还原型谷胱甘肽对重症患者使用万古霉素致药物性肾损伤的保护作用

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目的:观察重症患者使用万古霉素治疗后肾功能的变化,分析还原型谷胱甘肽(GSH)对万古霉素肾毒性的保护作用。方法:在上海交通大学医学院附属瑞金医院进修期间收集2012年1月至2019年10月瑞金医院急诊重症监护病房(ICU)收治的使用万古霉素或联合应用GSH的重症感染患者的临床资料,并分为万古霉素单用组和万古霉素联合GSH组。记录并分析入选患者的性别、年龄、体重、基础疾病、临床诊断、病情严重程度评分、用药前后肾功能、万古霉素和GSH的日平均剂量与疗程、ICU住院时间及临床结局等。结果:共纳入217例患者,万古霉素单用组127例,联合GSH组90例。两组患者的性别、体重、万古霉素疗程、慢性肾脏病病史及ICU病死率等差异均无统计学意义。217例患者入住ICU的病因主要为肺部感染、脓毒症/感染性休克和重症急性胰腺炎(SAP)等,其中万古霉素单用组以肺部感染居多(63.0%),而联合GSH组则以SAP居多(46.7%)。与万古霉素单用组相比,联合GSH组患者急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ)较低〔分:15.0(10.5,21.0)比27.0(20.0,31.0),n P<0.01〕,但快速序贯器官衰竭评分(qSOFA)较高〔分:1.0(0,1.0)比0(0,0.2),n P<0.01〕,且基础肾功能较差〔血肌酐(SCr,μmol/L):102.0(64.7,178.0)比56.0(42.0,71.0),血尿素氮(BUN,mmol/L):11.5(6.7,18.4)比4.7(3.5,8.1),均n P<0.05〕,万古霉素的日平均剂量较低(mg·kgn -1·dn -1:22.22±10.09比25.51±9.56,n P<0.05)。万古霉素单用组患者用药后肾功能较用药前恶化〔SCr(μmol/L):68.0(50.3,103.4)比56.0(42.0,71.0),BUN (mmol/L):5.4(3.6,9.6)比4.7(3.5,8.1),均n P<0.05〕;而联合GSH组患者用药后的肾功能指标较用药前改善〔SCr(μmol/L):81.0(61.0,129.0)比102.0(64.7,178.0),n P0.05〕,且ICU住院时间也较万古霉素单用组显著缩短〔d:29.0(14.0,54.2)比37.0(25.0,55.0),n P<0.05〕。n 结论:万古霉素所致药物性肾损伤发生率较高,GSH可以显著降低万古霉素的肾毒性,缩短患者住院时间。“,”Objective:To observe the changes of renal function in critically ill patients after using vancomycin and analyze the renal protective effect of reduced glutathione (GSH) on vancomycin nephrotoxicity.Methods:The clinical data of patients with severe infection who were administered with vancomycin or plus infusion of GSH admitted to intensive care unit (ICU) of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2012 to October 2019 were collected during the study period, and the patients were divided into only vancomycin group and vancomycin combined with GSH group. The gender, age, body weight, underlying diseases, clinical diagnosis, severity score, renal function before and after taking the medicine, average daily dose and treatment duration of vancomycin and GSH, length of ICU stay and clinical outcomes were recorded and analyzed.Results:A total of 217 patients were enrolled, with 127 patients in the only vancomycin group, and 90 in the combination with GSH group. There was no statistically significant difference between the two groups in terms of gender, body weight, duration of vancomycin treatment, history of chronic kidney disease, and ICU mortality. The main causes of 217 patients admitted to the ICU were lung infection, sepsis/septic shock, and severe acute pancreatitis (SAP) and so on. The majority of patients in only vancomycin group had lung infections (63.0%), while the main etiology in combination with GSH group was SAP (46.7%). Compared with the only vancomycin group, the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score in the combination with GSH group significantly decreased [15.0 (10.5, 21.0) vs. 27.0 (20.0, 31.0), n P < 0.01], but the quick sequential organ failure assessment (qSOFA) score was significantly higher [1.0 (0, 1.0) vs. 0 (0, 0.2), n P < 0.01], the basic renal function was poorer [serum creatinine (SCr, μmol/L): 102.0 (64.7, 178.0) vs. 56.0 (42.0, 71.0), blood urea nitrogen (BUN, mmol/L): 11.5 (6.7, 18.4) vs. 4.70 (3.5, 8.1), both n P < 0.05], and the average daily dose of vancomycin was lower (mg·kg n -1·dn -1: 22.22±10.09 vs. 25.51±9.56, n P < 0.05). The renal function of patients was getting worse significantly after vancomycin usage as compared with before [SCr (μmol/L): 68.0 (50.3, 103.4) vs. 56.0 (42.0, 71.0), BUN (mmol/L): 5.4 (3.6, 9.6) vs. 4.7 (3.5, 8.1), both n P < 0.05]. However, the renal function indexes of the combination with GSH group were better than those before treatment [SCr (μmol/L): 81.0 (61.0, 129.0) vs. 102.0 (64.7, 178.0), n P 0.05], and the length of ICU stay was significantly shorter than that in the only vancomycin group [days: 29.0 (14.0, 54.2) vs. 37.0 (25.0, 55.0), n P < 0.05].n Conclusions:The incidence of drug-induced renal injury caused by vancomycin is high. The GSH can significantly reduce their renal toxicity and shorten the length of hospital stay.
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