What is the recommended management for seizures in newborns?

Management of Seizures in Newborns

Phenobarbital should be used as the first-line antiseizure medication for neonatal seizures regardless of etiology, unless a channelopathy is suspected. 1

Initial Assessment and Stabilization

• Assess circulation, airway, and breathing (CAB) and provide appropriate airway protection interventions 2
• Administer high-flow oxygen to prevent hypoxia 2
• Check blood glucose level immediately to rule out hypoglycemia as a potential cause 2

First-Line Treatment

• Administer phenobarbital as the first-line antiseizure medication for neonatal seizures 1
• Use a loading dose of 15-20 mg/kg body weight given intravenously 3
• Therapeutic plasma concentration of phenobarbital (15-30 μg/ml) is usually reached within minutes of injection and remains stable for approximately 48 hours 3

Second-Line Treatment Options

For neonates with seizures not responding to phenobarbital, the following medications may be used as second-line therapy:

• Phenytoin 1
• Levetiracetam 1
• Midazolam 1
• Lidocaine 1

In neonates with cardiac disorders, levetiracetam may be the preferred second-line antiseizure medication 1

Maintenance Therapy

• For maintenance therapy, administer phenobarbital at a dose of 3-4 mg/kg/day 3
• Due to the long plasma half-life (69-165 hours), avoid doses exceeding 5 mg/kg/day to prevent drug accumulation 3
• Duration of therapy depends on the condition of the baby, but early discontinuation after 1-2 weeks is generally possible 3

Discontinuation of Antiseizure Medications

• Following cessation of acute provoked seizures without evidence for neonatal-onset epilepsy, antiseizure medications should be discontinued before discharge home, regardless of MRI or EEG findings 1

Treatment Efficacy

• Phenobarbital and levetiracetam show similar efficacy in maintaining low seizure burden in neonates 4
• Approximately 65% of patients treated with levetiracetam and 63% of those treated with phenobarbital maintain seizure burden <10% following initial treatment 4
• Phenobarbital may show a larger absolute reduction in average seizure burden in the hour before and after treatment compared to levetiracetam (-24.3 vs -14.2 minutes/h) 4
• Initial treatment with levetiracetam may be associated with shorter average time to seizure freedom (15 vs 21 hours) 4

Special Considerations

• Therapeutic hypothermia may reduce seizure burden in neonates with hypoxic-ischemic encephalopathy 1
• Treating both clinical and electrographic-only seizures to achieve a lower seizure burden may be associated with improved outcomes 1
• A trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6-dependent epilepsy and seizures unresponsive to second-line antiseizure medications 1

Common Pitfalls and Caveats

• No other anticonvulsant drug should be used until the phenobarbital plasma level exceeds 40 μg/ml 3
• Inadequate respiratory monitoring is a common pitfall, as benzodiazepines can cause respiratory depression, especially when combined with other sedative agents 2
• Current first-generation antiepileptic drugs are relatively ineffective for neonatal seizures, highlighting the need for further research on second-generation options 5
• Establishing a standardized pathway for the management of neonatal seizures in each neonatal unit is recommended 1
• Parents/guardians should be informed about the diagnosis of seizures and initial treatment options 1