title: Recovery and kinetic characteristics of desflurane and sevoflurane in volunteers after 8-h exposure, including kinetics of degradation products.
abstract: BACKGROUND
  Desflurane and sevoflurane permit speedier changes in anesthetic partial pressures than do older halogenated anesthetics. The authors determined the kinetic characteristics of desflurane and sevoflurane and those of compound A [CH2F-O-C(=CF2)(CF3)], a nephrotoxic degradation product of sevoflurane.
  
  
  METHODS
  Volunteers received 1.25 minimum alveolar concentration of desflurane or sevoflurane, each administered for 8 h in a fresh gas inflow of 2 l/min. Inspired (F(I)) and end-tidal (F(A)) concentrations of anesthetic and compound A were measured during administration, and F(A) relative to F(A0) (the last end-tidal concentration during administration) during elimination. The indices of recovery were also measured.
  
  
  RESULTS
  The ratio F(I)/F(A) rapidly approached 1.0, with values greater for sevoflurane (desflurane 1.06 +/- 0.01 vs. sevoflurane 1.11 +/- 0.02, mean +/- SD). The ratio F(A)/F(I) for compound A was approximately 0.8. The F(A)/F(A0) ratio decreased slightly more rapidly with desflurane than with sevoflurane, and objective measures indicated faster recovery with desflurane: The initial response to command (14 +/- 4 min vs. 28 +/- 8 min [means +/- SD]) and orientation (19 +/- 4 vs. 33 +/- 9 min) was quicker, and recovery was faster as defined by results of the Digit Symbol Substitution, P-deletion, and Trieger tests. Desflurane produced less vomiting (1 [0.5, 3]; median [quartiles] episodes) than did sevoflurane (5 [2.5, 7.5] episodes). The F(A)/F(A0) ratio for compound A decreased within 5 min to a constant value of 0.1.
  
  
  CONCLUSIONS
  These anesthetics have kinetics consistent with their solubilities. Sevoflurane's greater biodegradation probably increases F(I)/F(A) differences during anesthetic administration and decreases F(A)/F(A0) differences during elimination. The F(A) for compound A differs from F(I) by 20% (F(A)/F(I) = 0.8) because of substantial degradation. Recovery from anesthesia proceeds nearly twice as fast with desflurane than with sevoflurane. Differences in ventilation, or alveolar or tissue elimination, do not completely explain the slower recovery with sevoflurane.
authors.affiliation: Department of Anesthesia, University of California, San Francisco 94143-0464, USA. eger@zachary.ucsf.edu
authors.forename: E I
authors.initials: EI
authors.lastname: Eger
authors.forename: T
authors.initials: T
authors.lastname: Bowland
authors.forename: P
authors.initials: P
authors.lastname: Ionescu
authors.forename: M J
authors.initials: MJ
authors.lastname: Laster
authors.forename: Z
authors.initials: Z
authors.lastname: Fang
authors.forename: D
authors.initials: D
authors.lastname: Gong
authors.forename: J
authors.initials: J
authors.lastname: Sonner
authors.forename: R B
authors.initials: RB
authors.lastname: Weiskopf
mesh_terms: D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics*; D000077335:Desflurane; D004987:Ethers / Q000493:pharmacokinetics*; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000493:pharmacokinetics; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D008738:Methyl Ethers; D000077149:Sevoflurane; D013997:Time Factors
chemical_list: D018685:Anesthetics, Inhalation; D004987:Ethers; D006845:Hydrocarbons, Fluorinated; D008738:Methyl Ethers; D000077149:Sevoflurane; C078742:fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether; D000077335:Desflurane; D007530:Isoflurane