Himebauch Adam S, Kilbaugh Todd J, Zuppa Athena F
a Department of Anesthesiology and Critical Care Medicine, Perelman School of Medicine , University of Pennsylvania, The Children's Hospital of Philadelphia , Philadelphia , PA , USA.
b Center for Clinical Pharmacology , The Children's Hospital of Philadelphia , Philadelphia , PA , USA.
Expert Opin Drug Metab Toxicol. 2016 Oct;12(10):1133-42. doi: 10.1080/17425255.2016.1201066. Epub 2016 Jul 1.
Pediatric critical illness and associated alterations in organ function can change drug pharmacokinetics (PK). Extracorporeal membrane oxygenation (ECMO), a life-saving therapy for severe cardiac and/or respiratory failure, causes additional PK alterations that affect drug disposition.
The purposes of this review are to discuss the PK changes that occur during ECMO, the associated therapeutic implications, and to review PK literature relevant to pediatric ECMO. We discuss various classes of drugs commonly used for pediatric patients on ECMO, including sedatives, analgesics, antimicrobials and cardiovascular drugs. Finally, we discuss future areas of research and recommend strategies for future pediatric ECMO pharmacologic investigations.
Clinicians caring for pediatric patients treated with ECMO must have an understanding of PK alterations that could lead to either therapeutic failures or increased drug toxicity during this life-saving therapy. Limited data currently exist for optimal drug dosing in pediatric populations who are treated with ECMO. While there are clear challenges to conducting and analyzing data associated with clinical pharmacokinetic-pharmacodynamic studies of children on ECMO, we present techniques to address these challenges. Improved understanding of the physiology and drug disposition during ECMO combined with PK-PD modeling will allow for more adaptable and individualized dosing schemes.
儿科危重病及相关器官功能改变可改变药物的药代动力学（PK）。体外膜肺氧合（ECMO）是治疗严重心脏和/或呼吸衰竭的一种挽救生命的疗法，它会引起额外的药代动力学改变，影响药物处置。
本综述的目的是讨论体外膜肺氧合期间发生的药代动力学变化、相关治疗意义，并回顾与儿科体外膜肺氧合相关的药代动力学文献。我们讨论了常用于接受体外膜肺氧合治疗的儿科患者的各类药物，包括镇静剂、镇痛药、抗菌药物和心血管药物。最后，我们讨论了未来的研究领域，并推荐了未来儿科体外膜肺氧合药理学研究的策略。
护理接受体外膜肺氧合治疗的儿科患者的临床医生必须了解药代动力学改变，这些改变可能在这种挽救生命的治疗过程中导致治疗失败或药物毒性增加。目前，关于接受体外膜肺氧合治疗的儿科人群最佳药物剂量的数据有限。虽然在进行和分析与接受体外膜肺氧合治疗的儿童的临床药代动力学 - 药效学研究相关的数据方面存在明显挑战，但我们提出了应对这些挑战的技术。更好地理解体外膜肺氧合期间的生理学和药物处置情况，并结合药代动力学 - 药效学建模，将有助于制定更具适应性和个性化的给药方案。
