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Post -resuscitation management

of an asphyxiated neonate

DR MOHD MAGHAYREH
PRTH

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Hypoxic-Ischemic Encephalopathy
 Definition :
 The World Health Organization has defined
birth asphyxia as “failure to initiate and
sustain breathing at birth” and based on
Apgar score as an Apgar score of <7 at one
minute of life.

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INCIDENCE
 1 -1.5% of live births
 It is inversely related to gestational age
and birth weight
 It occur in (o.5%(of live born infants with
gestational age >36wk
 It account for 20% of perinatal deaths

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Risk factors
1. Ante partum events (20%)
1. Maternal:
– cardiac problem,
– hemorrhage,
– diabetes
– pre eclamptic toxemia,
2. fetal: IUGR, congenital anomalies
2. Intrapartum events (35%)
 birth trauma,
 abruption,
 uterine rupture,
 uteroplacental insufficiency
3. Ante partum and Intrapartum (35%)
4. Postpartum events (10%)
1. apnea,
2. bradycardia,
3. septic shock,
4. pulmonary disease,
5. some CHD (LVOT obstr), PDA (premie
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Mechanisms of asphyxia during labor, delivery,
and the immediate postpartum period
 Interruption of the umbilical circulation (cord
compression).
 Inadequate perfusion of the maternal side of the
placenta (maternal hypotension, hypertension,
abnormal uterine contractions).
 Impaired maternal oxygenation (cardiopulmonary
disease, anemia).
 Altered placental gas exchange (placental
abruption, previa, insufficiency).
 Failure of the neonate to accomplish lung
inflation and successful transition from fetal to
neonatal cardiopulmonary circulation
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The essential criteria for diagnosing perinatal
asphyxia as outlined by ACOG & AAP are

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

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Perinatal asphyxia
PATHOPHYSIOLOGY
1. Insult to the fetus / newborn

 Lack of oxygen - hypoxia
 &/or
 Lack of perfusion – ischemia

2. Effect of ischemia & hypoxia Both
contribute to tissue injury.

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CARDIOVASCULAR RESPONSES TO ASPHYXIA

ASPHYXIA (↓PaO2 ,↑PaCO2, ↓(pH

Redistribution of Cardiac Output

↓Renal, Intestinal ↑Cerebral, Coronary, Adrenal
Blood Flow Blood Flow

Ongoing Asphyxia
↓Cerebral Blood Flow

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PATHOPHYSIOLOGY
)Asphyxia ( continues

Shunting within the brain

Anterior Posterior
Circulation Circulation
Suffers Maintained
CEREBRAL CORTICAL LESIONS

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

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ISCHEMIA AND REPERFUSION INJURY

Ischemia ATP Calcium influx
depletion

Phospholipase activation

Arachidonic acid release

Prostaglandins Proteases, lipases

Vasodilation
Microvascular
Reperfusion permeability

ROS Release
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At cellular level

Cerebral O2 ↓

Substrate supply ↓

Synaptic inactivation (Reversible)

Energy failure

Memb. pump failure

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Major circulatory changesduring
)asphyxia )summary

1. Loss of cerebrovascular autoregulation under conditions of
 Hypercapnia,
 Hypoxemia,
 Acidosis
2.Cerebral blood flow (CBF) becomes "pressure passive," leaving
the infant at risk for
1. cerebral ischemia with systemic hypotension
2. cerebral hemorrhage with systemic hypertension

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CONTINUE

3. Increase in CBF secondary to
 Redistribution of cardiac output.
 Initial systemic hypertension.
 Loss of cerebrovascular auto regulation,
 Focal accumulation of vasodilator factors )H+, K+,
adenosine, and prostaglandins).
4. With prolonged asphyxia, there is a
 Decrease in cardiac output.
 Hypotension.
 Fall in CBF..

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Neuropathologic findings

A. Cortical changes.
 Cortical edema, with flattening of cerebral convolutions
 cortical necrosis
 cortical atrophy
 microcephaly.

B. Selective neuronal necrosis is the most common type of injury
observed in neonatal HIE.

C. Other findings seen in term infants include :
1-status marmoratus of the basal ganglia and thalamus
2-parasagittal cerebral injury

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Neuropathologic findings
continue

D-Periventricular leukomalacia (PVL)
3. It is hypoxic-ischemic necrosis of peri ventricular white matter resulting
from cerebral hypo perfusion and the vulnerability of the
oligodendrocyte within th white matter to free radicals, excitotoxin
neurotransmitters, and cytokines

5. It is the most significant problem contributing to long-term neurologic
deficit in the premature infant, although it does occur in sick full-term
infants as well.

