Neonatal hypoxic-ischemic encephalopathy (HIE) nursing: Sarnat staging, therapeutic cooling, and NCLEX tips

Hypoxic-ischemic encephalopathy (HIE) is the most common cause of neonatal brain injury in term and near-term infants, occurring in 1–3 per 1,000 live births in high-income countries and accounting for approximately 23% of neonatal deaths worldwide. It results from a combination of oxygen deprivation and impaired cerebral blood flow around the time of delivery — a dual insult that triggers a cascade of neuronal injury extending hours to days beyond the initial event.

For nursing students, HIE is high-yield for several reasons. The eligibility criteria for therapeutic hypothermia are NCLEX-tested directly. Sarnat staging is a foundational concept that appears in both examination questions and clinical decision-making. And the nursing role during therapeutic cooling — temperature monitoring, seizure surveillance, glucose management, and family support — is demanding and specific. This reference covers the full clinical picture: pathophysiology, Sarnat staging, the therapeutic hypothermia protocol (including the TOBY and CoolCap trial evidence), seizure management with amplitude-integrated EEG, multi-organ complications, and 10 high-yield NCLEX tips.

Use this alongside the neonatal resuscitation guide — neonatal resuscitation is the event that precedes HIE — and the neonatal hypoglycemia reference, since hypoglycemia complicates HIE management and shares glucose monitoring priorities.

Sarnat staging: quick reference

Source: Sarnat HB, Sarnat MS. “Neonatal encephalopathy following fetal distress.” Archives of Neurology 1976.

Pathophysiology: the two-phase energy failure model

Understanding the pathophysiology of HIE is essential to understanding why therapeutic hypothermia works — and why timing matters so precisely.

Primary energy failure

The initial hypoxic-ischemic event — placental abruption, cord prolapse, uterine rupture, prolonged variable or late decelerations, or any event that significantly reduces fetal oxygen delivery — triggers primary energy failure within minutes. Without adequate oxygen, mitochondrial oxidative phosphorylation fails and ATP production collapses. Neurons shift to anaerobic glycolysis, producing lactate and creating intracellular acidosis. Failure of the Na⁺/K⁺-ATPase pump allows sodium and calcium to flood into cells; glutamate is released in toxic quantities, causing excitotoxicity. Cellular swelling, apoptosis, and necrosis follow.

If the insult is severe enough, primary energy failure alone causes immediate cell death in the most vulnerable areas — the basal ganglia, thalamus, cortex, and brainstem. Critically, after the initial insult is resolved (through resuscitation and restoration of circulation), there is a short window — the latent phase — where cerebral energy metabolism partially recovers. Lactate clears, EEG improves transiently, and clinically the infant may appear less depressed than expected. This window is narrow — typically 1–6 hours.

Secondary energy failure and the therapeutic window

Six to 48 hours after the initial insult, secondary energy failure occurs. Mitochondrial dysfunction resumes despite restored oxygen delivery, driven by the reperfusion injury cascade: reactive oxygen species (ROS), nitric oxide toxicity, activation of apoptotic pathways, and cytokine-mediated inflammation. Secondary energy failure causes ongoing neuronal death in areas that survived the primary insult — this is where the bulk of preventable brain injury occurs.

Therapeutic hypothermia works by interrupting this secondary energy failure cascade. Cooling reduces the cerebral metabolic rate, suppresses glutamate release, inhibits apoptotic pathways, reduces ROS production, and limits mitochondrial membrane damage. The critical constraint is timing: cooling must begin within 6 hours of birth — ideally within 3–4 hours — before the secondary energy failure cascade becomes self-sustaining and irreversible. Cooling initiated after 6 hours has not been shown to provide meaningful neuroprotection.

This is why HIE is simultaneously a resuscitation priority, a diagnostic challenge, and a nursing emergency in the first hours of life.

Therapeutic hypothermia protocol

Therapeutic hypothermia is the only intervention with robust evidence for improving neurodevelopmental outcomes in HIE. The TOBY trial (Azzopardi et al., NEJM 2008) and CoolCap trial (Gluckman et al., Lancet 2005) established the evidence base for both whole-body cooling and selective head cooling, respectively. Meta-analyses confirm a number needed to treat of approximately 8 — for every 8 eligible infants cooled, one death or major disability is prevented.

