patent ductus arteriosus
TRANSCRIPT
Patent Ductus ArteriosusPatent Ductus Arteriosus
Dr. Shamshuddin Patel Sr.
Normally blood flows from the right side of the heart to the left. Deoxygenated blood enters the right atrium then right ventricle. Blood travels to the lungs through the pulmonary artery to become oxygenated. The left atrium then receives the oxygenated blood. After passing through the left atrium, blood travels to the left ventricle and then to the aorta, and finally out to the body. However, in fetal circulation, blood in the heart is shunted away from the lungs.
To the Body
RightAtrium
RightVentricle
PulmonaryArtery
Aorta
LeftAtrium
LeftVentricle
Fetal Circulation
Blood flow within the fetal heart is very similar to blood flow in the heart after birth. However, within the fetal circulation there are two shunts that direct blood flow away from the lungs. Blood must bypass the lungs because prior to birth the fetal lungs are not fully developed. These shunts are known as the foramen ovale and the ductus arteriosus. The foramen ovale is an opening located in the right atrium. This opening allows blood to be shunted from the right atrium directly to the left atrium and away from the fetal lungs. The ductus arteriosus is a vascular connection found directly between the pulmonary artery and the aorta. Blood is shunted from the pulmonary artery directly into the aorta and again away from the fetal lungs. The fetus is connected by the umbilical cord to the placenta of the mother. Oxygen and carbon dioxide exchange takes place at the placenta along with the elimination of waste products.
Ductus Arteriosus
ForamenOvale
Flow Chart of Fetal CirculationFlow Chart of Fetal Circulation
What Major Changes in Infant What Major Changes in Infant
Circulation occur following Circulation occur following
birth?birth?
• Lungs: o Lungs expando PaO2↑’s Pulmonary vasodilatation o Drop in pulmonary vascular resistance.
• Systemic Circulation:o Resistance ↑’s with placental removal
• PDA: o flow reverses to L R shuntingo Begins to functionally close due to ↑ PaO2, and decreased
PGE2 levels
PhysiologyPhysiology• Ductus Arteriosus closes within few hours after birth.• It occurs by 2 phases: Functional Closure and Anatomical
Closure• Functional Closure: Occurs in 1st few hours of life. It occurs
by vasoconstriction of DA. This depends on balance between Dilating and Contracting forces.o Mechanism: After delivery, increased PO2 and increased intrinsic tone of DA causes
DA constriction.
• After Birth, Factors causing DA constriction:o Increased O2o Decreased BP due to Decreased Pulmonary Vascular Resistanceo Decreased PGE2 due to Decreased placental PG synthesis and increased removal of
PG by lungs.
Anatomical Closure:it occurs due to :Initial Vasoconstriction of DA, causes DA wall Ischemia, which leads to loss of smooth muscle cells from tunica media along with increased local production of growth factors like Vascular Endothelial GF and Transforming GF-B.
HISTOLOGYHISTOLOGY
The smooth muscular layer fibers are arranged in cylindrical layers spiraling in opposite directions.
There is increased mucoid substance in the intimal layer.
Mechanism Mechanism
Factors Influencing closureof duct
Contractile Apparatus
Increased Pa Oxygen
AbsentOr reduced(asphyxia, high Altitude)
Relaxant influences Prostaglandins
UnresponsiveOr deficient(prematurity,Genetic)
PERSISTENT DUCTUS ARTERIOSUS
Definition: Ductus Arteriosus is a vessel that connects the pulmonary artery and aorta.
Failure of closure and continued patency of this fetal channel is termed PERSISENT DUCTUS ARTERIOSUS (PDA)
IncidenceIncidence
1/2000 births 5% to 10% of CHD With silent PDA ,Incidence is 1:500 F>M(2:1)
Etiologic factorsEtiologic factors
• Sporadic• Multifocal (genetic + environmental + low
O2(Asphyxia),rubella(First 4 weeks)/chemicals)
Chromosomal aberrations : Trisomy 21 Single-gene mutations : Holt-Oram
syndrome/ Char syndrome(TFAP2B mutations )
X-linked mutations
Factors with increased Factors with increased
incidenceincidence
Prematurity: Inversely related to gestational age. Found in approx. 45% of infants <1750gm
80% of infants <1000gm
RDS: Correlated with severity of RDS. After surfactant treatment increased risk of clinically symptomatic PDA
Fluid overloadAsphyxia
Antenatal steroid administrationIUGRProlonged rupture of membranes
Factors with decreased incidenceFactors with decreased incidence
Natural HistoryNatural History• Spontaneous closure may be delayed until 3 months of
life, after which the closure rate is less than 0.6%/Year• Silent PDA remain undetected for life• Premature : Closure could be delayed up to 1 year and
more PDA• Sibling :1% and 5%• Parents:3%• Persistent patency of the ductus arteriosus following
birth is inversely related to gestational age. • This may be due to the smaller amount of muscular
tissue in the media with lower intrinsic tone, and lower responsiveness to oxygen but higher sensitivity to the vasodilating effects of prostaglandin E2 and nitric oxide.
