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. 2021 Jul 20;9(7):1543.
doi: 10.3390/microorganisms9071543.

A Large Retrospective Assessment of Voriconazole Exposure in Patients Treated with Extracorporeal Membrane Oxygenation

Ruth Van Daele  1   2 , Britt Bekkers  2 , Mattias Lindfors  3   4 , Lars Mikael Broman  3   4 , Alexander Schauwvlieghe  5   6 , Bart Rijnders  6   7 , Nicole G M Hunfeld  8 , Nicole P Juffermans  9 , Fabio Silvio Taccone  10 , Carlos Antônio Coimbra Sousa  10 , Luc-Marie Jacquet  11 , Pierre-François Laterre  12 , Eric Nulens  13 , Veerle Grootaert  14 , Haifa Lyster  15   16 , Anna Reed  16   17 , Brijesh Patel  18   19 , Philippe Meersseman  20 , Yves Debaveye  21   22 , Joost Wauters  23   24 , Christophe Vandenbriele  19   25   26 , Isabel Spriet  1   2
Affiliations

A Large Retrospective Assessment of Voriconazole Exposure in Patients Treated with Extracorporeal Membrane Oxygenation

Ruth Van Daele et al. Microorganisms. .

Abstract

Background: Voriconazole is one of the first-line therapies for invasive pulmonary aspergillosis. Drug concentrations might be significantly influenced by the use of extracorporeal membrane oxygenation (ECMO). We aimed to assess the effect of ECMO on voriconazole exposure in a large patient population.

Methods: Critically ill patients from eight centers in four countries treated with voriconazole during ECMO support were included in this retrospective study. Voriconazole concentrations were collected in a period on ECMO and before/after ECMO treatment. Multivariate analyses were performed to evaluate the effect of ECMO on voriconazole exposure and to assess the impact of possible saturation of the circuit's binding sites over time.

Results: Sixty-nine patients and 337 samples (190 during and 147 before/after ECMO) were analyzed. Subtherapeutic concentrations (<2 mg/L) were observed in 56% of the samples during ECMO and 39% without ECMO (p = 0.80). The median trough concentration, for a similar daily dose, was 2.4 (1.2-4.7) mg/L under ECMO and 2.5 (1.4-3.9) mg/L without ECMO (p = 0.58). Extensive inter-and intrasubject variability were observed. Neither ECMO nor squared day of ECMO (saturation) were retained as significant covariates on voriconazole exposure.

Conclusions: No significant ECMO-effect was observed on voriconazole exposure. A large proportion of patients had voriconazole subtherapeutic concentrations.

Keywords: critically ill patients; exposure; extracorporeal membrane oxygenation; invasive fungal infections; pharmacokinetics; therapeutic drug monitoring; variability; voriconazole.

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Conflict of interest statement

LMB discloses the following conflicts of interest; Eurosets Srl., Medolla, Italy (Medical Advisory Board); Xenios AG, Heilbronn, Germany (Medical Advisory Board). AS has received non-financial support from Gilead Sciences and Pfizer, outside the context of this work. HF received honoraria for speaking at symposia from Pfizer but not related to the work under consideration. JW received speakers fee from MSD, Pfizer and Gilead, consultancy fee from Gilead and he obtained investigator-initiated grants from Gilead, Pfizer and MSD. IS is supported by the Clinical Research Fund of UZ Leuven and served as a consultant to and has received unrestricted travel and research grants from Gilead Sciences, Merck Sharpe and Dohme Corp., and Pfizer, Inc and Cidara. All contracts were through and invoiced by UZ and KU Leuven. RVD, BB, ML, BR, NGMH, PJ, FST, CACS, LMJ, PFL, EN, VG, AR, BP, PM, YD and CVDB have no conflicts of interest to declare related to this work.

Figures

Figure 1
Figure 1
Boxplot; Voriconazole trough concentrations, corrected for dose 24 h, on ECMO versus non-ECMO sampling days.
Figure 2
Figure 2
Scatterplot; Voriconazole concentrations on ECMO (grey) versus non-ECMO (black) sampling days with spearman-coefficient and p-value (n = 282). The dashed line represents the lower limit concentration of 2 mg/L.
Figure 3
Figure 3
Voriconazole trough concentration in function of the day of ECMO with spearman-coefficient and p-value (n = 145). The dashed line represents the lower limit concentration of 2 mg/L.
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