Phenobarbital

• Primary Uses: Status epilepticus, refractory seizures, severe alcohol withdrawal when benzodiazepines are inadequate
• Typical Loading: 15–20 mg/kg IV (slowly, monitor BP/respiratory status); additional 5–10 mg/kg may be given in refractory cases with close monitoring
• Chronic Maintenance: 1–3 mg/kg/day PO divided; very long half‑life (~80–120 hours) — drug accumulates
• Major Risks: Respiratory depression, hypotension, oversedation/coma; strong hepatic enzyme induction (CYP2C/CYP3A) with many drug interactions
• Monitoring: Continuous cardiorespiratory monitoring during loading; serum levels and cumulative dosing tracking in ICU/ward settings
• Note: Use with airway/resuscitation readiness — be prepared to intubate after loading doses

• Generic Name: Phenobarbital (phenobarbitone in some regions)
• Brand Names: Luminal; phenobarbital sodium injection; various generics

Long‑acting barbiturate that enhances and mimics GABA‑A mediated inhibition in the CNS. Used primarily as an anticonvulsant and sedative‑hypnotic with established roles in refractory status epilepticus and severe alcohol withdrawal.

Mechanism of Action:

• Binds to the barbiturate site on the GABA‑A receptor–chloride channel complex, increasing duration of chloride channel opening in the presence of GABA
• At higher concentrations, can directly activate GABA‑A receptors, producing profound CNS depression
• Reduces neuronal excitability and seizure propagation; suppresses some excitatory neurotransmission (e.g., AMPA-mediated glutamate)

Pharmacokinetics:

• Absorption: Complete oral absorption; IV/IM formulations allow rapid loading in emergencies
• Distribution: Moderate lipid solubility; Vd ≈0.5–0.9 L/kg; crosses BBB
• Metabolism: Primarily hepatic via CYP2C9/19; strong inducer of CYP2C and CYP3A enzymes
• Elimination: Renal excretion of metabolites and some unchanged drug; half‑life ~80–120 hours (long), longer in hepatic impairment
• Clinical note: Steady state takes many days; use loading doses for acute control, then maintenance dosing

• Status epilepticus (second‑ or third‑line after benzodiazepines and a non‑barbiturate antiseizure med)
• Refractory or super‑refractory status epilepticus — continuous infusion or repeated dosing in ICU (often after midazolam/propofol)
• Severe alcohol withdrawal or delirium tremens when benzodiazepines are inadequate
• Selected chronic seizure prophylaxis in certain populations (less common in many modern settings)
• High‑dose barbiturate coma for refractory intracranial hypertension (specialist use)

Available Forms:

• Injection: phenobarbital sodium (65 mg/mL, 130 mg/mL vials common)
• Tablets: e.g., 15 mg, 30 mg, 60 mg, 100 mg (varies by region)
• Oral elixirs/solutions for pediatric and chronic use

Adult Dosing (Common ED/ICU Regimens — follow local protocols):

Absolute Contraindications:

• Barbiturate hypersensitivity
• Porphyria (e.g., acute intermittent porphyria)
• Severe respiratory depression or obstructive pulmonary disease without airway support

Precautions:

• Elderly, frail, hemodynamically unstable patients: lower loading doses and consider early airway protection
• Hepatic impairment: decreased clearance and accumulation — use caution
• Renal impairment: monitor for accumulation and prolonged effects
• Concomitant CNS depressants (benzodiazepines, opioids, alcohol): additive sedation and respiratory depression
• CYP enzyme induction: many drug–drug interactions (warfarin, ASMs, calcineurin inhibitors, steroids)
• Long-term use: dependence, withdrawal seizures, cognitive effects — avoid abrupt discontinuation

Common:

• Sedation, drowsiness, ataxia
• Hypotension, dizziness
• Cognitive slowing and impaired concentration
• Nausea, vomiting

Serious (ED/ICU‑relevant):

• Respiratory depression, apnea, and need for intubation
• Profound hypotension, coma, and need for vasopressors
• Stevens–Johnson syndrome / toxic epidermal necrolysis (rare)
• Osteoporosis and fractures with chronic use
• Barbiturate withdrawal seizures and delirium if abruptly stopped after long-term use

Elderly & Frail:

• Increased sensitivity to CNS/respiratory depression and hypotension; reduce dose and monitor closely

Hepatic/Renal Impairment:

• Prolonged half‑life and accumulation; start low and monitor levels

Pregnancy & Lactation:

• Potential neonatal respiratory depression and withdrawal with chronic maternal use; weigh risks/benefits

• Continuous ECG, blood pressure, respiratory rate, and pulse oximetry during IV loading and high‑dose therapy
• Serum phenobarbital levels in ICU and chronic therapy after distribution phase; correlate with clinical effect and toxicity
• Neurologic status: seizure control, level of consciousness, brainstem reflexes in high‑dose therapy
• Electrolytes, renal and hepatic function during prolonged ICU use
• Watch for signs of drug–drug interactions (e.g., loss of seizure control or subtherapeutic warfarin)

• Support airway and breathing — provide assisted ventilation and intubate if necessary
• Support circulation with fluids and vasopressors for refractory hypotension
• No routine antidote — management is supportive; consider enhanced elimination approaches (e.g., hemodialysis) only in specific scenarios and specialist advice
• Consider ICU admission for monitoring and prolonged supportive care

• Warfarin: Phenobarbital induces warfarin metabolism — may reduce INR; monitor and adjust anticoagulation
• Other antiseizure medications: Induces metabolism of many ASMs (e.g., carbamazepine), altering levels
• Calcineurin inhibitors / steroids: Enzyme induction may reduce levels; monitor drug levels closely
• CNS depressants: Additive depressant effects with benzodiazepines, opioids, alcohol, propofol — use caution

• 1. Glauser, T., Shinnar, S., Gloss, D., et al. (2016). Evidence‑based guideline: Treatment of convulsive status epilepticus in children and adults. Epilepsy Currents, 16(1), 48–61.
• 2. Brodie, M. J., & Kwan, P. (2012). Phenobarbital: A long‑standing antiepileptic drug still often used today. Epilepsia, 53(S8), 12–16.
• 3. Rosenson, J., Clements, C., Simon, B., et al. (2013). Phenobarbital for acute alcohol withdrawal: A randomized controlled trial. Journal of Emergency Medicine, 44(3), 592–598.