MEASUREMENT OF ANESTHETIC POTENCIES—MINIMUM ALVEOLAR CONCENTRATION

An exploration of the mechanism by which anesthetics act requires knowledge of the relative anesthetic potencies for each of the agents. The best estimate of anesthetic potency is the minimum alveolar concentration (MAC) (at 1 atm) of an agent that produces immobility in 50% of subjects exposed to a noxious stimulus.^[5] For determination of the MAC in humans, the stimulus is a surgical skin incision. (Variations on the MAC concept may be used to estimate the potency of other anesthetic end points. For example, lack of response to verbal command [i.e., MAC awake] occurs at lower anesthetic concentrations, and lack of response to endotracheal intubation [i.e., MAC intubation] occurs at higher anesthetic concentrations than those needed to prevent movement to surgical skin incision [see Chapter 31 ]). In animals, the noxious stimulus is usually produced by clamping the tail or by passing electrical current through subcutaneous electrodes. The advantage of measuring the alveolar concentration is that, after a short period of equilibration, this concentration directly represents the partial pressure of anesthetic in the central nervous system (CNS) and is independent of the uptake and distribution of the agent to other tissues (see Chapter 5 and Chapter 31 ). Another advantage of MAC is its consistency for a given animal or species or between different species or classes of animals.^{[5] [6]} This consistency makes it possible to discern small changes in anesthetic requirement, which may give a clue about how anesthetics act.

The anesthetic concentration that abolishes the righting reflex in 50% of the animals is often used to measure anesthetic potencies in smaller animals; it is an anesthetic with a 50% effective dose (ED₅₀ ). Because the inspired rather than the alveolar concentrations are measured, the method applies best to rapidly equilibrating (poorly blood-soluble) agents. Only with equilibration can it be assumed that the partial pressure of the inspired gas equals that at the site of action. The use of small animals and inspired concentrations facilitates work with agents at very high pressures (i.e., tens or hundreds of atmospheres). The anesthetic ED₅₀ in the mouse, as determined by the rolling response (i.e., the righting reflex), correlates closely with the MAC in humans over a 500-fold change in anesthetic requirements ( Fig. 4-2 ).

The tail-clamp ED₅₀ (MAC) and the righting-reflex ED₅₀ are not identical. The tail-clamp ED₅₀ is higher than the righting-reflex ED₅₀ , and the ratio of these measurements averages approximately 2 ( Table 4-1 ). This ratio varies slightly with the anesthetic examined, implying that the righting reflex is depressed, at least in part, by a different mechanism from that which depresses the response to a noxious stimulus.^{[7] [8] [9]}

An important action of inhaled anesthetics is the ability to suppress learning and memory. In humans, volatile anesthetic concentrations equivalent to approximately 0.3 MAC are required to suppress learning of auditory or verbal information during nonsurgical conditions. In an animal model, the concentration of volatile anesthetic to suppress learning in rats depends on the conditioned stimulus employed and varies between about 0.2 and 0.6 MAC.^[10] The absolute and relative potencies of inhaled anesthetics depend on the end point measured. ^[11]

Figure 4-2 A close correlation exists between the minimum alveolar concentration (MAC) of various anesthetics, preventing a response to surgical incision in humans, and the inspired dose of an anesthetic (ED₅₀ ) required to abolish the righting reflex in the mouse. (Data from references ^{[5] [8] [180]} and from Eger EI II, Rutherford, NJ: Desflurane: A Compendium and Reference. Healthpress Publishing Group, 1993, p 13.)

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