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Minimum Alveolar Concentration (MAC)
Definition
MAC is the alveolar concentration of an inhaled anesthetic (expressed as volume % at 1 atmosphere) that prevents movement in response to a standardized surgical stimulus (typically a skin incision) in 50% of subjects. It was defined by Eger and colleagues in the 1960s and remains the primary measure of inhaled anesthetic potency.
Because alveolar concentration rapidly equilibrates with brain partial pressure (in well-perfused organs), MAC mirrors the concentration of anesthetic at its site of action in the CNS. It is therefore directly analogous to the EC₅₀ (median effective concentration) used for intravenous drugs.
"MAC is a useful measure because it mirrors brain partial pressure, allows comparisons of potency between agents, and provides a standard for experimental evaluations."
- Morgan & Mikhail's Clinical Anesthesiology, 7e
MAC Values of Common Agents
| Agent | MAC (%) |
|---|---|
| Nitrous oxide (N₂O) | ~105* |
| Halothane | 0.75 |
| Isoflurane | 1.2 |
| Sevoflurane | 2.0 |
| Desflurane | 6.0 |
*A MAC >100% means hyperbaric conditions are required to achieve 1.0 MAC at sea level. Lower MAC = higher potency.
MAC Variants
These are extension of the basic concept to different clinical endpoints:
| Variant | Description | Approximate value |
|---|---|---|
| Standard MAC | Prevents movement to incision in 50% | 1.0 MAC |
| 1.3 MAC | Prevents movement in ~95% (≈ EC₉₅) | 1.3× standard MAC |
| MAC-awake | Alveolar concentration at eye-opening to command | 0.15-0.5 MAC |
| MAC-BAR | Blunts adrenergic response to noxious stimuli | ~1.5× standard MAC |
| MAC-amnesia | Loss of awareness/recall | ~0.4-0.5 MAC |
The MAC-awake hysteresis is notable: patients lose consciousness at ~0.4-0.5 MAC but may regain it at lower concentrations (as low as 0.15 MAC), likely because of differing wash-in vs. wash-out kinetics.
MAC Additivity
MAC values from different agents are roughly additive for the immobility endpoint. For example:
- 0.5 MAC isoflurane + 0.5 MAC N₂O = ~1.0 MAC (equivalent suppression of movement)
However, additivity does not hold for all endpoints. Cardiovascular effects are not simply additive: 0.6 MAC N₂O + 0.6 MAC isoflurane causes less hypotension than 1.2 MAC isoflurane alone, because isoflurane is a more potent vasodilator and myocardial depressant per MAC equivalent than N₂O. - Barash, Cullen & Stoelting's Clinical Anesthesia, 9e
Meyer-Overton Correlation and Potency
The classic Meyer-Overton correlation shows that anesthetic potency (1/MAC) correlates with lipid-water partition coefficient - agents more soluble in lipid are more potent. This originally supported a lipid membrane theory of anesthetic action. However, modern understanding shows anesthetics bind directly to specific protein targets (e.g., GABA-A receptors, NMDA receptors).
The plot below illustrates this correlation across many compounds:
(From Miller's Anesthesia, 10e - each point is a different compound; the diagonal line shows the near-perfect log-log relationship)
Factors Modifying MAC
Factors that INCREASE MAC (more anesthetic required)
- Hyperthermia
- Hypernatremia
- Chronic ethanol abuse
- Elevated CNS catecholamines (MAO inhibitors, acute cocaine/amphetamine/ephedrine/levodopa)
- Red hair (MC1R mutations - ~19% increase, particularly in females)
Factors that DECREASE MAC (less anesthetic required)
- Increasing age - approximately 6% decrease per decade; ~22% decrease from age 40 to 80
- Hypothermia
- Hyponatremia / hypo-osmolality
- Metabolic acidosis
- Hypoxia (PaO₂ <38 mmHg)
- Severe hypotension (MAP <50 mmHg)
- Pregnancy
- Acute ethanol administration
- Drugs: opioids, benzodiazepines, barbiturates, ketamine, lidocaine, α₂-agonists (e.g., dexmedetomidine), verapamil, Δ-9-THC
- Severe anemia (<4.3 mL O₂/dL blood)
Factors that do NOT alter MAC
- Duration of anesthesia
- Sex (with the exception of the red hair effect)
- Type of surgical stimulation
- Thyroid dysfunction
- Hypo/hypercarbia (within usual clinical ranges)
- Metabolic alkalosis
- Hyperkalemia
- Magnesium levels
Clinical Limitations of MAC
MAC is a population median (ED₅₀), not a precise guide for the individual patient. It is most useful during maintenance, not during rapid concentration changes (induction/emergence). The 95% confidence range is approximately ±25% around stated MAC values. In practice, 1.2-1.3 MAC is the target during maintenance to reliably prevent movement in most patients.
Sources:
- Morgan & Mikhail's Clinical Anesthesiology, 7e, p. 294-295
- Barash, Cullen & Stoelting's Clinical Anesthesia, 9e, pp. 1407-1410
- Miller's Anesthesia, 10e, pp. 1807-1809, 2274
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