Eligibility criteria

Therapeutic hypothermia is indicated for neonates meeting all of the following:

• Gestational age ≥36 weeks (the evidence base is for term and late-preterm infants; use in <36 weeks is investigational)
• At least one of the following:
  • Apgar score ≤5 at 10 minutes of life
  • Continued need for resuscitation (PPV, chest compressions, or intubation) at 10 minutes of life
  • Cord blood or postnatal arterial blood gas (within 1 hour of birth) showing pH <7.0 or base excess ≤ −16 mEq/L
  • Abnormal neurological examination consistent with encephalopathy (altered tone, level of consciousness, or reflexes — i.e., Sarnat Grade II or III)

Infants must meet both criteria (gestational age threshold AND clinical/biochemical evidence) to be eligible. The APGAR score is directly embedded in the eligibility criteria — NCLEX questions test this connection explicitly.

Protocol: whole-body servo-controlled cooling

Exclusion criteria for cooling include major congenital anomalies incompatible with life, severe coagulopathy (relative), and gestational age below the threshold. Passive cooling during transport to a cooling center is appropriate when active servo-control is unavailable — but again, avoiding overshoot below 33°C is critical.

Nursing monitoring during therapeutic hypothermia

During the 72-hour cooling window, the nurse is the primary safety monitor. Key surveillance priorities:

Temperature integrity: Core temperature must remain within the 33–34°C window throughout the 72 hours. Overcooling below 33°C is associated with cardiac arrhythmias, coagulopathy, and impaired platelet function. Overshoot during rewarming (temperature rising above 37.5°C) is associated with worsened neurological outcomes — avoid it.

Seizure surveillance: Approximately 50% of infants with moderate-to-severe HIE will have clinically apparent or electrographic seizures within the first 24–48 hours. Hypothermia reduces seizure frequency but does not eliminate it. Observe for subtle signs: lip smacking, bicycling leg movements, eye deviation, apnea with tonic posturing. Report all suspected seizures immediately.

Minimal stimulation: Infants undergoing therapeutic hypothermia should be handled as little as possible. Cluster all nursing cares. Avoid loud noise and bright light. Painful stimuli can trigger seizures and spike cerebral metabolic rate during a phase when the brain’s metabolic reserve is depleted.

Skin integrity: Prolonged cooling increases pressure injury risk, particularly over the occiput, sacrum, and heels. Reposition within limits of tolerated stimulation. Inspect skin every 2–4 hours.

Seizure management in HIE

Seizures in HIE are a medical emergency. They increase cerebral metabolic demand at the moment when the injured brain has the least reserve. Every seizure minute matters — rapid recognition and treatment are the clinical priority.

Amplitude-integrated EEG (aEEG) monitoring

Conventional 19-electrode EEG requires a trained neurophysiologist to interpret and is not practical for continuous 72-hour NICU monitoring. Amplitude-integrated EEG (aEEG) uses two to four electrodes placed bilaterally over the cortex and displays a time-compressed, semi-logarithmic trace that nurses can monitor in real time. Key aEEG patterns:

• Normal continuous voltage — background margin 10–25 μV; reassuring
• Burst suppression — intermittent high-voltage bursts against a low-voltage background; consistent with moderate HIE
• Continuous low voltage — background consistently below 5 μV; consistent with severe HIE
• Seizure pattern — abrupt rise in minimum voltage with a characteristic “sawtooth” or crescendo-decrescendo appearance, returning to baseline after the seizure ends

aEEG cannot replace conventional EEG for definitive seizure diagnosis, but its continuous display allows nurses to detect evolving electrographic activity and alert the team promptly. Many subclinical electrographic seizures in HIE have no visible clinical correlate — aEEG surveillance is the only way to detect them.

Antiseizure medications

Phenobarbital is the first-line antiseizure medication for neonatal HIE-related seizures across all major guidelines (AAP, ILAE). Loading dose: 20 mg/kg IV over 15–30 minutes. If seizures continue, additional phenobarbital doses of 5–10 mg/kg IV can be given to a maximum cumulative dose of 40 mg/kg before escalating to second-line agents.

Phenobarbital monitoring responsibilities:

• Respiratory depression is the primary adverse effect — have bag-mask ventilation equipment immediately available at the bedside during and after loading
• Monitor respiratory rate and oxygen saturation continuously
• Draw phenobarbital level 24 hours after loading (therapeutic range: 20–40 mcg/mL)
• Report lethargy beyond the baseline HIE-related depression, apnea, or desaturation

Levetiracetam (Keppra) has emerged as a frequently used second-line agent and is being evaluated as an alternative first-line in ongoing trials. Loading dose: 20–60 mg/kg IV over 15 minutes (protocol varies by institution). Levetiracetam has a more favorable adverse-effect profile than phenobarbital — significantly less respiratory depression — but evidence for superiority over phenobarbital is not yet established (NEOLEV2 trial, Glass et al., JAMA Pediatrics 2021). Most NICUs use levetiracetam as a second-line agent when phenobarbital fails or when respiratory compromise makes further barbiturate loading unsafe.