Reopening of a Constricted Reopening of a Constricted
DuctusDuctus
• Before true anatomic closure occurs, the functionally closed Ductus may be dilated by a reduced arterial Po2 or an increased PGE2 concentration. The reopening of the constricted Ductus may occur in asphyxia and various pulmonary diseases (as hypoxia and acidosis relax ductal tissues).
PathophysiologyPathophysiology Small PDA : Asymptomatic throughout life. Accidental
detection by ECHO for murmur Moderate PDA: Compensate well throughout childhood and
may remain completely asymptomatic in early adulthood but will
eventually present with exercise intolerance and symptoms related to left ventricular
failure, usually starting in the third decade. Moderate to large: Large volume of blood leads to the very
early development of pulmonary congestion, decreased lung compliance, and failure of the left ventricle, often presenting within weeks after birth with failure to thrive, recurrent pulmonary infections, and even death. Pulmonary overcirculation remains uncorrected, the arteriolar medial hypertrophy, intimal proliferation, and eventual obliteration of pulmonary arterioles and capillaries will lead to an irreversible marked increase in pulmonary arterial pressure. When pulmonary vascular resistance exceeds the systemic vascular resistance, ductal shunting is reversed and becomes right to left (Eisenmenger syndrome)
Clinical ManifestationsClinical Manifestations• A small patent ductus does not usually have any
symptoms associated with it.• A large PDA will result in heart failure. Retardation
of physical growth may be a major manifestation in infants with large shunts.
• A large PDA will result in striking physical signs attributable to the wide pulse pressure, most prominently, bounding peripheral arterial pulses.
• The heart is normal in size when the ductus is small, but moderately or grossly enlarged in cases with a large communication.
• The apical impulse is prominent and, with cardiac enlargement, it is heaving.
Clinical ManifestationsClinical Manifestations• A thrill, maximal in the 2nd left interspace, is often
present and may radiate toward the left clavicle, down the left sternal border, or toward the apex. It is usually systolic but may also be palpated throughout the cardiac cycle.
• The classical continuous murmur is described as being like machinery or rolling thunder in quality. It begins soon after onset of the 1st sound, reaches maximal intensity at the end of systole, and wanes in late diastole. It may be localized to the 2nd left intercostal space or radiate down the left sternal border or to the left clavicle. When pulmonary vascular resistance is increased, the diastolic component of the murmur may be less prominent or absent
Model Case• Called to the bedside of a 5 day old 25 week
infant with worsening respiratory distress. He is requiring higher O2 settings and continues to have multiple desaturations despite increased ventilator settings
What is the initial differential What is the initial differential
for this infant’s respiratory for this infant’s respiratory
distress?distress?
• Respiratory:o Respiratory Distress
Syndrome (RDS)o Pneumothoraxo Pulmonary Hemorrhage
• Cardiaco Persistent Ductus Arteriosus
(PDA)o Ductal Dependent Heart
Lesion
• Otherso Sepsiso Pneumonia
• GIo NEC
• Neuro:o IVHo Seizures
Physical ExamPhysical Exam• Vitals: 160, RR 68, BP 45/20, SaO2 85%• Weight: 980 grams (up 80 grams from 1 day prior)• HEENT: unremarkable• Pulm: tachypneic, decreased lung sounds at bases,
crackles heard bilaterally posterior lung fields• CV: 3/6 systolic murmur loudest at LUSB<left upper
sternal border>, bounding palmar pulses, active precordium, 2+femoral pulses, CR <2 seconds
• Abdomen: soft, active bowel sounds• Skin: warm, dry
What is the likely cause of What is the likely cause of this infants respiratory this infants respiratory
distress?distress?A. Respiratory Distress SyndromeB. PDAC. SepsisD. NEC
What is the likely cause of this What is the likely cause of this
infants respiratory distress?infants respiratory distress?A. Respiratory Distress Syndrome
B.PDAC. SepsisD. NEC
What Physical Exam findings What Physical Exam findings are consistent with PDA?are consistent with PDA?
Murmur: systolic at LUSB/Left Infraclavicular, may progress to continuous (machinery)
Cardiac: Active Precordium, Widened Pulse Pressure, Bounding Pulses
Respiratory Sx: Tachypnea, Apnea, CO2, increased vent settings
What further diagnostic What further diagnostic
studies could be done to studies could be done to
confirm this?confirm this?• CXR• Echocardiogram
What findings on this CXR are What findings on this CXR are suggestive of a PDA?suggestive of a PDA?
Increased Pulmonary vascular makings
Cardiomegaly
Uptodate.com
EchocardiogramEchocardiogram• Gold standard for diagnosing PDA
Taken from Neo Reviews
Which Infants are at Which Infants are at greatest risk?greatest risk?
