Pharm 101: Propofol

Pharmacodynamics

• Multiple organ system effects, most notably central nervous system (CNS), cardiovascular and respiratory
• CNS:
  • Hypnotic
  • Anticonvulsant
  • Decreases intracranial pressure (due to decrease in both cerebral metabolic rate and cerebral blood flow)
  • Note no analgesic effect
• Cardiovascular:
  • Decreases preload and afterload, causing hypotension. This effect is increased with increasing age and reduced intravascular volume
  • Also some inhibition of normal baroreceptor reflex, leading to minimal reflex tachycardia
• Respiratory:
  • Dose-related central depression of respiratory drive, with reduced respiratory rate, and reduced response to hypercapnoea and hypoxia
  • Reduction in tidal volume
  • Reduction in upper airway reflexes
• Other:
  • Anti-emetic effect

Pharmacokinetics

• IV administration
• Rapid onset and offset due to redistribution from the brain to skeletal muscle and fat (c.f. metabolism)
• Distribution half life 2-4 minutes
• Metabolism and elimination:
  • Rapid metabolism in liver, some extra-hepatic (lung) as total body clearance is greater than hepatic blood flow
  • Excreted in urine as glucuronides and sulphates, <1% unchanged
  • Elimination half life of 4-23 minutes
• Duration of action 3-8 minutes

Clinical uses

• Procedural sedation
  • 0.5-1.0mg/kg single bolus or 10-20mg aliquots titrated
  • Use in conjunction with an analgesic agent
• Rapid Sequence Induction
  • 1-2.5mg/kg in adults
  • 2.5-3.5mg/kg in children
• Maintenance of anaesthesia

Adverse effects

• Adverse effects are often an extension of propofol’s pharmacodynamic effect
• Hypotension
  • Negative isotropic effect and venodilation
• Apnoea
• Loss of airway reflexes causing obstruction and aspiration
• Pain on injection
• Allergic cross-reactivity to egg/soy products
• Propofol infusion syndrome
  • Metabolic acidosis and tachycardia

Precautions/contraindications

• Elderly patients
• Poor cardiovascular reserve
• Haemodynamic instability

Further Reading

• Nickson C. Propofol-related Infusion Syndrome. LITFL
• Nickson C. Rapid Sequence Induction (RSI). LITFL
• Propofol – Part One – LITFL
• Cadogan M. Verdant waste. LITFL