ppt

1. PERINATAL ASPHYXIA
Dejene L

2. Introduction
• Hypoxemia refers to decreased arterial
concentration of oxygen.
• Hypoxia refers to a decreased oxygenation to
cells or organs.
• Ischemia refers to blood flow to cells or
organs that is insufficient to maintain their
normal function.
• Asphyxia - refers to progressive hypoxia,
hypercarbia and acidosis.

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

4. ETIOLOGY
• Incidence-1-1.5% of all deliveries and inversely
related to GA.
• Asphyxia can occur before, during, or after birth.
• Intrapartum or Antepartum (90%)
– Placental Insufficiency
• Post partum (10%)
– Pulmonary
– Cardiovascular
– Neurologic Insufficiency

5. Etiologic factors

6. Etiologic/risk factors
o Antepartum conditions
– Abnormal maternal oxygenation (eg, severe anemia, cardiopulmonary
disease)
– Inadequate placental perfusion and/or gas exchange (eg, maternal
HTN or severe hypotension, placental insufficiency caused by vascular
disease)
– Congenital infection or anomalies
o Intrapartum events
– Interruption of umbilical circulation (eg, true knot, cord prolapse)
– Traumatic delivery (eg, shoulder dystocia, difficult breech extraction)
– Inadequate placental perfusion and/or gas exchange (eg, placental
abruption, uterine rupture, severe maternal hypotension,)
– Abnormal maternal oxygenation (eg, pulmonary edema)
o Postnatal disorders
– Persistent pulmonary hypertension of the newborn
– Severe circulatory insufficiency (eg, acute blood loss, septic shock)
– Congenital heart disease

7. Pathology
• Target organs of perinatal asphyxia
– Kidneys 50%
– Brain 28%
– Heart 25%
– Lung 23%
– Liver, Bowel, Bone marrow < 5%

8. MULTIORGAN SYSTEMIC EFFECTS OF
ASPHYXIA

9. PATHOPHYSIOLOGY of PNA

10. PATHOPHYSIOLOGY…

11. Effects of Hypoxia-Ischemia on Carbohydrate
and
Energy Metabolism-Anaerobic Glycolysis
•  Brain Glycogen
•  Lactate production
•  Phosphocreatine
•  Brain Glucose
•  ATP
• Tissue acidosis

12. Adenosine Triphosphate (ATP)
• Critical regulator of cell function because of its role in
energy transformation.
• One major function is to preserve ionic gradients
across plasma and intracellular membranes, i.e., Na , K
, Ca 
• Ionic pumping utilizes 50-60% of total cellular
expenditure.

14. Deleterious Effects of Calcium in
Hypoxia-Ischemia
• Activates phospholipases →membrane injury
• Activates proteases →cytoskeleton degraded
• Activates nucleases →DNA breakdown
• Uncouples oxidative phosphorylation → ATP
• neurotransmitter release i.e. glutamate
• Activates NOS→generates nitric oxide

15. Additional Mediators of Cell Death During and
Following Hypoxia-Ischemia (HI)
Free radicals
– highly reactive compounds
– can react with certain cellular constituents e.g.
membrane lipids generating more radicals and thus a
chain reaction with irreversible biochemical injury.
Glutamate
– Excitatory amino acid acts on NMDA receptors to
facilitate intracellular Ca++ entry & delayed cell
death
– Glutamate accumulates during HI in part because of 
reuptake that requires ATP

16. Pathophysiology of HIE
Early compensatory adjustments
– Hypoxia and hypercapnia
– Increase in the CBF
– Increase cardiac output
– BP increase
As Early compensatory adjustments fail
– BP falls
– CBF falls below critical levels
– Brain suffers from diminished blood supply
– Lack of sufficient oxygen to meet its needs.

17. Pathophysiology…
During the early phases of brain injury, brain
temperature drops
• Local release of neurotransmitters, such as (GABA)
increase.
• Reduce cerebral oxygen demand, transiently
minimizing the impact of asphyxia.
The magnitude of the final neuronal damage depends
 Initial insult
 Damage due to energy failure
 Reperfusion injury
 Apoptosis

18. Pathophysiology of HIE

20. Mechanisms of Reperfusion
Injury
• The mechanisms of secondary energy failure likely secondary
to extended reactions from the primary insults e.g. calcium
influx, excitatory neurotoxicity, free radicals and nitric oxide
formation adversely alters mitochondrial function.
• Recent evidence suggests that circulatory and endogenous
inflammatory cells/mediators also contribute to the ongoing
injury.
• These processes result in apoptotic cell death.

