1. HYPOXIC ISCHEMIC ENCEPHALOPATHY
DR. MAHMOUD MOHAMED OSMAN
MBBCH, MSc (Pedia), MRCPCH (UK), FRCP (Edinburgh)
Consultant Pediatrician & Neonatologist
Al Yammamah Hospital, MOH

2. OF HYPOXIC-ISCHEMIC ENCEPHALOPATHY
LEARNING OBJECTIVES:
Introduction
Etiology
Pathophysiology
Clinical features
Diagnosis
Management
Prognosis
OF HYPOXIC-ISCHEMIC ENCEPHALOPATHY

3. Hypoxic-Ischemic Encephalopathy…………..
1. INTRODUCTION
Anoxia is a term used to indicate the consequences of complete lack of oxygen as a result of a number of primary causes.
Hypoxemia refers to decreased arterial concentration of oxygen.
Hypoxia refers to a decreased oxygenation to cells or organs.
Ischemia refers to insufficient blood flow to cells or organs to maintain their normal function.
Hypoxic-ischemic encephalopathy: It is an abnormal neurobehavioral state in which the predominant pathogenic mechanism is impaired cerebral blood flow that may result in neonatal death or be manifested later as cerebral palsy or developmental delay.

4. It occurs in 1-6 per 1000 live term births in developed countries
Hypoxic-Ischemic Encephalopathy…………..
Incidence of HIE:
Despite major advances in fetal and neonatal medicine hypoxic-ischemic encephalopathy (HIE), remains a serious condition that causes significant mortality and long-term morbidity.
It occurs in 1-6 per 1000 live term births in developed countries
The incidence of hypoxic-ischemic encephalopathy is reportedly high in developing countries.

5. Hypoxic-Ischemic Encephalopathy…………..
2. ETIOLOGY
Hypoxic-ischemic encephalopathy (HIE) can occur in the antepartum or intrapartum period as a result of impaired gas exchange across the placenta.
That leads to the inadequate provision of oxygen and removal of carbon dioxide and hydrogen from the fetus.
HIE can occur in the postpartum period, usually secondary to pulmonary, cardiovascular, or neurologic abnormalities.
HIE is characterized by clinical and laboratory evidence of acute or subacute brain injury due to asphyxia (hypoxia, ischemia, and acidosis).

6. Hypoxic-Ischemic Encephalopathy…………..
A- RISK FACTORS:
Most often, the exact timing and underlying cause remain unknown

7. Hypoxic-Ischemic Encephalopathy…………..
B- CAUSES OF FETAL HIE:

8. Hypoxic-Ischemic Encephalopathy…………..
3. PATHOPHYSIOLOGY
After an episode of hypoxia and ischemia, anaerobic metabolism occurs and generates amounts of lactate, inorganic phosphates, glutamate, free radicals and nitric oxide.
The initial circulatory response of the fetus is transient maintenance of perfusion of the brain, heart, and adrenals in preference to the lungs, liver, kidneys, and intestine.

9. Cardiovascular Response to Asphyxia
Pathophysiology……….
Cardiovascular Response to Asphyxia

10. Pathophysiology……….
The pathology of hypoxia-ischemia depends on the affected organ and the severity of the injury; these lead to signs of coagulation necrosis and cell death.
If fetal distress produces gasping, the amniotic fluid contents (meconium, squames, lanugo) are aspirated into the trachea or lungs.

11. Pathophysiology……….
Term infants demonstrate neuronal necrosis of the cortex (later, cortical atrophy) and parasagittal ischemic injury.
Preterm infants demonstrate Periventricular leukomalacia (later, spastic diplegia), basal ganglia injury, and IVH.
Term more often than preterm infants have focal or multifocal cortical infarcts that manifest clinically as focal seizures and hemiplegia.
Term
Premature

12. 4. CLINICAL MANIFESTATIONS
Continuous fetal heart rate recording may reveal a slow heart rate; or variable or late deceleration.
These signs should lead to giving high oxygen to the mother and consideration of immediate delivery to avoid fetal death and CNS damage.
The presence of meconium-stained amniotic fluid is evidence that fetal distress has occurred.
At birth, affected infants may be depressed and may fail to breathe spontaneously; with pallor, cyanosis, a slow heart rate, and unresponsiveness to stimulation.

13. Clinical Manifestations…………

14. Clinical Manifestations………..
During the next hours, they may remain hypotonic, change to a hypertonic state, or to a normal tone.
Cerebral edema may develop and result in profound brainstem depression.
During this time, seizure activity may occur; it may be severe and refractory to the usual doses of anticonvulsants.
Seizures in asphyxiated newborns may also be due to hypocalcemia, hypoglycemia, or infection.

