Perinatal asphyxia-Pathophysiologyical paradox and recent trends in Management-Dr.Rajesh

1. PERINATAL ASPHYXIA –
PATHOPHYSIOLOGYICAL PARADOX AND
RECENT TRENDS IN MANAGEMENT
Dr Rajesh R N

2. Defined as impaired respiratory gas
exchange accompanied by the
development af acidosis

3. PERINATAL ASPHYXIA
Insult to the fetus / Newborn
Lack of oxygen (Hypoxia)
Lack of perfusion (Ischemia)
Effect of hypoxia & Ischemia inseperable
Both contribute to tissue injury

4. ESSENTIAL CRITERIA FOR
PERINATAL ASPHYXIA
Prolonged metabolic or mixed acidemia (pH < 7.00)
on an umbilical cord arterial blood sample
Persistence of an Apgar score of 0-3 for > 5 minutes
Clinical neurological manifestations e.g. seizure,
hypotonia, coma or hypoxic-ischaemic
encephalopathy in the immediate neonatal period
Evidence of multiorgan system dysfunction in the
immediate neonatal periods

5. PERINATAL ASPHYXIA
Western
Scenario
India
(NNF data Base)
Incidence
Cause of Perinatal death
Still Birth + P. Mort.
1 – 1.5 / 1000
20%
50%
10%
26%
59%

6. ETIOLOGY
Intrapartum or Antepartum (90%)
Placental Insufficiency
Post partum (10%)
Pulmonary
Cardiovascular
Neurologic Insufficiency

7. FACTORS
↓ Mat.
Oxygenation
↓ Blood
flow mother
to placenta
↓ Blood flow
placenta to
fetus
↓ Gas Exchange
across placenta
or fetal tissue
↑ Fetal O2 Req.

8. PATHOPHYSIOLOGY
Hypoxia
Diving seal reflex
Shunting of blood
to brain adrenals
& heart
Away from
lungs, kidney
gut & skin
NON BRAIN ORGAN INJURY

9. PATHOPHYSIOLOGY
Asphyxia continues
Shunting within the brain
Anterior
Circulation
Suffers
Posterior
Circulation
Maintained
CEREBRAL CORTICAL LESIONS

10. PATHOPHYSIOLOGY
Near total asphyxia
Cord accidents
Maternal CP arrest
Hypoxia – ABRUPT & SEVERE
No time for compensation
THALAMUS & BRAIN STEM INJURY, CORTEX SPARED

11. PATHOLOGY
Target organs of perinatal asphyxia
Kidneys 50%
Brain 28%
Heart 25%
Lung 23%
Liver, Bowel, Bone marrow < 5%

12. NEUROPATHOLOGICAL CHANGES
Pattern seen in term babies
Selective neuronal necrosis (Spastic CP)
Status Marmoratus (Chorea, Athetoid, Dystonia)
Parasagittal cerebral injury (Prox Spastic Quadriparesis)
Focal and multifocal ischemic brain injury (sp.
Hemiparesis, cognitive defects, seizure)
Pattern predominant in preterm
Periventricular leukomalacia

13. PATHOLOGY
Cerebral O2 ↓
Substrate supply ↓
Synaptic inactivation (Reversible)
Energy failure
Memb. pump failure
Further ↓ in perfusion
At cellular level

14. ISCHEMIA-RELATED GENERATION OF
HYPOXANTHINE
I
S
C
H
E
M
I
A
ATP
↓
↓
AMP
↓
↓
Adenosine
↓
↓
Inosine
↓
↓
Hypoxanthine

15. ISCHEMIA AND REPERFUSION INJURY
Ischemia ATP
depletion
Calcium influx
Phospholipase activation
Arachidonic acid release
Prostaglandins Proteases, lipases
Vasodilation
Microvascular
permeabilityReperfusion
ROS Release

16. MECHANISM
RESUSCITATION ATP ASPHYXIA
HYPOXANTHINE
XANTHINE
URIC ACID
Oxygen
Oxygen free radicals
Oxygen
Oxygen free radicals
BLOCKED
BLOCKED

17. FREE RADICAL
Unpaired
Highly reactive

18. EFFECT OF ROS
ROS
DNA strand
breakage
Lipid
peroxidation
Neutrophil accumulation
Release of
proteases,
myeloperoxidase,
prostaglandins
Tissue damage
Phagocytosis
PMN
plugging of
capillaries
Ischemia
Membrane
damage
Cell death

19. HIE
↑ Glutamate
release
NMDA receptor
Ca Accumulation
In neurones
Neurtoxicity in HIE
Neurotoxic

20. CLINICAL MANIFESTATIONS OF HIE
Altered consciousness
Tone problems
Seizure activity
Autonomic disturbances
Abnormalities of peripheral
and stem reflexes

21. CLASSIFICATION OF HIE (LEVENE)
Mild Moderate
Consciousness
Tone
Seizure
Sucking / Resp.
Irritable
Hypotonia
No
Poor Suck
Lethargy
Marked
Yes
Unable to
suck
Feature Severe
Comatose
Severe
Prolonged
Unable to
sustain spont.
Resp.

