Bader Edward R, Allam Mazen M, Harris Thomas Gw, Suchdev Neena, Loke Yoon Kong, Barlas Raphae
Department of Neurological Surgery, Albert Einstein College of Medicine, Montefiore Medical Center, New York, USA.
Department of Urological Surgery, Hereford County Hospital, Wye Valley NHS Trust, Hereford, UK.
Cochrane Database Syst Rev. 2025 Jan 17;1(1):CD013748. doi: 10.1002/14651858.CD013748.pub2.
BACKGROUND: Aneurysmal subarachnoid haemorrhage continues to cause a significant burden of morbidity and mortality despite advances in care. Trials investigating local administration of thrombolytics have reported promising results. OBJECTIVES: - To assess the effect of thrombolysis on improving functional outcome and case fatality following aneurysmal subarachnoid haemorrhage - To determine the effect of thrombolysis on the risk of cerebral artery vasospasm, delayed cerebral ischaemia, and hydrocephalus following subarachnoid haemorrhage - To determine the risk of complications of local thrombolysis in aneurysmal subarachnoid haemorrhage SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (last searched 9 March 2023), MEDLINE Ovid (1946 to 9 March 2023), and Embase Ovid (1974 to 9 March 2023). We also searched ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP). We performed forward and reverse citation tracking of included studies using Google Scholar. SELECTION CRITERIA: We included randomised controlled trials comparing subarachnoid thrombolysis via any route of administration into any anatomical site continuous with the subarachnoid space versus placebo, sham thrombolysis, or standard treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion in the review. We extracted study data and used version 2 of the Cochrane risk-of-bias tool for randomised trials to assess the risk of bias in the studies. We resolved any disagreement through discussion with a third author. Our primary outcome was poor functional outcome. Secondary outcomes were case fatality, haemorrhagic complications, cerebral artery vasospasm, delayed cerebral ischaemia, cerebral infarction, and hydrocephalus. We performed meta-analyses for each outcome and performed sensitivity analysis excluding studies at high risk of bias. We presented results as risk ratios (RRs) with 95% confidence intervals (CIs). We performed further sensitivity analysis by including all intervention groups from studies reporting more than one intervention group. For each outcome, we used the GRADE criteria to determine the certainty of the evidence. MAIN RESULTS: We included eight studies from six countries in this review. The studies had a total of 410 participants, of whom 205 received thrombolysis. We identified three ongoing trials. We assessed one trial as having a high risk of bias for all outcomes; we assessed the remainder as having a low risk of bias or some concerns. Thrombolysis likely results in a reduction in poor functional outcome when compared to placebo or standard care (29.4% versus 39.7%, RR 0.73, 95% CI 0.56 to 0.94; 8 studies, 408 participants; moderate-certainty evidence). Thrombolysis likely results in little to no difference in case fatality (12.8% versus 17.7%, RR 0.71, 95% CI 0.46 to 1.10; 8 studies, 408 participants; moderate-certainty evidence). Thrombolysis may result in little to no difference in haemorrhagic complications (10.3% versus 7.2%, RR 1.40, 95% CI 0.73 to 2.68; 6 studies, 341 participants; low-certainty evidence). Thrombolysis likely results in a reduction in cerebral artery vasospasm (32.9% versus 47.6%, RR 0.70, 95% CI 0.54 to 0.91; studies, participants; moderate-certainty evidence), and may result in a reduction in delayed cerebral ischaemia (23.8% versus 38.2%, RR 0.62, 95% CI 0.45 to 0.88; studies, participants; low-certainty evidence). Thrombolysis may result in little to no difference in cerebral infarction (28.6% versus 37.5%, RR 0.76, 95% CI 0.44 to 1.31; studies, participants; low-certainty evidence), and likely results in little to no difference in the risk of hydrocephalus (18.3% versus 24.1%, RR 0.77, 95% CI 0.54 to 1.10; studies, participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: There is some evidence that thrombolysis can probably improve outcomes after aneurysmal subarachnoid haemorrhage, without increasing the risk of haemorrhagic complications. Thrombolysis likely reduces the risk of poor functional outcome and cerebral artery vasospasm, and may reduce the risk of delayed cerebral ischaemia, but it likely makes little to no difference to case fatality or hydrocephalus, and may make little to no difference to the risk of cerebral infarction. However, the current evidence is still uncertain. The uncertainty is primarily due to the small total number of participants and outcome events. Data from further studies are required to confirm the efficacy of thrombolysis for improving outcomes after aneurysmal subarachnoid haemorrhage.
