title: Ex Vivo Model to Decipher the Impact of Extracorporeal Membrane Oxygenation on Beta-lactam Degradation Kinetics.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: *Department of Clinical and Biological Pharmacology and Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes University Hospital; †Laboratory of Experimental and Clinical Pharmacology, Faculty of Medicine, Rennes 1 University; ‡Inserm, CIC-P 1414 Clinical Investigation Center, Rennes, France; §Department of Biochemistry, Pharmacology and Toxicology, Brest University Hospital, Brest, France; Departments of ¶Infectious Diseases and Intensive Care Unit, ‖Thoracic and Cardio-Vascular Surgery, and **Surgical Intensive Care Unit, Rennes University Hospital; ††Inserm 1099, CIC-IT, Clinical Investigation Centre, Rennes, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Leven
authors.forename: Pierre
authors.initials: P
authors.lastname: Fillâtre
authors.forename: Antoine
authors.initials: A
authors.lastname: Petitcollin
authors.forename: Marie-Clémence
authors.initials: MC
authors.lastname: Verdier
authors.forename: Jérôme
authors.initials: J
authors.lastname: Laurent
authors.forename: Nicolas
authors.initials: N
authors.lastname: Nesseler
authors.forename: Yoann
authors.initials: Y
authors.lastname: Launey
authors.forename: Pierre
authors.initials: P
authors.lastname: Tattevin
authors.forename: Eric
authors.initials: E
authors.lastname: Bellissant
authors.forename: Erwan
authors.initials: E
authors.lastname: Flécher
authors.forename: Florian
authors.initials: F
authors.lastname: Lemaitre
mesh_terms: D000900:Anti-Bacterial Agents / Q000097:blood* / Q000493:pharmacokinetics*; D015199:Extracorporeal Membrane Oxygenation / Q000379:methods; D006801:Humans; D007700:Kinetics; D047090:beta-Lactams / Q000097:blood* / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams