What is the initial management for a term neonate (Newborn Infant) with seizures, normal body temperature, and normal Random Blood Sugar (RBS), but unavailable serum electrolyte levels in the Neonatal Intensive Care Unit (NICU)?

Initial Management of Term Neonate with Seizures in NICU

Immediately administer phenobarbital 15-20 mg/kg IV as the first-line anti-seizure medication while simultaneously securing the airway, ensuring adequate oxygenation, and empirically treating potential hypocalcemia with IV calcium even without available electrolyte results. 1, 2, 3

Immediate Stabilization (First 5 Minutes)

Airway and Breathing

• Position the infant in a "sniffing" position to open the airway and ensure adequate oxygenation. 1, 4
• Administer high-flow oxygen to prevent hypoxia, as hypoxia worsens seizures and brain injury. 1
• Monitor oxygen saturation continuously with pulse oximetry. 1
• Consider elective intubation if the infant remains unconscious or has inadequate respiratory effort. 1

Vascular Access and Monitoring

• Establish IV or intraosseous access immediately to facilitate medication administration. 1
• Begin continuous monitoring of heart rate, respiratory rate, blood pressure, and temperature. 5, 1
• Maintain normothermia (36.5-37.5°C) using radiant warmers, avoiding both hypothermia and hyperthermia. 5, 1, 4

First-Line Anti-Seizure Treatment

Phenobarbital Administration

• Administer phenobarbital 15-20 mg/kg IV as a loading dose over 5-10 minutes. 1, 2, 3
• Phenobarbital is more effective than levetiracetam in achieving seizure control after first loading dose (RR 2.32,95% CI 1.63-3.30) and remains the evidence-based first-line agent regardless of etiology. 6, 3
• Therapeutic plasma levels (15-30 mcg/mL) are reached within minutes and remain stable for 48 hours due to the long half-life (69-165 hours). 2
• Monitor for respiratory depression and hypotension during administration, particularly if the infant is hemodynamically unstable. 7

Empiric Treatment Without Electrolyte Results

Calcium Administration

• Administer 10% calcium gluconate 100-200 mg/kg (1-2 mL/kg) IV slowly over 5-10 minutes as empiric treatment for potential hypocalcemia, which is a common cause of neonatal seizures. 5
• Hypocalcemia is particularly likely in infants of diabetic mothers, preterm infants, and those with birth asphyxia. 5
• Monitor heart rate during calcium infusion and stop if bradycardia develops. 5

Glucose Monitoring

• Although random blood sugar is normal, maintain IV glucose infusion with D10% isotonic solution at maintenance rate to prevent hypoglycemia during the acute phase. 5
• Hypoglycemia increases brain injury risk after seizures even if not the primary cause. 5

Second-Line Treatment (If Seizures Persist After 5 Minutes)

Repeat Phenobarbital

• If seizures continue 5 minutes after the first phenobarbital dose, administer an additional 10 mg/kg IV (maximum total loading dose 40 mg/kg). 1, 2
• Do not use alternative ASMs until phenobarbital plasma level exceeds 40 mcg/mL. 2

Alternative Second-Line Options

• If seizures persist after maximal phenobarbital loading, consider:
  • Levetiracetam 40 mg/kg IV bolus (maximum 2,500 mg), particularly if cardiac concerns exist. 1, 3
  • Phenytoin 15-20 mg/kg IV at rate ≤1 mg/kg/min, though avoid in cardiac disorders. 3
  • Midazolam 0.1 mg/kg IV/IO over 2-3 minutes, with caution for respiratory depression. 1, 7
  • Lidocaine 2 mg/kg IV bolus followed by infusion 6 mg/kg/hr (avoid if phenytoin already given). 3, 8

Diagnostic Workup While Treating

Urgent Laboratory Tests

• Send stat serum electrolytes (calcium, magnesium, sodium, glucose) immediately even though treatment has begun empirically. 5, 1
• Obtain blood gas to assess for metabolic acidosis (base excess, pH). 5, 4
• Consider pyridoxine trial (50-100 mg IV) if seizures are refractory to second-line ASM, as vitamin B6-dependent epilepsy requires specific treatment. 3

Neuroimaging and EEG

• Arrange continuous EEG monitoring or amplitude-integrated EEG to assess seizure burden and treatment response. 1, 3
• Consider cranial ultrasound and MRI to identify structural causes (intracranial hemorrhage, stroke, malformations). 1

Maintenance Therapy After Seizure Control

Phenobarbital Maintenance

• After seizure control, administer phenobarbital 3-4 mg/kg/day IV divided every 12 hours (do not exceed 5 mg/kg/day to avoid accumulation). 1, 2
• If levetiracetam was used, continue 15 mg/kg IV every 12 hours. 1

Duration of Treatment

• For acute provoked seizures without evidence of neonatal-onset epilepsy, discontinue ASMs before hospital discharge regardless of imaging or EEG findings. 3
• Maintenance therapy beyond the acute period may have little effect on long-term outcomes (mortality RR 0.94, neurodevelopmental disability RR 0.89). 6

Critical Pitfalls to Avoid

• Do not delay phenobarbital administration while waiting for electrolyte results, as seizures themselves cause brain injury and phenobarbital takes time to reach therapeutic levels. 2, 3
• Do not use rapid IV bolus of midazolam or calcium, as this causes bradycardia and hypotension. 5, 7
• Do not combine lidocaine with phenytoin, as both are sodium channel blockers and increase cardiac toxicity risk. 3, 8
• Do not restrict treatment to only clinically apparent seizures, as electrographic-only seizures also cause brain injury and treating lower seizure burden improves outcomes. 3
• Do not administer bicarbonate for mild metabolic acidosis (base excess -5 to -12), as this does not improve outcomes and may cause complications. 4

Special Considerations for Etiology

If Hypoxic-Ischemic Encephalopathy Suspected

• Initiate therapeutic hypothermia (33.5-34.5°C) within 6 hours of birth if moderate-to-severe HIE criteria are met, as this reduces seizure burden and improves neurodevelopmental outcomes (NNT=9). 5
• Continue cooling for 72 hours with slow rewarming over at least 4 hours. 5

If Suspected Channelopathy (Family History)

• Use phenytoin 15-20 mg/kg IV or carbamazepine as first-line instead of phenobarbital if family history suggests genetic sodium or potassium channelopathy. 3