title: Vancomycin population pharmacokinetics during extracorporeal membrane oxygenation therapy: a matched cohort study.
abstract: BACKGROUND
  The aim of this study was to describe the population pharmacokinetics of vancomycin in critically ill patients treated with and without extracorporeal membrane oxygenation (ECMO).
  
  
  METHODS
  We retrospectively reviewed data from critically ill patients treated with ECMO and matched controls who received a continuous infusion of vancomycin (35 mg/kg loading dose over 4 hours followed by a daily infusion adapted to creatinine clearance, CrCl)). The pharmacokinetics of vancomycin were described using non-linear mixed effects modeling.
  
  
  RESULTS
  We compared 11 patients treated with ECMO with 11 well-matched controls. Drug dosing was similar between groups. The median interquartile range (IQR) vancomycin concentrations in ECMO and non-ECMO patients were 51 (28 to 71) versus 45 (37 to 71) mg/L at 4 hours; 23 (16 to 38) versus 29 (21 to 35) mg/L at 12 hours; 20 (12 to 36) versus 23 (17-28) mg/L at 24 hours (ANOVA, P = 0.53). Median (ranges) volume of distribution (Vd) was 99.3 (49.1 to 212.3) and 92.3 (22.4 to 149.4) L in ECMO and non-ECMO patients, respectively, and clearance 2.4 (1.7 to 4.9) versus 2.3 (1.8 to 3.6) L/h (not significant). Insufficient drug concentrations (that is drug levels < 20 mg/dL) were more common in the ECMO group. The pharmacokinetic model (non-linear mixed effects modeling) was prospectively validated in five additional ECMO-treated patients over a 6-month period. Linear regression analysis comparing the observed concentrations and those predicted using the model showed good correlation (r(2) of 0.67; P < 0.001).
  
  
  CONCLUSIONS
  Vancomycin concentrations were similar between ECMO and non-ECMO patients in the early phase of therapy. ECMO treatment was not associated with significant changes in Vd and drug clearance compared with the control patients.
authors.affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik, 808 - 1070, Brussels, Belgium. katia_doc@yahoo.it.
authors.forename: Katia
authors.initials: K
authors.lastname: Donadello
authors.affiliation: Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia. j.roberts2@uq.edu.au.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
authors.affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik, 808 - 1070, Brussels, Belgium. cristallinimd@gmail.com.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cristallini
authors.affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik, 808 - 1070, Brussels, Belgium. mbeumier@ulb.ac.be.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Beumier
authors.affiliation: Critical Care Research Group, Adult Intensive Care Services, The Prince Charles Hospital, Brisbane, Australia. Kiran_Shekar@health.qld.gov.au.
authors.forename: Kiran
authors.initials: K
authors.lastname: Shekar
authors.affiliation: Department of Infectious Diseases, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik, 808 - 1070, Brussels, Belgium. fjacobs@ulb.ac.be.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Jacobs
authors.affiliation: Department of Thoracic Surgery, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik, 808 - 1070, Brussels, Belgium. abelhaj@ulb.ac.be.
authors.forename: Asmae
authors.initials: A
authors.lastname: Belhaj
authors.affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik, 808 - 1070, Brussels, Belgium. jlvincen@ulb.ac.be.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vincent
authors.affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik, 808 - 1070, Brussels, Belgium. ddebacke@ulb.ac.be.
authors.forename: Daniel
authors.initials: D
authors.lastname: de Backer
authors.affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik, 808 - 1070, Brussels, Belgium. ftaccone@ulb.ac.be.
authors.forename: Fabio Silvio
authors.initials: FS
authors.lastname: Taccone
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D015331:Cohort Studies; D016638:Critical Illness / Q000628:therapy*; D015199:Extracorporeal Membrane Oxygenation / Q000379:methods* / Q000639:trends; D006801:Humans; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D012189:Retrospective Studies; D014640:Vancomycin / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin