连续性静脉-静脉血液滤过对多器官功能障碍综合征患者亚胺培南药动学的影响

Effects of continuous venovenous hemofiltration on imipenem pharmacokinetics in patients with multiple organ dysfunction syndrome

目的:研究连续性静脉-静脉血液滤过(CVVH)对应用亚胺培南的多器官功能障碍综合征(MODS)患者药动学的影响,以指导临床合理用药。方法:根据患者肌酐清除率分为4组:Ccr<15mL.min-1(A组)、Ccr15～50mL.min-1(B组)、Ccr>50mL.min-1(C组)、Ccr>50mL.min-1未行CVVH治疗(D组),采用高效液相色谱法测定亚胺培南血药浓度,并计算药动学参数。结果:血浆亚胺培南在0.125～50mg.L-1范围呈良好线性关系,回收率大于98%,日内和日间RSD均小于10%;4组MODS患者血药峰浓度(Cmax)差别无统计学意义,与C组和D组相比,A组与B组血药谷浓度(Cmin)增高,总体清除率(CLT)降低,消除半衰期(t1/2)和药物平均滞留时间(MRT)延长,且与患者自身肾功能密切相关;与D组相比,C组CLT增加20%。接受CVVH治疗的3组患者t1/2与Ccr呈线性负相关,CLT与Ccr呈线性正相关。结论:CVVH可增加对亚胺培南体外清除,临床用药时应考虑多种影响因素,并监测血药浓度以提高疗效、减少不良反应。

dOBJECTIVE To investigate the effects of cokinetics in patients with multiple organ dysfunction syndrome （MODS）. METHODS The patients with MODS were divided into 4 groups, Ccr〈15 mL·min-1 （A group）, Cer 15- 50 mL·min-1 （B group）, Cer）50mL·min-1 （C group） and Cer）50 mL.min-1 but not receive CVVH （D group）. The serum concentrations of imipenem were determined by HPLC, and the imipenem pharmacokinetie parameters were calculated. RESULTS An excellent standard imipenem linear curve was obtained between 0. 125 mg.L-1 to 50 mg.L The recovery rate was 〉98%, the intra- and inter-day coefficients of variation were less than 10%. There was no difference of Cmax in four groups. Compared with C and D group, A and B groups Cmin increased,CLT decreased, tl/2 and MRT prolonged. These parameters were correlated with the patients renal functions. Compared with D group, C groups＇ CLT increased by 20%. t1/2 was negatively correlated with Ccr and CLT was positively correlated with Ccr in three groups received CVVH. CONCLUSION CVVH can increase the total clearance and generate extracorporeal clearance of imipenem. Many clinical factors should be considered and the serum concentrations should be monitored.