I.C.2 Inhalation anestheticsUptake and distributionMAC
Inhalation anesthetics
Why some gases put patients to sleep faster, how potent each one is, and the side effect each is famous for.
By the end you can
- Predict how solubility, cardiac output and ventilation change the speed of induction and emergence
- Use MAC values to compare potency and add agents together
- Match each agent to its hallmark side effect and choose safely around N2O and MH
Your case
OR 7 · Tympanoplasty · Preop holding
Ms. R, 34, 68 kg. Healthy, but she is very anxious and had severe nausea after her last anesthetic.
The surgeon plans a middle ear graft and asks for a smooth, fast wake-up. You plan an IV induction and volatile maintenance.
HR 112BP 148/88SpO2 99%Hgb 13.1
Hold that thought
- Her anxiety has raised her cardiac output. Does that speed up or slow down the rise of your volatile?
- Should nitrous oxide be part of her anesthetic?
- Which volatile gives her the fastest wake-up, and why?
You'll answer all three at the end of the lesson.
Concept 1 · Partial pressure
The goal is a brain partial pressure
Follow the gas downstream
- Vaporizer to circuit to alveolus: the inspired fraction is FI, the alveolar fraction is FA
- Alveolus to blood to brain: at steady state, brain partial pressure equals alveolar
- FA/FI is the ratio we track. When it nears 1, the patient is close to equilibrium
- End-tidal agent is your bedside estimate of FA
Pushes FA up (delivery)
- Higher inspired concentration
- Higher fresh gas flow
- More alveolar ventilation
Pulls FA down (uptake)
- Higher blood:gas solubility
- Higher cardiac output
- Bigger alveolar to venous gradient
Pearl: Uptake = solubility × cardiac output × (PA minus Pv) ÷ barometric pressure. If any term is zero, uptake stops and FA/FI climbs.
Quick check 1 of 4
Which change makes FA/FI rise faster?
More ventilation delivers agent to the alveolus faster than blood can remove it. Higher cardiac output is the tempting pick, but it increases uptake, which holds FA down and slows induction.
Concept 2 · Solubility
Low solubility means fast on, fast off
Think of blood as a sponge
- The blood:gas partition coefficient is how much agent blood holds at equilibrium compared with gas
- A soluble agent soaks into blood, so alveolar partial pressure stays low for longer
- An insoluble agent saturates blood quickly, so partial pressure rises fast
- The same logic runs in reverse at emergence
| Agent | Blood:gas | Speed |
|---|---|---|
| Desflurane | 0.42 | Fastest volatile |
| Nitrous oxide | 0.47 | Fast |
| Sevoflurane | 0.65 | Fast |
| Isoflurane | 1.4 | Slower |
| Halothane | 2.4 | Slowest (historic) |
Published values vary slightly by source (sevoflurane 0.65 to 0.69, isoflurane 1.4 to 1.46).
Blood:gas predicts speed of onset and offset. Oil:gas predicts potency (Meyer-Overton): the more lipid soluble, the lower the MAC.
The vessel-rich group (brain, heart, kidney, liver) gets about 75% of cardiac output and fills in minutes. Muscle fills over hours. Fat has huge capacity and fills slowly, which is why long cases of soluble agents wake up slower.
Signature interactive
Race the gases to equilibrium
Each curve is FA/FI over 30 minutes. Change cardiac output and ventilation and watch which agents care.
Wash-in race · FA/FI vs time
Cardiac output
Alveolar ventilation
Dashed lines show the normal baseline. Model: 70 kg adult, three tissue groups, no shunt. N2O is shown at 70% inspired, so the concentration effect lifts its curve. The volatiles are at low inspired levels.
Second gas effect: give 70% N2O with sevoflurane and the rapid uptake of N2O concentrates the sevoflurane left behind and pulls in fresh gas. Sevoflurane (and oxygen) FA rises faster than it would alone.
Quick check 2 of 4
An anxious patient has a high cardiac output at induction. Whose FA/FI is slowed the most?
Cardiac output changes matter most for soluble agents, because blood carries away much more of them per liter. Desflurane and N2O are so insoluble that their curves barely move.
