Antifungal Extraction by the Extracorporeal Membrane Oxygenation Circuit

• Published in: The Journal of extra-corporeal technology 2017-09, Vol.49 (3), p.150-159
• Main Authors: Watt, Kevin M, Cohen-Wolkowiez, Michael, Williams, Duane C, Bonadonna, Desiree K, Cheifetz, Ira M, Thakker, Dhiren, Benjamin, Jr, Daniel K, Brouwer, Kim L R
• Format: Article
• Language: English
• Subjects: Blood Circulation Time; Candidiasis - blood; Candidiasis - drug therapy; Dose-Response Relationship, Drug; Echinocandins - administration & dosage; Echinocandins - pharmacokinetics; Extracorporeal Membrane Oxygenation - instrumentation; Extracorporeal Membrane Oxygenation - methods; Fluconazole - administration & dosage; Fluconazole - pharmacokinetics; Hemofiltration - instrumentation; Hemofiltration - methods; Humans; Lipopeptides - administration & dosage; Lipopeptides - pharmacokinetics; Micafungin; Original; Protein Binding; Serum Albumin - metabolism
• ISSN: 0022-1058; 2969-8960
• DOI: 10.1051/ject/201749150

Invasive candidiasis is common and often fatal in patients supported with extracorporeal membrane oxygenation (ECMO), and treatment relies on optimal antifungal dosing. The ECMO circuit can extract drug and decrease drug exposure, placing the patient at risk of therapeutic failure. This ex vivo study determined the extraction of antifungal drugs by the ECMO circuit. Fluconazole and micafungin were studied separately in three closed-loop circuit configurations to isolate the impact of the oxygenator, hemofilter, and tubing on circuit extraction. Each circuit was primed with human blood, and flow was set to 1 L/min. Drug was dosed to achieve therapeutic concentrations. Each antifungal was added to a separate tube of blood to serve as a control. Serial blood samples were collected over 24 hours and concentrations were quantified with a validated assay. Drug recovery was calculated at each time point: (C /C )*100, with C and C the concentrations at time = and 1 minute, respectively. After 24 hours of recirculation, mean recovery of fluconazole in the ECMO circuit (95-98%) and controls (101%) was high. In contrast, mean recovery of micafungin was dependent on the time and circuit configuration. Recovery at 4 hours was only 46% when a hemofilter was in-line but was much higher when the hemofilter was removed (91%). By 24 hours, however, micafungin recovery was low in all circuit configurations (26-43%), regardless of the presence of a hemofilter, as well as in the controls (57%). In conclusion, these results suggest that micafungin is extracted by the ECMO circuit, which may result in decreased drug exposure in vivo.