Pediatric emergency medicine trisk 643

avoiding hyperthermia. For neonates encephalopathic immediately after birth,
therapeutic hypothermia initiated within 6 hours of life and continued for 72
hours is now an evidence-proven therapy that should be considered. Parenteral
fluids should be administered to ensure adequate cardiac output. Metabolic
derangements should be addressed in order to maintain serum sodium close to
140 to avoid exacerbations of cerebral edema, and hypoglycemia should be
treated aggressively to avoid secondary neuronal injury. Infants with evidence of
trauma or increased intracranial pressure may need to have emergent
neurosurgical interventions, and coagulation disturbances should be corrected to
try and control intracranial hemorrhage. Acute intoxication and/or IEM may
present with worsening encephalopathy, and in certain circumstances, may
require emergent dialysis to clear the offending metabolite.
CLINICAL PEARLS AND PITFALLS
The neonatal neurologic examination can be challenging due to subtle
changes in mental status in infants with underdeveloped CNSs.
Nonetheless, the neurologic examination can identify infants at high
risk for brain injury and timely interventions, such as hypothermia, can
result in neuroprotection.
In some circumstances, brainstem herniation can occur without bulging
of the anterior fontanelle because of isolated increased pressure in the
posterior fossa.
It is not uncommon for the infant to have waxing and waning of
neurologic signs, and careful documentation and serial evaluations are
important diagnostic and prognostic clues.
Perinatal hypoxia–ischemia is a major cause of neonatal
encephalopathy, however, additional etiologies for late-onset or
progressive encephalopathy must be evaluated.
Current Evidence
Hypoxic–ischemic injury during the perinatal period is the most common
identified cause of neonatal encephalopathy. The pathophysiology of injury
leading to cerebral edema, reperfusion injury, and neuronal cell death can also be

applied to any acute asphyxial event in the neonatal period. Brain injury in
response to such an event continues to evolve over a period of hours to days, and
can account for changes seen in the clinical examination.


Clinical Considerations
Clinical Recognition. Neonatal encephalopathy manifests as an acute change in
mental status and/or seizures. In its most profound presentation, the infant will
show depressed level of consciousness (as in stupor or coma) with global
hypotonia, and autonomic disturbances that include apnea, respiratory failure, or
abnormal cardiac rhythms. Moderate encephalopathy may manifest as a variable
change in alertness, with alternating periods of decreased arousal, or
hypervigilance, tremors, jitteriness, and irritability. The timing and pattern of
changes in degree of encephalopathy may help distinguish etiology; in acute
hypoxia–ischemia, there may be a period of “normalization” of the neurologic
examination 12 to 24 hours after the event or trauma. Acute intoxication or IEM
are more likely to present with progressive encephalopathy and typically do not
demonstrate this period of “pseudonormalization.”
Triage Considerations. The lethargic infant with decreased levels of alertness
should be triaged emergently, as these infants can quickly develop autonomic
instability and cardiorespiratory collapse. Additionally, if born outside a medical
setting and presenting within 6 hours of life, time-sensitive therapies are available
that offer neuroprotection.
Clinical Assessment. The clinical assessment requires detailed history regarding
the timing and onset of symptoms—initial symptoms may include decreased
arousal, increased lethargy, decreasing oral intake, and increasing irritability.
History may also reveal potential asphyxial events or trauma. Unexplained
intracranial hemorrhage should also warrant an evaluation for nonaccidental
trauma once the infant is stabilized. Given the risk of either autonomic
deterioration or a global asphyxial event that could result in multisystem

dysfunction, clinical assessment should include detailed cardiopulmonary
evaluation, including monitoring for apnea. Serum toxicology screen should be
sent, as well blood gas, BMP, liver function panel, ammonia level, and plasma
amino acids. Urine should be collected and sent for toxicology, urinalysis for
ketones, and urine for organic acids. Acute bilirubin encephalopathy (kernicterus)
is a rare cause of brain injury, but should be suspected if the infant also presents
with jaundice. Infants should also be evaluated for infection, including bacterial
and/or viral meningoencephalitis. IEM presenting with neonatal encephalopathy
are summarized in Table 96.5 . Other causes of neonatal hypotonia and weakness
are presented in Table 96.6 .


Management. The infant should be stabilized and if there are signs of respiratory
distress, should be supported with assisted ventilation. Patients with signs of
global asphyxial injury should be supported with fluid boluses or inotropes if
there are signs of poor cardiac output. For select patients presenting with
encephalopathy since birth, the consideration of therapeutic hypothermia should
be discussed with a neonatologist. A history that is concerning for trauma or
asphyxia, or infants with evidence of trauma or increased intracranial pressure,
should undergo emergent head imaging (noncontrast head CT). If there is
evidence of intracranial hemorrhage, cerebral edema, and/or herniation, pediatric
neurosurgery should be consulted. In addition, a complete blood count and
coagulation studies should be sent and abnormalities should be corrected
aggressively with transfusion of blood products to stabilize any hemorrhage. Any
metabolic derangements should be corrected—particularly hypoglycemia, with
the rapid infusion of parenteral dextrose bolus and then an ongoing infusion.
Tight control of serum sodium should be achieved to decrease the effects of
cerebral edema. Broad-spectrum antibiotics should be administered once the
cultures have been obtained. Acute hyperbilirubinemia with encephalopathy is
treated with hydration and exchange transfusion. Hyperammonemia is treated

with scavenger drugs and/or dialysis in conjunction with a pediatric nephrologist.
Once stabilized, many IEM can be managed by diet in conjunction with a
metabolic geneticist. Degenerative diseases such as Tay–Sachs, Menkes,
Neiman–Pick, Guacher, Crabber, and peroxisomal and mitochondrial disorders
have no effective treatments other than supportive care.


TABLE 96.5
INBORN ERRORS OF METABOLISM PRESENTING WITH
ENCEPHALOPATHY
Urea cycle defects

Maple syrup urine disease
Nonketotic hyperglycinemia

Organic acid disorders
Hypervalinemia
Phenylketonuria
Lysinuric protein intolerance

Vomiting, stupor and seizures
Hyperammonemia, acidosis with respiratory
alkalosis
Stupor, seizures, odor of maple syrup
Acidosis, hypoglycemia
Stupor, seizures, hiccups
Hyperglycinemia in CSF, serum, and urine
Absence of acidosis or ketones in urine
Stupor, coma, tachypnea, vomiting
Metabolic acidosis

Stupor and developmental delay
Vomiting and musty odor
Vomiting and hypotonia