An overview on the management of PPHN in newborns

1. Dr Boopathi Sellappan
Fellow Paediatric Cardiology, Bristol Childrens Hospital, Bristol,
United Kingdom.

2.  Characterised by sustained elevation in pulmonary vascuar
resistance (PVR) rather than the decrease in PVR which normally
happens after birth
 Causes severe hypoxemia secondary to right-to-left shunting of
blood through fetal circulatory pathways
 Often preceded by severe fetal hypoxemia, prolonged stress,
remodelling and abnormal vascularisation of pulmonary arteries

3. Fetal circulation.
Aortic arch
Ductal arch

4. PPHN
 2 to 6 per 1000 Live births
 10-30% mortality
 Full term>preterm
 Risk factors
 Meconium stained liqour
 Congenital pneumonia, surfactant deficiency
 Abnormal lung development-Pulmonary hypoplasia eg., potters sequele, CDH
etc.,
 Polycythemia
 Preterm with prolonged rupure of membranes
 Maternal problems- Sepsis, Anaemia, Diabetis, SSRI intake, NSAID Intake,
Caesarean birth
 Myocardial dysfunction, myocarditis, Congenital heart disease, Lt to Rt shunt
 ?Familial/ genetic predisposition.
Pediatrics. Aug 2007

5.  Idiopathic PPHN
 Due to remodelling of pulmonary vessels
 lung parenchymal diseases
 Meconium aspiration syndrome, Congenital pneumonia, Respiratory distress
etc
 Hypoplastic lungs/ Vasculature
 eg.,Congenital diaphragmatic hernia

6. Endothelin pathway
Nitric oxide pathway
Prostacyclin pathway
Vascular endothelial cell lining pulmonary arteryPreproendothelin
Proendothelin
Endothelin
L Arginine L Citrulline
Nitric Oxide
NO
Synthase
Arachidonic acid
Prostaglandin I2
Prostacyclin(PG I2)
CAMP
Smooth muscle cells in pulmonary artery
Vasoconstriction
and proliferation
Cyclic GMP
Vasodilation and antiproliferation
The Lancet, Vol. 358, 2001

7.  Respiratory distress
 Cyanosis- Differential
 Poor cardiac output and perfusion
 Prominent precordial impulse
 Single or narrow split, Loud S2, SM(TR)
 >10% difference in pre and postductal saturation
 Beware of shunting at foramen ovale

8.  Congenital heart disease
 Primary pulmonary parenchymal diseases
 Congenital pneumonia
 CCAM, RDS/SDLD
 Pulmonary sequestration
 Pulmonary hypoplasia etc.,
 Sepsis
 Alveolar capillary dysplasia

9.  Septic screen, FBC, Renal and liver functions, Ca, Po4, Magnesium,
 Chest X ray- Normal or e/o pulmonary parenchymal disease
 Transthoracic echocardiography (Urgent)
 Arterial Blood gas
 ECG- RV predominance, Myocardial ischemia or infarction
 Cranial USS Scan

10. MAP x100 x FiO2
PaO2 (mmHg)
 >25- Consider iNO
 >40 – Consider ECMO

11. • Confirm Diagnosis
• Access ventricular function
• Exclude congenital heart
defects
• Monitor progress
Findings
• Right to left shunting at level of
PDA/foramen ovale(Beware of
TAPVC)
• Flat septum/ pushed to the left
• Tricuspid regurtitation
• Pulmonary presure >=Systemic
pressure(4*r2)
Skinner J Echocardiography for the neonatologist. Churchill Livingstone 2000

12. Skinner J Echocardiography for the neonatologist. Churchill Livingstone 2000

13. LV
RV
RV
LV
IVS
IVS

14. RV
RA
LV
LA

16.  In Tertiary NICU/PICU/CICU
 Ongoing care and real time monitoring
 Synchronised Ventilation/Oscillation, Pulmonary vasodilatos,
Ionotropes
 Correct hypothermia, acidosis, hypoglycemia, hypocalcaemia or
hypomagnesaemia
 Minimal handling
 Exclude and treat other differentials

17. • Minimimize Barotrauma
– HFOV useful in parenchymal lung disease
– Oxygenation and ventilation with minimal tidal volume
• Sedation- Almost always
• Paralysis- May be
• ? Increased risk of death and disbility
• PH- High normal
• PCo2- > 35 mm Hg
• PO2- >50 mm Hg
• Consider early surfactant – Useful in parenchymal disease

