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neonatal.hypoxic-ischemic-encephalopathy.v1PRODUCTION
neonatal.hypoxic-ischemic-encephalopathy.v1

Neonatal Hypoxic-Ischemic Encephalopathy (HIE)

pediatricsacuteneonatalpediatric
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12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Frame eligibility per Papile AAP 2014: GA ≥36 wk, BW ≥1800 g, postnatal age ≤6 h, AND (acidosis with cord/first-hour pH <7.0 or BE ≤ -16) OR (acute perinatal event with continuing need for resuscitation), AND moderate-to-severe encephalopathy (Sarnat 2/3) OR abnormal aEEG.

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Cooling eligibility confirmed or excluded (clear pathway)

Patient inputs (18)

Persistent low Apgar (≤5 at 10 min) is a clinical criterion for cooling eligibility per Papile 2014

pH <7.0 OR base excess ≤ -16 mmol/L from cord or first-hour neonatal blood is a Papile 2014 eligibility criterion

Cooling eligibility per Papile AAP 2014 requires GA ≥36 wk; <36 wk → case-by-case with neurology / neonatology

Cooling eligibility requires BW ≥1800 g; per-kg dosing for phenobarbital + levetiracetam + morphine

Cooling window is ≤6 h of life; outside this window is investigational (late-hypothermia trial)

Serial ABG / CBG for metabolic acidosis + ventilation

WBC + platelets baseline; thrombocytopenia common during cooling (rewarming-induced)

Coagulopathy common in HIE; INR / aPTT / fibrinogen / D-dimer baseline + serial

Tight glucose control 70-150 mg/dL during cooling; hypoglycemia worsens injury

Electrolytes + creatinine + LFT; AKI common (kidney is most-affected organ after brain)

Lactate >5 mmol/L correlates with severity; serial trend tracks resuscitation

aEEG/EEG continuous monitoring detects subclinical seizures (50% of HIE seizures are subclinical) and trends background recovery

Bradycardia (HR 80-100) is expected during cooling; HR < 80 or arrhythmia → reassess depth

Hypotension is common during cooling — vasoactive support if MAP < gestational-age threshold

MRI brain at 4-7 d post-cooling (or by 10 d) — basal ganglia / thalamus / watershed pattern; prognostic anchor

Serial Sarnat staging (stage 1 mild, 2 moderate, 3 severe) drives eligibility + monitoring

Cooling target 33.5 °C ± 0.5; AVOID overcooling and AVOID hyperthermia (worsens injury)

Cranial US for IVH / extra-axial collections / acute structural injury before MRI

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No severity triggers declared for this engine.

