Hypoxic-Ischemic Encephalopathy

Dr Mohammad Al-Maghayreh
Princess Rahma teaching hospital
Definitions
Anoxia:
– Complete lack of oxygen.
Hypoxia:
– Decreased availability of oxygen
Hypoxemia:
– Decreased arterial concentration of oxygen. Lead to
decrease oxygen to cell and organ
Ischemia:
– Insufficient blood flow to cells or organ resulting in
interrupted
metabolism and death of the cell or organ affected.
 Perinatal Asphyxia (PA)
• Perinatal asphyxia, neonatal asphyxia, or
birth asphyxia is the medical condition
resulting from lack of oxygen to a newborn
infant that causes physical harm, mainly to
the brain.
 Perinatal Asphyxia
• The Perinatal Asphyxia may be defined as
hypoxic insult to the fetus severe enough to
cause
1) Metabolic acidosis,
2) Neonatal encephalopathy, and
3) Multiorgan system dysfunction.
If encephalopathy is moderate-severe
A. Apgar score < 5 at 5 and 10 minutes

B. Acidemia of fetal umbilical artery (pH < 7.0 and BE >- 12)
C. Neuroimaging evidence of acute brain injury on brain MRI or
MR Spectroscopy consistent with hypoxia– ischemia
D.Multisystem organ failure
HIE is the most likely cause of encephalopathy

2014 Task Force on Neonatal Encephalopathy,

American College of Obstetricians and Gynecologists
Incidence HIE
The incidence in developed world, is
estimated at 1-8 per 1,000 live births
The incidence in developing world, estimates
are as high as 26 per 1,000.
20–30% of infants with HIE die in the neonatal
period
33–50% of survivors are left with permanent
neurodevelopmental abnormalities
infants with severe fetal acidosis (pH <6.7) (90% death/impairment) and a base
deficit >25 mmol/L (72% mortality).
 Why it is important?

• Perinatal Asphyxia is one of the leading cause of neonatal

death
Etiology
• Full-term neonates with encephalopathy
demonstrate that
80% have acute injuries,
<1% have prenatal injuries, and
3% have non–hypoxic-ischemic diagnoses
Risk factors
Main Causes of Hypoxia
Antepartum (4-20% of cases): compromise placental gas exchange
• a. Maternal hypotension
• b. Trauma
• c. Severe anemia
Perinatal (10% of cases): compromise pulmonary gas exchange in newborn
• a. Prematurity- decreased surfactant
• b. Severe cardiopulmonary abnormalities
Intrapartum (56-80% of cases): compromise placental gas exchange
• a. Placental abruption- separation of placenta from lining of
uterus
• b. Umbilical cord prolapse- cord precedes fetus exit from uterus
Multiorgan Systemic Effects of
Asphyxia
Pathophysiology
Brain Regions vulnerable for damage
• Hippocampus,
• Purkinje Neurons in
Cerebellum
• Basal Ganglia, and
• Brain-stem.
Poor Predictive Variables for Death/Disability After
Hypoxic-Ischemic Encephalopathy
 Diagnosis
• Maternal history and fetal heart rate pattern
• Umbilical cord blood gases .
• Neonatal data(Apgar scores. )
• Laboratory studies.
• MRI is the most sensitive imaging modality for detecting hypoxic brain
injury the neonate.
• CT scans may be helpful in ruling out focal hemorrhagic lesions or large
arterial ischemic strokes
• US has limited utility in evaluation of hypoxic injury in the term infant, but
it too can be useful for excluding hemorrhagic lesions
• Electroencephalography
Major Aspects of MRI in Diagnosis of Hypoxic-Ischemic
Encephalopathy in the Term Infant
 Value of Electroencephalography in Assessment of
Asphyxiated Term Infants
Detection of severe abnormalities (i.e., CLV, FT, BSP) in 1st hours
of life has a positive predictive value of an unfavorable outcome
of 80–90%.
Severe abnormalities may improve within 24 hr (~50% of BSP
and 10% of CLV/FT).
Rapid recovery of severe abnormalities is associated with a
favorable outcome in 60% of cases.
The combination of early neonatal neurologic examination and
early aEEG enhances the positive predictive value and
specificity.
Electroencephalographic Patterns of Prognostic
Significance in Asphyxiated Term Infants
 Treatment
The management of infants with HIE begins
with the identification of perinatal patients at
high risk for asphyxia and optimal resuscitation in
the delivery room.

