Amiodarone Extraction by the Extracorporeal Membrane Oxygenation Circuit

Abstract

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.

Keywords: amiodarone; drug extraction; extracorporeal membrane oxygenation; pharmacokinetics.