propofol
intravenous anesthetic· Brands: Diprivan, Propofol-LipuroIV
Mechanism of action
Propofol enhances gamma-aminobutyric acid (GABA) activity at GABA-A receptors, increasing chloride conductance and hyperpolarising neuronal membranes. This produces dose-dependent sedation and hypnosis. It also inhibits the N-methyl-D-aspartate receptor, contributing to its anaesthetic effects.
Pharmacokinetics
Propofol has a rapid onset of action, with loss of consciousness within one minute of an intravenous induction dose. It is highly lipid soluble, redistributing rapidly from the brain to peripheral tissues. Recovery is fast due to rapid redistribution and hepatic metabolism to inactive metabolites, which are excreted renally. The context-sensitive half-life increases with prolonged infusion, leading to prolonged recovery after long infusions.
Indications & dosing
Induction of general anaesthesia in adults
Titrate to effect; reduce dose in elderly or haemodynamically unstable patients.
- adult · IV: 1.5–2.5 mg/kg single dose · Titrate to effect; reduce dose in elderly or haemodynamically unstable patients.
Maintenance of general anaesthesia in adults (TIVA)
Use with opioid analgesic; adjust to surgical stimulus.
- adult · IV: 4–12 mg/kg/h continuous infusion · Use with opioid analgesic; adjust to surgical stimulus.
Sedation in intensive care for ventilated adults
Administer by infusion pump; monitor for hypotension.
- adult · IV: 0.3–4 mg/kg/h continuous infusion · Administer by infusion pump; monitor for hypotension.
Procedural sedation in adults
Administer slowly; allow 1-2 min between increments.
- adult · IV: 0.5–1 mg/kg titrated bolus · Administer slowly; allow 1-2 min between increments.
Induction of general anaesthesia in children
May require higher dose than adults relative to body weight.
- pediatric · IV: 2–3 mg/kg single dose · May require higher dose than adults relative to body weight.
Contraindications & precautions
- Hypersensitivity to propofol or any component of the formulation (e.g., soya bean oil, egg lecithin) · Previous anaphylactic reaction to propofol or its excipients.
- Severe cardiovascular instability or hypovolaemia (e.g., shock) · Induction of anaesthesia may cause profound hypotension in these patients.
- Disorders of lipid metabolism · Propofol is a lipid emulsion; use with caution in patients with hyperlipidaemia or pancreatitis risk.
- Pregnancy (especially third trimester) · Propofol crosses the placenta; used in obstetric anaesthesia but with careful monitoring.
- Ensure airway equipment, suction, and oxygen are available before induction; monitor cardiovascular and respiratory status continuously.
- Titrate dose slowly to effect; avoid rapid bolus to minimise hypotension and apnoea.
- Use extreme caution in patients with cardiovascular instability, hypovolaemia, or poor cardiac reserve; consider reduced induction dose.
- For prolonged infusion (e.g., ICU sedation), monitor for propofol infusion syndrome (metabolic acidosis, rhabdomyolysis, cardiac arrhythmias); limit duration and dose where possible.
- Use strict aseptic technique when handling propofol; the lipid emulsion supports microbial growth and should be used promptly after opening.
Adverse effects
- Pain on injection
- Hypotension
- Apnoeaserious
- Bradycardia
- Anaphylaxisserious
- Propofol infusion syndromeserious
Renal & hepatic adjustment
- Hepatic impairment (severe): Caution and reduced dose may be required in severe hepatic impairment due to increased sensitivity and reduced clearance.
Monitoring, pregnancy & toxicity
- Blood pressure · continuous during induction and maintenance
- Heart rate · continuous
- Respiratory rate and oxygen saturation · continuous
- Depth of anaesthesia · clinical signs or processed EEG (e.g. bispectral index) if available
- Injection site · for pain or extravasation
- Lipid profile and serum lactate · during prolonged infusion (>48 hours) to monitor for propofol infusion syndrome
- Pregnancy: Propofol is used for anaesthesia during all stages of pregnancy. It crosses the placenta and may cause neonatal depression if used near delivery, but it is generally considered safe when administered by a specialist. Avoid in the first trimester unless absolutely necessary.
- Toxicity: Cardiorespiratory depression: hypotension, bradycardia, apnoea · Supportive care; intravenous fluids, vasopressors, ventilatory support as required.
- Toxicity: Pain at injection site · Administer into a large vein; consider pretreatment with a local anaesthetic or use a lipid emulsion formulation.
- Toxicity: Propofol infusion syndrome (PRIS): metabolic acidosis, rhabdomyolysis, hyperkalaemia, cardiovascular collapse · Discontinue propofol; provide supportive care including haemodialysis or haemofiltration, and correct electrolyte imbalances.
Clinical notes
Propofol is used for induction and maintenance of general anaesthesia, and for sedation in intensive care and procedural settings. Caution is required in haemodynamically unstable patients as it can cause hypotension and bradycardia. Pain on injection is common; giving a larger vein or mixing with lidocaine can reduce it. Propofol infusion syndrome is a rare but serious complication, characterised by metabolic acidosis, rhabdomyolysis and cardiac failure, especially with prolonged high-dose infusions in children.
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BNF; local formulary