22. SPECIFIC MANAGEMENT
PREVENT FURTHER BRAIN DAMAGE
Maintain temperature, perfusion,
oxygenation & ventilation
Correct & maintain normal metabolic
& acid base milieu
Prompt management of complications

23. SUMMARY OF INITIAL MANAGEMENT
Admit in newborn unit
Maintenance of temp
Check vital signs
Check hematocrit, sugar, ABG, electrolyte
I.V line
Consider vol. expander
Vit K, stomach wash, urine vol

24. TABCFMFMCF
T - Temperature
A - Airway
B - Breathing
C - Circulation
F - Fluid
M - Medications
F - Feed
M - Monitoring
C - Communication
F - Followup
SUPPORTIVE CARE

25. SUBSEQUENT MANAGEMENT
Oxygenation & ventilation
Adequate perfusion
Normal glucose & calcium
Normal hematocrit
Treat seizure

26. TREATMENT OF SEIZURES
Correction of hypoglycemia, hypocalcemia &
electrolyte
Prophylactic Phenobarbitone ?
Therapeutic Phenobarbitone
20 mg / kg (loading), 5 mg / kg / d (maintenance)
Lorazepam – 0.05 – 0.1 mg / kg
Diazepam to be avoided

27. CEREBRAL OEDEMA
Avoid fluid overload (SIADH, ATN)
30° Head raise
Maintain PaCo2 25-30mm Hg in ventilated
infants
Mannitol 20% (0.5 - 1g / kg) 6 hrly. x 24 hrs.
Frusemide 1.0 mg / kg every 12 hrs.

28. PERFUSION
CFT deranged
Maintain MAP to maintain CBF
Maintain CVP 5-8mm Hg – Term
3-5mm Hg – Preterm
Avoid Fluid, Colloid & SBC Boluses
Replace volume slowly

29. SUPPORTIVE CARE (RECENT ADVANCES)
Role of Mannitol, Steriod & Hyperglycemia ??
Regulatory gene (Regulon)
Hypothermia
Pentoxifylline
Enhancement of natural defence
- Neurotrophic factor & fibroblast growth factor

30. POTENTIAL THERAPEUTIC STRATEGIES
Target Compounds
Blockade of free-
radical generation
Scavenging of
oxidants after
generation
Blocking chain
propagation of
secondary oxidants
Substrate
manipulation
Xanthine oxidase
inhibitors
Antioxidant
enzymes
Radical scavengers
Iron
Calcium
Glucose
Allopurinol; Oxypurinol
SOD, Catalase,
Glutathione,
N-Acetylcysteine
DMSO, DMTU, 21-
Aminosteroids
α-Tocopherol
Deferoxamine;
calcium blockers
?Increase glucose
stores
Approach
(Contd…)

31. Blockade of secondary
metabolites or
inflammatory mediators
Blockade of coagulation
effects
Inhibition of excitatory
amino acids
Enhancing endogenous
antioxidant capability
PAF
Phospholipases
Neutrophils
Block platelet
adhesion
Glutamate receptor
(NMDA)
antagonists
Regulon regulation
PAF antagonists
Phospholipase
inhibitors
(quinacrine,
hydrocortisone)
Selection blockers
Reduce activation
Block adhesion
PAF receptor blockers
Magnesium; MK 801
POTENTIAL THERAPEUTIC STRATEGIES
Target CompoundsApproach

32. PREDICTORS OF POOR
NEURO DEVELOPMENTAL OUTCOME
Failure to establish respiration by 5 minutes
Apgar 3 or less in 5 mts
Onset of Seizure in 12 hrs
Refractory convulsion
Stage III HIE
Inability to establish oral feed by 1 wk
Abnormal EEG & failure to normalise by 7
days of life
Abnormal CT, MRI, MR spectroscopy in
neonatal period

33. HIE OUTCOME (METAANALYSIS)
Severe Moderate
Risk of Death
Risk of Severe
disability
61%
72%
5.6%
20%
Mild
< 1%
< 1%

34. FUTURE DIRECTIONS
No single magic bullet agent
Multitier combination therapies

36. & THE FINAL R…
Thank you
RELAX