Reversal of Severe Cerebral Vasospasm in Three Patients after Aneurysmal Subarachnoid Hemorrhage: Initial Observations Regarding the Use of Intraventricular Sodium Nitroprusside in Humans

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Abstract
The chronic delayed type of cerebral vasoconstriction that occurs after aneurysmal subarachnoid hemorrhage (SAH) is now the most important cause of mortality and neurological morbidity for patients who initially survive the rupture of cerebral aneurysms. Although intravascular volume expansion and cardiac performance enhancement have had a profound impact on the treatment of the chronic delayed type of cerebral vasoconstriction, this form of treatment is not tolerated by all patients and is unhelpful in some. A more specific and more reliable treatment for this condition has not been previously reported. Previous work in an animal model has demonstrated the efficacy of nitric oxide-donating compounds in reversing severe cerebral vasoconstriction when delivered to the adventitial side of the blood vessel. A clinical study was initiated after receiving approval from the United States Food and Drug Administration and the institutional review board. Three cases of prompt and substantial reversal of medically refractory vasospasm occurring after aneurysmal SAH in humans using an intrathecally administered nitric oxide donor and clinical, angiographic, and ultrasonographic documentation are presented. All patients developed severe vasospasm refractory to medical treatment 5 to 12 days after sustaining aneurysmal SAH. All patients manifested stupor of new onset (Glasgow Coma Scale score of 7) and new focal neurological deficit (hemiplegia). The condition was angiographically demonstrated in all cases. The patients were treated with intrathecally administered sodium nitroprusside, which caused the reversal of vasospasm, which was documented 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 parameters were not observed during or after the procedures. Radiographic evidence of the reversal of vasospasm and brain ischemia was obtained. The clinical outcomes of the treated patients were excellent. All patients presented with hemiplegia and stupor that resolved or markedly improved (within several days, two patients; within 12 hours, one patient). All three patients were discharged and were living at home at the time of manuscript submission. These preliminary observations suggest that sodium nitroprusside delivered by an intrathecal route of administration may be a useful treatment for severe vasospasm complicating SAH in humans.