Hypoxic Ischemic Encephalopathy - PowerPoint Presentation

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Hypoxic Ischemic Encephalopathy

Rand

Al-shayeb

Selena

Abboud

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Definitions

Hypoxia or Anoxia:

A partial (Hypoxia) or complete (Anoxia) lack of oxygen in the brain or blood.

Hypoxemia:

D

ecreased arterial concentration of Oxygen.

Ischemia:

The reduction or cessation of blood flow to an organ which compromises both oxygen and substrate delivery to tissue.

Asphyxia:

The state in which placental or pulmonary gas exchange is compromised or ceases altogether.

Hypoxic

Ischemic encephalopathy:

An acute

peripartum

or

intrapartum

event leading to

Abnormal neurological behavior in the neonatal period arising as a result of hypoxic ischemic event and The potential for significant mortality and long-term morbidity.

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Incidence OF HIE

Occurs in 2-5 per 1000 live term births in developed countries. (moderate to severe incidence is 1-2/1000 live births)

25% die or have multiple disabilities.

4% have mild to moderate forms of cerebral palsy.

10% have developmental delay.

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Maternal

Cardiac arrest

Asphyxiation

Severe anaphylaxis

Status

epilepticus

Hypovolemic shock

Uteroplacental Placental abruption.Cord prolapse.Uterine rupture. Hyper stimulation with oxytocic agents.Amniotic fluid embolism.

FetalFetomaternal hemorrhage (vasa praevia) Twin to twin transfusion syndromeSevere isoimmune hemolytic anemiaCardiac arrhythmiaIntrauterine growth restriction (IUGR)

Etiology of HIE

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The immature brain is in some ways more resistant to hypoxic-ischemic events compared to older children and

adult: This

may be due to:

Lower cerebral metabolic rate.

Immaturity in the development of the balance of the neurotransmitters.

Plasticity of the immature CNS.

Pathophysiology

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Acute HIE leads

t

o primary and secondary events:

Primary neuronal damage: (Injury - 6

hrs

)

Cytotoxic damage due to failure of microcirculation

 Inhibition of energy-producing molecular processes  ATPas membrane pump failure  cytotoxic edema and free radicles formation  compromised cellular integrity [Reduced cerebral perfusion  hypoxia and hypoglycemia leading to metabolic acidosis , ischemia and neuronal cell death]

[intracellular derangements  increased Intracellular Ca causing edema and cell death. Destruction of protein, membrane lipids and other cellular content leading to neuronal necrosis which can be found hours to days later]Secondary neuronal damage (6 - 72 hrs)May extend up to 72 hours or more after the acute insult and results in an inflammatory response and cell necrosis or apoptosis (fueled by reperfusion), reduced growth factor and impairment in protein synthesis, if untreated leads to sustained brain injury.Pathophysiology

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Gastrointestinal age plays an important role in the susceptibility of CNS structures

< 20 weeks: Insult leads to neuronal

hetrotropia

or

polymicrogyria

26-30 weeks: insult affects white matter, leading to polyventricular leukomalacia

Term: Insult affects primarily the gray matter Pathophysiology

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Pathological correlation of

preterm infant

with hypoxic ischemic encephalopathy

Pathological correlation of

preterm infant

with hypoxic ischemic encephalopathy

Pathology Clinical sign Periventricular leukomalacia Spastic diaplegia Status marmoratus of basal gangliaDystonia,

choreoathetosis

Thalamus

Mental retardation

Cerebral cortex

Mental retardation

Pathological correlation of

full term infant

with hypoxic ischemic encephalopathy

Pathological correlation of

full term infant

with hypoxic ischemic encephalopathy

Pathology

Clinical sign

Parasagittal cortical and subcortical neuronal necrosis

Spastic quadriplegia, especially arms. Intellectual deficits and cortical atrophy, focal seizures and hemiplegia

Cerebellum

Ataxia

Brain Stem

Pseudobulbar

palsy

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CNS factors that influence the distribution of CNS injury

Cellular susceptibility: (neurons most susceptible)

Regional susceptibility: (areas of higher metabolic rate

eg

. Thalamus)

Vascular territories: (watershed areas)

Degree of asphyxia

Pathophysiology

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Clinical staging of HIE

Sarnat

grading scale

Disability

Death

3

0%

10%100%60%Good outcome

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Diagnosis

Intrauterine

G

rowth

restriction and

I

ncreased

vascular resistances may be the 1st manifestation of fetal hypoxia. Intrapartum events Absence of an intrapartum sentinel event does not exclude the diagnosis of HIE.-A significant peripartum or intrapartum

hypoxic-ischaemic event including: Uterine rupture Placental abruption Cord prolapse Amniotic fluid embolism Fetal exsanguination from a vasa praevia or massive feto-maternal hemorrhage

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During labor

Variable or late deceleration pattern of continuous heart rate recording, fetal heart rate slows down, and beat-to-beat variability declines.

