Sevoflurane

Sevoflurane is a halogenated ether volatile anaesthetic with low blood solubility, non-pungent odour and rapid onset and recovery. It is the preferred volatile agent for inhalation induction, particularly in children, and is widely used for maintenance. It can trigger malignant hyperthermia and can form compound A with some carbon dioxide absorbents.

Class. Volatile (halogenated ether) general anaesthetic.

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

Pharmacokinetics. Blood-gas partition coefficient 0.65. Minimum alveolar concentration about 2.0% in oxygen in adults aged 40 years (about 1.4% with 60% nitrous oxide), 2.5 to 3.3% in infants and children, and about 1.5% at 65 years. Minimum alveolar concentration falls about 6% for each decade over 40. Metabolised 3 to 5% by CYP2E1 to hexafluoroisopropanol and inorganic fluoride; the rest is exhaled.

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

Adults

• Inhalation induction: start at 0.5 to 1% and increase by 0.5% every 2 to 3 breaths, or use a vital capacity breath at 8%, to a maximum 8%. Alternatively, induce with an intravenous agent.
• Maintenance: 0.5 to 3% (usually 1 to 2% with nitrous oxide or opioid), adjusted to age-corrected 0.7 to 1.3 minimum alveolar concentration.
• Fresh gas flow: at least 1 L/minute; lower flows are limited to 2 minimum alveolar concentration-hours in some labels because of compound A formation.

Children

• Inhalation induction: 6 to 8% in oxygen (with or without nitrous oxide), reducing to 2 to 4% for maintenance.
• Infants: higher minimum alveolar concentration (about 3.2%).
• Emergence delirium is more common in children; consider propofol 1 mg/kg or dexmedetomidine at the end of anaesthesia in preschool-age children.

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

Contraindications. Known or suspected susceptibility to malignant hyperthermia; history of hepatic dysfunction or jaundice after halogenated anaesthetics; hypersensitivity to halogenated agents; absence of an anaesthesia machine with appropriate vaporiser and scavenging.

Boxed-warning-level risks. Malignant hyperthermia (hypercarbia, tachycardia, rigidity, hyperthermia, hyperkalaemia, rhabdomyolysis); QT prolongation and torsades de pointes in susceptible patients; emergence agitation in children; carbon monoxide production with desiccated absorbents (heat, fire).

Adverse effects. Common: hypotension, nausea, vomiting, shivering, emergence agitation, cough (less than desflurane). Serious: malignant hyperthermia, arrhythmias, hepatic dysfunction (rare), renal effects with fluoride and compound A (clinically not shown), myocardial depression, apnoea.

Interactions. Opioids, benzodiazepines, nitrous oxide and neuromuscular blockers reduce required concentration or prolong effect. Volatile agents potentiate non-depolarising muscle relaxants. CYP2E1 inducers (isoniazid, chronic alcohol) increase fluoride production.

Common prescribing errors. Using in a patient with known malignant hyperthermia susceptibility; filling the wrong vaporiser; running low flows with desiccated absorbent; failing to switch to intravenous agent promptly in malignant hyperthermia; omitting scavenging.

Special groups

• Pregnancy: used for caesarean section at 0.5 to 1 minimum alveolar concentration to limit uterine relaxation; neonatal depression at high concentrations.
• Breastfeeding: compatible after recovery.
• Older adults: reduce concentration to match age-corrected minimum alveolar concentration.
• Kidney impairment: no adjustment; avoid flows below 1 L/minute.
• Liver impairment: acceptable; avoid after a history of hepatic dysfunction following halogenated agents.
• Regional: calibrate and service vaporisers, check the key-filling system so that each agent goes in its own vaporiser, and keep dantrolene and a malignant hyperthermia plan available in any theatre using volatile agents.

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

Administration. Deliver through a calibrated agent-specific vaporiser with scavenging. Use fresh, non-desiccated carbon dioxide absorbent. Warm and humidify the gas in long cases.

Baseline. Malignant hyperthermia and family history, previous reactions to anaesthesia, liver history, airway assessment, cardiovascular status.

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. Depth of anaesthesia monitoring in high-risk cases.

Therapeutic drug monitoring. Not used.

Dose reduction and stopping thresholds. Stop the agent immediately at any sign of malignant hyperthermia (rising end-tidal carbon dioxide despite increased ventilation, tachycardia, masseter rigidity, rising temperature). Reduce concentration for hypotension.

Referral and escalation. Malignant hyperthermia: stop all volatile agents and suxamethonium, change the circuit and absorbent if possible, hyperventilate with 100% oxygen at 10 L/minute or more, give dantrolene 2.5 mg/kg intravenously rapidly (repeat 1 mg/kg to 2.5 mg/kg up to a total of 10 mg/kg), actively cool, treat hyperkalaemia and acidosis, and transfer to intensive care.