Dr Varsha Atul ShahSenior Consultant

Department of Neonatal and Developmental MedicineSingapore General Hospital

ASPHYXIA NEONATORUMASPHYXIA NEONATORUM

Defined as impaired respiratory gas exchange

accompanied by the development of acidosis

ASPHYXIA NEONATORUMASPHYXIA NEONATORUM

Definition of perinatal asphyxiaWHO :

A failure to initiate and sustain breathing at birth.

NNF :Moderate asphyxia

Slow gasping breathing or an apgar score of 4-6 at 1 minute of age

Severe asphyxiaNo breathing or an apgar score of 0-3 at 1 minute of age

HOW DOES ASPHYXIA OCCUR? Interruption of umbilical cord blood flow, eg: cord

compression during labour

Failure of exchange across the placenta, eg: abruption

Inadequate perfusion of maternal side of placenta, eg: maternal hypotension

Compromised fetus who cannot tolerate transient intermittent hypoxia of normal labour

Failure to inflate lungs

CHARACTERSITICS OF PERINATAL ASPHYXIA

Profound metabolic acidosis (pH<7.00)Persistence of an Apgar score of 0 to 3 beyond 5 minutesClinical neurologic sequelae in the immediate neonatal

periodEvidence of of multiorgan system dysfunction in the

immediate neonatal period

- derived from the 1992 joint statement of the AAOP and ACOG and the 1999 International Cerebral Palsy Task Force

TO ASSESS THE SEVERITY OF ASPHYXIA - Apgar Scores

Signs 0 1 2

Colour Blue/pale Blue peripheries Pink

Heart rate 0 <100 >100

Respiration 0 Weak, gasping Regular

Suction response 0 Slight Cries

Tone 0 Fair Active

A -Appearance P- Pulse G- Grimace A-Activity R-Respiration

Quiz:At birth, a newborn infant is noted to have the following findings: heart rate – 70/min, respiratory effort – poor and irregular, limp, no reflex irritability, blue all over the body.

The Apgar score of the baby at this point is?

HR 1, RR 1, Tone 1, reflex 0, color 0

APGAR=3

PREDISPOSING FACTORS

Maternal Causes

Medical conditions eg Pulmonary hypertension Chronic HPT

Antenatal conditions eg Abnormal uterine contraction Antepartum haemorrhage Prolapsed cord Malpositions etc

PREDISPOSING FACTORS

Fetal Causes

Multiple pregnancies

Big baby with CPD

Fetal anomalies - Congenital abnormalities

of the lung

PATHOPHYSIOLOGY

Fetal adaptation to oxygen lack

1. Preferential flow to heart, brain and adrenals

aerobic anaerobic metabolism

glucose pyruvic acid lactic acid Acidosis

Acidosis failure of autoregulation impaired perfusion

increasing acidosis Death unless resuscitated

PATHOPHYSIOLOGY

2. Primary and Secondary apnoea

Occur as an attempt to minimize metabolic work

3.Fetal response to asphyxia

Respiratory metabolic acidosis

4. EEG changes

Loss of faster rhythm iso-electric rhythms Prolonged voltage suppression with burst of spike waves indicating risk of significant brain damage

CLINICAL FEATURES Apnoea, bradycardia

Altered respiratory pattern - grunting, gasping

Cyanosis

Pallor-shock

Hypotonia

Unresponsiveness

ORGANS INVOLVED IN ASPHYXIA (1)

Asphyxia results in alteration in blood flow to various organs, hence multiple organ injury

Kidney abnormalities occur in 50% of asphyxiated infants CNS abnormalities in 30% & CVS & pulmonary abnormalities in 25%

• Renal abnormalities - Oliguria, elevated β2 , microglobulin, • azotaemina, elevated serum creatinine, acute tubular necrosis

ORGANS INVOLVED IN ASPHYXIA (2)

CNS abnormalities - HIE, PV-IVH

CVS abnormalities - Ventricular failure (R > L) Tricuspid regurgitation

Hypotension

Pulmonary abnormalities - PFC, pulmonary haemorrhage

GIT abnormalities - bleeding GIT, NEC

Bone marrow abnormalities - Thrombocytopenia etc

PATHOLOGY OF BRAIN DAMAGEAcidosis alteration in cell membrane permeability fluid shift cerebral edema

Anoxia chromatolytic changes in neuron

neuron necrosis and neuroglia reactions

Neuron necrosis may be focal, multifocal or

diffusely over the cerebral cortex, brainstem,

thalamus, basal ganglia etc

PATHOLOGY OF BRAIN DAMAGEExtent of damage depends on:

duration of asphyxia

severity of asphyxia

gestational age

alteration in cerebral blood flow

changes in glucose/glycogen metabolism in vulnerable areas of brain.

