Ex Vivo Model to Decipher the Impact of Extracorporeal Membrane Oxygenation on Beta-lactam Degradation Kinetics

Cyril Leven (1, 2, 3, 4) , Pierre Fillâtre (4, 5) , Antoine Petitcollin , Marie-Clémence Verdier (2, 4) , Jérôme Laurent , Nicolas Nesseler (6) , Yoann Launey (1) , Pierre Tattevin (1) , Eric Bellissant (4, 7) , Erwan Flecher (8, 9) , Florian Lemaitre (1)

1 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
2 Department of clinical and biological pharmacology and pharmacovigilance
3 Laboratory of experimental and clinical pharmacology
4 CIC - Centre d'Investigation Clinique [Rennes]
5 Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes]
6 Service d'anesthésie réanimation chirurgicale [Rennes]
7 Service de Pharmacologie [Rennes]
8 LTSI - Laboratoire Traitement du Signal et de l'Image
9 Service de chirurgie thoracique cardiaque et vasculaire [Rennes] = Thoracic and Cardiovascular Surgery [Rennes]

BACKGROUND: As a consequence of drug sequestration, increase in volume of distribution, or alteration of elimination, extracorporeal membrane oxygenation (ECMO) might lead to inadequate plasma concentrations of vital drugs. The aim of this experimental study was to develop an ex vivo model to better characterize the impact of ECMO procedure on beta-lactam antibiotics pharmacokinetics. METHODS: Plasma concentrations of cefotaxime, ceftazidime, cefepime, piperacillin, oxacillin, amoxicillin, and ceftriaxone were measured in an ex vivo ECMO circuit primed with whole human blood and compared with controls stored in glass tubes and polyvinyl chloride tubing. Serial blood samples were collected over 48 hours, and the concentrations of beta-lactam antibiotics were quantified using a validated high-performance liquid chromatography assay. The concentrations' decay rate over time was compared between the ECMO circuits and controls using nonlinear mixed-effect modeling. RESULTS: Cefotaxime concentrations decreased markedly: 86% of the initial concentration remained after 4 hours and only 21% after 48 hours (P < 0.05 for the comparison in rate of decrease with both glass and polyvinyl chloride controls). There was no difference in the rate of decrease between ECMO circuit and controls for the other beta-lactam antibiotics. The average drug recoveries from the ECMO circuits at 48 hours were as follows: ceftazidime, 73%; cefepime, 67%; piperacillin, 71%; oxacillin, 46%; and amoxicillin, 72%. Concentrations of ceftriaxone remained stable throughout the 48-hour study both in ECMO circuits and in controls. CONCLUSIONS: Significant losses of cefotaxime were observed, whereas ceftazidime, cefepime, piperacillin, oxacillin, and amoxicillin decrease was moderate and similar to that of the control group, and ceftriaxone concentrations remained unchanged. These results are reassuring for the use of beta-lactam antibiotics in critically ill patients treated with ECMO.

Domaines: Ingénierie biomédicale

Cyril Leven, Pierre Fillâtre, Antoine Petitcollin, Marie-Clémence Verdier, Jérôme Laurent, et al.. Ex Vivo Model to Decipher the Impact of Extracorporeal Membrane Oxygenation on Beta-lactam Degradation Kinetics. Therapeutic Drug Monitoring, 2017, 39 (2), pp.180-184. ⟨10.1097/FTD.0000000000000369⟩. ⟨hal-01502244⟩