Peer-Review ReportEfficacy of Low-Dose Tissue-Plasminogen Activator Intracisternal Administration for the Prevention of Cerebral Vasospasm After Subarachnoid Hemorrhage
Introduction
Delayed cerebral vasospasm remains a major cause of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (SAH). The severity of cerebral vasospasm may be correlated with the volume and distribution of the subarachnoid clots. Many patients have been treated by evacuation of the subarachnoid hematoma in the early stages of ruptured aneurysm to prevent cerebral vasospasm (4, 7, 9, 13, 16, 20, 25). Fibrinolytic agents, such as urokinase or tissue plasminogen activator (t-PA), may be effective, but treatment with intracisternal t-PA might not prevent cerebral vasospasm caused by aneurysmal SAH (23). This treatment is also associated with severe risk of hemorrhagic complications such as intracranial hemorrhage. Therefore, evacuation of subarachnoid hematoma to prevent cerebral vasospasm is commonly accepted, but the optimal administration and dosage of fibrinolytic agents have not been established. Repeated low-dose administration with t-PA or continuous irrigation with urokinase might prevent cerebral vasospasm without severe complications (6, 7, 17, 18, 26). We believe that cisternal irrigation therapy with fibrinolytic agents is a potentially effective option if an appropriate dosage and safe administration method can be established, although previous investigations have not been promising (23).
The present study attempted to improve the functional outcome of patients with SAH by prevention of vasospasm, tried to confirm the efficacy of cisternal irrigation therapy with t-PA, and tried to establish the optimal protocol for t-PA by comparing intermittent administration and continuous irrigation with t-PA in patients with aneurysmal SAH.
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Patient Selection
The clinical trial protocol was reviewed and approval by Juntendo University Shizuoka Hospital ethical community. All patients or their legally authorized representatives provided written informed consent. This study included 60 consecutive patients presenting with SAH from February 2006 to May 2007. The etiology of SAH was the ruptured aneurysm in all patients. All patients were treated by surgical clipping. They were randomized into three groups by the stratified block randomization method
Patient Profile
The clinical characteristics of the 60 patients are summarized in Table 1. Mean age was 64.8 years old, and 40 patients were younger than 70 years old. The distribution of WFNS grades showed no statistical differences therefore the average neurological condition was moderate. The three groups had no significant differences in age, sex, or WFNS grade. The percentages of patients taking antiplatelet agents before onset were also not significantly different. The CT-based diagnosis and treatment
Discussion
Extensive removal of subarachnoid clot in the acute stage reduces the occurrence of vasospasm associated with ruptured aneurysm, as substances in the subarachnoid clot are widely accepted to induce vasospasm. Many previous investigations have shown that intracisternal administration of fibrinolytic agents can effectively remove subarachnoid clot and prevent the development of clinical vasospasm (3, 7, 9, 13, 20, 25). The present study confirmed that fibrinolytic therapy is effective in patients
Conclusions
Low-dose t-PA administration into the CSF space is safe and effective for clearance of subarachnoid clot, and may avoid hemorrhagic complications. The intermittent injection method effectively prevents the vasospasm after SAH. Further clinical study by randomized trials in multicenter studies is necessary.
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Conflict of interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.