Components of General Anesthesia: History of the Concept Transformation.

The concept that the state of general anesthesia consists of a number of components representing the distinct and desired central effects of general anesthetics was formulated when it was common to believe that all components of anesthesia have a lipid-centered mechanism of action. The transformation of this concept was associated with changes in our understanding of the mechanisms underlying general anesthetic action. First came the shift from a lipid- to a protein-centered mechanism of action, which opened the way to various molecular targets associated with general anesthesia. Then, it was found that different components of anesthesia may have completely different underlying mechanisms, such as blockade of movement in response to noxious stimulation by isoflurane centers at the spinal cord level, not at the brain, as is the case with other components. The chain of discoveries associated with newfound differences between components of anesthesia accompanied general progress toward a more comprehensive understanding of the mechanism of action of general anesthetics, including anesthetic binding sites, details of receptors and ion channels involved in neurotransmission, and the critical role of neuronal networks. There are several important consequences of our improved understanding. First, a single measurement of anesthetic depth (eg, minimum alveolar concentration index [MAC index]) might not be appropriate for the different component of anesthesia. Second, because the mechanism of action of the components varies, synergy for 1 component does not exclude an additive effect or even antagonism for another component.