Amiodarone extraction by continuous renal replacement therapy: results from an ex vivo study

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.