HYPOXIC-ISHCHEMIC ENCEPHALOPATHY (HIE)

Introduction

A variety of clinical problems are encountered during early neonatal period among babies who
are severely asphyxiated at birth. Hypoxia can cause damage to almost every tissue and organ of
the baby. Neonatal encephalopathy, following severe birth asphyxia or perinatal hypoxia is
referred to hypoxic ischemic encephalopathy.

Definition

Hypoxic ischemic encephalopathy is a type of brain damage that occurs when an infant’s brain
doesn’t receive enough oxygen and blood. It is a dangerous condition that requires immediate
medical intervention. In other words, HIE is a brain dysfunction caused by reduction in the
supply of oxygen to the brain and other tissues and organs. And encephalopathy refers to any
condition that results from reduced blood and oxygen supply to the brain.

Pathophysiology

Hypoxic damage to the neurons may lead to both cytotoxic and

vasogenic cerebral edema though brain swelling

In appropriate secretion of anti-diuretic hormone may also

contribute to the development of cerebral edema

Severe hypoxia causes selective neuronal necrosis in hippocampus,

thalamus, basal ganglia, brain stem and cerebellum.

Watershed infarcts due to preferential blood flow to brain stem rather than
cerebrum, leads to parasagital cerebral injury in term and post term infants.

Brain ischemia localized to zone between tissues supplied by

anterior posterior and middle cerebral arteries

In preterm infants, asphyxia damage on the other hand

leads to periventricular leucoomalacia.

Decreased blood flow causes brain tissues to soften up and leaving

behind fluid filled cyst.
Clinical features

The clinical syndrome of HIE must be preceded by at least one of the following three
antecedents,

 Evidences of fetal hypoxia

 Apgar score of three or less at 5 minutes and later
 Cord arterial blood Ph < 7.0

The main clinical features are,

 Multiorgan dysfunction
 Seizures within 6 to 12 hrs after birth
 CNS irritability
 Jitteriness
 Excessive crying followed by lethargy
 Inactivity
 Apneic spells and stuper
 Generalized hypotonia initially followed by hypertonia
 Anterior fontanel may be bulging due to cerebral edema and IVH
 Brain stem involvement is ominous and is characterized by irregularity of breathing,
apneic attacks, changes in papillary size and dysconjugate eye movements
 There may be no attempt to sucking and swallowing with pooling of secretions in the
oral cavity.
 Moro reflex may be hyper-reactive initially followed by incomplete or absent
 Associated metabolic and electrolyte disturbances may produce additional clinical
features.

Stages of HIE

Grading of encephalopathy provides a clue to the severity of the injury and thereby has
prognostic value. There have been several gradings proposed for HIE, but a simple clinical
grading prepared by Levine,

 Grade 1 – Mild
 Grade 2 – Moderate
 Grade 3 – Severe
 Grade 1: It is characterized by hyper alertness, normal or decreased spontaneous motor
activity, mild hypotonic and poor sucking.
Grade 2: This stage is characterized by seizures, lethargy and marked tonal abnormality,
with arms being relatively hypotonic compared to the legs. Most of the babies in this
stage requires tube feeding.
Grade 3: These neonates are comatose with new spontaneous movements and are
severely hypotonic. There may be severe and prolonged seizures and these newborn often
have difficulty in maintaining spontaneous respiration.

Management

The management aims efforts should be made to prevent further hypoxic damage to the brain
and correct any associated acid base and metabolic abnormalities. The main goals of
management are as follows,

 To evaluate and monitor injury to various organs

 To prevent secondary brain injury
 To document prognostic indicators

Clinical monitoring:

