title: Multi-level approach to anaesthetic effects produced by sevoflurane or propofol in humans: 2. BIS and tetanic stimulus-induced withdrawal reflex.
abstract: BACKGROUND
  General anaesthesia could be assessed at two sites: cortical structures and the spinal cord. However, the practicalities of measurement at these two sites differ substantially.
  
  
  METHODS
  We simultaneously analysed effects of sevoflurane (Group S; n = 16) or propofol (Group P; n = 17) on bispectral index (BIS) and the tetanic stimulus-induced withdrawal reflex (TIWR). TIWR was quantified by the area under the curve of the electromyogram of the biceps femoris muscle after electrical stimulation of the sural nerve. After loss of consciousness, TIWR was evoked once per minute. The anaesthetic was increased until TIWR disappeared. After discontinuation of the anaesthetic and reappearance of TIWR, the amount of anaesthetic was increased again. Using a sigmoid E(max) model and a first-order rate constant k(e0), we characterized the dose-response relationships for BIS and TIWR.
  
  
  RESULTS
  Concentration-dependent depression of TIWR was reasonably well modelled for sevoflurane, but poorly for propofol. TIWR was completely suppressed by sevoflurane, but not propofol. Sevoflurane reduced TIWR to 5 mV ms (very weak movement) at 1.68 vol% end-expired concentration [approximately minimum alveolar concentration (MAC value)]. The k(e0)s for TIWR were smaller than those for BIS: 0.25 (0.16-0.39) vs 0.41 (0.33-0.51) min(-1) for Group S; 0.25 (0.22-0.30) vs 0.34 (0.29-0.40) min(-1) for Group P [geometric mean (95% CI)].
  
  
  CONCLUSIONS
  High concentrations of sevoflurane depress TIWR more than propofol. With propofol, we frequently observed a paradoxical behaviour of muscles of the lower leg. TIWR lags behind BIS, indicating different effect sites for two intended anaesthetic effects: unresponsiveness to noxious stimulation and unconsciousness.
authors.affiliation: Department of Anaesthesia, Radboud University Nijmegen Medical Centre, Geert Grooteplein 10, 6500 HB Nijmegen, The Netherlands. j.mourisse@anes.umcn.nl
authors.forename: J
authors.initials: J
authors.lastname: Mourisse
authors.forename: J
authors.initials: J
authors.lastname: Lerou
authors.forename: M
authors.initials: M
authors.lastname: Struys
authors.forename: M
authors.initials: M
authors.lastname: Zwarts
authors.forename: L
authors.initials: L
authors.lastname: Booij
mesh_terms: D000328:Adult; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D008875:Middle Aged; D016343:Monitoring, Intraoperative / Q000379:methods; D015742:Propofol / Q000494:pharmacology*; D012018:Reflex / Q000187:drug effects*; D000077149:Sevoflurane; D013497:Sural Nerve / Q000502:physiology
chemical_list: D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D008738:Methyl Ethers; D000077149:Sevoflurane; D015742:Propofol