Lecture 6

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					lecture 6
Dr Numan Nafie Hameed ‫د. نعمان نافع الحمداني‬

Perinatal asphyxia
Definition. Perinatal asphyxia is a condition caused by a lack of oxygen in respired
air, resulting in impending or actual cessation of apparent life (Clinical).
Perinatal asphyxia is a condition of impaired blood gas exchange that, if it persists,
leads to progressive hypoxemia and hypercapnia with a metabolic
Essential characteristics defined jointly by the American Academy of Pediatrics
(AAP) and the American College of Obstetricians and Gynecologists (ACOG) should
be present:
(1) profound metabolic or mixed acidemia (pH 7.00) on umbilical cord arterial
blood sample, if obtained;
 (2) persistence of an Apgar score of 0-3 for 5 min;
(3) neurologic manifestations in the immediate neonatal period to include seizures,
hypotonia, coma, or hypoxic-ischemic encephalopathy (HIE); and
(4) evidence of multiorgan system dysfunction in the immediate neonatal period.
Biochemical indices. There is no specific blood test to diagnose perinatal asphyxia.
1. The normal umbilical arterial base excess is - 6 mEq/L with -10 to -12 mEq/L as
the upper statistical limit of normal. Base excess -20 mEq/L is required to show
neurologic damage associated with metabolic acidosis.
2. The precise value that is required to define damaging acidemia is not known. A pH
7.0 realistically represents clinically significant acidosis. Acidemia alone does not
establish that hypoxic injury has occurred.
Apgar score
1. Conceived to report on the state of the newborn and effectiveness of resuscitation.
It is a poor tool for assessing asphyxia.
Low Apgar scores are unlikely to be the cause of morbidity but rather the results of
prior causes.
2. An infant with an Apgar score of 0-3 at 5 min, improving to 4 by 10 min, has
99% chance of not having cerebral palsy (CP) at 7 years of age; 75% of children
who develop CP have normal Apgar scores at birth.
3. A 1996 revised AAP/ACOG statement again emphasized that the Apgar score
alone should not be used as evidence that neurologic damage was caused by hypoxia
resulting in neurologic injury or by inappropriate intrapartum management.
Mechanisms of asphyxia during labor, delivery, and the immediate postpartum
A. Interruption of the umbilical circulation (cord compression).
B. Inadequate perfusion of the maternal side of the placenta (maternal
hypotension, hypertension, abnormal uterine contractions).
C. Impaired maternal oxygenation (cardiopulmonary disease, anemia).
D. Altered placental gas exchange (placental abruption, previa, insufficiency).
E. Failure of the neonate to accomplish lung inflation and successful transition
from fetal to neonatal cardiopulmonary circulation.

A. Adaptive responses of the fetus or newborn to asphyxia. The fetus and neonate
are much more resistant to asphyxia than adults.
In response to asphyxia, the mature fetus redistributes the blood flow to the heart,
brain, and adrenals to ensure adequate oxygen and substrate delivery to these vital
B. Impairment of cerebrovascular autoregulation results from direct cellular
injury and cellular necrosis from prolonged acidosis and hypercarbia.
C. The majority of neuronal disintegration occurs after termination of the
asphyxial insult because of persistence of abnormal energy metabolism and low
(ATP) levels. A cascade of deleterious events is triggered, resulting in formation of
free radicals, increased extracellular glutamate, increased cytosolic Ca2+, and delayed
cell death.
D. Major circulatory changes during asphyxia
1. Loss of cerebrovascular autoregulation under conditions of hypercapnia,
hypoxemia, or acidosis.
Cerebral blood flow (CBF) becomes "pressure passive," leaving the infant at risk for
cerebral ischemia with systemic hypotension and cerebral hemorrhage with systemic
2. Increase in CBF secondary to redistribution of cardiac output, initial systemic
hypertension, loss of cerebrovascular autoregulation, and local accumulation of
vasodilator factors (H+, K+, adenosine, and prostaglandins).
3. With prolonged asphyxia, there is a decrease in cardiac output, hypotension, and
a corresponding fall in CBF. In general, brain injury occurs only when the asphyxia is
severe enough to impair CBF.
E. The postasphyxial human newborn is in a persistent state of vasoparalysis
and cerebral hyperemia, the severity of which is correlated with the severity of the
asphyxial insult.
Cerebrovascular hemorrhage may occur on reperfusion of the ischemic areas of the
brain. However, when there has been prolonged and severe asphyxia, local tissue
recirculation may not be restored because of collapsed capillaries in the presence of
severe cytotoxic edema.
F. Cerebral edema is a consequence of extensive cerebral necrosis rather than a
cause of ischemic cerebral injury.

