Thiopentone

At-a-glance clinical use

• Primary role: IV induction of anaesthesia (now less common than propofol); useful when haemodynamic stability is desired vs propofol, and where bronchodilation/antiemesis are not priorities.
• Other roles: rapid sequence induction (historical), neuroanaesthesia (reduces CMRO2/CBF/ICP), refractory status epilepticus (ICU infusion), ECT induction (historical).
• Avoid/contraindicated: acute porphyria; caution in shock/hypovolaemia, severe asthma/bronchospasm risk, severe cardiac disease, difficult airway (apnoea).

Typical dosing (adult)

• Induction: 3–5 mg/kg IV (reduce in elderly, hypovolaemia, cardiac disease; increase in young fit adults).
• Sleep dose concept: titrate to loss of eyelash reflex/response; onset ~30–45 s.
• Status epilepticus (ICU): bolus then infusion titrated to EEG burst suppression (local protocols; requires ventilation/vasopressors).

Preparation and administration

• Supplied as powder for reconstitution; commonly 2.5% (25 mg/mL) or 5% (50 mg/mL).
• Strongly alkaline solution (pH ~10–11): risk of tissue injury with extravasation; intra-arterial injection can cause severe vasospasm/ischaemia.
• Compatibility: precipitates with acidic drugs/solutions; avoid mixing in same line with many agents (flush well).

Classification and chemistry

• Ultra-short acting barbiturate; sulfur at C2 (thiobarbiturate) increases lipid solubility and speeds onset vs oxybarbiturates.
• Weak acid (pKa ~7.6): at physiological pH a significant fraction is unionised → rapid CNS penetration.
• Formulated as sodium salt in alkaline solution to maintain solubility.

Mechanism of action (CNS pharmacodynamics)

• Positive allosteric modulator of GABAA receptor; at higher concentrations can directly gate the chloride channel (GABA-mimetic).
• Also inhibits excitatory neurotransmission (e.g., AMPA) and reduces neuronal firing; produces hypnosis but poor analgesia.
• EEG: dose-dependent slowing → burst suppression at high doses.

Pharmacokinetics

• Onset: ~30–45 s (high lipid solubility; rapid brain uptake).
• Duration of a single bolus: 5–10 min mainly due to redistribution from vessel-rich group (brain) to muscle/fat, not metabolism.
• Protein binding: high (~80%); reduced binding (e.g., hypoalbuminaemia, pregnancy) increases free fraction and effect.
• Metabolism: hepatic oxidation to inactive metabolites; some extrahepatic metabolism; elimination slower than clinical effect after single bolus.
• Context-sensitive half-time increases with prolonged infusion due to accumulation in fat; prolonged sedation/hangover possible.

Cardiovascular effects

• Reduces arterial BP mainly via venodilation (↓ preload) and some arterial dilation (↓ SVR); myocardial depression also contributes.
• Reflex tachycardia may occur; overall haemodynamic depression generally less than propofol but clinically significant in hypovolaemia/cardiac disease.
• Reduces cerebral perfusion pressure if BP falls; in neuroanaesthesia balance ICP reduction vs systemic hypotension.

Respiratory effects

• Dose-dependent respiratory depression and apnoea; blunts ventilatory responses to CO2 and hypoxia.
• May provoke bronchospasm (histamine release and airway reflexes) particularly in reactive airways; less bronchodilation than propofol/volatile agents.
• Laryngospasm can occur if airway instrumentation at light planes (especially without adequate opioid/volatile depth).

CNS and cerebral physiology

• Decreases CMRO2, CBF, and ICP; preserves autoregulation and CO2 reactivity (generally).
• Neuroprotective rationale: reduces metabolic demand; evidence for outcome benefit is limited—used pragmatically for ICP control and burst suppression.
• Anticonvulsant at induction doses; can be used to terminate seizures; paradoxical excitatory phenomena are less common than with some agents but can occur.

Other system effects

• No intrinsic analgesia; may reduce uterine tone (less than volatile agents) and crosses placenta—neonatal depression possible if high dose close to delivery.
• PONV: not antiemetic; may be associated with higher PONV than propofol-based techniques.
• Immune/allergy: can cause histamine release; true anaphylaxis is rare but possible.

Indications and advantages (exam framing)

• Induction where propofol undesirable (e.g., severe hypotension risk) and ketamine not appropriate; familiarity in some units.
• Neuroanaesthesia: reduces ICP and CMRO2; can be used for burst suppression in refractory intracranial hypertension or seizures.
• Status epilepticus: barbiturate coma as third-line therapy (after benzodiazepine + second-line antiepileptic).

Contraindications and cautions

• Absolute: acute porphyria (induces hepatic ALA synthase → precipitates attack).
• Relative: hypovolaemia/shock, severe cardiac disease, severe asthma/reactive airways, sepsis with cardiovascular instability, difficult airway if apnoea risk unacceptable.
• Drug interactions: additive CNS depression with opioids/benzodiazepines; enzyme induction with repeated use (less relevant for single induction).

Adverse effects and complications

• Injection pain less than propofol but can occur; thrombophlebitis possible.
• Tissue injury with extravasation due to alkalinity; treat with stop injection, aspirate, elevate, analgesia; consider surgical review if severe.
• Intra-arterial injection: severe pain, vasospasm, thrombosis, distal ischaemia/necrosis; emergency management required.
• Prolonged sedation after repeated boluses/infusion due to accumulation (fat storage).

Intra-arterial injection: immediate management (viva-ready)

• Stop injection immediately; leave cannula in situ; call for help; assess limb perfusion and pain.
• Aspirate via cannula if possible; flush with 0.9% saline; consider intra-arterial local anaesthetic (e.g., lignocaine) to relieve spasm (local policy).
• Analgesia (often opioid), anticoagulation (e.g., heparin) and vasodilators may be used; urgent vascular/plastics input; document and incident report.
• Monitor for compartment syndrome; consider regional sympathetic block in specialist hands.