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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for METHOHEXITAL SODIUM (METHOHEXITAL SODIUM).
| Breastfeeding | Methohexital enters breast milk in low amounts; the infant dose is estimated at <1% of maternal weight-adjusted dose. M/P ratio is approximately 0.5. Due to potential for neonatal sedation and the drug's short half-life, breastfeeding should be avoided for at least 4-6 hours after maternal administration. |
| 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. |
■ 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 methohexital or other barbiturates","Acute intermittent porphyria or porphyria variegata","Uncontrolled severe hypotension or shock","Status asthmaticus","Severe respiratory insufficiency","Known or suspected massive drug overdose"]
| 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"] |
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| 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. |