Sequestration of Voriconazole and Vancomycin Into Contemporary Extracorporeal Membrane Oxygenation Circuits: An in vitro Study.

Genny Raffaeli,Birgit C P Koch,Giacomo Cavallaro,Dick Tibboel,Karel Allegaert,Enno D Wildschut,Fabio Mosca

doi:10.3389/fped.2020.00468

Abstract

Background: Bacterial and fungal infections are common and often contribute to death in patients undergoing extracorporeal membrane oxygenation (ECMO). Drug disposition is altered during ECMO, and adsorption in the circuit is an established causative factor. Vancomycin and voriconazole are widely used, despite the lack of evidence-based prescription guidelines.Objective: The objective of this study was to determine the extraction of voriconazole and vancomycin by the Xenios/Novalung ECMO circuits.Methods: We have set up nine closed-loop ECMO circuits, consisting of four different iLAActivve® kits for neonatal, pediatric, and adult support: three iLA-ActivveMiniLung® petite kits, two iLA-ActivveMiniLung® kits, two iLA-ActivveiLA® kits, and two iLA-Activve X-lung® kits. The circuits were primed with whole blood and maintained at physiologic conditions for 24 h. Voriconazole and vancomycin were injected as a single-bolus age-related dose into the circuits. Pre-membrane (P2) blood samples were obtained at baseline and after drug injection at 2, 10, 30, 180, 360 min, and 24 h. A control sample at 2 min was collected for spontaneous drug degradation testing at 24 h.Results: Seventy-two samples were analyzed in triplicate. The mean percentage of drug recovery at 24 h was 20% for voriconazole and 62% for vancomycin.Conclusions: The extraction of voriconazole and vancomycin by contemporary ECMO circuits is clinically relevant across all age-related circuit sizes and may result in reduced drug exposure in vivo.

Highlights

Ill patients on extracorporeal membrane oxygenation (ECMO) are at high risk of serious infections, with rates of 15.4 per 1,000 ECMO days across all age groups [1]
While the loss of voriconazole was similar across all age circuits, vancomycin levels decreased by 38% in the miniLung petite, by 25% in the minilung, by 38% in the ILA active, and by 50% in the XLung circuits (Table 1)
Suboptimal antimicrobial exposure may be associated with therapeutic failure, toxicity, antimicrobial resistance, and, worsened patient outcomes [2, 3]. In this in vitro study, we provide the equipment-related disposition of voriconazole and vancomycin in contemporary ECMO circuitry with iLAActivve, contributing insights into circuitand drug-specific determinants of PK changes during ECMO

Summary

Introduction

Ill patients on extracorporeal membrane oxygenation (ECMO) are at high risk of serious infections, with rates of 15.4 per 1,000 ECMO days across all age groups [1]. Bacteria remain the most common causative agents, fungi contribute to the healthcare burden being the second cause of nosocomial infection during ECMO [1], with a prevalence ranging from 0.04 to 5%, and differences based upon age and timing of infection [2, 5]. While the pharmacology of fluconazole, which is the recommended first-line treatment against Candida spp., has been extensively addressed in the pediatric ECMO population [9,10,11], scanty evidence is available for voriconazole, a first-line treatment for invasive aspergillosis [7, 12, 13]. Bacterial and fungal infections are common and often contribute to death in patients undergoing extracorporeal membrane oxygenation (ECMO). Vancomycin and voriconazole are widely used, despite the lack of evidence-based prescription guidelines

Methods

Results

Discussion

Conclusion