HIE isn't just brain injury—it's "hypoxic ischemic everything!" Every organ system is affected!

April is HIE Awareness Month!

🧠 What is HIE?

April is HIE Awareness Month, and this week we are talking all about one of the most critical and complex conditions we encounter in the NICU—Hypoxic Ischemic Encephalopathy (HIE).

HIE is a type of brain injury caused by a lack of oxygen (hypoxia) and reduced blood flow (ischemia) to a baby's brain. While it most commonly occurs during the perinatal period, HIE can happen at any point in life. Understanding the pathophysiology, treatment strategies, and evolving nature of this condition is essential to providing high-quality, neuroprotective care.

⚠️ Why Does HIE Happen?

While we often associate HIE with complications during delivery, it can occur at any point in life. Current research suggests that a significant portion of cases have no identifiable intrapartum cause and may be related to antepartum factors. Known contributors include:

• Maternal conditions: preeclampsia, HELLP syndrome, maternal diabetes, thyroid disorders

• Acute events: uterine rupture, cord prolapse, placental abruption, maternal cardiac arrest

• Delivery complications: shoulder dystocia, prolonged fetal heart rate decelerations, difficult instrumental delivery

Ultimately, HIE results from impaired fetal gas exchange, hypoxemia, and cerebral ischemia, leading to disruption of cerebral energy metabolism.

🔄 The Evolving Injury: Phases of HIE

HIE is not a one-time event—it unfolds in phases:

1. Primary Energy Failure The initial asphyxia event reduces oxygen and glucose to the brain. Cells switch to anaerobic metabolism, leading to:

• ATP depletion

• Intracellular flooding of sodium, water, & calcium

• Cellular swelling and necrotic cell death

• Release of excitatory amino acids (especially glutamate) and inflammatory markers

2. Latent Phase (0–6 hours post-resuscitation) This brief window shows partial clinical improvement, but the injury is still progressing on a cellular level. This is the crucial window for initiating therapeutic hypothermia.

3. Secondary Energy Failure (6–72 hours) The most damaging phase, with increased excitotoxicity, oxidative stress, mitochondrial failure, and delayed neuronal death via apoptosis.

4. Tertiary Phase (days to years later) Characterized by persistent inflammation, altered epigenetics, impaired oligodendrocyte maturation, and abnormal neuronal circuit development influencing long-term outcomes.

🧊 Therapeutic Hypothermia: The Gold Standard

Initiating cooling within 6 hours after birth is key. Therapeutic hypothermia slows metabolism, reduces glutamate release, and decreases free radical production. Multiple randomized controlled trials have shown that:

• Moderate hypothermia (33-34°C) for 72 hours

• Started within 6 hours of birth

• Reduces mortality and major neurodevelopmental disability in eligible infants by approximately 25%

Who qualifies?

• ≥36 weeks gestation and birth weight ≥1800g

• Evidence of perinatal depression with either:

  • Cord or postnatal blood gas (within 60 min) with pH <7.0 or base deficit ≥ -16

  • OR pH 7.01–7.15 with base deficit -10 to -15.9 AND history of acute perinatal event plus either need for ventilation at 10 minutes or Apgar ≤5 at 10 minutes

• Evidence of moderate to severe encephalopathy via modified Sarnat Exam

🧪 Diagnosing HIE: Tools We Use

A combination of clinical assessment and diagnostics helps us stage and manage HIE:

• Apgar scores (especially at 5, 10, and 15 minutes)

• Neurologic exam & modified Sarnat staging (assessing level of consciousness, tone, reflexes, autonomic function)

• Blood gases (cord and postnatal)

• EEG/aEEG monitoring (to detect subclinical seizures and assess background patterns)

• MRI findings (ideally performed 5-7 days after birth to assess pattern and extent of injury)

🩺 Clinical Considerations at the Bedside

These babies require vigilant, skilled nursing care:

🧠 Seizures

• HIE is the #1 cause of neonatal seizures, occurring in 30-60% of moderate to severe cases

• Continuous EEG/aEEG monitoring is essential as 50-65% of seizures may be clinically silent

• First-line treatment typically includes phenobarbital

  • Levetiracetam (Keppra) is a promising alternative for neonatal seizures. However, its efficacy can vary, and further research is needed to optimize dosing and fully understand its role in neonatal seizure management.

