Amiodarone Extraction by the Extracorporeal Membrane Oxygenation Circuit.
Amiodarone Extraction by the Extracorporeal Membrane Oxygenation Circuit.
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DOI：
10.1182/ject-2000053
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发表时间：
2021-03-01
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影响因子：
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通讯作者：
Watt, Kevin M
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文献类型：
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作者：
McDaniel, C Griffin;Honeycutt, C Cole;Watt, Kevin M
胺碘酮是一种抗心律失常药物，经常用于治疗危重成人和儿童的心动过速。由于胺碘酮的物理化学性质，体外膜氧合(ECMO)电路有望从循环中提取胺碘酮，增加治疗失败的风险。本研究旨在通过ECMO回路确定胺碘酮的提取。将胺碘酮应用于三种体外电路配置(每种配置3个)，以确定每个电路组件对药物提取的影响。电路中注入了人血；注射了标准剂量的胺碘酮；并在24小时内收集了一系列样本。用晶体流体填充额外的回路，以分析血液对提取的影响，并调查药物对回路的饱和程度。晶体回路在72小时内多次服用，包括48小时的大剂量。对于两种设置，流量都设置为1 L/分钟。将药物加入含有原液的单独试管中作为对照。用一种有效的分析方法量化药物浓度，并计算每个样本的药物回收率。电路和对照的平均恢复率被比较，以校正药物随时间的降解。胺碘酮被所有ECMO电路配置大量提取。给药后8小时，血液循环平均恢复率为13.5-22.1%。在晶体主回路中，药物回收率下降更快，30分钟时平均回收率为22.0%。同样，晶体质量组的药物回收率比血液质量组下降得更快。由于胺碘酮的最终浓度处于定量的下限，因此在晶体初始回路中没有达到饱和。结果表明，胺碘酮可以通过ECMO电路快速提取，而标准剂量并不能达到饱和。体内电路提取可能导致药物暴露的减少。
Amiodarone is an anti-arrhythmic agent that is frequently used to treat tachycardias in critically ill adults and children. Because of physicochemical properties of amiodarone, extracorporeal membrane oxygenation (ECMO) circuits are expected to extract amiodarone from circulation, increasing the risk of therapeutic failure. The present study seeks to determine amiodarone extraction by the ECMO circuit. Amiodarone was administered to three ex vivo circuit configurations (n = 3 per configuration) to determine the effect of each circuit component on drug extraction. The circuits were primed with human blood; standard amiodarone doses were administered; and serial samples were collected over 24 hours. Additional circuits were primed with crystalloid fluid to analyze the effect of blood on extraction and to investigate circuit saturation by drug. The crystalloid circuits were dosed multiple times over 72 hours, including a massive dose at 48 hours. For both setups, the flow was set to 1 L/min. Drug was added to separate tubes containing the prime solution to serve as controls. Drug concentrations were quantified with a validated assay, and drug recovery was calculated for each sample. Mean recovery for the circuits and controls were compared to correct for drug degradation over time. Amiodarone was heavily extracted by all ECMO circuit configurations. Eight hours after dosing, mean recovery in the blood prime circuits was 13.5-22.1%. In the crystalloid prime circuits, drug recovery decreased even more rapidly, with a mean recovery of 22.0% at 30 minutes. Similarly, drug recovery decreased more quickly in the crystalloid prime controls than in the blood prime controls. Saturation was not achieved in the crystalloid prime circuits, as final amiodarone concentrations were at the lower limit of quantification. The results suggest that amiodarone is rapidly extracted by the ECMO circuit and that saturation is not achieved by standard doses. In vivo circuit extraction may cause decreased drug exposure.