Critical Care Medicine Department, Cairo University Hospitals, Cairo University, 11562, Egypt.
Clinical Pharmacy Department, Ain Shams University, Cairo, 11566, Egypt.
F1000Res. 2021 Sep 16;10:929. doi: 10.12688/f1000research.55619.1. eCollection 2021.
Antioxidants show nephroprotective effect against vancomycin associated nephrotoxicity (VAN) in animals. This study aimed to assess the ascorbic acid nephro-protective role against VAN clinically. Forty-one critically ill patients were randomly assigned to one of two groups: intervention group (vancomycin IV plus ascorbic acid, n=21) or control group (vancomycin IV only, n=20). Primary outcomes were the incidence of VAN and the absolute change in creatinine parameters, while mortality rate was the secondary outcome. Nephrotoxicity was defined as an increase in serum creatinine (S.cr) by at least 0.5 mg/dL or 50% of baseline for at least two successive measurements. This study is registered at Clinicaltrials.gov (NCT03921099), April 2019. Mean absolute S.cr increase was significant when compared between both groups, -value = 0.036, where S.cr increased by 0.05(0.12) and 0.34(0.55) mg/dL in the intervention and control groups, respectively. Mean absolute Cr.cl decline was significant when compared between both groups, -value = 0.04, where Cr.cl was decreased by 5.9(17.8) and 22.3(30.4) ml/min in the intervention and control groups, respectively. Incidence of VAN was 1/21(4.7%) versus 5/20(25%) in the intervention and control groups, respectively (RR: 0.19; CI: 0.024-1.49; -value = 0.093). Mortality was higher in the control group; however, it was not statistically significant, value = 0.141. Co-administration of ascorbic acid with vancomycin preserved renal function and reduced the absolute risk of VAN by 20.3%, however, the reduction in VAN incidence didn't reach statistical significance level. Further large multicenter prospective trials are recommended.
抗氧化剂对万古霉素相关肾毒性(VAN)具有肾脏保护作用。本研究旨在临床评估抗坏血酸对 VAN 的肾脏保护作用。
41 例危重症患者随机分为两组:干预组(静脉万古霉素+抗坏血酸,n=21)或对照组(静脉万古霉素,n=20)。主要结局是 VAN 的发生率和肌酐参数的绝对变化,死亡率为次要结局。肾毒性定义为血清肌酐(S.cr)至少增加 0.5 mg/dL 或基线至少连续两次测量增加 50%。本研究于 2019 年 4 月在 Clinicaltrials.gov 注册(NCT03921099)。
两组间 S.cr 绝对值增加的差异有统计学意义,-值=0.036,干预组和对照组的 S.cr 分别增加了 0.05(0.12)和 0.34(0.55)mg/dL。两组间 Cr.cl 绝对值下降的差异有统计学意义,-值=0.04,干预组和对照组的 Cr.cl 分别下降了 5.9(17.8)和 22.3(30.4)ml/min。干预组和对照组的 VAN 发生率分别为 1/21(4.7%)和 5/20(25%)(RR:0.19;CI:0.024-1.49;-值=0.093)。对照组死亡率较高,但无统计学意义,-值=0.141。
万古霉素联合抗坏血酸可保护肾功能,降低 VAN 的绝对风险 20.3%,但 VAN 发生率的降低未达到统计学意义水平。建议开展进一步的大型多中心前瞻性试验。