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MAC (Minimum Alveolar Concentration) - Complete Anesthesiology Resident Reference

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1. Definition

• It is the ED50 (median effective dose) for the immobility endpoint
• It reflects brain partial pressure at steady state, since alveolar and brain partial pressures equilibrate
• It allows potency comparisons between agents
• It is a population median - has limited utility in managing individual patients, especially during rapidly changing concentrations (induction/emergence)

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2. MAC Values for Common Agents

• Nitrous oxide's MAC >100% means it cannot produce surgical anesthesia alone at normobaric conditions (any N₂O:O₂ mixture that allows survival cannot reach 105%)
• High MAC = low potency (more drug needed); Low MAC = high potency
• The inverse of MAC is an index of potency

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3. Key MAC Multiples (Clinically Critical)

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4. MAC Additivity

0.5 MAC N₂O + 0.5 MAC isoflurane = 1.0 MAC equivalent effect on immobility

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5. Factors That Modify MAC

Increase MAC (patient more resistant - need more drug)

Decrease MAC (patient more sensitive - need less drug)

Does NOT affect MAC

• Thyroid disease (hyper or hypothyroid)
• Sex
• Duration of anesthesia
• Hyper/hypokalemia
• PaCO₂ in the normal range

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6. Meyer-Overton Correlation (Basis of MAC / Potency)

• This is the Meyer-Overton rule: anesthetic potency correlates with lipid solubility
• Likely mechanism: anesthetics dissolve into hydrophobic domains of ligand-gated ion channels, particularly GABA-A receptors (enhanced) and NMDA receptors (inhibited)
• Glycine receptor α1-subunit and nicotinic ACh receptors are also implicated

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7. Partition Coefficients (Critical for Understanding Kinetics)

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8. Factors Affecting Uptake (FA/FI Rise)

1. Solubility in blood - Low blood/gas coefficient → FA/FI rises fast (desflurane, N₂O)
2. Cardiac output - High CO → more uptake → slows FA/FI rise → slows induction. Low CO states (e.g., heart failure, shock) → rapid rise → risk of overdose with soluble agents
3. Alveolar-venous partial pressure gradient - Tissue uptake drives this; larger gradient = more uptake = slower FA rise
4. Alveolar ventilation - Higher MV accelerates FA/FI equilibration (more so for soluble agents)
5. Functional residual capacity (FRC) - Larger FRC → slower washout and wash-in (more volume to fill)

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9. Levels of Sedation Context

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10. Practical Clinical Pearls for the OR

• At induction: FA is far below target MAC; use overpressure and IV co-induction agents (propofol, opioids) to reach effective depth fast
• At 0.5 MAC: N₂O + 0.5 MAC volatile is a common and effective combination
• MAC-awake (0.3-0.4): Patients may move, open eyes, but are still at risk for awareness if this is the sole agent
• MAC-BAR (~1.5): Needed to blunt sympathetic responses in high-stimulus moments (laryngoscopy, sternotomy)
• Age adjustment: A 70-year-old needs roughly 20-25% less volatile anesthetic than a 40-year-old
• Dexmedetomidine: Provides significant MAC reduction (useful opioid/volatile sparing strategy)
• Low-flow anesthesia: Using low fresh gas flow requires accurate end-tidal agent monitoring since inspired and alveolar concentrations diverge from vaporizer dial setting
• Desflurane caution: Its high vapor pressure (681 mmHg at 20°C) requires a heated pressurized vaporizer; rapid increases in desflurane concentration cause sympathetic stimulation and airway irritation (contraindicated for mask induction)
• Sevoflurane advantage: Low blood/gas coefficient + non-pungent smell = ideal for inhalation induction in children

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11. Additional MAC Concepts (Advanced)

• MAC-EI (endotracheal intubation): The MAC that prevents response to laryngoscopy/intubation - higher than skin incision MAC (~1.3 MAC for most agents) because intubation is a stronger stimulus
• MAC-hour: Cumulative anesthetic exposure dose (1.0 MAC × 1 hour = 1 MAC-hour). Used in PONV risk scoring (Apfel score) and in tracking exposure
• Context-sensitive half-time of volatiles: Unlike IVAs, wash-out of volatiles from tissues is not highly context-sensitive for agents with low blood/gas coefficients (desflurane, sevoflurane recover predictably)

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• Morgan & Mikhail's Clinical Anesthesiology, 7e - Chapter 8, pp. 281-296
• Miller's Anesthesia, 10e - Inhaled Anesthetics chapters
• Lippincott Illustrated Reviews: Pharmacology - Chapter 20, pp. 665-669
• Barash Clinical Anesthesia, 9e - Neuropharmacology of Inhaled Anesthetics

