General Anaesthetics

General anaesthetics produce reversible loss of consciousness, amnesia, immobility and blunted autonomic response to surgery. They include intravenous agents (propofol, thiopental, etomidate, ketamine) and inhalational agents (sevoflurane, isoflurane, desflurane, nitrous oxide, halothane in some settings), used with opioids, neuromuscular blockers and local anaesthetics as balanced anaesthesia.

Mechanism. Most potentiate GABA-A receptor chloride currents (propofol, etomidate, thiopental, volatiles) and inhibit excitatory transmission. Ketamine and nitrous oxide antagonise NMDA receptors. Volatile agents also activate two-pore potassium channels. Sites include cortex, thalamus, brainstem and spinal cord.

Potency and depth. Minimum alveolar concentration (MAC) is the alveolar concentration preventing movement in 50% of patients. MAC falls with age (about 6% each decade over 40), pregnancy, hypothermia, opioids, benzodiazepines and nitrous oxide, and rises with youth, hyperthermia and chronic alcohol use. Depth monitors (bispectral index 40 to 60) reduce awareness in total intravenous anaesthesia.

Pharmacokinetics. Intravenous induction is ended by redistribution from brain to muscle and fat, not by metabolism. Volatile uptake and recovery depend on blood:gas solubility (low solubility gives faster onset and offset), cardiac output and ventilation.

Maintenance. Volatile at 0.7 to 1.3 MAC, or propofol infusion 4 to 12 mg/kg/h (target-controlled infusion by effect-site concentration). Combine with an opioid and, where needed, a neuromuscular blocker.

• First-line. Propofol induction with sevoflurane or propofol maintenance for most adult surgery.
• Alternative. Ketamine in hypovolaemia, shock, asthma and where monitoring is limited; etomidate for unstable cardiac patients; sevoflurane inhalation induction in children without intravenous access.
• Specialist. Total intravenous anaesthesia for malignant hyperthermia susceptibility, neurosurgery and postoperative nausea risk; ketamine in burns and field anaesthesia.
• Emergency. Rapid sequence induction: ketamine 1 to 2 mg/kg, etomidate 0.3 mg/kg or reduced-dose propofol with suxamethonium 1 to 1.5 mg/kg or rocuronium 1.2 mg/kg.

Selection. Match agent to haemodynamic state and airway risk; reduce induction doses by 30 to 50% in older adults and shocked patients; prepare to manage hypotension and apnoea with every agent.

Contraindications. Hypersensitivity; malignant hyperthermia susceptibility for volatiles and suxamethonium; porphyria for thiopental; lack of airway skills and equipment; propofol with egg, soya or peanut allergy is a caution, not an absolute contraindication.

Serious adverse effects. Hypotension, apnoea, airway obstruction, aspiration, awareness, anaphylaxis, malignant hyperthermia, propofol infusion syndrome (infusions over 4 mg/kg/h for over 48 hours), emergence delirium, postoperative nausea and vomiting, hepatotoxicity (halothane), adrenal suppression (etomidate).

Malignant hyperthermia. Rising end-tidal carbon dioxide, tachycardia, rigidity, hyperthermia. Stop triggers, hyperventilate with 100% oxygen, give dantrolene 2.5 mg/kg intravenously, repeated until controlled (usual maximum 10 mg/kg), and treat hyperkalaemia, acidosis and hyperthermia.

Major interactions. Opioids and benzodiazepines add to respiratory depression and lower MAC; monoamine oxidase inhibitors and sympathomimetics with ketamine; neuromuscular blockers are potentiated by volatiles; alcohol and chronic opioid use raise requirements.

Common prescribing errors.

• Usual full induction doses in shock or frailty.
• Induction without airway equipment and suction.
• Nitrous oxide in pneumothorax, bowel obstruction and recent eye gas injection.
• Inadequate hypnosis during paralysis.
• Drug syringe confusion.

Special groups.

• Pregnancy: avoid elective surgery in the first trimester; reduce MAC; left lateral tilt after 20 weeks; aspiration precautions from about 18 to 20 weeks.
• Breastfeeding: can continue after recovery.
• Children: weight-based dosing; inhalation induction with sevoflurane; neurotoxicity concern with repeated or prolonged exposure under 3 years.
• Older adults: lower doses, slower titration.
• Kidney: avoid prolonged sevoflurane at flows under 1 L/min in renal impairment.
• Liver: avoid halothane.
• East Africa: ketamine anaesthesia is widely used where monitoring and supply are limited; confirm the availability of oxygen, suction, capnography and dantrolene.

Monitoring. ECG, saturation, capnography, blood pressure, temperature, inspired and expired anaesthetic concentration, depth monitor for total intravenous anaesthesia and neuromuscular block.

Referral and escalation. Failed intubation, anaphylaxis, malignant hyperthermia, prolonged emergence or unexplained postoperative neurological change need senior anaesthetic and intensive care input.

Comparison with alternative classes. General anaesthesia gives unconsciousness and control, but regional anaesthesia avoids airway management and may be safer where airway skills and monitoring are limited; sedation does not provide immobility.