7 The incidence of PVL increases with the length of survival and the
severity of postnatal cardiorespiratory disturbances

10 - involving the pyramidal tracts usually results in spastic diplegic or
quadriplegic CP. Visuoperception deficits may result from involvement
of the optic radiation

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Neuropathologic findings
continue
 E. Porencephaly, hydrocephalus,
hydranencephaly, and multicystic
encephalomalacia may follow focal and
multifocal ischemic cortical necrosis, PVL, or
intraparenchymal hemorrhage.
 F. Brainstem damage is seen in the most
severe cases of hypoxic-ischemic brain injury
and results in permanent respiratory
impairment

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Clinical consequences of perinatal
asphyxia
Brain ( Hypoxic Ischemic Encephalopathy, HIE )
 Altered sensorium
 Irritability,
 lethargy,
 deeply comatose
 Tone disturbances :hypotonia of proximal girdle
muscles )lack of head control & weakness of
shoulder muscle in term infants )

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consequences of perinatal
Clinical
).asphyxia )cont
 Brain ( Hypoxic Ischemic
Encephalopathy,HIE )
 Autonomic disturbances eg. hypotension,
increase salivation, abnormal pupillary reflex
 Altered neonatal reflexes -Moro’s, sucking ,
swallowing
 Seizures

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Fetal and neonatal assessment

 Fetal Heart rate monitoring
 fetal bradycardia
 repetitive late decelerations of the fetal heart rate,
 low fetal scalp or cord pH
 Passage of Meconium
 Failure to establish spontaneous
respiration
 low Apgar Scores

 Hypoxic - Ischemic Encephalopathy
 Multi organ Involvement
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Principles of management
 Prevent further organ damage
 Maintain oxygenation, ventilation & perfusion
 Correct & maintain normal metabolic & acid
base milieu
 Prompt management of complications

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Sarnat staging of hypoxic-ischemic encephalopathy.
Grade 1 (mild) Grade2 (moderate) Grade 3 (severe)

Level of consciousness Irritable/hyperalert Lethargy Coma

Muscle tone Normal or hypertonia Hypotonia Flaccid

Tendon reflexes Increased Increased Depressed or absent

Seizures Absent Frequent Frequent

Complex reflexes Normal weak Absent

Prognosis Good Variable High mortality and neurologicl
disability

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According to Sarnat classification of severity
stage 1 100 % normal

stage 2 80 % normal

stage 3 50 % death 50 % major sequalae

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Initial management
 Admit in nursery,if
 -Apgar score <3 at 1 minute
 -Babies requiring intubation chest
compressions or medications
 Nurse in thermo-neutral temperature to maintain skin
temperature at 36.5oC
 Secure IV line , fluids 2/3 rd of maintenance
 Fluid bolus if CRT > 3 secs or blood pressure low
 Inj vit k
 Stomach wash

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Clinical monitoring
 HR, RR, colour, CRT, O2 saturation, BP &
 temperature
 Assessment of neurologic status
 Tone, seizures, consciousness, pupillary size
& reaction, sucking, swallowing
 Abdominal circumference
 Urine output

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Biochemical monitoring
 Blood gases & pH
 Bedside blood sugar by Dextrostix
 Hematocrit
 S. electrolytes ( Na, K)
 S. calcium
 BUN, creatinine

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Other investigations
 Sepsis screen & blood culture to exclude in-
utero or acquired infection during
resuscitation
 X-ray chest to look for pneumothorax,
malformations, cardiac enlargement

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Computed tomography )CT) scan

 First week after an insult :
2. Cortical neuronal injury
3. Edema
 The value of CT several weeks after severe
asphyxial insults:
 The assessment of diffuse cortical neuronal
injury
 identification of focal and multiple ischemic brain
injury.
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Ultrasonography is the method of choice for routine
.screening of the premature brain

 1-intraventricular hemorrhage

 2- necrosis of basal ganglia and thalamus.

 3- It is superior to CT in identifying both the
acute and subacute-chronic manifestations of
periventricular white matter injury.

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Ultrasonography limitations in the first weeks
of life include its inability to

2. Reliably identify mild injury
3. Lesions that are peripherally located
4. Distinguish between hemorrhagic and
ischemic lesions in the cerebral
parenchyma.

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Magnetic resonance imaging )MRI) is
the technique of choice for evaluation of hypoxic ischemic cerebral injury in term and premature newborns

The advantages of MRI include the
following:
 It does not expose the neonate to radiation.
 better anatomic imaging detail and resolution.
 It clearly demonstrates the myelinization delay that
almost invariably accompanies asphyxial brain
injury.
 MRI may provide insight into the timing and
duration of the asphyxial injury..

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Magnetic resonance imaging
)MRI) CONTINUE

 4. MRI is probably the best method available
to diagnose hypoxic brain injuries in mildly to
moderately affected patients and to detect
discrete lesions of the cerebellum and
brainstem.
 5. It may provide clues to other disorders (eg,
metabolic or neurodegenerative disorders)
that may also present as obtundation or coma
in the newborn period.

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Magnetic resonance imaging
)MRI) CONTINUE

6. Ischemic lesions can be identified as early as
24 h after the insult.
7. MRI can help differentiate between partial
asphyxia and anoxia
8. MRI demonstrates the structural sequelae of
asphyxial injury on follow-up and has
prognostic value.
Repeat MRI at 3 months of age will usually
show the full extent of brain injury.

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Evoked electrical potentials
(auditory, visual, or somatosensory)
 performed within the first hours of life may
help to select infants for treatment with
neuroprotective agents.
 They also have prognostic value in defining
areas of CNS damage
 Persistence of deficits beyond the neonatal
period correlates with persistence of other
signs of brain injury.