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Recommended regimen

Neonatal HIE — therapeutic hypothermia + seizure control + comfort (Papile AAP 2014 PMID 24864176; NICHD/CoolCap/TOBY)
axis: hie_neuroprotection_and_seizure_control
Selected axis "Neonatal HIE — therapeutic hypothermia + seizure control + comfort (Papile AAP 2014 PMID 24864176; NICHD/CoolCap/TOBY)" by default fallback (first axis)
  • therapeutic_hypothermia_33_5C_x_72h
    first line
    neuroprotective_procedural
    Whole-body cooling to esophageal/rectal target 33.5 °C ± 0.5 × 72 h, initiated within 6 h of life; slow rewarming 0.5 °C per hour over 6-8 h • cooling_blanket_or_servo_controlled_cap • continuous × 72 h then rewarm
    triggers: hie_eligibility_per_papile_2014
    Standard of care per NICHD whole-body cooling (Shankaran NEJM 2005 PMID 16221780) + TOBY (Azzopardi NEJM 2009 PMID 19797281) + CoolCap selective head cooling (Gluckman Lancet 2005 PMID 15721471); reduces death + moderate-severe disability NNT ~7-9
  • phenobarbital
    first line
    barbiturate_anticonvulsant
    phenobarbital 20 mg/kg IV load over 20 min for neonatal seizure; maintenance 5 mg/kg/day divided BID • IV (load) then IV/PO maintenance • load once, then BID maintenance (max: max cumulative load 40 mg/kg (additional 10 mg/kg q15-30 min × 2 if seizure persists); maintenance max 5 mg/kg/day routine, up to 8 mg/kg/day if therapeutic level low)
    triggers: neonatal_seizure_in_hie
    First-line neonatal anticonvulsant per AAP / Neofax 2024; load achieves rapid serum levels; therapeutic 20-40 mcg/mL (Neofax 2024)
    rxcui 8134
  • levetiracetam
    add on
    anticonvulsant_SV2A_modulator
    levetiracetam 20-60 mg/kg IV load (start 20 mg/kg; escalate by 20 mg/kg if breakthrough seizure); maintenance 30-60 mg/kg/day divided BID • IV (load) then IV/PO • load once, then BID maintenance (max: max 60 mg/kg single load; maintenance max 60 mg/kg/day)
    triggers: hie_seizure_refractory_to_phenobarbital, phenobarbital_dose_capped
    Adjunct or alternative to phenobarbital in neonatal seizure; growing evidence for non-inferiority + better sedation profile vs phenobarbital (NEONATE trial Sharpe Pediatrics 2020 — PMID lookup pending; AAP Red Book 2024-2027; Neofax 2024)
    rxcui 114477
  • morphine
    add on
    opioid_analgesic
    morphine 0.05-0.1 mg/kg IV q4h PRN for shivering / discomfort during cooling; continuous infusion 5-10 mcg/kg/h if frequent dosing needed • IV • q4h PRN or continuous (max: max bolus 0.1 mg/kg; titrate continuous to comfort + avoid sedation that obscures neuro exam)
    triggers: shivering_or_distress_during_cooling
    Comfort during cooling reduces stress-induced metabolic increase; titrate to avoid masking neuro exam (Neofax 2024). Lactation: caution if mother breastfeeds — morphine transfers into milk; monitor infant for sedation / respiratory depression per AAP Section on Breastfeeding 2022
    rxcui 7052
  • avoid_hyperthermia_active_cooling_if_T_gt_37_5
    first line
    thermoregulation_procedural
    Maintain core T ≤ 37.5 °C even after rewarming completion; active cooling (turn off radiant warmer, fan) if T rises • passive_or_active_cooling • continuous monitoring
    triggers: hyperthermia_post_hie
    Hyperthermia worsens injury and reduces benefit of completed cooling; AAP / NICHD guidance

ed playbook — drug actions (2)

  1. 1. passive cooling (turn off warmer, expose infant)
    passive cooling targeting 33.5 °C • passive • continuous until active cooling at receiving center
    trigger: HIE eligibility confirmed at referring center
    Passive cooling effective during transport (NICHD operational guidance)
  2. 2. phenobarbital 20 mg/kg IV
    rxcui 8134
    20 mg/kg • IV over 20 min • load once
    trigger: Clinical or electrographic seizure
    First-line neonatal anticonvulsant (Neofax 2024)

Auto-drafted A&P note

ed

Subjective

- Possible entry pathways: Term/near-term neonate with low Apgar + need for prolonged resuscitation + perinatal acidosis (cord pH <7.0 or BE ≤ -16) (Papile AAP 2014 PMID 24864176); Moderate-to-severe encephalopathy on Sarnat staging (lethargy/stupor + abnormal tone + abnormal reflexes + seizures) within 6 h of life; Abnormal amplitude-integrated EEG (aEEG) pattern in first hours of life (burst suppression, continuous low voltage, flat trace).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Neonatal Hypoxic-Ischemic Encephalopathy (HIE)** (neonatal.hypoxic-ischemic-encephalopathy.v1).
Phenotype framing: HIE vs neonatal sepsis with shock (cultures + WBC + maternal risk; route to neonatal.early-onset-sepsis.v1). HIE vs metabolic / inborn error (acidosis + hyperammonemia + organic acid panel). HIE vs stroke (focal deficit, MRI). HIE vs congenital brain malformation (US / MRI). HIE vs neuromuscular (myopathy / SMA / mitochondrial — bilateral floppy with relatively preserved consciousness).
Scope: Frame eligibility per Papile AAP 2014: GA ≥36 wk, BW ≥1800 g, postnatal age ≤6 h, AND (acidosis with cord/first-hour pH <7.0 or BE ≤ -16) OR (acute perinatal event with continuing need for resuscitation), AND moderate-to-severe encephalopathy (Sarnat 2/3) OR abnormal aEEG.

