Which patient factors increase MAC, and which lower it?
Pharmacology — Inhalational Agents, MAC and the Determinants of Uptake
The question
Five patients are listed for surgery under general anaesthesia maintained with sevoflurane. In which of them would you expect the minimum alveolar concentration of sevoflurane to be HIGHER than in a healthy, normothermic 30-year-old?
- A 78-year-old man having a hemiarthroplasty
- A woman at 38 weeks of gestation having a Caesarean section
- A man who drinks 80 units of alcohol a week and is not intoxicated on admission
- A patient whose core temperature has drifted to 33 degrees Celsius during a long laparotomy
- A patient given a bolus of fentanyl 2 micrograms/kg at induction
The answer
A man who drinks 80 units of alcohol a week and is not intoxicated on admission
A 78-year-old man having a hemiarthroplasty — MAC decreases with age after infancy, declining approximately 6% per decade past the age of 40. An elderly patient requires less volatile agent, not more.
A woman at 38 weeks of gestation having a Caesarean section — Pregnancy reduces MAC substantially by term, by roughly a quarter to a third. This reduction is attributed to elevated progesterone levels and rising endogenous opioid concentrations.
A man who drinks 80 units of alcohol a week and is not intoxicated on admission — Correct. Chronic alcohol use increases anaesthetic requirement through cross-tolerance at the same central targets. Importantly, the stem specifies the patient is not acutely intoxicated; acute intoxication produces the opposite effect and lowers MAC.
A patient whose core temperature has drifted to 33 degrees Celsius during a long laparotomy — Hypothermia reduces MAC, by approximately 2-5% per degree Celsius of cooling. A hypothermic patient is at risk of being over-anaesthetised at what appears to be a modest end-tidal concentration.
A patient given a bolus of fentanyl 2 micrograms/kg at induction — Opioids are potent MAC-sparing drugs. Benzodiazepines, alpha-2 agonists, and nitrous oxide share this property, and their MAC-reducing effects are essentially additive.
Explanation
MAC is the alveolar concentration of a volatile agent, at one atmosphere, at which half of subjects do not move in response to a standard surgical stimulus. It is a measure of potency: a lower MAC indicates a more potent agent. Because MAC is defined at the alveolus, it serves as a surrogate for partial pressure at the brain, which is why it is expressed as a concentration rather than a dose and why MACs from different agents are additive. Half a MAC of sevoflurane plus half a MAC of nitrous oxide behaves as one MAC.
The derived values are worth knowing alongside the standard definition. MAC-awake (the concentration at which half of subjects open their eyes to command) sits at approximately 0.3-0.4 MAC. MAC-BAR (the concentration blocking the adrenergic response to incision in half of subjects) is approximately 1.3 to 1.5 MAC. One MAC prevents movement in only 50% of patients, which is why clinical practice typically maintains concentrations above it.
A useful organising principle for the long list of MAC modifiers is that almost everything lowers it. MAC falls with age past infancy (for most volatile agents the peak is around six months, though sevoflurane is the exception: its MAC is highest in neonates at approximately 3.3% and declines steadily from birth; past 40 all agents decline approximately 6% per decade). It falls with hypothermia, pregnancy, acute alcohol intoxication, opioids, benzodiazepines, alpha-2 agonists, nitrous oxide, lithium, and with physiological extremes: a mean arterial pressure below approximately 50 mmHg, severe anaemia, severe hypoxaemia, and marked hypercapnia or acidosis.
The shorter list of factors that raise MAC is the one to learn by name: hyperthermia (up to approximately 42 degrees Celsius, beyond which MAC falls again), chronic alcohol use, acute sympathomimetic intoxication (amphetamine, cocaine), hypernatraemia, and infancy. Several factors that might intuitively seem relevant have no clinically useful effect on MAC: sex, weight, height, duration of anaesthesia, and thyroid function do not alter it meaningfully, and PaCO2 within the normal range does not shift it either.
Tips for the candidate
The direction of the question should be identified before the options are read. "Increases MAC" and "decreases MAC" questions draw from the same list, and the most common way to lose the mark is to identify the correct physiology and then answer the wrong question. Underlining INCREASED or REDUCED in the stem is a reliable safeguard.
The asymmetry in the list is a useful tool. Since almost everything lowers MAC, a question asking what raises it has a very small answer set: hyperthermia, chronic alcohol use, sympathomimetic intoxication, hypernatraemia, and infancy. If those five are known, most such questions can be answered by elimination without ranking the remaining options.
The acute-versus-chronic distinction is a common examination trap. Chronic alcohol use raises MAC; acute intoxication lowers it. Chronic amphetamine use lowers MAC; a recent dose raises it. The stem usually specifies which scenario applies, often in a clause that appears to be scene-setting ("not intoxicated on admission", "having taken a dose this morning"). That clause warrants careful reading.
MAC concerns potency and partial pressure, not dose or volume. If an option mentions the volume of agent used, the fresh gas flow, case duration, or patient weight, it is almost certainly a distractor. Those variables affect how rapidly a given alveolar concentration is achieved, not what concentration is required.