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

Hypoxic-ischemic encephalopathy (HIE) is a leading cause of neonatal brain injury in term and near-term infants. A systematic review of developed-country data estimated neonatal encephalopathy of any cause at 3.0 per 1,000 live births and HIE specifically at 1.5 per 1,000 (Kurinczuk 2010). 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

Sources: Sarnat HB, Sarnat MS, Archives of Neurology 1976 (stages, EEG, duration); Conway et al., Early Human Development 2018 (mild HIE outcomes). Note that cooling trials and the 2026 AAP report use a modified Sarnat exam at the bedside, and the EEG row above is from the original 1976 description.

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 should begin within 6 hours of birth – ideally within 3–4 hours – before the secondary energy failure cascade becomes self-sustaining. That 6-hour window is where the evidence of benefit is strongest, and it is the target every transport and NICU protocol is built around. Missing it does not close the door entirely: the NICHD late-hypothermia trial (Laptook et al., JAMA 2017) randomized infants cooled between 6 and 24 hours of age and found a Bayesian probability of roughly 76% that late cooling reduces death or disability, though the effect size is small and the estimate imprecise. The 2026 AAP clinical report accordingly states that cooling started between 6 and 24 hours of life may be considered after discussion with the parent or guardian. Treat the 6-hour mark as the goal to protect; an infant who misses it can still be considered for cooling.

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 2009) and CoolCap trial (Gluckman et al., Lancet 2005) tested whole-body cooling and selective head cooling, respectively, and the NICHD trial (Shankaran et al., NEJM 2005) tested whole-body cooling to 33.5°C for 72 hours. In the NICHD trial, death or moderate-to-severe disability at 18–22 months fell from 62% to 44%. TOBY’s primary outcome (death or severe disability) did not reach significance on its own (relative risk 0.86), but cooled infants were more likely to survive without neurologic abnormality and had less cerebral palsy. The Cochrane review of 11 randomized trials found a number needed to treat of 7 (95% CI 5–10): for roughly every 7 eligible infants cooled, one death or major neurodevelopmental disability at 18 months is prevented.

Eligibility criteria

The 2026 AAP clinical report asks centers to use the inclusion criteria from the original trials. In practice an infant must meet all three of the following:

1. Gestational age ≥36 0/7 weeks. This is where the entire randomized evidence base sits, and it is the standard eligibility threshold. The 2026 AAP report adds a qualified exception: at 35 0/7 to 35 6/7 weeks the evidence on safety and effectiveness is limited, so cooling may be considered after a documented discussion of risks and benefits with the parent or guardian. Below 35 weeks, cooling is not recommended.
2. Evidence of a perinatal hypoxic-ischemic event – at least one of:
   • Apgar score ≤5 at 10 minutes of life
   • Continued need for resuscitation (positive-pressure ventilation, intubation, or chest compressions) at 10 minutes of life
   • Cord or postnatal blood gas within 1 hour of birth showing pH <7.0 or base deficit ≥16 mmol/L
3. Moderate or severe encephalopathy on neurological exam (Sarnat stage II or III), or seizures.

Criterion 3 is not optional. An infant with a cord pH of 6.9 and a normal neurological exam is not a cooling candidate, and an infant with clear moderate encephalopathy needs evidence of a hypoxic-ischemic event as well. The AAP report notes that a sentinel event (such as abruption or cord prolapse) does not have to be identified, and that when encephalopathy is clearly moderate or severe but the biochemical criteria are borderline, with no other identifiable cause, clinicians may still consider cooling. The APGAR score is directly embedded in criterion 2, and NCLEX questions test this connection explicitly.

Protocol: whole-body servo-controlled cooling

Common exclusions include major congenital anomalies incompatible with life, severe coagulopathy (relative), and gestational age below the threshold. Cooling during transport helps infants reach the 6-hour target. The 2026 AAP report prefers servo-controlled cooling over passive cooling whenever possible, because passive cooling carries a real risk of overshooting below 33°C. If passive cooling is used, measure core temperature continuously.

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: Seizures are common in moderate-to-severe HIE and usually appear in the first 1–2 days, and many are electrographic only. The 2023 ILAE neonatal seizure guideline found that hypothermia may reduce seizure burden, but it does not eliminate seizures. 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

The 2026 AAP report expects cooling centers to provide continuous neuromonitoring, with continuous conventional (video) EEG preferred and aEEG as the alternative. Conventional EEG needs a neurophysiologist to read it. Amplitude-integrated EEG (aEEG) uses a few electrodes and displays a time-compressed, semi-logarithmic trace that bedside nurses can follow in real time. Key aEEG background patterns (Hellström-Westas classification):

• Continuous normal voltage – upper margin about 10–50 μV, lower margin about 5–10 μV; the normal pattern
• Discontinuous normal voltage – discontinuous trace, lower margin variable but mostly above 5 μV; moderately abnormal
• Burst suppression – near-flat background (lower margin about 0–2 μV) interrupted by bursts above 25 μV; severely abnormal
• Continuous low voltage – background around or below 5 μV; severely abnormal
• Flat trace – inactive background below 5 μV; severely abnormal
• Seizure pattern – abrupt rise in the lower (and usually upper) margin, often followed by a short period of depressed activity

aEEG misses brief or focal seizures that conventional EEG would catch, so it cannot replace conventional EEG for definitive diagnosis. Its continuous display still lets nurses spot evolving electrographic activity and alert the team. Many electrographic seizures in HIE have no visible clinical sign, so EEG-based monitoring is the only way to detect them.