Concept 3 · High-concentration gas
When the gas itself is a big share of the breath
Only N2O is given in high enough concentration
- Concentration effect: the higher the FI, the faster FA/FI rises
- Uptake of a large volume of N2O shrinks the alveolar gas and concentrates what remains
- Fresh gas is then drawn in to replace the lost volume: augmented inflow
- Second gas effect: the companion volatile and O2 ride along and rise faster too
Shunted blood dilutes arterial partial pressure. Soluble agents partly make up for it with extra uptake in ventilated lung, but insoluble agents cannot. So a right-to-left shunt slows induction more with sevoflurane and desflurane than with isoflurane.
Blood recirculates through the lungs, so it changes the speed of inhalation induction very little. It matters more for slowing IV induction.
With low fresh gas flow, the circuit concentration lags the dial, because exhaled gas depleted of agent is rebreathed. Use high flows to wash in or wash out quickly.
Concept 4 · MAC
Potency is measured in MAC
- MAC: alveolar concentration at 1 atm that prevents movement to skin incision in 50% of patients
- It is a spinal cord effect, mostly. It does not measure amnesia
- MAC values add: 0.5 MAC of one agent + 0.5 MAC of another = about 1 MAC
- The lower the MAC, the more potent the agent
- MAC-awake
- About 0.3 to 0.4 MAC (roughly one-third): 50% open eyes to command
- 1 MAC
- No movement in 50%
- 1.3 MAC
- No movement in about 95%
- MAC-BAR
- About 1.5 MAC: blunts the sympathetic response to incision (varies by source)
Try it: add the MACs
A 40-year-old breathes 52% N2O (MAC 104%) and 1% sevoflurane (MAC 2%). Total MAC?
MAC
Worked answer: 52 ÷ 104 = 0.5 MAC N2O. 1 ÷ 2 = 0.5 MAC sevoflurane. Together about 1.0 MAC.
Concept 5 · What changes MAC
Up, down, or no change?
Lowers MAC
- Age (about 6% per decade after 40)
- Hypothermia, hyponatremia
- Pregnancy, acute alcohol
- Opioids, benzodiazepines, alpha-2 agonists, ketamine, lithium
Raises MAC
- Infancy (peaks around 1 to 6 months)
- Hyperthermia (below 42°C), hypernatremia
- Chronic alcohol use
- Acute cocaine or amphetamine; red hair
Rule of thumb: more CNS catecholamines raise MAC; anything that quiets the CNS lowers it.
Rapid fire
Hyperthyroidism raises MAC.
False. Thyroid status does not change MAC. Hyperthyroid patients may seem to need more because their higher cardiac output slows uptake.
MAC falls the longer a case runs.
False. Duration of anesthesia does not change MAC.
An 80-year-old needs less sevoflurane than a 40-year-old.
True. About 6% less per decade after 40, so roughly 24% less at 80.
Hyperkalemia lowers MAC.
False. Potassium does not change MAC. Sodium does, because it changes CNS osmolality.
Dexmedetomidine lowers MAC.
True. Alpha-2 agonists (dexmedetomidine, clonidine) lower MAC by reducing CNS norepinephrine release.
Male patients have a higher MAC than female patients.
False. Sex does not change MAC.
Concept 6 · Organ effects
What volatiles do, system by system
Cardiovascular
- MAP falls with dose, mainly from lower SVR (iso, des, sevo)
- Heart rate: rises with iso and des; little change with sevo
- Desflurane turned up fast above about 1 MAC causes a brief sympathetic surge
- Sevoflurane can prolong QT. Halothane sensitizes the heart to epinephrine
Respiratory
- Rapid, shallow breathing: RR up, tidal volume down, PaCO2 up
- Blunted response to CO2 and, even at low doses, to hypoxemia
- Bronchodilation; sevoflurane is the least irritating
- Desflurane (and isoflurane) are pungent: cough, breath-holding, laryngospasm
Central nervous system
- CMRO2 falls, but vessels dilate, so CBF and ICP can rise
- This uncoupling grows above about 1 MAC; autoregulation is impaired
- Evoked potentials: amplitude down, latency up. MEPs are most sensitive
- N2O raises CMRO2 and CBF too
Muscle, uterus, kidney, liver
- Potentiate nondepolarizing blockers
- Relax the uterus with dose (N2O does not)
- Lower renal and hepatic blood flow
- All potent volatiles are MH triggers
Quick check 3 of 4
A patient with a brain tumor and raised ICP needs a volatile. What is the main concern?
Volatiles dilate cerebral vessels, which raises CBF and ICP, especially above 1 MAC. They lower CMRO2, so B is backward. Many providers keep them at 1 MAC or less or use TIVA; practice varies.
