Safety of intrathecal sodium nitroprusside for the treatment and prevention of refractory cerebral vasospasm and ischemia in humans

Background ann Purpose-The delayed type of cerebral vasoconstriction known as cerebral vasospasm (DCV) remains an important cause of permanent neurolo gical 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 nitroprus side and results in 21 patients is reported. Methods-Candidates for treatment were patients with secured cerebral aneury sms presenting with clinical or radiographic SAH of grade 3 or higher. Pati ents with and without established DCV were treated. In 57% (12/21 patients) the diagnosis of severe DCV refractory to conventional treatment (HHH ther apy and nimodipine) was established before treatment. Ten patients received ITSNP prophylactically. All patients with established DCV were in grave ne urological condition before treatment. Procedures for vasospasm reversal we re performed under simultaneous angiographic control with extensive hemodyn amic and neurophysiologic monitoring. ITSNP was delivered by intraventricul ar or subdural catheter or by direct intraoperative suffusion. End points o f intervention for established DCV were (1) durable angiographic reversal o f vasoconstriction, (2) failure to effect reversal within 30 minutes, and ( 3) adverse effect. End points for DCV prevention were (1) post-SAM day 10 w ithout evidence of vasoconstriction and (2) adverse effect. Cerebral angiop lasty was used concomitantly in 9 treatments. The total number of treatment s recorded was 171, Results-The overall neurological outcome was good or excellent in 76% of pa tients (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 pres ented initially with severe neurological injury (clinical SAH grade 4). Ang iography demonstrated reversal or amelioration of vasoconstriction in 83% ( 5/6 cases) of established DCV treated by ITSNP alone. Among patients treate d prophylactically, none developed clinical DCV. Conclusions-These results suggest that ITSNP is a safe and potentially effe ctive treatment for established DCV and cerebral ischemia refractory to con ventional treatment. The preliminary results of prophylactic treatment are also favorable with regard to safety.