Green Danielle J, McKnite Autumn M, Hunt J Porter, Imburgia Carina E, Kelley Walter, Watt Kevin M
Division of Pediatric Critical Care, Departments of Pediatrics, University of Utah, PO Box 581289, Salt Lake City, UT, 84158, USA.
Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.
J Artif Organs. 2025 Jun;28(2):275-279. doi: 10.1007/s10047-024-01475-7. Epub 2024 Oct 14.
Continuous renal replacement therapy (CRRT) is a lifesaving therapy for critically ill patients with acute renal failure. Some patients supported with CRRT suffer from cardiac arrhythmias, which are often treated with amiodarone. While amiodarone is a very effective antiarrhythmic, it has a relatively narrow therapeutic window and a long half-life, making it challenging to dose safely. This is especially true in patients supported with CRRT, where drug pharmacokinetics are likely altered. This ex vivo study measured the extent of amiodarone extraction by the CRRT circuit. Amiodarone was administered to a closed-loop CRRT circuit. Drug was dosed to achieve therapeutic concentrations. Circuits were primed with a human blood-plasma mixture and maintained at physiologic temperature and pH. Serial blood samples were collected over time and drug concentrations were quantified. Amiodarone was heavily extracted by the ex vivo CRRT circuit with only 23% amiodarone remaining in the plasma at 6 h. The relative concentration was significantly greater in the controls than in the CRRT circuits within 2 h (n = 3; p = 0.0059). Amiodarone is heavily adsorbed by CRRT circuit components, suggesting that clinical dosing adjustments are likely required to achieve therapeutic targets.
连续性肾脏替代治疗(CRRT)是治疗急性肾衰竭危重症患者的一种挽救生命的疗法。一些接受CRRT治疗的患者会出现心律失常,常使用胺碘酮进行治疗。虽然胺碘酮是一种非常有效的抗心律失常药物,但其治疗窗相对较窄且半衰期较长,这使得安全给药具有挑战性。在接受CRRT治疗的患者中尤其如此,因为这些患者的药物药代动力学可能会发生改变。这项体外研究测量了CRRT回路对胺碘酮的清除程度。将胺碘酮应用于闭环CRRT回路。给药以达到治疗浓度。回路用人类血浆混合物预充,并维持在生理温度和pH值。随着时间的推移采集系列血样并对药物浓度进行定量。体外CRRT回路对胺碘酮的清除作用很强,6小时时血浆中仅残留23%的胺碘酮。在2小时内,对照组中的相对浓度显著高于CRRT回路中的相对浓度(n = 3;p = 0.0059)。胺碘酮被CRRT回路组件大量吸附,这表明可能需要进行临床给药调整以实现治疗目标。