PERSISTENT PULMONARY

HYPERTENSION IN NEWBORN

By : Dr. Abhay kumar

Moderator : Dr. Akhilesh kumar
Definition
 Disruption of normal perinatal fetal to neonatal
circulatory transition.
 Characterized by sustained elevation in pulmonary
vascular resistance rather than decrease that
normally occurs at birth.
Perinatal circulatory transition
 Rapid fall in PVR with first breath and marked
increase in systemic vascular resistance with the
clamping of umbilical cord.
 Circulating biochemical released due to increased
arterial oxygen content & pH and lowered Paco2
cause constriction of ductus arteriosus and
vasorelaxation of pulmonary circulation.
 These physiologic events raise SVR relative to PVR,
cause functional closure of foramen ovale.
 Pphnphysiology mimics fetal circulation wherein
PVR exceeds SVR & right to left shunting occurs
through foramen ovale &/or ductus arteriosus.
 Pphncauses diminished pulmonary perfusion and
systemic hypoxemia.
Epidemiology
 Occurs in 1-2 per 1000 live births and is most
common among full term and postterm infants.
 Risk factors :-
1. Perinatal :– meconium stained amniotic fluid
2. Maternal :- fever , anaemia , pulmonary
disease ,diabetes , UTI during pregnancy , SSRI
consumption during pregnancy , cesarian section
delivery.
3. Male infants
 Other perinatal & neonatal condition :-
1. Severe fetal asphyxia
2. Pulmonary parenchymal diseases :- surfactant
deficiency, pneumonia, aspiration syndromes
3. Abnormal pulmonary development :- pruning of
vascular tree (congenital diaphragmatic hernia,
potter syndrome), alveolar capillary dysplacia
(malalignment of pulmonary arteries & veins.
4. Myocardial dysfunction , myocarditis , intrauterine
constriction of ductus arteriosus
5. Pneumonia , sepsis of bacterial or viral origin
(suppression of endogenous NO production,
endotoxin, pulmonary vasoconstriction due to
thromboxanes.
6. Familial – genetic polymorphism involving ABCA,
ACE, SPINK5, FOXF1.
Pathology & pathophysiology

1. Pulmonary vascular remodeling

Stimulus – fetal hypoxemia
humoral growth factors released by hypoxemia
damaged endothelial cells.

vasoconstriction & overgrowth of pulmonary

vascular media l/t decreased cross sectional area
& elevated PVR
2. Pulmonary hypoplasia – affects both alveolar &
pulmonary arterial development.
It
can be isolated anomaly or with congenital
diaphragmatic hernia, oligohydramnios syndrome,
potter syndrome.
3. Reversible pulmonary vasospasm –
sepsis , hypoxemia , acidosis

suppression of endogenous NO, prostacyclin, or

bradykinin production, release of thromboxane A2 &
B2, leukotriene C4&D4
pulmonary vasoconstriction
4. Myocardial dysfunction with elevated pulmonary
vascular resistance
I. Right ventricular dysfunction – intrauterine
constriction of ductus arteriosus leads to post
natal pulmonary hypertension.
II. Left ventricular dysfunction – causes pulmonary
venous hypertension & secondary pulmonary
artery hypertension.
5. Mechanical factors
lower cardiac output – recruits fewer pulmonary
arterial channels and raises PVR .
Hyper viscosity – a/w polycythemia reduces
pulmonary microvascular perfusion.
DIAGNOSIS
1. Physical examination – marked cyanosis
2. Cardiac examination – prominent precordial
impulse , a single or narrowly split &
accentuated second heart sound , sometimes
systolic TR murmur.
3. ABG or transcutaneous oxygen saturation – a
gradient of 10% or more in oxygen saturation
between simultaneous preductal (right upper
extremity) & post ductal lower extremity.
Absence of differential cyanosis & Sao2 doesn’t
exclude PPHN.
4. Chest x-ray :- appears normal or shows pulmonary
parenchymal disease. Cardiac silhouette is normal
and pulmonary blood flow is normal or diminished.

