Desflurane

Desflurane is a fluorinated methyl ethyl ether volatile anaesthetic with the lowest blood solubility of the volatile agents, giving the fastest onset and recovery. It is pungent and irritates the airway, so it is not used for induction. It has the highest global-warming potential of the volatile agents, and its use is declining for environmental reasons.

Class. Volatile (halogenated ether) general anaesthetic.

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

Pharmacokinetics. Blood-gas partition coefficient 0.42. Minimum alveolar concentration about 6.0% in oxygen in adults aged 40 years (about 2.8% with 60% nitrous oxide); falls about 6% for each decade over 40; higher in children (about 8 to 10%). Only 0.02% is metabolised. Boiling point 22.8 degrees Celsius at sea level, so it requires an electrically heated, pressurised, agent-specific vaporiser.

Indications are maintenance of general anaesthesia in adults and in intubated children, and anaesthesia where rapid emergence matters (obesity, day surgery, neurosurgery, older adults).

Adults

• Induction: not used. Induce with an intravenous agent.
• Maintenance: 2 to 6% in oxygen or air (1 to 4% with nitrous oxide), adjusted to age-corrected 0.7 to 1.3 minimum alveolar concentration. Slow stepwise increases avoid sympathetic stimulation.
• Fresh gas flows of 1 to 2 L/minute are usual.

Children

• Not for induction or for maintenance in non-intubated infants and children because of laryngospasm, coughing and breath holding.
• Intubated children after induction with another agent: maintenance 5 to 10%, adjusted to age-corrected minimum alveolar concentration.

Contraindications. Known or suspected susceptibility to malignant hyperthermia; history of hepatic dysfunction after halogenated anaesthetics; induction of anaesthesia in infants and children; hypersensitivity; patients in whom increases in heart rate or blood pressure are hazardous (severe coronary disease, intracranial hypertension) when rapid increases occur.

Boxed-warning-level risks. Malignant hyperthermia; sympathetic stimulation (hypertension, tachycardia) with rapid increases in concentration; airway irritability including laryngospasm and bronchospasm; carbon monoxide production with desiccated absorbents.

Adverse effects. Common: cough, breath holding, salivation, laryngospasm on induction, hypotension, tachycardia, nausea, vomiting. Serious: malignant hyperthermia, arrhythmias, bronchospasm in asthma, post-anaesthetic hepatic dysfunction (rare), carbon monoxide poisoning.

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

Common prescribing errors. Using for inhalation induction; running high concentrations in a patient with ischaemic heart disease; using in an asthmatic with active bronchospasm; forgetting the specialised vaporiser requirements; using with dry absorbent.

Special groups

• Pregnancy: acceptable at 0.5 to 1 minimum alveolar concentration for caesarean section.
• 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: availability depends on the heated vaporiser and supply of the agent; many district settings do not have it. Where used, include environmental impact in agent choice.

Formulations. Liquid for heated electronic vaporiser (240 mL bottles).

Administration. Deliver through a heated, pressurised agent-specific vaporiser with scavenging. Use fresh, non-desiccated absorbent. Increase the concentration slowly.

Baseline. Malignant hyperthermia and family history, asthma, cardiac status, liver history, airway assessment.

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. Watch for tachycardia and hypertension with each step increase.

Therapeutic drug monitoring. Not used.

Dose reduction and stopping thresholds. Stop the agent immediately at any sign of malignant hyperthermia. Reduce concentration for sympathetic stimulation, 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 10 mg/kg), actively cool, treat hyperkalaemia and acidosis, and transfer to intensive care. Persistent bronchospasm needs salbutamol and deepening anaesthesia with an intravenous agent.