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neonatal.persistent-pulmonary-hypertension.v1PRODUCTION
neonatal.persistent-pulmonary-hypertension.v1

Persistent Pulmonary Hypertension of the Newborn (PPHN)

pediatricsacuteneonatalpediatric
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Care setting:

Encounter flow

12/12 authored

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

Current phase

Frame

Detailed

Frame by gestational age (iNO is for ≥ 34 wk PMA), postnatal age, and underlying driver (MAS, pneumonia, asphyxia, CDH, RDS, idiopathic). Pre-/post-ductal SpO₂ gradient + echo are the diagnostic anchor.

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Advance rule
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GA + driver classified; iNO eligibility determined

Patient inputs (14)

Pre-ductal SpO₂ (right hand) reflects post-PDA arterial flow

Post-ductal SpO₂ (lower limb) reflects R→L shunt across PDA; gradient > 10% supports PPHN

Tachypnea + retractions; intubation if escalating

Systemic hypotension worsens R→L shunting; vasoactive to keep MAP > pulmonary pressure

iNO indication is for ≥ 34 wk PMA hypoxic respiratory failure; preterm < 34 wk has more controversial benefit (Cochrane 2017)

Per-kg dosing for sildenafil, milrinone, dobutamine; ECMO eligibility weight thresholds (~2 kg)

Most PPHN presents within first 24 h; late-onset PPHN in chronic lung disease cohort distinct (BPD-PH per Berkelhamer Steinhorn 2018 PMID 30384985)

PaO₂ pre-/post-ductal gradient confirms shunt; OI calculation drives iNO + ECMO thresholds

Sepsis coinfection rule-out (route to neonatal.early-onset-sepsis.v1); polycythemia (Hct > 65) can co-cause PPHN

Sepsis-driven PPHN common; cover empirically + cultures

Lactate trend tracks tissue perfusion + cardiac output

Parenchymal driver identification (clear in pure PPHN; ground-glass in RDS; meconium pattern; pneumonia infiltrate; CDH bowel-in-chest)

Echo confirms PPHN (elevated RV pressure via TR jet, septal flattening, R→L shunt direction); also evaluates LV function for milrinone / dobutamine decision; CRITICAL to exclude duct-dependent CHD before iNO (hyperoxia can close PDA)

OI = (MAP × FiO₂ × 100) / PaO₂; OI ≥ 25 → iNO consideration; OI ≥ 40 → ECMO consideration

* = hard-required. Engine cannot meaningfully run until these are filled.

No severity triggers declared for this engine.

