The Ottawa Hospital, The Ottawa Hospital Research Institute, 501 Smyth Rd, Ottawa, ON, Canada.
Faculty of Medicine and School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia.
Clin Pharmacokinet. 2020 Mar;59(3):327-334. doi: 10.1007/s40262-019-00817-6.
Sustained low-efficiency dialysis (SLED) is a hybrid form of dialysis that is increasingly used in critically ill patients with kidney injury and hemodynamic instability. Antimicrobial dosing for patients receiving SLED is informed by pharmacokinetic studies that describe the drug clearance. Studies available to assist in the dosing of vancomycin in the context of SLED are lacking.
The objective of this prospective observational study was to describe the population pharmacokinetics of vancomycin in critically ill patients receiving SLED, and use simulation studies to propose dosing strategies.
Serial serum samples were obtained from 31 critically ill patients prescribed vancomycin while receiving SLED. Vancomycin concentrations were quantified in plasma using a validated liquid chromatography mass spectrometry/mass spectrometry method. A population pharmacokinetic model was developed, and Monte Carlo simulation was used to determine the probability of target attainment at different doses.
From a total of 335 serum samples from 31 patients receiving 52 sessions of SLED therapy, a two-compartment linear model with zero-order input was developed. The mean (standard deviation) clearance of vancomycin on and off SLED was 5.97 (4.04) and 2.40 (1.46) L/h, respectively. Using pharmacodynamic targets for efficacy (area under the concentration-time curve from time zero to 24 h [AUC]/minimum inhibitory concentration [MIC] ≥ 400) and safety (AUC ≥ 700), a loading dose of 2400 mg followed by daily doses of 1600 mg is recommended. Subsequent dosing should be informed by therapeutic drug monitoring of vancomycin levels.
In critically ill patients receiving SLED, vancomycin clearance is highly variable with a narrow therapeutic window. Empiric dosing is proposed but subsequent dosing should be guided by drug levels.
持续低效透析（SLED）是一种混合透析形式，越来越多地用于患有肾损伤和血流动力学不稳定的重症患者。接受 SLED 治疗的患者的抗菌药物剂量是根据描述药物清除率的药代动力学研究来确定的。目前缺乏用于协助 SLED 背景下万古霉素给药的研究。
本前瞻性观察性研究的目的是描述接受 SLED 治疗的重症患者万古霉素的群体药代动力学，并通过模拟研究提出给药策略。
从 31 名接受 SLED 治疗并开处方万古霉素的重症患者中获得了 335 个血清样本。使用经过验证的液相色谱-质谱/质谱法在血浆中定量检测万古霉素浓度。建立了群体药代动力学模型，并进行蒙特卡罗模拟以确定不同剂量下达到目标的概率。
从 31 名患者接受 52 次 SLED 治疗的总共 335 个血清样本中，开发了一个具有零级输入的两室线性模型。SLED 治疗期间和停止时的万古霉素平均（标准差）清除率分别为 5.97（4.04）和 2.40（1.46）L/h。使用疗效（从 0 到 24 小时的浓度-时间曲线下面积[ AUC ]/最小抑菌浓度[ MIC ]≥400）和安全性（ AUC ≥700）的药效学目标，建议负荷剂量为 2400 mg，随后每日剂量为 1600 mg。随后的剂量应根据万古霉素水平的治疗药物监测来确定。
在接受 SLED 治疗的重症患者中，万古霉素清除率变化很大，治疗窗口狭窄。建议经验性给药，但随后的给药应根据药物水平进行指导。
