PERINATAL ASPHYXIA – OUTLINE OF

PATHOPHYSIOLOGY AND RECENT

TRENDS IN MANAGEMENT

Prof. A Wasunna
Professor of Neonatal Medicine
And Pediatrics
 PERINATAL ASPHYXIA
 Insult to the fetus / Newborn
 Hypoxia
 Ischemia

 Effect of hypoxia & Ischemia inseparable

 Both contribute to tissue injury

 Definition

Prolonged Hypoxemia and Ischemia in the

Fetus/Newborn resulting in multi organ and
multi system dysfunction
 ESSENTIAL CRITERIA FOR
PERINATAL ASPHYXIA
 Prolonged metabolic or mixed acidemia (pH < 7.00)
on an umbilical cord arterial blood sample
 Persistent Apgar score of 0-3 for > 5 minutes
 Neurological dysfunction manifestations e.g.
seizure, hypotonia, coma or hypoxic-ischaemic
encephalopathy in the immediate neonatal period
 Evidence of multi organ/multi system dysfunction in
the immediate neonatal periods
PERINATAL ASPHYXIA: GLOBAL EPIDEMIOLGY

 Term HI is 3rd leading cause of Global childhood death

 Each year:
 0.7 million affected newborns die
 1.15 million develop acute cerebral dysfunction (NE)
 Neonatal Encepalopathy (NE) 2nd commonest cause of
childhood neurodisability
 PERINATAL
ASPHYXIA:EPIDEMIOLGY

Western Typical
Scenario Devel.Country

Incidence 1 – 1.5 / 1000 10%

Cause of Perinatal death 20% 26%

Still Birth + P. Mort. 50% 59%

 ETIOLOGY

 Intrapartum or Antepartum (90%)

Placental/Cord Insufficiency

 Post partum (10%)

Pulmonary
Cardiovascular
Neurologic Insufficiency
 MECHANISM OF INJURY

Acute HI : O2, Glucose

1° Cell Death ATP

Failure of Na , K Pump

Neuronal Depolarization

Synaptic Cleft Floods With GLUTAMATE

Activates NMDA , AMPA Receptors

CALCIUM Influx Into The Cell

Activates NO Synthase Neurotoxicity/Inflammation Cell Edema

MITOCHONDRIAL DYSRUPTION, RELEASE OF O3, GUTATHIONE

 Latent Period

 During this period, there is abating of cell destruction

 Duration of the period is inversely proportional to the severity of the injury
 Lasts 2 – 8 hours

Reperfusion

Partial of Excitatory Amino Acids and Edema

Damage
 Secondary Energy Failure

 Lasts 6 – 24 Hrs
 Cerebral Metabolism resulting in
 Cytotoxic edema
 Seizures
 Raised cytokine levels
 Mitochondrial failure
 PATHOPHYSIOLOGY
Hypoxia

Diving reflex

Shunting of blood Away from

to brain adrenals lungs, kidney
& heart gut & skin

LITTLE
LITTLE BRAIN/HEART
BRAIN/HEART INJURY
INJURY
 PATHOPHYSIOLOGY
Asphyxia continues

Shunting within the brain

Anterior Posterior
Circulation Circulation
Suffers Maintained

CEREBRAL
CEREBRAL CORTICAL
CORTICAL LESIONS
LESIONS
 PATHOPHYSIOLOGY
 Near total asphyxia
 Cord accidents
 Maternal CP arrest

 Hypoxia – ABRUPT & SEVERE

 No time for compensation

THALAMUS
THALAMUS &
& BRAIN
BRAIN STEM
STEM INJURY,
INJURY, CORTEX
CORTEX SPARED
SPARED
 PATHOLOGY
 Target organs of perinatal asphyxia
 Kidneys 50%
 Brain 28%
 Heart 25%
 Lung 23%
 Liver, Bowel, Bone marrow < 5%
 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
 EFFECT OF O3
O3
DNA strand Lipid Neutrophil accumulation
breakage peroxidation

Release of
Membrane PMN
proteases,
damage plugging of
myeloperoxidase,
capillaries
prostaglandins Phagocytosis
Ischemia
Cell death
Tissue damage
CLINICAL MANIFESTATIONS OF HIE

 Altered consciousness
 Tone problems
 Seizure activity
 Autonomic disturbances
 Abnormalities of peripheral
and stem reflexes
 CLASSIFICATION OF HIE (LEVENE)
Feature Mild Moderate Severe

Consciousness Irritable Lethargy Comatose

Tone Hypotonia Marked Severe

Seizure No Yes Prolonged

Sucking / Resp. Poor Suck Unable to Unable to

suck sustain spont.
Resp.
 Preventing Further Injury

 Maintain adequate perfusion,

oxygenation & ventilation
 Correct & maintain normal metabolic
& acid base milieu
 Prompt management of complications
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
OVERALL CARE PLAN
- Temperature
- Airway
- Breathing
- Circulation
- Fluid
- Medications
- Feed
- Monitoring
- Communication
- Follow up care
SUBSEQUENT MANAGEMENT

 Oxygenation & ventilation

 Adequate perfusion

 Normal glucose & calcium

 Normal hematocrit

 Treat seizure
 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
 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.
 PERFUSION

 Maintain MAP to maintain CBF

 Maintain CVP 5-8mm Hg – Term

3-5mm Hg – Preterm

 Avoid Fluid, Colloid & SBC Boluses

 Replace volume slowly

SUPPORTIVE CARE (RECENT ADVANCES)

 THERAPEUTIC HYPOTHERMIA

 Role of Mannitol, Steriod & Hyperglycemia ??

 Regulatory gene (Regulon)

 Pentoxifylline

 Enhancement of natural defence
- Neurotrophic factor & fibroblast growth factor
 POTENTIAL THERAPEUTIC STRATEGIES
Approach Target Compounds
Blockade of free- Xanthine oxidase Allopurinol; Oxypurinol
radical generation inhibitors
Scavenging of Antioxidant SOD, Catalase,
oxidants after enzymes Glutathione,
generation N-Acetylcysteine
Radical scavengers DMSO, DMTU, 21-
Aminosteroids
Blocking chain -Tocopherol
propagation of
secondary oxidants
Substrate Iron Deferoxamine;
manipulation Calcium calcium blockers
Glucose ?Increase glucose
stores
(Contd…)
 POTENTIAL THERAPEUTIC STRATEGIES
Approach Target Compounds
Blockade of secondary PAF PAF antagonists
metabolites or Phospholipases Phospholipase
inflammatory mediators inhibitors
(quinacrine,
hydrocortisone)
Neutrophils Selection blockers
Reduce activation
Block adhesion
Blockade of coagulation Block platelet PAF receptor blockers
effects adhesion
Inhibition of excitatory Glutamate receptor Magnesium; MK 801
amino acids
Enhancing endogenous (NMDA)
antioxidant capability antagonists
Regulon regulation
 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
 HIE OUTCOME (METAANALYSIS)

Severe Moderate Mild

Risk of Death 61% 5.6% < 1%

Risk of Severe 72% 20% < 1%

disability