一例体外膜肺氧合及肾脏替代治疗并行患者的美罗培南药动学/药效学

目的：测定一例体外膜肺氧合（extracorporeal membrane oxygenation，ECMO）及肾脏替代治疗（renal replacement therapy，RRT）并行患者不同时间点的美罗培南血药浓度，得出药动学参数，将浓度值与最低抑菌浓度（MIC）作比较，探讨ECMO及RRT同时进行治疗对美罗培南药动学/药效学（PK/PD）的影响。方法：选自重症监护室（ICU）的一位进行体外膜肺氧合及肾脏替代治疗的急性循环衰竭患者，按美罗培南1 g q8h，静脉滴注30 min。采用HPLC法测定美罗培南给药前和给药后0.25、0.5、0.75、1、2、4、8h的血药浓度。将测得的血药浓度代入药代动力学软件Winnonlin5.2，求出该患者的药代动力学参数。计算不同MIC值时PK/PD靶目标100%T>MIC的达标情况。结果：该患者美罗培南给药后30 min的峰浓度（Cmax）为44.94μg·mL-1，经8 h谷浓度（Cmin）为9.79μg·mL-1，0~8 h药-时曲线下面积（AUC0-8）为133.69 h·μg-1·mL-1，半衰期（t1/2）为2.68 h，表观分布容积（Vd）为33.12 L，清除率（CL）为4.38 L·h-1。当MIC为敏感值2μg·mL-1或中介值8μg·mL-1时，PK/PD靶目标100%T>MIC均达标。结论：进行体外膜肺氧合及肾脏替代治疗的急性循环衰竭患者使用美罗培南时，药动学参数发生了一定变化，但常规剂量1 g q8h/30 min延长静脉滴注能够满足抗感染的PK/PD靶目标，提示该类患者治疗初期可经验性给予常规剂量的美罗培南进行抗感染的治疗，之后根据血药浓度监测进行剂量的调整。

Combined Effects in One Patient of Extracorporeal Membrane Oxygenation and Renal Replacement Therapy on Meropenem Pharmacokinetics/pharmacodynamics

Objective: Plasma concentrations of meropenem in one patient under extracorporeal nem-brane oxygenation (ECMO) and renal replacement therapy (RRT) were tested. Besides, pharmacokinetic pa-rameters were calculated and the concentrations were compared with minimal inhibitory concentration to discuss possible altered pharmacokinetics/pharmacodynamics of meropenem that could be caused by ECMO and RRT. Methods: One patient with a diagnosis of acute circulatory failure that treated with ECMO com-bined RRT was studied, to whom meropenem was given at 1 g, q8h, 30 min infusion. The demographic data were collected and serum concentrations of meropenem were determined by high performance liquid chro-matography before and 0.25, 0.5, 0.75, 1, 2, 4, 8 hours after drug administration. Pharmacokinetic parame-ters were obtained by Winnonlin5.2 software with the measured plasma concentration time profiles. 100%T>MIC was used as the pharmacokinetic/pharmacodynamic target to describe the effect of ECMO combined with RRT on meropenem plasma concentrations. Results: Meropenem plasma concentration at 30 min after administration was 44.94μg·mL-1 as the peak concentration and the concentration at 8 h after administration was 9.79μg·mL-1 as the trough concentration. AUC0-8, t1/2, Vd and CL were 133.69 h·μg-1·mL-1, 2.68 h, 33.12 L and 4.38 L·h-1, respectively. When the MIC value were 2 or 8μg·mL-1, the PK/PD result could achieve both the targets of 100%T>MIC. Conclusion: Although meropenem in this patient under ECMO and RRT exhibit high PK variability, PK/PD targets were reached by regular dose of 1.0 g, q8h/30 min ex-tended infusion. In such patients, regular dose of meropenem administration might be applied empirically at early treatment and then the dose should be adjusted by TDM.