Department of Anesthesiology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
Institute of Functional Genomics, University of Regensburg, Regensburg, Germany.
Neurocrit Care. 2019 Aug;31(1):32-39. doi: 10.1007/s12028-019-00676-w.
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.
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.
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.
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.
口服尼莫地平用于预防和治疗颅内动脉瘤或中脑周围蛛网膜下腔出血(SAH)患者的迟发性脑缺血。在严重难治性脑血管痉挛的情况下,可能需要持续的动脉内(IA)尼莫地平输注(CIAN)以避免脑缺血。尼莫地平可能导致需要减少剂量或停止治疗的动脉低血压。本研究的目的是检查不同尼莫地平制剂对颅内动脉瘤或中脑周围 SAH 患者动脉血压的影响,并测量口服片剂或溶液和 IA 输注后尼莫地平的血浆水平。
在一项前瞻性研究中,在 1 年的观察期内,对 38 例在重症监护病房接受颅内动脉瘤或中脑周围 SAH 治疗的患者的动脉血压和尼莫地平剂量进行了数据收集。此外,通过液相色谱-串联质谱法测量了尼莫地平的血浆浓度。
每天 4 小时口服 60mg 尼莫地平的全剂量仅能在 57.2%的检查日给药。在治疗的前 14 天内观察到 97 次与尼莫地平给药相关的动脉低血压发作。与片剂相比,尼莫地平口服液给药后血压下降的发生率约高 3 倍。然而,两种制剂之间的尼莫地平血浆水平没有差异。在患有较高等级 SAH 的患者中,动脉低血压和随后的尼莫地平剂量减少或停药比在患有较低等级 SAH 的患者中更频繁。CIAN 期间的尼莫地平血浆浓度未超过口服给药时的水平。
在较高等级的 SAH 患者中,经常需要减少或停止口服尼莫地平的剂量。口服尼莫地平溶液比片剂更频繁地导致血压下降。小于 1mg/h 的 IA 输注速率导致静脉血浆中尼莫地平的浓度与口服应用 60mg 每 4 小时相似。