Physostigmine reverses propofol-induced unconsciousness and attenuation ofthe auditory steady state response and bispectral index in human volunteers

Background: It is postulated that alteration of central cholinergic transmi ssion plays an Important role in the mechanism by which anesthetics produce unconsciousness. The authors investigated the effect of altering central c holinergic transmission, by physostigmine and scopolamine, on unconsciousne ss produced by propofol. Methods: Propofol was administered to American Society of Anesthesiologists physical status 1 (n = 17) volunteers with use of a computer-controlled In fusion pump at increasing concentrations until unconsciousness resulted (In ability to respond to verbal commands, abolition of spontaneous movement). Central nervous system function was assessed by use of the Auditory tory St eady State Response (ASSR) and Bispectral Index (BIS) analysis of electrooc ulogram. During continuous administration of propofol, reversal of unconsci ousness produced by physostigmine (28 mu g/kg) and block of this reversal b y scopolamine (8.6 mu g/kg) were evaluated. Results: Propofol produced unconsciousness at a plasma concentration of 3.2 +/- 0.8 (+/- SD) mu g/ml (n = 17). Unconsciousness was associated with red uctions in ASSR (0.10 +/- 0.08 mu V [awake baseline 0.32 +/- 0.18 mu V], P < 0.001) and BIS (55.7 +/- 8.8 [awake baseline 92.4 +/- 3.9], P < 0.001). P hysostigmine restored consciousness in 9 of 11 subjects, with concomitant I ncreases in ASSR (0.38 +/- 0.17 mu V, P < 0.01) and BIS (75.3 +/- 8.3, P < 0.001). In all subjects (n = 6) scopolamine blocked the physostigmine-induc ed reversal of unconsciousness and the increase of the ASSR and BIS (ASSR a nd BIS during propofol-induced unconsciousness: 0.09 +/- 0.09 mu V and 58.2 +/- 7.5, respectively; ASSR and BIS after physostigmine administration: 0. 08 +/- 0.06 mu V and 56.8 +/- 6.7, respectively, NS). Conclusions These findings suggest that the unconsciousness produced by pro pofol is mediated at least in part via interruption of central cholinergic muscarinic transmission.