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