Diagnosis and Management of PPHNDr Boopathi SellappanFellow Paediatric Cardiology, Bristol Childrens Hospital, Bristol, United Kingdom.

Persistent pulmonary hypertension(or persistent fetal circulation)

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

Fetal circulation.Aortic arch

Ductal arch

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

Types of PPHN

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

Endothelin pathwayNitric 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

Regulation Of PA pressures

Vasoconstriction and proliferation

Cyclic GMP

Vasodilation and antiproliferation

The Lancet, Vol. 358, 2001

Clinical presentation of PPHN 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

Differential diagnosis Congenital heart disease

Primary pulmonary parenchymal diseasesCongenital pneumoniaCCAM, RDS/SDLDPulmonary sequestrationPulmonary hypoplasia etc.,

Sepsis

Alveolar capillary dysplasia

Investigations 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

Oxygenation Index MAP x100      x FiO2

PaO2 (mmHg)

>25- Consider iNO>40 – Consider ECMO

Transthoracic ECHO in PPHN• 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

PPHN - Rt to Lt Shunt across PDA

Skinner J Echocardiography for the neonatologist.  Churchill Livingstone 2000

Flat Septum/D Shaped Lt Ventricle

LV

RV

RV

LV

IVS IVS

Significant TR

RV

RA

LV

LA

Management Goals

• Pulmonary Vasodilation

• Systemic perfusion

• Oxygenation

• Minimal Iatrogenic trauma

Management 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

Ventilation• 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

Blood Gases• PH- High normal• PCo2- > 35 mm Hg• PO2- >50 mm Hg

• Consider early surfactant – Useful in parenchymal disease

Haemodynamics 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

Pulmonary Vasodilators 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

Nitric Oxide (iNO)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

Sildenafil in PPHN 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

Alternatives Bosentan- Endothelin receptor antagonist

Few case reports and ongoing clinical trialsHepatotoxicity, 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

Endothelin pathwayNitric oxide pathway

Prostacyclin pathwayVascular 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

Synergistic action of iNO

Vasoconstriction and proliferation

Cyclic GMPVasodilation and antiproliferation

Bosentan

Exogenous iNO

Epoprostenol

Sildenafil (PDE5

inhibitor)

Nitric Oxide

Beware of Systemic Hypotension with pulmonary vasodilators

Special Situations

PPHN in preterm

PPHN and Therapeutic hypothermia

Prematurity and PPHN 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

PPHN and therapeutic hypothermia

Therapeutic hypothermia is not a risk factor for PPHN

Can be safely done in infants wih PPHN

Ela Chakkarapani, Perinatology 2010; 3:20-29

• 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, Polycythemia

Oxygnation Index• > 25- Consider INO• >40 - Consider ECMO

Specific Rx- Pulmonary VasodilatorsO2Nitric OxideSildenafil- Oral/IV(± INO)Milrinone,Prostoglandins, Bosentan etc

Consider ECMO if no response

Sum

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Don’t forget the Parents

Thank you