What is the recommended dose of phenobarbitone (phenobarbital) for seizure control in children?

Phenobarbitone Dosing for Seizure Control in Children

For seizure control in children, phenobarbitone (phenobarbital) should be administered at a dose of 15-20 mg/kg as a loading dose, followed by 5-8 mg/kg/day divided into 1-2 doses for maintenance therapy.

Loading Dose Recommendations

The loading dose is crucial for achieving therapeutic levels quickly in acute seizure management:

• Status epilepticus: 20 mg/kg IV, infused over 10 minutes. May repeat once after 15 minutes if necessary (maximum total dose: 40 mg/kg) 1
• Neonatal seizures: 10 mg/kg IV 1
• Children with seizures: 15-20 mg/kg IV/IO 1

Administration Considerations

• IV loading dose should be administered slowly over 10-20 minutes
• Infusion rate should not exceed 1 mg/kg per minute to minimize risk of hypotension and respiratory depression
• For IV administration, phenobarbital should be diluted in normal saline to avoid precipitation 1

Maintenance Dosing

After the loading dose, maintenance therapy should be initiated:

• Children: 5-8 mg/kg/day divided into 1-2 doses 2
• Neonates: Due to decreased protein binding and slower metabolism, lower doses of 3.5-4.5 mg/kg/day for preterm infants (≤35 weeks gestation) and 4.0-5.0 mg/kg/day for term infants (>35 weeks gestation) are recommended 3

Therapeutic Monitoring

• Target therapeutic serum concentration: 15-40 mcg/mL 3
• Monitoring should begin 4 hours after loading dose and continue at 24,48, and 72 hours 4
• More frequent monitoring is recommended during the first month of life as clearance can change substantially 3

Special Considerations

Neonates

• Phenobarbital has a long half-life in neonates (59-182 hours) 5
• Peak concentration (in mcg/mL) after IM injection approximately equals 1.3 × the dose (in mg/kg) 5
• Neonates with hypoxic-ischemic encephalopathy (HIE) may have impaired drug metabolism, requiring lower maintenance doses 4
• Therapeutic hypothermia can further affect drug levels, with higher serum concentrations observed in babies undergoing cooling 4

Efficacy Considerations

• Phenobarbital controls seizures in approximately 43-45% of neonates when used as monotherapy 6
• Response rates are better in patients with mild seizures or seizures that were already decreasing in severity before treatment 6
• Efficacy is often poor in neonates with significantly abnormal background EEG 7

Adverse Effects to Monitor

• Respiratory depression (especially when combined with other sedative agents)
• Hypotension with rapid IV administration
• Sedation and behavioral disturbances
• Paradoxical hyperactivity (especially in young children)

Important Cautions

• Have resuscitation equipment readily available when administering IV phenobarbital
• Monitor vital signs closely, particularly respiratory rate and blood pressure
• Loading doses beyond 20 mg/kg should be used with close monitoring of serum drug levels 4
• In neonates with HIE undergoing therapeutic hypothermia, even standard loading doses can result in supratherapeutic levels 4

Phenobarbital remains a first-line agent for seizure control in children despite its incomplete efficacy, with approximately half of patients requiring additional anticonvulsant therapy for complete seizure control.