1. Sevoflurane - 3 marks

Basic mechanism of action

• Produces CNS depression by enhancing inhibitory neurotransmission:
  • potentiates GABA-A and glycine receptor activity
  • opens background potassium channels causing neuronal hyperpolarisation
• Reduces excitatory neurotransmission, including NMDA receptor activity.
• Final effects: unconsciousness, amnesia, immobility and suppression of autonomic responses.

Uptake and clinical pharmacology

• Blood:gas partition coefficient = 0.65.
• Low blood solubility causes rapid rise of alveolar concentration and hence rapid, smooth induction and recovery.
• It is non-pungent, causes minimal airway irritation, and produces bronchodilatation.
• Therefore, it is the preferred volatile agent for mask induction, especially in children.
• MAC in adults = about 2%.
• About 3%-5% is metabolised by CYP2E1, producing inorganic fluoride and hexafluoroisopropanol.
• It can react with CO₂ absorbents to form Compound A, hence fresh gas flow should not be very low during prolonged administration.

Adverse effects / limitations

• Dose-dependent hypotension and respiratory depression.
• May increase cerebral blood flow and intracranial pressure at high concentration.
• Emergence agitation may occur in children.
• Rarely, may trigger malignant hyperthermia in susceptible patients.

2. Desflurane - 3 marks

Basic mechanism of action

• Enhances inhibitory neurotransmission through:
  • GABA-A receptors
  • glycine receptors
  • potassium channel activation leading to neuronal hyperpolarisation
• Inhibits excitatory neuronal pathways, including NMDA-mediated transmission.
• This produces unconsciousness, amnesia, immobility and autonomic suppression.

Uptake and clinical pharmacology

• Blood:gas partition coefficient = 0.42, the lowest among commonly used volatile agents.
• Very low blood solubility produces:
  • very rapid change in depth of anaesthesia
  • rapid emergence and early recovery
• MAC in adults = about 6%, so it is less potent than sevoflurane.
• It is minimally metabolised, about 0.02%, and more than 99% is eliminated unchanged via the lungs.
• It has very high vapour pressure and boiling point close to room temperature; hence it requires a special heated, pressurised vaporizer.

Adverse effects / limitations

• It is pungent and irritates the airway.
• May cause coughing, breath holding, laryngospasm and increased secretions.
• Abrupt increase in concentration can cause sympathetic stimulation with tachycardia and hypertension.
• Therefore, it is unsuitable for inhalational induction, especially in children.
• It causes dose-dependent hypotension and respiratory depression.
• May trigger malignant hyperthermia in susceptible patients.

Uptake of inhalational anaesthetic agent

Factors affecting uptake

1. Blood:gas solubility
   • Higher solubility means more agent dissolves in blood.
   • Alveolar partial pressure rises slowly.
   • Induction is slow.
   • Example: sevoflurane is faster than more soluble agents; desflurane is fastest because it has very low solubility.
2. Cardiac output
   • Increased cardiac output increases pulmonary blood flow and uptake.
   • Alveolar concentration rises slowly, so induction is delayed.
   • Low cardiac output causes rapid rise in alveolar concentration and faster induction.
3. Alveolar ventilation
   • Increased ventilation delivers more anaesthetic to alveoli.
   • This increases alveolar concentration and speeds induction.
   • Effect is more marked with soluble agents.
4. Inspired concentration
   • Higher inspired concentration increases the alveolar concentration rapidly.
   • This is called the concentration effect or overpressure technique.

Comparison: Sevoflurane vs Desflurane