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 adequateanaesthesia are unclear. Methods: We simultaneously analysed the effects of sevoflurane (GroupS; n = 18) or propofol (Group P; n = 29) on the bispectral index(BIS) and the first component of the blink reflex (R1). Thedose of anaesthetic agent was increased until loss of blinkreflex. After discontinuation and reappearance of blink reflexactivity, the amount was increased again. The area under curveR1 (area-R1) of the electromyogram of the orbicularis oculimuscle after electrical stimulation of the supraorbital nervewas measured. Using a sigmoid E_max model and a first-order rateconstant k_e0, we characterized the dose–response relationshipsfor BIS and area-R1. Results: Concentration-dependent depression of BIS and area-R1 was adequatelymodelled. The concentration that causes an effect midway betweenminimum and maximum (EC₅₀) for area-R1 was smaller than EC₅₀for BIS in both groups [0.34 (0.19) vs 1.29 (0.19) vol% and1.78 (0.65) vs 2.69 (0.67) µg ml^–1; mean (SD)].At doses of sevoflurane and propofol with equivalent depressionof BIS, sevoflurane depressed area-R1 more than propofol. Thek_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^–1for 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 sevofluraneor propofol than BIS (forebrain function). Sevoflurane suppressesthe blink reflex more than propofol. Different k_e0s for blinkreflex vs BIS indicate different effect sites.