Fetal scalp blood analysis may show a pH <7.20.



These signs should lead to the administration of high concentrations of

Oxygen to the mother and

Immediate delivery to avoid fetal death or CNS damage.

At deliveryThe presence of yellow, meconium-stained amniotic fluid is evidence that fetal distress had occurred.

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At

birth

these

infants are

F

requently

depressed and fail to breathe spontaneously. During the ensuing hours, they M

ay remain hypotonic or change from hypotonic to hypertonic, or their tone may appear normal. Pallor, cyanosis, apnea, a slow heart rate, and unresponsiveness to stimulation. LaterCerebral edema may develop during the next 24 hr and result in profound brain stem depression. During this time, seizure activity may occur; it may be severe and refractory to the usual doses of anticonvulsants. In addition to CNS dysfunction, systemic hypoperfusion occurs in 80% of cases including;

Heart failure and cardiogenic shock, hypotension, persistent pulmonary hypertension, respiratory distress syndrome, gastrointestinal perforation, hematuria, and acute tubular or cortical necrosis, subcutaneous fat necrosisAdrenal hemorrhage, inappropriate secretion of antidiuretic hormone, and metabolic derangements, DIC.

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There is no clear diagnostic

test.

Abnormal findings

on

neurological

examination

in the first few days after birth is the most useful predictor that the brain insult has occurred in the perinatal

period.Essential criteria for diagnosis of HIE: Fetal umbilical artery acidaemia: pH less than 7 and/or base excess worse than or equal to minus 12 mmol/L.Apgar score of less than or equal to

5 at 5 and 10 minutes.Examination consistent with mild, moderate or severe encephalopathy.Onset of multisystem organ failure which may include renal injury, hepatic injury, hematologic abnormalities, cardiac dysfunction, metabolic derangements, and gastrointestinal injury.Diagnosis

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APGAR SCORE

The scores are broken down as follows:

1-3 points: Critically low

4-6 points: Below normal

7+ points: Normal APGAR score

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Laboratory studies

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Neuroimaging

Cranial Ultrasound:

not the best in assessing

abnormalities

in term infants,

echogenicity develops gradually over

days.

Convenient, noninvasive, low-cost and non –radiation screening examination of the hemodynamically unstable neonate at the bedside/ preterm infant. Doppler study and resistive index (RI) provide additional information on cerebral perfusion. To rule out hemorrhagic lesions.

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CT:

least sensitive for detecting

changes in

HIE because

of

poor parenchymal contrast resolution

due to:-High

water content in the neonatal brain. -High protein content of the cerebrospinal fluid. To rule out focal hemorrhagic lesions or large arterial ischemic strokes.When MRI is not available or prevented due to clinical disability.Loss of gray white differentiation and injury to basal ganglia is detected in severe HIE

Diffuse cortical swelling and hypoattenuation in the white matter

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MRI:

Most appropriate technique and is able to show different patterns of injury

.

Presence

of

signal abnormality in the internal capsule later in the

first week has a very high predictive value for neurodevelopmental outcome.Ischemic injury generally results in T1 hypointensity &T2 hyperintensity (white matter)due to ischemia induced edema.

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Diffusion weighted sequences obtained in the first 3-5 days following a presumed sentinel event are optimal for identifying acute injury.

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Standard EEG

Generalized

depression of the background rhythm and

voltage

with varying degrees of superimposed

seizures

are early findings.

EEG characteristics associated with abnormal outcomes include:A) Background amplitude of Less than 30 MV. B) Interburst interval of more than 30 seconds.C) Electrographic seizures.

D) Absence of sleep-wake cycle at 48 hours.

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Amplitude-integrated EEG (

aEEG

)

When

performed early, it may reflect dysfunction rather than permanent

injury.

Most useful in infants who have

moderate to severe encephalopathy- Discontinuous tracing characterized by a lower margin below 5 mV and an upper margin above 10 mV Burst suppression pattern characterized by a background with minimum amplitude (0-2 mV) without variability and occasional high voltage bursts (>25 mV)

Continuous low voltage pattern characterized by a continuous low voltage background (< 5 mV) Inactive pattern with no detectable cortical activity Seizures usually seen as an abrupt rise in both the lower and upper marginMarginally abnormal or normal aEEG is very reassuring of good outcome.Severely abnormal aEEG in infant with moderate HIE raises the probability of death or severe disability from 35% to 75%.

