Isoflurane

8 min read Last updated April 8, 2026

At-a-glance exam facts

  • Halogenated ether volatile anaesthetic; pungent; not ideal for inhalational induction.
  • MAC (adult, 40y) ≈ 1.15% (higher in infants/children; lower in elderly).
  • Blood:gas partition coefficient ≈ 1.4 → slower onset/offset than sevo/des but faster than halothane.
  • Cardiovascular: dose-dependent vasodilation → ↓SVR and ↓BP; relative preservation of CO vs halothane; mild tachycardia possible.
  • Respiratory: dose-dependent respiratory depression; bronchodilation but airway irritant (cough/laryngospasm).
  • CNS: ↓CMRO2, ↑CBF (dose-dependent), may ↑ICP unless ventilation controlled.
  • Triggers malignant hyperthermia; rare immune-mediated hepatitis; minimal metabolism (~0.2%) → low fluoride burden vs sevo.

How it behaves in theatre (practical points)

  • Maintenance agent: robust, inexpensive; useful where sevo/des not available or cost-limited.
  • Avoid inhalational induction (pungency/irritation); consider IV induction then switch.
  • If raised ICP risk: ensure adequate ventilation (target normocapnia or mild hypocapnia) and avoid high MAC without control of PaCO2.
  • Hypotension management: reduce MAC, add opioid/adjunct, treat vasodilation with vasopressor (e.g. metaraminol/phenylephrine) and optimise volume status.

Chemical/physical properties

  • Halogenated methyl ethyl ether; structural isomer of enflurane.
  • Non-flammable; clear, colourless, volatile liquid with characteristic pungent odour.
  • Vapour pressure at 20°C ≈ 240 mmHg → requires calibrated variable bypass vaporiser.
  • Oil:gas partition coefficient high (potent agent); blood:gas ≈ 1.4 (moderate solubility).

Potency and uptake/distribution

  • MAC decreases with age; reduced by opioids, benzodiazepines, alpha-2 agonists, hypothermia; increased by hyperthermia and chronic alcohol use.
  • Moderate blood solubility: slower wash-in/wash-out than sevoflurane/desflurane; influenced by alveolar ventilation, cardiac output, and inspired concentration (concentration effect).
    • Higher CO slows rise in FA/FI (greater uptake).
    • Increased alveolar ventilation speeds rise in FA/FI.

Mechanism of action (exam level)

  • General anaesthetic effect via modulation of ligand-gated ion channels: enhances inhibitory transmission (e.g. GABAA, glycine) and reduces excitatory transmission (e.g. NMDA to a lesser extent for volatiles).
  • Immobilisation predominantly spinal cord mediated; amnesia/hypnosis predominantly cortical/subcortical.

Cardiovascular effects

  • Dose-dependent systemic vasodilation → ↓SVR and ↓MAP; CO often relatively maintained (less myocardial depression than halothane).
  • Heart rate: may increase slightly (less baroreflex suppression than halothane).
  • Coronary circulation: causes coronary vasodilation; historical “coronary steal” concern—clinically small effect; maintain perfusion pressure in IHD.
  • Arrhythmias: less sensitisation to catecholamines than halothane; still caution with high sympathetic states.

Respiratory effects

  • Dose-dependent respiratory depression: ↓tidal volume, ↑respiratory rate; overall ↓minute ventilation → ↑PaCO2 if spontaneous.
  • Blunts ventilatory responses to CO2 and hypoxia.
  • Airway: irritant/pungent → coughing, breath-holding, laryngospasm risk; bronchodilator effect once established.
  • Increases V/Q mismatch and may reduce HPV (hypoxic pulmonary vasoconstriction) in a dose-dependent manner.

CNS effects

  • ↓CMRO2 and EEG depression; at higher doses may produce burst suppression.
  • Cerebral vasodilation → ↑CBF and potentially ↑ICP; effect mitigated by controlled ventilation (↓PaCO2).
  • Maintains cerebral autoregulation better than halothane at lower concentrations; progressively impaired at higher MAC.

