Intravenous Anaesthetic Agents
Intravenous anaesthetic agents are used for induction and maintenance of general anaesthesia. Propofol is the most widely used agent; alternatives include thiopental, ketamine, and etomidate.
Key Facts
Propofol (1-2.5mg/kg IV) is the most commonly used induction agent — rapid onset (30s), smooth induction, antiemetic properties Thiopental (3-5mg/kg IV): Barbiturate; rapid onset; significant cardiovascular depression; now rarely used in UK Ketamine (1-2mg/kg IV): NMDA antagonist; provides dissociative anaesthesia with preserved airway reflexes and haemodynamic stability Etomidate (0.3mg/kg IV): Minimal cardiovascular depression — used for haemodynamically unstable patients; causes adrenocortical suppression Propofol acts primarily via GABA-A receptor potentiation; also has NMDA antagonist and sodium channel effects TIVA (Total IV Anaesthesia): Propofol + remifentanil via TCI pumps — avoids volatile agents; essential for patients susceptible to malignant hyperthermia Propofol infusion syndrome (PRIS) is a rare, fatal complication of prolonged high-dose propofol infusion (>4mg/kg/hr for >48h) in ICU Ketamine is the induction agent of choice in haemodynamic instability, severe asthma, and burns
Overview
Key Facts
IV anaesthetic agents provide rapid induction of unconsciousness and are fundamental to modern anaesthetic practice. Understanding their pharmacology, indications, and side effects is essential for safe anaesthesia.
Epidemiology
Propofol is used in >90% of IV inductions in the UK. TIVA accounts for approximately 15-20% of all GAs and is increasing. PRIS is rare but fatal — reported in prolonged ICU sedation.
Aetiology
IV anaesthetic agents produce unconsciousness by enhancing inhibitory neurotransmission (GABA-A: propofol, thiopental, etomidate) or blocking excitatory transmission (NMDA: ketamine). Each agent has a distinct pharmacokinetic profile governed by redistribution (initial offset) and metabolism (terminal elimination).
Pathophysiology
Propofol: Highly lipid-soluble → rapid brain uptake → unconsciousness in one arm-brain circulation time (20-30s). Redistribution to muscle and fat causes awakening. Hepatic and extrahepatic metabolism. Causes dose-dependent cardiovascular depression (reduced SVR, mild negative inotropy) and respiratory depression (apnoea at induction doses).
Ketamine: Produces dissociative anaesthesia — eyes remain open, muscle tone preserved. Sympathomimetic effects (releases catecholamines) maintain BP and HR. Bronchodilator. Increases secretions. Emergence phenomena (hallucinations, nightmares) occur in ~10-30% of adults.
Etomidate: Minimal cardiovascular effect — ideal for shock. Inhibits 11-beta-hydroxylase → adrenocortical suppression even after single dose (24h). Not recommended for repeated/prolonged use.
Clinical Presentation
Propofol
- Rapid smooth induction, antiemetic
- Pain on injection (~30-40%) — reduce with lidocaine 20-40mg IV pre-treatment
- Cardiovascular depression: hypotension (~20-30% BP drop)
- Respiratory depression: apnoea at induction
- Green discolouration of urine (harmless)
Ketamine
- Dissociative state: eyes open, nystagmus, preserved airway reflexes
- Sympathomimetic: tachycardia, hypertension, bronchodilation
- Increased salivation (give glycopyrrolate 200mcg IV)
- Emergence phenomena: nightmares, hallucinations (reduce with midazolam 1-2mg IV)
- Raises ICP (controversial — may be safe with controlled ventilation)
Etomidate
- Haemodynamic stability — minimal BP change
- Myoclonus (~30-60%) — reduce with opioid pre-treatment
- Adrenocortical suppression — avoid in sepsis, Addison's disease
- Pain on injection, nausea/vomiting
Red Flags
- Severe hypotension after propofol — consider hypovolaemia, reduce dose
