This document discusses persistent pulmonary hypertension of the newborn (PPHN). It begins by describing the normal fetal to neonatal circulation transition at birth. PPHN occurs when the pulmonary hypertension persists, causing severe hypoxia. There are three types of PPHN based on etiology: maladaptation, underdevelopment, and maldevelopment. Management involves three steps - relieving pulmonary vasoconstriction with supportive measures, recruiting alveoli through ventilation techniques, and using pulmonary vasodilators like inhaled nitric oxide. Echocardiography is important for diagnosis and shows three key findings - increased pulmonary pressures, tricuspid regurgitation, and septal wall abnormalities. The prognosis depends on severity, with mortality

1. Persistent Pulmonary
Hypertension of the Newborn
Dr Gururaja R
MD, DNB (Paed)

2. Objectives
• Fetal to Neonatal Transition
• Molecules of PPHN
• PPHN
– Defnition
– Types
– Etiology
– Presentation
– Diagnosis
– Management

3. Fetal Circulation

4. Normal Post natal transition
• Baby starts crying
• Lungs expand
• Umbilical Cord is
clamped and cut
• Placental supply is
removed
• Drop in pulmonary
vascular resistance
• Increase in systemic
resistance

5. What is PPHN?
• Persistence of Pulmonary hypertension
resulting in severe hypoxia

6. PPHN - etiology

7. Three types of PPHN
• Maladaptation
• Underdevelopment
• Maldevelopment

8. Mal-adaptation
• Reflex vasoconstriction
• Asphyxia
• MAS
• CDH
• Pneumonia
• RDS
• Acidosis
• Hypocalcemia
• hypothermia

9. Persistent Pulmonary Pressures
• Muscularization of Pulmonary acinar arteries
(Maldevelopment)
– Chronic in-utero hypoxia (IUGR), Post maturity
– Maternal Salicylate or indomethacin therapy
Decreased Pulmonary arterioles (Underdeveloped)
– Hypoplastic lungs, CDH,Alveo-capillary dysplasia

10. Major causes of PPHN
• MAS – 30%
• RDS – 20%
• CDH – 16%
• Primary PPHN -15%

11. PPHN in preterm infants with BPD
• Severe BPD : Incidence of PPHN up to 50%
• Echo signs of PPHN in early phase (72 hrs and
14 days) associated with increased incidence
of moderate to severe BPD

12. Three
pathways for PPHN

13. When to suspect PPHN?
• Severe hypoxia disproportionate to chest x-ray
• Labile or fluctuating oxygenation
• Heart murmur (TR, PDA)
• ABG – hypoxia and normal CO2
• Post ductal saturation > 10% difference compared to
preductal
• Normal chest X-ray!!!

14. How to confirm PPHN?
• Pre and post ductal saturations
• Hyperoxia test
• Echocardiography (Gold standard)– TR, PDA
• Septal bulge to left
• Dilated RA and RV
• Brain natriuretic peptide (BNP) ->550 pg/ml -85% sensitive
and 100% specific

16. Chest X-ray in PPHN
• Lung disease disproportionate to hypoxia
• Good lung volume, right heart enlargement

18. Echo in PPHN
• Gold standard
• Pulmonary pressure 30 to 60 mm Hg
• R-L shunt across PDA
• TR
• Septal bulge to left
• Dilated RA and RV
• Rule out CHD

19. Tricuspid regurgitation

20. PDA in PPHN

21. How to assess severity of PPHN?
• Oxygenation index
• MAP X FiO2/PaO2 X 100
• Mild - <15
• Moderate – 15 to 25
• Severe - 25 – 40
• Very severe > 40
• Oxygen saturation index
• MAP X FiO2/SpO2 X 100
• 2 X OSI = OI

22. Management steps
• 1. reverse reflex vasoconstriction
• 2. recruit alveoli
• 3. select pulmonary vasodilators

23. General supportive measures - relieve
pulmonary vasoconstriction
• Thermo neutral environment
• Minimizing unnecessary handling
• Sedation , analgesia
• Fluid balance maintenance
• Glucose and calcium homeostasis
• Correct hypotension, anemia,Polycythemia
• Maintain PaO2 : 50-80 mm Hg
• Increase systemic pressure (fluids and inotropes)

24. Recruit Alveoli : Ventilation
• Target pH - >7.25
• Target PaCO2 – 40-60
• Target PaO2 - 50 -70 (SpO2 – 90-97%)
• Rate – Match to Patient rate
• PIP – min for chest rise
• Switch over to HFV if PIP >28 and TV > 6ml/kg
• HFV useful in lung parenchymal disease
• Surfactant in RDS and MAS

25. Rescue High Frequency ventilation to
recruit alveoli

26. Pulmonary Vasodilators
• Endothelin Pathway
– Eta and Etb antagonist : Bosentan, Sitaxsentan
• Nitric oxide pathway
– Inhaled Nitric Oxide
– Sildenafil
• Prostacyclin Pathway
– Epoprostenol, Prostaglandin E
– Milrinone

28. Inhaled nitric oxide therapy
for pulmonary vasodilatation
• Frequently used with
HFOV
• Increases cyclic GMP
resulting in pulmonary
vasodilatation

29. Microselective action of inhaled nitric
oxide

31. Sildenafil
• Potent selective pulmonary vasodilator
• Loading dose – 0.4 mg/kg over 3 hrs --- 0.07
mg/kg/hr or 1.6 mg/kg/day –infusion
• Oral dose – 1-2 mg/kg/dose 6 hrly
• Major side effects – Pulmonary haemorrhage
and hypotension

32. Further management in case nitric
oxide/sildenafil is not working
• DO ECHO
• L to R shunt at PDA
– Lung recruitment most effective
– HFV, Surfactant
• R to L shunt at PDA
– Vasodilators are effective
• LV dysfunction
– Consider Milrinone

33. Recent Advances - Evolving Therapies
• Hydrocortisone : improves O2, increases c-GMP
• Inhaled prostaglandins – iloprost, epoprostenol
• Antioxidants – (r-human superoxide dismutase)
• L-Citrulline – precursors of nitric oxide
• Soluble Guanyl cyclase (Cinaciguat)
• Rhokinase inhibitors (Myosin phosphorylation)

35. Prevention of PPHN
• Good antenatal care
• Avoid NSAID during pregnancy
• Prevention of asphyxia
• Good supportive care – normothermia,
oxygenation, normoglycemia, normocalcemia
• Avoid unnecessary interventions

36. Prognosis
• Depend on multiple factors
• Mortality – 10 to 20%
• Neurological handicap – 25%

37. Summary – rule of 3 in PPHN
• 3 communications
• 3 molecules
• 3 types of PPHN
• 3 steps of management
• 3 echo findings

38. •THANK YOU