HYPOXIC ISCHEMIC ENCEPHALOPATHY

Introduction:- hypoxic-ischemic encephalopathy or HIE is the brain

injury caused by oxygen deprivation to the brain, also commonly known as
intrapartum asphyxia. The newborns body can compensate for brief periods
of depleted oxygen, but if the asphyxia lasts too long, brain tissue is
destroyed
Background:- Despite major advances in monitoring technology and
knowledge of fetal and neonatal pathologies, perinatal asphyxia or, more
appropriately, hypoxic-ischemic encephalopathy (HIE), remains a serious
condition that causes significant mortality and long-term morbidity.

Hypoxic-ischemic encephalopathy is characterized by clinical and

laboratory evidence of acute or subacute brain injury due to asphyxia (ie,
hypoxia, acidosis). Most often, the exact timing and underlying cause
remain unknown.
Definition:-

• Anoxia
is a term used to indicate the consequences of complete lack of oxygen as a
result of a number of primary causes
• Hypoxia
refers to an arterial concentration of oxygen that is less than normal
• Ischemia
refers to blood flow to cells or organs that is insufficient to maintain their
normal function
• Hypoxic-ischemic encephalopathy
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 mental deficiency.

1996 guidelines from the AAP and ACOG for hypoxic-ischemic

encephalopathy (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
Epidemiology:-
• Frequency
a) Birth asphyxia is the cause of 23% of all neonatal deaths worldwide.
b) It is one of the top 20 leading causes of burden of disease in all age
groups by the World Health Organization.
c) It is the fifth largest cause of death of children younger than 5 years
(8%)
d) More than a million children who survive birth asphyxia develop
problems such as cerebral palsy, mental retardation, learning
difficulties, and other disabilities.

• Mortality/Morbidity:
a) In severe hypoxic-ischemic encephalopathy, the mortality rate is
reportedly 25-50%.
b) As many as 80% of infants who survive severe hypoxic-ischemic
encephalopathy develop serious complications, 10-20% develop
moderately serious disabilities, and as many as 10% are healthy.
c) The infants who survive moderately severe hypoxic-ischemic
encephalopathy, 30-50% may have serious long-term complications,
and 10-20% have minor neurological morbidities.
d) Infants with mild hypoxic-ischemic encephalopathy tend to be free
from serious CNS complications.
• Race
No predilection is noted.
• Sex
No predilection is observed.
• Age
Most often, the condition is noted in infants who are term at birth.
Risk factor:-

Preconceptional:-
• IDDM
• Thyroid disease
• Fertility treatments
• Nulliparity
• Advanced maternal age.
Antepartum:-
• Severe pre- eclampsia
• Placental abruption
• IUGR
 • Antepartum haemorrhage
Intrapartum:-
• Breech
• Cord prolapse
• Stat C-section
• Induction
• Maternal pyrexia
pathophysiology :-

decreased blood flow to placenta

decreased oxygen delivery to the fetus

increased oxygen consumption in mother and fetus

Brief asphyxia
Prolong asphyxia
Anaerobic metabolism.

Fetal response to asphyxia illustrating the initial redistribution of

blood flow to vital organs. With prolonged asphyxial insult and
failure of compensatory mechanisms, cerebral blood flow falls,
leading to ischemic brain injury.
 Pathophysiology of hypoxic-
ischemic brain injury in the
developing brain. During the
initial phase of energy
failure, glutamate mediated
excitotoxicity and Na+/K+
ATPase failure lead to necrotic
cell death. After transient
recovery of cerebral energy
metabolism, a secondary
phase of apoptotic neuronal
death occurs. ROS = Reactive
oxygen species.

CLINICAL FEATURE:-

Stage 1 Stage 2 Stage 3

Level of Hyperalert Lethargic/obtunded Stuporous

conciousness

Neuromuscular control

Muscle tone Normal Mild hypotonia Flaccid

Posture Mild distal flexion Strong distal flexion Intermittent

decerebratio
n

Stretch reflex Overactive Overactive Decreased/a

bsent
Segmental Present Present Absent
myoclonus

Complex Reflexes

Suck Weak Weak/absent Absent

Moro Strong, low Weak; incomplete, Absent

threshold high threshold

Oculovestibular Normal Overactive Weak/absent

Tonic neck Slight Strong Absent

 Diagnosis:-
• There are nor specific tests to confirm or exclude a diagnosis of
hypoxic- ischemic encephalopathy (HIE) because the diagnosis is
made based on the history, physical and neurological examinations,
and laboratory evidence.
• Laboratory studies include :-
Study
Serum electrolyte 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 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.
Imaging studies:-
Cranial US:
a) Doppler study and resistive index (RI) provide additional
information on cerebral perfusion.
Cranial CT
a) CT technology provides a rapid mode of screening for ICH &
hydrocephalus in a sick neonate without the need for sedation.
MRI
a) The most sensitive and specific imaging technique for examining
infants with suspected hypoxic- ischemic brain injury
Other study :-
a)Amplitude-integrated electroencephalography (aEEG)

