Hypoxic Ischaemic Encephalopathy (HIE)
Summary
Hypoxic Ischaemic Encephalopathy (HIE) is a specific type of Neonatal Encephalopathy resulting from a distinct, clinically evident event of Perinatal Asphyxia (lack of oxygen/blood flow) in the term infant (>35 weeks). It is a major cause of worldwide neonatal mortality and long-term neurodisability (Cerebral Palsy, Epilepsy). The injury occurs in two phases: the primary insult (at birth) and the secondary energy failure (6-72 hours later). This secondary phase offers a unique "therapeutic window" where Therapeutic Hypothermia (Cooling) can prevent apoptosis and significantly improve outcomes. [1,2]
Key Facts
- Sentinel Events: Treating HIE requires identifying a cause, e.g., Uterine Rupture, Placental Abruption, Cord Prolapse, or Shoulder Dystocia.
- Sarnat Staging: The clinical grading system used to determine eligibility for cooling.
- Stage 1 (Mild): Hyper-alert, Tachycardia, No Seizures. Typically resolves.
- Stage 2 (Moderate): Lethargy, Hypolithia, Seizures, Constricted pupils. Requires Cooling.
- Stage 3 (Severe): Coma, Flaccid, Absent reflexes, Apnoea. High mortality. Requires Cooling.
- Outcome Prediction: MRI scan performed at Day 4-7 is the best predictor of long-term neurodisability.
Clinical Pearls
The 6 Hour Window: Therapeutic Hypothermia MUST be started within 6 hours of birth. After this, the secondary phase of injury has already begun, and cooling is ineffective. Time is Brain.
Passive Cooling: While waiting for the transport team (neonatal transfer service) to bring the cooling blanket, turn off the heater on the resuscitaire. Monitor rectal temp continuously. Aim for 33.5°C.
Don't forget the Kidneys: Asphyxia hits all organs. Acute Tubular Necrosis (ATN) is common. Monitor Urine Output and Creatinine.
Incidence
- 1-3 per 1000 live births in developed countries.
- Account for 23% of all neonatal deaths worldwide.
Risk Factors (Antenatal/Intrapartum)
- Thick Meconium.
- Cardiotocograph (CTG) abnormalities (bradycardia/late decelerations).
- Assisted delivery / Emergency C-Section.
The "Double Hit" Hypothesis
- Primary Energy Failure: Occurs during the asphyxial event. Hypoxia -> Anaerobic metabolism -> Lactate accumulation -> Pump failure -> Depolarisation.
- Latent Phase: 1-6 hours. Reperfusion occurs. Brain metabolism recovers transiently. Child may look deceptively well.
- Secondary Energy Failure: 6-72 hours. Oxidative stress, excitotoxicity (Glutamate), inflammation, and Apoptosis occur. This causes the permanent damage. Cooling blocks this phase.
Immediate Post-Natal
Sarnat & Sarnat Scoring (Simplified)
| Feature | Stage 1 (Mild) | Stage 2 (Moderate) | Stage 3 (Severe) |
|---|---|---|---|
| Consciousness | Hyperalert | Lethargic | Coma |
| Tone | Normal/Hyper | Hypotonic (Floppy) | Flaccid |
| Reflexes | Exaggerated | Suppressed | Absent |
| Pupils | Dilated | Constricted | Fixed/Dilated |
| Seizures | No | Common | Uncommon (Electrical only) |
Bedside
- aEEG (Cerebral Function Monitor - CFM): continuous single-channel EEG.
- Trave Pattern: Normal (Continuous Voltage) vs Abnormal (Burst Suppression / Flat Trace).
- Criteria for cooling: Moderately or Severely abnormal trace.
- Glucose: Hypoglycaemia exacerbates brain injury. Maintain Normoglycaemia.
Imaging
- Cranial Ultrasound: Day 1. To rule out haemorrhage. (HIE changes not visible yet).
- MRI Brain: Day 5-10. Gold standard.
