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Objectives: To determine the safety and tolerability of super-selective intra-arterial magnesium sulfate in combination with intra-arterial nicardipine in patients with cerebral vasospasm after subarachnoid hemorrhage.Methods: Patients were treated in a prospective protocol at two teaching medical centers. Emergent cerebral angiography was performed if there was either clinical, ultrasound, and/or computed tomographic (CT) perfusion deficits suggestive of cerebral vasospasm. Intra-arterial magnesium sulfate (0.25-1 g) was administered via a microcatheter in the affected vessels in combination with nicardipine (2.5-20.0 mg). Mean arterial pressures (MAP) and intracranial pressures (ICP) were monitored during the infusion. Immediate and sustained angiographic and clinical improvement was determined from post-treatment angiograms and clinical follow-up. Angiographic and clinical outcomes were compared to two published case series that has used nicardipine alone.Results: A total of 58 vessels were treated in 14 patients (mean age 42 years; 11 women) with acute subarachnoid hemorrhage. The treatment was either intra-arterial nicardipine and magnesium sulfate alone or in conjunction with primary angioplasty. Forty vessels (69%) had immediate angiographic improvement with intra-arterial nicardipine and magnesium sulfate alone and 18 vessels (31%) required concomitant balloon angioplasty with complete reversal of the vasospasm. Retreatment was required in 13 vessels (22%) and the median time for retreatment was 2 days (range 1-13 days). Nicardipine treatment resulted in the reduction of MAP (12.3 mmHg, standard error [SE] 1.34, P-value <0.0001) without any significant change in ICP. Magnesium sulfate infusion was not associated with change in MAP or ICP. Among 31 procedures, immediate neurological improvement was observed in 22 (71%) procedures. In 12 (86%) patients, there were no infarctions in the follow-up CT scan acquired between 24 and 48 h. No statistical significant difference was observed in angiographic and clinical outcome of patients treated with the combination therapy in comparison with historical controls treated with nicardipine alone.Conclusion: Administration of intra-arterial magnesium sulfate in combination with nicardipine was well tolerated in patients with subarachnoid hemorrhage and cerebral vasospasm without a significant change in MAP and ICP. The efficacy of this combination therapy should be evaluated in a larger, controlled setting. [ABSTRACT FROM AUTHOR]