神经外科术后患者静脉持续输注较大剂量万古霉素时脑脊液药物浓度的研究  

Study of the concentration of vancomycin in cerebrospinal fluid during continuous intravenous infusion

作　　者：陈光强[1] 王佳庆[2] 武元星[1] 李新刚[2] 王强[1] 赵志刚[2] 周建新[1] 

机构地区：[1]首都医科大学附属北京天坛医院ICU,100050 [2]首都医科大学附属北京天坛医院药剂科,100050

出　　处：《北京医学》2014年第7期540-543,共4页Beijing Medical Journal

摘　　要：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脑脊液药物浓度变化规律,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,顺序采取脑脊液标本,测定万古霉素浓度。结果共有24例患者入选,万古霉素首剂负荷量1 g泵入结束2 h后脑脊液的药物浓度达到相对稳定:(1.45±1.24)mg/L^(3.43±1.43)mg/L。万古霉素脑脊液稳态药物浓度达到并超过神经外科术后颅内感染常见致病菌耐甲氧西林金黄色葡萄球菌(MRSA)的MIC(≤1.0 mg/L),其脑脊液穿透率,以脑脊液与血清药物浓度-时间曲线下面积之比计算,每24 h分别为16.1%、13.3%、8.6%。所有入组患者均未出现任何不良反应。结论较大剂量万古霉素(3 g/d)与常规剂量(2 g/d)相比,静脉持续输注时,脑脊液可以较快达到有效浓度,即达到或超过颅内感染主要致病菌的MIC水平,而且初步观察该治疗是安全的,但本研究样本量小,结果仅为阶段性结果,仍需进一步的大样本的临床研究论证。Objective To study the pharmacokinetics/pharmacodynamics of vancomycin in cerebrospinal fluid （CSF） after continuous infusion. Methods Twenty-four neurosurgical postoperative patients with ventricular drainage were enrolled into this study. In each patient, a loading dose of 1 g vancomycin of was administered for 1 h followed by a continuous infusion of 3 g during the 24 hours. CSF specimens were collected. Results The steady state concentrations in the CSF [（2.23±1.20）mg/L-（3.42±1.18）mg/L] were achieved after 2 h, which exceeded the minimum inhibitory concentration [MIC（≤1.0 mg/L）] of common pathogens （MRSA） in intracranial infection. The penetration rate of vancomycin in CSF, represented by the proportion of area under the CSF concentration curve and the area under the serum concentration curve, was 16.1%, 13.3% and 8.6% every 24 hour respectively. No patients had side effects or adverse reactions. Conclusion Higher dosage is possibly necessary to reach good pharmacokinetics/pharmacodynamics index. This preliminary observation has shown that the treatment is safe, but the present study only has limited number of samples, and only has the limited stage outcome, further clinical studieswith of large samples are necessary.

关 键 词：万古霉素 持续输注 脑脊液药物浓度 药物代谢动力学 药效动力学 

分 类 号：R96[医药卫生—药理学]