Impact of extracorporeal membrane oxygenation on voriconazole plasma concentrations: A retrospective study

Abstract

Aims: We aimed to assess the impact of extracorporeal membrane oxygenation (ECMO) on voriconazole exposure.Methods: Adult critically ill patients with or without ECMO support receiving intravenous voriconazole therapy were included in this retrospective study conducted in a tertiary referral intensive care unit. The first therapeutic drug monitoring (TDM) results of voriconazole in ECMO patients and non-ECMO patients were collected, and the prevalence of subtherapeutic concentrations was analyzed. Multivariate analyses were performed to evaluate the effect of ECMO on voriconazole exposure.Results: A total of 132 patients (including 66 patients with ECMO support) were enrolled and their respective first voriconazole trough concentrations (Cmin) were recorded. The median Cmin of the ECMO group and the non-ECMO group was 1.9 (1.4–4.4) and 4.4 (3.2–6.9) mg/L, respectively (p = 0.000), and the proportion of the two groups in subtherapeutic concentrations range (<2 mg/L) was 51.5% and 7.6%, respectively (p = 0.000). Multiple linear regression analysis of voriconazole Cmin identified that the use of ECMO and coadministration of glucocorticoids were associated with significantly reduced concentrations, while increasing SOFA score and increasing daily dose were associated with significantly increased concentrations. The model accounted for 32.2% of the variability of voriconazole Cmin. Furthermore, binary logistic regression demonstrated that the use of ECMO was an independent risk factor (OR = 7.78, p = 0.012) for insufficient voriconazole exposure.Conclusion: Our findings showed that, in addition to the known drug interactions, ECMO is a significant covariable affecting voriconazole exposure. In addition, SOFA score was identified as a factor associated with increased voriconazole concentration.

Factors influencing voriconazole plasma level in intensive care patients

“…published similar results but defined another target range as subtherapeutic. 21 Thus, our study supports the potential influence of ECMO use independently of underlying target range. However, van Daele et al did not detect any influence of ECMO on voriconazole plasma level.…”

“…In the past, an increasing number of ex vivo studies, case studies and clinical studies examined the impact of ECMO use on voriconazole plasma levels. 18 , 21 , 36–39 Compared to our study, the results of the aforementioned studies are mainly based on non-clinical approaches or a proportionally small sample size. In a comparable study concerning patient cohort and design, Ye et al .…”

Enhancing voriconazole therapy in liver dysfunction: exploring administration schemes and predictive factors for trough concentration and efficacy

“…Overall, the VRZ daily dose was positively correlated with its trough concentration significantly, which demonstrates that the necessity of reducing the VRZ dose in patients with liver dysfunction. Besides, some other factors that contribute to unpredictability of VRZ trough concentrations have been reported in published literature, such as inflammation ( van Wanrooy et al, 2014 ; Encalada Ventura et al, 2016 ), polymorphism within drug transporters ( Tilen et al, 2022 ), and the use of extracorporeal membrane oxygenation ( Ye et al, 2022 ). In the analysis of relationship between CYP2C19 and initial VRZ trough concentration, our results were similar to previously studies ( Kim et al, 2019 ; Zhang et al, 2021 ).…”

Antifungal Dosing in Critically Ill Patients on Extracorporeal Membrane Oxygenation

“…Common adverse effects include liver toxicity and QT-prolongation (except with isavuconazole), and they all exhibit to different degrees drug–drug interactions via the cytochrome P450 enzyme system and/or P-glycoprotein transporters. Fluconazole [ 41 , 42 ], isavuconazole [ 43 , 44 ], posaconazole [ 45 ] and voriconazole [ 46 , 47 ] PK have been studied in critically ill patients on ECMO support.…”