Key Facts

Inhalational anaesthetic agents remain fundamental to anaesthetic practice for maintenance of general anaesthesia. They offer predictable pharmacokinetics, ease of administration, and built-in monitoring (end-tidal concentration correlates with brain concentration).

Epidemiology

Approximately 80-85% of general anaesthetics in the UK use volatile agents for maintenance (remainder are TIVA). Sevoflurane has largely replaced isoflurane for routine use. There is increasing awareness of the environmental impact — desflurane has a global warming potential 2,500 times that of CO2.

Aetiology

The mechanism of action of volatile agents is not fully understood. The Meyer-Overton hypothesis correlates potency with lipid solubility. Modern theory focuses on actions at specific protein targets: GABA-A receptor potentiation (enhances inhibition), NMDA receptor antagonism (reduces excitation), glycine receptor modulation, and two-pore-domain potassium channel activation.

Pathophysiology

Pharmacokinetics:

• Delivery is determined by inspired concentration, alveolar ventilation, and cardiac output
• Uptake depends on blood:gas partition coefficient (lower = faster onset)
• Blood:gas coefficients: Desflurane 0.42, sevoflurane 0.65, isoflurane 1.4
• Recovery is essentially the reverse of uptake — agents with low solubility allow faster emergence
• Metabolism is minimal for most agents; sevoflurane produces Compound A (fluoride ion) in closed circuits with soda lime

Sevoflurane

• Non-pungent — suitable for inhalational induction (especially paediatrics)
• Rapid onset and offset
• Mild cardiovascular depression
• Can cause emergence agitation in children

Desflurane

• Fastest offset of all volatiles (blood:gas 0.42)
• Pungent — NOT suitable for inhalational induction (causes coughing, laryngospasm)
• Sympathetic activation at rapid concentration increases
• Highest environmental impact (GWP)

Isoflurane

• Moderate onset/offset
• Good muscle relaxation, coronary vasodilation
• Pungent — not ideal for inhalational induction

Nitrous Oxide

• Analgesic at sub-anaesthetic concentrations (Entonox = 50% N2O + 50% O2)
• Second gas effect (accelerates uptake of co-administered volatile)
• Diffusion hypoxia on discontinuation (give 100% O2 for 5 min)
• Inhibits methionine synthase (B12 inactivation) — avoid in B12 deficiency, prolonged use

Red Flags

• Rising ETCO2 + tachycardia + rigidity + hyperthermia — malignant hyperthermia (stop volatile, dantrolene)
• Sudden hypotension with volatile — check depth, consider hypovolaemia or anaphylaxis
• Post-operative hepatitis (rare) — halothane was most common cause (now obsolete in UK)

Bedside

• End-tidal agent monitoring: Mandatory — correlates with brain concentration at steady state
• AAGBI standard monitoring: SpO2, ECG, NIBP, ETCO2, temperature
• Agent analyser: Confirms correct agent and concentration

Bloods

• LFTs: If post-operative hepatitis suspected (historical with halothane)
• Fluoride levels: Not routinely measured; relevant to sevoflurane metabolism
• CK, potassium, ABG: If malignant hyperthermia suspected

Imaging

• Not specific to volatile agent use

Special Tests

• Malignant hyperthermia susceptibility testing: In vitro contracture test (IVCT) — gold standard, performed at specialist centres (Leeds, London)
• Caffeine halothane contracture test: Muscle biopsy-based diagnostic

Non-pharmacological

• Vaporiser use: Agent-specific calibrated vaporisers (Tec 6 for desflurane — requires heating)
• Low-flow anaesthesia: Reduce fresh gas flow to 0.5-1L/min to reduce agent consumption and environmental impact
• Scavenging: Active scavenging systems mandatory in all theatres to reduce occupational exposure

Pharmacological

• Sevoflurane: MAC 2.0% in 100% O2; adjusted for age, opioids (reduce MAC by 50-70%), N2O (reduces MAC by 25-30%)
• Desflurane: MAC 6.0%; maintenance typically 3-6% in air/O2
• Isoflurane: MAC 1.15%; maintenance typically 0.5-1.5% in air/O2
• N2O: 50-70% as carrier gas with volatile; Entonox (50:50) for analgesia
• MAC reduction: Age >70 (~30% reduction), opioids, benzodiazepines, alpha-2 agonists, hypothermia

Surgical/Interventional

• Not applicable

Referral Criteria

• Suspected malignant hyperthermia — specialist centre referral for IVCT
• Environmental concerns — hospital sustainability teams promoting TIVA and low-flow techniques

• Volatile anaesthetics have an excellent safety profile with decades of clinical use
• Malignant hyperthermia mortality: <5% with early recognition and dantrolene treatment (previously >70%)
• Environmental impact: Volatile anaesthetic agents contribute approximately 5% of the NHS carbon footprint
• POCD: Some evidence of neurotoxicity in developing brains (animal models); clinical significance debated
• Sevoflurane nephrotoxicity: Compound A concerns in closed circuits have not translated to clinical harm at standard flows

MAC Values and Factors Affecting MAC

Environmental Impact of Volatile Agents