“Hypoxic Ischemic Encephalopathy” From PedsCases

This post contains links to the podcast and transcript of Hypoxic Ischemic Encephalopathy [Link to Podcast] [Link to Transcript], by Carina.Lauzon Aug 15, 2018 from PedsCases.*

*Here is the complete list of the Table Of Contents of the PedsCases website. On this page the site has organized all of the contents into two groups: Clinical Presentation and Specialty Area.

Here are excerpts from the transcript:

Summary [from the end of the transcript]

  1. In HIE, injury to the brain occurs in two phases: the primary and secondary phases. The primary phase refers to the initial period of hypoxia and ischemia, in which damage occurs in the form of necrosis. The secondary phase occurs 12- 36 hours after the injury and in this phase, cell death occurs via apoptosis.
  2. Risk factors for HIE include anything that decreases oxygen and blood flow to the brain. This includes umbilical cord issues, placental complications, and birth complications.
  3. The signs and symptoms of HIE vary between mild, moderate, and severe HIE, but general symptoms include decreased level of consciousness, hypotonia, weak primary reflexes, and seizures.
  4. The mainstay of treatment for HIE is therapeutic hypothermia. Infants born at or after 35 weeks gestation who have moderate to severe HIE should be cooled within the first 6 hours of life to a rectal temperature in between 33 and 34 degrees Celsius for a period of 72 hours. Therapeutic hypothermia reduces the damage that occurs during the secondary phase of HIE and thus, decreases mortality and morbidity.
    5. The prognosis of HIE ranges from an almost 0% morbidity and mortality rate in mild HIE, to a 80% mortality rate and nearly 100% incidence of adverse neurodevelopmental outcomes in severe HIE. The rate of neurodevelopmental impairment is between 20 and 35% in moderate HIE; however, it is difficult to predict which infants will go on to develop adverse outcomes and the severity of impairment cannot always be determined until the child is three to four years old.

Clinical Case

Let’s start with a clinical case: you are a third year medical student working on your pediatrics rotation. During your evening shift, you are called for an emergency Caesarean section for a term baby who has persistent fetal bradycardia. At the time of delivery, the obstetric team told the pediatric team that there was a placental abruption. The baby is born flat, is cyanotic, and is not breathing. The resuscitation team initiates positive pressure ventilation, and despite a good technique, no heart sounds are heard.
The team inserts a breathing tube and starts chest compressions. After one minute of CPR there are still no heart sounds. They give epinephrine into the breathing tube and resume CPR. After three minutes, some faint heart sounds are heard. A second dose of epinephrine is given in an umbilical venous catheter that was urgently inserted. Two minutes later, a heart rate is recorded and the team is able to stop chest compressions, the heart rate steadily increases above 100. As the baby is still not breathing, a mechanical ventilator is attached to the breathing tube to ventilate and oxygenate the
baby. Considering what you know about this patient, what should your next steps be in terms of brain protection? We will review the answer to this case at the end of the podcast.

What is HIE?

Hypoxic Ischemic Encephalopathy (HIE) is caused by brain injury that occurs due to impairment of oxygen delivery (hypoxia) and blood perfusion (ischemia) to the brain. This happens as a result of an impairment of the exchange of oxygen and carbon dioxide, which leads to hypoxia, hypercapnia, metabolic acidosis, and other acute nutrient deficiencies. HIE is the leading cause of death or severe impairment, including
epilepsy, cerebral palsy, neurodevelopmental delay, and cognitive impairment, in infants worldwide.

In HIE, injury to the brain occurs in two phases, known as the primary and
secondary phases. The primary phase refers to the hypoxic ischemic injury itself.

The secondary phase of brain injury due to HIE is perhaps more significant than the first, and it is on this phase that current treatment regimens are focused. The secondary phase begins 12-36 hours after injury and may last up to 14 days without treatment.

Risk factors/Causes of HIE

HIE is caused by reduced blood and oxygen delivery to the brain and therefore, anything that causes this is a risk factor for HIE. The main categories of risk factors for HIE include umbilical cord issues, placental complications, and birth complications.