Plan

Regimen axis: **Neonatal HIE — therapeutic hypothermia + seizure control + comfort (Papile AAP 2014 PMID 24864176; NICHD/CoolCap/TOBY)**.
1. therapeutic_hypothermia_33_5C_x_72h Whole-body cooling to esophageal/rectal target 33.5 °C ± 0.5 × 72 h, initiated within 6 h of life; slow rewarming 0.5 °C per hour over 6-8 h cooling_blanket_or_servo_controlled_cap continuous × 72 h then rewarm (neuroprotective_procedural, first line) — Standard of care per NICHD whole-body cooling (Shankaran NEJM 2005 PMID 16221780) + TOBY (Azzopardi NEJM 2009 PMID 19797281) + CoolCap selective head cooling (Gluckman Lancet 2005 PMID 15721471); reduces death + moderate-severe disability NNT ~7-9
2. phenobarbital phenobarbital 20 mg/kg IV load over 20 min for neonatal seizure; maintenance 5 mg/kg/day divided BID IV (load) then IV/PO maintenance load once, then BID maintenance (barbiturate_anticonvulsant, first line) — First-line neonatal anticonvulsant per AAP / Neofax 2024; load achieves rapid serum levels; therapeutic 20-40 mcg/mL (Neofax 2024)
3. levetiracetam levetiracetam 20-60 mg/kg IV load (start 20 mg/kg; escalate by 20 mg/kg if breakthrough seizure); maintenance 30-60 mg/kg/day divided BID IV (load) then IV/PO load once, then BID maintenance (anticonvulsant_SV2A_modulator, add on) — Adjunct or alternative to phenobarbital in neonatal seizure; growing evidence for non-inferiority + better sedation profile vs phenobarbital (NEONATE trial Sharpe Pediatrics 2020 — PMID lookup pending; AAP Red Book 2024-2027; Neofax 2024)
4. morphine morphine 0.05-0.1 mg/kg IV q4h PRN for shivering / discomfort during cooling; continuous infusion 5-10 mcg/kg/h if frequent dosing needed IV q4h PRN or continuous (opioid_analgesic, add on) — Comfort during cooling reduces stress-induced metabolic increase; titrate to avoid masking neuro exam (Neofax 2024). Lactation: caution if mother breastfeeds — morphine transfers into milk; monitor infant for sedation / respiratory depression per AAP Section on Breastfeeding 2022
5. avoid_hyperthermia_active_cooling_if_T_gt_37_5 Maintain core T ≤ 37.5 °C even after rewarming completion; active cooling (turn off radiant warmer, fan) if T rises passive_or_active_cooling continuous monitoring (thermoregulation_procedural, first line) — Hyperthermia worsens injury and reduces benefit of completed cooling; AAP / NICHD guidance

Setting playbook (ed) — Delivery-room or referring-hospital initial decision — confirm eligibility, initiate passive cooling, arrange transport to NICU (icu in dossier vocabulary) cooling center; do NOT delay cooling for transport.
6. passive cooling (turn off warmer, expose infant) passive cooling targeting 33.5 °C passive continuous until active cooling at receiving center — HIE eligibility confirmed at referring center (Passive cooling effective during transport (NICHD operational guidance))
7. phenobarbital 20 mg/kg IV 20 mg/kg IV over 20 min load once — Clinical or electrographic seizure (First-line neonatal anticonvulsant (Neofax 2024))

Non-pharmacologic actions:
- Initiate transport call to NICU cooling center
- IV access (UVC if possible)
- Avoid radiant warmer / heating during transport
- Continuous monitoring (SpO₂, HR, temp)

