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The concept of minimum alveolar concentration (MAC) was first introduced by Dr. Edmund Eger in 1965. Prior to this time, there was no accurate way to measure the anesthetic potencies or adequate dosing. Earlier methods focused on the assessment of clinical signs, such as pupil diameter, eyelid reflex, and lacrimation during the different stages of anesthesia. Compared to the limitations associated with these signs, the principle of MAC targets a single clinical end point: immobility in response to surgical stimulus. MAC is defined as the minimum alveolar concentration of inhaled anesthetic at sea level required to suppress movement to a surgical incision in 50% of the patients. It is often referred to as the ED50 for immobility, MAC-movement, or median alveolar concentration.

Minimum alveolar concentration values were extrapolated from volatile agents using a pool of healthy human volunteers aged 30-55 years. After equilibration for 15 minutes at a particular end-tidal anesthetic concentration, a standard noxious stimulus was applied to the volunteer and observed for head or limb movement. A dose–response curve was developed based on the increasing or decreasing anesthetic concentration against movement (Figure 50-1). Minimum alveolar concentration or ED50 is the point on the curve at which 50% did not move in response to the stimulus. One standard deviation (SD) is about 10% of the MAC value. Therefore, 2 SDs will indicate a MAC value of 1.2 corresponding to the ED95; 95% of the patients will not move with noxious stimulation. MAC is quantitative and can be applied to all inhaled anesthetics. The summation of each volatile agent’s MAC value is additive, but the equipotent administration may differ on the physiologic effects, such as respiratory and hemodynamic effects.


The anesthetic concentration and the percentage of patients not moving in response to noxious stimulus. (Reproduced from Aranake A et al. Minimum alveolar concentration: ongoing relevance and clinical utility. Anaesthesia. 2013; 68(5):512-522.)


Voluntary Response (MAC-Awake)

The definition of MAC is generally used to measure the potency for immobility. Minimum alveolar concentration can be used to determine the potency for other desirable clinical features, which includes unconsciousness, amnesia, and eye-opening and autonomic response. MAC-awake has been used to measure the potency at which voluntary response to verbal command (ie, eye opening). It is defined as the anesthetic concentration needed to suppress the response to verbal command in 50% of the patients when anesthetic concentration is lowered during emergence. In contrast, MAC-unawake occurs when 50% of the patients remains responsive to verbal commands during an increase in anesthesia concentration during induction. Therefore, the induction pathway requires higher concentration for immobility and unresponsiveness than the concentration for restored movement. MAC-awake is generally one-third of its MAC for the commonly used inhaled agents (desflurane, sevoflurane, ...

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