K. Watt,1 M. Cohen-Wolkowiez,1 D. Williams,2 D. Bonadonna,1 I. Cheifetz,1 D. K. Benjamin, Jr,1 K. L. Brouwer3; 1Duke University Medical Center, Durham, NC, 2Children's Hospital of Richmond, Richmond, VA, 3University of North Carolina Eshelman School of Pharmacy, Chapel Hill, NC

BACKGROUND: Invasive candidiasis is common and often fatal in children on Extracorporeal Membrane Oxygenation (ECMO), and treatment relies on optimal dosing. The ECMO circuit can adsorb drug and decrease drug exposure, placing the child at risk of therapeutic failure. This ex vivo study determined the extraction of antifungal drugs by the ECMO circuit.
METHODS: Fluconazole and micafungin were studied separately in 3 closed-loop circuit configurations to isolate the impact of the oxygenator, hemofilter, and tubing (Fig). Each circuit was primed with blood and flow 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 4 h and concentrations quantified with a validated assay. Drug recovery was calculated at each time point: [(C0-Ci)/C0]*100, with C0 and Ci the concentrations at time=0 and i, respectively.
RESULTS: After 4 h of recirculation, fluconazole extraction by the ECMO circuit was minimal (mean recovery 89-106%). In contrast, micafungin was extracted extensively; mean recovery at 4 h was only 25% of the initial dose in the presence of a hemofilter. Micafungin was not extracted in circuits without a hemofilter (recovery 92-98%; Figure).
CONCLUSION: The ex vivo hemofilter adsorbs micafungin, which may result in decreased drug exposure in vivo.