Inhalational Anaesthetics

Inhalational anaesthetics are volatile liquids and gases delivered through the lungs to produce and maintain general anaesthesia. They include sevoflurane, isoflurane, desflurane, halothane (still seen in some resource-limited settings) and nitrous oxide. Their uptake and elimination follow ventilation, cardiac output and solubility, and their depth of action is titrated by end-tidal concentration.

Mechanism. Potentiation of GABA-A and glycine receptors, opening of two-pore potassium channels and, for nitrous oxide, NMDA receptor antagonism. Effects are dose related: amnesia, then unconsciousness, then immobility.

Pharmacokinetics.

• Blood:gas partition coefficient: desflurane 0.42, nitrous oxide 0.47, sevoflurane 0.65, isoflurane 1.4, halothane 2.4; lower values give faster change in depth.
• MAC at age 40: desflurane 6%, sevoflurane 2%, isoflurane 1.15%, halothane 0.75%, nitrous oxide 104%.
• MAC falls by about 6% each decade over 40 and by 25 to 40% in pregnancy.
• Metabolism: halothane 20%, sevoflurane 2 to 5%, isoflurane and desflurane under 1%.

Sevoflurane. Sweet smell, minimal airway irritation, suitable for inhalation induction in children (up to 8% initially). Degraded by carbon dioxide absorbents to compound A; use fresh gas flow of 1 to 2 L/min or more.

Isoflurane. Pungent, cheaper, causes vasodilation and tachycardia on rapid rise; coronary steal is not clinically proven.

Desflurane. Fastest onset and offset; pungent, airway irritant, sympathetic stimulation; requires heated vaporiser; high global warming potential.

Halothane. Potent, sweet, bronchodilating; sensitises the myocardium to catecholamines; causes halothane hepatitis (1 in 6000 to 35 000) after repeated exposure; avoid in adults with prior unexplained jaundice after halothane.

Nitrous oxide. Analgesic, weak anaesthetic. Used at 50 to 70% in oxygen. Diffuses into closed spaces; inactivates vitamin B12-dependent methionine synthase.

Maintenance. Sevoflurane 1.5 to 2.5%, isoflurane 1 to 1.5%, desflurane 5 to 7%, adjusted to age-adjusted MAC of 0.7 to 1.3 with an opioid.

• First-line. Sevoflurane for most adult and paediatric maintenance and for inhalation induction.
• Alternative. Isoflurane where cost matters; desflurane for rapid emergence in obesity or day surgery when supply and environmental considerations allow.
• Specialist. Sevoflurane or isoflurane for sedation in intensive care using a reflector device; nitrous oxide for labour and procedural analgesia as 50% mixture; volatile agent for refractory status asthmaticus or status epilepticus (specialist).
• Emergency. Inhalation induction in difficult airway with spontaneous breathing, using sevoflurane.

Selection. Choose by airway irritation, speed, cost and environmental impact; avoid desflurane in children for induction; use low fresh gas flows to reduce cost and pollution.

Contraindications. Personal or family history of malignant hyperthermia (all volatiles); halothane after prior hepatitis; nitrous oxide in pneumothorax, bowel obstruction, middle ear surgery, recent intraocular gas, air embolism, decompression illness, and untreated vitamin B12 deficiency; desflurane in reactive airways.

Serious adverse effects. Dose-related hypotension and myocardial depression; malignant hyperthermia; respiratory depression; airway irritation (desflurane); emergence delirium in children (sevoflurane); postoperative nausea; hepatitis (halothane); arrhythmia with halothane and adrenaline; carbon monoxide formation with dry absorbents; bone marrow and neurological effects from prolonged nitrous oxide.

Major interactions. Opioids, benzodiazepines and nitrous oxide reduce MAC; neuromuscular blockers are potentiated; adrenaline with halothane risks arrhythmia; sympathomimetics and monoamine oxidase inhibitors alter haemodynamics; methotrexate toxicity may rise with nitrous oxide.

Common prescribing errors.

• Vaporiser filled with the wrong agent.
• Desflurane in airway irritation.
• Nitrous oxide in closed gas spaces.
• Dry absorbent not replaced.
• Using halothane with adrenaline infiltration.

Special groups.

• Pregnancy: avoid nitrous oxide in early pregnancy where alternatives exist; MAC is lower; volatile agents relax the uterus, which aids surgery but may cause postpartum haemorrhage at over 1 MAC.
• Breastfeeding: compatible after recovery.
• Children: higher MAC in infants (sevoflurane 3 to 3.3% in infancy); laryngospasm risk with irritants.
• Older adults: lower MAC; prolonged emergence.
• Kidney: use sevoflurane at fresh gas flows of at least 1 to 2 L/min.
• Liver: avoid halothane.
• East Africa: halothane and isoflurane may be encountered; check the vaporiser label and availability of scavenging, capnography and oxygen analysers.

Monitoring. End-tidal anaesthetic concentration, end-tidal carbon dioxide, inspired oxygen, ECG, saturation, blood pressure and temperature.

Referral and escalation. Rising end-tidal carbon dioxide with tachycardia and rigidity (malignant hyperthermia); persistent jaundice after halothane; prolonged emergence.

Comparison with alternative classes. Volatile agents allow measurable depth control and inhalation induction without venous access, but are less suited to patients with malignant hyperthermia risk, high postoperative nausea risk and where scavenging is unavailable; total intravenous anaesthesia avoids pollution.