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Recommended regimen

PPHN — iNO + sildenafil + milrinone + dobutamine + surfactant for parenchymal driver; HFOV + ECMO non_pharm (Cochrane Barrington 2017 PMID 28056166; Steinhorn IV sildenafil PMID 19836028; BPD-PH Berkelhamer Steinhorn 2018 PMID 30384985)
axis: pphn_pulmonary_vasodilation_and_inotropy
Selected axis "PPHN — iNO + sildenafil + milrinone + dobutamine + surfactant for parenchymal driver; HFOV + ECMO non_pharm (Cochrane Barrington 2017 PMID 28056166; Steinhorn IV sildenafil PMID 19836028; BPD-PH Berkelhamer Steinhorn 2018 PMID 30384985)" by default fallback (first axis)
  • inhaled_nitric_oxide_iNO_20_ppm
    first line
    inhaled_pulmonary_vasodilator_NO_donor
    iNO 20 ppm via ventilator circuit; titrate down 5 ppm q4h based on OI response; minimum 5 ppm to avoid rebound; wean off over 12-24 h • inhaled_via_ventilator • continuous inhaled
    triggers: oi_ge_25_in_term_or_near_term_pphn, pphn_with_pre_post_ductal_gradient
    First-line per Cochrane Barrington 2017 (PMID 28056166): iNO 20 ppm effective in term / near-term hypoxic respiratory failure without diaphragmatic hernia; reduces death + ECMO with NNT ~ 5. CDH cohort has reduced response (consider earlier ECMO). Composite procedural (medical gas, not a single RxCUI for inhalation form)
  • sildenafil
    add on
    PDE5_inhibitor
    sildenafil 0.5-1 mg/kg PO q6h (start at 0.5 mg/kg; titrate to response); IV form 0.4 mg/kg over 3 h then 1.6 mg/kg/day continuous (Steinhorn J Pediatr 2009 PMID 19836028) • PO (preferred) or IV • q6h (PO) (max: max 8 mg/kg/day PO (= 2 mg/kg q6h); IV per Steinhorn 2009 protocol; rare 10 mg/kg/day off-label)
    triggers: adjunct_to_ino_for_persistent_oxygenation_failure, weaning_off_ino_to_prevent_rebound_pulmonary_htn
    PDE5 inhibition potentiates cGMP → pulmonary vasodilation; adjunct to iNO and weaning aid; Steinhorn et al J Pediatr 2009 (PMID 19836028) IV form well-tolerated. Lactation: limited data (Neofax 2024 caution); IV form not lactation-relevant (infant-administered)
    rxcui 136411
  • milrinone
    add on
    PDE3_inhibitor_inotrope_vasodilator
    milrinone 0.25-0.75 mcg/kg/min IV continuous (start at 0.25; titrate); optional 50 mcg/kg loading dose over 30-60 min (consider omitting in hypotensive infants) • IV continuous • continuous infusion (max: max 0.75 mcg/kg/min routinely; up to 1 mcg/kg/min off-label)
    triggers: pphn_with_LV_dysfunction_on_echo, pphn_post_cardiac_surgery_overlap_consideration
    Inotropic + vasodilatory; especially useful in PPHN with LV dysfunction or post-bypass; monitor BP closely (hypotension common); Neofax 2024
    rxcui 52769
  • dobutamine
    add on
    beta1_agonist_inotrope
    dobutamine 5-20 mcg/kg/min IV continuous (start at 5; titrate to cardiac output and BP response) • IV continuous • continuous infusion (max: max 20 mcg/kg/min routinely)
    triggers: pphn_with_low_cardiac_output_requiring_inotropic_support
    Beta1 inotropic + mild pulmonary vasodilator; supports cardiac output without aggressive afterload increase; Neofax 2024
    rxcui 3616
  • poractant alfa
    comorbidity specific
    pulmonary_surfactant_porcine
    poractant alfa 200 mg/kg intratracheal (same dosing as RDS engine) • intratracheal_LISA_or_INSURE_or_ETT • single dose; may repeat 100 mg/kg if persistent need (max: max 2 doses (200 + 100 mg/kg))
    triggers: pphn_with_meconium_aspiration_or_pneumonia_or_rds_parenchymal_driver
    Parenchymal driver (MAS, pneumonia, RDS) requires surfactant; cross-reference neonatal.respiratory-distress-syndrome.v1; Sweet 2022 + Neofax 2024
    rxcui 236381
  • hfov_high_frequency_oscillatory_ventilation
    add on
    mechanical_ventilation_advanced
    HFOV with optimal MAP titrated to lung volume on CXR; frequency 8-12 Hz typical • mechanical_ventilation • continuous
    triggers: severe_parenchymal_lung_disease_with_pphn_overlap, rescue_when_conventional_mv_failing_at_high_settings
    HFOV improves lung-recruitment in MAS / pneumonia / severe RDS-PPHN overlap; lung-protective for PPHN with parenchymal disease
  • ecmo_extracorporeal_membrane_oxygenation
    rescue
    extracorporeal_life_support
    VV or VA ECMO per institutional protocol; weight ≥ 2 kg + GA ≥ 34 wk + reversible cause + no major CNS injury • extracorporeal_VV_or_VA • continuous until reversibility
    triggers: oi_ge_40_on_max_therapy_with_reversible_cause, failure_of_ino_and_adjuncts_with_eligible_infant
    ELSO neonatal guidelines (2023) — ECMO improves survival in OI ≥ 40 with reversible cause; CDH cohort has earlier ECMO threshold

ed playbook — drug actions (2)

  1. 1. intubation if respiratory failure
    Per NRP guidelines • endotracheal • as needed
    trigger: Persistent hypoxemia on face mask O₂
    Standard NRP
  2. 2. IV fluid bolus 10 mL/kg NS slowly if hypotensive
    10 mL/kg • IV • single bolus, reassess
    trigger: Hypotension worsens R→L shunt
    Maintain MAP > pulmonary pressure to reduce shunt

Auto-drafted A&P note

ed

Subjective

- Possible entry pathways: Pre-/post-ductal SpO₂ gradient > 10% (or PaO₂ gradient > 20 mmHg) in term / near-term neonate — classic PPHN sign; Severe hypoxemia in term / near-term neonate with clear or minimally abnormal CXR — pure PPHN phenotype; Echo showing elevated RV pressure (TR jet), flat septum, R→L shunting across PDA / PFO — PPHN diagnostic anchor (Steinhorn body of work).

Objective

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

Assessment

**Persistent Pulmonary Hypertension of the Newborn (PPHN)** (neonatal.persistent-pulmonary-hypertension.v1).
Phenotype framing: PPHN vs cyanotic CHD (echo distinguishes; hyperoxia test traditional but echo definitive). PPHN vs RDS (parenchymal vs vascular — RDS has ground-glass CXR; pure PPHN has clear lungs). PPHN vs sepsis with shock (cultures + maternal risk; can co-occur). PPHN vs CDH (scaphoid abdomen + bowel-in-chest). PPHN secondary to congenital pulmonary anomalies (lobar emphysema, CCAM, sequestration — imaging).
Scope: Frame by gestational age (iNO is for ≥ 34 wk PMA), postnatal age, and underlying driver (MAS, pneumonia, asphyxia, CDH, RDS, idiopathic). Pre-/post-ductal SpO₂ gradient + echo are the diagnostic anchor.