Neuropathologic findings
A. Cortical changes. Cortical edema, with flattening of cerebral convolutions, is
followed by cortical necrosis until finally a healing phase results in gradual cortical
atrophy. Cortical atrophy, if severe, may result in microcephaly.
B. Selective neuronal necrosis is the most common type of injury observed in
neonatal HIE.
C. Other findings seen in term infants include status marmoratus of the basal
ganglia and thalamus (the marbled appearance is a result of the characteristic feature
of hypermyelinization) and parasagittal cerebral injury.
D. Periventricular leukomalacia (PVL) is hypoxic-ischemic necrosis of
periventricular white matter resulting from cerebral hypoperfusion.
Injury to the periventricular white matter 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. The incidence of PVL increases with the length of survival
and the severity of postnatal cardiorespiratory disturbances. PVL involving the
pyramidal tracts usually results in spastic diplegic or quadriplegic CP.
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.

Clinical presentation
A. The majority of infants who experience intrauterine hypoxic-ischemic insults
do not exhibit overt neonatal neurologic features or subsequent neurologic
evidence of brain injury.
It is generally accepted that after acute perinatal asphyxia there should be an acute
encephalopathy, often accompanied by multiorgan malfunction.
B. Occurrence of neonatal neurologic syndrome The primary signs of CNS injury
in the term infant include seizures, apnea, posturing and movement disorders,
impaired suck, and jitteriness. The absence of this neonatal neurologic syndrome
rules out intrapartum insult as the cause of major brain injury.
C. The severity of HIE correlates with the duration and severity of the asphyxial
A constellation of neurologic signs evolves over the first 72 h of life best
characterized by Sarnat and Sarnat in 1976:
stage I (hyperalert, awake state),
stage 2 (lethargic, obtunded, hypotonic, seizures),
 stage 3 (stuporous, comatose, flaccid, posturing).
Moderately to severely affected infants are usually obtunded if not comatose, with
generalized hypotonia and paucity of spontaneous movements.
Depressed reflexes and cranial nerve palsies are common findings.
Presentation of hypertonicity and irritability generally are not noted until the second
week of life.
D. Occurrence of seizures within the first 12-24 h after birth is indicative of
intrapartum insult until proven otherwise. Seizures may also be secondary to
E. Hypoxic-ischemic spinal cord injury. Ischemic injury to anterior horn cells
within the spinal cord gray matter is relatively common among hypotonic and
hyporeflexic neonates after severe perinatal hypoxia-ischemia.
Electromyographic examinations show injury to the lower motor neuron above the
level of the dorsal root ganglion .
F. Clinical presentation may be further obscured by the coexistence of skull
fracture, subdural hematoma, or subarachnoid hemorrhage resulting from traumatic
G. Multiple organ involvement.
 involvement of 1 or more organs occurred in 82% of infants with perinatal asphyxia.
The central nervous system (CNS) is the organ most frequently involved .
1. Cardiovascular system. Shock, hypotension, tricuspid insufficiency, myocardial
necrosis, congestive heart failure, and ventricular dysfunction.
2. Renal function. Oliguria-anuria, acute tubular or cortical necrosis (hematuria,
proteinuria), and renal failure.
3. Hepatic function. Elevated serum -glutamyl transpeptidase activity, ammonia
and indirect bilirubin, and decreased clotting factors at 3-4 days' postnatal age in
moderate to severe asphyxia.
4. Gastrointestinal tract. Paralytic ileus or delayed (5-7 days) necrotizing
5. Lungs. Respiratory distress syndrome from surfactant deficiency or dysfunction,
pulmonary hemorrhage (shock lung), and persistent pulmonary hypertension.
6. Hematologic system. Thrombocytopenia can result from shortened platelet
survival or DIC. Increased numbers of nucleated red blood cells have been reported .
7. Metabolic. Acidosis, hypoglycemia (hyperinsulinism), hypocalcemia (increased
phosphate load, correction of metabolic acidosis), and hyponatremia/syndrome of
inappropriate antidiuretic hormone secretion (SIADH).

