Methohexital

Methohexital is a short-acting oxybarbiturate intravenous hypnotic with faster clearance than thiopental and more excitatory activity. It is used mainly for electroconvulsive therapy and for brief procedures, because it lowers the seizure threshold less than other agents. It causes dose-dependent respiratory depression and hypotension and can precipitate seizures in susceptible patients.

Class. Intravenous general anaesthetic (oxybarbiturate).

Mechanism. Positive modulation of GABA-A receptor chloride channels.

Pharmacokinetics. Onset 30 to 60 seconds, duration 5 to 7 minutes. Protein binding about 73%. Elimination half-life about 4 hours, with faster hepatic clearance than thiopental and less accumulation. Hepatic oxidation and demethylation; renal excretion.

Indications are induction of anaesthesia, short procedures, and anaesthesia for electroconvulsive therapy.

Adults

• Induction: 1 to 1.5 mg/kg intravenously of a 1% solution at about 1 mL every 5 seconds.
• Electroconvulsive therapy: 0.75 to 1 mg/kg intravenously.
• Maintenance for short procedures: 20 to 40 mg (2 to 4 mL of 1%) every 4 to 7 minutes as needed.
• Older adults, shock, hypovolaemia: reduce by 30 to 50%.

Children

• Intramuscular: 6.6 to 10 mg/kg of a 5% solution for sedation before procedures (specialist).
• Rectal: 25 mg/kg of a 1% solution in sedation for imaging (specialist, where available).
• Intravenous induction: 1 to 2 mg/kg.
• Not suitable for neonates.

Contraindications. Acute intermittent porphyria and other porphyrias; hypersensitivity to barbiturates; status asthmaticus; severe hypovolaemia or shock (relative); epilepsy where seizure threshold lowering is undesirable (relative); absence of resuscitation equipment.

Boxed-warning-level risks. Tissue necrosis from extravasation or intra-arterial injection; apnoea and hypotension; precipitation of acute porphyria; excitatory movements and seizures.

Adverse effects. Common: pain on injection, hiccups, coughing, involuntary movements, tremor, hypotension. Serious: laryngospasm, seizures, respiratory depression, tachycardia, thrombophlebitis, anaphylaxis, acute porphyria attack.

Interactions. Opioids, benzodiazepines and other sedatives add respiratory depression. Phenothiazines can lower seizure threshold. Antiepileptics interact variably. Acidic drugs precipitate when mixed.

Common prescribing errors. Using in a patient with porphyria; exceeding the dose in older adults; using the 10% concentration for intravenous injection; mixing with acidic solutions or muscle relaxants in the same line.

Special groups

• Pregnancy: avoid unless needed (electroconvulsive therapy in pregnancy needs specialist input).
• Breastfeeding: compatible after single doses.
• Older adults: reduce dose by 30 to 50%.
• Kidney impairment: no adjustment of dose for single doses.
• Liver impairment: reduce dose and prolong intervals.
• Regional: availability is limited outside a few markets; check supply and storage.

Formulations. Powder for reconstitution (500 mg, 2.5 g).

Administration. Reconstitute with sterile water to 1% (10 mg/mL) for intravenous use, 5% (50 mg/mL) for intramuscular use. Give slowly into a large vein with free-flowing fluid. Do not use solutions that are cloudy or older than 24 hours.

Baseline. Porphyria and allergy history, seizure history, airway assessment, cardiovascular status and volume status.

Monitoring. Continuous electrocardiogram, oxygen saturation, capnography and blood pressure. Electroencephalogram or seizure duration monitoring during electroconvulsive therapy.

Therapeutic drug monitoring. Not used.

Dose reduction and stopping thresholds. Stop injection on pain in the limb, change in colour, or signs of intra-arterial injection. Reduce the dose in older adults, shock and liver disease.

Referral and escalation. Intra-arterial injection: stop, leave the cannula in place, dilute with 0.9% sodium chloride, and give heparin and papaverine or lidocaine as local practice directs. Extravasation: stop, aspirate, and infiltrate with hyaluronidase or lidocaine. Seizures: benzodiazepine and airway support. Anaphylaxis needs intramuscular adrenaline.