Evaluation of Altered Drug Pharmacokinetics in Critically Ill Adults Receiving Extracorporeal Membrane Oxygenation

Michael Ha, A. Sieg
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引用次数: 86

Abstract

Extracorporeal membrane oxygenation (ECMO) is a life‐support modality used in patients with refractory cardiac and/or respiratory failure. A significant resurgence in the use ECMO has been seen in recent years as a result of substantial improvements in technology and survival benefit. With expanding ECMO use, a better understanding of how ECMO affects drug pharmacokinetics (PK) is necessary. The vast majority of PK studies in patients receiving ECMO have been conducted within neonatal or pediatric populations or within a controlled environment (e.g., in vitro or ex vivo). Because of significant differences in absorption, distribution, metabolism, and excretion, it may be inappropriate to extrapolate these PK data to adults. Thus, the aims of this review are to evaluate the changes in drug PK during ECMO and to summarize the available PK data for common drugs used in the adult critically ill patients during ECMO support. A search of the PubMed (1965–July 2016), EMBASE (1965–July 2016), and Cochrane Controlled Trial Register databases was performed. All relevant studies describing PK alterations during ECMO in ex vivo experiments and in adults were included. Evaluation of the data indicated that drug PK in adults receiving ECMO support may be significantly altered. Factors influencing these alterations are numerous and have intricate relationships with each other but can generally be classified as ECMO circuit factors, drug factors, and patient factors. Commonly used drugs in these patients include antimicrobials, sedatives, and analgesics. PK data for most of these drugs are generally lacking; however, recent research efforts in this patient population have provided some limited guidance in drug dosing. With an improved understanding of altered drug PK secondary to ECMO therapy, optimization of pharmacotherapy within this critically ill population continues to move forward.
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危重成人接受体外膜氧合后药物药代动力学改变的评价
体外膜氧合(ECMO)是一种生命支持方式,用于难治性心脏和/或呼吸衰竭患者。近年来,由于技术的重大进步和生存效益的提高,ECMO的使用有了显著的复苏。随着ECMO应用的扩大,更好地了解ECMO如何影响药物药代动力学(PK)是必要的。绝大多数接受ECMO患者的PK研究都是在新生儿或儿科人群中或在受控环境中进行的(例如,体外或离体)。由于在吸收、分布、代谢和排泄方面存在显著差异,因此将这些PK数据外推到成人可能不合适。因此,本综述的目的是评估ECMO期间药物PK的变化,并总结成人危重患者在ECMO支持期间常用药物的PK数据。检索PubMed(1965 - 2016年7月)、EMBASE(1965 - 2016年7月)和Cochrane对照试验注册数据库。所有描述体外和成人ECMO过程中PK改变的相关研究均被纳入。数据评估表明,接受ECMO支持的成人药物PK可能会发生显著改变。影响这些改变的因素很多,彼此之间的关系也很复杂,但一般可以分为ECMO回路因素、药物因素和患者因素。这些患者常用的药物包括抗菌剂、镇静剂和镇痛药。大多数这些药物的PK数据普遍缺乏;然而,最近在这一患者群体中的研究工作在给药方面提供了一些有限的指导。随着对继发于ECMO治疗的药物PK改变的理解的提高,在这一危重患者群体中药物治疗的优化继续向前发展。
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