What is the management approach for a newborn or adult with hypoxic ischemic encephalopathy (HIE) following a significant hypoxic event?

Management of Hypoxic-Ischemic Encephalopathy

Therapeutic hypothermia (cooling to 33-34°C for 72 hours) is the only proven treatment for moderate-to-severe HIE in term and near-term infants (≥36 weeks gestational age), and must be initiated within 6 hours of birth to reduce death or major neurodevelopmental disability. 1, 2

Patient Selection Criteria

Therapeutic hypothermia should be offered to infants who meet ALL of the following criteria: 2

• Gestational age ≥36 weeks (some protocols specify ≥37 weeks) 1, 2
• Evidence of perinatal asphyxia (documented hypoxic event) 2
• Moderate-to-severe encephalopathy on clinical examination 1
• Age <6 hours from birth at time of treatment initiation 1, 2

Cooling Protocol Requirements

The protocol must follow strict parameters established in randomized trials: 1, 2

• Initiate within 6 hours of birth - efficacy decreases significantly after this window 1, 2
• Target core temperature: 33-34°C (33.5-34.5°C) 1
• Duration: 72 hours of continuous cooling 1, 2
• Rewarming: Over at least 4 hours at approximately 0.5°C per hour 1, 2
• Both whole-body cooling and selective head cooling are acceptable methods 1

Expected Outcomes

The magnitude of benefit is substantial and varies by severity: 2, 3

• Overall: 22-33% reduction in death or major neurodevelopmental disability 2, 3
• Number needed to treat: 5-7 infants to prevent one case of death or significant disability 2, 3
• Moderate HIE: 33% risk reduction (RR 0.67; 95% CI 0.56-0.81) 3
• Severe HIE: 17% risk reduction (RR 0.83; 95% CI 0.74-0.92) 3
• Cerebral palsy: 48% reduction (RR 0.52; 95% CI 0.37-0.72) 2, 3
• Blindness: 52% reduction (RR 0.48; 95% CI 0.22-1.03) 2, 3
• Deafness: 58% reduction (RR 0.42; 95% CI 0.21-0.82) 2, 3

Facility Requirements

Cooling should ONLY be performed in facilities with comprehensive neonatal intensive care capabilities: 1, 2, 3

• Intravenous therapy and volume expansion capability 2, 3
• Respiratory support and mechanical ventilation 2, 3
• Continuous pulse oximetry and cardiorespiratory monitoring 2, 3
• Antibiotics and anticonvulsant medications 2, 3
• Blood transfusion services 2, 3
• Radiology including ultrasound and ideally MRI 2, 3
• Pathology testing for metabolic workup 2, 3
• Multidisciplinary care team with longitudinal follow-up 1, 2

Supportive Care During Cooling

Immediate Resuscitation

If the infant requires resuscitation at birth: 1

• Establish adequate ventilation first - bradycardia in newborns is usually from inadequate lung inflation or hypoxemia 1
• Use room air initially for term infants rather than 100% oxygen 1
• Epinephrine (if heart rate <60 despite adequate ventilation and compressions): IV route preferred at 0.01-0.03 mg/kg of 1:10,000 concentration 1
• Volume expansion: 10 mL/kg isotonic crystalloid or blood if blood loss suspected 1
• Avoid rapid volume infusions in premature infants due to intraventricular hemorrhage risk 1

Metabolic Management

Glucose monitoring and correction are critical: 1

• Avoid hypoglycemia - lower glucose levels increase risk of brain injury after hypoxic-ischemic insult 1
• Start IV glucose infusion as soon as practical after resuscitation 1
• No specific target glucose range has been identified, but hypoglycemia must be prevented 1

Physiological Stability During Cooling

Maintain the following parameters: 2

• Adequate ventilation and oxygenation 2
• Target PaCO₂: 4.5-5.0 kPa 2
• Systolic blood pressure >110 mmHg 2
• Monitor for complications: thrombocytopenia and hypotension are known adverse effects of cooling 1

Seizure Management

Seizures occur in 46-65% of HIE cases, with 90% occurring within the first 2 days: 4

• Correct metabolic derangements BEFORE anticonvulsants: hypocalcemia, hypomagnesemia, and hypoglycemia 4
• Continuous video-EEG monitoring is essential - many seizures are subclinical 4
• Do not use naloxone as part of initial resuscitation for respiratory depression 1

Diagnostic Workup

Neuroimaging Algorithm

Based on clinical stability: 4

• Head ultrasound: Initial bedside imaging if infant unstable or MRI unavailable - identifies hemorrhage, hydrocephalus, white matter changes 4
• MRI with diffusion-weighted imaging: Gold standard for HIE, most sensitive for hypoxic-ischemic injury 4
• CT head: Limited role, specific for hemorrhagic lesions with birth trauma history 4

Laboratory Evaluation

Essential immediate testing: 4

• Electrolytes (sodium, calcium, magnesium) 4
• Blood gas analysis 4
• Complete blood count 4
• Blood culture if infection suspected 4
• Point-of-care glucose testing (mandatory) 4

Critical Pitfalls to Avoid

Do not initiate cooling beyond 6 hours of life - efficacy decreases significantly after this window 2

Do not rewarm rapidly - rewarming must occur over at least 4 hours to prevent complications 1, 2

Do not perform cooling without proper protocols and monitoring - risk of extreme hypothermia and other complications 3

Do not delay metabolic correction - hypoglycemia, hypocalcemia, and hypomagnesemia must be addressed immediately 4

Do not perform lumbar puncture in comatose infants - risk of herniation 4

Resource-Limited Settings

Therapeutic hypothermia is ONLY recommended when suitable supportive care is available - the World Health Organization gives this a weak recommendation with low-certainty evidence due to the absolute requirement for comprehensive monitoring and support capabilities 2