persistent pulmonary hypertension (pphn)
DESCRIPTION
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. VASOCONSTRICTORS - PowerPoint PPT PresentationTRANSCRIPT
Persistent Pulmonary Persistent Pulmonary Hypertension (PPHN)Hypertension (PPHN)
F. Hazel R. Villa, MDF. Hazel R. Villa, MD
PL1PL1
ObjectivesObjectives
to review the fetal,transitional and postnatal to review the fetal,transitional and postnatal circulation in relation to PPHNcirculation in relation to PPHN
To understand the pathophysiology of PPHN To understand the pathophysiology of PPHN as it applies to clinical manifestations and as it applies to clinical manifestations and managementmanagement
Pulmonary vesselsPulmonary vessels
VASOCONSTRICTORSVASOCONSTRICTORS
(Maintain high fetal PVR)(Maintain high fetal PVR)
NorepinephrineNorepinephrine
A-adrenergic stimulationA-adrenergic stimulation
HypoxiaHypoxia
EndothelinEndothelin
ThromboxanesThromboxanes
LeukotrienesLeukotrienes
Platelet activating factorPlatelet activating factor
PGF2aPGF2a
VASODILATORSVASODILATORS(Decrease PVR during (Decrease PVR during
transition)transition)
PGI2PGI2, PGD2, PGE2, PGD2, PGE2
Nitric oxideNitric oxide
Cyclic GMPCyclic GMP
Cyclic AMPCyclic AMP
OxygenOxygen
AdenosineAdenosine
BradykininBradykinin
Fetal circulation
Fetal circulationFetal circulation
pO2, PGI2, NOpO2, PGI2, NO ADMA -- competes with arginineADMA -- competes with arginine
inhibit NOSinhibit NOS
VasoconstrictionVasoconstriction
Postnatal circulation
Transitional circulation
Transitional to postnatalTransitional to postnatal
At birth At birth increase in NO, NOS-increase in NO, NOS- cGMP cGMP
increase guanylate cyclase-increase guanylate cyclase- cGMP cGMP
increase in PGI2 (effect of estrogen)increase in PGI2 (effect of estrogen) cAMP cAMP
DDAH metabolizes ADMADDAH metabolizes ADMA
VasodilatationVasodilatation
Transitional to postnatalTransitional to postnatal
At birthAt birth
ventilationventilation
increase pulmonary blood flowincrease pulmonary blood flow
OxygenationOxygenation
Transitional to postnatalTransitional to postnatal
Oxygen- stimulates NOS, COX1Oxygen- stimulates NOS, COX1 Pulmonary blood flow- release of NO, PGI2Pulmonary blood flow- release of NO, PGI2
Evidence: NO-cGMP pathway is a more Evidence: NO-cGMP pathway is a more potent modulator of pulmonary vascular tonepotent modulator of pulmonary vascular tone
Increase in SVRIncrease in SVR
Removal of the placentaRemoval of the placenta
Catecholamine associated with birth Catecholamine associated with birth
Cold environmentCold environment
Postnatal decrease in PVRPostnatal decrease in PVR
Expansion of the lungExpansion of the lung
Adequate ventilation, oxygenationAdequate ventilation, oxygenation
Clearance of fetal lung fluidClearance of fetal lung fluid
3 types of abnormalities3 types of abnormalities
MaladaptationMaladaptation
MaldevelopmentMaldevelopment
UnderdevelopmentUnderdevelopment
MaladaptationMaladaptation
Prototype: Meconium aspiration pneumoniaPrototype: Meconium aspiration pneumonia Pneumonia, RDSPneumonia, RDS
Obstruction of the airwaysObstruction of the airways Chemical pneumonitisChemical pneumonitis Release of endothelin,thromboxaneRelease of endothelin,thromboxane
vasoconstrictorsvasoconstrictors
MaldevelopmentMaldevelopment
Prototype: Idiopathic PPHN Prototype: Idiopathic PPHN (“black lung” PPHN)(“black lung” PPHN) Vessel wall thickeningVessel wall thickening Smooth muscle hyperplasiaSmooth muscle hyperplasia Cause – intrauterine exposure to NSAIDCause – intrauterine exposure to NSAID constriction of ductus arteriosus constriction of ductus arteriosus geneticgenetic
Disruption of NO-cGMP pathwayDisruption of NO-cGMP pathway Disruption of PGI2-cAMP pathwayDisruption of PGI2-cAMP pathway Guanylate cyclase is less activeGuanylate cyclase is less active Increased ROS (reactive oxygen species)Increased ROS (reactive oxygen species)
vasoconstrictorvasoconstrictor Increased thromboxane, endothelinIncreased thromboxane, endothelin
