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Peer-reviewedCC BY 4.0Critical Care Explorations

The Impact of an Ex Vivo Pediatric Extracorporeal Membrane Oxygenation Circuit on Sequestration of Antimicrobials

Abstract

OBJECTIVES: To determine if common antimicrobials ( n = 11) are sequestered or degraded during a pediatric extracorporeal membrane oxygenation (ECMO) simulation. DESIGN: An ex vivo model of a closed ECMO circuit was established to simulate the treatment of a 3 kg infant. A control was used to quantify spontaneous antimicrobial degradation. SETTING: University research laboratory. PARTICIPANTS: None. MAIN OUTCOMES AND MEASURES: The ECMO circuit was primed and maintained at physiologic pH and temperature for 7 hours. After baseline sampling, the antimicrobials were administered as a single bolus into the circuit. Eight plasma samples were taken from the controls and ECMO circuits over 7 hours. Antimicrobial concentrations were measured using validated high-performance liquid chromatography–tandem mass spectrometry methodology. The antimicrobial recovery was compared with baseline. Each simulation was performed in triplicate to assess simulation variability. RESULTS: The recovery mean (%) in ECMO at 7 hours for ampicillin 78%, cefotaxime 92%, flucloxacillin 72%, meropenem 81%, micafungin 72%, piperacillin 84%, and voriconazole 42% was significantly different from the baseline ( p < 0.05). The recovery in the control at 7 hours for ampicillin 83%, cefotaxime 76%, flucloxacillin 90%, gentamicin 85%, meropenem 76%, piperacillin 92%, and tazobactam 93% was also significantly different from the baseline ( p < 0.05). A significant relationship was identified in the ECMO model between the antimicrobial recovery (%) and the log partition coefficient (log p ) of the studied antimicrobials ( R 2 = 0.52; p = 0.01). No significant relationship was identified between the protein binding and antimicrobial recovery ( R 2 = 0.23; p = 0.13). CONCLUSIONS AND RELEVANCE: The lipophilicity of an antimicrobial is a predictor of antimicrobial recovery in ECMO. Concentrations were significantly reduced at 7 hours for greater than 60% of the study antimicrobials in the ECMO models. Clinical studies are required for children receiving ECMO to determine if the current dosing regimens for antimicrobials provide therapeutic concentrations.

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BibTeX
@article{cree2026impact,
  title = {{The Impact of an Ex Vivo Pediatric Extracorporeal Membrane Oxygenation Circuit on Sequestration of Antimicrobials}},
  author = {Michele Cree and Mohd Hafiz Abdul-Aziz and Emma Haisz and Steven Wallis and Hayoung Won and Chandra Sumi and Dusan Marjanovic and Jenny Ordóñez and Luregn Schlapbach and Jason A. Roberts},
  journal = {Critical Care Explorations},
  year = {2026},
  month = oct,
  doi = {10.1097/cce.0000000000001338},
  url = {https://hal.science/hal-05801378v1},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - The Impact of an Ex Vivo Pediatric Extracorporeal Membrane Oxygenation Circuit on Sequestration of Antimicrobials
AU  - Michele Cree
AU  - Mohd Hafiz Abdul-Aziz
AU  - Emma Haisz
AU  - Steven Wallis
AU  - Hayoung Won
AU  - Chandra Sumi
AU  - Dusan Marjanovic
AU  - Jenny Ordóñez
AU  - Luregn Schlapbach
AU  - Jason A. Roberts
PY  - 2026
DA  - 2026/10/15
JO  - Critical Care Explorations
DO  - 10.1097/cce.0000000000001338
UR  - https://hal.science/hal-05801378v1
AB  - OBJECTIVES: To determine if common antimicrobials ( n = 11) are sequestered or degraded during a pediatric extracorporeal membrane oxygenation (ECMO) simulation. DESIGN: An ex vivo model of a closed ECMO circuit was established to simulate the treatment of a 3 kg infant. A control was used to quantify spontaneous antimicrobial degradation. SETTING: University research laboratory. PARTICIPANTS: None. MAIN OUTCOMES AND MEASURES: The ECMO circuit was primed and maintained at physiologic pH and temperature for 7 hours. After baseline sampling, the antimicrobials were administered as a single bolus into the circuit. Eight plasma samples were taken from the controls and ECMO circuits over 7 hours. Antimicrobial concentrations were measured using validated high-performance liquid chromatography–tandem mass spectrometry methodology. The antimicrobial recovery was compared with baseline. Each simulation was performed in triplicate to assess simulation variability. RESULTS: The recovery mean (%) in ECMO at 7 hours for ampicillin 78%, cefotaxime 92%, flucloxacillin 72%, meropenem 81%, micafungin 72%, piperacillin 84%, and voriconazole 42% was significantly different from the baseline ( p < 0.05). The recovery in the control at 7 hours for ampicillin 83%, cefotaxime 76%, flucloxacillin 90%, gentamicin 85%, meropenem 76%, piperacillin 92%, and tazobactam 93% was also significantly different from the baseline ( p < 0.05). A significant relationship was identified in the ECMO model between the antimicrobial recovery (%) and the log partition coefficient (log p ) of the studied antimicrobials ( R 2 = 0.52; p = 0.01). No significant relationship was identified between the protein binding and antimicrobial recovery ( R 2 = 0.23; p = 0.13). CONCLUSIONS AND RELEVANCE: The lipophilicity of an antimicrobial is a predictor of antimicrobial recovery in ECMO. Concentrations were significantly reduced at 7 hours for greater than 60% of the study antimicrobials in the ECMO models. Clinical studies are required for children receiving ECMO to determine if the current dosing regimens for antimicrobials provide therapeutic concentrations.
SN  - 2639-8028
ER  -