Perinatal asphyxia

1. Perinatal Asphyxia – Pathophysiology &
Recent Trends In Management
Dr. S.K.Verma
Consultant pediatrician
Mannat Nursing Home Pvt. Ltd.
Sitamarhi

2. Perinatal Asphyxia
Definition - A condition of impaired gas
exchange that leads , if persistent, to fetal
hypoxemia and hypercarbia. It occurs
during the first and second stage of labor
and is identified by fetal acidosis , as
measured in umbilical arterial blood ( PH <
7)

3. PERINATAL ASPHYXIA
Insult to the fetus / Newborn
Lack of oxygen (Hypoxia)
Lack of perfusion (Ischemia)
Impaired gas exchange
Hypoxemia and hypercarbia ( fetal acidosis PH < 7)
Both contribute to tissue injury

4. Pathophysiology cont-
Cellular level
Hypoxia and ischemia -----Cerebral O2 ↓
Failure of oxidative phosphorylation & ATP production
Accumulation of Na, Cl, Ca intracellular
Accumulation of K & excitatory neurotransmitters
(Glutamate ) Extracellular
Neuronal Death

5. Immediate neuronal death-
Due to intracellular osmotic overload of Na & Ca
Delayed neuronal death –
.Uncontrolled activation of enzymes and 2nd
messenger
system in cell
. Generation of free radicals & leukotriens
. Generation of NO
. Depletion of Energy stores
Reperfusion- Previously ischemic tissues
formation of excess reactive Oxygen sp.( superoxide,
hydrogen peroxide, hydroxyl & singlet oxygen ) leading
( Apparent transient improvement after 12 hrs and deteriorate further
on 2 and 3 rd days due to re perfusion injury )

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

7. ESSENTIAL CRITERIA FOR
PERINATAL ASPHYXIA
Prolonged acidemia (pH < 7.00) on an umbilical cord arterial blood sample
Persistence of Apgar score of 0-3 for > 5 minutes
Fetal HR < 60 Beats / min
Seizures within 24 to 48 hours after birth ( 50 % of seizures are not asphyxia )
Need for Positive pressure ventilation for > 1 min
First cry delayed > 5 min
Burst suppression pattern in EEG
Evidence of multiorgan system dysfunction in the immediate neonatal periods

8. PERINATAL ASPHYXIA
Western
Scenario
India
(NNF data Base)
Incidence
Cause of Perinatal death
1 – 1.5 / 1000
20%
10%
26%

9. ETIOLOGY
Intrapartum or Antepartum (90%)
Impaired gas exchange across
Placenta
Post partum (10%)
Pulmonary
Cardiovascular
Neurologic Insufficiency

10. FACTORS increases risk of PA
1.↓ Mat.
Oxygenation
2.↓ Blood
flow from
mother to
placenta
3.↓ Blood
flow from
placenta to
fetus
4.↓ Gas
Exchange
across placenta
or fetal tissue
5.↑ Fetal O2
Req.

11. Factors
Maternal
Hypertension- ( Acute & chronic )
Hypotension
Diabetes
intrauterine Infections
Anemia, malnutrition
Hypoxia- pulmonary / cardio vascular disease
Bronchial asthma
Prolonged and difficult 2 nd stage of labor

12. Fetal factors
Anemia
intra uterine infections
Cardiomyopathy
Severe cardiac insufficiency
hydrops fetalis
Meconium aspiration
cong. Malformation- choanal atresia , Diaphragmatic hernia
Neonatal factors
cyanotic CHD
PPHN of newborn
Placental: infarction/fibrosis/abruption/ hydrops
Chord accidents: Prolapse/true
knot/compression/ entanglement

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

14. PATHOPHYSIOLOGY
Asphyxia continues ( prolonged asphyxia )
Shunting within the brain
Anterior
Circulation
Suffers
Posterior
Circulation
Maintained
CEREBRAL CORTICAL LESIONS

15. PATHOLOGY
Target organs of perinatal asphyxia
Kidneys ( MC ) 50%
Brain ( 2 nd mc) 28%
Heart 25%
Lung 23%
Liver, Bowel, Bone marrow < 5%

16. NEUROPATHOLOGICAL CHANGES
Pattern seen in term babies
Parasaggital area ( watershed zone – mostly suffered )
Diffuse hypo density in parieto - occipital region
bilaterally (white matter injury )
Pattern predominant in preterm
Periventricular area ( watershed zone ) – focal or
multifocal cortical necrosis
Cystic lesion called as Periventricular leucomalacia

17. CLINICAL SPECTRUM OF HIE
Based on Sarnat & Sarnat stages
Abnormal neurobehavioral state in which
impaired cerebral blood flow is main pathological
mechanism
Altered consciousness
Tone problems
Seizure activity
Autonomic disturbances
Abnormalities of peripheral and
stem reflexes

18. APGAR SCORE
Appearance,Pulse,Grimace,Activity,Respiration
0 1 2
Heart rate absent < 100 > 100
Respiration absent slow, irregular Good ,crying
Reflex stimulation No response grimace Cry, cough
Color Blue or pale Body – pink, limb-
blue
All pink
Muscle Tone flaccid Some flexion of
extremity
active

