Minimum alveolar concentration
Minimum alveolar concentration or MAC is the concentration of a vapour in the lungs that is needed to prevent movement (motor response) in 50% of subjects in response to surgical (pain) stimulus. MAC is used to compare the strengths, or potency, of anaesthetic vapours. MAC was introduced in 1965.
MAC actually is a median value, not a minimum as term implies. The original paper proposed MAC as the minimal alveolar concentration, which was shortly thereafter revised to minimum alveolar concentration. A lower MAC value represents a more potent volatile anesthetic.
Other uses of MAC include MAC-BAR (1.7-2.0 MAC), which is the concentration required to block autonomic reflexes to nociceptive stimuli, and MAC-awake (0.3-0.5 MAC), the concentration required to block voluntary reflexes and control perceptive awareness.
The MAC is the concentration of the vapour (measured as a percentage at 1 atmosphere, i.e. the partial pressure) that prevents patient movement in response to a supramaximal  stimulus (traditionally a set depth and width of skin incisions) in 50% of subjects. This measurement is done at steady state (assuming a constant alveolar concentration for 15 minutes), under the assumption that this allows for an equilibration between the gasses in the alveoli, the blood and the brain. MAC is accepted as a valid measure of potency of inhalational general anaesthetics because it remains fairly constant for a given species even under varying conditions.
The MAC of a volatile substance is inversely proportional to its lipid solubility (oil:gas coefficient), in most cases. This is the Meyer-Overton hypothesis put forward in 1899–1901 by Hans Horst Meyer and Charles Ernest Overton. MAC is inversely related to potency, i.e. high MAC equals low potency.
The hypothesis correlates lipid solubility of an anaesthetic agent with potency (1/MAC) and suggests that onset of anaesthesia occurs when sufficient molecules of the anaesthetic agent have dissolved in the cell's lipid membranes, resulting in anaesthesia. Exceptions to the Meyer-Overton hypothesis can result from:
- convulsant property of an agent
- specific receptor (various agents may exhibit an additional effect through specific receptors)
- co-administration of Alpha2 agonists (dexmedetomidine) and/or opioid receptor agonists (morphine/fentanyl) can decrease the MAC
- Mullin's critical volume hypothesis
- Positive modulation of GABA at GABAA receptors by barbiturates or benzodiazepines
Certain physiological and pathological states may alter MAC. MAC is higher in infants and lower in the elderly. Also, MAC increases with hyperthermia, hypernatremia and chronic alcohol ingestion. Likewise, hypothermia, hypotension (MAP < 40 mmHg), and pregnancy seem to decrease MAC. Duration of anesthesia, gender, height and weight seem to have little effect on MAC. Opioid analgesics and sedative-hypnotics, often used as adjuvants to anesthesia, decrease MAC. It should also be noted that MAC values are additive. For instance, when applying 0.3 MAC of drug X and 1 MAC of drug Y the total MAC achieved is 1.3 MAC. In this way nitrous oxide is often used as a "carrier" gas to decrease the anesthetic requirement of other drugs.
Common MAC values
Values are known to decrease with age and the following are given are based on a 40-year-old (MAC40):
- Nitrous oxide - 104 
- Xenon - 72 
- Desflurane - 6.6 
- Ethyl Ether - 3.2
- Sevoflurane - 1.8 
- Enflurane - 1.63 
- Isoflurane - 1.17 
- Halothane - 0.75 
- Chloroform - 0.5
- Methoxyflurane - 0.16
- "Policy: Ban on Use of Ether". Laboratory Animal Science Center. Archived from the original on 2008-06-09. Retrieved 2008-11-10.
- Eger EI, Saidman LJ, Brandstater B (1965). "Minimum alveolar anesthetic concentration: a standard of anesthetic potency". Anesthesiology. 26 (6): 756–63. doi:10.1097/00000542-196511000-00010. PMID 5844267.
- Merkel, Giles; Eger, Edmond I. (1963-05-01). "A Comparative Study of Halothane and Halopropane AnesthesiaIncluding Method for Determining Equipotency". The Journal of the American Society of Anesthesiologists. 24 (3): 346–357. ISSN 0003-3022.
- Eger, Edmond I.; Saidman, Lawrence J.; Brandstater, Bernard (1965-11-01). "Minimum Alveolar Anesthetic ConcentrationA Standard of Anesthetic Potency". The Journal of the American Society of Anesthesiologists. 26 (6): 756–763. ISSN 0003-3022.
- Miller ANESTHESIOLOGY
- * Daniel M, Weiskopf RB, Noorani M, Eger EI (January 1998). "Fentanyl augments the blockade of the sympathetic response to incision (MAC-BAR) produced by desflurane and isoflurane: desflurane and isoflurane MAC-BAR without and with fentanyl". Anesthesiology. 88 (1): 43–9. doi:10.1097/00000542-199801000-00009. PMID 9447854.
- Katoh T, Kobayashi S, Suzuki A, Iwamoto T, Bito H, Ikeda K (February 1999). "The effect of fentanyl on sevoflurane requirements for somatic and sympathetic responses to surgical incision". Anesthesiology. 90 (2): 398–405. doi:10.1097/00000542-199902000-00012. PMID 9952144.
- * Nickalls, R. W. D., & Mapleson, W. W. (August 2003). "Age-related iso-MAC charts for isoflurane, sevoflurane, and desflurane in man". British Journal of Anaesthesia. 91 (2): 170–4. doi:10.1093/bja/aeg132. PMID 12878613.