Persistent Pulmonary

Hypertension (PPHN)
F. Hazel R. Villa, MD
PL1
 Objectives
 to review the fetal,transitional and postnatal
circulation in relation to PPHN

 To understand the pathophysiology of PPHN

as it applies to clinical manifestations and
management
 Pulmonary vessels
VASOCONSTRICTORS VASODILATORS
(Maintain high fetal PVR) (Decrease PVR during
transition)
Norepinephrine
A-adrenergic stimulation PGI2, PGD2, PGE2
Hypoxia Nitric oxide
Endothelin Cyclic GMP
Thromboxanes Cyclic AMP
Leukotrienes Oxygen
Platelet activating factor Adenosine
PGF2a Bradykinin
Fetal circulation
 Fetal circulation

 pO2, PGI2, NO
 ADMA -- competes with arginine
inhibit NOS

 Vasoconstriction
Postnatal circulation
Transitional circulation
 Transitional to postnatal

 At birth
 increase in NO, NOS- cGMP
increase guanylate cyclase- cGMP
increase in PGI2 (effect of estrogen) cAMP
DDAH metabolizes ADMA

 Vasodilatation
 Transitional to postnatal

 At birth
ventilation
increase pulmonary blood flow

Oxygenation
 Transitional to postnatal
 Oxygen- stimulates NOS, COX1
 Pulmonary blood flow- release of NO, PGI2

 Evidence: NO-cGMP pathway is a more potent

modulator of pulmonary vascular tone
 Increase in SVR
 Removal of the placenta

 Catecholamine associated with birth

 Cold environment
 Postnatal decrease in PVR
 Expansion of the lung

 Adequate ventilation, oxygenation

 Clearance of fetal lung fluid

 3 types of abnormalities
 Maladaptation

 Maldevelopment

 Underdevelopment
 Maladaptation
 Prototype: Meconium aspiration pneumonia
 Pneumonia, RDS

 Obstruction of the airways

 Chemical pneumonitis
 Release of endothelin,thromboxane
vasoconstrictors
 Maldevelopment
 Prototype: Idiopathic PPHN
 (“black lung” PPHN)
 Vessel wall thickening
 Smooth muscle hyperplasia
 Cause – intrauterine exposure to NSAID
 constriction of ductus arteriosus
 genetic
 Maldevelopment
 Disruption of NO-cGMP pathway
 Disruption of PGI2-cAMP pathway
 Guanylate cyclase is less active
 Increased ROS (reactive oxygen species)
vasoconstrictor
 Increased thromboxane, endothelin
 Underdevelopment
 Prototype: Congenital diaphragmatic hernia
 Pulmonary hypoplasia
 Decreased cross sectional area of pulmonary
vasculature
 Decreased pulmonary blood flow
 Abnormal muscular hypertrophy of the pulm
arterioles
 Clinical signs and symptoms
 PE:
 meconium staining
 Prominent precordial impulse
 Narrow split accentuated P2
 Systolic murmur LLSB
 Labs
 CXR: CDH, decreased vascular markings,
parenchymal disease
 ECG: RV predominance, ST elevation
 ABG: hyperoxic test (pO2 < 100 at 100% O2)
 Pre and postductal ABG (R radial artery:
umbilical artery/lower extremity)
 10-15% saturation and or 10-15mmHg pO2
 Labs
 Echocardiography
 Structural heart disease is determined
 R-L shunting (Ductus or FO)
 Pulmonary arterial pressure is measured
 Management
 Oxygen 100% pO2 should be kept between
50-90mmHg (O2 saturation >90%)
 Correct factors promoting vasoconstriction:
hypoglycemia, hypocalcemia, anemia, hypovolemia

 Optimize cardiac function (inotropic agents, volume

expansion

 Mechanical ventilation
 Surfactant
 Management
 Inhaled Nitric oxide- an ideal selective
pulmonary vasodilator
 OI of >25
 OI=(MAP x FiO2)/pO2 x 100
 Contraindications: CHD which are PDA dependent
 (aortic stenosis, interrupted aortic arch, hypolastic heart
syndrome)
 May worsen pulmonary edema in obstructed TAPVR

Used to transport patient for ECMO

 Management
 ECMO
 Goal of this treatment:
 maintain adequate tissue oxygenation and
 avoid irreversible lung injury, while PVR
decreases and correcting pulm HTN
 ECMO if OI is >40
 Other Pulmonary Vasodilators
 Sildenafil- PDE5 inhibitor increased cGMP
 Milrinone- PDE3 inhibitor increased cAMP
 Inhaled PGI2
 Superoxide dismutase-superoxide scavenger
 Dilates pulm vessels, and increase endogenous NO
 References
 http://neoreviews.aappublications.org/cgi/content/full/8/1/e14
 http://www.utdol.com/utd/content/topic.do?topicKey=neonatol
/1427&view=print
 www.emedicine.com/ped/topic2530.htm
 www.emedicine.com/PED/topic2530.htm
 phassociation.org/medical/.../Summer_2006/persisten
t_ph_newborn.pdf
Thank you!