Sites of Central Nervous System Action and Anesthetic End Points

Traditionally, most investigators assumed that surgical anesthesia resulted from a supraspinal event. Although it remains probable that an interaction of inhaled anesthetics with various brain structures is required for the production of amnesia, the ability of anesthetics to prevent a motor response to noxious stimulation likely results from a site of action in the spinal cord and not in the brain.

The isoflurane MAC in rats is not altered by bilateral decerebration, including removal of thalamus and hippocampus^[28] ( Fig. 4-5 ), nor by high thoracic spinal cord transection and functional separation of the rat brain from the spinal cord.^[29] The cerebral blood supply of the goat allows for the preferential anesthetization of its forebrain, which results in an isoflurane MAC that is more than twice the value found when anesthetic is administered through the goat's native circulation.^[30] This finding in a second species confirms the importance of extracranial structures in anesthesia as defined by the MAC.

If anesthesia is defined as consisting of at least two components, amnesia and immobility in response to a noxious stimulus, there must be two separate anatomic sites of inhaled anesthetic action: a supraspinal site involved in the production of amnesia and a spinal site involved in the prevention of movement in response to noxious stimuli.^[31] Given that the human CNS consists of billions of neurons, each having thousands of synapses, the discovery of the exact nature of these sites of anesthetic action presents a formidable challenge. Attempts to reduce this complexity have led to experiments on isolated neuronal preparations.