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 (RI). 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 RI (area-RI) of the electromyogram of the orbicularis oculi muscle after electrical stimulation of the supraorbital nerve was measured. Using a sigmoid Em. model and a first-order rate constant k(e0), we characterized the dose-response relationships for BIS and area-RI. Results. Concentration-dependent depression of BIS and area-RI was adequately modelled. The concentration that causes an effect midway between minimum and maximum (EC50) for area-RI 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) mu g ml(-1); mean (se)]. At doses of sevoflurane and propofol with equivalent depression of BIS, sevoflurane depressed area-RI more than propofol. The k(e0) for area-RI 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.