HYPOXIC-ISCHEMIC ENCEPHALOPATHY (HIE)

Definitions of HIE and Related Clinical Diagnoses

Asphyxia is the term used to describe an insult to the fetus or newborn due to lack of oxygen or lack of perfusion to various organs.   The biochemical definition of asphyxia includes the components of hypoxemia, metabolic acidosis and hypercapnia.   Asphyxia is defined as a combination of several findings:   Apgar <5 at 5 minutes, PH<7.00, and evidence of seizures or other organ involvement.

Neonatal encephalopathy (NE) is defined clinically on the basis of findings of abnormal consciousness, depressed tone and reflexes, abnormal respiration or seizures in an infant beyond 35 weeks gestational age.   Hypoxic-ischemic encephalopathy (HIE) is the term for brain injury associated with asphyxia.   HIE is a subset of NE; however, less than 30% of cases of NE meet criteria for intrapartum hypoxia. Cerebral palsy (CP) is a chronic disability of CNS origin characterized by aberrant control of movement and posture which appears early in life and is not due to progressive neurologic disease. Although NE does not always result in permanent neurologic impairment, the pathway from an intrapartum hypoxic-ischemic injury to CP MUST progress through NE.

The following items will determine the likelihood that an acute peripartum or intrapartum event occurred contributing to neonatal encephalopathy in infants > 35 weeks:

I. Neonatal Signs Consistent with Acute Peripartum or Intrapartum Event

  1. Apgar score of less than 5 at 5 and 10 minutes of age
  2. Fetal umbilical artery ischemia (pH <7.0 or base deficit ≥ 12mmol/L)
  3. Neuroimaging evidence of early acute brain injury on MRI (ideally between 24-96 hours of age)
  4. Presence of multisystem organ failure (renal failure, hepatic injury, hematologic abnormalities, cardiac dysfunction, metabolic derangements, GI injury)

II. Type and Timing of Contributing Factors Consistent with Acute Peripartum or Intrapartum Event

  1. A sentinel hypoxic or ischemic event occurring immediately before or during labor and delivery (uterine rupture, abruption placentae, cord prolapse, maternal cardiovascular collapse or severe hypotension and hypoxemia, fetal exsanguination)
  2. A sudden and sustained fetal bradycardia or the absence of fetal heart rate variability in the presence of persistent, late, or variable decelerations, usually after a hypoxic sentinel event when the pattern was previously normal (original Category I tracing then converts to Category III).
  3. Imaging pattern and brain injury type consistent with acute peripartum or intrapartum event
    1. Cranial ultrasound: shows echogenicity or echodensity 48 hours or longer after an ischemic cerebral injury
    2. CT:   often normal for the first 24-48 hours after an injury
    3. MRI and magnetic resonance spectroscopy: most sensitive at 24-96 hours with diffusion abnormalities most prominent at this time. A second scan at 10 days of life or later will show extent of injury.
  4. No evidence of other contributing factors (abnormal fetal growth, maternal infection, fetomaternal hemorrhage, neonatal sepsis, chronic placental lesions)

III. Developmental Outcome is Spastic Quadriplegia or Dyskinetic Cerebral Palsy

Incidence of HIE

The incidence of moderate or severe HIE has remained essentially unchanged over the past 20 years (1.4-1.8 per 1000 live births). About 15-20% will die and 20-25% of survivors will be disabled.

Etiology/Pathogenesis of HIE

Infants suspected of having sustained an asphyxial event can generally be identified by the prenatal and perinatal history. Recognition of conditions placing the infant at high risk for asphyxia or depression allows for advanced preparation of a neonatal resuscitation.

Conditions associated with increased risk of fetal asphyxia are: 1) altered placental exchanges (placenta abruptio, placenta previa, prolapsed cord, postmaturity), 2) altered maternal blood flow to the placenta (maternal hypotension, maternal hypertension, abnormal uterine contractions), or 3) reduced maternal arterial oxygen saturation (maternal hypoventilation, maternal hypoxia, maternal cardiopulmonary disease).

A low Apgar score indicates an abnormal condition but not a specific cause. It is important to remember that infants lose their color, respirations, tone, reflexes and heart rate in that order. Effective resuscitation restores functions in a different order: heart rate, reflexes, color, respirations and tone. The amount of time required for restoration of tone and respirations may assist in indicating the severity or duration of the asphyxial insult to the CNS.

The CNS is the organ most frequently affected (72%) by asphyxia, and includes selective neuronal necrosis, status marmorata of basal ganglia and thalamus (more in term infants) and periventricular leukomalacia (more common in prematures)

Associated complications in asphyxiated infants include: hypoglycemia, hypocalcemia, seizures, myocardial ischemia (30%), acute tubular necrosis (42%), renal failure, disseminated intravascular coagulation, hepatic injury (30%), pulmonary hypertension, pulmonary hemorrhage, blood pressure instability with hypotension, subarachnoid hemorrhage, intraventricular hemorrhage, CNS ischemia and infarction.