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Potentially useful techniques

1. Magnetic resonance spectroscopy (MRS) provides a measure of "energy reserve."
Using phosphorus-/(31P) MRS
It has been shown that asphyxiated newborns tend to have lower phosphocreatine/inorganic
phosphate ratios (impaired brain oxidative phosphorylation)
 lower ATP/total phosphorus ratios than normal patients.

2. Proton MRS allows noninvasive observations to be made of the derangement of
cerebral
 metabolites (N-acetylaspartate (NAA) and lactic acid) when oxidative phosphorylation is
impaired.
 The normalization of phosphorous metabolite ratios with time may reflect loss of severely
affected neurons. Neuronal loss, gliosis, and delay in myelination would be reflected by a
relative loss of NAA.

3. Near-infrared spectroscopy on the first day after injury may demonstrate increased
cerebral
 venous oxygen saturation and decreased cerebral oxygen extraction, despite increased
cerebral
 oxygen delivery, suggestive of a postasphyxial decrease in oxygen utilization

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EEG
1. Evolution of EEG changes may provide
information on the severity of the asphyxial
injury,
2. The type of EEG abnormality may be
indicative of a specific pathologic variety.
3. Identification of EEG abnormalities within
the first hours after delivery may be helpful
in selecting infants for treatment with
neuroprotective agents

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Aims of specific management
 Maintain temperature, perfusion, oxygenation,
ventilation & normal metabolic state
 Temperature 36.5° C – 37.5° C
 Perfusion:
 BP Mean 40-60 mm Hg ( Term)
 CRT maintain < 3 sec
 Oxygen
 PaO2 60-80mmHg
 saturation 90-93 %
 CO2 35-45 mm of Hg
 Glucose 70-110 mg/dl
 Calcium 9-11 mg/dl

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Specific management
 Maintain perfusion
 Normal blood pressure
 CRT < 3 secs
 Normal urine output ( >1ml/kg/hr)
 Absence of metabolic acidosis

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Specific management
Maintain perfusion
 Maintain mean arterial pressure and CRT by
giving slow bolus of crystalloid 10 ml/kg over 20
minutes. Repeat one more time , if still does not
improve
 Use vasopressors Dopamine and /or
Dobutamine to increase BP
 Sodium bicarbonate 1-2 ml/kg diluted in 5 %
dextrose can be used for babies with
documented acidosis after establishing
respiration
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SUBSEQUENT
MANAGEMENT
 Oxygenation & ventilation
 Adequate perfusion
 Normal glucose & calcium
 Normal hematocrit
 Treat seizure

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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
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 Phenobarbital is the drug of choice.
 continued until the EEG is normal and there
are no clinical seizures for ³2 months.
 The benefit of prophylactic therapy remains
controversial.

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Potential new therapies should aim at preventing
delayed neuronal death

 once an asphyxial insult has occurred.

 It is estimated that there is a 6- to 12-h window of
opportunity after acute asphyxia whereby administration of a
neuroprotective agent could reduce or prevent brain damage.

 1. Magnesium has an
 inhibitory effect on excitation of the N-methyl-D- aspartate type of
glutamate receptors
 competitively blocks Ca2+ entry through voltage-dependent Ca2+
channels during hypoxia
 SIDE EFFECT
 Apnea may occur, and
 Higher doses carry a significant risk of hypotension.
 Use of magnesium sulfate (MgSO4) remains controversial.

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Prevention of free radical formation ))CONTINUE

 . Xanthine oxidase inhibitor. In a pilot study (Van Bel et al,
1998), allopurinol
– reduced free radical formation and
– enhanced electrical brain activity in severely asphyxiated
newborns.
– addition, allopurinol reduced nonprotein iron ( prooxidant)
 Resuscitation with room air. In the Resair 2 trial
(Saugstad 2001), room air-resuscitated
1. infants recovered more quickly as assessed by time
to first cry, 5-min Apgar score, and sustained pattern
of respiration.
2. Neonates resuscitated with 100% oxygen manifest
biochemical changes indicative of prolonged oxidative
stress at 4 weeks of age (Vento et al, 2001
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Potential new therapies should aim at
)preventing delayed neuronal death )CONTINUE
 3. Excitatory amino acid antagonists.
 4. Calcium channel blockers.
 5. Inhibition of nitric oxide production. Increased
plasma nitric oxide levels has been shown as a
marker for severity of brain injury and poor neurologic
outcome )Shi et al, 2000).
 6. Selective head cooling. Hypothermia is thought to
protect the brain from injury by preventing the decline
in high-energy phosphates. Phosphocreatine and
adenosine triphosphate are maintained

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Predictors of poor neuro-
developmental outcome
 Failure to establish resp. by 5 minutes
 Apgar score of 3 or less at 5 minutes
 Onset of seizures with in 12 hours
 Abnormal EEG & failure to normalise by 7
days of life
 Refractory seizures
 Stage III HIE
 Inability to establish oral feeds by 1 wk
 Abnormal neuro-imaging

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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

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There is always more to come!

Thank you
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