Methohexital: A Comprehensive Review

Methohexital is an ultra-short-acting barbiturate anaesthetic primarily used to induce general anaesthesia and procedural sedation, particularly for brief diagnostic and therapeutic interventions. Marketed under the brand name Brevital, Methohexital works by swiftly depressing central nervous system (CNS) activity, leading to unconsciousness within approximately 30 seconds when administered intravenously. Owing to its rapid onset and short duration of action, Methohexital is especially valuable in outpatient surgical settings, minor interventions, and emergency procedures. As a Schedule IV controlled substance, strict adherence to handling and administration protocols is mandatory.

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Clinical Applications

Methohexital is widely used in both adult and paediatric patients for the induction of anaesthesia in short-duration procedures. It is especially effective in ambulatory surgeries, electroconvulsive therapy (ECT), and endoscopic examinations. Additionally, Methohexital serves as a sedative in procedural settings, either alone or in combination with other agents. Its rapid pharmacokinetics allow for precise titration, which is essential in environments requiring rapid patient turnover and recovery.

Dosage and Routes of Administration

Methohexital is available as a lyophilised powder requiring reconstitution with sterile water or saline. The intravenous (IV) route is most common. Adult induction doses typically range from 1.0 to 1.5 mg/kg, administered slowly over 10–15 seconds. In paediatric sedation, particularly for imaging studies, the rectal route is employed with doses of 20–30 mg/kg. Redosing may be required during longer procedures. Intra-arterial administration must be avoided due to the risk of vasospasm and tissue necrosis.

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Dose Adjustments in Specific Conditions

Renal Impairment: Although Methohexital is primarily metabolised hepatically, renal impairment may affect the excretion of metabolites, potentially prolonging sedation. Dose reduction and close monitoring are recommended.
Hepatic Impairment: Impaired hepatic metabolism may delay Methohexital clearance, necessitating lower initial doses and cautious titration.
Pregnancy: Methohexital crosses the placenta and may cause neonatal CNS depression. Its use should be restricted to situations where maternal benefit outweighs fetal risk. Postnatal monitoring of the neonate is essential.

Therapeutic Effects and Adverse Reactions

Methohexital's key therapeutic benefit is its rapid induction of anaesthesia with a brief duration of action. Common adverse effects include myoclonus, sneezing, hiccups, and coughing during induction. More serious risks involve hypotension, respiratory depression, and in rare cases, bronchospasm or allergic reactions. Continuous monitoring of airway and cardiovascular status is mandatory during use.

Concomitant Drug Use and Infusion Considerations

Methohexital is often administered with adjunct anaesthetic agents such as opioids, benzodiazepines, and neuromuscular blockers. It should not be mixed in the same IV line with other drugs. During administration, vital signs including oxygen saturation, heart rate, and blood pressure must be continuously monitored. Emergency resuscitation equipment should always be available due to the risk of synergistic CNS depression.

Pharmaceutical Forms

Form	Strength	Route
Powder for reconstitution	50 mg/vial	Intravenous
Powder for reconstitution	500 mg/vial	Rectal/Intravenous

Reconstituted solutions should be used immediately to minimise the risk of microbial contamination and chemical degradation.

Pharmacokinetics and Pharmacodynamics

Methohexital's high lipophilicity enables it to rapidly cross the blood-brain barrier, inducing anaesthesia within 30 seconds. The effect lasts 5–10 minutes before redistribution into muscle and adipose tissues. It undergoes hepatic metabolism through oxidation, producing inactive metabolites excreted renally. Mechanistically, Methohexital enhances GABA-A receptor activity, increasing neuronal inhibition. Methohexital has no antibacterial properties.

Drug Interactions

Methohexital’s sedative effects are enhanced by concurrent use of other CNS depressants such as opioids, alcohol, and benzodiazepines. Enzyme inducers (e.g., carbamazepine, phenytoin) can reduce its efficacy, while enzyme inhibitors (e.g., erythromycin, cimetidine) may increase its potency. Thorough review of patient medication history is essential before administration.

Comparison with Other Intravenous Anaesthetics

Drug	Onset	Duration	Route	Notable Features
Methohexital	~30 sec	5–10 min	IV, Rectal	Ideal for ECT and short procedures
Thiopental	30–60 sec	5–30 min	IV	Longer residual sedation
Propofol	~40 sec	10–20 min	IV	Anti-emetic, smooth emergence
Etomidate	30–60 sec	3–5 min	IV	Preserves cardiovascular stability

Precautions and Clinical Considerations

Only trained anaesthesia professionals should administer Methohexital. It is contraindicated in patients with hypersensitivity to barbiturates and in those with acute intermittent porphyria. Special caution is required in elderly patients, those with compromised respiratory function, and hypotensive individuals. Aseptic technique is mandatory during reconstitution, and prepared solutions should not be stored.

Toxicity and Overdose Management

Overdose may result in profound CNS depression, hypotension, respiratory failure, and coma. There is no specific antidote; management is supportive, including airway protection, mechanical ventilation, fluid resuscitation, and vasopressors. Activated charcoal may be administered in alert patients following oral overdose.

2025 Updates and Guidelines

NICE guidelines (2025) continue to endorse Methohexital for ECT and ambulatory procedures due to its rapid onset and brief recovery period. Research is underway into its use in paediatric sedation. Newer formulations have improved solubility and longer shelf life, making it more practical in emergency care.