Isoflurane

Isoflurane is a halogenated ether volatile anaesthetic with moderate blood solubility and a pungent odour, which makes it unsuitable for inhalation induction. It is stable, inexpensive and widely available, and remains in common use for maintenance of anaesthesia, including in settings with draw-over vaporisers. It can trigger malignant hyperthermia and causes dose-dependent vasodilatation and hypotension.

Class. Volatile (halogenated ether) general anaesthetic.

Mechanism. Positive modulation of GABA-A and glycine receptors, with inhibition of NMDA and nicotinic receptors and potassium channel activation.

Pharmacokinetics. Blood-gas partition coefficient 1.4. Minimum alveolar concentration about 1.15% in oxygen in adults aged 40 years (about 0.5% with 70% nitrous oxide). Falls about 6% for each decade over 40. Only 0.2% is metabolised (trifluoroacetic acid); the rest is exhaled.

Indications are maintenance of general anaesthesia in adults and children, and sedation of ventilated patients in some intensive care units.

Adults

• Induction by inhalation: 1.5 to 3% (rarely used; coughing, laryngospasm and breath holding are common). Preferably induce with an intravenous agent.
• Maintenance: 0.5 to 2% (usually 1 to 1.5% in oxygen, 0.5 to 1% with nitrous oxide), adjusted to age-corrected 0.7 to 1.3 minimum alveolar concentration.
• Fresh gas flows of 1 to 2 L/minute are usual; closed-circuit techniques are possible.

Children. Not preferred for inhalation induction. Maintenance 1 to 2%, with age-adjusted minimum alveolar concentration (higher in infants, about 1.6 to 1.9%).

Intensive care. Delivered through an anaesthetic conserving device for sedation (specialist use only).

Contraindications. Known or suspected susceptibility to malignant hyperthermia; history of hepatic dysfunction or jaundice after halogenated anaesthetics; hypersensitivity; airway irritation (relative); absence of suitable vaporiser, scavenging and absorbent.

Boxed-warning-level risks. Malignant hyperthermia; coronary steal in patients with ischaemic heart disease (contested); carbon monoxide production with desiccated absorbents.

Adverse effects. Common: hypotension from vasodilatation, tachycardia, cough, laryngospasm on induction, nausea, vomiting, shivering. Serious: malignant hyperthermia, arrhythmias, hepatic dysfunction (rare), uterine atony at high concentration, respiratory depression.

Interactions. Opioids, benzodiazepines, nitrous oxide and alpha-2 agonists reduce required concentration. Volatile agents potentiate non-depolarising muscle relaxants. Catecholamines can cause arrhythmias, less than halothane. Beta blockers and calcium channel blockers add hypotension.

Common prescribing errors. Using for inhalation induction; leaving it on at the end of the case (delayed emergence); confusing vaporisers; omitting scavenging; using in malignant hyperthermia susceptibility.

Special groups

• Pregnancy: used for caesarean section at 0.5 to 1 minimum alveolar concentration; uterine relaxation at higher concentrations.
• Breastfeeding: compatible after recovery.
• Older adults: reduce concentration in line with age-corrected minimum alveolar concentration.
• Kidney impairment: no adjustment.
• Liver impairment: acceptable; avoid after previous hepatic dysfunction from halogenated agents.
• Regional: draw-over vaporisers allow isoflurane delivery in settings without compressed gas or electricity; ensure the vaporiser is agent-specific, calibrated and used with an oxygen supplement and airway monitoring.

Formulations. Liquid for agent-specific vaporiser (100 and 250 mL bottles).

Administration. Deliver through a calibrated agent-specific vaporiser with scavenging. Use fresh, non-desiccated absorbent. In draw-over systems, ensure adequate ventilation and oxygen supplement.

Baseline. Malignant hyperthermia and family history, previous anaesthetic reactions, liver history, airway assessment, cardiac status (ischaemia).

Monitoring. End-tidal agent concentration (aim for 0.7 to 1.3 age-adjusted minimum alveolar concentration), electrocardiogram, blood pressure, oxygen saturation, capnography and temperature.

Therapeutic drug monitoring. Not used.

Dose reduction and stopping thresholds. Stop the agent immediately at any sign of malignant hyperthermia. Reduce concentration for hypotension or arrhythmia.

Referral and escalation. Malignant hyperthermia: stop all volatile agents and suxamethonium, hyperventilate with 100% oxygen at 10 L/minute or more, give dantrolene 2.5 mg/kg intravenously rapidly (repeat as needed up to a total of 10 mg/kg), actively cool, treat hyperkalaemia and acidosis, and transfer to intensive care.