- Pattern: High signal in Basal Ganglia and Thalamus (BGT) indicates severe outcome (these areas have highest metabolic rate). White matter injury indicates milder outcome.
Management Algorithm
BIRTH ASPHYXIA EVENT
↓
RESUSCITATION (NLS)
↓
ASSESS CRITERIA A, B, C
A = Apgarless than 5 OR pHless than 7.0 OR Vent >10m
B = Mod/Severe Encephalopathy (Sarnat)
C = aEEG Abnormal (optional)
↓
┌─────────────┴─────────────┐
DO NOT START START COOLING
(Criteria not met) (Target 33.5°C)
(For 72 Hours)
↓
REWARMING
(0.5°C per hour)
1. Therapeutic Hypothermia (Total Body Cooling)
- Indication: Infants >35 weeks gestation / >1.8kg with evidence of HIE.
- Method: Cooling mattress/wrap.
- Target: 33.5°C.
- Duration: 72 hours.
- Mechanism: Slows metabolism, reduces free radicals, prevents apoptosis.
- Rewarming: Must be slow (0.5 degrees/hr) to prevent hypotension/seizures.
2. Seizure Management
- Treat electrical seizures on CFM even if no clinical signs.
- First Line: Phenobarbital (20mg/kg IV loading).
- Second Line: Phenytoin / Levetiracetam / Lidocaine.
3. Supportive Care
- Ventilation: Often required. Avoid Hypocapnia (vasoconstricts cerebral vessels).
- BP Support: Inotropes to maintain cerebral perfusion pressure.
- Cerebral Palsy: Dyskinetic / Quadriplegic.
- Epilepsy.
- Blindness/Deafness.
- Multi-organ Failure: Necrotising Enterocolitis (NEC), Renal Failure, Cardiomyopathy.
- Without Cooling: Death/Disability 60%.
- With Cooling: Death/Disability 45%. (NNT = 6).
- Normal MRI at Day 10: Excellent prognosis.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| HIE | TOBY Register | Clear criteria for cooling. Passive cooling during transfer. |
| Resuscitation | NLS (Resus Council) | If no Heart Rate by 20 minutes, consider stopping resuscitation. |
Landmark Trials
1. TOBY Trial (Total Body Hypothermia) - NEJM 2009
- Findings: Cooling increased the rate of survival without disability.
- Impact: Established cooling as standard of care.
2. NICHD Trial: Similar findings.
What happened?
Your baby didn't get enough oxygen during the birth. We call this a "hypoxic" injury. The brain needs oxygen to work, and if levels drop, the brain cells get stressed.
Why are you making my baby cold?
We know that after the initial lack of oxygen, the brain tries to recover but can over-react, causing swelling and more damage. By cooling the body down to 33.5 degrees, we put the brain into "hibernation". It slows everything down, giving the brain cells a chance to heal without burning out.
Will they be okay?
We have to wait and see. We cool them for 3 days, then warm them up slowly. After that, we will do a special MRI scan which gives us the best idea of the future. Many babies do very well, but some may have problems with movement or learning later in life.
Primary Sources
- Azzopardi DV, et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy (TOBY). N Engl J Med. 2009;361:1349-1358. PMID: 19797281.
- Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol. 1976.
- Shankaran S, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005.
Common Exam Questions
- Paediatrics: "Best investigation for prognosis in HIE?"
- Answer: MRI Brain (Day 4-10).
- Neonatology: "Criteria for cooling?"
- Answer: Gestation >35w + Evidence of Asphyxia (pH less than 7) + Signs of Encephalopathy.
- Pathology: "Region of brain most affected?"
- Answer: Basal Ganglia and Thalamus (high metabolic rate).
- Pharmacology: "First line AED for neonates?"
- Answer: Phenobarbital.
Viva Points
- Therapeutic Window: Why 6 hours? Based on animal studies showing the latent phase ends at 6 hours. Cooling after this is ineffective.
- Cooling Adverse Effects: Bradycardia (normal sinus bradycardia of 80-100 is expected), Thrombocytopenia, Subcutaneous Fat Necrosis (rare).
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.