Antagonism of sevoflurane anaesthesia by physostigmine: effects on the auditory steady-state response and bispectral index†

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Physostigmine, a centrally acting anticholinesterase, antagonizes the hypnotic effect of propofol, as shown by the return of consciousness (response to commands) or wakefulness (spontaneous eye-opening without response to commands) and by recovery of auditory evoked potentials (40 Hz auditory steady-state response (ASSR)) and the bispectral index (BIS). We measured the effects of physostigmine on the hypnotic effect of inhaled volatile anaesthetics, using sevoflurane as the representative agent.


Eight healthy volunteers received sevoflurane adjusted to produce loss of consciousness. Physostigmine (plus glycopyrrolate) was given while the end-tidal concentration of sevoflurane was kept constant.


Loss of consciousness was accompanied by a significant (P<0.02) decrease in ASSR amplitude (to 21% of awake value) and BIS (to 70% of awake value). Five subjects had return of consciousness or wakefulness after physostigmine. The others showed no behavioural change. Physostigmine caused a significant increase of the mean ASSR amplitude from 0.11 (SD 0.04) to 0.17 (0.06) µV (P<0.05). The BIS also increased, from 66 (12) to 74 (12), but the difference was not significant.


Physostigmine can antagonize, at least partially, the hypnotic effect of sevoflurane and changes in arousal after physostigmine are shown by ASSR measurements. However, the antagonism is not as clear or reliable as with propofol.

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