Fosphenytoin (or phenytoin) may be used as a third-line agent. Midazolam continuous infusion is used for refractory neonatal status epilepticus.

Multi-organ complications

HIE is not an isolated brain injury. The same global hypoxia-ischemia that injures the brain simultaneously injures multiple other organ systems — a syndrome sometimes called hypoxic-ischemic multiorgan injury. Recognizing and monitoring for these complications is a central nursing responsibility.

The combination of multi-organ injury with the constraints of therapeutic hypothermia (altered drug metabolism, adjusted fluid balance, cardiac tolerance of bradycardia) makes the HIE infant one of the most complex nursing patients in the NICU.

Nursing interventions: synthesis

The nursing care plan for an infant undergoing therapeutic hypothermia for HIE integrates multiple simultaneous priorities.

Temperature management is the central intervention during the 72-hour cooling window. Verify servo-controlled device function at least hourly. Document core temperature every 30–60 minutes. Any drift outside the 33–34°C target requires immediate correction. During rewarming, measure temperature every hour and verify the rise does not exceed 0.5°C per hour.

Glucose monitoring cannot be deprioritized. Hypoglycemia directly worsens neuronal injury in an already-damaged brain. Hyperglycemia is also harmful — cerebral lactate production is worsened by excess glucose in ischemic conditions. Target blood glucose 50–110 mg/dL throughout cooling and the rewarming phase. Monitor every 1–2 hours and adjust IV dextrose infusion accordingly. See the full protocol in the neonatal hypoglycemia nursing reference.

Seizure observation requires vigilance throughout the cooling period and for at least 24–48 hours afterward. Subtle neonatal seizures — lip smacking, eye deviation, tonic limb extension, apnea with posturing, bicycling — are easy to miss during routine cares. Document all suspected clinical events with time, duration, and description. aEEG leads should be in place throughout. Notify the provider immediately for any suspected seizure.

Vascular access is typically via an umbilical venous catheter (UVC) and/or umbilical arterial catheter (UAC) for continuous blood pressure monitoring, blood sampling, and medication/fluid administration. Maintain line patency and monitor insertion sites for signs of infection or positional compromise.

Nutritional support — enteral feeds are typically withheld during therapeutic hypothermia because of bowel motility concerns (gut ischemia risk) and the need to minimize handling and stimulation. Parenteral nutrition via UVC is the standard approach during the 72-hour window. When rewarming is complete and the infant is clinically stable, cautious enteral feeding can begin — initially with colostrum or breastmilk drops for oropharyngeal immune stimulation before advancing to full feeds.

Family support in HIE is among the most important and most difficult aspects of care. Parents arrive at the NICU having just experienced a terrifying delivery, often with no preparation for what is ahead. The infant is on a cooling device and may be sedated, have limited responsiveness, or be having seizures. Provide clear, consistent, non-technical explanations of what HIE is, what therapeutic hypothermia accomplishes, and what the monitoring shows. Prepare families early for the range of possible outcomes. Encourage presence, eye contact, and verbal interaction — while reinforcing the minimal stimulation protocol. Connect families with NICU social work and chaplaincy support where available.

Long-term outcomes

MRI of the brain at 24–72 hours and again at 7–10 days of life is the most reliable predictor of long-term outcome. Basal ganglia and thalamic injury on MRI correlates with motor deficits and cognitive impairment. Watershed cortical injury correlates more with cognitive and language outcomes. A normal MRI does not guarantee normal outcome in moderate HIE, but is reassuring.

All infants who receive therapeutic hypothermia for HIE should be enrolled in neurodevelopmental follow-up programs — typically through 24–36 months corrected age and ideally through school age — to detect and treat emerging delays as early as possible.

NCLEX tips

1. Therapeutic hypothermia eligibility requires ≥36 weeks gestational age. This is a hard threshold in the evidence base. Infants below 36 weeks are not eligible under current standard-of-care protocols. NCLEX questions may offer an infant at 34 or 35 weeks — the answer is that cooling is not indicated.

2. The Apgar score at 10 minutes is the relevant threshold — not 1 or 5 minutes. An Apgar ≤5 at 10 minutes of life (not 1 minute, not 5 minutes) is one of the eligibility criteria for therapeutic cooling. The APGAR scoring guide reviews scoring domains; know that sustained depression at 10 minutes signals significant asphyxia.

3. Target core temperature is 33–34°C, not 32°C or 35°C. Both overcooling and undercooling are harmful. Below 33°C increases arrhythmia and coagulopathy risk; above 34°C provides inadequate neuroprotection. Servo-controlled devices maintain this narrow range.

