Effect Of ECMO On Pharmacokinetics Of Imipenem/cilastatin Sodium In Patients With ARDS

Objective:To study the effect of ECMO on pharmacokinetics of IMI/CIL,an common antimicrobial in patients with ARDS treated with ECMO,and to provide reference for adjusting IMI/CIL dosage regimen in patients with ARDS treated with ECMO.Methods:1.Determination of imipenem in serum by HPLC-UV,and determination of cilastatin in serum by HPLC-MS,then the reliability of the analysis methods was verified.2.Selection of patients admitted to ICU of a University Affiliated Hospital from March 2018 to March 2019 according to inclusion and excluding criteria who were diagnosed as ARDS and required IMI/CIL treatment.The dosage regimen is 1 g every 6 hours and the pumping time is 1 hour.The patients were divided into experimental group with ECMO and control group without ECMO.Blood samples were collected 0 hours,15 min,30 min,45 min,1 h,1.5 h,2 h,3 h,4 h and 6 h.Pathophysiological data and ECMO-related parameters were recorded.3.The pharmacokinetic parameters of IMI and CIL in the experimental group and the control group were calculated by WinNonlin.The effects of ECMO on IMI/CIL pharmacokinetics in patients with ARDS were analyzed by PASW20.0 combination with the patient’s pathophysiological status.Results:1.Both methods of inspection fits to the requirements of biological samples.The linearity of IMI serum concentration was good in the range of 0.1953⁵0.1μg/mL,the regression equation was y=0.235x-0.000447 and its coefficient correlation is 0.9993.The linearity of CIL serum concentration was good in the range of0.2041⁵2.25μg/mL,the regression equation was y=0.20117x-0.0105208 and its coefficient correlation is 0.9991.2.A total of 19 subjects were collected,6 received ECMO treatment,12 did not receive ECMO treatment,and 1 received combined ECMO and CRRT treatment.The average plasma concentration of IMI in the ECMO group was higher than that in non-ECMO（P>0.05）.The average plasma concentration of CIL in the ECMO group at 15min and 30min was higher than that in the non-ECMO group,and the average plasma concentration of CIL at other sampling time points less than non-ECMO group（P>0.05）.The mean values of AUC_0-t,AUC_0-∞,and T_1/2/2 of the IMI in the ECMO group were larger than those in the non-ECMO group,and the mean values of MRT_0-t,Vd,CL,and Cmax were smaller than those in the non-ECMO group（P>0.05）.The mean values of AUC_0-t,AUC_0-∞,MRT_0-t,and T_1/2/2 of the CIL in the ECMO group were larger than those in the non-ECMO group,and the mean values of Vd,CL,and Cmax were smaller than those in the non-ECMO group（P>0.05）.Conclusions:1.The method established in this study is suitable for routine detection of IMI blood concentration.2.In this study,compared with the control group without ECMO adjuvant therapy,ECMO adjuvant therapyt had no significant effect on the plasma concentration and pharmacokinetics of IMI and CIL.Because of the high variability of the PK parameters of IMI,it is suggested that TDM be applied to IMI during the treatment of critical patients.