 careful history
thorough physical examination
 appropriate laboratory studies
Neurodiagnostic and neuroimaging studies
EEG. may provide information on the severity of the asphyxia injury, and the type of
EEG abnormality may be indicative of a specific pathologic variety.
Identification of EEG abnormalities within the first hours after delivery may be
helpful in selecting infants for treatment with neuroprotective agents.
 CT scan. The value of CT in the assessment of diffuse cortical neuronal injury is
most apparent several weeks after severe asphyxial insults.
 It is of particular value in the identification of focal and multiple ischemic brain
During the first week after an insult, the striking, bilateral, diffuse hypodensity
reflects marked cortical neuronal injury, with associated edema corresponding closely
to the occurrence of maximum intracranial pressure.
Ultrasonography is the method of choice for routine screening of the premature
brain. It is of major value in the identification of IVH and necrosis of basal ganglia
and thalamus. It is superior to CT in identifying both the acute and subacute-chronic
manifestations of periventricular white matter injury.
Its limitations in the first weeks of life include its inability to reliably identify mild
injury, to visualize lesions that are peripherally located, and to distinguish between
hemorrhagic and ischemic lesions in the cerebral parenchyma.
MRI is the technique of choice for evaluation of hypoxic ischemic cerebral injury in
term and premature newborns.

A. Optimal management is prevention. The first goal is to identify the fetus being
subjected to or likely to experience hypoxic-ischemic insults with labor and delivery.
B. Immediate resuscitation. Any newborn that is apneic at birth must be promptly
resuscitated because it cannot be determined whether the infant is in primary or
secondary apnea.
1. Maintenance of adequate ventilation. Use an assisted ventilatory rate to maintain
physiologic levels of PCO2. Hypercarbia can further increase cerebral intracellular
acidosis and impair cerebrovascular autoregulation, whereas hypocarbia (PaCO2 20-
25 mm Hg) has been associated with PVL in preterm infants and late-onset
sensorineural hearing loss in full-term infants.
2. Maintenance of adequate oxygenation (PaO2 40 in premature infants and PaO2
50 in term infants). Avoid hyperoxia , which may lead to additional brain injury
from possible reduction in CBF and vaso-obliterative changes.
3. Maintenance of adequate perfusion. Maintain arterial blood pressure in the
"normal" range for gestational age and weight. Volume expanders and inotropic
support are often required. With the loss of cerebrovascular autoregulation, it is
important to avoid systemic hypotension and hypertension.
4. Correct metabolic acidosis with cautious use of volume expanders. The primary
objective is to sustain tissue perfusion. Perfuse or lose! Use bicarbonate only when
cardiopulmonary resuscitation (CPR) is prolonged and the infant remains
unresponsive. Bicarbonate administration may lead to hypercarbia and intracellular
acidosis and increase lactate.
5. Maintain a normal serum glucose level (~75-100 mg/dL) to provide adequate
substrate for brain metabolism. Avoid hyperglycemia to prevent hyperosmolality and
a possible increase in brain lactate levels.
6. Control of seizures:
a. Phenobarbital is the drug of choice. It is usually continued until the EEG is
normal and there are no clinical seizures for 2 months. The benefit of prophylactic
therapy remains controversial. High-dose phenobarbital (40 mg/kg) reduced the
incidence of seizures and improved neurologic outcome at 3 years in term
asphyxiated newborns .
b. If seizures persist despite therapeutic phenobarbital levels--- diazepam, lorazepam,
and phenytoin may be used
7. Prevention of cerebral edema. The cornerstone of prevention of serious brain
swelling is avoidance of fluid overload. Maintain slight to moderate fluid restriction
(eg, 60 mL/kg). If cerebral edema is severe, further restriction of fluid intake to 50
mL/kg is imposed. Observe the infant for SIADH. Glucocorticoids and osmotic
agents are not recommended.

