Departments of Critical Care Medicine & Clinical Neurosciences, University of Calgary, Room EG23 J, Foothills Medical Center, 403 29th St NW, Calgary, AB T2N 2T9, Canada.
Neurocrit Care. 2011 Jun;14(3):489-99. doi: 10.1007/s12028-010-9429-z.
The volume and clearance rate of blood in the basal cisterns and ventricles are important predictors of complications following aneurysmal subarachnoid hemorrhage (SAH). Thus, there is a strong rationale for interventions aimed at accelerating the clearance of blood.
We systematically searched MEDLINE, EMBASE, Cochrane databases, references of review articles and gray literature sources to identify randomized controlled trials (RCTs) assessing the efficacy of locally-administered, intrathecal thrombolytics in patients with SAH. Primary outcomes included the occurrence of poor neurologic recovery and delayed neurologic deficits (DNDs). Secondary outcomes included angiographic vasospasm, chronic hydrocephalus and treatment-related complications. Data were extracted and appraised independently and in duplicate, using standardized forms. Fixed or random effects models, as appropriate based on the degree of study heterogeneity were applied to calculate summary measures.
Five RCTs, enrolling 465 patients, met eligibility criteria. The methodology, results and risk of bias varied considerably across individual studies. Overall, use of intrathecal thrombolytics was associated with significant reductions in the development of poor outcomes (OR 0.52, 0.34-0.78, P < 0.01), DNDs (OR 0.54, 0.34-0.87, P = 0.01), angiographic vasospasm (OR 0.32, 0.15-0.70, P < 0.01) and chronic hydrocephalus (OR 0.33, 0.15-0.74, P < 0.01), without any increment in hemorrhagic or infectious complications. These findings were dampened by the exclusion of a study which concomitantly administered intrathecal vasodilators and thrombolytics.
Current data suggests that intrathecal thrombolytics improve outcomes following SAH. However, there are important limitations to existing RCTs, with considerable risk of bias. Further standardization of techniques and evaluation in larger, more rigorous RCTs is required.
基底池和脑室中的血液体积和清除率是预测蛛网膜下腔出血（SAH）后并发症的重要指标。因此，有充分的理由进行旨在加速血液清除的干预。
我们系统地检索了 MEDLINE、EMBASE、Cochrane 数据库、综述文章的参考文献和灰色文献来源，以确定评估鞘内局部给予溶栓药物治疗 SAH 患者疗效的随机对照试验（RCT）。主要结局包括不良神经恢复和迟发性神经功能缺损（DND）的发生。次要结局包括血管痉挛、慢性脑积水和与治疗相关的并发症。数据由两人独立提取和评估，使用标准化表格。根据研究异质性的程度，应用固定或随机效应模型计算汇总指标。
五项 RCT 共纳入 465 例患者，符合入选标准。各项研究的方法、结果和偏倚风险差异很大。总体而言，鞘内溶栓药物的使用与不良结局（OR 0.52，0.34-0.78，P < 0.01）、DND（OR 0.54，0.34-0.87，P = 0.01）、血管痉挛（OR 0.32，0.15-0.70，P < 0.01）和慢性脑积水（OR 0.33，0.15-0.74，P < 0.01）的发生率降低有关，且未增加出血或感染并发症。排除同时给予鞘内血管扩张剂和溶栓药物的研究后，这些发现有所减弱。
目前的数据表明，鞘内溶栓药物可改善 SAH 后的结局。然而，现有 RCT 存在重要的局限性，存在较大的偏倚风险。需要在更大、更严格的 RCT 中进一步规范技术和评估。
