Methohexital (Brevital)

• Primary Uses: Procedural anesthesia, electroconvulsive therapy (ECT), brief procedural sedation when rapid on/off sedation is desired
• Typical Dosing: Induction 1–1.5 mg/kg IV for anesthesia; procedural sedation 0.5–1 mg/kg IV; ECT dose ~0.75–1 mg/kg
• Onset & Duration: Onset within seconds; hypnotic duration ~5–10 minutes after bolus; prolonged infusions accumulate
• Key Risks: Profound respiratory depression/apnea, hypotension and myocardial depression; pro-convulsant activity (used intentionally in ECT)
• Environment: Requires full airway/resuscitation capability, continuous monitoring, and experienced anesthesia-level personnel
• Comparison: Faster onset but shorter duration than propofol; more hemodynamic instability and higher risk of myoclonus

• Generic Name: Methohexital sodium
• Brand Names: Brevital (Brevital Sodium); availability varies by region

Ultra–short-acting barbiturate sedative–hypnotic. Enhances GABAergic inhibition at the GABA-A receptor; at higher doses can directly activate GABA-A receptors causing rapid loss of consciousness. Rapid redistribution leads to short duration after bolus, but accumulation with repeated dosing extends recovery time.

Mechanism of Action:

• Binds to barbiturate site on the GABA‑A receptor complex, increasing duration of chloride channel opening and enhancing inhibitory GABAergic transmission
• At higher doses, may directly activate GABA‑A receptors even without GABA, producing profound CNS depression
• Decreases cerebral metabolic rate and cerebral blood flow; can lower intracranial pressure (specialist use)
• Pro‑convulsant in some settings—facilitates seizure induction (useful for ECT) and can produce myoclonic or tonic–clonic movements

Pharmacokinetics:

• Route: IV (primary); occasionally rectal in pediatrics
• Onset: Within 10–30 seconds after IV bolus
• Duration: Hypnosis ~5–10 minutes after a single bolus due to rapid redistribution
• Distribution: Highly lipophilic with rapid brain penetration and large volume of distribution
• Metabolism: Hepatic oxidative metabolism to inactive metabolites
• Elimination: Renal excretion of metabolites; context‑sensitive half‑time increases with repeated doses/infusions

• Induction of anesthesia for short procedures (preferably in OR/monitored environments)
• Anesthetic agent for electroconvulsive therapy (ECT) due to rapid onset and short duration
• Brief procedural sedation when rapid on/off sedation is required and full airway support is available
• Neuroanesthesia situations requiring rapid control of ICP and cerebral metabolic rate (specialist use)

Available Forms:

• Lyophilized powder for reconstitution; commonly provided as 0.5 g or 2.5 g vials; reconstitute to concentrations such as 10 mg/mL
• IV use only in most acute care settings (rectal forms have historical pediatric use in some protocols)

Adult Dosing (General – Follow anesthesia/clinical protocols):

Absolute Contraindications:

• Known hypersensitivity to barbiturates
• Porphyria (acute intermittent or variegate) — barbiturates can precipitate porphyric crises
• Marked hypotension or shock where further myocardial depression would be dangerous (unless full hemodynamic support available)

Precautions:

• Severe cardiovascular disease: risk of hypotension and decreased cardiac output — reduce dose and titrate slowly
• Respiratory disease: causes significant respiratory depression and apnea — airway must be secured or immediately supportable
• Hepatic or renal impairment: prolonged sedation possible — dose adjustments and monitoring required
• Elderly and frail patients: increased sensitivity — use reduced dosing and slow titration
• Concomitant CNS depressants (opioids, benzodiazepines, alcohol): synergistic respiratory and CNS depression — monitor closely

Common:

• Hypotension
• Tachycardia
• Apnea, hypoventilation, oxygen desaturation
• Injection site pain or thrombophlebitis
• Myoclonic movements or muscle twitching; tonic–clonic movements (particularly in ECT)

Serious:

• Profound cardiovascular collapse and refractory hypotension in hypovolemia or severe cardiac disease
• Prolonged apnea requiring intubation and mechanical ventilation
• Laryngospasm or bronchospasm
• Porphyric crises in susceptible individuals

Elderly / Frail:

• Markedly increased sensitivity; start at lower doses and titrate carefully
• Higher risk of hypotension and prolonged sedation

Hepatic / Renal Impairment:

• Hepatic impairment may prolong effect due to slower metabolism; use caution and consider lower doses
• Renal impairment may increase duration of metabolites — monitor recovery time

Respiratory Disease:

• Avoid or use extreme caution in patients with limited respiratory reserve; ensure airway support is immediately available

• Continuous ECG, blood pressure, and pulse oximetry during and after administration
• End‑tidal CO2 (capnography) when used for procedural sedation or anesthesia
• Monitor depth of sedation and recovery of airway reflexes and mental status
• Monitor hemodynamics closely, especially in patients with limited cardiac reserve
• For repeated doses/infusions: track cumulative dose and recovery time

• Profound CNS and respiratory depression or apnea — secure airway and provide assisted ventilation; intubate if necessary
• Support blood pressure with fluids and vasopressors if refractory hypotension occurs
• No specific antagonist for barbiturate overdose; management is supportive and may include activated charcoal if recent oral ingestion in pediatrics (not commonly relevant for IV use)
• Consider ICU admission for monitoring and prolonged supportive care after large overdose

• 1. Brevital (methohexital sodium) prescribing information.
• 2. Miller, R. D. (latest ed.). Miller’s Anesthesia. Elsevier.
• 3. American College of Emergency Physicians. Clinical Policy on Procedural Sedation in the Emergency Department.