• The Youngest: risk increases with decreasing gestational age
• The Smallest: 80% of ELBW infants (BW <1000g) with a murmur progress to large persistent PDAs
What are complications of What are complications of
having hemodynamically having hemodynamically
significant PDA?significant PDA?• Pulmonary Edema• Pulmonary Hemorrhage• BPD• NEC• Heart Failure• IVH• Prolonged ventilator/O2 support• Longer Duration of hospitalization.
What makes a PDA What makes a PDA
Hemodynamically Significant?Hemodynamically Significant?
Systemic Hypoperfusion (↓ Qs)
Pulmonary Overcirculation (↑ Qp)
Systemic HypotensionEnd-Organ HypoperfusionRenal InsufficiencyNECIVHAcidosis (metabolic, lactic)
Oxygenation failureIncreased Vent RequirementsPulmonary Edema Cardiomegaly
What are three main What are three main
options for treatment?options for treatment?1. Conservative/Supportive Management2. Pharmacotherapy3. Surgery
What Supportive Measures can What Supportive Measures can
you take in an infant with a you take in an infant with a
symptomatic PDA?symptomatic PDA?• Ventilator Strategies:
o Adequate Oxygenationo Permissive Hypercapneao Use of PEEP
• Mild Fluid restriction: 110-130 ml/kg/day• Heme: Maintenance of HCT 35-40%
PharmacotherapyPharmacotherapy• What 2 agents are typically used?
o Indomethacino Ibuprofen
IndomethacinIndomethacin• MOA:
o Cyclooxygenase inhibitor o COX enzyme necessary for generating PGE2 (potent vasodilator)
• Adverse-Effects:o reduces cerebral, gastrointestinal, and renal blood flowo Decreased urine outputo Platelet dysfunction
• Would you continue/start feeds on this infant?o given concern for increased risk of NEC many neonatologists
hold feeds during indomethacin therapy
Prophylactic: Timing: usually within 1st 24 hours of life.Indication: All infant <1250gm birth weight who
have respiratory distress.
Therapeutic:Timing: usually within 1st 14 days of life.Indications:
1. If there is any clinical sign of PDA In preterm baby.2. There are signs of overt failure or congestive cardiac failure.3. Re-treatment after failure of the first course indomethacin.4. Recurrence of PDA after first course of indomethacin.
Dose of Indomethacin: O.2mg/kg stat followed by
IbuprofenIbuprofenDose: Initial dose of 10mg/kg followed at 24
hour intervals by two doses of 5mg/kg.
As Ibuprofen has less Adverse effect than Indomethacin, So Ibuprofen is superior than Indomethacin.
What are some contraindications What are some contraindications
to indomethacin?to indomethacin? Proven/ suspected infection Active bleeding
e.g. IVH, NEC Thrombocytopenia and/or coagulation defects Necrotizing enterocolitis Severe Renal Impairment Congenital heart disease with ductal
dependent lesion
Complications to watch for…Complications to watch for…• What are you going to instruct the Nurse to
notify you about in this patient?o Decreased Urine Output
• Indocin should be held if UrineOutPut < 1 ml/kg/h
o Abdominal Changeso Signs/Sx of bleeding
• Are there any labs you would like to check before/after starting indomethacin?o CBC: to check plateletso BMP: to check BUN and Creatinine
After two trials of indomethacin After two trials of indomethacin
your patient still has a your patient still has a
symptomatic PDA what next steps symptomatic PDA what next steps
might you take?might you take?
• Continue supportive therapy through ventilator and fluid management
• If infant continues to require high ventilator support and echo demonstrates a large PDA consider surgical ligation
Surgical LigationSurgical Ligation• Indications?
o Persistent Symptomatic PDA after 1-2 trials of Indomethacin or Motrin
o Contraindication to Indomethacin or Motrin
• Complications?o recurrent laryngeal nerve paralysiso blood pressure fluctuationso respiratory compromiseo infectiono intraventricular hemorrhageo chylothoraxo BPDo Death
• Timing: After 6months of age.• Procedure: ligation and division of ductus via
thoracotomy.
Surgical LigationSurgical Ligation
• Long Term Outcomeso Current studies do not demonstrate that ligation
decreases incidence of BPDo Some data to suggest infants that have surgical
ligation are at greater risk for neurocognitive delays
• Surgery should only be used for infants that have failed medical management and are symptomatic
References:References:• Chorne N, Leonard C, Piecuch R, Clyman RI. Patent
ductus arteriosus and its treatment as risk factors for neonatal and neurodevelopmental morbidity. Pediatrics. 2007;119(6):1165.
• Gien, J. Controversied in the Management of Patent Ductus Arteriosus. Neoreviews 2008: 9, 477-482
• Masalli, R. Optimal Fluid Management in Premature Infants with PDA. Neoreviews 2010; 11: 495-502
• Philips , Joseph B. Management of patent ductus arteriosus in premature infants. UptoDate (www.uptodate.com)
• Phillips, J. Pathophysiology, clinical manifestations, and diagnosis of patent ductus arteriosus in premature infants. UptoDate (www.uptodate.com)
• Nelson Text Book of Pediatrics