Original Articles

Antifungal Extraction by the Extracorporeal Membrane Oxygenation Circuit

^* Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina
^† Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
^‡ Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina
^§ Department of Pediatrics, Children's Hospital of Richmond, Richmond, Virginia; and
^¶ Perfusion Services, Duke University Medical Center, Durham, North Carolina

Address correspondence to: Kevin M. Watt, MD, PhD, Duke University, Pediatrics, Duke Clinical Research Institute, PO Box 3499, Durham, NC 27710. E-mail: kevin.watt@duke.edu

Received: 30 January 2017
Accepted: 22 March 2017

Abstract

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_t/C_i)*100, with C_t and C_i the concentrations at time = t 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.