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Published on: October 24, 2018
Sequestration of Voriconazole and Vancomycin Into Contemporary Extracorporeal Membrane Oxygenation Circuits: An in
Genny Raffaeli1,2,3, Giacomo Cavallaro3, Karel Allegaert4,5
1Intensive Care and Department of Pediatric Surgery Erasmus MC-Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, Netherlands.
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.
Insights
Extracorporeal membrane oxygenation (ECMO) circuits significantly reduce vancomycin and voriconazole levels. This study found substantial drug loss in ECMO circuits, impacting patient treatment efficacy.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Critical Care Medicine
- Biomaterials and Medical Devices
Background:
- Bacterial and fungal infections are leading causes of mortality in patients requiring extracorporeal membrane oxygenation (ECMO).
- Altered drug disposition during ECMO, particularly drug adsorption within the circuit, is a known issue.
- Current clinical practice lacks evidence-based guidelines for prescribing vancomycin and voriconazole during ECMO.
Purpose of the Study:
- To quantify the extent of voriconazole and vancomycin extraction by Xenios/Novalung ECMO circuits.
- To assess the impact of different ECMO circuit configurations on drug adsorption.
- To provide data for optimizing antimicrobial dosing in ECMO patients.
Main Methods:
- Nine closed-loop ECMO circuits (four types: iLAActivveMiniLung petite, iLAActivveMiniLung, iLAActivveiLA, iLAActivve X-lung) were utilized.
- Circuits were primed with whole blood and maintained under physiological conditions for 24 hours.
- Single-bolus doses of voriconazole and vancomycin were administered, with blood samples collected at multiple time points to determine drug recovery.
Main Results:
- After 24 hours, the mean drug recovery was significantly low: 20% for voriconazole and 62% for vancomycin.
- Drug extraction was observed across all tested ECMO circuit sizes, indicating a consistent adsorption phenomenon.
- Control samples showed minimal spontaneous drug degradation, confirming circuit adsorption as the primary cause of drug loss.
Conclusions:
- Contemporary ECMO circuits clinically relevantly extract both voriconazole and vancomycin.
- This extraction can lead to significantly reduced drug exposure in patients undergoing ECMO.
- Further research is needed to develop adjusted dosing strategies to ensure therapeutic drug concentrations.
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