Pathology

•Severity and distribution is dependent on several factors

•Certain vulnerable areas

- cerebral cortex , hippocampus , basal ganglia, thalamus, brain stem, subcortical and periventricular white matter

•In full term infants gray matter structures affected and in premature infants white matter

•Four basic and clinically important lesions

- Neuronal necrosis, status marmoratus, para-sagittal cerebral injury, periventricular leucomalacia

In hypoxic-ischaemic encephalopathy, as the

cerebral edema develops, the brain function is

affected in descending order.

PATHOCLINICAL CORRELATIONFull term infant

Pathology Clinical Signs

• Parasagittal cortical and Spastic quadriplegia subcortical neurosis especially arms

Intellectual deficits

• Cerebellum Ataxia

• Brainstem Pseudobulbar palsy

PATHOCLINICAL CORRELATION Preterm infant

Pathology Clinical Signs

• Periventricular leukomalacia Spastic diplegia

• Status marmoratus of Dystonia,

• Basal ganglia choreoathetosis

• Thalamus Mental retardation

• Cerebral Cortex Mental retardation

SEVERITY OF HIE - SARNAT & SARNAT STAGE Stage I Stage II Stage III

Consciousness Hyperalert Lethargic Stuporose

Muscle Tone NAD Mild Hypotonia Flaccid Reflexes active Reflexes active intermittent

decerebration

Primitive Reflexes Present Incomplete Absent sucking weak suck weak or -ve suck -ve

Autonomic Function Sympathetic Parasympathetic Both depresseddepressed depressed

Seizures None Common None

EEG Normal Seizure, Isopotential background burst mildly abnormal suppression

Mild HIE

• Muscle tone may be increased slightly • Deep tendon reflexes may be brisk during the first

few days. • Transient behavioral abnormalities, such as poor

feeding, irritability, or excessive crying or sleepiness, may be observed.

• By 3-4 days of life, the CNS examination findings become normal.

Moderate HIE

• Lethargic, significant hypotonia • Diminished deep tendon reflexes. • Grasp, Moro, and sucking reflexes may be sluggish

or absent. • Occasional periods of apnea. • Seizures may occur within the 1st 24 hours of life. • Full recovery within 1-2 weeks is possible and is

associated with a better long-term outcome.

Severe HIE

• Stupor or coma is typical. • may not respond to any physical stimulus. • Breathing may be irregular, and the infant often requires ventilatory

support. • Generalized hypotonia and depressed deep tendon reflexes are

common. • Neonatal reflexes (e.g., sucking, swallowing, grasping, Moro) are

absent.• Disturbances of ocular motion, such as a skewed deviation of the

eyes, nystagmus, bobbing, and loss of "doll's eye" (i.e., conjugate) movements may be revealed by cranial nerve examination.

• Pupils may be dilated, fixed, or poorly reactive to light.

Preventing asphyxia

• Perinatal assessment– Regular antenatal check ups – High risk approach– Anticipation of complications during labour– Timely intervention ( eg. LSCS)

• Perinatal management– Timely referral– Management of maternal complications Prevention,

PREVENTION

Recognition of at risk pregnancies

Antenatal monitoring fetal movements, fetal growth CTG for change in baseline, loss of variability, decelerations fetal scalp pH < 7.2 --------------------- immediate delivery 7.2 - 7.25 ------------- repeat in 1 hour 7.25 ------------------- normalCo-ordinated care at delivery by paediatrician

MANAGEMENT-InvestigationsHx - of pregnancy and resuscitation

O/E to exclude other abnormality

Metabolic tests - sugar, Ca/P04/Mg, cord BG, ABG, metabolic screen

CSF - to exclude infection; assay brain specific creatine kinase

EEG - to help with seizure Dx and prognosis

Tech. scan - for abnormal uptake in damaged area

MANAGEMENT U/S - to exclude PV-IVH

CT scan - to exclude IVH/trauma, demonstrate severity of edema and for prognosis

MRI scan

• Supportive care Monitor B/p, To, blood sugar, correct acidosis and electrolyte

inbalance Care of renal failure - low fluid, dialysis Care of cardiac failure - Dopamine, restrict fluid Management of inappropriate ADH secretion - prevent overhydration

MANAGEMENT-1

BASIC CARE :Should be a daily routine in the management of all these babies -

1. Strict asepsis.2. Ensure neutral thermal environment.3. Monitor vital parameters – HR,RR,BP,and Pulse Oximetry.4. Urine output.5. Daily weight.6. Nutrition.

