Onset = blood:gas. Potency = oil:gas. Two different coefficients answering two different questions.
Low blood:gas → low solubility in blood → high alveolar partial pressure builds quickly → fast onset.
High solubility in blood → the blood acts as a reservoir → alveolar partial pressure rises slowly → slow onset.
Counter-intuitive but true: the less soluble an agent is, the faster it works.
The numbers
Agent
MAC (%)
Blood:gas
Oil:gas
SVP (mmHg at 20 °C)
Xenon
63–71
0.17 — lowest
1.9
Gas
Desflurane
6.0 — highest
0.42
19 — lowest
664 — highest
Nitrous oxide
105 — least potent
0.47
1.4
Gas (39 000)
Sevoflurane
2.0
0.68
80
160
Isoflurane
1.15–1.17
1.4
98
240
Enflurane
1.7
1.9
97
172
Halothane
0.75 — most potent
2.4 — highest
224 — highest
243
Methoxyflurane
0.16
12
970
23
The two extremes — the clean contrast
Desflurane: oil:gas 19 (MINIMUM) · MAC 6.0 (MAXIMUM) · blood:gas 0.42 (MINIMUM) → least potent, fastest onset.
Halothane: oil:gas 224 (MAXIMUM) · MAC 0.75 (MINIMUM) · blood:gas 2.4 (MAXIMUM) → most potent, slowest onset.
They sit at opposite ends of every column — which is why quoting these two answers most ranking questions.
Rankings
Blood:gas, most to least (i.e. slowest to fastest onset): methoxyflurane > halothane > enflurane > isoflurane > sevoflurane > nitrous oxide > desflurane > xenon.
Speed of onset (fastest first): desflurane < sevoflurane < isoflurane — remembering that a lower blood:gas means faster.
Potency, least to most: nitrous oxide → desflurane → sevoflurane → enflurane → isoflurane → halothane.
Metabolism, least to most: desflurane (0.02%) < isoflurane (0.2%) < sevoflurane (3–5%) < halothane (20%).
Physical properties compared
Property
Isoflurane
Sevoflurane
Desflurane
State at 20 °C
Liquid
Liquid
Liquid (only just)
Light stability
Stable
Stable
Not stable
SVP at 20 °C
32 kPa (240 mmHg)
22 kPa (160 mmHg)
89 kPa (664 mmHg)
Boiling point
48.5 °C
58.5 °C
23.5 °C
Volatility
Moderate
Moderate
Extremely volatile — boils at 17 °C at altitude
Flammable
No
No
No
Rubber solubility
Yes
Low
Low
Additive/preservative
No
No
No
Smell
Pungent
Pleasant
Pungent
Suitability for gas induction
Poor
Good — agent of choice
Poor
Induction / emergence
Slow
Moderate
Rapid
Metabolism
0.2%
3–5%, by cytochrome P450
0.02%
Toxic metabolites
None
Compound A with dry soda lime
CO with desiccated absorbent
Renal toxicity
No
Fluoride ions — not clinically significant
No
Safe in pregnancy
Yes
Yes
Yes
Vaporiser
Standard
Standard
Tec 6 — heated to 39 °C and pressurised
Cost
Cheap
Expensive
Expensive
Shared organ effects
All volatiles are bronchodilators.
CVS: ↓SVR and ↓BP with cardiac output largely maintained. Halothane causes the greatest fall in cardiac output — it is the most myocardial-depressant.
Respiratory: ↓tidal volume, ↑respiratory rate, ↑dead space ventilation, ↓alveolar ventilation → PaCO₂ rises. They also inhibit hypoxic pulmonary vasoconstriction.
Cerebral: ↓CBVR (cerebral vascular resistance) and ↓CMRO₂ but ↑CBF and ↑ICP — the uncoupling that makes them second-choice in neurosurgery.
All are malignant hyperthermia triggers and all relax uterine smooth muscle.
What changes speed of onset
Faster onset
↑ FiO₂ and ↑ inspired concentration of volatile — a bigger gradient reaches equilibrium sooner.
↑ Alveolar ventilation.
↓ Cardiac output. Counter-intuitively, a high cardiac output SLOWS induction, because more blood carries agent away from the lungs and alveolar partial pressure rises more slowly.
Low blood:gas coefficient — the agent property itself.
Shunts
Right-to-left shunt SLOWS inhalational induction (more marked for the less soluble agents, such as desflurane and nitrous oxide) — because shunted blood bypasses the lungs entirely.
The same right-to-left shunt SPEEDS intravenous induction, since drug reaches the brain without first passing through the lungs.
A left-to-right shunt has little clinical effect on either.
Vaporiser filling errors
Put an agent of higher SVP into a vaporiser calibrated for a lower-SVP agent → increased output (e.g. isoflurane in a sevoflurane vaporiser).
Put a lower-SVP agent into a higher-SVP vaporiser → reduced output (e.g. methoxyflurane in a desflurane vaporiser).
Halothane in an isoflurane vaporiser gives roughly the same output — their SVPs are almost identical (243 vs 240 mmHg).
Nitrous oxide, and what alters MAC
Nitrous oxide
Molecular weight
44
Boiling point
−88 °C
Critical temperature
36.5 °C — lowered to about −5.5 °C in Entonox (the pseudocritical temperature)
Critical pressure
72 bar
MAC
105% — the least potent agent
Oil:gas
1.4 — the lowest
Blood:gas
0.47
MAC modifiers
MAC INCREASES with: raised temperature (pyrexia), infancy (peak at ~6 months), chronic alcohol use, hypernatraemia, and sympathomimetics such as amphetamine.
MAC DECREASES with: hypothermia, hypotension, ketamine, local anaesthetics, pregnancy, opioids, α₂ agonists, acute alcohol, hyponatraemia, hypercalcaemia, increasing age, and hypothyroidism.
Built from handwritten pages IMG_1285–1289. Values shown are the standard reference figures; where your page carried a differing figure the conventional one is given.