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document
Physostigmine reverses propofol-induced unconsciousness and attenuation of the auditory steady state response and bispectral index in human volunteers . BACKGROUND It is postulated that alteration of central cholinergic transmission plays an important role in the mechanism by which anesthetics produce unconsciousness . The authors investigated the effect of altering central cholinergic transmission , by physostigmine and scopolamine , on unconsciousness produced by propofol . METHODS Propofol was administered to American Society of Anesthesiologists physical status 1 ( n = 17 ) volunteers with use of a computer-controlled infusion pump at increasing concentrations until unconsciousness resulted ( inability to respond to verbal commands , abolition of spontaneous movement ) . Central nervous system function was assessed by use of the Auditory Steady State Response ( ASSR ) and Bispectral Index ( BIS ) analysis of electrooculogram . During continuous administration of propofol , reversal of unconsciousness produced by physostigmine ( 28 microgram/kg ) and block of this reversal by scopolamine ( 8.6 microgram/kg ) were evaluated . RESULTS Propofol produced unconsciousness at a plasma concentration of 3.2 +/- 0.8 ( +/- SD ) microgram/ml ( n = 17 ) . Unconsciousness was associated with reductions in ASSR ( 0.10 +/- 0.08 microV [ awake baseline 0.32 +/- 0.18 microV ] , P < 0.001 ) and BIS ( 55.7 +/- 8.8 [ awake baseline 92.4 +/- 3.9 ] , P < 0.001 ) . Physostigmine restored consciousness in 9 of 11 subjects , with concomitant increases in ASSR ( 0.38 +/- 0.17 microV , P < 0.01 ) and BIS ( 75.3 +/- 8.3 , P < 0.001 ) . In all subjects ( n = 6 ) scopolamine blocked the physostigmine-induced reversal of unconsciousness and the increase of the ASSR and BIS ( ASSR and BIS during propofol-induced unconsciousness : 0.09 +/- 0.09 microV and 58.2 +/- 7.5 , respectively ; ASSR and BIS after physostigmine administration : 0.08 +/- 0.06 microV and 56.8 +/- 6.7 , respectively , NS ) . CONCLUSIONS These findings suggest that the unconsciousness produced by propofol is mediated at least in part via interruption of central cholinergic muscarinic transmission .
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Intervention_Pharmacological
Physostigmine
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Intervention_Pharmacological
physostigmine
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Intervention_Pharmacological
scopolamine
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Intervention_Pharmacological
Propofol
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Intervention_Pharmacological
physostigmine
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Intervention_Pharmacological
scopolamine
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Outcome_Physical
Central nervous system function
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Outcome_Physical
Auditory Steady State Response ( ASSR ) and Bispectral Index ( BIS ) analysis of electrooculogram .
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Outcome_Physical
reversal of unconsciousness
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Outcome_Physical
block of this reversal
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Outcome_Physical
unconsciousness
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Outcome_Physical
plasma concentration
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Outcome_Physical
Unconsciousness
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Outcome_Physical
ASSR
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Outcome_Physical
BIS
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Outcome_Physical
restored consciousness
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Outcome_Physical
ASSR
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Outcome_Physical
BIS
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Outcome_Physical
physostigmine-induced reversal of unconsciousness
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Outcome_Physical
increase of the ASSR and BIS ( ASSR and BIS
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Outcome_Physical
ASSR and BIS
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Participant_Condition
American Society of Anesthesiologists physical status 1
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Participant_Sample-size
17