Methohexital

IV inj or rectal: As 1% solution: Reconstitute vial labelled as 500 mg with 50 mL of sterile water for inj, dextrose 5% in water or NaCl 0.9% solution. IV infusion: As 0.2% solution: Reconstitute vial labelled as 500 mg with 15 mL of dextrose 5% in water or NaCl 0.9% solution, then further dilute with 235 mL of the original diluent to make a total volume of 250 mL. IM: As 5% solution: Dilute vial labelled as 500 mg with 10 mL of sterile water for inj or NaCl 0.9% solution.

Incompatible with lactated Ringer's inj and acidic solutions (e.g. atropine sulfate, metocurine iodide, succinylcholine chloride).

Latent or manifest porphyria.

Patient with haemodynamic instability (e.g. hypotension, shock) or severe hypertension; severe anaemia, CV disease (e.g. heart failure), pulmonary disease (e.g. asthma, COPD); history of seizure disorder. Debilitated and extremely obese patients. Renal and hepatic impairment. Children and elderly. Pregnancy and lactation.

Significant: CNS depression, temporary hypotension and tachycardia, laryngospasm; enhanced pre-existing circulatory depression, severe CV instability or a shock-like condition; cumulative effects including extended somnolence, protracted unconsciousness (prolonged use).
Gastrointestinal disorders: Abdominal pain, salivation, nausea, vomiting, hiccups.
General disorders and administration site conditions: Inj site reaction (e.g. pain).
Investigations: Abnormal LFTs.
Musculoskeletal and connective tissue disorders: Muscle twitching.
Nervous system disorders: Headache, dizziness, drowsiness, postanaesthetic shivering.
Psychiatric disorders: Emergence delirium, restlessness, anxiety.
Respiratory, thoracic and mediastinal disorders: Dyspnoea, apnoea, bronchospasm, rhinitis, cough.
Skin and subcutaneous tissue disorders: Erythema, pruritus, urticaria.
Vascular disorders: Thrombophlebitis.
Potentially Fatal: Respiratory depression (particularly in the presence of an impaired airway).

This drug may cause drowsiness, if affected, do not drive or operate machinery.

Monitor respiratory status (e.g. pulse oximetry, capnography); CV status (e.g. cardiac monitoring, blood pressure, heart rate); CNS status.

Symptoms: CNS depression, respiratory depression, hypotension, loss of peripheral vascular resistance, muscular hyperactivity (ranging from twitching to convulsive-like movements), convulsions and allergic reactions; pulmonary oedema, circulatory collapse with loss of peripheral vascular tone and cardiac arrest may occur after massive exposure. Management: Establish adequate airway, ensure oxygenation and ventilation. Resuscitative measures must be started immediately. In case of hypotension, administer IV fluids and raise the patient's legs; may administer vasopressors and/or inotropic drugs if desired increase in blood pressure is not achieved. May give IV diazepam and phenytoin for convulsions. General anaesthesia and paralysis with a neuromuscular blocking agent may be needed if seizures are refractory to diazepam and phenytoin. Monitor and maintain vital signs, blood gases and serum electrolytes. May administer repeated doses of activated charcoal.

Additive CNS depressant effect with other CNS depressants. Decreased therapeutic effect with prior chronic administration of other barbiturates or phenytoin. May affect the metabolism of other concurrently used drugs including anticoagulants, corticosteroids and halothane.

Additive CNS depressant effect with alcohol.

Description:
Mechanism of Action: Methohexital is an ultra-short-acting barbiturate anaesthetic. It enhances membrane ion conductance (mainly to chloride), decreases glutamate-induced depolarisations and potentiates gamma-aminobutyric acid (GABA) inhibitory effects. Additionally, it enhances benzodiazepine and GABA receptor binding, depresses the sensory cortex, reduces motor activity and alters cerebellar function which results in drowsiness, sedation and hypnosis.
Onset: Within 30 seconds (IV); 2-10 minutes (IM); 5-15 minutes (rectal).
Duration: 5-15 minutes (IV); 1-1.5 hours (IM); 45-60 minutes (rectal).
Pharmacokinetics:
Absorption: Bioavailability: 17% (rectal).
Distribution: Crosses the placenta and enters breast milk. Plasma protein binding: Approx 73%.
Metabolism: Rapidly metabolised in the liver via demethylation and oxidation.
Excretion: Via urine. Elimination half-life: 1.6-3.9 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 9034, Methohexital. https://pubchem.ncbi.nlm.nih.gov/compound/Methohexital. Accessed Mar. 27, 2025.

Store between 20-25°C. Reconstituted solution: Stable at room temperature for 24 hours.

Anaesthetics - Local & General

N01AF01 - methohexital ; Belongs to the class of barbiturates. Used as general anesthetics.
N05CA15 - methohexital ; Belongs to the class of barbiturates. Used as hypnotics and sedatives.

Anon. Methohexital. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 06/12/2024.

Brayfield A, Cadart C (eds). Methohexital. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/12/2024.

Brevital for Injection (Par Pharmaceutical). U.S. FDA. https://www.fda.gov. Accessed 06/12/2024.

Methohexital Sodium Injection (Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/12/2024.

Methohexital. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 06/12/2024.

Methohexital. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 06/12/2024.