神经外科术后患者静脉持续输注较大剂量万古霉素时血清药物浓度的研究

Study on the serum concentration of vancomycin during continuous high dose intravenous infusion after neurological surgery

目的探讨神经外科术后患者静脉持续输注较大剂量万古霉时血清药物浓度变化规律,并初步观察其安全性。方法选择开颅术后保留脑室引流管,主管医生决定使用万古霉素的患者。开始以万古霉素1.0 g泵入1 h,后以3 g/24 h匀速持续泵入,顺序采静脉血标本,测定万古霉素浓度。结果共有24例患者入选,万古霉素负荷量1.0 g泵入结束即刻血药浓度为(34.27±19.50)mg/L,16 h浓度最低[(14.82±12.23)mg/L],24 h后相对稳定[(18.53±13.30)^(25.72±19.09)mg/L]。万古霉素血清稳态药物浓度可以达到耐甲氧西林金黄色菌葡萄球菌对万古霉素敏感折点(2 mg/L)10倍以上,以最低抑菌浓度为1 mg/L计算,血清AUC/MIC>400。所有入组患者未发现明显不良反应。结论较大剂量万古霉素(3 g/d)与既往常规剂量(2 g/d)相比,静脉持续输注时,血浆药物浓度可以达到良好的药代/药效动力学指标,且初步观察该治疗是安全的,但仍需进一步大样本的临床研究证实。

Objective To study the pharmacokinetics/pharmacodynamics of vancomycin in the serum after continuous infusion. Methods Twenty-four neurosurgical postoperative patients with ventricular drainage were enrolled in this study. A loading dose of vancomycin of 1.0 g was administered for 1 h followed by a continuous infusion of 3 g/24 h for each patient. Venous blood samples were collected. Results The peak vancomycin concentrations in the serum were （34.27±19.50）mg/L after 1 h, the trough concentration occurred in the 16th hour [（14.82±12.23）mg/L], the relative steady state concentrations of vancomyein in the serum [（18.53±13.30）±（25.72±19.09）mg/L] were achieved at the 24th h, which were 10 folds higher than the MIC90 （2 mg/L）, the area under the serum concentration curve, AUC/MIC, was more than 400 （MIC=1 mg/L）. Conclusion High dosage is possibly necessary in order to get good pharmacokinetics/pharmacodynamies index. The treatment is safe from this preliminary observation, but further clinical study of large samples is needed.