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Brainstem auditory

evoked potentials,

visual

evoked potentials and

somatosensory

evoked potentials can be used in

full-term infants with HIE.More sensitive and specific than

aEEG alone.However, not as available as aEEG and there is a lack of experience among neurologists Therefore aEEG is preferred because of easy access, application and interpretation

Evoked Potentials

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Histology

Watershed

infarctions secondary to global

hypoperfusion

.

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Complications

Brain injury

Stroke

Cerebral palsy

Epilepsy, seizures

Severe hearing impairment

Blindness and vision impairment

Problems in learning, thinking and speaking/ cognitive deficitProblems in walking and coordination/ developmental delay

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Management

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Initial Resuscitation and Stabilization

• Delivery room management follows standard Neonatal Resuscitation Program (NRP) guidelines. Pay attention to

appropriate oxygen delivery

,

perfusion

status, and

avoidance of hypoglycemia and hyperthermia

. • Resuscitation with room air versus 100% oxygen in the delivery room. • International Liaison Committee on Resuscitation (ILCOR) recommendations include initiating neonatal resuscitation with concentrations of oxygen between 21-100%

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Supportive Care

• 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. Nitric oxide (NO) may be used according to published guidelines.

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Perfusion and Blood Pressure Management

• A mean blood pressure (BP)

above 35-40 mmHg

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

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Fluid and Electrolytes Management

•

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 dysfunctionIncreased creatine clearance

Increased glomerular filtration rate (GFR)Decreased b2 microglobulin excretion. • Avoid hypoglycemia and hyperglycemia because both may accentuate brain damage.

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Start

CFAM ( Cerebral function analysis monitoring)

Single or 2 channel (right and left hemispheres) machines available

Display raw EEG and a compressed amplitude integrated recording

Pattern of EEG is used for classification of background activity

Normal CFAM (EEG) recording (term infants):

Lower margin <= 5 when awake , upper margin >=10

Evidence of sleep wake cycling , no seizures.

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Treatment of Seizures

• Hypoxic-ischemic encephalopathy is the

most common cause of seizures in the neonatal period.

•

Phenobarbital has been shown to be effective in only 29-50% of cases.

(20mg/kg)

•

Benzodiazepines particularly lorazepam may offer some additional efficacy. (0.1mg/kg)

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Therapeutic hypothermia

(avoid hyperthermia

)

Has

become standard of care.

Cooling is achieved using a temperature controlled mattress or

wrap.

Eligible infants have their core(rectal) temperature lowered to 33-34 C within 6h of insult.Hypothermia is maintained for 72h before re-warming.

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Head cooling is not used anymore

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Hypothermia principles

(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

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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. NPO due to risk of necrotizing enterocolitis because of ischemia.• 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.

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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).

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Further Outpatient Care

•

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. Follow up in the first two years to monitor complications, cooling effectiveness and development.

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Xenon

Gas (inhaled anesthetic), neuroprotective qualities, such as affecting other ion channels and reducing neurotransmitter release in general. Approved and used with cooling.

Erythropiotine

Neuroprotection against apoptosis and anti-inflammatory effect (not approved yet.)

Melatonin

Anti-inflammatory effect (no studies yet)

Stem cell transplant

May increase levels of brain trophic factors and anti-apoptotic factors, decrease inflammation, preserve endogenous tissue, support replacement of damaged cell (no studies yet)New in treatment

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Metabolic Abnormalities

Congenital Abnormalities

Meningitis

Hypoglycaemia

Hyperbilirubinaemia

Chronic Placental Insufficiency

Other Causes Of Seizures/Encephalopathy In Neonates Include Intracranial

Haemorrhage

, Perinatal Stroke, Drug WithdrawalDifferential diagnosis:

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Depends on the

severity

of injury and

gestational age

of the infant

.

Term infants with mild

encephalopathy generally have good prognosis and show complete recovery, 20% of infants may die in the neonatal period and 25% may develop significant neurological deficit.EEG at about 7 days that reveals

normal background activity is a good prognostic sign. Persistent feeding difficulties 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.Prognosis

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Poor predictive variables for death/disability

Low (0-3) 10 minute

apgar

score

Need for CPR in the delivery room

Delayed onset >= 20 minutes of spontaneous breathing

Severe neurological signs (coma,

hypotonia, hypertonia)Seizure onset <= 12 hours or difficult to treatSevere prolonged (7day) EEG findings including burst suppression pattern, Increase lactate on MRS within 24 hours of lifeProminent MRI basal ganglia/ thalamic lesionsAbnormal neurologic exam >= 14 daysOliguria or anuria > 24 hours

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THANK YOU

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