Multi-level approach to anaesthetic effects produced by sevoflurane or propofol in humans: 1. BIS and blink reflex.
BACKGROUND
The relative roles of forebrain and brainstem in producing adequate anaesthesia are unclear.


METHODS
We simultaneously analysed the effects of sevoflurane (Group S; n = 18) or propofol (Group P; n = 29) on the bispectral index (BIS) and the first component of the blink reflex (R1). The dose of anaesthetic agent was increased until loss of blink reflex. After discontinuation and reappearance of blink reflex activity, the amount was increased again. The area under curve R1 (area-R1) of the electromyogram of the orbicularis oculi muscle after electrical stimulation of the supraorbital nerve was measured. Using a sigmoid E(max) model and a first-order rate constant k(e0), we characterized the dose-response relationships for BIS and area-R1.


RESULTS
Concentration-dependent depression of BIS and area-R1 was adequately modelled. The concentration that causes an effect midway between minimum and maximum (EC50) for area-R1 was smaller than EC50 for BIS in both groups [0.34 (0.19) vs 1.29 (0.19) vol% and 1.78 (0.65) vs 2.69 (0.67) mug ml(-1); mean (sd)]. At doses of sevoflurane and propofol with equivalent depression of BIS, sevoflurane depressed area-R1 more than propofol. The k(e0) for area-R1 was about half that for BIS in both groups: 0.24 (0.19-0.29) vs 0.48 (0.38-0.60) min(-1) for Group S; 0.28 (0.23-0.34) vs 0.46 (0.40-0.54) min(-1) for Group P, geometric mean (95% CI).


CONCLUSIONS
The blink reflex (brainstem function) is more sensitive to sevoflurane or propofol than BIS (forebrain function). Sevoflurane suppresses the blink reflex more than propofol. Different k(e0)s for blink reflex vs BIS indicate different effect sites.
Mourisse
J
J
Department of Anaesthesia, Radboud University Nijmegen Medical Centre, Geert Grooteplein 10, 6500 HB Nijmegen, The Netherlands. j.mourisse@anes.umcn.nl
Lerou
J
J
Struys
M
M
Zwarts
M
M
Booij
L
L
D000328:Adult; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D001767:Blinking / Q000187:drug effects* / Q000502:physiology; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects*; D004576:Electromyography; D005260:Female; D006801:Humans; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D008875:Middle Aged; D016343:Monitoring, Intraoperative / Q000379:methods; D015742:Propofol / Q000494:pharmacology*; D016548:Prosencephalon / Q000187:drug effects / Q000502:physiology; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D008738:Methyl Ethers; D000077149:Sevoflurane; D015742:Propofol