Elsevier

World Neurosurgery

Volume 73, Issue 6, June 2010, Pages 675-682
World Neurosurgery

Peer-Review Report
Efficacy of Low-Dose Tissue-Plasminogen Activator Intracisternal Administration for the Prevention of Cerebral Vasospasm After Subarachnoid Hemorrhage

https://doi.org/10.1016/j.wneu.2010.04.002Get rights and content

Background

Vasospasm is one of the important factors associated with the functional prognosis after subarachnoid hemorrhage (SAH). Intracisternal administration of thrombolytic agents to dissolve subarachnoid clots may be responsible for bleeding complications. The efficacy and safety of cisternal irrigation therapy using low-dose tissue plasminogen activator were evaluated.

Methods

Sixty patients with SAH were treated by surgical clipping, and randomly divided into three groups: 1) the control group (n = 20) treated only with baseline treatment; 2) the intermittent group (n = 20) received intermittent administration of clotlysis agent (tisokinase 960,000 IU); and 3) the continuous group (n = 20) received continuous irrigation using pH-adjusted lactate Ringer's solution containing tisokinase (96 IU/mL) infused at 20 mL/hr for 48 hours. The clearance of subarachnoid clots was measured by laboratory examinations and postoperative computed tomography. Ischemia-related vasospasm was evaluated by neurological status and computed tomography. Neurological outcome was evaluated by the modified Rankin scale at 3 months after onset.

Results

The subarachnoid clot was efficiently and significantly removed without major complication in the intermittent and continuous groups (P < 0.05). The incidence of ischemic lesion in the intermittent group was significantly lower than in the control group (P < 0.05). The intermittent group had significantly better neurological outcome than the control group (P < 0.05).

Conclusions

Cisternal irrigation therapy using low-dose tissue plasminogen activator is effective and safe. Intermittent injection is most effective and may decrease the risk of symptomatic vasospasm in patients with SAH.

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.

Section snippets

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.

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