Show the model answerAttempt it first — that is what makes it stick
3 marks
MAC, its variants, and the Meyer-Overton hypothesis
What earns the marks3 marks
| The definition | Alveolar concentration, steady state, 1 atmosphere, standard surgical stimulus, movement, 50% of subjects |
|---|---|
| What it measures | Potency: the ED50, and really a partial pressure |
| The variants | MAC-awake, MAC-BAR, MAC for intubation, MAC95, each with its end point |
| Meyer-Overton | Potency rises with lipid solubility: MAC × oil:gas coefficient is roughly constant |
| Its limits | A correlation, not the mechanism |
Read the question: “Its variant” asks for the variants by name and by end point. MAC-awake and MAC-BAR written as bare labels say nothing about what each one prevents, which is the only thing that distinguishes them.
- Steady state matters because only then does the alveolar partial pressure equal the partial pressure in the central nervous system.
- The immobility it measures is mediated mainly in the spinal cord: decerebration does not change it.
- MAC varies only 10 to 15% between individuals, and MAC values of different inhaled agents are additive: 0.5 MAC of nitrous oxide with 0.5 MAC of isoflurane behaves as 1 MAC.
The variants
| Variant | End point prevented in 50% | Relation to MAC |
|---|---|---|
| MAC-awake | Perceptive awareness: consciousness | About 0.34 × MAC for the potent volatile agents; about 0.7 × MAC for nitrous oxide |
| MAC-BAR | The sympathetic response to incision: a rise in heart rate or mean arterial pressure of more than 15% | Reduced by opioids, with a ceiling |
| MAC for tracheal intubation | Movement in response to tracheal intubation | The highest of the stimulus-specific values: intubation is a stronger stimulus than incision |
| MAC95 | Movement at incision in 95% of subjects | About 1.3 × MAC, because the dose-response curve is steep |
MAC-awake lying well below MAC is what makes an ED50 usable at all: a surgeon may tolerate movement in half of patients, but awareness in half would not be acceptable. Some texts give MAC-awake as about half of MAC; the point that carries the mark is that it is a fraction of MAC, and a larger fraction for nitrous oxide.
The relationship with the Meyer-Overton hypothesis
Meyer and Overton observed, independently, that the potency of an anaesthetic rises with its lipid solubility, measured as the oil:gas partition coefficient. Because potency is the reciprocal of MAC, a plot of log MAC against log oil:gas coefficient is a straight line with a negative slope, and the product of the two is roughly constant.
| Agent | Oil:gas coefficient | MAC (%) | MAC × oil:gas |
|---|---|---|---|
| Halothane | 224 | 0.75 | 168 |
| Enflurane | 98 | 1.63 | 160 |
| Isoflurane | 98 | 1.17 | 115 |
| Sevoflurane | 55 | 1.8 | 99 |
| Desflurane | 18.7 | 6.6 | 123 |
| Nitrous oxide | 1.4 | 104 | 146 |
Across a 160-fold range of oil:gas coefficients, the product stays between 99 and 168. One standard text uses 150 as the average, so an estimated MAC is 150 divided by the oil:gas coefficient. The correlation is a line of best fit, not an identity: enflurane and isoflurane share an oil:gas coefficient of 98 and have different MACs.
3 marks
Factors affecting MAC
What earns the marks3 marks
| Direction for every factor | Increase, decrease, or no change |
|---|---|
| Physiological | Age, temperature, pregnancy |
| Pharmacological | Drugs that raise or lower central catecholamines; opioids, sedatives, α2 agonists, alcohol, other anaesthetics |
| Pathological | Sodium, severe hypoxaemia and hypotension |
| No change | Sex, duration, PaCO2 across a wide range, potassium |
Read the question: The stem is about a 50-year-old. Age is the factor that applies to this patient, and saying so is the difference between an outline and a list copied from a table.