Concept 7 · Agent hallmarks
Every agent has a signature problem
Tap an agent, then its hallmark side effect.
The fine print
- Compound A: sevoflurane label says avoid flows under 1 L/min; at 1 to 2 L/min, limit to 2 MAC-hours
- Carbon monoxide: desiccated absorbent with strong bases; worst with desflurane
- Metabolism: halothane about 20%, sevo 2 to 5%, iso 0.2%, des 0.02%
- Emergence delirium in children is most linked to sevoflurane and desflurane
Concept 8 · Nitrous oxide
The gas that moves into air pockets
- MAC 104%: it can never be a complete anesthetic alone at 1 atm
- Good analgesic, minimal muscle relaxation, not an MH trigger
- About 30 times more soluble than nitrogen, so it enters air spaces faster than N2 can leave
Compliant spaces grow: 75% N2O can double a pneumothorax in about 10 minutes; bowel gas grows over hours. Rigid spaces gain pressure: middle ear (graft displacement, PONV) and intraocular gas bubbles (SF6, C3F8), where blindness has been reported. Also avoid with air embolism and pneumocephalus.
At the end of the case, large volumes of N2O pour out of the blood into the alveoli and dilute oxygen and CO2. On room air, SpO2 can fall. Give 100% O2 for the first several minutes after stopping N2O.
N2O oxidizes the cobalt in B12 and inactivates methionine synthase. Long or repeated exposure can cause megaloblastic anemia and neuropathy, most in patients already B12 deficient.
N2O raises PONV risk, mostly with longer exposure. It can raise pulmonary vascular resistance, a concern with pulmonary hypertension.
Quick check 4 of 4
For which patient is 50% nitrous oxide least concerning?
A healthy patient with no trapped gas space has no N2O-specific risk. An intraocular gas bubble is the most dangerous choice: rising eye pressure can occlude the retinal artery. Pneumothorax and bowel obstruction are closed spaces that will expand.
Concept 9 · Physical properties
Vapor pressure, vaporizers and absorbents
- Vapor pressure at 20°C: desflurane 669 (681 in some texts), isoflurane 238, sevoflurane 157 mmHg
- Desflurane boils at about 23°C, so it needs a vaporizer heated to 39°C and pressurized to about 2 atm
- The desflurane vaporizer delivers a set percent. At altitude, turn the dial up to keep the same partial pressure
- Variable-bypass vaporizers (sevo, iso) hold partial pressure steady across altitude
Fill the blanks
Sevoflurane is , so it is the agent for mask induction.
Desflurane needs a vaporizer.
Dry absorbent with desflurane can make .
Potency tracks the coefficient.
Nitrous oxide a trigger for malignant hyperthermia.
Apply it · Branching case
An MH-susceptible patient
Mr. T, 28, needs an ACL repair. His father had malignant hyperthermia under anesthesia. What is your maintenance plan?
Every potent volatile is a trigger, including sevoflurane. Avoiding succinylcholine alone is not enough.
Right. Nontriggering: propofol, opioids, nondepolarizers, local anesthetics and nitrous oxide are all safe.
Desflurane is a volatile and a trigger. Flow rate does not change that.
The machine ran sevoflurane in the previous case. How do you prepare it?
Agent lingers in the plastic and rubber parts of the machine and circuit. A new absorbent alone leaves the vaporizers in place and agent in the system.
Too short, and no filters. A 90-second flush is only enough when charcoal filters go on next. Without filters, flush times run from about 20 to over 100 minutes, depending on the machine.
Right. MHAUS: remove or disable vaporizers, use a fresh circuit and absorbent, flush at 10 L/min or more for 90 seconds, then add activated charcoal filters to both limbs and keep fresh gas flow at 3 L/min or more. Follow the manufacturer's flush time if not using filters.
The case goes well with propofol and 60% N2O. Two minutes after extubation on room air, SpO2 drifts to 91%. Temperature and EtCO2 were normal. Next step?
No signs of MH, and N2O is not a trigger. Dantrolene is for rising EtCO2, rigidity, tachycardia and fever.
Right. This is diffusion hypoxia: N2O flooding out of the blood dilutes alveolar O2. Give 100% O2 for the first several minutes after N2O.
Too aggressive for a mild, expected drop. Treat the cause first with supplemental oxygen.
Safe from start to finish
- No volatiles and no succinylcholine for MH-susceptible patients
- Prepare the machine per MHAUS and the manufacturer; have dantrolene available
- N2O is safe for MH but still needs 100% O2 at emergence
Lock it in
Who wakes up first?