背景:尽管在治疗方面取得了进展,但动脉瘤性蛛网膜下腔出血仍然造成了巨大的发病和死亡负担。研究局部应用溶栓药物的试验报告了有前景的结果。 目的:- 评估溶栓对改善动脉瘤性蛛网膜下腔出血后的功能结局和病死率的影响 - 确定溶栓对蛛网膜下腔出血后脑动脉血管痉挛、迟发性脑缺血和脑积水风险的影响 - 确定动脉瘤性蛛网膜下腔出血局部溶栓并发症的风险 检索方法:我们检索了Cochrane对照试验中心注册库(最后检索时间为2023年3月9日)、MEDLINE Ovid(1946年至2023年3月9日)和Embase Ovid(1974年至2023年3月9日)。我们还检索了ClinicalTrials.gov和世界卫生组织国际临床试验注册平台(ICTRP)。我们使用谷歌学术对纳入研究进行了正向和反向引文跟踪。 入选标准:我们纳入了随机对照试验,这些试验比较了通过任何给药途径将溶栓药物注入与蛛网膜下腔连续的任何解剖部位与安慰剂、假溶栓或标准治疗。 数据收集与分析:两位综述作者独立选择纳入综述的研究。我们提取了研究数据,并使用Cochrane随机试验偏倚风险工具第2版评估研究中的偏倚风险。我们通过与第三位作者讨论解决了任何分歧。我们的主要结局是功能结局不良。次要结局是病死率、出血并发症、脑动脉血管痉挛、迟发性脑缺血、脑梗死和脑积水。我们对每个结局进行了荟萃分析,并进行了敏感性分析,排除了偏倚风险高的研究。我们将结果表示为风险比(RRs)及95%置信区间(CIs)。我们通过纳入报告多个干预组的研究中的所有干预组进行了进一步的敏感性分析。对于每个结局,我们使用GRADE标准确定证据的确定性。 主要结果:我们在本综述中纳入了来自六个国家的八项研究。这些研究共有410名参与者,其中205名接受了溶栓治疗。我们确定了三项正在进行的试验。我们评估一项试验在所有结局方面存在高偏倚风险;我们评估其余试验存在低偏倚风险或有一些担忧。与安慰剂或标准治疗相比,溶栓可能会降低功能结局不良的发生率(29.4%对39.7%,RR 0.73,95%CI 0.56至0.94;8项研究,408名参与者;中等确定性证据)。溶栓在病死率方面可能几乎没有差异(12.8%对17.7%,RR 0.71,95%CI 0.46至1.10;8项研究,408名参与者;中等确定性证据)。溶栓在出血并发症方面可能几乎没有差异(10.3%对7.2%,RR 1.40,95%CI 0.73至2.68;6项研究,341名参与者;低确定性证据)。溶栓可能会降低脑动脉血管痉挛的发生率(32.9%对47.6%,RR 0.70,95%CI 0.54至0.91;研究,参与者;中等确定性证据),并且可能会降低迟发性脑缺血的发生率(23.8%对38.2%,RR 0.62,95%CI 0.45至0.88;研究,参与者;低确定性证据)。溶栓在脑梗死方面可能几乎没有差异(28.6%对37.5%,RR 0.76,95%CI 0.44至1.31;研究,参与者;低确定性证据),并且在脑积水风险方面可能几乎没有差异(18.3%对24.1%,RR 0.77,95%CI 0.54至1.10;研究,参与者;中等确定性证据)。 作者结论:有一些证据表明,溶栓可能改善动脉瘤性蛛网膜下腔出血后的结局,而不会增加出血并发症的风险。溶栓可能会降低功能结局不良和脑动脉血管痉挛的风险,并且可能会降低迟发性脑缺血的风险,但对病死率或脑积水可能几乎没有影响,对脑梗死风险可能也几乎没有影响。然而,目前的证据仍然不确定。不确定性主要是由于参与者和结局事件的总数较少。需要进一步研究的数据来证实溶栓对改善动脉瘤性蛛网膜下腔出血后结局的疗效。
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