Impact of extracorporeal membrane oxygenation modes on voriconazole exposure in critically ill patients

Voriconazole is widely used for invasive fungal infections in critically ill patients, but its pharmacokinetics may be significantly altered by extracorporeal membrane oxygenation (ECMO). Data on the impact of different ECMO modes are limited.

We performed a retrospective observational study including all patients admitted to the ICU from January 2018 to May 2025 who were treated with voriconazole for suspected fungal infections. Voriconazole trough concentrations (Cmin) were compared between ECMO and non-ECMO patients. Multivariate linear regression was used to identify clinical predictors of Cmin, and subgroup analyses were performed by ECMO mode and other relevant covariates.

A total of 166 patients (492 samples) were included, including 33 ECMO patients (111 samples) and 133 non-ECMO patients (381 samples). There was no significant difference in voriconazole trough concentrations between the ECMO and non-ECMO groups. When stratified by mode, VAV-ECMO was associated with significantly lower concentrations than non-ECMO (P = 0.004), whereas VV- and VA-ECMO were comparable to non-ECMO. In multivariate linear regression, increasing age and coadministration with amiodarone were associated with higher voriconazole Cmin, whereas lower albumin levels and concomitant CRRT were associated with reduced concentrations.

ECMO support did not significantly reduce voriconazole Cmin compared with the non-ECMO group. However, VAV-ECMO is associated with reduced voriconazole exposure, suggesting a configuration-specific rather than uniform ECMO effect. Routine therapeutic drug monitoring remains essential.