Isoflurane

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.

Test yourself…