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Blood/Gas Partition Coefficient - Simple Explanation

The Core Idea: Blood as a "Sponge"

• The goal of inhalational anesthesia is to get the anesthetic from the alveolus → into the blood → into the brain
• The brain only responds to partial pressure, not total amount
• So you need to build up partial pressure in the alveolus fast - and whatever "steals" the drug away from the alveolus slows that build-up

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What the Number Actually Means

Blood/gas partition coefficient = concentration in blood / concentration in gas, at equilibrium (equal partial pressures)

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The Golden Rule

High blood/gas coefficient = HIGH blood solubility = HIGH uptake = SLOW induction (and slow emergence) Low blood/gas coefficient = LOW blood solubility = LOW uptake = FAST induction (and fast emergence)

Simple Analogy:

• Desflurane/N₂O = tiny leak. Bucket fills fast → brain partial pressure rises fast → fast induction.
• Isoflurane = big leak. Water keeps draining out → bucket takes ages to fill → slow induction.

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Induction & Emergence Curves (FA/FI)

• N₂O and desflurane - FA/FI shoots up rapidly (low blood solubility, not "stolen" by blood)
• Isoflurane - FA/FI rises slowly (high solubility, blood keeps absorbing it)
• Emergence mirrors induction: the same agents that induce slowly also have prolonged recovery

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Factors Affecting Uptake - Full Explanation

Uptake = Solubility (λ b/g) × Cardiac Output × (Alveolar PP - Venous PP)

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Factor 1: Solubility in Blood (Blood/Gas Coefficient)

• The more drug blood "steals" from the alveolus per unit time
• The slower FA rises
• The slower induction proceeds

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Factor 2: Cardiac Output (Alveolar Blood Flow)

High Cardiac Output → Slower Induction

• More blood per minute flows through the lungs
• More drug is picked up from the alveolus each minute
• FA/FI rise is slowed (more drug "drained away")
• Brain gets drug at a dilute concentration for a longer time
• Induction is delayed

Low Cardiac Output → Faster Induction (but DANGER)

• Less blood passes the alveolus per minute
• Less drug is removed → FA builds up rapidly
• But crucially: the brain is also perfused less, so there's a competing effect
• Net result: for soluble agents (isoflurane), low CO dramatically accelerates alveolar build-up → risk of overdose
• For insoluble agents (desflurane, N₂O), CO matters much less because very little is taken up anyway regardless

Danger scenario: A patient in cardiogenic shock getting isoflurane. The low CO causes rapid FA rise → accidental overdose → further BP drop → disaster. This is why sick patients need much lower dial settings.

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Factor 3: Alveolar-to-Venous Partial Pressure Gradient (A-V Gradient)

• Blood returning from the tissues (venous blood) has been giving up anesthetic to the organs
• The more the tissues take up, the lower the venous partial pressure
• A large A-V gradient means tissues are hungry for drug → they keep pulling it out of the blood → blood keeps pulling it from the alveolus → FA rises slowly

What drives this gradient?

The Four Tissue Compartments:

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Additional Factors Affecting Alveolar Concentration (FA)

4. Alveolar Ventilation

• Higher minute ventilation → faster wash-in → faster FA rise toward FI
• Ventilation matters most for soluble agents (because they are rapidly "drained" - so you need to push more in)
• For insoluble agents, the effect of increased ventilation is minor (FA already rises fast)
• Hypoventilation (opioid respiratory depression) slows induction of soluble agents considerably

5. Functional Residual Capacity (FRC)

• Large FRC = large reservoir of non-anesthetic gas in the lungs at the start
• Takes more breaths to "wash in" the agent → slower initial rise of FA
• This is why pre-oxygenation/denitrogenation is important and why obese/FRC-reduced patients have faster wash-in

6. Concentration Effect

1. Concentrates the remaining gas in the alveolus (raises FA)
2. Draws in more fresh gas from the airways (increases effective ventilation)

7. Second Gas Effect

• Concentrates the volatile agent in the alveolus
• Simultaneously augments ventilation (drawing in more volatile)

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Summary: The Big Picture

FA/FI rises FASTER when:          FA/FI rises SLOWER when:
- Low blood/gas coefficient        - High blood/gas coefficient
- Low cardiac output               - High cardiac output
- Small A-V gradient               - Large A-V gradient
- High minute ventilation          - Low minute ventilation
- Small FRC                        - Large FRC
- High inspired concentration      - Low inspired concentration
  (concentration effect)