Persistent Pulmonary Hypertension (PPHN)

1
Persistent Pulmonary Hypertension (PPHN)

• F. Hazel R. Villa, MD
• PL1

2
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

3
Pulmonary vessels

• VASOCONSTRICTORS
• (Maintain high fetal PVR)
• Norepinephrine
• A-adrenergic stimulation
• Hypoxia
• Endothelin
• Thromboxanes
• Leukotrienes
• Platelet activating factor
• PGF2a

• VASODILATORS
• (Decrease PVR during transition)
• PGI2, PGD2, PGE2
• Nitric oxide
• Cyclic GMP
• Cyclic AMP
• Oxygen
• Adenosine
• Bradykinin

4
(No Transcript)
5
Fetal circulation
6
Fetal circulation

• pO2, PGI2, NO
• ADMA -- competes with arginine
• inhibit NOS
• Vasoconstriction

7
Postnatal circulation
8
Transitional circulation
9
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

10
Transitional to postnatal

• At birth
• ventilation
• increase pulmonary blood flow
• Oxygenation

11
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

12
Increase in SVR

• Removal of the placenta
• Catecholamine associated with birth
• Cold environment

13
Postnatal decrease in PVR

• Expansion of the lung
• Adequate ventilation, oxygenation
• Clearance of fetal lung fluid

14
3 types of abnormalities

• Maladaptation
• Maldevelopment
• Underdevelopment

15
Maladaptation

• Prototype Meconium aspiration pneumonia
• Pneumonia, RDS
• Obstruction of the airways
• Chemical pneumonitis
• Release of endothelin,thromboxane?
  vasoconstrictors

16
Maldevelopment

• Prototype Idiopathic PPHN
• (black lung PPHN)
• Vessel wall thickening
• Smooth muscle hyperplasia
• Cause intrauterine exposure to NSAID
• constriction of ductus arteriosus
• genetic

17
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

18
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

19
Clinical signs and symptoms

• PE
• meconium staining
• Prominent precordial impulse
• Narrow split accentuated P2
• Systolic murmur LLSB

20
Labs

• CXR CDH, decreased vascular markings,
  parenchymal disease
• ECG RV predominance, ST elevation
• ABG hyperoxic test (pO2 lt 100 at 100 O2)
• Pre and postductal ABG (R radial artery
  umbilical artery/lower extremity)
• 10-15 saturation and or 10-15mmHg pO2

21
Labs

• Echocardiography
• Structural heart disease is determined
• R-L shunting (Ductus or FO)
• Pulmonary arterial pressure is measured

22
Management

• Oxygen 100 pO2 should be kept between
  50-90mmHg (O2 saturation gt90)
• Correct factors promoting vasoconstriction
  hypoglycemia, hypocalcemia, anemia, hypovolemia
• Optimize cardiac function (inotropic agents,
  volume expansion
• Mechanical ventilation
• Surfactant

23
Management

• Inhaled Nitric oxide- an ideal selective
  pulmonary vasodilator
• OI of gt25
• 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
24
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 gt40

25
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

26
References

• http//neoreviews.aappublications.org/cgi/content/
  full/8/1/e14
• http//www.utdol.com/utd/content/topic.do?topicKey
  neonatol/1427viewprint
• www.emedicine.com/ped/topic2530.htm
• www.emedicine.com/PED/topic2530.htm
• phassociation.org/medical/.../Summer_2006/persiste
  nt_ph_newborn.pdf

27
Thank you!