Multi-level approach to anaesthetic effects produced by sevoflurane or propofol in humans: 2. BIS and tetanic stimulus-induced withdrawal reflex.

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.