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

Frontiers in Pediatrics

article

Genny Raffaeli¹  Giacomo Cavallaro³  Karel Allegaert⁴  Birgit C. P. Koch⁵  Fabio Mosca²  Dick Tibboel¹  Enno D. Wildschut¹ 

[1] Intensive Care and Department of Pediatric Surgery Erasmus MC–Sophia Children's Hospital, University Medical Center Rotterdam;Department of Clinical Sciences and Community Health, University of Milan;Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico;Department of Development and Regeneration and Department of Pharmaceutical and Pharmacological Sciences;Hospital Pharmacy

关键词: extracorporeal membrane oxygenation;    pharmacokinetics;    pharmacology;    antibiotics;    infection;    antifungals;    drug disposition;   

DOI  :  10.3389/fped.2020.00468

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

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 .

【 授权许可】

CC BY