Reversal of severe cerebral vasospasm in three patients after aneurysmal subarachnoid hemorrhage: Initial observations regarding the use of intraventricular sodium nitroprusside in humans

OBJECTIVE AND IMPORTANCE: The chronic delayed type of cerebral vasoconstric tion that occurs after aneurysmal subarachnoid hemorrhage (SAH) is now the most important cause of mortality and neurological morbidity for patients w ho initially survive the rupture of cerebral aneurysms. Although intravascu lar volume expansion and cardiac performance enhancement have had a profoun d impact on the treatment of the chronic delayed type of cerebral vasoconst riction, this form of treatment is not tolerated by all patients and is unh elpful in some. A more specific and more reliable treatment for this condit ion has not been previously reported. Previous work in an animal model has demonstrated the efficacy of nitric oxide-donating compounds in reversing s evere cerebral vasoconstriction when delivered to the adventitial side of t he blood vessel. A clinical study was initiated after receiving approval fr om the United States Food and Drug Administration and the institutional rev iew board. CLINICAL PRESENTATION: Three cases of prompt and substantial reversal of me dically refractory vasospasm occurring after aneurysmal SAH in humans using an intrathecally administered nitric oxide donor and clinical, angiographi c, and ultrasonographic documentation are presented. All patients developed severe vasospasm refractory to medical treatment 5 to 12 days after sustai ning aneurysmal SAH. All patients manifested stupor of new onset (Glasgow C oma Scale score of 7) and new focal neurological deficit (hemiplegia). The condition was angiographically demonstrated in all cases. INTERVENTION: The patients were treated with intrathecally administered sod ium nitroprusside, which caused the reversal of vasospasm, which was docume nted by angiography and transcranial Doppler ultrasonography up to 54 hours later and also by dramatic clinical improvement. Complications related to intracranial pressure elevation, changes in vital signs, and hemodynamic pa rameters were not observed during or after the procedures. Radiographic evi dence of the reversal of vasospasm and brain ischemia was obtained. The cli nical outcomes of the treated patients were excellent. All patients present ed with hemiplegia and stupor that resolved or markedly improved (within se veral days, two patients; within 12 hours, one patient). All three patients were discharged and were living at home at the time of manuscript submissi on. CONCLUSION: These preliminary observations suggest that sodium nitroprussid e delivered by an intrathecal route of administration may be a useful treat ment for severe vasospasm complicating SAH in humans.