The Anesthetic Cascade

ADEQUATE surgical anesthesia must achieve three goals: immobility, amnesia, and absence of awareness. After the evidence of anesthetic lipophilicity was presented by Meyer1and Overton,2it was widely assumed that all these actions were accomplished at some unitary site.2A body of evidence has now accumulated demonstrating that for many anesthetic agents, the dose required to suppress consciousness exceeds the amnestic dose but is substantially less then that required for surgical immobility during noxious stimuli.3,4This suggests that these three dimensions may be mediated by different regions of the central nervous system. As has been pointed out by Rampil,5the variability among anesthetics of the ratios of concentrations needed to suppress consciousness, to block memory, and to achieve surgical immobility further invalidate the unitary hypothesis.A comprehensive explanation of the mechanism by which anesthetics cause loss of consciousness (LOC) has not yet been developed. Abundant in vitro and in vivo evidence has been provided of effects of anesthetics on a wide variety of molecular and cellular processes. Campagna et al. 6have recently provided a review of current understanding of the molecular mechanisms of anesthesia, summarizing evidence showing that inhaled anesthetics achieve immobilization by depressing the spinal cord, whereas amnesic actions are mediated within the brain. They document research indicating that subtle differences in the clinical actions of inhaled anesthetics may be attributed to actions on a of molecular evidence that actions and at many different and in many different are by anesthetic not these different less effects the of which of awareness. to explanation in of the of that are for the of that is to a of the of research in the was to that anesthetics achieve immobilization by actions on the spinal were by that the and are to anesthetics the spinal that is and spinal are by inhaled and evidence further at the of the spinal by that to noxious by of and of the spinal evidence was provided by the that the anesthetic body of evidence the that immobility may be by at the of the spinal the of by spinal anesthesia the of the the different of the nervous research on and mediated of are for that of for After a review of the on the of et al. that on a inhaled anesthetics achieve immobility and actions on many are evidence that among the not yet out are and whereas and are is to that the amnestic effects of anesthetics are mediated by some that block awareness. Abundant that be at of anesthetic that not suppress awareness. As for many anesthetics the dose to suppress consciousness exceeds that required to et al. of by during spinal anesthesia in a the at indicating of the is loss of consciousness and on of consciousness in of the of at the of the of the was by these a of to anesthetic by of suppress and surgical et al. of these to these effects of of required for to They of the in during of that of the that to the anesthetics the and the of of the at the the in the and the not of these was that the at which was not a of the some in the the a of of of of during et al. evidence to the showing that the effects of anesthetics on are to actions on the in the and may be of in that the to which the effects of these on may the of regions in of on the must be and that of the of the but not that is not but is that is consciousness is not evidence the that anesthetics on different regions of the nervous to amnesia, and absence of and that immobilization is mediated by effects on the spinal is mediated by effects on the is on the and less of anesthetics to suppress consciousness, which the absence of awareness. is the to the by which is the current of understanding of the molecular mechanisms be of of anesthetics suppress consciousness been to and molecular for anesthetic the of the within the at the that are for the of anesthetic and of anesthetic in was of many that anesthetics by the of was that within in the of and that be in of these which in evidence the of the of and to anesthetic on the effects of anesthetics in the central nervous on and and on and that at the molecular anesthetics by to by in They that at anesthetics on a wide variety of at clinical concentrations are and by to a of in the central nervous system. were to be are to clinical concentrations of to be at and and of and of may be in anesthetic some at at that anesthetic of the of a wide variety of anesthetic anesthetics by of in and has been that anesthetics at the at the and that anesthetics by that are for and and and that the evidence that and may be by concentrations of of of a been to for the effects of anesthetics on a different to that the for consciousness to be by a that to that are of are by which the of and that are by that on the of the is and that the a the a of of and the of the the and of that be the were the not be which to They that the of anesthetic is the of processes. They that of is the and for to anesthetic the showing that many to of the review of research on different of inhaled anesthetics on molecular and to has recently been provided by Campagna et al. the that consciousness the of in which are by some to the molecular of anesthetic that are by of to which anesthetics required for and may the of and the of in the of anesthetic in be to has presented a that consciousness the of by by in of of is are to by in and that consciousness on in in the of by a are on on and on by They that is at that the anesthetic to the of anesthetics within the of of of in the is to the of in the the molecular of the by that anesthetic the the of and that of and are for and to that of the molecular mechanisms of anesthesia a wide is of body of research and anesthetics may on a variety of and the effects are the brain. not by but are a are a are and are is not for a of anesthesia to be on of some effects of anesthetic on on some molecular cellular of on that of actions in the of pointed is accomplished by and that are Abundant evidence suggests that within and among these regions may a in a at all a in the of understanding of anesthetics consciousness of at some of the of the central nervous and the of of at that to the of effects at of must the the of anesthesia and these of is to these and and to understanding the mechanisms by which anesthetics suppress is to for in the and consciousness the effects of a variety of anesthetic is a variety of that been to of the of anesthesia, of the that by the and the are in are on different the in on of effects that are the brain. evidence that dimensions of and effects of the of a wide variety of that in is these of some in cellular to anesthetics suppress to the of of the of the the by on of that anesthesia was by of of in to regions and in regions and of of during anesthesia was in has been in to in to the of anesthesia on the provided by the that is a of at a of a the of a of the to of in the is by a 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of in be pointed out that may and the of a by et al. these may that are in a that to and a may be that the of on the on the are in to the in of by of anesthetics by et al. of in the and the of to the in of the of the in to by of the of in anesthesia of within may some of regions is of is in the is that of may the of may at of the and the to of is at which is and for to of the of awareness. is molecular on a cellular that by of anesthesia, may be to in the actions of anesthetic to achieve immobilization to concentrations to be further the of these that is to suppress to in the spinal must be attributed to the of the effects of anesthetics on in the of the effects the of may not be to of the in these of has been that the the the the is which the that and that is to and a in a in of in the concentrations of by in that and of by and that the that in the is the of the to the of the in in and evidence the of a mechanism for anesthesia, at many different at the cellular to of within of within a to the of many and the of that of the was in of and and in of of the on were in