1. Hypothermia
2. Chemical Therapy
3. Cellular Therapy
Management: Supportive
 A. Supportive care
1. Resuscitation. initiating resuscitation with room air or
blended oxygen with a targeted preductal Spo2 of 60–65% by 1
minute of life and 80–85% by 5 minutes of life in all term and
preterm infants.
2. Ventilation. Assisted ventilation may be required to maintain
Pco2 within the physiologic range.
3. Perfusion.
Arterial blood pressure should be maintained in the normotensive range
for gestational age and weight.
.
4. Acid-base status.
The base deficit is thought to increase in the first 30 minutes of life due to
an initial washout effect secondary to improved perfusion and transient
increase in lactic acid levels..
Sodium bicarbonate therapy is not recommended as it causes a
concomitant rise in intracellular Pco2 levels, negating any changes in pH, and
is associated with increased rates of intraventricular hemorrhage and
mortality.
• 5. Fluid status. Initial fluid restriction is recommended as
HIE infants are predisposed to a fluid overload state from
renal failure secondary to acute tubular necrosis (ATN) and
SIADH.
The avoidance of volume overload helps avert cerebral
edema.
• A single dose of Theophylline (8 mg/kg) may be
considered within the first hour to increase glomerular
filtration by blocking adenosine mediated renal
vasoconstriction
6. Blood glucose.
Initial hypoglycemia (<40 mg/dL) in the context of HIE amplifies
the risk of progression from moderate to severe encephalopathy.
Timely and frequent monitoring of blood glucose levels is
therefore essential.
7. Seizures.
Seizure activity is both a consequence and determinant of brain
injury
1. Hypothermia
Prerequisite for TH
• Gestation ≥ 36 weeks
• Apgar score of ≤5 and need for resuscitation beyond 10 minutes after birth
• Acidosis with cord arterial blood pH of < 7.0 in the first hour of life (where
available) and base deficit -16
• Neurological signs – hypotonia, hypertonia, weak/absent suck, seizures
• Age ≤ 6 hours from birth
• Abnormal aEEG pattern (where available)
• Sarnat staging of moderate or severe asphyxia
• Ability to provide adequate supportive care and monitoring
• Absence of major congenital abnormalities
Principle of TH •
• Achieve rectal temperature of 33ºC – 34.5ºC within 3 to 4
hours
• Maintain rectal temperature steadily between 33ºC and
34.5ºC for 72 hours
• Rewarm the baby at a steady rate of 0.5ºC per hour until a
rectal temperature of 37±0.5ºC is attained
• Monitor the baby closely until 80 hours
• Maintain adequate supportive care and close monitoring
throughout the TH and continue intensive care after the TH
Efficacy of TH

TH has been shown in various studies to reduce composite

outcome of:
 Death or major neurodevelopmental disability
 Mortality
 Major disability at the age of 18 months
 Cerebral palsy
 Developmental delay
 Blindness
 Adverse Effects of TH

Sinus bradycardia
Thrombocytopenia
Background abnormal aEEG/Seizures

Increased multiorgan injury

 Treating seizures associated with HIE,
• phenobarbital , the l firstline drug for neonatal
seizures, continues to be used in many instances.
• refractory seizuresphenytoin (20 mg/kg loading
dose) or lorazepam (0.1mg/kg) have been
preferred, currently the use of levetiracetam is
preferred (at times even as a first-line agent) as
the most used second-line agent
 Treating seizures associated with HIE,
phenobarbital , the l firstline drug for neonatal
seizures, continues to be used in many instances.
Refractory seizures phenytoin (20 mg/kg loading
dose) or lorazepam (0.1mg/kg) have been
preferred, currently the use of levetiracetam is
preferred (at times even as a first-line agent) as
the most used second-line agent
 Second- or third-line agents commonly used include
midazolam, topiramate, and lidocaine.
 Pyridoxine should also be attempted, particularly in
ongoing refractory seizures with highly abnormal EEG
background
 Status epilepticus, multifocal seizures, and multiple
anticonvulsant medications during therapeutic
hypothermia are associated with a poor prognosis
3. Cellular Therapy
No universal agreement has been reached
regarding the definition of neonatal brain
death
There is no agreement on brain death criteria
in preterm infants.
Brain death after neonatal HIE is diagnosed from
the clinical findings of
 Coma unresponsive to pain, auditory, or visual
stimulation;
 Apnea with PCO 2 rising from 40 to >60 mm Hg
without ventilatory support; and absence of
brainstem reflexes (pupillary, oculocephalic,
oculovestibular, corneal, gag, sucking)
 These findings must occur in the absence of hypothermia,
Hypotension, and Elevations of depressant drugs
(phenobarbital), which may take days to weeks to be
metabolized and cleared completely from the blood.
 An absence of cerebral blood flow on radionuclide scans
and of electrical activity on EEG (electrocerebral silence) is
inconsistently observed in clinically brain-dead neonatal
infants.
 Persistence of the clinical criteria for 24 hr in term infants
predicts brain death in most asphyxiated newborns.
 There is no agreement on brain death criteria in preterm
infants
• Consideration of withdrawal of life
support should include discussions
with the family, the healthcare team,
and, if there is disagreement, an
ethics committee