C. Potential new therapies should aim at preventing delayed neuronal death
once an asphyxial insult has occurred.
1. Magnesium has an inhibitory effect on excitation of the N-methyl-D- aspartate
type of glutamate receptors and competitively blocks Ca2+ entry through voltage-
dependent Ca2+ channels during hypoxia.
2. Prevention of free radical formation
a. Xanthine oxidase inhibitor. allopurinol reduced free radical formation and
enhanced electrical brain activity in severely asphyxiated newborns.
b. Resuscitation with room air.
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
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 while cerebral lactate levels are reduced.

 Most survivors of perinatal asphyxia do not have major sequelae.
A. Findings associated with increased risk of neurologic sequelae
1. Apgar score of 0-3 at 20 min of age.
2. Presence of multiorgan failure, particularly oliguria persisting beyond 24 h of
3. Severity of the neonatal neurologic syndrome. Severe HIE (Sarnat stage 3)
carries a mortality rate of ~80%, and survivors often have multiple disabilities,
including spastic CP, severe or profound mental retardation, cortical blindness, or
seizure disorder . There is no permanent sequelae for mild HIE (Sarnat stage 1).
Moderately affected (stage 2) patients have outcomes that vary with their overall
clinical course and duration of their neurologic condition. Stage 2 beyond 5 days is a
poorer prognostic sign.
4. Duration of neonatal neurologic abnormalities. Disappearance of neurologic
abnormalities by 1-2 weeks and the ability to nipple feed normally is an excellent
prognostic sign.
5. Presence of neonatal seizures, especially if they occur within the first 12 h after
birth and are difficult to control.
6. An abnormal MRI obtained in the first 24-72 h is associated with a poor
outcome, irrespective of birth variables.
7. Severity and duration of EEG abnormalities.
Normal to mildly abnormal EEG patterns within the first days after delivery are
significantly correlated with normal outcomes.
 moderately to severely abnormal EEG patterns are significantly related to abnormal
outcomes .
8. Persistent abnormalities of brainstem function are generally incompatible with
long-term survival.
9. Abnormal visual, auditory, or somatosensory evoked potentials persisting
beyond day 7 of life.

10. Subsequent hearing is normal in most children who have suffered perinatal
or postnatal asphyxia.
11. Microcephaly at 3 months of age is predictive of poor neurodevelopmental
12. Decreased cerebral concentrations of phosphocreatine or ATP at birth on
quantitative 31P MRI .
13. Elevated brain lactate levels ,elevated ratio of lactate to Nacetylaspartate and
lactate to choline on proton MRS, and low CSF cyclic adenosine monophosphate
(cAMP) levels.
14. Increased CBF on Doppler sonography in the first 3 days after birth .
15. Decreased cerebral resistive index on Doppler sonography .
16. The presence of optic atrophy is an indicator of poor visual outcome .
Many children with postasphyxial CNS abnormalities have lower visual acuity scores
and smaller visual fields.

Respiratory and cardiovascular effects during prolonged asphyxia


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