Renal/hepatic/endocrine and other effects

  • Metabolism minimal (~0.2%) via CYP2E1 → trifluoroacetic acid (TFA) and fluoride; low risk of fluoride nephrotoxicity compared with methoxyflurane; far less inorganic fluoride than sevoflurane produces.
  • Hepatic blood flow may decrease secondary to reduced MAP/CO; rare halogenated-anaesthetic hepatitis (immune mediated) much less common than with halothane.
  • Uterus: relaxes uterine smooth muscle (dose-dependent) → may increase PPH risk at higher MAC.
  • Skeletal muscle: potentiates non-depolarising neuromuscular blockers; triggers malignant hyperthermia in susceptible individuals.
  • PONV: volatile-associated risk; minimise exposure and use multimodal prophylaxis where indicated.

Drug interactions and special situations

  • Synergistic with opioids/benzodiazepines/propofol: reduces MAC requirement.
  • With non-depolarising NMBs: increased potency and duration (reduced MAC and direct NMJ effects).
  • With sympathomimetics: less arrhythmogenic than halothane, but avoid excessive catecholamine surges (light anaesthesia, hypercarbia).
  • Neurosurgery: acceptable with controlled ventilation; consider TIVA if tight ICP control required.

Adverse effects and toxicity

  • Malignant hyperthermia trigger: hypercarbia, tachycardia, rigidity, hyperthermia (late), acidosis, hyperkalaemia; treat with dantrolene and supportive care.
  • Hypotension from vasodilation; treat by reducing agent and supporting SVR/volume.
  • Airway irritation: coughing/laryngospasm, especially in children and smokers.
  • Rare hepatic injury: immune-mediated hepatitis (cross-sensitisation possible with other halogenated agents producing TFA).

Key comparisons (frequent FRCA theme)

  • Compared with sevoflurane: isoflurane is more pungent, slower onset/offset (higher blood:gas), less suitable for inhalational induction; cheaper; less compound A concern.
  • Compared with desflurane: isoflurane is less pungent than des but still irritant; slower kinetics; less sympathetic stimulation on rapid concentration increases.
  • Compared with halothane: less myocardial depression and arrhythmogenicity; more vasodilation; faster kinetics; much lower metabolism and hepatitis risk.
Describe isoflurane and give its key physical properties relevant to clinical use.

Aim: show you can link physical properties to onset/offset and equipment.

  • Halogenated ether volatile anaesthetic; clear, colourless liquid; pungent/irritant.
  • Vapour pressure at 20°C ≈ 240 mmHg → delivered via variable bypass vaporiser calibrated for isoflurane.
  • Blood:gas ≈ 1.4 (moderate solubility) → slower induction/recovery than sevo/des.
  • MAC (adult) ≈ 1.15% → moderate potency.
Explain how blood:gas solubility affects the speed of induction and recovery with isoflurane.

Common FRCA viva: relate FA/FI to solubility and uptake.

  • Higher blood solubility increases uptake into blood, slowing the rise of alveolar partial pressure (FA) toward inspired (FI).
  • Isoflurane blood:gas ≈ 1.4 → slower wash-in and wash-out than sevoflurane (≈0.65) and desflurane (≈0.42).
  • Clinical implications: slower changes in depth; slower wake-up after long cases compared with low-solubility agents.
What are the main cardiovascular effects of isoflurane and how do they differ from halothane?

A frequent comparison question.

  • Isoflurane: dose-dependent vasodilation → ↓SVR and ↓MAP; CO relatively preserved; mild tachycardia possible (baroreflex less suppressed).
  • Halothane: more myocardial depression, more bradycardia, greater catecholamine sensitisation and arrhythmogenicity.
  • Practical: isoflurane hypotension often responds to vasopressors and reducing MAC; halothane hypotension may be more inotrope-sensitive.
Describe the respiratory effects of isoflurane and its suitability for inhalational induction.

Expect to mention ventilatory depression and airway irritation.

