What is the treatment for a newborn with Hypoxic-Ischemic Encephalopathy (HIE) Stage 3?

Treatment for HIE Stage 3

Newborns with Stage 3 (severe) HIE should receive therapeutic hypothermia initiated within 6 hours of birth, though the benefit is substantially reduced compared to moderate HIE, with only a 17% reduction in death or major neurodevelopmental disability versus 33% for moderate HIE. 1, 2

Therapeutic Hypothermia Protocol

Initiate cooling immediately if the infant meets criteria and is within 6 hours of birth, as efficacy decreases significantly after this window and is lost entirely after 6 hours in severe HIE. 3, 4

Core Temperature Management

• Target core temperature: 33.5-34°C maintained for exactly 72 hours 3, 1
• Both whole body cooling and selective head cooling are appropriate strategies 3
• Rewarm over at least 4 hours at approximately 0.5°C per hour to prevent complications 1, 2
• Avoid iatrogenic hyperthermia during and after rewarming 3

Critical Timing Considerations

Stage 3 HIE has significantly worse outcomes with hypothermia than moderate HIE - the number needed to treat is approximately 7 for moderate HIE but much higher for severe HIE, with only 17% risk reduction versus 33% for moderate disease. 1, 2 Research demonstrates that in severe HIE, hypothermia therapy shows curative effects only when started within 6 hours, not in the 6-12 hour window. 4

Facility Requirements

Transfer immediately to a NICU with full multidisciplinary capabilities, as cooling should ONLY be conducted in facilities equipped with: 1, 5

• Intravenous therapy and continuous infusion capabilities
• Mechanical ventilation readily available
• Continuous pulse oximetry monitoring
• Anticonvulsant medications (phenobarbital, levetiracetam, fosphenytoin)
• Transfusion services
• Radiology including ultrasound and MRI with diffusion-weighted imaging
• Pathology testing capabilities

Supportive Care During Cooling

Metabolic Management

• Start intravenous glucose infusion immediately to avoid hypoglycemia, as lower glucose levels increase brain injury risk after hypoxic-ischemic insult 3
• Check point-of-care glucose before or concurrent with any antiseizure medication 5
• No specific target glucose range is established, but avoid hypoglycemia 3

Respiratory Support

• Ensure patent airway and provide high-flow oxygen to maintain adequate oxygenation 5
• Consider elective intubation if the infant remains unconscious (Glasgow Coma Score ≤8) 5
• Target PaCO₂ of 4.5-5.0 kPa 1

Cardiovascular Support

• Maintain systolic blood pressure >110 mmHg 1
• Monitor closely for thrombocytopenia and hypotension, which are known adverse effects of cooling 3, 1

Seizure Management

90% of HIE-related seizures occur within the first 2 days of life, but electrographic seizures are rare in the first few hours if the insult occurred during labor and delivery. 5, 6

Antiseizure Protocol

• Do NOT give prophylactic antiepileptic drugs 6
• If seizures occur, administer phenobarbital 20 mg/kg IV loading dose (maximum 1,000 mg) as first-line treatment, which controls 77% of neonatal seizures 5
• If seizures persist: levetiracetam 40 mg/kg IV bolus (maximum 2,500 mg) over 5-10 minutes, or fosphenytoin 5
• Implement EEG and/or amplitude-integrated EEG monitoring as soon as possible 6, 7

Diagnostic Workup

• Perform MRI with diffusion-weighted imaging when the infant is stable, as this identifies etiology in 39.8% more cases than ultrasound 5
• Perform lumbar puncture to exclude meningitis, but do NOT perform in comatose infants due to herniation risk 5
• Measure neuron-specific enolase (NSE) before and after 3 days of therapy for prognostic information 4

Critical Pitfalls to Avoid

• Never initiate cooling beyond 6 hours of life in severe HIE - research shows no benefit and potential harm 1, 4
• Never rewarm rapidly - must occur over at least 4 hours to prevent metabolic complications and rebound injury 1, 2
• Never cool without proper monitoring equipment and NICU capabilities - risk of extreme hypothermia and inability to manage complications 1, 2
• Avoid hyperthermia during and after treatment, as it worsens outcomes 3

Prognosis and Follow-Up

Stage 3 HIE has substantially worse outcomes than moderate HIE, even with optimal hypothermia treatment. The absolute risk reduction is only 17% for severe HIE compared to 33% for moderate HIE. 2

All treated infants require longitudinal follow-up to screen for: 1, 5

• Cerebral palsy (48% risk reduction with treatment)
• Blindness (52% risk reduction with treatment)
• Deafness (58% risk reduction with treatment)
• Postneonatal epilepsy
• Neurodevelopmental disabilities