Barbiturate · Sedative · Antiepileptic
Pentobarbital (Nembutal)
Also called Nembutal, pentobarb
Indications
- Raised ICP refractory to maximal medical and surgical treatment, as barbiturate coma (BTF 2016; off-label)
- Refractory status epilepticus by EEG-titrated infusion (NCS 2012); the label covers anticonvulsant use in anesthetic doses
- Emergency control of convulsions in tetanus, eclampsia or local anesthetic toxicity (label)
- Sedation and preanesthesia (label; now rare); sedation of children for imaging (off-label)
Dosing
Pentobarbital drip card and mL/h converterStart: Refractory ICP (Eisenberg regimen): 10 mg/kg over 30 minutes, then 5 mg/kg/h for 3 hours, then 1 mg/kg/h. Refractory status epilepticus: load 5–15 mg/kg (5–10 more if needed), then 0.5–5 mg/kg/h (NCS 2012). Load no faster than 50 mg/min
Mechanism of action
Pentobarbital is a positive allosteric modulator of the GABA-A receptor, binding transmembrane pockets between subunits that are separate from the benzodiazepine site. It lengthens each chloride channel opening and, at coma doses, opens the channel without GABA, so there is no ceiling; it also blocks AMPA and kainate glutamate receptors. Deep neuronal suppression lowers the cerebral metabolic rate for oxygen, and because flow stays coupled to metabolism, cerebral blood flow, blood volume and ICP fall with it; at EEG burst suppression further dosing adds little.
Pharmacology
- CNS: dose-related sedation, anesthesia and coma; anticonvulsant; EEG burst suppression at coma doses; no analgesia
- Cardiovascular: venodilation and myocardial depression lower BP and cardiac output; hypotension in about 1 in 4 treated for head injury (Cochrane 2012)
- Respiratory: dose-related depression and apnea, laryngospasm with fast injection (label); coma needs mechanical ventilation
- GI: ileus and feeding intolerance
- Immune and temperature: impaired leukocyte function with pneumonia and sepsis; hypothermia
- Hepatic: induces liver enzymes; can trigger attacks of porphyria (label)
Pharmacokinetics
| Onset | IV almost immediate; maximal CNS depression may take 15 min (label) |
|---|---|
| Duration | Hours after a single dose; days after coma doses as tissue stores drain |
| Half-life | 15–50 h, dose-dependent (label) |
| Distribution | Rapid to all tissues, highest in brain, liver and kidneys (label); crosses the placenta |
| Protein binding | 35–45% (HSDB) |
| Metabolism | Liver microsomal oxidation (label) |
| Elimination | Urine, as metabolites (label) |
| Rate limit | No faster than 50 mg/min IV (label) |
| Levels | Neurologic testing for brain death waits for a level under 5 mcg/mL, or uses a flow study |
Chemistry
- Sodium 5-ethyl-5-(1-methylbutyl)barbiturate: an oxybarbiturate whose branched side chain makes it more lipid-soluble and shorter-acting than phenobarbital, though less so than thiopental
- Chiral at the 1-methylbutyl carbon and sold as the racemate
- Weak acid, pKa about 8.1 (PubChem): roughly 80% un-ionized at pH 7.4, so it enters the brain quickly
- Injection 50 mg/mL in 40% propylene glycol and 10% alcohol, pH about 9.5 (label): alkaline, so it precipitates with acidic drugs and injures tissue if it leaks
Adverse effects and cautions
In the one-pagers
- Neuro: ICP and StrokeTBI and tiered ICP therapy: SIBICC avoids continuous mannitol, lumbar drainage, PaCO₂ below 30 and steroids. Pentobarbital (classic regimen 10 mg/kg over 30 min, 5 mg/kg/h for 3 h, then 1 mg/kg/h to burst suppression) causes hypotension, ileus, immunosuppression and hypothermia, and can leave pupils small and unreactive.
- End of Life, Brain Death and Organ DonationBrain death: physiology and the 2023 standard: Levels: Pentobarbital <5 mcg/mL; alcohol ≤80 mg/dL
- Pediatric Assessment and EmergenciesDKA, cerebral edema and status epilepticus: Over 40 min: Anesthetic infusion: Midazolam, pentobarbital or propofol, with EEG
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Sources
- Label: Pentobarbital Sodium Injection (Sagent, 2025)
- Eisenberg 1988 (high-dose barbiturates and ICP)
- Brophy 2012 (NCS status epilepticus guideline)
- Roberts 2012 (Cochrane: barbiturates for head injury)
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow the order, the label and your institution's protocols.