Plan

Regimen axis: **PPHN — iNO + sildenafil + milrinone + dobutamine + surfactant for parenchymal driver; HFOV + ECMO non_pharm (Cochrane Barrington 2017 PMID 28056166; Steinhorn IV sildenafil PMID 19836028; BPD-PH Berkelhamer Steinhorn 2018 PMID 30384985)**.
1. inhaled_nitric_oxide_iNO_20_ppm iNO 20 ppm via ventilator circuit; titrate down 5 ppm q4h based on OI response; minimum 5 ppm to avoid rebound; wean off over 12-24 h inhaled_via_ventilator continuous inhaled (inhaled_pulmonary_vasodilator_NO_donor, first line) — First-line per Cochrane Barrington 2017 (PMID 28056166): iNO 20 ppm effective in term / near-term hypoxic respiratory failure without diaphragmatic hernia; reduces death + ECMO with NNT ~ 5. CDH cohort has reduced response (consider earlier ECMO). Composite procedural (medical gas, not a single RxCUI for inhalation form)
2. sildenafil sildenafil 0.5-1 mg/kg PO q6h (start at 0.5 mg/kg; titrate to response); IV form 0.4 mg/kg over 3 h then 1.6 mg/kg/day continuous (Steinhorn J Pediatr 2009 PMID 19836028) PO (preferred) or IV q6h (PO) (PDE5_inhibitor, add on) — PDE5 inhibition potentiates cGMP → pulmonary vasodilation; adjunct to iNO and weaning aid; Steinhorn et al J Pediatr 2009 (PMID 19836028) IV form well-tolerated. Lactation: limited data (Neofax 2024 caution); IV form not lactation-relevant (infant-administered)
3. milrinone milrinone 0.25-0.75 mcg/kg/min IV continuous (start at 0.25; titrate); optional 50 mcg/kg loading dose over 30-60 min (consider omitting in hypotensive infants) IV continuous continuous infusion (PDE3_inhibitor_inotrope_vasodilator, add on) — Inotropic + vasodilatory; especially useful in PPHN with LV dysfunction or post-bypass; monitor BP closely (hypotension common); Neofax 2024
4. dobutamine dobutamine 5-20 mcg/kg/min IV continuous (start at 5; titrate to cardiac output and BP response) IV continuous continuous infusion (beta1_agonist_inotrope, add on) — Beta1 inotropic + mild pulmonary vasodilator; supports cardiac output without aggressive afterload increase; Neofax 2024
5. poractant alfa poractant alfa 200 mg/kg intratracheal (same dosing as RDS engine) intratracheal_LISA_or_INSURE_or_ETT single dose; may repeat 100 mg/kg if persistent need (pulmonary_surfactant_porcine, comorbidity specific) — Parenchymal driver (MAS, pneumonia, RDS) requires surfactant; cross-reference neonatal.respiratory-distress-syndrome.v1; Sweet 2022 + Neofax 2024
6. hfov_high_frequency_oscillatory_ventilation HFOV with optimal MAP titrated to lung volume on CXR; frequency 8-12 Hz typical mechanical_ventilation continuous (mechanical_ventilation_advanced, add on) — HFOV improves lung-recruitment in MAS / pneumonia / severe RDS-PPHN overlap; lung-protective for PPHN with parenchymal disease
7. ecmo_extracorporeal_membrane_oxygenation VV or VA ECMO per institutional protocol; weight ≥ 2 kg + GA ≥ 34 wk + reversible cause + no major CNS injury extracorporeal_VV_or_VA continuous until reversibility (extracorporeal_life_support, rescue) — ELSO neonatal guidelines (2023) — ECMO improves survival in OI ≥ 40 with reversible cause; CDH cohort has earlier ECMO threshold

Setting playbook (ed) — Initial resuscitation if delivered outside NICU — establish airway + ventilation + pre-/post-ductal SpO₂ + arrange transfer to NICU (icu) with iNO + ECMO capability.
8. intubation if respiratory failure Per NRP guidelines endotracheal as needed — Persistent hypoxemia on face mask O₂ (Standard NRP)
9. IV fluid bolus 10 mL/kg NS slowly if hypotensive 10 mL/kg IV single bolus, reassess — Hypotension worsens R→L shunt (Maintain MAP > pulmonary pressure to reduce shunt)

Non-pharmacologic actions:
- Transfer to NICU with iNO + ECMO capability
- Continuous monitoring during transport
- Avoid hypothermia and acidosis (both worsen PPHN)
- Avoid hyperoxia (target SpO₂ 92-98%; closing PDA in unidentified ductal-dependent CHD is fatal)

