Behal Michael L, Flannery Alexander H, Barreto Erin F
Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, Kentucky.
Department of Pharmacy Services, University of Kentucky HealthCare, Lexington, Kentucky.
Clin J Am Soc Nephrol. 2023 Aug;18(8):1080-1088. doi: 10.2215/CJN.0000000000000101. Epub 2023 Feb 1.
AKI occurs frequently in critically ill patients. Patients with AKI, including those who require KRT, experience multiple pharmacokinetic and pharmacodynamic perturbations that dynamically influence medication effectiveness and safety. Patients with AKI may experience both subtherapeutic drug concentrations, which lead to ineffective therapy, and supratherapeutic drug concentrations, which increase the risk for toxicity. In critically ill patients with AKI not requiring KRT, conventional GFR estimation equations, especially those based on serum creatinine, have several limitations that can limit the accuracy when used for medication dosing. Alternative methods to estimate kidney function may be informative, including use of measured urinary creatinine clearance, kinetic eGFR, and equations that integrate novel kidney biomarkers. For critically ill patients with AKI requiring KRT, physicochemical properties of the drug, the KRT prescription and circuit configuration, and patient-specific factors each contribute to medication clearance. Evidence-based guidance for medication dosing during AKI requiring KRT is often limited. A working knowledge of the basic tenets of drug elimination during KRT can provide a framework for how to approach decision making when the literature is lacking. Iterative re-evaluation of a patient's progress toward therapeutic goals with a medication must occur over the arc of critical illness, including and especially in the setting of dynamic kidney function.
急性肾损伤(AKI)在危重症患者中频繁发生。患有AKI的患者,包括那些需要肾脏替代治疗(KRT)的患者,会经历多种药代动力学和药效学扰动,这些扰动会动态影响药物的有效性和安全性。AKI患者可能会出现治疗药物浓度不足,导致治疗无效,以及治疗药物浓度过高,增加毒性风险。在不需要KRT的AKI危重症患者中,传统的肾小球滤过率(GFR)估算方程,尤其是基于血清肌酐的方程,存在一些局限性,用于药物剂量计算时可能会限制准确性。估算肾功能的替代方法可能会提供有用信息,包括使用测量的尿肌酐清除率、动态GFR以及整合新型肾脏生物标志物的方程。对于需要KRT的AKI危重症患者,药物的物理化学性质、KRT处方和回路配置以及患者特异性因素都会影响药物清除。在需要KRT的AKI期间进行药物剂量计算的循证指南通常有限。了解KRT期间药物消除的基本原理可以为在缺乏文献时如何进行决策提供一个框架。在危重症期间,包括特别是在肾功能动态变化情况下,必须对患者使用药物实现治疗目标的进展进行反复重新评估。