METHOHEXITAL SODIUM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for METHOHEXITAL SODIUM (METHOHEXITAL SODIUM).
Methohexital sodium is a barbiturate that acts as a GABA-A receptor agonist, enhancing chloride conductance and causing neuronal hyperpolarization. It produces rapid sedation and anesthesia by depressing the central nervous system.
| Metabolism | Primarily hepatic metabolism via CYP2B6 and other microsomal enzymes; undergoes oxidation and glucuronidation. Active metabolites are minimally important. |
| Excretion | Renal: <1% unchanged; hepatic metabolism followed by renal excretion of metabolites accounts for >95% of elimination. Fecal: negligible (<1%). |
| Half-life | Terminal elimination half-life is 1.6–4.8 hours (mean ~3.9 hours) in adults. Context: Rapid redistribution shortens clinical duration; elimination half-life is longer in elderly and hepatic impairment. |
| Protein binding | 85–90% bound to albumin. |
| Volume of Distribution | 2.0–3.0 L/kg; context: High Vd due to extensive tissue distribution, especially to adipose tissue. |
| Bioavailability | Intramuscular: ~90–100%; Rectal: ~70–80%; Oral: not available (inactive due to first-pass metabolism). |
| Onset of Action | Intravenous: 30–60 seconds. Intramuscular: 2–5 minutes. Rectal: 5–10 minutes. |
| Duration of Action | Intravenous: 5–10 minutes (single dose) due to redistribution; context: Longer with repeated dosing or infusion due to accumulation. Intramuscular: 10–20 minutes. Rectal: 20–40 minutes. |
| Molecular Weight | 284.29 |
Induction of anesthesia: 1-1.5 mg/kg IV bolus over 15-30 seconds. Maintenance: intermittent IV boluses of 20-40 mg every 4-7 minutes as needed.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment required for GFR 30-89 mL/min. For GFR <30 mL/min or dialysis: use with caution; consider reduced dose due to potential prolonged effect. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 25-50%. Child-Pugh Class C: use alternative agent or reduce dose by 50% with careful titration. |
| Pediatric use | Induction: 1-2 mg/kg IV bolus. Maintenance: 0.5-1 mg/kg IV bolus as needed. Maximum single dose: 100 mg. |
| Geriatric use | Reduce initial dose by 25-50% (0.5-1 mg/kg IV) and titrate slowly due to increased sensitivity and prolonged recovery. |
| 1st trimester | Avoid unless clearly needed; may cross placenta and cause fetal depression. |
| 2nd trimester | Use with caution; limited data suggest potential risk of maternal hypotension and fetal hypoxia. |
| 3rd trimester | Avoid in pregnancy near term due to risk of neonatal respiratory depression and lethargy. |
Clinical note
Comprehensive clinical and safety monograph for METHOHEXITAL SODIUM (METHOHEXITAL SODIUM).
| Placental transfer | Rapidly crosses the placenta; achieves fetal concentrations approximately 50% of maternal levels. |
| Breastfeeding | Excreted into breast milk in low concentrations; considered compatible with breastfeeding if single dose used. Monitor infant for sedation and respiratory depression. |
| Lactation Rating |
■ FDA Black Box Warning
Risk of respiratory depression and apnea; intravenous administration should be performed only by persons trained in the use of general anesthetics and able to maintain a patent airway and support ventilation. Continuous monitoring of respiratory function is required.
| Serious Effects |
Hypersensitivity to barbituratesAcute intermittent porphyriaStatus asthmaticusSevere hepatic impairment
| Precautions | Respiratory depression and apnea, Hypotension and bradycardia, Injection site reactions (thrombophlebitis, necrosis, extravasation), Risk of emergence delirium and postoperative confusion, Laryngospasm and bronchospasm, Accumulation with repeated doses in patients with hepatic or renal impairment |
| Food/Dietary | No specific food interactions are documented for methohexital sodium. However, it is recommended to avoid heavy meals immediately before anesthesia to reduce risk of aspiration. Grapefruit juice may theoretically increase barbiturate levels by inhibiting CYP3A4, though clinical significance is unclear. Always follow pre-operative fasting instructions. |
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| Teratogenic Risk | Methohexital sodium is a barbiturate anesthetic. Use in the first trimester may be associated with a small increased risk of major malformations based on limited human data; animal studies show developmental toxicity at high doses. In the second and third trimesters, there is a risk of fetal depression and neonatal withdrawal if used chronically near term. Avoid in first trimester if possible; use only if clearly needed. |
| Fetal Monitoring | Monitor maternal vital signs, respiratory rate, oxygen saturation, and level of consciousness. Continuous fetal heart rate monitoring is recommended during administration in pregnancy. Observe neonatal for respiratory depression and sedation if used near delivery. |
| Fertility Effects | No specific human studies on fertility effects. Barbiturates may alter reproductive hormone levels in animal studies; impact on human fertility is unknown. Use only when necessary in women attempting conception. |
| Clinical Pearls | METHOHEXITAL SODIUM is an ultra-short-acting barbiturate used for induction of general anesthesia. It has a rapid onset (less than 30 seconds) and short duration (5-10 minutes) due to redistribution. It is highly protein-bound and should be used with caution in patients with hypoalbuminemia. Contraindicated in porphyria. Avoid extravasation as it is a tissue irritant. May cause apnea, laryngospasm, and hypotension. Dose reduction needed in elderly or debilitated patients. |
| Patient Advice | This medication will cause you to lose consciousness quickly and is only given by a healthcare professional. · You will be closely monitored during and after administration. · You may experience drowsiness, dizziness, or confusion after waking up; do not drive or operate machinery for 24 hours. · Inform your doctor if you have any allergies, porphyria, or liver/kidney disease. · Avoid alcohol and other sedatives for at least 24 hours after receiving this medication. |