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 (R2 = 0.52; p = 0.01). No significant relationship was identified between the protein binding and antimicrobial recovery (R2 = 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.