What is the recommended use and dosage of Phenobarbital (phenobarbitone) for seizure disorders and sedation?

Phenobarbital for Seizure Disorders and Sedation

Phenobarbital remains an effective first-line medication for status epilepticus and seizure disorders, with recommended adult dosing of 20 mg/kg IV for acute seizures and 30-120 mg daily in 2-3 divided doses for maintenance therapy. 1

Dosage for Seizure Disorders

Status Epilepticus

• Adults: 20-320 mg IV/IM, may be repeated in 6 hours as necessary 1
• Children: 15-20 mg/kg IV over 10-15 minutes 1
• For intramuscular administration when IV access is unavailable (though IV is preferred when possible) 2
• Slow IV injection is essential, not exceeding 60 mg/min for adults, with careful monitoring of vital signs 1

Maintenance Therapy for Seizure Control

• Adults: 30-120 mg daily in 2-3 divided doses 1
• Children: 4-6 mg/kg/day for 7-10 days to achieve blood levels of 10-15 mcg/mL 1
• Once-daily low-dose phenobarbital can be effective for long-term management of certain generalized epilepsies 3

Dosage for Sedation

• Daytime Sedation (Adults): 30-120 mg daily in 2-3 divided doses 1
• Bedtime Hypnosis (Adults): 100-320 mg 1
• Preoperative Sedation (Adults): 100-200 mg IM 60-90 minutes before surgery 1
• Preoperative Sedation (Children): 1-3 mg/kg IM or IV 1

Administration Guidelines

Intravenous Administration

• IV injection should be restricted to conditions where other routes are not feasible 1
• Rate of IV injection should not exceed 60 mg/min for adults 1
• Use larger veins to minimize irritation and thrombosis risk 1
• Avoid administration into varicose veins or small veins on the dorsum of the hand 1
• Careful technique including aspiration is necessary to avoid intraarterial injection 1

Intramuscular Administration

• Should be injected deeply into a large muscle 1
• Volume should not exceed 5 mL at any one site to prevent tissue irritation 1
• Avoid injection near peripheral nerves to prevent permanent neurological deficit 1

Efficacy and Comparative Studies

• The VA Cooperative Study showed phenobarbital to be equally efficacious in managing status epilepticus compared to lorazepam, phenytoin, and phenytoin plus diazepam 2
• In a study comparing phenobarbital with diazepam and phenytoin, status epilepticus duration was shorter with phenobarbital, and 61% of phenobarbital patients did not require additional phenytoin to terminate status epilepticus 2
• Recent studies suggest phenobarbital is at least as effective as lorazepam in first-line treatment of early status epilepticus and significantly better than valproic acid in benzodiazepine-resistant status epilepticus 4

Monitoring and Safety Considerations

• Blood levels should be maintained at 10-15 mcg/mL for anticonvulsant effect 1
• Major concerns include potential for respiratory depression and hypotension, particularly when combined with other sedatives 2
• In ventilated patients in modern intensive care settings, higher doses can be used more safely than in settings without ventilatory support 2
• Equipment for resuscitation and artificial ventilation should be available during administration 1
• Phenobarbital has a long half-life (approximately 100 hours in adults), requiring careful consideration for long-term use 5

Special Considerations

• Phenobarbital may cause cognitive impairment, particularly in children, with studies showing lower IQ scores in children on long-term therapy 6
• Despite concerns about side effects, phenobarbital remains cost-effective and may be the drug of choice for certain patients with generalized epilepsy 3, 4
• Seizure prophylaxis with phenobarbital is not recommended in certain conditions like cerebral malaria due to increased mortality risk when combined with other sedatives in unventilated patients 2

Pharmacokinetics

• Phenobarbital is metabolized in the liver primarily by CYP2C9 with minor metabolism by CYP2C19 and CYP2E1 5
• Approximately 25% of the dose is excreted unchanged in urine 5
• Half-life is approximately 100 hours in adults, 103 hours in term infants, and 141 hours in preterm infants 5

By following these dosing guidelines and monitoring protocols, phenobarbital can be used effectively and safely for both seizure control and sedation in appropriate clinical scenarios.