Antiseizure medications

Phenobarbital is the first-line antiseizure medication for neonatal seizures regardless of cause, per the 2023 ILAE Task Force guideline (Pressler et al.). The ILAE also advises treating electrographic-only seizures, since a lower seizure burden may be associated with better outcome. 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 levels per unit protocol; drug handling changes during cooling, and the 2026 AAP report includes a table of pharmacologic considerations during hypothermia
• Report lethargy beyond the baseline HIE-related depression, apnea, or desaturation

Levetiracetam (Keppra) is widely used as a second-line agent. Loading doses of 40–60 mg/kg IV are common (protocols vary). It was tested head to head as a first-line drug in the NEOLEV2 randomized trial (Sharpe et al., Pediatrics 2020), and phenobarbital won clearly: 80% of infants given phenobarbital were seizure-free for 24 hours on EEG, compared with 28% given levetiracetam. Adverse effects were more frequent with phenobarbital, though the difference was not statistically significant. That trade-off is why phenobarbital stays first-line and levetiracetam is a second-line option, particularly when respiratory compromise makes more barbiturate loading unsafe.

The 2023 ILAE guideline lists phenytoin/fosphenytoin, levetiracetam, midazolam, or lidocaine as acceptable second-line agents, with levetiracetam preferred in infants with cardiac disorders. A midazolam continuous infusion is used for refractory seizures.

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. In a post hoc analysis of the CoolCap trial (Basu 2016), hypoglycemia (≤40 mg/dL) and hyperglycemia (>150 mg/dL) in the first 12 hours were each independently associated with death or severe disability at 18 months. Keep glucose within the unit’s target range throughout cooling and rewarming, check it frequently, and adjust the 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 – practice varies. Many units historically withheld enteral feeds during cooling over concern about gut ischemia and NEC, and relied on IV dextrose or parenteral nutrition. A UK population study of 6,030 cooled infants (Gale 2021) found NEC was rare (about 1%) and that infants fed milk during cooling had fewer late-onset infections, higher survival to discharge, and more breastfeeding at discharge, and its authors concluded the data support starting milk feeds during hypothermia. Follow the unit protocol. Oral colostrum care is a low-risk way to start whichever approach is used.

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

The most reliable outcome figures come from the randomized trials, which enrolled infants with moderate or severe HIE together:

Severity matters within those totals. Outcomes are worst after Sarnat stage III and more variable after stage II. Mild HIE (stage I) is not automatically benign either: a 2018 systematic review of 20 studies found an abnormal outcome (death, cerebral palsy, or a developmental score more than 1 standard deviation below the mean) in 86 of 341 children with mild HIE, about 25% (Conway 2018). Infants with mild HIE are not cooling candidates under current criteria, but they still need follow-up.

The 2026 AAP report expects every cooling center to obtain a brain MRI before discharge, and most units image after rewarming, within the first week or so. 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 starts at ≥36 0/7 weeks gestational age. That is the threshold the randomized trials used and the one NCLEX will test: an infant at 34 weeks is not a cooling candidate. Know the nuance one level up, because the 2026 AAP clinical report added it – at 35 0/7 to 35 6/7 weeks the evidence is inconclusive rather than negative, so cooling may be considered in selected infants after a documented risk discussion with parents. Below 35 0/7 weeks it is not recommended.

2. The Apgar score at 10 minutes is the relevant threshold. An Apgar ≤5 at 10 minutes of life (rather than at 1 or 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 is no faster than 0.5°C per hour, so it takes at least about 6 hours. Rapid rewarming risks rebound hyperthermia and seizures and may undo some of the neuroprotective benefit. The rate is slow and controlled – this is NCLEX-tested.

5. Phenobarbital is the first-line treatment for neonatal seizures in HIE (ILAE 2023). Loading dose is 20 mg/kg IV. Respiratory depression is the key adverse effect – have airway support available. Levetiracetam is a common second-line agent: in the NEOLEV2 trial it controlled seizures less often than phenobarbital as a first-line drug (28% vs 80% seizure-free at 24 hours).

6. Sarnat Grade II is moderate HIE: lethargy, hypotonia, weak Moro and suck, constricted pupils, and seizures are common. Be able to distinguish Grade II from Grade I (hyperalert, irritable, hyperactive reflexes, no seizures) and Grade III (stupor or coma, flaccid, absent reflexes, burst-suppression or isopotential EEG). These findings drive the clinical assessment for cooling eligibility and prognosis discussions.

7. Cooling works by interrupting secondary energy failure, and the benefit is greatest inside 6 hours. This is why HIE management is a time-sensitive emergency, and 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. Treat the 6-hour mark as the target to protect. Past it, the NICHD late-hypothermia trial still supports considering cooling at 6–24 hours of age, with a smaller and less certain benefit.

8. aEEG monitors for subclinical seizures throughout the cooling period. Many HIE seizures are electrographic only – no visible clinical signs. aEEG gives a continuous bedside display, though continuous conventional EEG is preferred where available (AAP 2026). Recognize burst suppression as a severely abnormal background and the seizure signature (abrupt rise in the lower margin).

9. Glucose derangement in either direction worsens HIE outcome. In the CoolCap analysis, glucose values ≤40 mg/dL or >150 mg/dL in the first 12 hours were each independently linked to death or severe disability. Correct hypoglycemia promptly, avoid overshooting into hyperglycemia, and check glucose frequently through cooling and rewarming. See the neonatal hypoglycemia nursing reference for glucose management.

10. Expect multi-organ dysfunction. The same oxygen deprivation that injures the brain simultaneously injures the kidneys (AKI, SIADH), heart (myocardial dysfunction, PPHN), liver (elevated LFTs, coagulopathy), and gut (feeding intolerance; NEC is a theoretical concern but was rare in a large UK cooling cohort). 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

References

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