21. Clinical manifestations
• IUGR with increased vascular resistance may be the
1st indication of fetal hypoxia.
• During labor, the fetal heart rate slows and beat-to-
beat variability declines.
• At delivery, the presence of MSAF is evident that
fetal distress has occurred.
• At birth, affected infants may be depressed and
may fail to breathe spontaneously.

22. Clinical …
• Pallor, cyanosis, apnea, a slow heart rate, and
unresponsiveness to stimulation are also signs of HIE.
• Cerebral edema may develop during the next 24 hr and result
in profound brainstem depression.
• seizure may occur; it may be severe and refractory to
treatment.
• seizures in asphyxiated newborns may due to
– HIE,
– hypocalcemia,
– hypoglycemia, or
– infection

23. Clinical…
• The severity of neonatal encephalopathy depends on the
duration and timing of injury.
• Symptoms develop over a series of days, making it important
to perform serial neurologic examinations .
• In addition to CNS dysfunction, heart failure and cardiogenic
shock, PPHN, RDS, GI perforation, hematuria, and ATN.

24. Staging of HIE (Sarnat stage}

25. TOPOGRAPHY OF BRAIN INJURY IN TERM
INFANTS WITH HIE AND CLINICAL CORRELATES

26. 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

27. Important investigations
CBC
Serum electrolytes
 In severe cases, daily assessment of serum
electrolytes are valuable
Renal function studies
Cardiac and liver enzymes
Coagulation profiles
ABG

28. Important inv…
MRI
CT scan
>>Cerebral edema
>>Ventricular hemorrhage
Echocardiography
>>Myocardial contractility
>>Structural heart defects
EEG

29. Management
• Adequate resuscitation in delivery room is
very important.
• Oxygenation and ventilation
• Optimal fluid, electrolyte and nutritional
management.
• Aggressive treatment and control of seizure
• Avoid hyperthermia in those patients.

30. Management
• Hypothermia Treatment
– Mild hypothermia 3-4°C below the baseline temp
Mechanism of action
– Reduce metabolic rate
– Energy depletion
– Decreased excitatory transmitter release
– Reduced alterations in ion flux
– Reduced apoptosis due to hypoxic - ischemic
encephalopathy
– Reduced vascular permeability, edema, and
disruptions of blood - brain barrier functions.

31. Management…
• Hypothermia Treatment…
Timing of initiation of hypothermia therapy:
 Cooling must begin early, within 1 hour of
injury
• Favorable outcome may be possible if the
cooling begins within 6 hours after injury
• The greater the severity of the initial injury,
the longer the duration of hypothermia
needed for optimal neuroprotection

32. Management…
• Hypothermia Treatment…
Selective head cooling
• CoolCap (Acap) with channels for circulating cold water
is placed over the infant's head, and a pumping device
facilitates continuous circulation of cold water.
• Nasopharyngeal or rectal temp is then maintained at
34-35 °C for 72 hours
Whole body cooling
• Infant is placed on a commercially available cooling
blanket, through which circulating cold water flows, so
that the desired level of hypothermia is reached
quickly and maintained for 72 hours

34. Prognosis
• varies depending on the severity of the insult
and the treatment.
Patients with increased risk of death/severe
neuro developmental impairment:-
– initial cord or initial blood pH <6.7.
– Apgar scores of 0-3 at 5 min.
– decerebrate posture, and lack of spontaneous
activity .

35. Prognosis..
severe encephalopathy (stagell/lll) cxzed by
flaccid coma, apnea, absence of oculocephalic
reflexes,
refractory seizures.(Mortality risk is highest
for seizures that begin within 12 hrs of birth )
A low Apgar score at 20 min &absence of
spontaneous respirations at 20 min of age.
persistence of abnormal neurologic signs on
EEG at 2 wk of age.

36. Prognosis…
• The overall mortality rate is 10% to 30%.
• The frequency of neurodevelopmental sequelae
in surviving infants is approximately 15% to 45%.
• The risk of CP in survivors of perinatal asphyxia is
5% to 10% .
• Outcome based on HIE staging
• Stage l:- almost 100% complete recovery
• Stage ll:-variable (50% recovery,20% death and
30% with disability)
• Stage lll:-80% death & all the rest have CNS
sequelae.

37. Predictors of outcomes of neonates
diagnosed with HIE
• <23: no death or
moderate/severe
disability even
without
hypothermia;
• 23-28: probable
benefit from
hypothermia;
• 29-52: possible
benefit;
• >52: death/disability
likely despite
hypothermia