What is the treatment protocol for managing convulsions in newborns, including drug doses and method of administration?

Management of Neonatal Convulsions: Treatment Protocol

Phenobarbital is the first-line anticonvulsant for neonatal seizures, administered as an IV loading dose of 15-20 mg/kg over 10-15 minutes, followed by sequential boluses if needed. 1, 2, 3

Initial Assessment and Stabilization

Before administering anticonvulsants, immediately:

• Ensure patent airway and adequate oxygenation 1
• Check blood glucose immediately and correct hypoglycemia if present 1
• Establish IV or intraosseous access for medication administration 1
• Monitor vital signs continuously, including heart rate, blood pressure, and oxygen saturation 1, 2
• Have resuscitation equipment and respiratory support immediately available 1, 2

First-Line Treatment: Phenobarbital

Dosing Protocol

• Loading dose: 15-20 mg/kg IV over 10-15 minutes 1, 2, 3
• Maximum infusion rate: 60 mg/min (though slower rates are appropriate for neonatal weight-based dosing) 2
• Target serum level: 10-15 mcg/mL initially, up to 40 mcg/mL if needed 2, 4

Sequential Dosing for Persistent Seizures

• If seizures persist after initial loading, administer additional boluses of 5-10 mg/kg until seizures cease or serum concentration reaches 40 mcg/mL 4
• 77% of neonates respond to phenobarbital at serum levels ≤40 mcg/mL 4
• Therapeutic effect plateaus at 40 mcg/mL; beyond this level, adding a second agent is more effective than further phenobarbital 4

Administration Considerations

• Use deep intramuscular injection only if IV access is impossible, injecting into large muscle with maximum 5 mL per site 2
• Never administer subcutaneously due to tissue irritation risk 2
• Avoid small veins (dorsum of hand/wrist); use larger veins to minimize thrombosis risk 2
• Aspirate before injection to avoid inadvertent intraarterial administration, which can cause gangrene 2

Monitoring and Adverse Effects

• Monitor for respiratory depression and hypotension, particularly due to vasodilatory and cardiodepressive effects 1
• Serum concentrations >50 mcg/mL may cause feeding difficulty and sedation, but are generally well-tolerated 4
• Preterm infants (<32 weeks gestation) respond better to phenobarbital than term infants 4
• Neonates with severe asphyxia should receive doses at the lower end of the range 5

Second-Line Treatment Options

When to Escalate

If seizures persist after phenobarbital loading to 40 mcg/mL serum level, immediately initiate second-line therapy 1, 3, 4

Phenytoin/Fosphenytoin

• Dose: 18-20 mg/kg IV over 10-20 minutes 1
• Maximum infusion rate: 1 mg/kg per minute 1
• Must be diluted in normal saline only; incompatible with glucose-containing solutions 1
• Monitor heart rate continuously; reduce infusion rate if heart rate decreases by 10 beats per minute 1
• Risk of hypotension and arrhythmias, especially with rapid infusion 1
• Preferred first-line agent if channelopathy is suspected (e.g., family history of genetic epilepsy) 3

Levetiracetam

• Dose: 20-30 mg/kg IV 1
• Efficacy rate: 68-73% 1
• Preferred second-line agent in neonates with cardiac disorders 3
• Better safety profile with less respiratory depression and hypotension compared to phenobarbital 1, 3

Midazolam

• Loading dose: 0.15-0.20 mg/kg IV 1
• Continuous infusion: Start at 1 mcg/kg per minute, increase by 1 mcg/kg per minute every 15 minutes (maximum: 5 mcg/kg per minute) until seizures stop 1
• High risk of respiratory depression; intubation support often required 1

Lidocaine

• May be used as second-line agent in neonates with seizures refractory to phenobarbital 3
• Particularly useful in neonates where cardiac effects of phenytoin are concerning 3

Refractory Status Epilepticus (>40 minutes)

Management Protocol

• Call anesthesiology for rapid sequence intubation 1
• Initiate continuous midazolam infusion as described above 1
• Consider pentobarbital infusion (92% success rate, but 77% require vasopressor support for hypotension) 1
• Transfer to neonatal intensive care unit with continuous EEG monitoring 1, 3

Special Considerations

Pyridoxine-Dependent Seizures

If seizures are unresponsive to second-line agents and clinical features suggest vitamin B6-dependent epilepsy, administer a trial of pyridoxine 3

Therapeutic Hypothermia

In neonates with hypoxic-ischemic encephalopathy, therapeutic hypothermia may reduce seizure burden 3

Duration of Treatment

Once acute provoked seizures cease without evidence of neonatal-onset epilepsy, discontinue anticonvulsants before hospital discharge, regardless of MRI or EEG findings 3

Critical Pitfalls to Avoid

• Never use flumazenil to reverse benzodiazepine effects in seizure patients, as it counteracts anticonvulsant effects and may precipitate seizures 6, 1
• Never mix phenytoin with glucose-containing solutions, which causes precipitation 1
• Never infuse phenytoin/fosphenytoin too rapidly, as this significantly increases risk of hypotension and cardiac arrhythmias 1
• Never continue escalating phenobarbital beyond 40 mcg/mL serum level without adding a second agent, as efficacy plateaus 4
• Never delay respiratory support preparation when administering any anticonvulsant, particularly benzodiazepines or phenobarbital 1, 2