title: Renal and hepatic integrity in long-term sevoflurane sedation using the anesthetic conserving device: a comparison with intravenous propofol sedation in an animal model.
abstract: BACKGROUND
  Critically ill patients are sedated with intravenous agents because the use of inhaled agents is limited by their potential risk of toxicity. Increasing levels of inorganic fluorides after the metabolism of these agents have been considered potentially nephrotoxic. However, hepatic involvement after prolonged administration of sevoflurane has not yet been studied. The present study evaluated the potential renal and hepatic toxicity caused by prolonged administration (72h) of sevoflurane.
  
  
  METHODS
  For this experimental, prospective, randomized, controlled trial, 22 Landrace x Large-White female pigs were randomly assigned to two groups: intravenous propofol (P) or inhaled sevoflurane via the AnaConDa™ device (S, end-tidal 2.5 vol%). The P group remained sedated for 108h with propofol. In the S group, sevoflurane was administered for 72h and then changed to propofol for the remaining 36h in order to observe the kinetics of fluoride after discontinuation of sevoflurane. Serum creatinine was the primary outcome variable, but inorganic fluoride concentrations and other renal, hepatic, and cardiorespiratory variables were also measured.
  
  
  RESULTS
  Both groups of animals were comparable at baseline. No differences were found between the two groups for plasma creatinine and urea or creatinine clearance throughout the study. Fluoride levels were significantly higher in the sevoflurane group. No correlation was found between inorganic fluoride and serum creatinine values. No significant differences were observed for hepatic function. Hemodynamic, respiratory, and blood gas variables were comparable between the groups.
  
  
  CONCLUSIONS
  Long-term sedation with sevoflurane using AnaConDa™ or propofol does not negatively affect renal or hepatic function.
authors.affiliation: Servicio de Anestesiología y Reanimación, Hospital Universitario Miguel Servet, Zaragoza, España. Electronic address: lgallegoligorit@gmail.com.
authors.forename: L
authors.initials: L
authors.lastname: Gallego
authors.affiliation: Servicio de Anestesiología y Reanimación, Hospital Clínico Universitario, Valencia, España.
authors.forename: M
authors.initials: M
authors.lastname: Soro
authors.affiliation: Servicio de Anestesiología y Reanimación, Hospital Clínico Universitario, Valencia, España.
authors.forename: A
authors.initials: A
authors.lastname: Alvariño
authors.affiliation: Departamnto de Cirugía, Universitat de València, Valencia, España.
authors.forename: I
authors.initials: I
authors.lastname: Noguera
authors.affiliation: Servicio de Anestesiología y Reanimación, Hospital Clínico Universitario, Valencia, España; Departamnto de Cirugía, Universitat de València, Valencia, España.
authors.forename: F J
authors.initials: FJ
authors.lastname: Belda
mesh_terms: D000769:Anesthesia, Inhalation / Q000295:instrumentation; D000771:Anesthesia, Intravenous / Q000295:instrumentation; D000818:Animals; D003404:Creatinine / Q000097:blood; D054810:Deep Sedation / Q000295:instrumentation*; D005260:Female; D005459:Fluorides / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008099:Liver / Q000187:drug effects* / Q000503:physiopathology; D008657:Metabolic Clearance Rate; D008738:Methyl Ethers / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D015742:Propofol / Q000008:administration & dosage / Q000633:toxicity; D011446:Prospective Studies; D011897:Random Allocation; D000077149:Sevoflurane; D013552:Swine; D014508:Urea / Q000097:blood
chemical_list: D006993:Hypnotics and Sedatives; D008738:Methyl Ethers; D000077149:Sevoflurane; D014508:Urea; D003404:Creatinine; D005459:Fluorides; D015742:Propofol
keywords: AnaConDa(®); AnaConDa™; Inhalational sedation; Renal toxicity; Sedación inhalatoria; Sevoflurane; Sevoflurano; Toxicidad renal