Sherwin Jennifer, Heath Travis, Watt Kevin
Department of Pediatrics, Duke University, Durham, North Carolina.
Department of Pediatrics, Duke University, Durham, North Carolina.
Clin Ther. 2016 Sep;38(9):1976-94. doi: 10.1016/j.clinthera.2016.07.169. Epub 2016 Aug 21.
Extracorporeal membrane oxygenation (ECMO) is a cardiopulmonary bypass device that is used to temporarily support the most critically ill of patients with respiratory and/or cardiac failure. Infection and its sequelae may be an indication for ECMO or infections may be acquired while on ECMO and are associated with a mortality >50%. Effective therapy requires optimal dosing. However, optimal dosing can be different in patients on ECMO because the ECMO circuit can alter drug pharmacokinetics. This review assessed the current literature for pharmacokinetic data and subsequent dosing recommendations for anti-infective drugs in patients on ECMO.
We searched the PubMed and Embase databases (1965 to February 2016) and included case reports, case series, or studies that provided pharmacokinetic data for anti-infective drugs including antibiotics, antifungals, and antivirals being used to treat patients of all age groups on ECMO. Pharmacokinetic parameters and dosing recommendations based on these data are presented.
The majority of data on this topic comes from neonatal studies of antibiotics from the 1980s and 1990s. These studies generally demonstrate a larger volume of distribution due to ECMO and therefore higher doses are needed initially. More adult data are now emerging, but with a predominance of case reports and case series without comparison with critically ill controls. The available pharmacokinetic analyses do suggest that volume of distribution and clearance are unchanged in the adult population, and therefore dosing recommendations largely remain unchanged. There is a lack of data on children older than 1 year of age. The data support the importance of therapeutic drug monitoring when available in this population of patients.
This review found reasonably robust dosing recommendations for some drugs and scant or no data for other important anti-infectives. In order to better determine optimal dosing for patients on ECMO, a systematic approach is needed. Approaches that combine ex vivo ECMO experiments, animal studies, specialized pharmacokinetic modeling, and human clinical trials are being developed.
体外膜肺氧合（ECMO）是一种心肺旁路设备，用于临时支持患有呼吸和/或心力衰竭的最危重患者。感染及其后遗症可能是使用ECMO的指征，或者感染可能在使用ECMO期间获得，并且与死亡率>50%相关。有效的治疗需要最佳剂量。然而，ECMO患者的最佳剂量可能不同，因为ECMO回路会改变药物的药代动力学。本综述评估了当前关于ECMO患者抗感染药物药代动力学数据及后续给药建议的文献。
我们检索了PubMed和Embase数据库（1965年至2016年2月），纳入了病例报告、病例系列或研究，这些研究提供了用于治疗各年龄组ECMO患者的抗感染药物（包括抗生素、抗真菌药和抗病毒药）的药代动力学数据。基于这些数据的药代动力学参数和给药建议被呈现。
关于这个主题的大多数数据来自20世纪80年代和90年代的抗生素新生儿研究。这些研究通常表明，由于ECMO，分布容积更大，因此最初需要更高的剂量。现在有更多的成人数据出现，但主要是病例报告和病例系列，没有与重症对照进行比较。现有的药代动力学分析确实表明，成人人群的分布容积和清除率没有变化，因此给药建议基本保持不变。1岁以上儿童的数据缺乏。这些数据支持了在这类患者中进行治疗药物监测可用时的重要性。
本综述发现，对于某些药物有相当可靠的给药建议，而对于其他重要的抗感染药物则数据稀少或没有数据。为了更好地确定ECMO患者的最佳剂量，需要一种系统的方法。结合体外ECMO实验、动物研究、专门药代动力学建模和人体临床试验的方法正在开发中。
