蒙特卡罗模拟优化CRRT脓毒症患者的美罗培南给药方案

Monte Carlo Simulation Optimization of Meropenem Regimen in CRRT Sepsis Patients

目的应用蒙特卡罗模拟(MCS)优化美罗培南在连续肾脏替代治疗(CRRT)患者中抗感染的给药方案。方法通过文献检索美罗培南的PK/PD参数,应用Crystal Ball软件模拟在不同CRRT治疗剂量下,不同给药方案的美罗培南治疗铜绿假单胞菌感染的达标率,总结最佳给药方案。结果美罗培南的清除率在连续性静脉-静脉血液滤过(CVVH)较连续性静脉-静脉血液透析(CVVHD)清除率大,随着CRRT治疗剂量的增加,美罗培南的清除增加。设定铜绿假单胞菌最小抑菌浓度(MIC)为2 mg·L^(-1)时,所列CRRT治疗方案及美罗培南治疗方案的f%T>4×MIC均能达到40%以上;日总剂量相同时,500 mg q6h的给药方案药效学指标优于1 000 mg q12h;首剂加倍给药方案的f%T>4×MIC均有升高,但由于各方案均能达到40%,并未能显示首剂加倍的优势。当MIC为4 mg·L^(-1)时,大部分治疗方案的f%T>4×MIC可达到40%以上,但CRRT治疗剂量为35 m L·kg^(-1)·h^(-1),美罗培南日总剂量为2 g达不到药效学指标。结论美罗培南在行CRRT脓毒症患者中,若治疗敏感的铜绿假单胞菌,推荐500 mg q6h的给药方案,若为中介,需加大给药剂量及频次,日总剂量为2 g不能达到药效学指标;负荷剂量未见明显优势,对于中介及耐药菌,建议进行治疗药物监测来达到给药的个体化。

OBJECTIVE To optimize the anti-infection regimen of meropenem in CRRT patients by Monte Carlo Simulation(MCS).METHODS The parameters of PK/PD of meropenem were retrieved through literature,and Crystal Ball software was used to simulate the target rate of meropenem with different dosage regimens for the treatment of pseudomonas aeruginosa infection at different CRRT dosages,and to analyze and summarize the best regimen.RESULTS The clearance rate of meropenem was higher in CVVH than in CVVHD.With the increase of CRRT dosage,the clearance rate of meropenem increased.When the MIC of pseudomonas aeruginosa was set at 2 mg·L-1,the f%T>4×MIC of meropenem treatment schemes could reach more than 40%.When the total daily dose was the same,the pharmacodynamic index of 500 mg q6 h was better than 1 000 mg q12 h,the f%T>4×MIC of the first dosage doubling scheme increased,but all schemes could reach 40%,it could not show the advantage of the loading dosage.When the MIC was4 mg·L-1,the f%T>4×MIC of most treatments could reach more than 40%,but the CRRT dose was 35 m L·kg-1·h-1,and the total dose of meropenem was 2 g per day,which could not reach the pharmacodynamic index.CONCLUSION For sepsis patients with CRRT treated with meropenem,500 mg q6 h administration regimen is recommended for sensitive pseudomonas aeruginosa.If it is a mediator,the dosage and frequency of meropenem should be increased.The total daily dose of meropenem is 2 g,which can not meet the pharmacodynamic index.There is no obvious advantage in load dose.It is suggested that therapeutic drug monitoring should be carried out to achieve the individualization of administration.