AVOID / contraindication checks:
- Exclude ductal dependent CHD by echo before iNO or hyperoxia (Neonatal cardiology principle)
- INO rebound pulmonary hypertension on abrupt discontinuation wean slowly and consider sildenafil bridge (Steinhorn 2009)
- INO methemoglobinemia check MetHb level q24h (Neofax 2024)
- Milrinone hypotension monitor BP closely and omit loading dose if hypotensive (Neofax 2024)
- Sildenafil retinopathy of prematurity risk in preterm monitor eye exam (FDA labeling caveat in pediatric PAH)
- ECMO eligibility weight ge 2kg GA ge 34 wk reversible cause no major CNS injury (ELSO 2023)
- CDH cohort reduced iNO response consider earlier ECMO evaluation (Cochrane 2017 PMID 28056166)
- Avoid alkalosis induction older practice superseded by iNO (neonatology consensus)

Monitoring

Regimen monitoring:
- Continuous pre-/post-ductal SpO₂ + ECG + invasive BP + ETCO₂
- Serial ABG (pre- and post-ductal) q4-6h initially
- OI calculation q4h initially
- MetHb level q24h while on iNO
- Echo daily during iNO (RV function, septal position, shunt direction, LV function)
- CBC + platelets serial (iNO can cause platelet dysfunction)
- Sildenafil response over 12-24 h
- Cardiac output / lactate trend
- Hearing screen (AABR) before discharge — PPHN + iNO + ECMO survivors at risk
- BPD-PH surveillance per Berkelhamer Steinhorn 2018 if chronic lung disease emerges

Setting (ed) monitoring:
- Pre-/post-ductal SpO₂
- HR + BP continuous
- Temperature q15 min

Follow-up plan: High-risk follow-up clinic at 3-6-12-24 mo (Bayley III, neurodev). Hearing screen (AABR) before discharge + audiology surveillance (PPHN + iNO + ECMO survivors at risk for sensorineural hearing loss). Echo at 1-3-6 mo if persistent PH suspected (route to BPD-PH evaluation per Berkelhamer Steinhorn 2018 PMID 30384985). Pulmonology follow-up if BPD or chronic lung disease. RSV prophylaxis (nirsevimab) per AAP / ACIP.
- Close-out criterion: Outpatient follow-up scheduled; hearing + echo surveillance plan documented

Monitoring phase: Continuous pre-/post-ductal SpO₂ + ECG + invasive BP + ETCO₂ if intubated. Serial ABG. OI calculated q4h initially. Echo daily during iNO. Serial CBC + platelets (iNO can cause methemoglobinemia; check MetHb level if cyanosis disproportionate to SpO₂). Cardiac output / lactate trend. Sildenafil response over 12-24 h.

Disposition

Current setting: ed — Initial resuscitation if delivered outside NICU — establish airway + ventilation + pre-/post-ductal SpO₂ + arrange transfer to NICU (icu) with iNO + ECMO capability.

Disposition criteria:
- Transfer to NICU (icu) cooling center / ECMO center as soon as possible

Escalation triggers (move to higher acuity):
- Worsening hypoxemia despite intubation → urgent transfer to NICU (icu)
- Hemodynamic collapse → vasoactive + fluid + reassess for shock differential

Earlier-Return Triggers

- No severity triggers declared for this engine.

Citations

- Berkelhamer SK, Mestan KK, Steinhorn RH — BPD-Associated PH Update (Semin Perinatol 2018 PMID 30384985, Steinhorn co-author body of work on PPHN); Cochrane Barrington 2017 (PMID 28056166) iNO for term / near-term hypoxic respiratory failure; Steinhorn IV sildenafil (J Pediatr 2009 PMID 19836028) for adjunct + weaning. [PMID:30384985](https://pubmed.ncbi.nlm.nih.gov/30384985/)
- Cited evidence (PMID 28056166) [PMID:28056166](https://pubmed.ncbi.nlm.nih.gov/28056166/)
- Cited evidence (PMID 19836028) [PMID:19836028](https://pubmed.ncbi.nlm.nih.gov/19836028/)

Last reconciled with current guidelines: 2026-05-26.
References
  • Berkelhamer SK, Mestan KK, Steinhorn RH — BPD-Associated PH Update (Semin Perinatol 2018 PMID 30384985, Steinhorn co-author body of work on PPHN); Cochrane Barrington 2017 (PMID 28056166) iNO for term / near-term hypoxic respiratory failure; Steinhorn IV sildenafil (J Pediatr 2009 PMID 19836028) for adjunct + weaning. — PMID:30384985
  • Cited evidence (PMID 28056166) — PMID:28056166
  • Cited evidence (PMID 19836028) — PMID:19836028