HYPOXIC-ISCHEMIC

ENCEPHALOPATHY
 OBJECTIVES

1. Know the etiology of hypoxic-ischemic encephalopathy (HIE)

2. Know the manifestations of HIE
3. Know the criteria used to diagnose HIE
4. Review the clinical severity grading of HIE
5. Be able to describe the pathophysiology of HIE
6. Know the management of HIE
 DEFINITIONS

• Hypoxemia- decreased arterial concentration of oxygen

• Hypoxia- decreased oxygenation to cells or organs
• Ischemia- refers to blood flow to cells or organs that is
inadequate to maintain physiologic function
• Asphyxia- the state in which placental or pulmonary gas
exchange is compromised or ceases altogether
• Encephalopathy- an umbrella term that includes any type of
neurological dysfunction.
 INCIDENCE OF HIE

• 1-8 per 1,000 live births in developed countries

• As high as 26 per 1,000 in developing countries
• Appproximately 20-30% of infants with HIE (depending
on severity) die in the neonatal period
• 33-50% of survivors are left with permanent
neurodevelopmental abnormalities
 ETIOLOGY

• MATERNAL:
• inadequate oxygenation of maternal blood
• low maternal blood pressure
• inadequate relaxation of the uterus
• premature separation of the placenta
• impedance to the circulation of blood through the umbilical cord
• placental insufficiency
 ETIOLOGY

• FETAL:
• failure of oxygenation
• severe anemia
• Shock
• failure to breathe after birth
PATHOPHYSIOLOGY
 Episode of hypoxia and ischemia

Drop in cellular high-energy

phosphate levels

Anaerobic metabolism

Lactate Inorganic phosphate Glutamate Free radicals Nitric oxide

Activation of NMDA, AMPA and

Kainate receptors

Increase cellular permeability to

sodium and calcium ions

Cytotoxic edema, neuronal and

apoptotic death
 INFLAMMATION
APOPTOSIS
OXIDATIVE INJURY
DECREASE GROWTH FACTORS
IMPAIRED PROTEIN SYNTHESIS
 ADAPTIVE RESPONSE OF THE FETUS
TO ASPHYXIA

• is increased shunting through the ductus venosus, ductus

arteriosus, and foramen ovale
• with transient maintenance of perfusion of the brain,
heart, and adrenals in preference to the lungs (because of
pulmonary vasoconstriction), liver, kidneys, and intestine.
 HYPOXIC-ISCHEMIA OUTSIDE THE CNS

• Early congestion, fluid leak from increased capillary permeability, and endothelial
cell swelling may lead to signs of coagulation necrosis and cell death.
• Congestion and petechiae
• pericardium, pleura, thymus, heart, adrenals, and meninges
• Prolonged intrauterine hypoxia may result in inadequate perfusion of the
periventricular white matter, resulting in PVL
• Pulmonary arteriole smooth muscle hyperplasia
• Subsequent complications, including pulmonary hypertension and
pneumothoraces.
 CLINICAL MANIFESTATIONS

• Intrauterine growth restriction with increased vascular resistance

• During labor, the fetal heart rate slows and beat-to-beat variability declines
(variable or late deceleration pattern)
• At delivery, the presence of meconium-stained amniotic fluid
• At birth, affected infants may be depressed and may fail to breathe
spontaneously; with pallor, cyanosis, apnea, slow heart rate, and
unresponsiveness to stimulation.
 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.
 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)
B. APGAR SCORING SYSTEM
C. 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.

TREATMENT
1. Hypothermia Therapy:
 Selective head or whole body hypothermia of a core temperature of 33.5 Cº applied
within the first 6 hours of birth for 72 hours 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.
5. Reduced vascular permeability, edema, and disruptions of blood-brain barrier
functions.
• High-dose erythropoietin given as an adjunct to therapeutic hypothermia shows some
promise in decreasing MRI indicators of brain injury and short-term motor outcomes.
Olympic Cool Cap System
WHOLE BODY HYPOTHERMIA
Whole Body Hypothermia
 COMPLICATIONS

• Thrombocytopenia (usually without bleeding)

• Reduced heart rate
• Subcutaneous fat necrosis
• Overcooling and cold injury syndrome
2. Aggressive treatment of seizures:

 Phenobarbital, the drug of choice for seizures, is given as IV loading dose

(20 mg/kg); additional doses of 5-10 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) have been preferred for
refractory seizures.
• Currently the use of levetiracetam is preferred (at times even as a first-line agent) as
the most used second-line agent.
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.
 Aggressive treatment of seizures is critical and may necessitate continuous EEG
monitoring

28
 PROGNOSIS

• Infants with initial cord or initial blood pH <6.7 have a 90% risk for
death or severe neurodevelopmental impairment at 18 mo of age.
• infants with Apgar scores of 0-3 at 5 min, high base deficit (>20-25
mmol/L), decerebrate posture, severe basal ganglia/thalamic (BG/T)
lesions, persistence of severe HIE by clinical examination at 72 hr, and
lack of spontaneous activity are also at increased risk for death or
impairment.
PROGNOSIS
B. APGAR SCORING SYSTEM

Death or disability occurs in 76–82% of infants with

APGAR scores of 0-2 at 10 min.
 BRAIN DEATH

• Coma unresponsive to pain, auditory, or visual stimulation

• Apnea with PCO 2 rising from 40 to >60 mm Hg without
ventilatory support
• Absence of brainstem reflexes (pupillary, oculocephalic,
oculovestibular, corneal, gag, sucking)
• All survivors of moderate to severe encephalopathy require
comprehensive high-risk medical and developmental follow-
up. Early identification of neurodevelopmental problems
allows prompt referral for developmental, rehabilitative, and
neurologic early intervention services so that the best possible
outcomes can be achieved.
THANK YOU!!!