18.  Aim for high normal blood pressures to minimise Rt to Lt shunting
 Ionotropes
 Dopamine, Noradrenaline, adrenaline,
 Dobutamine, Milrinone (To enhance myocardial contractility)
 Real time monitoring of BP, saturations, pre and postductal
saturations
 4-6 hourly blood gases, Lactate
 Crystalloids or colloids for filling
 UAC/Peripheral arterial lines, UVC, Spare Jugulars for ECMO

19.  Oxygen – Start with 100% FiO2
 Nitric Oxide- Start at 20 PPM
 Phosphodiestase inhibitors(Sildenafil PDE5, Milrinone PDE3)
 Endothelin receptor antagonists- Bosentan
 Prostacyclin I2 - Epoprostenol
 Others- Sodium nitroprusside, Adenosine, Magnesium Sulphate
 Exclude left to right shunt
Pediatric Clin N Am 2012

20. Advantages
 Superior speed of action,
 Targeted pulmonary effects,
 lack of reliance on gastric absorption
 Easy titrability
Disadvantages
 Cost
 Rebound PHT
 30-40% unresponsive to iNO Rx
 Methaemoglobinemia
Cochrane Database of Systematic Reviews 2000

21.  Phosphodiesterase type 5 (PDE5) inhibitor
 Oral or IV, T1/2- 4hours
 Enteral route- 40% Peak bioavailability in 30-90 mins
 Multiple case reports and case series, few trials with small number
 Sildenafil in the treatment of PPHN-has significant potential especially in resource
limited settings. However, a large scale randomised trial comparing sildenafil with the
currently used vasodilator, inhaled nitric oxide, is needed to assess efficacy and safety.
Cochrane database syst 2011 Aug 10
 Minimal and reversible side effects with short term use
 Enteral and IV preperations available

22.  Bosentan- Endothelin receptor antagonist
 Few case reports and ongoing clinical trials
 Hepatotoxicity, teratogenicity, male infertility
 Inhaled/IV Prostacyclin- Small studies have shown improvement in
oxygenation
 Short T1/2,Ventilation perfusion mismatch , systemic hypotension,
unstable at neutral/acid PH, room temperature,rebound PHT
 Adenosine infusions in small trials improved oxygenation
 Magnesium sulphate, Sodium nitroprusside
Pediatric Clin N Am 2012

23. Endothelin pathway
Nitric oxide pathway
Prostacyclin pathway
Vascular endothelial cell lining pulmonary artery
Preproendothelin
Proendothelin
Endothelin
L Arginine L Citrulline
NO
Synthase
Arachidonic acid
Prostaglandin H2
Prostacyclin(PG I2)
Smooth muscle cells in pulmonary artery
Vasoconstriction
and proliferation
Cyclic GMP
Vasodilation and antiproliferation
Bosentan
Exogenous
iNO
Epoprostenol
Sildenafil
(PDE5
inhibitor)
Nitric Oxide

24.  Beware of Systemic Hypotension with pulmonary
vasodilators

25.  PPHN in preterm
 PPHN and Therapeutic hypothermia

26.  Premature infants with PPROM and presumed severe hypoxemic
respiratory failure because of hypoplastic lungs often have
significant PPHN and may show improvement in oxygenation after
treatment with HFOV and INO
 Early functional ECHO results in earlier identification and treatment
of infants with PPHN in this high-risk group.
J Paediatr Child Health. 2011

27.  Therapeutic hypothermia is not a risk factor for PPHN
 Can be safely done in infants wih PPHN
Ela Chakkarapani, Perinatology 2010; 3:20-29

28. •Confirm diagnosis
•Exclude/treat differential
•Ongoing Care(ABC) in a tertiary centre
•Ventilation,Oxygenation, Normal BP
•Sedation , ± paralysis,
•Secure access- UAC,UVC
•Exclude CHD
•Correct hypothermia, hypoglycemia,
hypocalcaemia, hypomagnesaemia, PolycythemiaOxygnation Index
• > 25- Consider INO
• >40 - Consider ECMO
Specific Rx- Pulmonary Vasodilators
O2
Nitric Oxide
Sildenafil- Oral/IV(± INO)
Milrinone,
Prostoglandins, Bosentan etc
Consider ECMO if no
response