5. ECG – RV predominance.

6. Echocardiography – hemodynamic shunting,

evaluate ventricular function & exclude congenital
heart disease.
TR or a ventricular septum that is flattened or
bowed to the left suggest pulmonary hypertension.
color Doppler – assess intracardiac or ductal
shunting.
Other diagnostic consideration :-
Rule out other causes of secondary pulmonary
hypertension which may be misdiagnosed as PPHN.

1. Structural cardiovascular abnormalities

associated with right to left ductal or atrial
shunting viz.,
a) Obstruction to pulmonary venous return :
infradiaphragmatic total pulmonary venous
return , hypoplastic left heart syndrome ,
congenital mitral stenosis.
b) Myopathic LV disease : endocardial fibroelastosis
, pompe disease .
c) Obstruction to LV outflow : critical aortic stenosis ,
supravalvular aortic stenosis , interrupted aortic
arch , coarctation of aorta.

d) Obligatory left to right shunt : endocardial cushion

defect , coronary arteriovenous fistula.
2. Primary LV or RV dysfunction associated with
right to left hemodynamic shunting

LV dysfunction due to ischemia or obstruction to LV

outflow might present may lead to right to left
ductus arteriosus shunt.

RV dysfunction as a result of decreased diastolic

compliance & elevated end diastolic pressure may
be associated with right to left atrial shunting
7. Signs favouring cyanotic congenital cardiac disease
over PPHN –
cardiomegaly, grade 3+ murmur, weak pulses,
active precordium, pulse differential between
upper and lower limb, pulmonary edema, ad
persistent pre and post ductal arterial oxygen
tension < 40 mm Hg.
Management

 PPHN is a medical emergency , immediate

intervention required to reverse hypoxemia ,
improve systemic & pulmonary perfusion and
preserve end organ function.

1. Supplemental oxygen :
hypoxia is a powerful vasoconstrictor so in
infants with suspected or documented PPHN , pre &
post ductal Sao2 should be continuously monitored.
 Aim – maintain postductal Sao2 > 93% ; ensure
adequate tissue oxygenation & avoid hypoxia
induced pulmonary vasoconstriction.
fio2 < 98 % ; prevent complication due to free
radical damage.

2. Intubation and mechanical ventilation :

When hypoxemia persists despite maximal
administration of supplemental oxygen and/or
respiratory failure indicated by marked hypercapnea
and academia.
 Target goals: Sao2 94% to 97%, Paco2 40 – 50 mm hg
& pH 7.3 – 7.4 .

 In absence of pulmonary alveolar disease mechanical

ventilation with rapid, low pressure and short
inspiratory time – minimize elevated intrathoracic
pressure and modulate effects of ventilation on
pulmonary venous return and cardiac output.

 PPHN complicated by pulmonary parenchymal

diseases high frequency oscillatory ventilation
(HFOV) more effective in delivering iNO than
conventional mechanical ventilation.
 High frequency jet ventilation for meconium
aspiration pneumonitis and air leaks.
 Surfactant administration in cases of primary or
secondary (meconium induced) surfactant
deficiency.

3. iNO –
a) NO diffuses into smooth muscle cells, increases
intracellular cGMP, relaxes vascular smooth
muscle (pulmonary vasodilation)
b) Usual starting dose is 20 ppm & delivered by
ventilator circuit.
c) As baby improves and Fio2 is < 50 – 60 %, iNO is
tapered gradually every 4 hourly : 20 to 15, 15 to
10, 10 to 5, 5 to 2, 2 to 1 and then off.

d) Oxygen saturation at each step is observed

weaning or discontinuing medication.

