Thrombolysis for aneurysmal subarachnoid haemorrhage.

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.