🫁 Respiratory Support

• Risk for PPHN, MAS, and respiratory failure

• Avoid both hypercarbia (worsens acidosis) and hypocarbia (decreases cerebral blood flow)

• Maintain normal oxygenation (SpO2 92-98%) to avoid secondary injury from hypoxemia or hyperoxemia

❤️ Cardiovascular Management

• Risk of myocardial dysfunction and hypotension (present in up to 62% of HIE infants)

• Individualize use of inotropes and vasoactive drugs to maintain blood pressure

• Consider echocardiography to guide cardiovascular support

🩸 Metabolic & Hematologic Issues

• Avoid rapid sodium bicarbonate boluses—this is linked to worse outcomes and intracranial hemorrhage

• Monitor and treat hypoglycemia aggressively (maintain glucose >45-50 mg/dL)

• Anticipate thrombocytopenia and coagulopathy

👶 Multisystem Impacts

• Renal: Acute kidney injury in 30-70% of cases, fluid overload (SIADH), and acute tubular necrosis

• Hepatic: Poor glucose regulation, elevated transaminases, coagulopathy

• GI: Paralytic ileus, NEC risk from mesenteric hypoperfusion

I'll never forget one speaker talking about HIE at a conference clearly stating, HIE isn't just brain injury—it's "hypoxic ischemic everything!" Every organ system is affected!

🧬 What’s New in HIE Research? Cooling in Late Preterms May Not Help—and Might Harm

A 2025 randomized clinical trial published in JAMA Pediatrics investigated whether whole-body therapeutic hypothermia (cooling) benefits preterm infants born at 33–35 weeks gestation with moderate or severe HIE. Until now, evidence has supported cooling only for infants ≥36 weeks, but this study explored whether that could extend to slightly younger babies.

Study design highlights:

• 168 infants (33–35 weeks GA) randomized to hypothermia vs normothermia within 6 hours of birth

• Cooling was maintained at 33.5°C for 72 hours

• Primary outcome: death or moderate/severe disability at 18–22 months

Key findings:

• No benefit of cooling was observed in this group

• In fact, hypothermia may increase harm:

  • 74% probability of increased harm

  • 87% probability of increased death

• Preterm infants who were cooled were more likely to experience overshooting into dangerously low temperatures (<32°C), which may have contributed to worse outcomes

• The authors concluded: therapeutic hypothermia is not recommended for infants under 36 weeks gestation unless future trials prove otherwise

🧠 Why it matters for NICU nurses:
This study shifts how we think about HIE in late preterm infants. While cooling remains the gold standard for term infants, we must be cautious about extrapolating protocols to younger gestations. As NICU nurses, it’s critical to advocate for individualized, evidence-based care—especially for these vulnerable patients.

Want more info on HIE?

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What questions do you have about HIE or therapeutic hypothermia. I'm planning on adding a video about HIE to my YouTube channel. Email me back and let me know what you'd like me to cover or if you have any questions.

Wishing you the best

Amanda

References

Faix RG, Laptook AR, Shankaran S, et al. Whole-Body Hypothermia for Neonatal Encephalopathy in Preterm Infants 33 to 35 Weeks' Gestation: A Randomized Clinical Trial. JAMA Pediatr. 2025;179(4):396-406. doi:10.1001/jamapediatrics.2024.6613

Volpe, J. (2025). Volpe's Neurology of the Newborn, Seventh Edition. Elsevier

Verklan, M. T., &Walden, M. (2015). Core curriculum for neonatal intensive care nursing (Fifth ed.). St. Louis, Missouri: Elsevier Saunders

Gardner, S. L., Carter, B. S., Hines, M. E., & Hernandez, J. A. (2016). Merenstein & Gardner's Handbook of Neonatal Intensive Care (Eighth ed.). St. Louis, Missouri: Elsevier.

Gomella T, & Eyal F.G., & Bany-Mohammed F(Eds.), (2020). Gomella's Neonatology: Management, Procedures, On-Call Problems, Diseases, and Drugs, 8e. McGraw Hill.

Hope for HIE (2023) What is HIE: HIE Overview. Retrieved from https://www.hopeforhie.org/whatishie/

Douglas-Escobar, Martha & Weiss, Michael. (2015). Hypoxic-Ischemic Encephalopathy: A Review for the Clinician. JAMA pediatrics. 169. 10.1001/jamapediatrics.2014.3269.

Power, B., McGinley, J., Sweetman, D.U., & Murphy, J.F. (2019). The Modified Sarnat Score in the Assessment of Neonatal Encephalopathy: A Quality Improvement Initiative. Irish medical journal, 112 7, 976 .

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