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Veno-Venous Extracorporeal Membrane Oxygenation in a Mouse
Published on: October 24, 2018
Variable Sequestration of Antifungals in an Extracorporeal Membrane Oxygenation Circuit
Haifa Lyster1,2, Timothy Pitt1, Olaf Maunz1
1From the Royal Brompton and Harefield Hospitals, Part of Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
Abstract:
Fungal infections are common and frequently associated with clinical failure in patients receiving extracorporeal membrane oxygenation (ECMO). Antifungal drugs have physicochemical characteristics associated with a higher likelihood of sequestration onto ECMO circuitry potentially leading to a subtherapeutic drug concentration. The percentage of sequestration of the antifungal drugs-caspofungin, posaconazole, and voriconazole-was determined using an ex vivo ECMO model. The circuits were primed with whole human blood, sodium chloride 0.9%, and human albumin solution. Serial 2 ml samples were taken at baseline, 0.5, 1, 2, 6, 12, and 24 hours after drug addition, paired with non-ECMO controls stored in a water bath at 37°C. Mean loss from the blood-primed ECMO circuits and controls at 24 hours relative to baseline were 80% and 61% for caspofungin ( p = ns), 64% and 11% for posaconazole ( p < 0.005), and 27% and 19% for voriconazole ( p < 0.05). Calculated AUC 0-24 showed a 44% for caspofungin ( p = ns), 30.6% posaconazole ( p < 0.005), and 9% loss for voriconazole ( p = 0.003) compared with the controls, suggesting therapeutic concentrations of these antifungal agents cannot be guaranteed with standard dosing in patients on ECMO. Posaconazole exhibited the greatest loss to the ECMO circuit correlating with both high lipophilicity and protein binding of the drug.
Insights
Antifungal drug sequestration onto extracorporeal membrane oxygenation (ECMO) circuits leads to subtherapeutic concentrations. Posaconazole showed the greatest loss, indicating standard dosing may be insufficient for patients on ECMO.
Area of Science:
- Pharmacology
- Critical Care Medicine
- Infectious Diseases
Background:
- Fungal infections pose a significant risk in patients undergoing extracorporeal membrane oxygenation (ECMO).
- Antifungal drugs may be sequestered by ECMO circuitry, compromising therapeutic efficacy.
- Understanding drug-circuit interactions is crucial for optimizing antifungal therapy in critically ill patients.
Purpose of the Study:
- To quantify the sequestration of caspofungin, posaconazole, and voriconazole onto ECMO circuitry.
- To evaluate the impact of ECMO on antifungal drug concentrations over time.
- To determine if standard dosing ensures therapeutic drug levels in patients on ECMO.
Main Methods:
- An ex vivo ECMO model was utilized, priming circuits with human blood, saline, and albumin.
- Serial blood samples were collected from ECMO circuits and controls over 24 hours post-drug administration.
- Drug concentrations were measured, and sequestration percentages were calculated relative to baseline and controls.
Main Results:
- Significant sequestration of caspofungin (80%), posaconazole (64%), and voriconazole (27%) onto ECMO circuits was observed at 24 hours.
- Posaconazole exhibited the highest loss, correlating with its lipophilicity and protein binding.
- AUC 0-24 analysis revealed substantial drug loss for caspofungin (44%), posaconazole (30.6%), and voriconazole (9%) compared to controls.
Conclusions:
- Standard dosing of caspofungin, posaconazole, and voriconazole may not achieve therapeutic concentrations in patients on ECMO due to circuit sequestration.
- Posaconazole's physicochemical properties contribute to its significant loss in ECMO circuits.
- Further research and dose adjustments are warranted to ensure effective antifungal treatment in ECMO patients.
