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.
Download ReportTranscript 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.
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 (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 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!