Understanding Hypoxic-Ischemic Encephalopathy (HIE) and Therapeutic Hypothermia

Hypoxic-Ischemic Encephalopathy (HIE) is one of the most time-sensitive and impactful diagnoses in neonatal care. It’s a condition that can unfold rapidly and leave lasting effects, but with timely intervention — specifically therapeutic hypothermia — outcomes can be improved. In this post, we’re diving into the pathophysiology, risk factors, cooling criteria, and what NICU nurses need to know to care for these high-risk infants.

The Scope of the Problem

HIE affects approximately 2.4 per 1,000 births in the United States. Globally, birth asphyxia is responsible for 23% of neonatal deaths — contributing to over 920,000 deaths each year and linked to an additional 1.1 million intrapartum stillbirths. HIE is also the leading cause of neonatal seizures, and the fifth leading cause of death for children under the age of five.

So... why is this happening?

What is HIE?

Hypoxic-Ischemic Encephalopathy occurs when the brain is deprived of adequate oxygen (hypoxia) and blood flow (ischemia) around the time of delivery. This results in neurologic injury that can range from mild to severe and can affect motor function, cognition, and long-term development.

Pathophysiology of HIE

When oxygen and glucose delivery to the brain is interrupted:

• The brain shifts to anaerobic metabolism, leading to lactic acid buildup and cellular acidosis.

• ATP stores deplete, and ion pumps begin to fail, causing cellular swelling.

• Glutamate, an excitatory neurotransmitter, is released in excess — resulting in calcium influx, oxidative stress, and neuronal death.

• This begins a cascade of inflammation and secondary injury, often evolving over hours to days.

Risk Factors for HIE

Placental Risks

• Placental abruption

• Placental insufficiency

• Vasa previa

Cord Risks

• Nuchal cord

• True knots

• Cord prolapse or cord accidents

Uterine Risks

• Uterine rupture

• Prolonged second stage of labor

• Uterine hyperstimulation

Other Risks

• Shoulder dystocia

• Maternal trauma or hypoxia

• Meconium aspiration syndrome

• Severe fetal anemia

• Maternal hypotension or cardiac arrest

Who Gets Cooled? Criteria for Therapeutic Hypothermia

Not every baby with distress at birth qualifies for cooling. Current criteria generally include:

• Gestational age >36 weeks

• Birth weight >1800 grams

• Age <6 hours at time of evaluation

• Apgar score <5 at 5 minutes

• Cord pH <7.0 or base deficit >12

• Clinical signs of moderate to severe encephalopathy on neurologic exam (Sarnat staging)

A comprehensive neurologic assessment — including tone, level of consciousness, reflexes, and seizure activity — helps determine eligibility.

What is Therapeutic Hypothermia?

Therapeutic hypothermia is a neuroprotective treatment that lowers the core body temperature of the infant to 33.5°C for 72 hours, followed by slow rewarming. It may be done using a cooling blanket or a cooling cap, depending on the unit's protocols.

Pathophysiology of Cooling: Why It Works

After the initial injury, the brain enters a latent phase where damaged cells may still recover — this is the window for intervention.

Therapeutic hypothermia works by:

• Slowing metabolism and reducing cellular energy demands

• Decreasing glutamate release and calcium influx

• Limiting free radical formation

• Reducing inflammation

• Delaying or halting apoptosis (programmed cell death)

Cooling stabilizes the injury and prevents damage from spreading to healthy surrounding tissue.

Why Do We Cool?

Cooling doesn’t reverse brain damage that has already occurred — but it can:

• Stop the spread of injury

• Preserve borderline cells

• Minimize inflammation and secondary damage

This provides the brain with a better opportunity to heal and recover.

Monitoring During Cooling

Therapeutic hypothermia requires intensive monitoring:

• Continuous temperature monitoring (core vs. skin)

• EEG or aEEG for seizures

• Cardiovascular monitoring (bradycardia is expected)

• Blood pressure, glucose, and coagulation panels

• Watching for electrolyte shifts, hypoglycemia, and coagulopathy

Parent Education: What to Say

HIE and therapeutic hypothermia are overwhelming topics for families. Here’s what we can share:

• Their baby experienced an event that affected oxygen and blood flow to the brain.

• We are cooling their baby’s body to slow down the injury and give the brain time to heal.

• Cooling helps protect the brain, but we won’t know the full outcome right away and may not for months to years.

• We will monitor brain function, heart rate, temperature, and lab values closely during treatment.

• This is a highly specialized treatment shown to improve long-term outcomes in babies with HIE.

Compassionate, honest communication goes a long way in building trust and supporting families during this critical time.

In Summary

HIE is a serious diagnosis that carries significant risks, but early identification and intervention with therapeutic hypothermia can significantly improve outcomes. As NICU nurses, we are often the first to recognize the signs of encephalopathy and advocate for treatment. Understanding the science behind both the injury and the therapy empowers us to give the best care to our tiniest patients — and support their families every step of the way.