Antifungal Dosing in Critically Ill Patients on Extracorporeal Membrane Oxygenation

Extracorporeal membrane oxygenation (ECMO) is an established advanced life support system, providing temporary cardiac and/or respiratory support in critically ill patients. Fungal infections are associated with increased mortality in patients on ECMO. Antifungal drug dosing for critically ill patients is highly challenging because of altered pharmacokinetics (PK). PK changes during critical illness; in particular, the drug volume of distribution (V-d) and clearance can be exacerbated by ECMO. This article discusses the available literature to inform adequate dosing of antifungals in this patient population. The number of antifungal PK studies in critically ill patients on ECMO is growing; currently available literature consists of case reports and studies with small sample sizes providing inconsistent findings, with scant or no data for some antifungals. Current data are insufficient to provide definitive empirical drug dosing guidance and use of dosing strategies derived from critically patients not on ECMO is reasonable. However, due to high PK variability, therapeutic drug monitoring should be considered where available in critically ill patients receiving ECMO to prevent subtherapeutic or toxic antifungal exposures.