2. Contents
• Why choose this SSC?
•What is Birth Asphyxia and HIE?
•Prognosis
•Treatment and Management
• Conservative & Supportive
• New therapies:
-Hypothermia
-Chemical Therapy
-Cellular Therapy
• Evidence Based Medicine?
•Disability, Disadvantage and Diversity
•Ethics, Law and Medicine
•References
3. What is Birth
Asphyxia and HIE?
Birth Asphyxia: The result of a critical reduction in O2 delivery
to the fetus either antenatally, during labour and/or delivery
that is sufficient to produce a lactic acidosis and render the
infant in distress at birth.
Hypoxic-Ischaemic Encephalopathy (HIE) describes the
clinical manifestation of brain injury starting immediately or
up to 48hrs post-asphyxia.
4. Pattern of Injury in
HIE
Miller et. al, (2005) Journal of Paediatrics
10. 1. Hypothermia
Reduced Oxygen Supply
Cellular Hypoxia
Primary Energy Failure Primary Neuronal Death
Resuscitation
Pseudo-normal period
Secondary Energy Failure
Encephalopathy
Delayed Neuronal Death
Seizures
11. 1. Hypothermia
Mechanism
• Modifies cells programmed for apoptosis
• Reduces cerebral metabolic rate, therefore production of toxic NO
and Free Radicals.
Who is treated?
• Neonates with an abnormal aEEG- fairly predictive
What happens?
• Aims to lower basal ganglia temperature 32-34°c
• Whole body or Just head
Disadvantages
• Little benefit if severe brain damage
• Not yet trialled in pre-term infants
14. 2. Chemical Therapy
Reduced Oxygen Supply
Cellular Hypoxia
Primary Energy Failure Primary Neuronal Death
Resuscitation
Pseudo-normal period
Secondary Energy Failure
Encephalopathy
Delayed Neuronal Death
Seizures
15. 2. Chemical Therapy
Agents that inhibit glutamate release, uptake, or blockage of
glutamate receptors
Blockade of free radical generation or removal- free radical
inhibitor
Blockade of downstream effects and inhibitors of inflammatory
effects
Magnesium Xenon
Deferoxamine Allupurinol
Indomethacin
Erythropoetin
16. 3. Cellular Therapy
Stem cells that may help repair ischaemic neuronal tissue
• Neural Stem cells
• Multi-potent adult progenitor stem cells
• Mesenchymal Stem cells (MSCs)
• Human Umbilical Cord Stem Cells
MSCs can differentiate into neurones and oligodendrocytes,
therefore help repair ischaemic neural tissue.
May also help with restoration of functional networks via
axonal sprouting and synaptogenesis.
17. 3. Cellular Therapy
• 9 day old mice
• HIE artificially induced with R common carotid artery
occlusion.
• MSCs injected into mice: 1st dose 3d, 2nd dose 10d.
Velthoven et al. 2010 Journal of Neuroscience
Diagnosis of HIE only made if:
Evidence of hypoxia antenatally eg. Antepartum haemorrhage
- during labour (eg. Cord prolapse)
- Delivery (eg. Shoulder dystocia)
- Resucitation needed
- Fatures of encephalopathy
Hypoxic damage to organs (eg. Liver, kidney, heart)
No other post-natal/antenatal cause identified
Characteristic neuroimigery findings
Neonatal encephalopathy is a clinical syndrome of “disturbed neurological function in the earliest days of life in the term infant, manifested by difficulty with initiating and maintaining respiration, depression of tone and reflexes, subnormal level of consciousness, and often seizures.
Extent of injury is dependent on severity and temporal characteristics of the insult.
Final pattern of injury also depends on the gestational age of the infant when the injury occurs
Severe prolonged hypoxia
Diffuse neuronal injury
Moderate- severe, relatively prolonged
Deep cortical grey matter structures affeted eg. Basal ganglia and thalamus
Severe, abrupt
Deep nuclear brain-stem injuries.
“watershed injury”- another common pattern of injury- parasaggital end artery regions of 3 major cerebral arteries.
MRI scan of brain – term infant
Left normal scan. Grey basal ganglia and white signal fro myelin in posterior limb of internal capsule.
Right- HIE- abnormal signal in basal ganglia and thalami (shown by arrows)- absence of signal in the internal capsule bilaterally
Picture: Brain damage from severe birth asphyxia at term following a sudden, severe antepartum haemorrhage caused this child to become microcephalic, blind and deaf and to have spastic quadriplegia.
Mild: may also have ‘stary eyes’
Moderate: if they make a full clinical neurological recovery and feeding within 7 days, generally excellent prognosis.
- > 10 days persistence, full recovery unlikely
Severe: Poor prognosis: 80% neurodevelopmental problems.
Secondary energy failure:
Hyperaemia
- Cytotoxic oedeme
- Mitochondrial failure
- Accumulatuib if excitotoxins
Apoptosis
No synthesis
Free radical damage
Resucitation: In the delivery room- oxygen- room air rather than 100% o2 due to potential deleteirous effects of oxygen during primary pahse.
Correct any metaboloic acidosis. Avoid hyper or hypo capnia.
RESTORE CONDITIONS THAT DELAY RECOVERY FROM PRIMARY PHASE OF BRAIN INJURY- hypoxia, hypoglycaemia, hypotension.
Respiratory ensure adequate ventilation- changes in PCO2 can affect cerebral blood flow. Hypocapnia- vasoconstriction therefore compromised o2 supply
Seizre: phenobarbital, phosphenytoin, lorazepam
CAI EEG: Cerebral Function Monitoring – confirm early encephalopathy
onitors general neurological status
Monitors and records frequency and intensity of seizures to assist in the management of anticonvulsive therapy
Assists in identifying need for full EEG
Assists in identifying and predicting outcome from hypoxic-ischemic encephalopathy (HIE)
Hypotension: Most commonly related to LV dysfunction following hypoxic-ischaemic injury and endothelial damage therefore give inotropes such as dobutamine. May be hypovolaemic due to placental abruption therefore give fluids.
Fluid restriction: Potential renal injury
U&E- SIADH and cerebral oedema common. Also due to kidney injury may have derranged u&ess
Secondary energy failure:
Hyperaemia
- Cytotoxic oedeme
- Mitochondrial failure
- Accumulatuib if excitotoxins
Apoptosis
No synthesis
Free radical damage
Published by group in New York- Summary of clinical trials on x- axis
Baby receiving hypotherimic treatment via cooling cap.
Target different steps in the cacade and pathways leading to neuronal cell death
Categorised based on mechanism of action/effect
Mag and Xenon- NMDA inhibitors (xenon- also an anaesthetic!)
Free radical inhibitors- block reaction in production of xanthine
Improved sensory motor function, and reduced lesion size- motor: time spent on rotaroad, forepaw initiation differnece- sensory function
VEH- = vehicle ie. placebo.
In the netherlands- applicable in clinical setting treatment in 4years...