Management

After the initial steps of neonatal resuscitation, management of an asphyxiated infant includes: assisting the infant to obtain adequate ventilation, oxygenation, pulmonary perfusion, and cardiac output, minimizing body heat loss and maintaining peripheral circulation. The next steps in management would include to:

  1. Provide a continuous infusion of glucose to maintain serum blood glucose greater than or equal to 40 mg/dl.
  2. Provide oxygen to maintain normal oxygenation by transcutaneous and/or arterial oxygen monitoring. (paO2>50),
  3. Maintain carbon dioxide levels in the normal to low normal range to prevent excess cerebral blood flow to potentially injured and ischemic areas. Avoid hypo-or   hypercarbia.
  4. Load with phenobarbital 20-40mg/kg total dose, depending on the clinical situation.
  5. Maintain cerebral perfusion by maintaining a steady mean arterial blood pressure with pressor agents (dopamine and dobutamine), if necessary. Avoid fluctuations in blood pressure by not administering rapid infusions of volume expanders, sodium bicarbonate and hyperosmotic solutions.
  6. Restrict total fluid intake to 60-80 cc/kg/day.
  7. Monitor the urine output. These infants are at high risk for acute tubular necrosis and the effects of inappropriate excretion of ADH. Care should be taken in administering medications that may be nephrotoxic in asphyxiated infants by closely monitoring levels or adjusting normally administered doses. In the severely asphyxiated infant or a paralyzed infant placement of a bladder catheter may be desired. Urine electrolytes, urine osmolalities and urine dipstick may also be necessary.
  8. Obtain a set of electrolytes and calcium, magnesium and phosphorous levels. If the infant's calcium or magnesium are low these will need to be corrected and followed. Correction may improve cardiac function by improving contractility with resultant improved cardiac output and perfusion.
  9. Obtain a complete blood count. Monitor the hematocrit and platelet count (if initially abnormal) every 12 hours. Correct platelet counts in the acute period to maintain a platelet count greater than or equal to 70,000. Maintain a hematocrit greater than or equal to 35.
  10. Do a complete neurologic examination and head circumference. Make note of the reflexes involving the cranial nerves, deep tendon reflexes, spontaneous movement of the extremities, Moro, grasp, suck, the tone, and overall response of the infant to pain or stimulation. THIS IS VERY IMPORTANT.
  11. A head ultrasound and/or CT scan may be considered in infants with suspected IVH, subarachnoid hemorrhage, subdural or subgaleal hemorrhage MRI or suspected intracranial defect.
  12. Close observation for development of evidence of seizures. The incidence of seizures in perinatal asphyxia occurs generally within the first 12 hours after birth. In severely perinatal asphyxiated infants anticonvulsant therapy may be considered before evidence of clinical seizures.
  13. Consider an EEG evaluation to determine the overall electrical activity and pattern whether or not there is evidence of seizure activity.
  14. Controlled hypothermia should be initiated within 6 hours of birth and continued for 48-72 hours for neonates with HIE over Stage I (see Sarnat criteria below).

In the general management of the asphyxiated patient, eliminating the hypoxia, alleviating tissue ischemia, and providing supportive care for anticipated problems in an expeditious manner is imperative. Each infant will respond differently and overall outcomes are difficult to predict.

Findings associated with poor prognosis are:

Determining Severity

A staging procedure designed by Sarnat and Sarnat for hypoxic-ischemic encephalopathy may be helpful to determine the severity of the asphyxial event and suspected long term outcome based upon their findings.   The stages in this table reflect the clinical state of infants over 36 weeks' gestational age. (Source: H.B. Sarnat and M.S. Sarnat, Neonatal encephalopathy following fetal distress: A clinical and electroencephalographic study. Arch. Neurol. 33:696, 1976.)

Careful assessment of the baby to assign a stage is very useful (see following table).

SARNAT STAGING CRITERIA FOR HIE

 

Stage

 

Stage I

 

Stage II

 

Stage III

 

Level of consciousness

 

Hyperalert

 

Lethargic or obtunded

 

Stuporous

 

Neuromuscular control

        Muscle tone

        Posture

        Stretch reflexes

        Segmental myoclonus

 

 

Normal

Mild distal flexion

Overactive

Present

 

 

Mild hypotonia

Strong distal flexion

Overactive

Present

 

 

Flaccid

Intermittent decerebration

Decreased or absent

Absent

 

Complex reflexes

        Suck

        Moro

 

 

Stage

        Oculovestibular

        Tonic neck

 

 

Weak

Strong, low threshold

 

Stage I

Normal

Slight

 

 

Weak or absent

Weak, incomplete high threshold

 

Stage II

Overactive

Strong

 

 

Absent

Absent

Weak or absent

 

Stage III

Absent

 

Autonomic function

        Pupils

        Heart rate

        Bronchial and salivary secretions

        Gastrointestinal

motility

 

Generalized sympathetic

Mydriasis

Tachycardia

Sparse

Normal or decreased

 

Generalized parasympathetic

Miosis

Bradycardia

Profuse

Increased diarrhea

 

Both systems depressed

Variable, often unequal, poor light reflex

Variable

Variable

Variable

 

Seizures

 

None

 

Common focal or multifocal

 

Uncommon (excluding decerebration)

 

Electroencephalographic findings

 

Normal (awake)

 

Early: low-voltage, continuous delta and theta

Later: periodic pattern (awake); seizures focal; 1.0-1.5 Hz spike-and-wave

 

Early: periodic pattern with isopotential phases

Later: totally isopotential

 

Duration

 

 

<24 hr

 

2-14 days

 

Hours to weeks

 

Reference

ACOG/AAP Task Force on Neonatal Encephalopathy, 2014

 


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