Safety of Intrathecal Sodium Nitroprusside for the Treatment and Prevention of Refractory Cerebral Vasospasm and Ischemia in Humans

Abstract

Background and Purpose —The delayed type of cerebral vasoconstriction known as cerebral vasospasm (DCV) remains an important cause of permanent neurological injury and death following aneurysmal subarachnoid hemorrhage despite best current medical therapy. The mechanism of DCV remains unknown. A new treatment for refractory DCV using intrathecally delivered sodium nitroprusside and results in 21 patients is reported. Methods —Candidates for treatment were patients with secured cerebral aneurysms presenting with clinical or radiographic SAH of grade 3 or higher. Patients with and without established DCV were treated. In 57% (12/21 patients) the diagnosis of severe DCV refractory to conventional treatment (HHH therapy and nimodipine) was established before treatment. Ten patients received ITSNP prophylactically. All patients with established DCV were in grave neurological condition before treatment. Procedures for vasospasm reversal were performed under simultaneous angiographic control with extensive hemodynamic and neurophysiologic monitoring. ITSNP was delivered by intraventricular or subdural catheter or by direct intraoperative suffusion. End points of intervention for established DCV were (1) durable angiographic reversal of vasoconstriction, (2) failure to effect reversal within 30 minutes, and (3) adverse effect. End points for DCV prevention were (1) post-SAH day 10 without evidence of vasoconstriction and (2) adverse effect. Cerebral angioplasty was used concomitantly in 9 treatments. The total number of treatments recorded was 171. Results —The overall neurological outcome was good or excellent in 76% of patients (16/21) overall and in 88.9% of patients (16/18) having at least a 1-month follow-up. Of the 5 patients with less-than-good outcome, 4 had presented initially with severe neurological injury (clinical SAH grade 4). Angiography demonstrated reversal or amelioration of vasoconstriction in 83% (5/6 cases) of established DCV treated by ITSNP alone. Among patients treated prophylactically, none developed clinical DCV. Conclusions —These results suggest that ITSNP is a safe and potentially effective treatment for established DCV and cerebral ischemia refractory to conventional treatment. The preliminary results of prophylactic treatment are also favorable with regard to safety.