Overview of treatment of persistent pulmonary hypertension of the newborn (PPHN)

Identify and correct metabolic derangements:

• Metabolic acidosis should be avoided because it increases PVR; add acetate (2 to 3 mEq/kg per day) to IVF; avoid rapid infusion of sodium bicarbonate
• Treat hypoglycemia
• Treat hypocalcemia

• Mild hypoxemia: OI <15
• Moderate hypoxemia: OI ≥15 and <25
• Severe hypoxemia: OI ≥25 and <40
• Very severe hypoxemia: OI ≥40

Severity of PH based upon echocardiography:

• Mild to moderate PPHN – Estimated RVp between one-half to three-quarters systemic BP
• Moderate to severe PPHN – Estimated RVp greater than three-quarters systemic BP but less than systemic BP
• Severe PPHN – Estimated RVp greater than systemic BP

• Begin with CMV using a patient-triggered volume-targeted mode
• Start with Tv of 4 to 6 mL/kg and PEEP of 5 to 7 cm H₂O
• If gas exchange targets are not met with low Tv ventilation, the Tv setting can be liberalized
• If an FiO2 >0.6 is required achieve the target SpO2, increase PEEP or transition to HFV
• Other reasons to transition to HFV:
  • Tvs of >7 to 8 mL/kg are required to maintain gas exchange targets
  • Peak pressures of 28 to 30 cm H₂O are required to achieve adequate ventilation
  • Neonate develops signs of ventilator-induced lung injury (eg, pneumothorax)
• If OI is ≥25 despite optimizing MV and sedation, start iNO (see below)

Gas exchange targets:

• Preductal SpO2: 90 to 95%
• Pre- and postductal SpO2 difference: <3 to 5%
• PaCO2: 40 to 45 mmHg initially; can liberalize to 40 to 50 mmHg as neonate's ventilatory becomes more stable

• Begin with opioid analgesia (morphine or fentanyl) alone or in combination with a benzodiazepine (midazolam)
• Reserve NMBAs (eg, vecuronium, pancuronium) for neonates with dyssynchronous breathing associated with persistent severe hypoxemia without another identified cause

• Maintain adequate intravascular volume with IVF
• Provide inotropic and/or vasopressor support to maintain hemodynamic goals
• Dopamine, epinephrine, and milrinone are the most commonly used agents

Hemodynamic goals:

• BP at upper limit of normal (eg, for term neonates, mean BP 45 to 55 mmHg; systolic BP 50 to 70 mmHg)
• Normal lactate level
• Improved right ventricular function and reduction in right-to-left shunting on serial echocardiography (if performed)

• Dose: 20 ppm (do not use higher doses since this increases risk of toxicity without improving response)
• Weaning:
  • Start weaning once FiO2 is ≤0.6
  • Wean by 5 ppm every 2 to 4 hours as tolerated until reaching a dose of 5 ppm
  • Then wean by 1 ppm every 2 to 4 hours as tolerated until reaching a dose of 1 ppm
  • If the neonate is stable on 1 ppm, discontinue iNO and monitor for rebound
  • If the neonate has worsening hypoxemia and/or hemodynamic instability after stopping iNO, restart iNO at 5 ppm until the patient stabilizes, and subsequently wean more slowly

• PPHN associated with MAS or RDS
• PPHN associated with significant parenchymal lung disease, even if the etiology is not clearly MAS or RDS

Transfusion: Threshold for RBC transfusion in neonates with severe PPHN is Hgb <15 g/dL (HCT <40%)

• Pre- and post-ductal oxygen saturation (eg, with pulse oximetry probes placed on the right thumb and either great toe), monitored continuously
• Serial clinical assessments, including assessment of perfusion
• BP, monitored continuously with an indwelling arterial line
• Serial blood gases, monitored every 4 to 6 hours initially; then spaced out once the neonate's clinical status stabilizes
• Blood lactate levels
• Ventilator data (eg, peak inspiratory pressures and exhaled Tvs)
• Follow-up echocardiography, as needed
• Chest radiographs, as needed (eg, to assess lung volumes after initiating HFV or if there is an acute change in the neonate's clinical status)