AVOID / contraindication checks:
- Cooling contraindicated if GA lt 36wk or BW lt 1800g without neurology consult (Papile AAP 2014)
- Cooling contraindicated if postnatal age gt 6h (window has passed; investigational late cooling trial exists)
- Do not delay cooling for transport passive cool at referring center (NICHD operational guidance)
- Avoid hyperthermia actively cool if T gt 37 5 (NICHD operational guidance)
- Morphine lactation caution monitor infant for sedation (AAP Section on Breastfeeding 2022)
- Phenobarbital respiratory depression monitor during loading (Neofax 2024)
- Tight glucose control 70 to 150 mg per dL hypoglycemia worsens injury (NICHD guidance)

Monitoring

Regimen monitoring:
- Continuous aEEG / EEG × 72 h cooling + 24 h post-rewarming
- Continuous SpO₂ + cardiorespiratory + invasive BP + core temp via esophageal / rectal probe
- Serial Sarnat staging q6-12 h
- ABG + lactate q4-6 h
- CBC + coag + electrolytes + glucose + LFT + renal q6-12 h
- Phenobarbital level if breakthrough seizures (therapeutic 20-40 mcg/mL)
- MRI brain at 4-7 d post-cooling (prognostic anchor)
- Hearing screen (AABR) + ophthalmology + neuro / developmental follow-up

Setting (ed) monitoring:
- Core temperature q15 min
- SpO₂ + HR continuous
- Glucose at presentation + q1h

Follow-up plan: Neurology + developmental peds follow-up at 3 + 6 + 12 + 18-24 mo (Bayley III). Hearing screen (AABR) + audiology at 3 mo. Ophthalmology if cortical visual impairment suspected. PT / OT / speech / feeding therapy as needed. Anticonvulsant taper / continuation per epilepsy status. Family / parental support + grief counseling for severe outcomes.
- Close-out criterion: Long-term follow-up plan documented; family education complete

Monitoring phase: Continuous aEEG / EEG × 72 h cooling + 24 h post-rewarming. Continuous SpO₂ + cardiorespiratory + invasive BP + core temperature. Serial neuro exam + Sarnat staging. Labs: ABG + lactate q4-6h; CBC + coag + electrolytes + glucose + LFT + renal q6-12h. Phenobarbital level if breakthrough seizures. MRI at 4-7 d post-cooling.

Disposition

Current setting: ed — Delivery-room or referring-hospital initial decision — confirm eligibility, initiate passive cooling, arrange transport to NICU (icu in dossier vocabulary) cooling center; do NOT delay cooling for transport.

Disposition criteria:
- Transfer to NICU (icu) cooling center as soon as transport ready

Escalation triggers (move to higher acuity):
- Seizure → phenobarbital + levetiracetam
- Refractory hypoxemia → intubate + ventilate
- Hypotension → vasoactive (dopamine 5 mcg/kg/min)

Earlier-Return Triggers

- No severity triggers declared for this engine.

Citations

- Papile L-A et al — AAP 2014 Hypothermia and Neonatal Encephalopathy (Pediatrics 2014 PMID 24864176); NICHD (Shankaran NEJM 2005 PMID 16221780) + TOBY (Azzopardi NEJM 2009 PMID 19797281) + CoolCap (Gluckman Lancet 2005 PMID 15721471) demonstrate cooling efficacy. [PMID:24864176](https://pubmed.ncbi.nlm.nih.gov/24864176/)
- Cited evidence (PMID 16221780) [PMID:16221780](https://pubmed.ncbi.nlm.nih.gov/16221780/)
- Cited evidence (PMID 19797281) [PMID:19797281](https://pubmed.ncbi.nlm.nih.gov/19797281/)
- Cited evidence (PMID 15721471) [PMID:15721471](https://pubmed.ncbi.nlm.nih.gov/15721471/)

Last reconciled with current guidelines: 2026-05-26.
References
  • Papile L-A et al — AAP 2014 Hypothermia and Neonatal Encephalopathy (Pediatrics 2014 PMID 24864176); NICHD (Shankaran NEJM 2005 PMID 16221780) + TOBY (Azzopardi NEJM 2009 PMID 19797281) + CoolCap (Gluckman Lancet 2005 PMID 15721471) demonstrate cooling efficacy. — PMID:24864176
  • Cited evidence (PMID 16221780) — PMID:16221780
  • Cited evidence (PMID 19797281) — PMID:19797281
  • Cited evidence (PMID 15721471) — PMID:15721471