Thiopental

Thiopental is an ultra-short-acting thiobarbiturate once the most common induction agent worldwide. It is still used where supply exists, particularly for rapid sequence induction, neuroprotection and refractory status epilepticus. It causes dose-dependent cardiovascular and respiratory depression, histamine release, and tissue necrosis if extravasated or injected into an artery. It is contraindicated in acute porphyrias.

Class. Intravenous general anaesthetic (thiobarbiturate).

Mechanism. Positive modulation of GABA-A receptor chloride channels, prolonging channel opening.

Pharmacokinetics. Onset 20 to 30 seconds. Duration 5 to 10 minutes after a single bolus, ended by redistribution from brain to muscle and fat. Protein binding about 80%. Elimination half-life 5 to 12 hours, with saturable hepatic metabolism, so repeated doses accumulate and delay recovery. Hepatic oxidation to inactive metabolites, renal excretion.

Indications are induction of anaesthesia, rapid sequence induction, short procedures, reduction of raised intracranial pressure and cerebral metabolism, and refractory seizures (specialist).

Adults

• Induction: 3 to 5 mg/kg intravenously of a 2.5% (25 mg/mL) solution, given over 15 to 30 seconds (50 to 100 mg increments every 20 seconds if titrating).
• Rapid sequence induction: 4 to 5 mg/kg (reduce in shock).
• Older adults, shock, hypovolaemia: 1 to 3 mg/kg, titrated.
• Intracranial hypertension (specialist): 1.5 to 3.5 mg/kg bolus.
• Refractory status epilepticus or barbiturate coma (specialist, intensive care): loading 3 to 5 mg/kg bolus, then infusion 3 to 5 mg/kg/hour, titrated to burst suppression on electroencephalogram.
• No intramuscular or subcutaneous use. Do not give by infusion for routine maintenance.

Children

• Induction: 4 to 6 mg/kg intravenously.
• Infants under 1 year: 5 to 8 mg/kg.
• Neonates: 3 to 4 mg/kg, with extreme caution.

Contraindications. Acute intermittent porphyria and other acute porphyrias; hypersensitivity to barbiturates; status asthmaticus; airway obstruction without secured airway; severe hypovolaemia or shock (relative); fixed cardiac output states; myotonic dystrophy; absence of equipment for resuscitation.

Boxed-warning-level risks. Tissue necrosis and gangrene with extravasation or intra-arterial injection; profound hypotension and apnoea; precipitating acute porphyria attacks.

Adverse effects. Common: hypotension, respiratory depression, cough, hiccups, laryngospasm, bronchospasm in asthma. Serious: anaphylaxis, intra-arterial injection (severe pain, ischaemia), extravasation necrosis, acute porphyric attack, myocardial depression, prolonged recovery with repeated dosing.

Interactions. Opioids, benzodiazepines and other sedatives add respiratory depression. Sulphonamides and aspirin displace thiopental from protein and increase free fraction. Acidic solutions (for example neuromuscular blockers, atracurium) precipitate in lines, so flush between agents.

Common prescribing errors. Using in a patient with a history of porphyria; mixing in the same syringe as muscle relaxants; using the 5% solution; giving through a small vein or a line that may be intra-arterial; assuming recovery is quick after repeated doses.

Special groups

• Pregnancy: used for induction at caesarean section with neonatal depression at high doses.
• Breastfeeding: compatible after single doses.
• Older adults: reduce dose by 30 to 50%.
• Kidney impairment: reduce dose in uraemia (higher free fraction).
• Liver impairment: reduce dose and prolong intervals.
• Regional: supply is unreliable in many regions; check expiry and storage of powder vials and reconstitute fresh solution for each patient.

Formulations. Powder for reconstitution 500 mg and 1 g.

Administration. Reconstitute 500 mg in 20 mL of sterile water to give 25 mg/mL (2.5%). Inject slowly into a large vein with a free-flowing infusion; test with 1 to 2 mL for pain and reaction. Use freshly prepared solution; discard after 24 hours at 2 to 8 degrees Celsius. Do not mix with acidic agents.

Baseline. Porphyria and allergy history, airway assessment, blood pressure, volume status, asthma, current medicines.

Monitoring. Continuous electrocardiogram, oxygen saturation, capnography and blood pressure. For burst suppression, continuous electroencephalogram and drug level if available.

Therapeutic drug monitoring. Plasma thiopental may be measured in barbiturate coma.

Dose reduction and stopping thresholds. Stop injection on severe pain in the limb, change in colour, or any sign of intra-arterial injection. Reduce the dose in older adults, shock and low albumin.

Referral and escalation. Intra-arterial injection: leave the cannula in place, dilute with 0.9% sodium chloride, give heparin and papaverine or lidocaine as local practice directs, and consider sympathetic blockade and vascular surgery review. Extravasation: stop, aspirate, infiltrate with hyaluronidase or lidocaine. Anaphylaxis needs intramuscular adrenaline.