HYPOXIC ISCHEMIC ENCEPHALOPATHY

DR. MANSOOR ELAHI

It is the term used to designate the clinical andneuropathological findings of an encephalopathy that occurs in a full term infant who has experienced a significant episode of intrapartum asphyxia.

DEFINITION

Etiology of HIE

• Maternal:– Cardiac arrest

– Asphyxiation

– Severe anaphylaxis

– Status epilepticus

– Hypovolemic shock

• Uteroplacental:– Placental abruption

– Cord prolapse

– Uterine rupture

– Hyperstimulation with oxytocic agents

• Fetal:– Fetomaternal hemorrhage

– Twin to twin transfusion

– Severe isoimmune hemolytic disease

– Cardiac arrhythmia

• Fifteen to 20% of infants with hypoxic-ischemic encephalopathy (HIE) die in the neonatal period, and 25–30% of survivors are left with permanent neurodevelopmental abnormalities (cerebral palsy, mental retardation)

FETAL HYPOXIA CAUSED BY VARIOUS DISORDERS IN MOTHER

(1) inadequate oxygenation of maternal blood from hypoventilation during anesthesia, cyanotic heart disease, respiratory failure, or carbon monoxide poisoning;

(2) low maternal blood pressure from acute blood loss, spinal anesthesia, or compression of the vena cava and aorta by the gravid uterus;

(3) inadequate relaxation of the uterus to permit placental filling as a result of uterine tetany caused by the administration of excessive oxytocin;

(4) premature separation of the placenta;

(5) impedance to the circulation of blood through the umbilical cord as a result of compression or knotting of the cord; and

(6) placental insufficiency from toxemia or postmaturity.

SIGNS STAGE 1 STAGE 2 STAGE 3

Level of consciousness Hyperalert Lethargic Stuporous, coma

Muscle tone Normal Hypotonic Flaccid

Posture Normal Flexion Decerebrate

Tendon reflexes/clonus Hyperactive Hyperactive Absent

Myoclonus Present Present Absent

Moro reflex Strong Weak Absent

Pupils Mydriasis Miosis Unequal, poor light reflex

Seizures None Common Decerebration

EEG Normal Low voltage changing to seizure activity

Burst suppression to isoelectric

Duration <24 hr if progresses; otherwise, may remain normal

24 hr to 14 days Days to weeks

Outcome Good Variable Death, severe deficits

Hypoxic-Ischemic Encephalopathy in Term Infants

SARNAT AND SARNAT STAGING

Due to ischemia, anaerobic metabolism, lactate &

inorg.phosphates accumulate

Excitatory and toxic amino acids, particularly

glutamate, accumulate in the damaged tissue

ATP, failure of NaK ATPasepump, depolarization of

neuronal cells, influx of Ca, Na& osmotic influx of water

Ca by activating xanthineoxidase, N2O,PGs release

free radicals

Ca activates proteases & lipases which generates

02 free radicals

Damage to cell membranes &

infarction

Diving sea reflex-Redistribution of blood to

more vital organs

Potential pathways for brain injury after hypoxia-ischemia.

SYSTEM EFFECT

Central nervous system Hypoxic-ischemic encephalopathy, infarction, intracranial hemorrhage, seizures, cerebral edema, hypotonia, hypertonia

Cardiovascular Myocardial ischemia, poor contractility, cardiac stun, tricuspid insufficiency, hypotension

Pulmonary Pulmonary hypertension, pulmonary hemorrhage, respiratory distress syndrome

Renal Acute tubular or cortical necrosis

Adrenal Adrenal hemorrhage

Gastrointestinal Perforation, ulceration with hemorrhage, necrosis

Metabolic Inappropriate secretion of antidiuretic hormone, hyponatremia, hypoglycemia, hypocalcemia, myoglobinuria

Integument Subcutaneous fat necrosis

Hematology Disseminated intravascular coagulation

MULTIORGAN SYSTEMIC EFFECTS OF ASPHYXIA

What is the diagnosis ?

Diagnosis

• There is no clear diagnostic test for HIE

• Abnormal findings on the neurologic exam in the first few days after birth is the single most useful predictor that brain insult has occurred in the perinatal period

• Essential Criteria for Diagnosis of HIE:– Metabolic acidosis (cord pH <7 or base deficit of >12)

– Early onset of encephalopathy

– Multisystem organ dysfunction

INVESTIGATIONS

• Exclude other causes of acute resp. distress

• Chest X ray- to exclude pneumothorax, CDH, Congenital pneumonia

• Sepsis screening and bl. Culture

• Serum electrolytes

Hyponatremia – SIADH

Hyperkalemia – acute renal shutdown/ tissue catbolism

Hyperphosphatemia, hypocalcemia – tissue injuryBUN & CREATININE, LACTATE, PYRUVATE, BRAIN SPECIFIC CREATINE KINASE, HYPOXANTHINE, NON-ESTERIFIED FFA

• 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• Marginally abnormal or normal aEEG is very reassuring of

good outcome

• Severely abnormal aEEG in infants with moderate HIE raises the probability of death or severe disability from 25% to 75%

• CRANIAL ULTRASOUND

On 2, 7,21 days & before discharge to ruleoutIVH. It shows echogenic focus head of caudate or caudothalamic notch.

CT SCAN after 2 wks to prevent radiation damage.

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

MANAGEMENT

• TABC• IV fluids – first 48hrs 10% dextrose to prevent

hypoglycemia• Maintain 2/3 rd of fluid to prevent SIADH• Ca gluconate 2ml/kg for 2 days• 7.5% NaHCo3, 2-3ml/kg diluted with equal vol. of

distilled water or 5%D• Hypotension by inotropes like dopamine, dobutamine• Avoid mannitol- worsen due to endothelial damage in

HIE.• Prophylactic Phenobarbitone to combat seizures.

Criteria for Hypothermia

• Hypothermia is not effective for every baby– Currently only used in infants > 35 weeks

• Time interval between birth and initiation of treatment important– Treatment must be started within 6 hours of birth to be

effective

COOL CAP

Hypothermia - Mechanism of Action

• Reduces cerebral metabolism, prevents edema• Decreases energy utilization• Reduces/suppresses cytotoxic amino acid accumulation

and nitric oxide• Inhibits platelet-activating factor, inflammatory cascade• Suppresses free radical activity• Attenuates secondary neuronal damage• Inhibits cell death• Reduces extent of brain damage

– DEATH OR SEVERE DISABILITY AT 18 MONTHS OF AGE SIGNIFICANTLY REDUCED!!

– Brain cooling DONE UPTO 72hrs.

CONTRAINDICATIONS TO COOLING

· Infants likely to require surgery during first three days after birth

· Other abnormalities indicative of poor long term outcome are presente.g. structural anomalies

· Appears moribund

Newer Treatment modalities:

• Brain death after neonatal HIE is diagnosed by the clinical findings of coma unresponsive to pain, auditory, or visual stimulation; apneawith Pco2 rising from 40 to over 60 mm Hg without ventilatory support; and absent brainstem reflexes (pupil, oculocephalic, oculovestibular, corneal, gag, sucking). These findings must occur in the absence of hypothermia, hypotension, and elevated levels of depressant drugs (phenobarbital).