比较浓度-时间曲线下面积与谷浓度指导万古霉素治疗重症患者的临床随机对照研究  

Comparison between area under the concentration-time curve and trough concentration in guiding the vancomycin treatment for critically ill patients by randomized controlled clinical trials

作　　者：王锐[1] 何囡囡 席振创 罗延年[1] 高雪花[1] 李美玲 曹雯[1] Wang Rui;He Nannan;Xi Zhenchuang;Luo Yannian;Gao Xuehua;Li Meiling;Cao Wen(Intensive Care Unit,the Second Hospital of Lanzhou University,Lanzhou 730030,China)

机构地区：[1]兰州大学第二医院重症医学科,甘肃兰州730030

出　　处：《中国急救医学》2024年第11期996-1001,共6页Chinese Journal of Critical Care Medicine

基　　金：甘肃省自然科学基金(20JR10RA749);甘肃省卫生行业科研计划项目(GSWSKY-2015-66);兰州市城关区科技计划项目(2019JSCX0052)。

摘　　要：目的探讨浓度-时间曲线下面积和谷浓度指导万古霉素治疗重症患者的临床安全性和疗效差异。方法入选2021年1月至2023年12月收住兰州大学第二医院重症医学科因革兰阳性菌感染且经医师确认需使用万古霉素治疗的患者,经纳排标准筛选后,采用随机数字表法将入选患者分为两组进行前瞻性、随机、单盲对照研究,对照组以万古霉素谷浓度10~20 mg/L为目标靶值,观察组以万古霉素浓度-时间曲线下面积400~600 mg·h/L为目标靶值。经过监测,最终对照组77例、观察组79例符合目标靶值范围并进行相关统计学分析与比较。结果观察组万古霉素相关急性肾损伤(AKI)发生率明显低于对照组(P=0.002),两组临床疗效及总治疗时间差异无统计学意义。根据多因素Logistic回归分析显示,谷浓度(OR=1.021,95%CI 1.019~1.577,P=0.033)及急性生理学和慢性健康状况评价Ⅱ(APACHEⅡ)评分(OR=1.189,95%CI 1.055~1.339,P=0.004)是万古霉素相关AKI独立危险因素,采样总数量(OR=0.476,95%CI 0.247~0.917,P=0.000)是临床转归独立危险因素。对谷浓度与万古霉素相关AKI进行受试者工作特征(ROC)曲线分析,谷浓度预测万古霉素相关AKI临界值为15.65 mg/L,敏感度为0.786,特异度为0.697,ROC曲线下面积为0.727。结论基于浓度-时间曲线下面积为目标靶值的药物监测方法,可以减少万古霉素相关AKI发生,但临床疗效无差别。Objective To compare the clinical safety and efficacy of two therapeutic drug monitoring methods including area under the concentration-time curve and trough concentration in critically ill patients receiving vancomycin treatment.Methods The patients of Gram-positive bacterial infection with vancomycin treatment admitted to the Intensive Care Unit of the Second Hospital of Lanzhou University from January 2021 to December 2023 were enrolled and divided into two groups by random number table method for prospective,randomized,single-blind,controlled trial.The vancomycin trough concentration of 10-20 mg/L was regarded as the target value in the control group,and the area under the concentration-time curve of vancomycin(400-600 mg·h/L)was regarded as the target value in the observation group.After therapeutic drug monitoring,77 cases in the control group and 79 cases in the observation group finally met the target value range,the relevant statistical analysis and comparison were conducted.Results The incidence of vancomycin-associated acute kidney injury(AKI)in the observation group was significantly lower than that in the control group(P=0.002).There was no significant difference in clinical efficacy and total treatment time between the two groups.Multivariate Logistic regression analysis showed that trough concentration(OR=1.021,95%CI 1.019-1.577,P=0.033)and acute physiology and chronic health evaluationⅡ(APACHEⅡ)score(OR=1.189,95%CI 1.055-1.339,P=0.004)were independent risk factors for vancomycin-associated AKI.Total sampling number(OR=0.476,95%CI 0.247-0.917,P=0.000)was an independent risk factor for clinical outcomes.Receiver operating characteristic(ROC)curve analysis showed that the critical value of trough concentration for predicting vancomycin-associated AKI was 15.65 mg/L,with a sensitivity of 0.786,a specificity of 0.697 and area under ROC curve of 0.727.Conclusions The drug monitoring method based on area under the concentration-time curve as the target value can decrease the incidence of vancomycin-

关 键 词：浓度-时间曲线下面积 谷浓度 万古霉素 肾毒性 

分 类 号：R459.7[医药卫生—急诊医学]