HYPOXIC ISCHEMIC

ENCEPHALOPATHY

Hypoxic-ischemic encephalopathy, is
characterized by clinical and laboratory evidence
of acute or subacute brain injury due to asphyxia.
The primary causes of this condition are systemic
hypoxemia and/or reduced cerebral blood flow
(CBF).

Guidlines of AAP and ACOG for 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 (eg, seizures, coma,
hypotonia)
Multiple organ involvement (eg, kidney, lungs, liver,
heart, intestines)

Risk Factors

Preconceptual

Antepartum

Intrapartum

IDDM
Thyroid disease
Fertility
treatments
Nulliparity
Advanced
maternal age.

Severe preeclampsia
Placental
abruption
IUGR
Antepartum
haemorrhage

Breech
Cord prolapse
Stat C-section
Induction
Maternal pyrexia

Pathophysiology
Primary energy failure
Initial reduction in CBF,dec.ATP and inc.lactate.failure of Na/k+
pump,depolarization of neurons,release of glutamate,cerebral
edema,ischemia,microvascular damage with necrosis and
apoptosis
Brief period of recovery (latent period)
Optimal timing for therapeutic intervention

 Secondary energy failure

Occurs 6-48 hrs
Exact mechanism unknown
Related to oxidative stress,excitotoxicity and inflammation

Incidence
In the United States and in most developed countries, the

incidence of hypoxic-ischemic encephalopathy is 1-8

cases per 1000 births.
The incidence of hypoxic-ischemic encephalopathy is

reportedly high in developing countries.

Clinical Presentation
CNS Manifestation
Clinical manifestations and course vary depending on hypoxicischemic encephalopathy severity.
Mild hypoxic-ischemic encephalopathy
Muscle tone may be slightly increased and deep tendon reflexes
may be brisk during the first few days.
Transient behavioral abnormalities, such as poor feeding,
irritability, or excessive crying or sleepiness.
The neurologic examination findings normalize by 3-4 days of life.

 Moderately severe hypoxic-ischemic encephalopathy

The infant is lethargic, with significant hypotonia and

diminished deep tendon reflexes.

The grasping, Moro, and sucking reflexes may be sluggish or
absent.
The infant may experience occasional periods of apnea.
Seizures may occur within the first 24 hours of life.
Full recovery within 1-2 weeks is possible and is associated
with a better long-term outcome.

 Severe hypoxic-ischemic encephalopathy

Stupor or coma is typical.
Irregular breathing and need of ventilatory support.
Generalized hypotonia and depressed deep tendon reflexes
Neonatal reflexes are absent.
Pupils may be dilated, fixed, or poorly reactive to light.
Seizures occur early, usually generalized and may be initially

resistant to conventional treatments.

Irregularities of heart rate and blood pressure (BP) are
common,death from cardiorespiratory failure.
The infants who survive severe HIE;
Level of alertness improved by day 4-5
Hypotonia and feeding difficulties persist for weeks to months

Multiorgan dysfunction
Heart
Lungs
Renal
Liver
GI dysfunction
Hematological

 Diagnosis
Diagnosis is made based on the history, physical and

neurological examinations, and laboratory evidence.

Laboratory studies include : Serum electrolyte .
Renal function
Cardiac & liver enzymes
Coagulation system
ABG

 Imaging Studies
Cranial ultrasonography
Global increase in cerebral echogenicity,obliteration CSF containing

spaces suggestive of cerebral edema.

Head CT scanning
A CT scan of the head shows cerebral edema, manifested as

narrowness of the lateral ventricles and flattening of gyri. Areas of

reduced density that indicate evolving zones of infarction may be
present. Evidence of hemorrhage in the ventricles or in the cerebral
parenchyma may also be seen.

