Ex Vivo Model to Decipher the Impact of Extracorporeal Membrane Oxygenation on Beta-lactam Degradation Kinetics
Ex Vivo Model to Decipher the Impact of Extracorporeal Membrane Oxygenation on Beta-lactam Degradation Kinetics
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DOI：
10.1097/ftd.0000000000000369
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发表时间：
2017-04-01
影响因子：
2.5
通讯作者：
Lemaitre, Florian
中科院分区：
文献类型：
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作者：
Leven, Cyril;Fillatre, Pierre;Lemaitre, Florian
背景资料：由于药物隔离、分布容积增加或消除改变，体外膜氧合（ECMO）可能导致重要药物的血浆浓度不足。本实验研究的目的是开发一种体外模型，以更好地表征ECMO程序对β-内酰胺类抗生素的药代动力学的影响。方法：头孢噻肟，头孢他啶，头孢吡肟，哌拉西林，苯唑西林，阿莫西林，头孢曲松的血浆浓度进行了测量，在体外ECMO电路与全血启动，并与控制存储在玻璃管和聚氯乙烯管。在48小时内收集系列血液样本，并使用经验证的高效液相色谱法测定β-内酰胺抗生素的浓度。使用非线性混合效应modeling.Results比较ECMO回路和对照之间的浓度随时间的衰减率：头孢噻肟浓度显著降低：4 h后保留初始浓度的86%，48 h后仅为21%（玻璃和聚氯乙烯对照的降低率比较P< 0.05）。对于其他β-内酰胺类抗生素，ECMO回路和对照组之间的下降率无差异。48小时ECMO回路的平均药物回收率如下：头孢他啶，73%;头孢吡肟，67%;哌拉西林，71%;苯唑西林，46%;阿莫西林，72%。头孢曲松的浓度保持稳定，在整个48小时的研究都在ECMO电路和controls.Conclusions：观察到头孢噻肟的显着损失，而头孢他啶，头孢吡肟，哌拉西林，苯唑西林，阿莫西林减少是温和的，类似于对照组，头孢曲松浓度保持不变。这些结果对于ECMO治疗的危重患者使用β-内酰胺类抗生素是令人放心的。
Background: As a consequence of drug sequestration, increase in volume of distribution, or alteration of elimination, extracorporeal membrane oxygenation (ECMO) might lead to inadequate plasma concentrations of vital drugs. The aim of this experimental study was to develop an ex vivo model to better characterize the impact of ECMO procedure on beta-lactam antibiotics pharmacokinetics.Methods: Plasma concentrations of cefotaxime, ceftazidime, cefepime, piperacillin, oxacillin, amoxicillin, and ceftriaxone were measured in an ex vivo ECMO circuit primed with whole human blood and compared with controls stored in glass tubes and polyvinyl chloride tubing. Serial blood samples were collected over 48 hours, and the concentrations of beta-lactam antibiotics were quantified using a validated high-performance liquid chromatography assay. The concentrations' decay rate over time was compared between the ECMO circuits and controls using nonlinear mixed-effect modeling.Results: Cefotaxime concentrations decreased markedly: 86% of the initial concentration remained after 4 hours and only 21% after 48 hours (P< 0.05 for the comparison in rate of decrease with both glass and polyvinyl chloride controls). There was no difference in the rate of decrease between ECMO circuit and controls for the other beta-lactam antibiotics. The average drug recoveries from the ECMO circuits at 48 hours were as follows: ceftazidime, 73%; cefepime, 67%; piperacillin, 71%; oxacillin, 46%; and amoxicillin, 72%. Concentrations of ceftriaxone remained stable throughout the 48-hour study both in ECMO circuits and in controls.Conclusions: Significant losses of cefotaxime were observed, whereas ceftazidime, cefepime, piperacillin, oxacillin, and amoxicillin decrease was moderate and similar to that of the control group, and ceftriaxone concentrations remained unchanged. These results are reassuring for the use of beta-lactam antibiotics in critically ill patients treated with ECMO.