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

4. Etiology HIE 1. Maternal Causes 2. Placental / Unbilical Causes
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 Placental Causes 1. Early placental separation
2. Placental dysfunction
Prematurity、Postmaturity
Placentitis
Placental edema
Placenta
Umbilical vein
Umbilical arteries

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

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
Secondary energy failure
Primary cell death (necrotic)
Secondary cell death (apoptotic)
6 h
6~24h
HIE

10. Depending on HIE severity
Clinical Manifestations
Mild
Depending on HIE severity
Moderate
Severe

11. Clinical Manifestations (CNS)
Mild
Moderate
Severe
Consciousness
Hyperalert
Lethargic
Stupor
Primary Reflexes
Normal
or No No
Pupils
Mydriasis
Miosis
Variable
Muscle tone
hypotonia
Flaccid
Seizures
Common
Yes
EEG
low-voltage
Isopotential
Time
< 3 d
< 14d
weeks

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
CT: Cerebral edema
Normal
Cerebral edema

17. Accessory tests CT
Normal
Hemorrhage

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
MRI: Cerebral edema
Normal
Cerebral edema

20. Accessory tests Hypoperfusion injury；signal intensity Normal

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.
4 pregnancies, 2 term infants, 0 premature, 1 abortion, and 2 living children

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
partial pressure of carbon dioxide, partial pressure of oxygen, Arterial Oxygen Saturation, bicarbonate radical, base excess

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!
(O)