Because the umbilical cord is the fetus’ only source of oxygen and nutrients, its function is critical. Occlusion or compression of the umbilical cord decreases the amount of blood flow to the fetus. This can happen as a result of many factors, [cord prolapse, nuchal chord, knotted cord, and others]. Oligohydraminos and polyhydramnios are additional risk factors for umbilical cord compression.

Placental complications that are associated with HIE include placental abruption, ruptured vasa previa, and preeclampsia. Maternal hypotension can result in decreased placental perfusion and thus, decreased delivery of blood to the fetus, and can occur for a variety of reasons, including infection, intrapartum haemorrhage, and uterine rupture.

Finally, complications that occur during and around the time of birth are a risk factor for HIE. These include birth injury due to cephalopelvic disproportion, shoulder dystocia, and improper use of forceps or vacuum extractor during delivery. Additionally, any condition that has the potential to block the baby’s airways or impair the lungs’ or heart’s function for an extended period of time may lead to decreased oxygenation and perfusion of the brain after birth.

Signs and Symptoms

The clinical presentation of HIE depends on the severity of the insult. HIE can be grouped into three categories of symptoms: mild, moderate, or severe.

Mild signs and symptoms include hyperalertness, tachycardia, mydriasis, and a weak suck reflex. Tone is normal or increased, stretch reflexes are overactive, and segmental myoclonus is present. There are no seizures.

Moderate signs and symptoms of HIE include lethargy, hypotonia, bradycardia, periodic respirations, and weak primitive reflexes. Overactive stretch reflexes, segmental myoclonus, and miosis are also seen, and seizures are commonly present.

In severe HIE, signs and symptoms include stupor or coma, flaccidness, absent primitive reflexes, and apnea. Seizures are less commonly present than in moderate HIE.


The mainstay of treatment for HIE is therapeutic cooling. Achieving therapeutic hypothermia to a rectal temperature between 33 and 34 degrees Celsius prevents delayed cell death in the secondary phase of HIE and decreases mortality and long term neurodevelopmental disabilities in term infants. The number needed to treat is 7 for the combined outcome of death and major neurodevelopmental disability. Cooling has a broad inhibitory effect on a variety of harmful cell processes that occur during the secondary phase of HIE. 

Cooling should be initiated as soon as possible, within the first 6 hours of life in infants with HIE, and the optimal duration of cooling is 72 hours.

In order to be a candidate for cooling, an infant must be less than 6 hours old, greater than or equal to 35 weeks gestational age, and must meet criteria A and B and, in some centres, criteria C. 

[Please see p 4 of the transcript PDF for details on Criteria A, B, and C. See p 4 also for details on cooling and on rewarming.]

In addition to therapeutic cooling, management of HIE includes avoidance of hyper and hypoglycemia, as both are associated with death and long-term disability at 18 months of age in infants with moderate to severe HIE. For all term infants, resuscitation in room air is preferred over resuscitation with 100% oxygen. This is because the use of high concentrations of oxygen can cause hyperoxia, which can lead to excessive release of oxygen free radicals and aggravation of brain injury.


The prognosis of HIE depends upon the severity of the injury, and the ability to determine the prognosis is hindered by the difficulty in determining the actual severity of the insult. The mortality rate ranges from 0% in mild HIE, to 5% in moderate HIE, to 80% in severe HIE. However, death is often the result of withholding and/or withdrawing care, and is not always the natural progression of the injury in babies with severe HIE.
In infants with moderate to severe HIE treated with therapeutic hypothermia, the mortality rate is about 24-38%.

Another important part of prognosis to consider is the child’s risk of adverse neurodevelopmental outcomes.

In infants who suffer from mild HIE, the rate of adverse neurodevelopmental outcomes does not differ significantly from the general population.

In infants with moderate HIE, the rate is about 20-35%, and the risk is higher if seizures are present.

In severe HIE, nearly 100% of survivors will have significant impairments. Possible long-term impairments include cognition and developmental delay, learning disabilities, cerebral palsy, blindness, gross motor and coordination problems, epilepsy, deafness, and behavioural problems.

In infants with moderate HIE, it is difficult to predict who will suffer from adverse neurodevelopmental outcomes and the severity of impairment sometimes cannot be determined until the child is three to four years old.


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