4. Rewarming rate is 0.2–0.5°C per hour, over 6–12 hours. Rapid rewarming causes rebound hyperthermia, seizures, and potentially reverses some neuroprotective benefit. The rate is slow and controlled — this is NCLEX-tested.

5. Phenobarbital is the first-line treatment for neonatal seizures in HIE. Loading dose is 20 mg/kg IV. Respiratory depression is the key adverse effect — have airway support available. Levetiracetam is an emerging second-line agent with fewer respiratory effects.

6. Sarnat Grade II is moderate HIE: lethargy, hypotonia, weak Moro and suck, seizures, burst suppression on EEG. Be able to distinguish Grade II from Grade I (irritable, hyperactive reflexes, no seizures) and Grade III (comatose, flaccid, absent reflexes, flat EEG). These findings drive the clinical assessment for cooling eligibility and prognosis discussions.

7. Cooling works by interrupting secondary energy failure — but only if started within 6 hours. The therapeutic window closes by 6 hours postbirth. This is why HIE management is a time-sensitive emergency. NCLEX may ask why cooling must start so quickly — the answer is the secondary energy failure cascade (reperfusion injury) that begins 6–48 hours after birth.

8. aEEG monitors for subclinical seizures throughout the cooling period. Many HIE seizures are electrographic only — no visible clinical signs. aEEG provides continuous monitoring without requiring a full 19-electrode EEG setup. Recognize the burst-suppression pattern and the seizure signature (abrupt voltage rise).

9. Hypoglycemia worsens HIE brain injury and must be corrected immediately. Blood glucose below 40–50 mg/dL in an infant with HIE compounds neuronal injury from the ischemic insult itself. Monitor glucose every 1–2 hours; target 50–110 mg/dL throughout cooling and rewarming. See the neonatal hypoglycemia nursing reference for glucose management.

10. Multi-organ dysfunction is expected, not incidental. The same oxygen deprivation that injures the brain simultaneously injures the kidneys (AKI, SIADH), heart (myocardial dysfunction, PPHN), liver (elevated LFTs, coagulopathy), and gut (bowel motility suppression). NCLEX questions on HIE often focus on complications — know which system each complication comes from and what the nursing monitoring priority is. See the AKI nursing reference for renal monitoring priorities and the seizure nursing reference for seizure management principles.

Related references

• Neonatal resuscitation nursing — NRP algorithm, APGAR scoring, the transition from delivery room to NICU; neonatal resuscitation is the event that immediately precedes and responds to perinatal asphyxia
• Neonatal nursing reference — NICU assessment, vital sign norms, Ballard score, NEC staging, NICU nursing priorities
• Neonatal hypoglycemia nursing — glucose screening protocols, at-risk groups, dextrose gel, IV dextrose management; hypoglycemia compounds HIE neuronal injury
• Neonatal sepsis nursing — sepsis shares many HIE signs (hypothermia, tone changes, seizures) and must be on the differential; both may occur simultaneously in the asphyxiated infant
• Neonatal RDS nursing — respiratory complications and ventilator management in the NICU; PPHN is a complication shared between HIE and severe RDS
• Seizure nursing reference — seizure management principles, antiseizure medications, monitoring; neonatal seizure management in HIE uses phenobarbital as first-line
• AKI nursing reference — renal monitoring, SIADH, oliguria, creatinine interpretation; AKI is a common multi-organ complication of HIE
• APGAR score — the 10-minute Apgar is embedded in the eligibility criteria for therapeutic hypothermia

Clinical sources: Sarnat HB, Sarnat MS, “Neonatal encephalopathy following fetal distress,” Archives of Neurology 1976; Azzopardi DV et al. (TOBY trial), “Moderate hypothermia to treat perinatal asphyxial encephalopathy,” NEJM 2008; Gluckman PD et al. (CoolCap trial), “Selective head cooling with mild systemic hypothermia after neonatal encephalopathy,” Lancet 2005; Shankaran S et al. (NICHD trial), “Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy,” NEJM 2005; Glass HC et al. (NEOLEV2), “Treatment with levetiracetam vs phenobarbital for neonatal seizures,” JAMA Pediatrics 2021; Douglas-Escobar M, Weiss MD, “Hypoxic-ischemic encephalopathy: a review for the clinician,” JAMA Pediatrics 2015; Johnston MV et al., “Hypoxic and ischemic central nervous system disorders in infants and children,” Advances in Pediatrics 2011; Bonifacio SL, Glass HC, “Neonatal seizures,” Seminars in Neonatology 2011; Kenner C, Lott JW, Comprehensive Neonatal Nursing Care, 6th ed.