MaldevelopmentMaldevelopment
UnderdevelopmentUnderdevelopment
Prototype: Congenital diaphragmatic herniaPrototype: Congenital diaphragmatic hernia Pulmonary hypoplasiaPulmonary hypoplasia
Decreased cross sectional area of pulmonary Decreased cross sectional area of pulmonary vasculaturevasculature
Decreased pulmonary blood flowDecreased pulmonary blood flow Abnormal muscular hypertrophy of the pulm Abnormal muscular hypertrophy of the pulm
arteriolesarterioles
Clinical signs and symptomsClinical signs and symptoms
PE:PE: meconium stainingmeconium staining Prominent precordial impulseProminent precordial impulse Narrow split accentuated P2Narrow split accentuated P2 Systolic murmur LLSBSystolic murmur LLSB
LabsLabs
CXR: CDH, decreased vascular markings, CXR: CDH, decreased vascular markings, parenchymal diseaseparenchymal disease
ECG: RV predominance, ST elevationECG: RV predominance, ST elevation ABG: hyperoxic test (pO2 < 100 at 100% O2)ABG: hyperoxic test (pO2 < 100 at 100% O2) Pre and postductal ABG (R radial artery: Pre and postductal ABG (R radial artery:
umbilical artery/lower extremity) umbilical artery/lower extremity) 10-15% saturation and or 10-15mmHg pO210-15% saturation and or 10-15mmHg pO2
LabsLabs
EchocardiographyEchocardiography Structural heart disease is determinedStructural heart disease is determined R-L shunting (Ductus or FO)R-L shunting (Ductus or FO) Pulmonary arterial pressure is measuredPulmonary arterial pressure is measured
ManagementManagement
Oxygen 100% pO2 should be kept between Oxygen 100% pO2 should be kept between 50-90mmHg (O2 saturation >90%)50-90mmHg (O2 saturation >90%)
Correct factors promoting vasoconstriction: Correct factors promoting vasoconstriction: hypoglycemia, hypocalcemia, anemia, hypovolemiahypoglycemia, hypocalcemia, anemia, hypovolemia
Optimize cardiac function Optimize cardiac function (inotropic agents, volume (inotropic agents, volume expansion expansion
Mechanical ventilationMechanical ventilation SurfactantSurfactant
Inhaled Nitric oxide- an ideal selective Inhaled Nitric oxide- an ideal selective pulmonary vasodilatorpulmonary vasodilator OI of >25 OI of >25 OI=(MAP x FiO2)/pO2 x 100OI=(MAP x FiO2)/pO2 x 100 Contraindications: CHD which are PDA dependentContraindications: CHD which are PDA dependent
(aortic stenosis, interrupted aortic arch, hypolastic heart (aortic stenosis, interrupted aortic arch, hypolastic heart syndrome)syndrome)
May worsen pulmonary edema in obstructed TAPVRMay worsen pulmonary edema in obstructed TAPVR
ManagementManagement
Used to transport patient for ECMO
ECMO ECMO Goal of this treatment: Goal of this treatment: maintain adequate tissue oxygenation and maintain adequate tissue oxygenation and avoid irreversible lung injury, while PVR avoid irreversible lung injury, while PVR
decreases and correcting pulm HTNdecreases and correcting pulm HTN ECMO if OI is >40ECMO if OI is >40
ManagementManagement
Other Pulmonary VasodilatorsOther Pulmonary Vasodilators
Sildenafil- PDE5 inhibitorSildenafil- PDE5 inhibitor increased cGMP increased cGMP Milrinone- PDE3 inhibitorMilrinone- PDE3 inhibitor increased cAMP increased cAMP Inhaled PGI2Inhaled PGI2 Superoxide dismutase-superoxide scavengerSuperoxide dismutase-superoxide scavenger
Dilates pulm vessels, and increase endogenous NODilates pulm vessels, and increase endogenous NO
ReferencesReferences
http://neoreviews.aappublications.org/cgi/content/full/8/1/e14http://neoreviews.aappublications.org/cgi/content/full/8/1/e14 http://www.utdol.com/utd/content/topic.do?http://www.utdol.com/utd/content/topic.do?
topicKey=neonatol/1427&view=printtopicKey=neonatol/1427&view=print www.emedicine.com/ped/topic2530.htmwww.emedicine.com/ped/topic2530.htm www.emedicine.com/PED/topic2530.htmwww.emedicine.com/PED/topic2530.htm phassociation.org/medical/phassociation.org/medical/....../Summer_2006//Summer_2006/
persistent_ph_newborn.pdfpersistent_ph_newborn.pdf
Thank you!