 Brain MRI
Choice for the diagnosis and follow-up of infants with moderate-to-

severe hypoxic-ischemic encephalopathy (HIE). Demonstrates the

injury pattern as area of hyperintensity
Amplitude-integrated electroencephalography (aEEG)
aEEG performed within a few hours of birth can help evaluate the

severity of brain injury in the infant with hypoxic-ischemic

encephalopathy

Standard EEG
generalized depression of backgrond rhythem and voltage,with

varying degrees of superimposed seizures are early findings

Treatment
Medical care
Initial Resuscitation and Stabilization Close attention should be paid to appropriate oxygen delivery,

perfusion status, and avoidance of hypoglycemia and hyperthermia.

International Liaison Committee on Resuscitation (ILCOR)
recommendations include initiating neonatal resuscitation with
concentrations of oxygen between 21-100%

 Supportive Care in Patients with Hypoxic-ischemic

Encephalopathy
Most infants with severe hypoxic-ischemic encephalopathy need

ventilatory support during first days of life.

Infants with hypoxic-ischemic encephalopathy are also at risk for
pulmonary hypertension and should be monitored. Nitric oxide (NO)
may be used according to published guidelines.

 Perfusion and Blood Pressure Management

A mean blood pressure (BP) above 35-40 mm Hg is necessary to avoid

decreased cerebral perfusion.

Dopamine or dobutamine can be used to achieve adequate cardiac
output in these patients. Avoiding iatrogenic hypertensive episodes is
also important.

 Fluid and Electrolytes Management

Fluid restriction
f

Prophylactic theophylline, given early after birth helps in reducing renal

dysfunction
A single dose of theophylline (5-8 mg/kg) given within 1 hour of birth
resulted in
decreased severe renal dysfunction (defined as creatinine level >1.5
mg/dL for 2 consecutive days);
2. increased creatine clearance;
3. increased glomerular filtration rate (GFR); and
4. decreased b2 microglobulin excretion.
1.

Avoid hypoglycemia and hyperglycemia because both may accentuate

brain damage.

 Treatment of Seizures
Hypoxic-ischemic encephalopathy is the most common cause of

seizures in the neonatal period.

Current therapies available to treat neonates with seizures include
phenobarbital, phenytoin, and benzodiazepines.
Phenobarbital has been shown to be effective in only 29-50% of
cases.
Phenytoin only offers an additional 15% efficacy.
Benzodiazepines, particularly lorazepam, may offer some additional
efficacy

 Hypothermia Therapy
Mild hypothermia (3-4C below baseline temperature) applied within a

few hours (no later than 6 h) of injury is neuroprotective. Possible

mechanisms include
1.
2.
3.
4.
5.

reduced metabolic rate and energy depletion;

decreased excitatory transmitter release;
reduced alterations in ion flux;
reduced apoptosis due to hypoxic-ischemic encephalopathy; and
reduced vascular permeability, edema, and disruptions of bloodbrain barrier functions.

Therapeutic hypothermia when applied within 6 hours of birth and

maintained for 48-72 hours is a promising therapy for mild-tomoderate cases of hypoxic-ischemic encephalopathy.

Diet
In most cases (particularly in moderately severe and
severe hypoxic-ischemic encephalopathy), the infant is
restricted to nothing by mouth (NPO) during the first 3
days of life or until the general level of alertness and
consciousness improves. In addition, infants
undergoing hypothermia therapy should remain NPO
until rewarmed. Enteral feeds should be carefully
initiated about 5 mL every 3-4 h.

Complications
Cerebral palsy(30%)
Epilepsy(16%)
Blindness(14_17%)
Hearing problems(6%)

Prognosis
Lack of spontaneous respiratory effort within 20-30 minutes of

birth is almost always associated with death.

The presence of seizures is an ominous sign.
Abnormal clinical neurological findings persisting beyond the first
7-10 days of life usually indicate poor prognosis.
EEG at about 7 days that reveals normal background activity is a
good prognostic sign.
Persistent feeding difficulties, which generally are due to
abnormal tone of the muscles of sucking and swallowing, also
suggest significant CNS damage.
Poor head growth during the postnatal period and the first year of
life is a sensitive finding predicting higher frequency of neurologic
deficits

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