1. Hypoxic Ischemic ecephalopathy
By : Dr. Sanjeev

2. HYPOXIC – ISCHEMIC ENCEPHALOPATHY
Damage to cells in the central nervous system (the brain and spinal cord) from inadequate oxygen

3. Pathophysiology
The brain depends on a second by second supply of oxygen and glucose by the blood.
A drop in cerebral perfusion, hypoxia, hypoglycemia, and severe anemia can cause a critical shortage of energy (energy crisis).
In generalized seizures, neurons use up glucose and oxygen faster than they are supplied, and discharge glutamate with the same result.

4. Cont…
The first result of energy depletion is failure of Na+ and K+ pumps, leading to depolarization of the neuronal membrane .
Synaptic function and conductivity cease at this point. Depolarization causes neurons to release glutamate into the synaptic cleft. Glutamate is the most common excitatory neurotransmitter.
In small amounts, it is essential for neuronal function.
In excessive amounts, it is a neuronal poison, a toxin, and has been called excitotoxin.
Some glutamate receptors are non-selective cation-permeable ion channels.

5. Cont…
Initially, over-activation of these channels causes a passive influx of  Cl- (and Na+) into cells causing osmotic (cytotoxic) edema and rapid death.
Additional structural damage develops hours or days later as a result of Ca++ influx into neurons.
The NMDA and AMPA receptors of glutamate are channels that are permeable to Ca++.
Activation of these receptors by excess glutamate causes massive influx of Ca++ into neurons. Ca++ activates catabolic enzymes (proteases, phospholipases, endonucleases). Ca++ also activates NO synthase, resulting in formation of the free radical NO.
--- NMDA = N-methyl-D-aspartate and
--- AMPA = amino-3-hydroxy-5-methyl-4 isoxazole propionate

6. Cont…
Free radicals and activated catabolic enzymes destroy structural proteins, membrane lipids, nucleic acids, and other cellular contents, causing neuronal necrosis.
DNA damage from endonucleases and mitochondrial injury from free radicals trigger apoptosis.
Counteracting the action of glutamate is the basis of neuroprotective strategies .

8. HYPOXIC – ISCHEMIC ENCEPHALOPATHY
The clinical manifestation of the HIE belong to the following five main domains:
Altered consciousness
Tone problems
Seizures activity
Autonomic disturbances
Abnormalities of the reflexes

9. A simple and practical classification of HIE by severity of manifestation provided by Levene is recommended for the routine use is as follows:
Features
Mild
Moderate
Severe
Consciousness
Irritable
Lethargy
Comatosed
Tone
Hypotonia
Marked Hypotonia
Severe Hypotonia
Seizures No
Yes
Prolonged
Suckling / Respiration
Poor suck
Unable to suck
unable to sustain spontaneous respiration

10. Management of HIE Monitoring : Vitals parameters
Accurate record of the urine output
If required blood gases analysis can be done .
Periodic blood biochemistry such as:
blood sugar charting (2 hourly x 2 ,then 4 hrly on the 1st day and 6 hrly thereafter .
Hematocrit – (6 to 8 hrly for the first 2 days ,the once a day)
Serum sodium,potssium and calcium (once a day).
Assessment of the of sensorium,tone,seizures autonomic disturbances and reflexes should be done every 4 to 6 hours

11. Investigation : EEG: Only has prognostic importance.
Cranial ultrasound: hypoechoic area are seen in very severe case having a large area of infraction .
Computed tomography : CT scan in the acute stage of HIE in term babies may show generalized low attenuation of the brain parenchyma.
In general EEG ,US and CT do not help a great deal in the management and is essential in assessing the prognosis .

12. Management of HIE Maintain oxygenation and ventilation
Bag and mask or ET or even artificial ventilation may require.
Maintain adequate perfusion: the marker of normal perfusion are normal BP ,capillary refilling time of less then 3 secs, normal urine output and no metabolic acidosis. BP should be maintained in the upper normal range which can be achieved by the judicious of the volume expander.
Maintain normal blood glucose: requirement of the glucose is high in HIE hence maintain of the blood glucose above 40 mg/dl but not exceeding 100 mg/dl.

13. HYPOXIC – ISCHEMIC ENCEPHALOPATHY
Maintain normal calcium level:
It is provided in the maintenance dose 8ml/kg/day of 10% of the calcium gluconate in continuous infusion or in slow diluted boluses 6 hrly for 1 to 2 days , so as to maintain the serum calcium level.
Maintain normal hematocrit:
Anemia and polycythemia should be corrected. Hematocrit should be in the range of 50 % to 55%.
Treatment of the seizures.

14. HYPOXIC – ISCHEMIC ENCEPHALOPATHY
Other medication are:
Neuro-protectives such as –allopurinol ,oxypurinal (blocks the free radicals generation )
Scavenging of oxidants ---superoxide dismutase, gluthathione,N-acetylcysteine and alpha tocopherol .
Calcium channel blockers such as—flunarizine, nimodipine.
Blockade of inflammatory mediators such as---indomethacin
Use of phenobarbitone at the stage of initial management even before the onset of the seizures associates with the better long term outcome .

15. HYPOXIC – ISCHEMIC ENCEPHALOPATHY
One promising modality is cerebral hypothermia . Mild reduction in the temperature of the body as a whole or of the head has been shown to minimize the effect of the HIE.
It may be noted that none of the modalities mentioned are used routinely.

16. Prognosis of HIE
With mild HIE all survivors have normal long term out come.
Over 80% of neonates with moderate HIE have normal long term out come.
Half of the neonates with severe HIE will die and the survivors have long term out come.

17. The predictors of adverse prognosis
Abnormal cranial ultra sound /CT
Severe / uncontrolled seizures
Time taken to start suckling
Abnormal neurological status at time of discharge.