Does Intracisternal Thrombolysis Prevent Vasospasm after Aneurysmal Subarachnoid Hemorrhage? A Meta-analysis

OBJECTIVE: Despite existing strategies for the treatment of vasospasm after aneurysmal subarachnoid hemorrhage, vasospasm remains a persistent contributor to death and disability. The intracisternal application of thrombolytic agents to dissolve subarachnoid clot has been advocated. The goal of this analysis was to assess the currently available evidence regarding the effectiveness of this treatment. METHODS: We conducted a systematic review of the published literature; all controlled trials were included. The outcomes of interest were delayed ischemic neurological deficits, poor Glasgow Outcome Scale scores, and death. A formal metaanalysis was performed with a random-effects model. RESULTS: The search revealed nine trials or trial subgroups (only one of which was randomized), with a total enrollment of 652 patients. Pooled results demonstrated beneficial effects of treatment, with absolute risk reductions of 14.4% (95% confidence interval, 6.5-22.5%; P < 0.001) for delayed ischemic neurological deficits, 9.5% (95% confidence interval, 4.2-14.8%; P < 0.01) for poor Glasgow Outcome Scale scores, and 4.5% (95% confidence interval, 1.5-7.5%; P < 0.05) for death. Regression analysis revealed that treatment effects did not significantly differ among the studies on the basis of the type of thrombolytic agent used (tissue plasminogen activator versus urokinase) or the method of administration (intraoperative versus postoperative) (P > 0.10). Studies that enrolled only patients at high risk for vasospasm seemed to demonstrate greater treatment effects. CONCLUSION: The meta-analysis suggests a clinically relevant and statistically significant beneficial effect of intracisternal thrombolysis. However, the results of the analysis are limited by the predominance of nonrandomized studies. Further randomized, blinded, placebo-controlled trials of high-risk patients would be justified.