| Increase MAC | Decrease MAC | |
|---|---|---|
| Age | Infancy | Increasing age, about 6% per decade; the neonatal period |
| Temperature | Hyperthermia | Hypothermia |
| Pregnancy | Pregnancy, by nearly 30%, and the early postpartum period | |
| Sodium | Hypernatraemia | Hyponatraemia |
| Central catecholamines | Drugs that raise them: acute amphetamine or methamphetamine, cocaine | Drugs that lower them; chronic amphetamine use |
| Central depressants | Premedication and sedatives, acute opioids (synergistic), α2 agonists, acute alcohol, lithium, lidocaine, neuraxial opioids | |
| Other anaesthetics | Additive: nitrous oxide lowers the volatile concentration needed | |
| Cardiorespiratory | PaO2 below 5.1 kPa (38 mmHg); mean arterial pressure below 40 mmHg | |
| Other | Red hair (melanocortin-1 receptor variants); ciclosporin; chronic opioid use | Cardiopulmonary bypass (inconsistent) |
No change: sex, duration of anaesthesia, anaesthetic metabolism, PaCO2 from 2.0 to 12.7 kPa (15 to 95 mmHg), PaO2 above 5.1 kPa, mean arterial pressure above 40 mmHg, and hyperkalaemia or hypokalaemia.
In this patient: published MAC values are quoted for adults of about 40. At 50, with MAC falling about 6% per decade, the same end point needs roughly 6% less agent, before any opioid, sedative or temperature effect is added.
4 marks
Factors that dictate the speed of onset
What earns the marks4 marks
| The principle | The brain equilibrates with the alveolus; onset tracks the rise of FA/FI |
|---|---|
| Delivery to the alveolus | Inspired concentration (overpressure, concentration effect), fresh gas flow and circuit, alveolar ventilation, FRC |
| Uptake from the alveolus | Blood:gas partition coefficient, cardiac output, alveolar to venous partial pressure difference |
| From blood to brain | Brain:blood coefficient and cerebral blood flow |
| Modifiers | Second gas effect, shunt, airway irritability of the agent |
Read the question: “Describe” needs the direction and the reason for each factor. The one most often written backwards is solubility: a more soluble agent is slower, not faster, because blood keeps taking it away from the alveolus.
From vaporiser to brain, and what sets the speed at each step
Uptake into blood, which slows the rise
| Factor | Faster onset when | Why |
|---|---|---|
| Inspired concentration | Higher | More input offsets uptake; the higher the inspired concentration, the more rapidly FA approaches FI (the concentration effect) |
| Fresh gas flow and circuit | High flow, small circuit volume | The circuit is a reservoir to be filled before the patient receives the dialled concentration |
| Alveolar ventilation | Higher | More agent delivered per minute; the effect is greatest for soluble agents. Spontaneous breathing gives negative feedback, as the agent depresses ventilation; controlled ventilation removes it |
| FRC | Small relative to ventilation | Less gas to dilute the incoming agent. Alveolar ventilation to FRC is about 5:1 in neonates against 1.5:1 in adults, so induction is faster in neonates |
| Blood:gas partition coefficient | Low | Little agent must dissolve before blood partial pressure rises. Anaemia lowers solubility (about 20% less at a haematocrit of 21%); a fatty meal raises it by about 20% |
| Cardiac output | Low | Less agent carried away from the alveolus. Greatest effect with soluble agents; a low output state can produce an unexpectedly deep anaesthetic |
| Alveolar to venous difference | Narrow | Once vessel-rich tissues, 10% of body mass taking 75% of cardiac output, have equilibrated, less is taken up from the lung |
| Second gas effect | Given with high-concentration nitrous oxide | Rapid nitrous oxide uptake concentrates the volatile agent in a smaller alveolar volume and draws in more inspired gas |
| Right-to-left shunt | Absent | Shunted blood dilutes arterial partial pressure; this slows poorly soluble agents more than soluble ones |
| Airway irritability | Non-pungent agent | A pungent agent such as desflurane cannot be breathed at a high inspired concentration without coughing, breath-holding or laryngospasm |
| Agent | Blood:gas coefficient | Onset |
|---|---|---|
| Desflurane | 0.42 | Fastest |
| Sevoflurane | 0.69 | |
| Isoflurane | 1.46 | |
| Enflurane | 1.9 | |
| Halothane | 2.54 | Slowest |