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

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.