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[体外膜肺氧合治疗脓毒症儿童时抗生素的药代动力学和药效学]

[Pharmacokinetics and pharmacodynamics of antibiotics in septic children treated with extracorporeal membrane oxygenation].

作者信息

Zhang H X, Huang J T, Dong J, Gong T Z, Zhang K Y, Lu X L, Guo S W

机构信息

Department of Pharmacy, Hunan Children's Hospital, Changsha 410007, China.

Department of Critical Medicine, Hunan Children's Hospital, Changsha 410007, China.

出版信息

Zhonghua Er Ke Za Zhi. 2023 Jul 2;61(7):631-636. doi: 10.3760/cma.j.cn112140-20230205-00076.

Abstract

To investigate the characteristics of pharmacokinetic (PK) and pharmacodynamic (PD) parameters of antibacterial agents in children with sepsis treated by extracorporeal membrane oxygenation (ECMO). In this prospective cohort study, 20 children with sepsis (confirmed or suspected) who were treated with ECMO and antimicrobial in the Department of Critical Medicine of Hunan Children's Hospital from March 2021 to December 2022 were enrolled as the ECMO group. Through therapeutic drug monitoring (TDM), the PK-PD parameters of antibacterial agents were analyzed. Twenty five children with sepsis in the same department who were treated with vancomycin but no ECMO at the same time were enrolled as the control group. The individual PK parameters of vancomycin were calculated by Bayesian feedback method. The PK parameters in the two groups were compared, and the correlation between trough concentration and area under the curve (AUC) was analyzed. Wilcoxon rank sum test was used for inter group comparison. Twenty patients in the ECMO group, included 6 males and 14 females, with an onset age of 47 (9, 76) months. In the ECMO group, 12 children (60%) were treated with vancomycin, and the trough concentration was less than 10 mg/L in 7 cases, 10-20 mg/L in 3 cases, and >20 mg/L in 2 cases; AUC/minimum inhibitory concentration (MIC) (MIC=1 mg/L)<400 was in 1 case, 400-600 in 3 cases, and >600 in 8 cases. Among the 11 children (55%) who were treated with β-lactam antibiotics, there were 10 cases with drug concentration at 50% dosing interval (C)>4 MIC and 9 cases with trough concentration>MIC, both C and trough concentration of cefoperazone reached the target. Among the 25 cases of control group, 16 were males and 9 females, with an onset age of 12 (8, 32) months. There was a positive correlation between vancomycin trough concentration and AUC (0.36, 0.001). The half-life of vancomycin and the 24-hour AUC (AUC) in the ECMO group were higher than those in the control group (5.3 (3.6, 6.8) 1.9 (1.5, 2.9) h, and 685 (505, 1 227) 261 (210, 355) mg·h/L, =2.99, 3.50, respectively; both 0.05), and the elimination rate constant and clearance rate was lower than those in the control group (0.1 (0.1, 0.2) 0.4 (0.2, 0.5), 0.7 (0.5, 1.3) 2.0 (1.1, 2.8) L/h, =2.99, 2.11, respectively; both 0.05). The PK-PD parameters in septic children treated by ECMO varied with a longer half-life, higher AUC, lower elimination rate constant and clearance rate.

摘要

探讨体外膜肺氧合(ECMO)治疗的脓毒症患儿抗菌药物的药代动力学(PK)和药效学(PD)参数特点。在这项前瞻性队列研究中,选取2021年3月至2022年12月在湖南省儿童医院重症医学科接受ECMO和抗菌药物治疗的20例脓毒症(确诊或疑似)患儿作为ECMO组。通过治疗药物监测(TDM)分析抗菌药物的PK-PD参数。选取同期在同一科室接受万古霉素治疗但未使用ECMO的25例脓毒症患儿作为对照组。采用贝叶斯反馈法计算万古霉素的个体PK参数。比较两组的PK参数,并分析谷浓度与曲线下面积(AUC)之间的相关性。组间比较采用Wilcoxon秩和检验。ECMO组20例患儿,男6例,女14例,发病年龄47(9,76)个月。ECMO组中,12例患儿(60%)使用万古霉素治疗,7例谷浓度低于10mg/L,3例为10 - 20mg/L,2例高于20mg/L;AUC/最低抑菌浓度(MIC)(MIC = 1mg/L)<400的有1例,400 -600的有3例,高于600的有8例。在接受β-内酰胺类抗生素治疗的11例患儿(55%)中,10例给药间隔50%时药物浓度(C)>4 MIC,9例谷浓度>MIC,头孢哌酮的C和谷浓度均达到目标值。对照组25例患儿,男16例,女9例,发病年龄12(8,32)个月。万古霉素谷浓度与AUC呈正相关(0.36,P = 0.001)。ECMO组万古霉素的半衰期和24小时AUC高于对照组(分别为5.3(3.6,6.8)对1.9(1.5,2.9)h,以及685(505,1227)对261(210,355)mg·h/L,Z = 2.99,3.50,P均<0.05),消除速率常数和清除率低于对照组(分别为0.1(0.1,0.2)对0.4(0.2,0.5),0.7(0.5,1.3)对2.0(1.1,2.8)L/h,Z = 2.99,2.11,P均<0.05)。ECMO治疗的脓毒症患儿的PK-PD参数存在差异,半衰期更长,AUC更高,消除速率常数和清除率更低。

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