Numbers to know cold (tap to reveal)
MAC in O2 for a 40-year-old. MAC runs the opposite way to oil:gas: higher oil:gas, lower MAC, more potent.
- Isoflurane MAC: · oil:gas
- Sevoflurane MAC: · oil:gas
- Desflurane MAC: · oil:gas
- Nitrous oxide MAC: · oil:gas
- Halothane MAC: · oil:gas
Pattern: MAC roughly goes 1, 2, 6 for iso, sevo, des. Multiply MAC by oil:gas for iso, sevo or des and you land near 100 each time. That is Meyer-Overton: potency tracks lipid solubility.
Board traps
What the NCE will try to trick you with
False. More blood flow carries more agent away from the alveoli, so FA/FI rises slower. It speeds IV induction, which is where the confusion comes from. Low output (shock) speeds the volatile rise and risks overdose.
False. Blood:gas predicts speed. Potency follows oil:gas. Desflurane is the fastest volatile and also the least potent (MAC 6%).
False. The shunt slows insoluble agents more (desflurane, sevoflurane, N2O). Soluble agents partly make up the difference through extra uptake in ventilated lung.
False. The desflurane vaporizer delivers a fixed percent. Lower ambient pressure means a lower partial pressure, so you must turn it up. Variable-bypass vaporizers self-correct.
Cheat card
The whole lesson on one card
Speed (blood:gas)
- Des 0.42, N2O 0.47, sevo 0.65, iso 1.4
- Ventilation up = faster
- Cardiac output up = slower
- Soluble agents feel both most
Potency (MAC)
- Iso 1.15, sevo 2, des 6, N2O 104%
- MACs add; 1.3 MAC = 95%
- Age: minus 6% per decade after 40
- Potency follows oil:gas
Hallmarks
- Sevo: compound A, mask induction
- Des: pungent, sympathetic surge, CO
- Iso: coronary steal (theoretical)
- Halothane: hepatitis
Nitrous oxide
- Expands closed gas spaces
- Diffusion hypoxia: give 100% O2
- B12 and methionine synthase
- Second gas effect; not an MH trigger
The printable PDF version of this card is in the Cheat Sheets library.
Lesson quiz · 1 of 5
A 40-year-old receives isoflurane 1.2% with 50% nitrous oxide. About how many MAC?
Isoflurane 1.2 ÷ 1.15 is about 1.0 MAC, and N2O 50 ÷ 104 is about 0.5 MAC. MACs add, so the total is about 1.5. Choosing 1.0 means forgetting to count the N2O.
Lesson quiz · 2 of 5
A 5-year-old without an IV needs a mask induction. Which agent?
Sevoflurane is nonpungent and low in solubility, so induction is smooth and fast. Desflurane is faster on paper, but it irritates the airway and causes coughing and laryngospasm. N2O alone cannot reach 1 MAC.
Lesson quiz · 3 of 5
70% N2O ran until extubation. Two minutes later on room air, SpO2 is 89%. Most likely cause?
N2O leaving the blood dilutes alveolar oxygen in the first minutes after it is stopped. The timing and the missing 100% O2 point here. The others can cause hypoxemia, but the setup describes diffusion hypoxia.
Lesson quiz · 4 of 5
Which of these lowers MAC?
Pregnancy lowers MAC, likely through progesterone. Chronic alcohol use and hypernatremia raise it, and thyroid status does not change it. Acute intoxication lowers MAC, which makes A the tempting choice.
Lesson quiz · 5 of 5
A 3-hour case runs sevoflurane near 1 MAC at 1 L/min fresh gas flow. Main concern?
The sevoflurane label limits flows of 1 to 2 L/min to 2 MAC-hours because of compound A. This case is about 3 MAC-hours. Fluoride is tempting, but clinical kidney injury from sevoflurane fluoride has not been shown.
Wrap-up
0 / 5
Quiz score
Back to OR 7 · Ms. R, tympanoplasty
High cardiac output? It slows the rise of FA/FI, most for soluble agents. Expect a slightly slower wash-in, not a faster one.
Nitrous oxide? Best avoided. It raises middle ear pressure and can lift the graft, and it adds to her PONV risk.
Fastest wake-up? Desflurane, the lowest blood:gas coefficient (0.42). Sevoflurane (0.65) is a close, smoother second. Given her PONV history, propofol TIVA is also a reasonable choice (varies by provider).
Keep going