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Hypoxic-Ischemic Encephalopathy (HIE)

Hypoxic-Ischemic Encephalopathy (HIE). Dezhi Mu MD/PhD Department of Pediatrics/Children’s Medical Center West China Second University Hospital, Sichuan University. Contents. 1. Etiology. 2. Pathophysiology. 3. Clinical manifestations. 4. Laboratory tests. 5. Treatment. Definition.

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Hypoxic-Ischemic Encephalopathy (HIE)

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  1. Hypoxic-Ischemic Encephalopathy (HIE) Dezhi Mu MD/PhD Department of Pediatrics/Children’s Medical Center West China Second University Hospital, Sichuan University

  2. Contents 1.Etiology 2. Pathophysiology 3. Clinical manifestations 4. Laboratory tests 5. Treatment

  3. Definition Incidence: 3~9 per 1000 live births Hypoxia: PaO2↓ HIE + Ischemia: Blood flow↓

  4. Etiology 1. Maternal Causes 2. Placental / Unbilical Causes HIE 3. Neonatal Causes

  5. Etiology • Maternal Causes 1. Reduced maternal oxygen delivery Anemia Cardiovascular disease Hypotension/hypertension 2. Reduced uterine blood flow Abnormal uterine contractions

  6. Etiology Placenta Umbilical vein Umbilical arteries • Placental Causes 1. Early placental separation 2. Placental dysfunction Prematurity、Postmaturity Placentitis Placental edema

  7. Etiology Placenta Umbilical vein umbilical cord Umbilical arteries Umbilical Causes Reduced umbilical blood flow Excessive length of umbilical cord Short of umbilical cord Knots of umbilical cord

  8. Etiology Neonatal Causes 1. Preterm、Low birth weight、SGA、LGA 2. Diseases Asphxia、Septicemia Pulmonary disease Congenital cardiovascular disease

  9. Pathophysiology Hypoxemia Brain hypoxia and ischemia Reperfusion injury Depleting ATP: energy failure Secondaryenergy failure Primary cell death (necrotic) Secondary cell death (apoptotic) 6 h 6~24h HIE

  10. Clinical Manifestations Mild Depending on HIE severity Moderate Severe

  11. Clinical Manifestations (CNS)

  12. Clinical Manifestations (CNS)

  13. Accessory tests- laboratory test No specific test to confirm the diagnosis. Tests are performed to assess the injury and to monitor functional status of the organs.

  14. Accessory tests • Electroencephalogram (EEG) 1. Assess the severity of the injury 2. Evaluate for subclinical seizures 3. A suppressed or seizure activity of EEG A poor prognosis

  15. Accessory tests • Cranial Computed tomograph scan 1、Cerebral edema 2、Hemorrhage Potentially harmful radiation

  16. Accessory tests Cerebral edema Normal CT: Cerebral edema

  17. Accessory tests Normal Hemorrhage CT

  18. Accessory tests • Brain MRI 1、Accurately demonstrate the injury pattern as area of hyperintensity 2、Diagnosis and follow-up of infants with moderate-to-severe HIE

  19. Accessory tests Cerebral edema Normal MRI: Cerebral edema

  20. Accessory tests Hypoperfusion injury Normal Hypoperfusion injury；signal intensity

  21. Treatments Supportive treatment Specific treatment: N/A Recovery treatment

  22. Treatments Management aims at: 1. Early identification 2. To maintain adequate perfusion 3. To stop the processes of ongoing injury

  23. Treatments • Therapeutic Window 1. Clinic: No direct evidence 2. Studies: Animal models 3. When: 6h

  24. Treatments Supportive treatments 1. Adequate ventilation 2. Adequate perfusion 3. Adequate Glucose

  25. Treatments Adequate ventilation 80mmHg<PaO2<100mmHg 20mmHg<PaCO2<40mmHg pH: 7.35~7.45

  26. Treatments Supportive care 1. Adequate ventilation 2. Adequate perfusion 3. Adequate Glucose

  27. Treatments • Adequate perfusion • Peripheral perfusion • Blood pressure: 70/50 mmHg • Echocardiography (ECHO) Fluids: 60~80 mL/kg .d Dopamine: 2.5～5μg/kg. min

  28. Treatments Supportive care 1. Adequate ventilation 2. Adequate perfusion 3. Adequate glucose

  29. Treatments Aim: Avoidance of hypoglycemia/hyperglycemia Maintain the glucose: 40~90mg/dl Maintain the normal electrolytes

  30. Treatments Symptomatic treatment 1. Treatment of seizures 2. Treatment of intracranial pressure

  31. Treatments Neonatal seizures 1. HIE is the most common cause of seizures 2. About 30% of HIE at the first 24 hours 3. Increase the risk of additional injury

  32. Treatments • Treatment of seizures Drug: Phenobarbitone (first line treatment) 20 mg/kg, intravenously repeated once as needed daily dosing 5 mg/kg/day (target level 40–60 g/mL)

  33. Treatments Symptomatic treatment 1. Treatment of seizures 2. Treatment of intracranial pressure

  34. Treatments • Treatment of intracranial pressure • Fluids: 60~80 mL/kg .d • Furosemide ？ • Mannitol ？

  35. Treatments Current potential treatment Hypothermia

  36. Treatments • Hypothermia is used for the following: • ≥ 35 weeks gestational age • ≥ 1800g • moderate to severe encephalopathy • intrapartum hypoxia indicated as following: (1) Apgar score ≤ 5 at 10 minutes (2) blood gas with pH ≤ 7.00

  37. Treatments • Optimal timing of initiation • Within 6 hours, the earlier the better • Temperature • 3~4℃ below baseline temperature, 33.0~34.0℃ • Optimal duration • 72h, the greater severity, the longer • Methods • Selective head / Whole body cooling

  38. Prognosis Death: 15~20% in neonatal period Neurodevelopmental abnormalities: 25~30% survivors Mild: recover completely Moderate: about 20% neurological complications Severe: most die or severe brain injury

  39. Case discussion Male infant, 30 minutes. Complaint: Poor response after resuscitation for 30 minutes, convulsed once. History: Born by emergency CS for suspected fetal distress. Apgar score: 0, 0, 2 at 1, 5, 10minutes. Meconium-staining of amniotic fluid.

  40. To be continued No breath and heart beat at birth, intubated in the delivery room. Hypotonia and pale skin were noted. Face-masked pressure respiration, chest compression and epinephrine were used. 10 minutes after resuscitation, his eyes starred for about 1 minute.

  41. To be continued PE: Poor response, cyanotic lips. Normal anterior fontanelle tension. Muscular tension was low. Primary reflections could not be elicited.

  42. To be continued Investigation: Chest X-ray: neonate pneumonia. Blood gas analysis: pH 6.948，SaO2 82%， HCO3- 11mmol/L. Liver and kidney function, blood electrolytes, Blood-Rt, CRP: normality

  43. Case discussion continued Question: 1. What is the diagnosis? 2. What is the investigation? 3. What is the treatment?

  44. Case discussion continued Diagnosis: 1. Hypoxic ischemic encephalopathy (severe) 2. Neonatal asphyxia (severe)

  45. Case discussion continued Investigation: 1. Brain CT and MRI: decreased density of intracranial cerebral white matter; the left frontal top soft tissue swelling. 2. EEG: abnormal, a spike or wide sharp wave repeatedly issuing.

  46. Case discussion continued Treatment: 1. supportive treatment. 2. hypothermia 3. rehabilitation

  47. Thank you! mudz@scu.edu.cn • 028-85501313(O)

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