15. Clinical Manifestations………..
Heart failure and cardiogenic shock, respiratory distress syndrome, gastrointestinal perforation, and acute tubular necrosis may occur.
The severity of neonatal encephalopathy depends on the duration and timing of injury. Symptoms develop over a series of days.

16. Consequences of Hypoxic-Ischemic Encephalopathy

17. 5. DIAGNOSIS A. Criteria For Diagnosis of HIE:
Profound metabolic or mixed acidemia (pH< 7) in an umbilical artery blood sample, if obtained.
Persistence of an Apgar score of 0-3 for longer than 5 minutes.
Neonatal neurologic sequelae. (seizures, coma, hypotonia)
Multiple organ involvement. (kidney, lungs, liver, heart, intestines)

18. Diagnosis………
There are no specific tests to confirm or exclude a diagnosis of hypoxic-ischemic encephalopathy.
The diagnosis is made based on the history, physical and neurological examinations, and laboratory evidence.

19. Diagnosis………
B. The Apgar Score:

20. C. Laboratory Evaluation Of Asphyxia:
Diagnosis………
C. Laboratory Evaluation Of Asphyxia:
Serum electrolytes
Markedly low serum sodium, potassium, and chloride levels in the presence of reduced urine flow and excessive weight gain may indicate acute tubular damage or (SIADH) secretion, particularly during the initial 2-3 days of life.
Renal function tests
Serum creatinine levels, creatinine clearance, and BUN levels
Cardiac & liver enzymes
Assess the degree of hypoxic-ischemic injury to other organs
Coagulation system
Prothrombin time, partial thromboplastin time, and fibrinogen levels.
ABG
Assess acid-base status and to avoid hyperoxia and hypoxia as well as hypercapnia and hypocapnia

21. D. Neuroimaging Includes:
Diagnosis………
D. Neuroimaging Includes:
MRI is the preferred imaging modality in neonates with HIE because of its increased sensitivity and specificity early in the process and its ability to outline the topography of the lesion.
CT scans are helpful in identifying focal hemorrhagic lesions, diffuse cortical injury, and damage to the basal ganglia.
Ultrasonography has limited utility in evaluation of hypoxic injury in the term infant; it is the preferred modality in evaluation of the preterm infant.
Amplitude-integrated electroencephalography(aEEG); or EEG.

22. 6. MANAGAMENT 1. Hypothermia Therapy:
Selective head or whole body hypothermia of a core temperature of 33.5 Cº applied within 6 hours of birth for hours is neuroprotective.
Possible mechanisms include:
Reduced metabolic rate and energy depletion.
Decreased excitatory transmitter release.
Reduced alterations in ion flux.
Reduced apoptosis due to hypoxic-ischemic encephalopathy.
Reduced vascular permeability, edema, and disruptions of blood-brain barrier functions.
Several clinical trials demonstrate that therapeutic hypothermia is a promising therapy for mild-to-moderate cases of HIE. It reduces mortality and major neurodevelopmental impairment.

23. 2. Aggressive treatment of seizures:
MANAGAMENT……….
2. Aggressive treatment of seizures:
It is critical and may necessitate continuous EEG monitoring.
Phenobarbital, the drug of choice for seizures, is given as IV loading dose (20 mg/kg); additional doses of  mg/kg (up to 40-50 mg/kg total). And maintenance therapy (5 mg/kg/24hr)
Phenytoin (20 mg/kg loading dose) or lorazepam (0.1 mg/kg) may be needed for refractory seizures.
There is some clinical evidence that high-dose prophylactic phenobarbital may decrease neurodevelopmental impairment.

24. 3. General supportive measures:
MANAGAMENT……..
3. General supportive measures:
Hyperthermia has been found to be associated with impaired neurodevelopment, so it is important to prevent hyperthermia before initiation of hypothermia.
Careful attention to ventilatory status and, hemodynamic status (adequate oxygenation, blood pressure, acid-base balance).
Secondary hypoxia or hypotension due to complications of HIE must be prevented.
Careful attention to possible infection is important.

25. Olympic Cool Cap System

27. Whole Body Hypothermia

28. 7. PROGNOSIS
In severe hypoxic-ischemic encephalopathy, the mortality rate is reported as 25-50%.
As many as 80% of infants who survive severe HIE develop serious complications, 10% develop moderately serious disabilities, and as many as 10% are healthy.
The infants who survive moderately severe HIE 30-50% may have serious long-term complications, and 10-20% have minor neurological morbidities.
Infants with mild hypoxic-ischemic encephalopathy tend to be free from serious CNS complications.

29. Hypoxic-Ischemic Encephalopathy…………..
Predictors of Mortality and Neurologic Morbidity after Perinatal Hypoxic-Ischemic Insult

33. Hypoxic-Ischemic Encephalopathy…………..
BEST WISHES

34. Sarnat & Sarnat staging (1976)