神经外科术后静脉输注万古霉素时血清和脑脊液药物浓度变化

摘要

目的 探讨神经外科术后患者静脉持续输注万占霉素的血清药代与药效学特点.方法 选择开颅术后保留脑室引流患者12例.术后12 h内开始以万古霉素0.5 g泵入60 min,然后以2 g/24 h匀速持续泵入,在不同时间点采集静脉血和脑脊液标本,测定万占霉素浓度.结果 万古霉素0.5 g泵入结束即刻血药浓度达峰值(26.19 ±9.38)mg/L,2 h后浓度最低(7.87±2.25)mg/L,12 h后相对稳定(10.10±3.40)mg/L～(12.87±4.89)mg/L.万古霉素血清稳态药物浓度超过耐甲氧西林金黄色葡萄球菌对万占霉素90%最小抑菌浓度(MIC90)敏感折点(2 mg/L)5倍以上,以此计算,24 h血清药物浓度-时间曲线下面积(AUC)与MIC90的比值AUC0-24/MIC90为124.7;AUC24-48/MIC90为144.23;AUC48-72/MIC90为138.9.结论 对于高度耐药菌株,为保证AUC/MIC90大于400而提高疗效,提高剂量可能是需要的.%Objective Pharmacokinetics/pharmacodynamics of vancomycin in serum were studied after continuous infusion.Method Twelve neurosurgical postoperative patients with ventricular drainage were enrolled in this study.In each patient,a loading dose of vancomycin of O.5 g was administered for 1 h followed by a continuous infusion of 2 g/d.Venous blood specimens were collected ,vancomycin concentration in specimens were measured by high performance liquid chromatography.Results The peak vancomycin concentrations in serum were (26.19 ±9.38)mg/L,trough concentration occurred in 2 h(7.87 ±2.25 )mg/L,the relative steady state concentrations of vancomycin in serum ( 10.10 ± 3.40 )mg/L ～ ( 12.87 ± 4.89 )mg/Lwere achieved in 12 h, which exceeded the 90% minimum inhibitory concentration(2 mg/L) of common pathogens( Staphylococcus), and they were more than 5 -fold of MIC90, area under the serum concentration curve AUC0-24/MIC90 was 124.7; AUC24-48/MIC90 was 144.23; AUC48-72/MIC90 was 138.9.Conclusions Higher dosage is possibly necessary in order to reach AUC/MIC90 ＞ 400 and better clinical outcome.