e) iNO most effective when administered after

adequate alveolar recruitment by concomitant use of
HFOV and/or surfactant administration when diffuse
parenchymal disease complicates PPHN.
4. ECMO
 In absence of pulmonary hypoplasia, it is a life
saving therapy(75 – 85% infants with PPHN) , who
fail conventional management &/or iNO.
 ECMO criteria
1. Alveolar arterial oxygen difference (AaDo2) >600
or
2. Oxygenation index (OI) > 30 on 2 ABGs done 30
min apart.
5. Sedation and analgesia
a) Fentanyl : 1-4 microgram/kg/hour infusion
b) Morphine : 0.05-0.1 mg/kg/hour infusion
c) Midazolam : 0.06 mg/kg/hour infusion

6. Hemodynamic support
Guided by systemic blood pressure needed to
override elevated PVR or eliminate right to left
shunt.
End organ perfusion assessed by acid base balance
(i.e, lactic acidosis +/-)
 Goal – gradually increase systemic blood pressure
to 50 -70 mm hg (systolic) and 45 – 55 mm hg
(mean)

1. Volume expansion
PPHN with intravascular volume depletion
(haemorrhage or capillary leak) or decreased SVR
(septic shock)

normal saline 10 ml/kg over 20 -30 minutes

2. Packed red blood cells used when in addition
anaemia present
2. Pharmacological treatment
 Inotropic agents such as dobutamine or milrinone,
and vasopressors, such as dopamine, epinephrine
or vasopressin.
A. Dobutamine : for
cardiac dysfunction in setting of PPHN
high doses (5-10 microgram/kg/min) leads
tachycardia & increased myocardial oxygen
consumption.
B. Milrinone :
1) Selective phosphodiesterase 3 inhibitor
2) Both inotropic and vasodilatory properties
3. Milrinone (0.3 – 1 microgram/kg/min) may be
combined with iNO to increase pulmonary
vasodilation and RV performance.
4. Side effect: systemic vasodilation ;dose limiting
ADR

C. Vasopressor therapy : dopamine or epinephrine

increase SVR but donot improve pulmonary blood
flow.
D. Norepinephrine (0.05 – 1 microgram/kg/min)
1. Stimulates both α1 & α2 adrenergic receptors
2. Raises SVR disproportionately to PVR
3. Rarely used due to paucity of data.

E. Any agent with α adrenergic effects(epinephrine,

norepinephrine, dopamine) ≥ 5 microgram/kg/min
; potential to increase PVR. So infants need to
closely monitored and therapy modified if clinical
deterioration observed.
F. Arginine vasopressin (AVP)
I. V1 receptor agonist
II. Selectively vasodilates coronary , cerebral ,
pulmonary and renal vascular bed & cause
vasoconstriction in other systemic vascular beds.
III. Low dose AVP (0.1mU/kg/min to 1.2 mU/kg/min);
adjunctive therapy in infants with PPHN refractory
to iNO treatment, improve blood pressure, urine
output & oxygenation index.
G. Correction of metabolic abnormalities
1. Hypoglycemia and hypocalcemia
2. Provide adequate substrates for myocardial
function and appropriate responses to inotropic
agents.

F. Correction of polycythemia
I. Hyperviscosity increases PVR & increases
vasoactive substances through platelet activation.
II. Partial exchange transfusion to reduce
haematocrit to 50% to 55% when haematocrit
exceeds 65%.
Additional pharmacologic agents

 Sildenafil

1. Phosphodiesterase 5 inhibitor increases

endogenous NO by inhibiting its metabolism.
2. Oral (1-2 mg/kg/dose every 6 hourly.
3. Intravenous (0.4mg/kg over 3 hour followed by
1.6mg/kg/day) ; ADRs- systemic hypotension .
So, not recommended for routine use in
treatment of PPHN.
Post neonatal outcomes in PPHN

 Combined availability of iNO & ECMO led to

reduction in mortality from 25% - 50% to 10% -15%.
 Survivors
of PPHN remain at risk of medical and
neurodevelopmental sequelae.
 20% risk of rehospitalisation within 1 year of
discharge.
 20% - 46% risk of audiologic, neurodevelopmental,
or cognitive impairments.