histological finding:-:-
 Bilateral acute infarctions of the frontal lobe are shown.
 presence of pyknotic and hyperchromatic nuclei, the loss of
cytoplasmic Nissl substance, and neuronal shrinkage and angulation
(arrow). These alterations begin to appear approximately 6 hours
following hypoxic- ischemic insult.
 Reactive astrocytosis is evident approximately 24-48 hours after the
primary hypoxic-ischemic event.
 Periventricular leukomalacia is depicted.
Note the extensive hemorrhage within the cystic space as well as the
hemosiderin-laden macrophages around the lesional rim.

Treatment:-
Medical care
a) Initial Resuscitation and Stabilization-
• Delivery room management follows standard Neonatal Resuscitation
Program (NRP) guidelines. Close attention should be paid to
appropriate oxygen delivery, perfusion status, and avoidance of
hypoglycemia and hyperthermia.
b) Supportive Care in Patients with Hypoxic-ischemic
Encephalopathy
• Most infants with severe hypoxic-ischemic encephalopathy need
ventilatory support during first days of life.
• The role of mechanical ventilation is to maintain the blood gases and
acid-base status in the physiological ranges and prevent
hypoxia, hyperoxia, hypercapnia, and hypocapnia.
• Infants with hypoxic-ischemic encephalopathy are also at risk for
pulmonary hypertension and should be monitored
 c) Perfusion and blood pressure managemnet
• A mean blood pressure (BP) above 35-40 mm Hg is necessary to
avoid decreased cerebral perfusion.
• Hypotension is common in infants with severe hypoxic-ischemic
encephalopathy and is due to myocardial dysfunction, capillary leak
syndrome, and hypovolemia; hypotension should be promptly
treated.
• Dopamine or dobutamine can be used to achieve adequate
cardiac output in these patients. Avoiding iatrogenic hypertensive
episodes is also important.

d) Fluid and electrolyte management

e)treatment of seizure:-
• 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.

f) Medication summary

Anti Cardiovascular
convulsants agents

Phenobarbital Dopamine
(20mg/kg I V)

Phenytoin dobutamine
(20mg/kg)

Lorazepam
(0.1mg/kg)

g)Hypothermia therapy
 • Mild hypothermia (3-4°C below baseline temperature) applied within
a few hours (no later than 6 h) of injury is neuroprotective. Possible
mechanisms include
(1) reduced metabolic rate and energy depletion;
(2) decreased excitatory transmitter release;
(3) reduced alterations in ion flux;
(4) reduced apoptosis due to hypoxic-ischemic encephalopathy;
and
(5)reduced vascular permeability, edema, and disruptions of blood-brain
barrier functions.
• Therapeutic hypothermia when applied within 6 hours of birth and
maintained for 48-72 hours is a promising therapy for mild-to-
moderate cases of hypoxic-ischemic encephalopathy.

h)diet:-
• In most cases, 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 and
the use of trophic feeds is initially advisable (about 5 mL every 3-4
h).
• Infants should be monitored carefully for signs and symptoms of
necrotizing enterocolitis, for which infants with perinatal asphyxia
are at high risk.

Surgical care:-
• In cases of posterior cranial fossa hematoma, surgical drainage may
be lifesaving if no additional pathologies are present.
Further Inpatient Care
• Close physical therapy and developmental evaluations are needed
prior to discharge in patients with hypoxic-ischemic encephalopathy
(HIE).
Further outpatient care:-
• The goal of follow-up is to detect impairments and promote early
intervention for those infants who require it.
• Growth parameters including head circumference should be closely
monitored in all infants with hypoxic-ischemic encephalopathy.
• In infants diagnosed with moderate-to-severe hypoxic-ischemic
encephalopathy with either abnormal neurologic examination
 findings or feeding difficulties, intensive follow-up is recommended.
include follow-up by developmental pediatrician and pediatric
neurologic.
• In infants with moderate hypoxic-ischemic encephalopathy but no
feeding difficulties and normal neurologic examination findings,
routine care is appropriate.
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.