Incidence of Therapeutic Azole Dosing in ECMO Patients

Introduction: Extracorporeal membrane oxygenation (ECMO) is a lifesaving supportive intervention that is indicated in patients with cardiac and/or respiratory failure. ECMO can theoretically alter drug pharmacokinetics and pharmacodynamics, particularly in drugs with high degrees of lipophilicity and protein binding, including triazole antifungals. The goal of this study was to describe incidence of therapeutic concentrations for triazoles during ECMO and describe required dosing.


Methods: This retrospective cohort study included patients on ECMO receiving voriconazole or posaconazole for either treatment or prevention of invasive fungal infection with concomitant therapeutic drug monitoring between July 2015 and July 2025. The primary outcome was percent of therapeutic concentrations. Secondary outcomes included dosing strategies to achieve therapeutic concentrations (mg/kg or mg/day) and proportion of therapeutic concentrations with initial monitoring.


Results: A total of 12 patients received ECMO and concomitant azole therapy, with 36 monitoring labs. The population had a median age of 42 years (IQR 26-60) and 58% were male. The most common indications were Aspergillosis and lung transplant prophylaxis (N=4 each, 33%). Of the 36 concentrations, 15 were therapeutic (41.6%), including 39% of voriconazole and 50% of posaconazole concentrations, with 6 (16.7%) being supratherapeutic after dose titrations. Ten patients were new start azole with ECMO and only 4/10 concentrations were therapeutic on initial monitoring. The median total daily dose needed to achieve therapeutic concentrations was voriconazole 4 mg/kg (IQR 4-6.8) and posaconazole 300 mg/day (IQR 200-500).


Conclusions: Azole antifungals during ECMO are therapeutic only 41.6% of the time, with voriconazole having a higher proportion of subtherapeutic concentrations (39% vs 50%). Voriconazole had a large variation in dosing required to be therapeutic and subsequent studies should investigate which patients may be more likely to need higher doses.