title: Comparison of the neuroapoptotic properties of equipotent anesthetic concentrations of desflurane, isoflurane, or sevoflurane in neonatal mice.
abstract: BACKGROUND
  Volatile anesthetics facilitate surgical procedures and imaging studies in millions of children every year. Neuronal cell death after prolonged exposure to isoflurane in developing animals has raised serious concerns regarding its safe use in children. Although sevoflurane and desflurane are becoming more popular for pediatric anesthesia, their cytotoxic effects have not been compared with those of isoflurane. Accordingly, using newborn mice, the current study established the respective potencies of desflurane, isoflurane, and sevoflurane and then compared equipotent doses of these anesthetics regarding their effects on cortical neuroapoptosis.
  
  
  METHODS
  Minimum alveolar concentrations were determined in littermates (aged 7-8 days, n = 42) using tail-clamp stimulation in a bracketing study design. By using equipotent doses of approximately 0.6 minimum alveolar concentration, another group of littermates was randomly assigned to receive desflurane, isoflurane, or sevoflurane or to fast in room air for 6 h. After exposure, animals (n = 47) were euthanized, neocortical apoptotic neuronal cell death was quantified, and caspase 3 activity was compared between the four groups.
  
  
  RESULTS
  The minimum alveolar concentration was determined to be 12.2% for desflurane, 2.7% for isoflurane, and 5.4% for sevoflurane. After a 6-h exposure to approximately 0.6 minimum alveolar concentration of desflurane, isoflurane, or sevoflurane, neuronal cell death and apoptotic activity were significantly increased, irrespective of the specific anesthetic used.
  
  
  CONCLUSIONS
  In neonatal mice, equipotent doses of the three commonly used inhaled anesthetics demonstrated similar neurotoxic profiles, suggesting that developmental neurotoxicity is a common feature of all three drugs and cannot be avoided by switching to newer agents.
authors.affiliation: Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
authors.forename: George K
authors.initials: GK
authors.lastname: Istaphanous
authors.forename: Jennifer
authors.initials: J
authors.lastname: Howard
authors.forename: Xinyu
authors.initials: X
authors.lastname: Nan
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Hughes
authors.forename: John C
authors.initials: JC
authors.lastname: McCann
authors.forename: John J
authors.initials: JJ
authors.lastname: McAuliffe
authors.forename: Steve C
authors.initials: SC
authors.lastname: Danzer
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Loepke
mesh_terms: D000280:Administration, Inhalation; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects*; D001784:Blood Gas Analysis; D053148:Caspase 3 / Q000032:analysis / Q000378:metabolism; D003124:Colorimetry; D000077335:Desflurane; D005260:Female; D007150:Immunohistochemistry; D007530:Isoflurane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects*; D011650:Pulmonary Alveoli / Q000378:metabolism; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D000077335:Desflurane; D007530:Isoflurane; D053148:Caspase 3