1. Management of shock

1.Hypovolumic shock needs replacement with fluids, plasma, or blood.

2.Cardiogenic shock warrants use of pressors like dopamine and / or dobutamine. In case of refractory shock inspite of use of pressors of 20 microgram/kg/mt steroids may be tried.

3.Septic shock should be suspected based on intrapartum risk factors for sepsis, core axillary mismatch and results of sepsis screen.

2-MANAGEMENT of Cerebral Oedema

• Minimise cerebral edemaVentilation - to prevent apnoea and maintain PC02 of 25 - 30

mmHgEnsure adequate oxygenationRestrict fluid intakeMannitol/frusemide - if urine output is established

• Not all seizures require treatment. Only lif seizures are more than 3 in a hour or lasting for 3 mts or more they warrant anticonvulant.

• Phenobarbitone,Phenytoin,initially by loading dose followed by maintenance dose are the first line drugs.

• In refractory seizures use of drip of midazolam,lorazepam or diazepam may be required.

• Role of sodium valproate is occasional. Use of newer anticonvulants like lamotrigene,clobazam,gabapentin etc is not well known in neonates.

3-Manangement of seizures

4-MANAGEMENT OF KIDNEY FAILUREUrine output is by itself not a reliable marker renal

parameters need to be monitored.

2.Fluid restriction is required once renal failure sets in. A careful evaluation of electrolytes would direct the fluid management.

3.Daily monitoring of urine output, urine specific gravity, and body weight are adjuvant to basic care.

4.Rarely peritoneal dialysis is required in case of persistent oliguria

5-Management of metabolic derangement

1.Hypoglycemia needs to be corrected by 10 % D.Only if it is symptomatic it warrants a bolus otherwise in asymptomatic cases maintenance infusion is all that is required.

2.Only symptomatic hypocalcemia needs correction.Evaluate for hypomagnesemia in case of persistent hypocalcemia.

3.Hyponatremia should be anticipated and prevented by restricted fluid administration.

Newer modalities

• Antagonists of excitotoxic neurotransmitter receptors - NMDA receptor blockers

• Free radical inhibitors / scavengers- vitamin E, superoxide dismutase

• Ca channel blockers• Nitric oxide synthetase inhibitors

•Hypothermia

Hypothermia as a Treatment for HIE

• Studies have shown that hypoxic ischemic injury can be reduced by brain cooling.

• Favorable effect on many of the pathways contributing to brain injury– Excitatory amino acids– Cerebral energy state– Cerebral blood flow and metabolism– Nitric oxide production – Apoptosis

Whole Body Hypothermia Selective Head Cooling

OUTCOMEDeath CNS sequelae

Stage I 0% 0%

Stage II 5% 21%

Stage III 75% 100%

Outcome generally good in those who do not reach stage III and spend < 5/7 in stage II

DIFFERENTIAL DIAGNOSISDrug depression - maternal drugs, GA

Prematurity

Trauma - tentorial tear

Anaemia

Neuromuscular disorder

Infection

Inborn error of metabolism - Pyridoxine Dependency

Respiratory tract malformation

Prognosis based on Apgars•Score at 1, 5 minutes does not give prognosis indicator •The longer the score remains lower, the greater its significance•0-3 @ 1min has mortality of 5-10%•may be increased to 53% if at 20min apgars score 0-3 •0-3 @ 5min , CP risk app. 1%•may be increased to 9%if for 15min•dramatic rise to 57% CP risk if for 20min

Predictors of poor neuro-developmental outcome

1. Failure to establish resp. by 5 minutes2. Apgar score of 3 or less at 5 minutes3. Onset of seizures with in 12 hours4. Refractory seizures5. Inability to establish oral feeds by 1 wk6. Abnormal EEG, neuro-imaging

That’s a wrap

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