Hypoxic-Ischemic Encephalopathy (HIE)

Sunil Kumar Daha

HYPOXIC ISCHEMIC ENCEPHALOPATHY

•Hypoxia: Decrease oxygenation to cells/ organs

• Ischemia: blood flow to cells or organs that is insufficient to maintain normal function

• Encephalopathy: a disease in which the functioning of the brain is affected by some agent or condition

- Important cause of permanent damage to CNS tissue that may result in neonatal death/ cerebral palsy/ developmental delay. (20-30% HIE die, ~33-50% survivors with permanent neurodevelopmental abnormalities)

ETIOLOGYBefore birth fetal hypoxia caused by:1. Inadequate oxygenation: hypoventilation during anesthesia,

respiratory failure, carbon monoxide poisoning2. low maternal blood pressure: Blood loss, spinal anesthesia,

compression of vena cava & aorta by gravid uterus3. inadequate relaxation of uterus: excessive oxytocin4. premature separation of placenta5. Knotting of the cord: 6. placental insufficiency from toxemia/post maturity

After birth hypoxemia caused by:1. Failure of oxygenation: due to cynotic heart disease, pulmonary

disease2. severe anemia: haemorrhage, hemolytic disease3. shock: sepsis, massive blood loss, intracranial haemorrhage

Pathophysiology

Clinical manifestation:• Intrauterine growth restriction with increased vascular resistance• Slow HR during labor• presence of meconium-stained amniotic fluid• depressed and may fail to breathe spontaneously• hypotonic/ hypertonic state• pallor, cyanosis, apnea, slow heart rate, unresponsive to

stimulation• seizure• Heart failure & cardiogenic shock, PPH, respiratory distress

syndrome, hematuria, ATN with perinatal asphyxia secondary to inadequate perfusion

SIGNS STAGE 1 STAGE 2 STAGE 3

Level of consciousness Hyperalert Lethargic Stuporous, coma

Muscle tone Normal Hypotonic Flaccid

Posture Normal Flexion Decerebrate

Tendon reflexes/clonus Hyperactive Hyperactive Absent

Myoclonus Present Present Absent

Moro reflex Strong Weak Absent

Pupils Mydriasis Miosis Unequal, poor light reflex

Seizures None Common Decerebration

Electroencephalographic findings Normal Low voltage changing to seizure activity Burst suppression to isoelectric

Duration<24 hr if progresses; otherwise, may remain normal 24 hr-14 days Days to weeks

Outcome Good Variable Death, severe deficits

Sarnat Classification of Hypoxic-ischemic Encephalopathy in Term Infants

Diagnosis• MRI is the preferred imaging modality in neonates with HIE

• CT scans : identifies focal hemorrhagic lesions, diffuse cortical injury, and

damage to the basal ganglia;

• CT has limited ability to identify cortical injury during the 1st few days of life.

• Ultrasonography has limited utility in evaluation of hypoxic injury in the term

infant; it is the preferred modality in evaluation of the preterm infant

• Apmlitude-integrated electroencephalography (aEEG) determine which

infant are at high risk for long term brain injury.

A- MRI showing focal neuronal injury; B- Diffuse weighted MRI showing HIE

Treatment

Hypothermia

Selective cerebral or whole body (systemic) therapeutic hypothermia

Decreases rate of apoptosis & suppress production of neurotoxic, glutamate,

free radical, NO, lactate

Reduces mortality or major neurodevelopmental impairment in term and near-

term infants with HIE. Effective if apply within 6 hrs. temperature should be 33.5C

Drug Therapy• Phenobarbital is drug of choice for seizure, IV loading dose (20mg/kg) +

additional 5-10mg/kg (up to 40-50mg/kg) may be needed

• Level should be monitored 24 hrs. after loading dose & maintenance therapy (5mg/kg/24hrs)

• Phenytoin (20mg/kg loading dose) or lorazepam (0.1mg/kg) for refractory seizure

Additional Therapy• Supportive care (management of organ system dysfunction) • Management of hyperthermia is important

• Ventilatory status & adequate oxygenation blood pressure, hemodynamic status acid- base balance & possible infection is important.

• Secondary hypoxia or hypotension due to complication of HIE must be prevented

• Aggressive treatment of seizure is critical and do with continuous EEG monitoring

Prognosis:• Depend up on timing & severity of the insult

• Ranging from complete recovery to death

• Infant with initial blood pH <6.7 have 90% risk of death/ severe neurological impairement

• Infant with apgar 0-3 at 5 minutes has high risk for death and impairement

• Severe encephalopathy:flaccid, coma, apnea, absence of oculocephalic reflexes & refractory seizure is poor prognosis

• Combined use of early EEG and MRI help to predicting outcomes in term infant with HIE

• Microcephaly/ poor head growth during 1st yrs of life is correlate with injury to basal ganglia & white matter & adverse developmental outcomes

• Brain death after neonatal HIE is diagnosed from clinical findings: coma, unresponsive to pain, auditory & visual stimuli, apnea with Pco2 from 40- >60 mmhg without ventilatory support and absence of brain stem reflexes.

Cont..

Refrence:• Nelson text book of paediatrics 19th edition• Ghai, Essential Paediatrics, 7th edition

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