Meropenem extraction by ex vivo extracorporeal life support circuits.
Meropenem extraction by ex vivo extracorporeal life support circuits.
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DOI：
10.1051/ject/2023035
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发表时间：
2023-12
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背景：美罗培南是一种广谱碳青霉烯类抗生素，常用于治疗广谱β-内酰胺酶（ESBL）产肠杆菌科危重患者。由于许多患者需要体外膜氧合（ECMO）和/或持续肾替代治疗（CRRT），因此了解这些体外生命支持回路如何影响美罗培南的药代动力学是很重要的。基于美罗培南的理化性质，预计ECMO回路将最低限度地提取美罗培南，而CRRT回路将快速清除美罗培南。本研究旨在确定体外ECMO和CRRT电路中美罗培南的提取，并阐明不同ECMO电路组件对提取的贡献。方法：将标准剂量的美罗培南给予三种不同配置的体外ECMO回路（每种配置n = 3个），并在24小时内进行连续取样。同样，将标准剂量的美罗培南给予CRRT回路（n = 4），并在4小时内进行连续取样。将美罗培南施用于带有循环血液的分离管中作为对照，以解释药物降解。定量测定美罗培南浓度，计算每个样品的回收率。结果：美罗培南在不同配置ECMO回路（n = 3）和对照组（n = 6）的清除率相似，24 h时的平均（标准差）回收率在完全回路为15.6%(12.9)，氧合器回路为37.9%(8.3)，泵回路为47.1%(8.2)，对照组为20.6%（20.6）。在CRRT回路（n = 4）中，美罗培南的清除速度比对照组（n = 6）快，回路2 h的平均回收率为2.36%(1.44)，对照组为93.0%（7.1）。结论：美罗培南在CRRT中可通过血液滤过快速清除。美罗培南对ECMO电路元件的吸附极小；然而，在生理条件下，美罗培南会经历显著的降解和/或血浆代谢。这些体外研究结果将为药剂师和医生提供适当的美罗培南剂量建议。
Background: Meropenem is a broad-spectrum carbapenem-type antibiotic commonly used to treat critically ill patients infected with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. As many of these patients require extracorporeal membrane oxygenation (ECMO) and/or continuous renal replacement therapy (CRRT), it is important to understand how these extracorporeal life support circuits impact meropenem pharmacokinetics. Based on the physicochemical properties of meropenem, it is expected that ECMO circuits will minimally extract meropenem, while CRRT circuits will rapidly clear meropenem. The present study seeks to determine the extraction of meropenem from ex vivo ECMO and CRRT circuits and elucidate the contribution of different ECMO circuit components to extraction. Methods: Standard doses of meropenem were administered to three different configurations (n = 3 per configuration) of blood-primed ex vivo ECMO circuits and serial sampling was conducted over 24 h. Similarly, standard doses of meropenem were administered to CRRT circuits (n = 4) and serial sampling was conducted over 4 h. Meropenem was administered to separate tubes primed with circuit blood to serve as controls to account for drug degradation. Meropenem concentrations were quantified, and percent recovery was calculated for each sample. Results: Meropenem was cleared at a similar rate in ECMO circuits of different configurations (n = 3) and controls (n = 6), with mean (standard deviation) recovery at 24 h of 15.6% (12.9) in Complete circuits, 37.9% (8.3) in Oxygenator circuits, 47.1% (8.2) in Pump circuits, and 20.6% (20.6) in controls. In CRRT circuits (n = 4) meropenem was cleared rapidly compared with controls (n = 6) with a mean recovery at 2 h of 2.36% (1.44) in circuits and 93.0% (7.1) in controls. Conclusion: Meropenem is rapidly cleared by hemodiafiltration during CRRT. There is minimal adsorption of meropenem to ECMO circuit components; however, meropenem undergoes significant degradation and/or plasma metabolism at physiological conditions. These ex vivo findings will advise pharmacists and physicians on the appropriate dosing of meropenem.