Vancomycin clearance during continuous venovenous haemofiltration in critically ill patients
Vancomycin clearance during continuous venovenous haemofiltration in critically ill patients
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DOI：
10.1007/s001340051018
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发表时间：
1999-10-01
影响因子：
38.9
通讯作者：
van Dijk, A
中科院分区：
文献类型：
--
作者：
Boereboom, FTJ;Ververs, FFT;van Dijk, A
目的：研究万古霉素的药代动力学与连续性静脉-静脉血液滤过（CVVHF）治疗的急性肾功能衰竭危重患者设计：开放标签研究设置：医院药房中心和医学重症监护室的大学医学中心Utrecht.Materials和方法：在实验室环境中，万古霉素的筛选系数（S）的聚丙烯腈（PAN）不同表面积的血液滤过器进行了研究。在1例患者中，研究了万古霉素单次给药后万古霉素的药代动力学。另一例患者根据文献数据接受万古霉素给药方案治疗，但高谷浓度使得停药24小时后有必要降低剂量。两次给药250 mg后，采集血清和超滤液样本进行药代动力学评价。干预：CVVHF，具有以下操作特征：血液流量200 ml/min，超滤液流量25 ml/min，后稀释，PAN 06中空纤维血液滤过器。测量和结果：PAN 03、06和10血液滤过器的体外平均筛分系数分别为0.73 +/- 0.06、0.86 +/- 0.11和0.80 +/- 0.06。通过增加超滤速率导致的筛分系数变化无临床意义。第1例患者静脉输注单剂量万古霉素1000 mg。获得了以下药代动力学数据：表观分布容积（Vd）55.81，终末半衰期（t（1/2）（term））15.4 h，总清除率（Cl-tot）2.5 l/h，CVVHF清除率（CLCVVHF，形式1）1.4 l/h，和体清除率（Cl-体）1.1 l/h研究期间的平均筛分系数为0.89 +/-0.03。在第二例患者中，在剂量降低后研究了万古霉素的药代动力学：Vd 41.7 l，t（1/2 term）20.3 h，Cl-tot 1.4 l/h，Cl-CVVHF，Cl-型1 1.4 l/h，Cl-体< 0.1 l/h。研究期间的平均筛分系数为0.88 +/- 0.03。在12小时研究期间，通过CVVHF清除的万古霉素累积量在患者1中为245 mg，在患者2中为228 mg。结论：CVVHF联合PAN 06血液滤过器可有效清除2例危重患者的万古霉素。CVVHF清除的万古霉素量约为每12小时250 mg。观察到两名患者的身体清除率存在明显差异。我们对接受CVVHF治疗的危重患者的万古霉素剂量建议为负荷剂量15-20 mg/kg，24 h后250 - 500 mg每日2次，并密切监测血清和超滤液万古霉素浓度。
Objective: To study the pharmacokinetics of vancoymcin in critically ill patients with acute renal failure treated with continuous venovenous haemofiltration (CVVHF).Design: Open-label study.Setting: Hospital pharmacy centre and medical intensive care unit of the University Medical Centre Utrecht.Materials and methods: In a laboratory setting, the sieving coefficient (s) of vancomycin by polyacrilonitrile (PAN) haemofilters of different surface areas was studied. In one patient, the pharmacokinetics of vancomycin were studied following a single dose of vancomycin. Another patient was treated with a vancomycin dosing regimen based on data from the literature, but high trough concentrations made dose reduction necessary after 24 h of withholding therapy. After two doses of 250 mg, serum and ultrafiltrate samples were collected for pharmacokinetic evaluation.Intervention: CVVHF with the following operational characteristics: blood flow 200 ml/min, ultrafiltrate flow 25 ml/min, postdilution, PAN 06 hollow fibre haemofilter.Measurements and results: The average sieving coefficient in vitro was 0.73 +/- 0.06, 0.86 +/- 0.11, and 0.80 +/- 0.06 for the PAN 03, 06, and 10 haemofilters, respectively. Changes in the sieving coefficient by increasing the ultrafiltration rate were not clinically significant. The first patient was given a single dose of vancomycin, 1000 mg by intravenous infusion. The following pharmacokinetic data were obtained: apparent volume of distribution (Vd) 55.81, terminal half-life time (t(1/2) (term)) 15.4 h, total clearance (Cl-tot) 2.5 l/h, CVVHF clearance (CLCVVHF,form 1) 1.4 l/h, and body clearance (Cl-body) 1.1 l/h The average sieving coefficient during the study period was 0.89 +/- 0.03. In the second patient, the pharmacokinetics of vancomycin were studied following dose reduction: Vd 41.7 l, t(1/2 term) 20.3 h, Cl-tot 1.4 l/h, Cl-CVVHF,Cl-form 1 1.4 l/h, and Cl-body < 0.1 l/h. The average sieving coefficient during the study period was 0.88 +/- 0.03. The cumulative amount of vancomycin removed by means of CVVHF during the 12-h study period was 245 mg in patient 1 and 228 mg in patient 2.Conclusion: CVVHF with a PAN 06 haemofilter effectively removed vancomycin in two critically ill patients. The amount of vancomycin removed with CVVHF was about 250 mg per 12 h. A clear difference in body clearance in the two patients was observed. Our dosage recommendation for vancomycin in critically ill patients receiving CVVHF is a loading dose of 15-20 mg/kg followed after 24 h by 250 to 500 mg twice daily with close monitoring of the serum and ultrafiltrate vancomycin concentration.