title: Ageing delays emergence from general anaesthesia in rats by increasing anaesthetic sensitivity in the brain.
abstract: BACKGROUND
  Little is known about ageing-related changes in the brain that affect emergence from general anaesthesia. We used young adult and aged Fischer 344 rats to test the hypothesis that ageing delays emergence from general anaesthesia by increasing anaesthetic sensitivity in the brain.
  
  
  METHODS
  Time to emergence was determined for isoflurane (1.5 vol% for 45 min) and propofol (8 mg kg(-1) i.v.). The dose of isoflurane required to maintain loss of righting (LOR) was established in young adult and aged rats. The efficacy of methylphenidate to reverse LOR from general anaesthesia was tested. Separate young adult and aged rats with implanted electroencephalogram (EEG) electrodes were used to test whether ageing increases sensitivity to anaesthetic-induced burst suppression.
  
  
  RESULTS
  Mean time to emergence from isoflurane anaesthesia was 47 s [95% CI 33, 60; young adult) compared with 243 s (95% CI 185, 308; aged). For propofol, mean time to emergence was 13.1 min (95% CI 11.9, 14.0; young adult) compared with 23.1 min (95% CI 18.8, 27.9; aged). These differences were statistically significant. When methylphenidate was administered after propofol, the mean time to emergence decreased to 6.6 min (95% CI 5.9, 7.1; young adult) and 10.2 min (95% CI 7.9, 12.3; aged). These reductions were statistically significant. Methylphenidate restored righting in all rats during continuous isoflurane anaesthesia. Aged rats had lower EEG power and were more sensitive to anaesthetic-induced burst suppression.
  
  
  CONCLUSIONS
  Ageing delays emergence from general anaesthesia. This is due, at least in part, to increased anaesthetic sensitivity in the brain. Further studies are warranted to establish the underlying causes.
authors.affiliation: Department of Anaesthesia, Critical Care, and Pain Medicine and.
authors.forename: J J
authors.initials: JJ
authors.lastname: Chemali
authors.affiliation: Department of Anaesthesia, Critical Care, and Pain Medicine and.
authors.forename: J D
authors.initials: JD
authors.lastname: Kenny
authors.affiliation: Department of Anaesthesia, Critical Care, and Pain Medicine and.
authors.forename: O
authors.initials: O
authors.lastname: Olutola
authors.affiliation: Department of Anaesthesia, Critical Care, and Pain Medicine and Department of Anaesthesia, Harvard Medical School and.
authors.forename: N E
authors.initials: NE
authors.lastname: Taylor
authors.affiliation: Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA Department of Neurology, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
authors.forename: E Y
authors.initials: EY
authors.lastname: Kimchi
authors.affiliation: Department of Anaesthesia, Critical Care, and Pain Medicine and Department of Anaesthesia, Harvard Medical School and.
authors.forename: P L
authors.initials: PL
authors.lastname: Purdon
authors.affiliation: Department of Anaesthesia, Critical Care, and Pain Medicine and Department of Anaesthesia, Harvard Medical School and Department of Brain and Cognitive Sciences Institute for Medical Engineering and Science, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: E N
authors.initials: EN
authors.lastname: Brown
authors.affiliation: Department of Anaesthesia, Critical Care, and Pain Medicine and Department of Anaesthesia, Harvard Medical School and ksolt@mgh.harvard.edu.
authors.forename: K
authors.initials: K
authors.lastname: Solt
mesh_terms: D000375:Aging / Q000502:physiology*; D000768:Anesthesia, General; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D004569:Electroencephalography / Q000187:drug effects; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000777:Anesthetics; D008774:Methylphenidate; D007530:Isoflurane; D015742:Propofol
keywords: ageing; delayed emergence from anaesthesia; electroencephalography