What is the immediate seizure management protocol for a newborn in the Neonatal Intensive Care Unit (NICU) presenting with seizures due to birth asphyxia?

Birth Asphyxia Seizure Protocol in NICU

For neonatal seizures due to birth asphyxia, immediately initiate therapeutic hypothermia within 6 hours of birth, confirm seizures with continuous EEG monitoring, and administer phenobarbital 20 mg/kg IV as first-line treatment, followed by fosphenytoin or levetiracetam if seizures persist. 1, 2, 3

Immediate Stabilization (First 30 Minutes)

Therapeutic Hypothermia - Critical Time Window

• Initiate therapeutic hypothermia within 6 hours of birth for term or near-term infants with evolving moderate-to-severe hypoxic-ischemic encephalopathy 1
• Target core temperature of 33.5°C to 34.5°C using either whole body cooling or selective head cooling 1
• Continue cooling for 72 hours, then rewarm over at least 4 hours 1
• This intervention reduces death or neurodevelopmental disability by 151 per 1000 infants (number needed to treat = 7) and reduces cerebral palsy by 89 per 1000 infants (number needed to treat = 12) 1

Airway and Oxygenation

• Ensure patent airway and provide high-flow oxygen to maintain adequate oxygenation and prevent hypoxia 2
• Have ventilatory support equipment immediately available, as respiratory depression is the most important risk with antiseizure medications 4
• Consider elective intubation if the infant remains unconscious (Glasgow Coma Score ≤8) 2

Metabolic Correction - Do Not Delay

• Check point-of-care blood glucose immediately and correct hypoglycemia before or concurrent with antiseizure medication administration 2, 3, 5
• Administer D10%-containing isotonic IV solution at maintenance rate if hypoglycemia is present 5
• Hypoglycemia increases brain injury risk after hypoxic-ischemic insult, though no specific threshold has been identified 1

Seizure Confirmation and Monitoring

EEG Monitoring - Essential for Diagnosis

• Initiate continuous EEG monitoring immediately, as subclinical seizures are common in hypoxic-ischemic encephalopathy 6
• All 11 major level IV NICUs surveyed have 24/7 conventional EEG initiation, monitoring, and review capability 7
• EEG confirmation should guide treatment decisions rather than clinical observation alone 7

Antiseizure Medication Protocol

First-Line: Phenobarbital

• Administer phenobarbital 20 mg/kg IV loading dose (maximum 1,000 mg) as first-line treatment 2, 3, 7
• This achieves therapeutic plasma levels within minutes and controls 77% of neonatal seizures 2
• Phenobarbital is universally recommended as first-line across all major institutional protocols 7, 6
• Important caveat: Phenobarbital may be more effective when administered before or very early after the hypoxic-ischemic insult rather than after established seizures 8

Bridging Benzodiazepine (If EEG or Loading Delayed)

• Administer IV benzodiazepine if EEG confirmation or phenobarbital loading is delayed 7
• Lorazepam 0.1 mg/kg IV/IO (maximum 4 mg) given slowly at 2 mg/min is recommended 2
• Critical warning: Lorazepam clearance is reduced by 80% and half-life is prolonged 3-fold in neonates with birth asphyxia compared to normal adults 4

Second-Line: Fosphenytoin or Levetiracetam

• If seizures persist after adequate phenobarbital levels, administer either:
  • Levetiracetam 40 mg/kg IV bolus (maximum 2,500 mg) over 5-10 minutes 2, OR
  • Fosphenytoin (dosing varies by institutional protocol) 7
• Institutional pathways show variable preference between these two agents, with no clear consensus on superiority 7

Third-Line Options

• Most commonly fosphenytoin or levetiracetam (whichever was not used second-line) 7
• Alternative third-line agents include topiramate or lacosamide 7

Refractory Seizures: Continuous Infusions

• Escalate to continuous midazolam infusion for seizures refractory to initial medication trials 7
• Midazolam (0.3 or 1 mg/kg) is effective when administered before or after asphyxia, unlike phenobarbital which may lose efficacy post-insult 8
• Lidocaine infusion is included in some institutional protocols as an alternative 7

Critical Diagnostic Workup

Neuroimaging

• Perform MRI with diffusion-weighted imaging when the infant is stable - this is the gold standard 3, 5
• MRI identifies etiology in 39.8% more cases than ultrasound and is most sensitive for hypoxic-ischemic encephalopathy 5
• Head ultrasound can serve as initial bedside imaging if the infant is unstable or MRI unavailable, identifying intraventricular hemorrhage, hydrocephalus, and white matter changes 3, 5
• Absence of major cerebral lesions on MRI is highly predictive of normal neurological outcome 5

Infection Evaluation

• Perform lumbar puncture in all infants <12 months with seizures to exclude meningitis, as meningeal signs may be absent 3, 5
• Do NOT perform lumbar puncture in comatose infants due to herniation risk 5
• Obtain blood culture and initiate empirical antibiotics immediately if infection is suspected 5
• Obtain urinalysis to exclude urinary tract infection 3

Timing and Etiology Considerations

Seizure Onset Patterns

• 90% of hypoxic-ischemic encephalopathy-related seizures occur within the first 2 days of life 3, 5
• Seizures occurring after day 7 are more likely related to infection, genetic disorders, or malformations of cortical development 3
• Hypoxic-ischemic encephalopathy accounts for 46-65% of all neonatal seizures 2, 3

Medication Discontinuation

Early Discontinuation After Acute Resolution

• Discontinue antiseizure medications early after resolution of acute provoked seizures, prior to discharge home 6
• Nine of 11 institutional pathways include guidance on discontinuation with variable timing 7
• This recommendation reflects International League Against Epilepsy guidelines 6

Common Pitfalls to Avoid

• Never delay metabolic correction (hypoglycemia, hypocalcemia, hypomagnesemia) while waiting for anticonvulsants 5
• Do not miss the 6-hour therapeutic hypothermia window - this is the most critical neuroprotective intervention 1
• Do not rely on clinical observation alone - subclinical seizures are common and require EEG confirmation 6
• Avoid lumbar puncture in comatose infants without experienced evaluation due to herniation risk 5
• Do not use bumetanide as adjunctive therapy - it has been proven ineffective in both animal models and human trials 8, 9
• Monitor closely for respiratory depression, thrombocytopenia, and hypotension during therapeutic hypothermia and antiseizure medication administration 1, 4

Supportive Care Requirements

NICU Capabilities Required

• Therapeutic hypothermia should only be conducted in facilities with capabilities for multidisciplinary care including: 1
  • Intravenous therapy
  • Respiratory support with mechanical ventilation readily available
  • Pulse oximetry
  • Antibiotics
  • Antiseizure medications
  • Transfusion services
  • Radiology including ultrasound
  • Pathology testing

Monitoring Parameters

• Continuously monitor oxygen saturation 2
• Assess neurological status using AVPU scale or pediatric Glasgow Coma Scale 2
• Check pupillary size and reaction - unilateral sluggish or absent responses are the most reliable signs of raised intracranial pressure 2
• Monitor for known adverse effects of cooling including thrombocytopenia and hypotension 1

Long-Term Follow-Up

• All treated infants should be followed longitudinally to screen for postneonatal epilepsy and support neurodevelopment 1, 6
• Reevaluate within 24 hours if managed as outpatient, though most neonatal seizures require inpatient management 3