万古霉素负荷剂量对重症患者前 24 小时内达到目标万古霉素暴露水平的影响及其伴随的肾毒性风险。
Impact of a vancomycin loading dose on the achievement of target vancomycin exposure in the first 24 h and on the accompanying risk of nephrotoxicity in critically ill patients.
机构信息
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Department of Intensive Care, OLVG Hospital, Oosterpark 9, 1091 AC Amsterdam, The Netherlands.
出版信息
J Antimicrob Chemother. 2021 Oct 11;76(11):2941-2949. doi: 10.1093/jac/dkab278.
BACKGROUND
The advocated pharmacokinetic/pharmacodynamic (PK/PD) target for vancomycin, AUC/MIC ≥ 400 mg·h/L, may not be reached with a conventional fixed starting dose of 1000 mg in critically ill patients, but increasing the dose may cause nephrotoxicity.
OBJECTIVES
To evaluate the effect of a weight-based loading dose of 25 mg/kg vancomycin on PK/PD target attainment in the first 24 h (AUC0-24) in critically ill patients and to evaluate whether this increases the risk of acute kidney injury (AKI).
PATIENTS AND METHODS
A prospective observational before/after study was performed in ICU patients, comparing the percentage of vancomycin courses with AUC0-24 ≥ 400 mg·h/L and the incidence of AKI, defined as worsening of the risk, injury, failure, loss of kidney function and end-stage kidney disease (RIFLE) score. The conventional dose group received 1000 mg of vancomycin as initial dose; the loading dose group received a weight-based loading dose of 25 mg/kg. A population PK model developed using non-linear mixed-effects modelling was used to estimate AUC0-24 in all patients.
RESULTS
One hundred and four courses from 82 patients were included. With a loading dose, the percentage of courses achieving AUC0-24 ≥ 400 mg·h/L increased significantly from 53.8% to 88.0% (P = 0.0006). The percentage of patients with new-onset AKI was not significantly higher when receiving a 25 mg/kg loading dose (28.6% versus 37.8%; P = 0.48). However, the risk of AKI was significantly higher in patients achieving AUC0-24 > 400 mg·h/L compared with patients achieving AUC < 400 mg·h/L (39.0% versus 14.8%; P = 0.031).
CONCLUSIONS
A weight-based loading dose of 25 mg/kg vancomycin led to significantly more patients achieving AUC0-24 ≥ 400 mg·h/L without increased risk of AKI. However, some harm cannot be ruled out since higher exposure was associated with increased risk of AKI.
背景
万古霉素的推荐药代动力学/药效学（PK/PD）目标为 AUC/MIC≥400mg·h/L，但对于危重症患者，常规起始剂量 1000mg 可能无法达到该目标，而增加剂量可能会导致肾毒性。
目的
评估 25mg/kg 万古霉素负荷剂量对危重症患者第 24 小时（AUC0-24）PK/PD 目标的影响，并评估其是否会增加急性肾损伤（AKI）的风险。
患者和方法
对 ICU 患者进行了一项前瞻性观察性前后对照研究，比较了 AUC0-24≥400mg·h/L 的万古霉素疗程百分比和 AKI 发生率（定义为风险、损伤、衰竭、肾功能丧失和终末期肾病（RIFLE）评分的恶化）。常规剂量组给予万古霉素 1000mg 作为初始剂量；负荷剂量组给予体重 25mg/kg 的负荷剂量。使用非线性混合效应模型进行群体 PK 模型建立，以估算所有患者的 AUC0-24。
结果
纳入 82 例患者的 104 个疗程。使用负荷剂量后，AUC0-24≥400mg·h/L 的疗程百分比从 53.8%显著增加至 88.0%（P=0.0006）。接受 25mg/kg 负荷剂量的患者新发生 AKI 的百分比没有显著升高（28.6%比 37.8%；P=0.48）。然而，与 AUC0-24<400mg·h/L 的患者相比，AUC0-24>400mg·h/L 的患者 AKI 的风险明显更高（39.0%比 14.8%；P=0.031）。
结论
万古霉素的体重基础负荷剂量为 25mg/kg，可显著增加 AUC0-24≥400mg·h/L 的患者比例，且不会增加 AKI 的风险。然而，由于更高的暴露与 AKI 的风险增加相关，因此不能排除存在一定的危害。
Zotero 插件