RESUMEN
BACKGROUND: Oral nimodipine is used for prophylaxis and treatment of delayed cerebral ischemia in patients with aneurysmal or perimesencephalic subarachnoid hemorrhage (SAH). In cases of serious refractory cerebral vasospasm, a continuous intra-arterial (IA) infusion of nimodipine (CIAN) may be required to avoid cerebral ischemia. Nimodipine can cause arterial hypotension requiring either a dosage reduction or its discontinuation. Aim of the present study was to examine the effect of different nimodipine formulations on arterial blood pressure in aneurysmal or perimesencephalic SAH patients and to measure the plasma levels after both, peroral administration as tablet or solution and IA infusion. METHODS: In a prospective setting, over a 1-year observation period, data on the course of arterial blood pressure and nimodipine dosage were collected for 38 patients undergoing treatment for aneurysmal or perimesencephalic SAH in an intensive care unit. In addition, plasma concentrations of nimodipine were measured by liquid chromatography-tandem mass spectrometry. RESULTS: The intended full dose of 60 mg of nimodipine given orally every 4 h could only be administered on 57.2% of the examined days. Ninety-seven episodes of relevant arterial hypotension probably caused by the administration of nimodipine were observed within the first 14 days of treatment. Drops in blood pressure occurred about three times as often after administration of nimodipine as oral solution than as tablet. However, there were no differences in nimodipine plasma levels between the two formulations. In patients suffering from higher-grade SAH, arterial hypotension and consequent dosage reduction or discontinuation of nimodipine were more frequent than in patients with lower-grade SAH. Plasma concentrations of nimodipine during CIAN did not exceed those achieved by oral administration. CONCLUSIONS: Dosage reduction or discontinuation of oral nimodipine is often necessary in patients with higher-grade SAH. Oral nimodipine solutions cause drops in blood pressure more frequently than tablets. Intra-arterial infusion rates of less than 1 mg/h result in venous plasma concentrations of nimodipine similar to those observed after oral application of 60 mg every 4 h.