Intravenous Anaesthetics

Intravenous anaesthetics induce unconsciousness within one arm-brain circulation time and can maintain anaesthesia by infusion. The class includes propofol, thiopental, etomidate, ketamine and benzodiazepines such as midazolam, with dexmedetomidine used for sedation. They differ in cardiovascular effect, respiratory depression, analgesia and adverse effects.

Mechanism. Propofol, etomidate, thiopental and midazolam enhance GABA-A receptor activity at different sites. Ketamine blocks NMDA receptors, producing dissociative anaesthesia. Dexmedetomidine is an alpha-2 agonist in the locus coeruleus.

Pharmacokinetics. Onset is 30 to 60 seconds. Termination of a bolus is by redistribution; propofol is cleared in the liver and extrahepatic sites (half-life of redistribution 2 to 4 minutes), and ketamine hepatically with active norketamine. Context-sensitive half-time lengthens with thiopental and midazolam infusions, much less with propofol.

Propofol. Induction 1.5 to 2.5 mg/kg (0.5 to 1 mg/kg in older, frail or shocked patients); maintenance 4 to 12 mg/kg/h; sedation 1 to 4 mg/kg/h. Antiemetic, bronchodilating, anticonvulsant. Hypotension and apnoea are dose related; pain on injection (use larger veins or add lidocaine 20 to 40 mg).

Thiopental. 3 to 5 mg/kg (reduced in shock). Anticonvulsant; hypotension; extravasation and intra-arterial injection cause tissue necrosis; contraindicated in porphyria and asthma (relative).

Etomidate. 0.2 to 0.3 mg/kg. Minimal haemodynamic change; reversible suppression of cortisol synthesis lasting 24 hours or longer after a single dose; myoclonus, nausea, pain on injection.

Ketamine.

• Induction 1 to 2 mg/kg intravenously or 4 to 10 mg/kg intramuscularly.
• Sedation and procedural analgesia 0.5 to 1 mg/kg intravenously.
• Analgesic dose 0.1 to 0.3 mg/kg.
• Raises heart rate and blood pressure, preserves airway tone and ventilation, bronchodilates; emergence reactions, hypersalivation and raised intraocular pressure.

Midazolam. Sedation 0.5 to 1 mg intravenously titrated up to 2.5 mg; induction 0.1 to 0.2 mg/kg; reduced by 50% in older adults. Reversal with flumazenil 0.2 mg intravenously, repeated up to 1 mg.

Dexmedetomidine. Loading 1 microgram/kg over 10 minutes (omit in unstable patients), maintenance 0.2 to 1.4 micrograms/kg/h; sedation with preserved respiration; bradycardia and hypotension.

• First-line. Propofol for induction and short sedation; ketamine for analgesia, haemodynamic instability and resource-limited settings.
• Alternative. Etomidate for cardiac or unstable patients; midazolam for sedation and anxiolysis; thiopental when propofol is unavailable.
• Specialist. Dexmedetomidine for awake fibreoptic intubation and intensive care sedation; total intravenous anaesthesia; ketamine infusion for refractory pain or status asthmaticus.
• Emergency. Ketamine 1 to 2 mg/kg or etomidate 0.3 mg/kg for rapid sequence induction in shock; propofol or thiopental for status epilepticus requiring anaesthesia (specialist).

Selection. Preserve cardiac output in shock (ketamine, etomidate, reduced propofol); use propofol when rapid awakening and antiemetic effect matter; avoid etomidate for repeated doses or infusions in sepsis.

Contraindications. Hypersensitivity; thiopental in porphyria; etomidate by infusion (use in septic shock is debated); ketamine in severe hypertension, eclampsia, raised intracranial pressure without airway control, active psychosis and ischaemic heart disease; propofol in unsupported airway; dexmedetomidine in advanced heart block.

Serious adverse effects. Hypotension, apnoea, anaphylaxis, propofol infusion syndrome (metabolic acidosis, rhabdomyolysis, arrhythmia, renal failure), adrenal suppression, tissue necrosis from thiopental extravasation, paradoxical agitation with midazolam in older adults and children, hypersalivation and laryngospasm with ketamine.

Major interactions. Opioids and benzodiazepines with propofol: marked respiratory depression; midazolam with CYP3A4 inhibitors (clarithromycin, azoles, ritonavir): prolonged effect; ketamine with sympathomimetics: hypertensive crisis; alpha-2 agonists with beta-blockers: bradycardia.

Common prescribing errors.

• Full induction dose in shock.
• Propofol infusion beyond 4 mg/kg/h for over 48 hours without monitoring.
• Midazolam dose not reduced in older adults.
• Thiopental in porphyria.
• Ketamine given by unmonitored operators.

Special groups.

• Pregnancy: propofol and ketamine acceptable; thiopental widely used for caesarean section.
• Breastfeeding: can resume after recovery.
• Children: propofol 2.5 to 3.5 mg/kg for induction; ketamine 1 to 2 mg/kg intravenously or 5 to 10 mg/kg intramuscularly.
• Older adults: reduce doses by 30 to 50%.
• Kidney: little effect; reduced midazolam clearance in severe disease.
• Liver: reduced propofol clearance and prolonged midazolam effect in cirrhosis.
• East Africa: ketamine is often the main induction agent where anaesthesia monitoring, oxygen and ventilators are limited; use continuous pulse oximetry and have suction ready.

Monitoring. ECG, saturation, capnography, blood pressure; sedation scale; triglycerides, creatine kinase and lactate with prolonged propofol; cortisol deficiency if etomidate used repeatedly.

Referral and escalation. Persistent hypotension, anaphylaxis, signs of propofol infusion syndrome, prolonged unconsciousness, or respiratory depression requiring ventilatory support.

Comparison with alternative classes. Intravenous agents give rapid induction and avoid airway irritation compared with volatile agents but cause more hypotension and apnoea and need an infusion pump and pharmacokinetic familiarity for maintenance.