19. APGAR SCORE
Assessment
7 or more ---- Normal
4-6 ---- moderately low
0-3 ---- very low

20. Sarnat & Sarnat stages of HIE
FEATURE STAGE 1
MILD
STAGE 2
MODERATE
STAGE 3
SEVERE
1 Level of
consciousness
Hyper alert
irritable
Lethargic
obtunded
Stuperous
Comatose
2. Neuromuscular
control
Muscle tone Normal Hypo Flaccid
Posture N flexion decerebration
Reflex increased increased absent
3. MORO strong weak absent
SUCKING weak Weak/ absent absent

21. SARNAT Cont.---
4. Autonomic sympath Parasymp Both depressed
Bronchial/ salivary sparse profuse variable
PUPIL mydriasis miosis midposition
RESP spontan sponta Periodic / apnea
HR tachycardia Bradycardia Variable
5. Seizure None Common Uncommon
6. EEG Normal abnormal Abnormal

22. Sarnat cont.---
7. DURATION < 24 hr 2 days – 14 days Days-weeks
8. OUTCOME Good
98-100 %
NORMAL
< 1 % mortality
Variable
80 % normal,20-
37 % die OR
Abnormal if
symptoms > 5
days
About 50-89 %
death
Remainder with
severe sequel

23. Laboratory evaluations of effects of asphyxia
CBC, CRP, LFT
Metabolic- Blood sugar, S. Electrolytes
Cardiac evaluation -*Cardiac troponin I & cardiac troponin T- marker
of myocardial injury
*Serum creatine kinase myocardial bound CK-MB elevated
Brain injury- Serum CK-BB plus low chord blood arterial PH
Renal evaluation- Blood urea nitrogen & serum creatinine raised
Cranial imaging
1. cranial USG- less useful
2. CT Scan-
3. MRI T1 & T2 Weighted – best modality for edema, midline
shift, cortical or post. Fossa hemorrhage & ventricular
compression
EEG- Amplitude integrated EEG To evaluate for seizure and
background pattern

24. Perinatal management of high risk pregnancy
Fetal HR/ rhythm abnormalities may provides
supporting evidence of asphyxia especially if
accompanied by + ce of thick Meconium.
Measurement of Fetal scalp PH / Blood lactate
Monitoring of progress of labor with awareness of
other sign of in utero stress.

25. SPECIFIC MANAGEMENT
PREVENT FURTHER BRAIN DAMAGE
Ventilation – maintain co2, Positive pressure ventilation
Oxygenation- hypoxemia should be treated with o2 supplementation
Temperature-
Perfusion – cardiovascular stability is maintained for adequate cerebral
perfusion pressure
If CRT >3 sec – IV bolus NS 10 ml/k. may repeat and add DOPAMINE
Maintain physiological metabolic state - Hypocalcaemia ,Hypoglycemia
and Acidosis treated properly
Judicious fluid management – SIADH is often seen 3-4 days after HIE, is
manifested by hyponatremia & hypo osmolarity with inappropriate
concentrated urine.
Injection vitamin K
Antibiotics are to be started pending investigation result. Sepsis scr

26. Control of seizures
* 20-50 % of HIE, Starts between 6 -24 hrs, mostly in 2
stage
* may be subtle, Tonic, or multifocal clonic.
* Generalized seizure is uncommon
* Treatment of Hypoglycemia, Hypocalcaemia,
Hyponatremia excluded before ACT
* Difficult to control
* Once level of conventional AC are maximized, little
utility in eliminating every twitch until unless
cardiopulmonary compromise from seizures

27. control of seizure cont-
ACT--
Phenobarbitone: DOC
LD- 20 mg/k/dose, 10 mg/k/dose
MD- 3-5 mg/k/day
Phenytoin
LD – 15-20 mg/k/dose
MD- 4-8 mg/k/day
Lorazepam- 0.05-0.1 mg/k/dose

28. Weaning of ACT
Weaning when clinical exam & EEG
indicates no longer seizures
If EEG shows evidence of seizure ,
Phenobarbitone should be continued for 3-
6 months

29. Mannitol can be given only if immediate
mortality is likely due to increased
intracranial pressure like irregular
respiration and dilated pupil.
Prophylactic Phenobarbitone may be
considered in all moderate and severe HIE
even no seizures. ??? Current evidence
does not support.
Selective head cooling- moderate cooling
by few degree for 2-3 days may be
considered in many studies. ????

30. Feeding strategy
Withhold feed for 48 hours as ischemic
injury to GIT may exists
Trophic feeds “ expressed breast milk “ can
be started after 48 hrs if general condition
is stable.
Formula feed precipitate NEC

31. 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.

32. Neuroprotective strategy
1. Agents: tested in animals with little data in human
• Ketamine- Antogonists of excitotoxic neurotransmitters
receptors
• Free radical scavengers- Allopurinol , superoxide dismutase,
• Vitamin E
• Calcium channel blockers- mag sulph,Nimodipine,
• Cyclooxygenase inhibitor- Indomethacin
• Benzodiazepine receptor stimulation- Midzolam
• Enhancer of protein synthesis- Dexamethasone
2. Mild induced hypothermia ??

33. 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

34. * Overall Mortality- 10-30 %
Neurodevelopment sequele-15-45 %
Risk of CP in survivors- 5-10 % compared
to 0.2 % in general population.
Most CP is not related to perinatal asphyxia
and most perinatal asphyxia does not
cause CP.
Only 3-13 % of CP have evidence of
asphyxia.

35. If seizure last for > 3 days , chances of
CP(46 %) and Epilepsy (40%)
Presence of seizure increases risk of CP
50-70 fold.
Mortality risk is highest for seizure that
begins within 12 hrs of birth.

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

37. Thank you
RELAX