Minimum alveolar concentration

Minimum alveolar concentration or MAC is a concept used to compare the strengths, or potency, of anaesthetic vapours;^[1] in simple terms, it is defined as the concentration of the vapour in the lungs that is needed to prevent movement (motor response) in 50% of subjects in response to surgical (pain) stimulus. Thus, it is actually a median value; the use of minimum would appear to be descended from the original paper in which the concept appeared, although the term there was minimal alveolar concentration. A lower MAC value represents a more potent volatile anesthetic.

The concept was introduced in 1965.^[2]

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.

Formal definition

The MAC is the concentration of the vapour (measured as a percentage at 1 atmosphere, i.e the partial pressure) that prevents the reaction to a standard surgical 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. MACbar,the end-tidal concentration inhibiting autonomic reflexes to pain in 50% of subjects(1.3 MAC of isoflurane)

Meyer-Overton hypothesis

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^[3][4]
• Mullin's critical volume hypothesis
• Positive modulation of GABA at GABA_A receptors by barbiturates or benzodiazepines

Altered MAC

Certain physiological and pathological states may alter MAC. MAC is higher in infants and lower in the elderly. Also, MAC increases with anxiety and thyrotoxicosis. Likewise, hypothermia, hypotension, hypothyroidism, and pregnancy seem to decrease MAC. 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

• Nitrous oxide - 104^[5]
• Xenon - 72
• Desflurane - 6^[5]
• Ethyl Ether - 3.2
• Sevoflurane - 2^[5]
• Enflurane - 1.7
• Isoflurane - 1.2^[5]
• Halothane - 0.75^[5]
• Chloroform - 0.5
• Methoxyflurane - 0.16

References