- Prolonged propofol infusion >4mg/kg/hr in ICU — risk of PRIS (metabolic acidosis, rhabdomyolysis, cardiac failure)
- Emergence delirium with ketamine — treat with benzodiazepine
Differential Diagnosis
| Agent | Best Indication | Key Advantage | Key Disadvantage |
|---|---|---|---|
| Propofol | Routine induction/TIVA | Smooth induction, antiemetic, rapid recovery | Hypotension, pain on injection |
| Thiopental | Status epilepticus (historical) | Reliable, fast onset | CVS depression, no reversal, tissue necrosis if extravasation |
| Ketamine | Haemodynamic instability, asthma, burns | CVS stability, bronchodilation, analgesia | Emergence phenomena, raised ICP (debated) |
| Etomidate | Cardiovascular compromise | Haemodynamic stability | Adrenal suppression, myoclonus |
| Midazolam | Sedation, co-induction | Anxiolysis, amnesia, flumazenil reversal | Slow onset, unpredictable as sole agent |
Diagnosis / Investigation
Bedside
- Haemodynamic monitoring: BP, HR — propofol causes significant drops
- BIS (Bispectral Index): Depth of anaesthesia monitoring for TIVA — target 40-60
- ETCO2: Ventilation monitoring
Bloods
- ABG/VBG: If PRIS suspected (metabolic acidosis, raised lactate)
- CK: Rhabdomyolysis in PRIS
- Triglycerides: Propofol emulsion contains soy bean oil — monitor in prolonged infusion
- Cortisol: If etomidate-induced adrenal suppression suspected
Imaging
- Not routinely required for IV anaesthetic agent use
Special Tests
- Processed EEG (BIS/Entropy): Monitor depth of anaesthesia during TIVA to reduce awareness risk
Management
Non-pharmacological
- Dose adjustment: Reduce propofol dose in elderly, hypovolaemic, and ASA III-IV patients
- Pre-treatment: Lidocaine 20-40mg IV or mixed with propofol to reduce injection pain
- Fasting: Standard pre-operative fasting guidelines
Pharmacological
- Propofol induction: 1-2.5mg/kg IV (elderly 0.5-1.5mg/kg); TIVA maintenance: TCI 3-6mcg/mL (Marsh/Schnider model)
- Ketamine induction: 1-2mg/kg IV or 4-6mg/kg IM; maintenance 0.5-1mg/kg IV boluses or infusion 1-2mg/kg/hr
- Etomidate: 0.3mg/kg IV — single use for induction only
- Thiopental: 3-5mg/kg IV — declining use in UK; still used for refractory status epilepticus
- Midazolam: 1-2mg IV as co-induction agent (reduces propofol requirement by 20-30%)
Surgical/Interventional
- Not applicable
Referral Criteria
- Suspected PRIS — ICU management, stop propofol, switch to alternative sedation
- Severe emergence delirium with ketamine — anaesthetic/psychiatric support
Prognosis
- Propofol: Excellent safety profile; PRIS mortality >50% if not recognised early
- Ketamine: Resurgence in use for procedural sedation, analgesia, and treatment-resistant depression
- Etomidate: Adrenal suppression lasts ~24 hours after single dose — clinically significant in sepsis (CORTICUS trial context)
- Awareness under TIVA: Risk reduced to ~1:8,000 with BIS monitoring (vs 1:19,600 overall per NAP5)
Other Relevant Information
Pharmacokinetic Comparison
| Agent | Onset | Duration (single dose) | Metabolism | Context-Sensitive Half-Time |
|---|---|---|---|---|
| Propofol | 30s | 5-10 min | Hepatic + extrahepatic | Short (suitable for TIVA) |
| Thiopental | 30s | 5-10 min | Hepatic | Long (accumulates) |
| Ketamine | 60s | 10-20 min | Hepatic (CYP3A4) | Moderate |
| Etomidate | 30s | 5-10 min | Hepatic + plasma esterases | Short |
Propofol Infusion Syndrome (PRIS)
| Feature | Detail |
|---|---|
| Risk factors | >4mg/kg/hr for >48h, catecholamine infusion, steroid use, head injury |
| Presentation | Metabolic acidosis, rhabdomyolysis, hyperkalaemia, renal failure, cardiac failure |
| Mechanism | Impaired mitochondrial fatty acid oxidation |
| Treatment | Stop propofol, haemofiltration, supportive care |
| Mortality | >50% |