral ischemia (DCI), cerebral infarction, poor functional outcome, and mortality after SAH, causal relationships are subject to discussion. Therefore, it was the aim of our study to investigate the relationship between various outcome measures and poor functional outcome in clinical trials on pharmaceutical treatment of SAH.
Based on data from two systematic reviews and a post hoc exploratory analysis, the relationship between the following outcome measures was investigated: (1) radiographic vasospasm, (2) DCI, (3) cerebral infarction, (4) poor functional outcome, and (5) death.
A reduction of angiographic vasospasm did not correlate with an improvement on dichotomous Glasgow Outcome Scale/modified Rankin Scale (GOS/mRS). In contrast, a reduction of cerebral infarction correlated with better neurological outcomes. The heterogeneous definition of DCI in previous clinical trials did not allow pooling of the data.
Future clinical trials may use cerebral infarction and functional outcome as main outcome measures to -investigate the true impact of an intervention, assuming that the intervention targets cerebral infarction and hereby improves outcome.
尽管血管造影显示的血管痉挛有显著减轻,但在动脉瘤性蛛网膜下腔出血(SAH)的临床试验中,降低不良功能结局仍具有挑战性。虽然人们普遍认为血管痉挛与SAH后的迟发性脑缺血(DCI)、脑梗死、不良功能结局和死亡率有关,但因果关系仍有待探讨。因此,我们研究的目的是在SAH药物治疗的临床试验中,研究各种结局指标与不良功能结局之间的关系。
基于两项系统评价的数据和一项事后探索性分析,研究了以下结局指标之间的关系:(1)影像学血管痉挛,(2)DCI,(3)脑梗死,(4)不良功能结局,(5)死亡。
血管造影显示的血管痉挛减轻与二分制格拉斯哥预后量表/改良Rankin量表(GOS/mRS)的改善无关。相反,脑梗死的减轻与更好的神经功能结局相关。既往临床试验中DCI的定义不统一,无法合并数据。
未来的临床试验可将脑梗死和功能结局作为主要结局指标,以研究干预措施的真正效果,前提是该干预措施针对脑梗死并由此改善结局。