title: Population pharmacokinetics of sevoflurane in conjunction with the AnaConDa: toward target-controlled infusion of volatiles into the breathing system.
abstract: BACKGROUND
  The Anesthetic Conserving Device (AnaConDa) uncouples delivery of a volatile anesthetic (VA) from fresh gas flow (FGF) using a continuous infusion of liquid volatile into a modified heat-moisture exchanger capable of adsorbing VA during expiration and releasing adsorbed VA during inspiration. It combines the simplicity and responsiveness of high FGF with low agent expenditures. We performed in vitro characterization of the device before developing a population pharmacokinetic model for sevoflurane administration with the AnaConDa, and retrospectively testing its performance (internal validation).
  
  
  METHODS
  Eighteen females and 20 males, aged 31-87, BMI 20-38, were included. The end-tidal concentrations were varied and recorded together with the VA infusion rates into the device, ventilation and demographic data. The concentration-time course of sevoflurane was described using linear differential equations, and the most suitable structural model and typical parameter values were identified. The individual pharmacokinetic parameters were obtained and tested for covariate relationships. Prediction errors were calculated.
  
  
  RESULTS
  In vitro studies assessed the contribution of the device to the pharmacokinetic model. In vivo, the sevoflurane concentration-time courses on the patient side of the AnaConDa were adequately described with a two-compartment model. The population median absolute prediction error was 27% (interquartile range 13-45%).
  
  
  CONCLUSIONS
  The predictive performance of the two-compartment model was similar to that of models accepted for TCI administration of intravenous anesthetics, supporting open-loop administration of sevoflurane with the AnaConDa. Further studies will focus on prospective testing and external validation of the model implemented in a target-controlled infusion device.
authors.affiliation: Department of Anesthesia & Intensive Care, Central Hospital, Västerås, Sweden. mats.enlund@ltv.se
authors.forename: M
authors.initials: M
authors.lastname: Enlund
authors.forename: D
authors.initials: D
authors.lastname: Kietzmann
authors.forename: T
authors.initials: T
authors.lastname: Bouillon
authors.forename: K
authors.initials: K
authors.lastname: Züchner
authors.forename: I
authors.initials: I
authors.lastname: Meineke
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018685:Anesthetics, Inhalation / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D010880:Piperidines / Q000008:administration & dosage; D011237:Predictive Value of Tests; D015742:Propofol / Q000008:administration & dosage; D000077208:Remifentanil; D012121:Respiration, Artificial / Q000295:instrumentation* / Q000379:methods; D000077149:Sevoflurane; D013997:Time Factors; D014835:Volatilization
chemical_list: D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D008738:Methyl Ethers; D010880:Piperidines; D000077149:Sevoflurane; D000077208:Remifentanil; D015742:Propofol