  • Dose-dependent respiratory depression and blunting of CO2/hypoxic ventilatory responses.
  • Airway irritant/pungent → coughing, breath-holding, laryngospasm; therefore poor choice for inhalational induction (especially in children).
  • Bronchodilation once established can be helpful in bronchospasm, but induction phase irritation limits use.
What are the effects of isoflurane on cerebral physiology and how would you use it in a patient with raised ICP?

Classic FRCA physiology/pharmacology crossover.

  • ↓CMRO2 but causes cerebral vasodilation → ↑CBF and potential ↑ICP, especially at higher MAC.
  • Management: control PaCO2 with ventilation (normocapnia or mild hypocapnia), avoid excessive MAC, maintain MAP to preserve CPP.
  • Consider TIVA if very tight ICP control is required or if volatile effects are undesirable.
Outline the metabolism of isoflurane and the clinical relevance (renal/hepatic).

Often asked alongside sevoflurane fluoride/compound A and halothane hepatitis.

  • Very low metabolism (~0.2%) via CYP2E1 producing TFA and fluoride ions.
  • Renal: low fluoride load → negligible risk of fluoride nephrotoxicity in routine practice (contrast with methoxyflurane; and sevo produces more fluoride and compound A concerns).
  • Hepatic: rare immune-mediated hepatitis; risk far lower than halothane but cross-sensitisation possible with other TFA-producing agents.
What is MAC? Give the MAC of isoflurane and factors that increase or decrease it.

A recurring written/viva theme.

  • MAC: alveolar concentration preventing movement in response to surgical stimulus in 50% of subjects.
  • Isoflurane MAC (adult) ≈ 1.15%.
  • Decreases with age, hypothermia, pregnancy, opioids/benzodiazepines/alpha-2 agonists; increases with hyperthermia and chronic alcohol use.
Discuss the interaction between isoflurane and neuromuscular blocking drugs.

Often tested in the context of volatile potentiation of NMBs.

  • Volatile agents potentiate non-depolarising NMBs (reduced dose requirement and prolonged duration).
  • Mechanisms: central depression of motor neurones, reduced muscle blood flow, and effects at the neuromuscular junction.
  • Practical: use nerve stimulator monitoring and titrate NMB dose; anticipate longer recovery if high MAC/long exposure.
A patient becomes hypotensive on isoflurane maintenance. How do you reason the cause and manage it?

Management-focused viva; show physiology and safe practice.

  • Likely mechanism: vasodilation → ↓SVR; consider contributing factors (depth, hypovolaemia, bleeding, sepsis, anaphylaxis, myocardial ischaemia, arrhythmia).
  • Immediate actions: check monitors, surgical field/bleeding, end-tidal agent, ECG; reduce volatile concentration; increase FiO2 if needed.
  • Treat: fluid bolus if appropriate; vasopressor for low SVR (metaraminol/phenylephrine); consider inotrope if low CO suspected; reassess frequently.
Explain malignant hyperthermia in relation to isoflurane: triggers, recognition, and immediate management.

High-yield safety viva.

  • Triggers: volatile anaesthetics (including isoflurane) and suxamethonium in susceptible individuals.
  • Early signs: rising ETCO2, tachycardia, metabolic/respiratory acidosis, muscle rigidity; later hyperthermia, hyperkalaemia, rhabdomyolysis, arrhythmias.
  • Management: stop triggers, call for help, 100% O2 high flows, hyperventilate, give dantrolene, active cooling, treat hyperkalaemia/acidosis, manage arrhythmias, ICU and MH hotline/local protocol.
Compare isoflurane, sevoflurane and desflurane for day-case anaesthesia.

Common FRCA comparison: kinetics, airway, haemodynamics, cost.

  • Kinetics: des > sevo > iso for speed of onset/offset (lowest to highest blood:gas).
  • Airway: sevo least irritant (best for inhalational induction); des and iso are irritant/pungent (des often worst).
  • Haemodynamics: iso causes vasodilation and hypotension; des can cause sympathetic stimulation with rapid increases; sevo generally smooth.
  • Cost/availability: isoflurane often cheaper; may be chosen for longer cases where rapid wake-up is less critical.

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