 All these newborns should be clinically monitored for the evidence of multisystem
involvement.
 Vital signs should be monitored preferably with the help of a multi-channel vital sign
monitor.
 Colour of the baby should be closely watched for cyanosis, greyness, pallor and for
jaundice.
 Detailed record should be maintained to assess CNS integrity with the help of Sarnat
staging system.
 Tissue perfusion should be evaluated by capillary refilling time on blanching which
should be less than 2 seconds.
 Abdominal girth should be monitored to identified abdominal distension
 Renal perfusion should be monitored by recording urine out put which must be kept
above 2ml/kg/hr
 Development of septicemia should be monitored by undertaking frequent screening tests
for sepsis.
Laboratory/ Biochemical monitoring

 Acid base parameters and blood gases should be monitored

 Blood glucose should be frequently checked to identify hypoglycemia/hyperglycemia
 Serum electrolytes should be monitored for hyponatreamia/hypernatreamia
 Skiagram of chest should be taken in all case except pneumothorax
 Sepsis screening and blood culture should be taken to make an early diagnosis of
bacterial infection.
 EEG should preferably be taken during first three days of life to identify any
abnormalities like burst suppression, low voltage or iso-electric pattern
 Ultrasound of brain should be taken to identify periventricular and intraventricular
hemorrhage and leucomalacia.
 CT scan should be taken to diagnose parasagital infraction

Treatments

Brain oriented resuscitation: Infants with absence of spontaneous breathing efforts by 10 mts
or those with clinical evidences of HIE demands energetic measures to reduce cerebral edema.
The infant should be intubated and attached to a mechanical ventilator and provided with a
hyperventilation to maintain pao2 above 80mmhg and pao2 between 25-30mmhg.

Thermal control: Hyperthermia should be avoided and normothermia( core temp 36-37 and
skin temp 36-36.3) needs to be maintained.

Respiratory support: Asphyxiated newborns are predisposed to respiratory distress due to

meconium aspiration or CCF. If they are hypoxic they should be provided supplemental oxygen.

Cardiovascular support: Maintaining adequate blood pressure ensures adequate cerebral

perfusion pressure. If hypovolemia is detected then adequate volume replacement with 10ml/kg
of saline must be carried out to maintain a central venous pressure of 5-8 cm. Mean arterial
pressure must be maintained above the 50 th centile for gestation and systolic blood pressure
above 45-50mmhg in babies <1kg.

Fluid therapy: The infants should be started on iv fluids at the rate of 60ml/kg/day as 10%
dextrose solution. The aim of this therapy is to maintain the blood glucose levels of between 40
and 80mg/dl.
Feeding: Oral feeding can be initiated as soon as there is evidence of adequate urine output and
gut mortility. Feeding with breastmilk can be initiated by the nasogastric route. Babies that suck
well can be allowed to feed from the breast.

Seizure control: Seizures are common in asphyxiated newborns. Seizures are controlled with
anticonvulsant drugs such as phenobarbitone, which is given as the loading dose of 20mg/kg iv
for immediate control and then as maintenance therapy of 3-5 mg/kg/day in two divided doses
iv/im.

Cerebral edema management: Current evidence does not support the use of anticerebral
edema measures such as manitol, corticosteroids, hyperventilation, elevation of head end etc.

Newer therapies: Many new therapies such as free radical scavengers, calcium channel blockers
and cerebral cooling have tried to offer neuro-protection.

Prognosis

Asphyxiated infants who suffer from multisystem failure often die in the neonatal period.
Survivors can have long term neuro developmental sequelae. Predictors of these adverse
outcomes are,

 Failure to establish respiration by 5 mts

 Apgar score of 3 or less at 10 mts
 Moderate encephalopathy for >5 days or severe encephalopathy at any time
 Onset of seizures on day 1 requiring multiple drugs for their control
 A term baby not breast feeding by day 10 of life.
 EEG shows background abnormalities.

Prevention

Once asphyxia occurs, there is bound to some residual damage especially the neonates has been
severely asphyxiated. It is there for best to prevent it. Asphyxia cannot be eliminated, however
its incidence and severity can be reduced by proper antenatal care, detecting and taking care of
maternal illness and ensuring that the neonates are delivering in a setup were resuscitation can be
done by a trained person.