This infant is a 5 day old 25 week preemie with worsening respiratory distress requiring increased oxygen and ventilator support. On exam, the infant has a systolic murmur and signs of increased cardiac output including bounding pulses. An echocardiogram is needed to confirm a diagnosis of a hemodynamically significant patent ductus arteriosus (PDA), which could be contributing to the respiratory distress. Treatment options for a large PDA include supportive care, medications like indomethacin or ibuprofen to close the ductus, or surgery.

1. PPaatteenntt DDuuccttuuss AArrtteerriioossuuss
Dr. Shamshuddin Patel Sr.

2. 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
Right
Atrium
Right
Ventricle
Pulmonary
Artery
Aorta
Left
Atrium
Left
Ventricle
Fetal Circulation

3. 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
Foramen
Ovale

4. FFllooww CChhaarrtt ooff FFeettaall CCiirrccuullaattiioonn

5. WWhhaatt MMaajjoorr CChhaannggeess iinn IInnffaanntt
CCiirrccuullaattiioonn ooccccuurr ffoolllloowwiinngg bbiirrtthh??
• Lungs:
o Lungs expand
o 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 shunting
o Begins to functionally close due to ↑ PaO2, and decreased PGE2 levels

6. PPhhyyssiioollooggyy
• 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 O2
o Decreased BP due to Decreased Pulmonary Vascular Resistance
o Decreased PGE2 due to Decreased placental PG synthesis and increased
removal of PG by lungs.

7. 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.

8. HHIISSTTOOLLOOGGYY
The smooth muscular layer fibers are
arranged in cylindrical layers spiraling in
opposite directions.
There is increased mucoid substance in the
intimal layer.

9. MMeecchhaanniissmm

10. Factors
Influencing closure
of duct
Increased Pa Oxygen
Contractile
Apparatus
Absent
Or reduced
(asphyxia, high
Altitude)
Relaxant influences Prostaglandins
Unresponsive
Or deficient
(prematurity,
Genetic)

11. 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)

13. IInncciiddeennccee
 1/2000 births
 5% to 10% of CHD
 With silent PDA ,Incidence is 1:500
 F>M(2:1)

14. EEttiioollooggiicc ffaaccttoorrss
• 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

15. FFaaccttoorrss wwiitthh iinnccrreeaasseedd iinncciiddeennccee
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 overload
Asphyxia

16. FFaaccttoorrss wwiitthh ddeeccrreeaasseedd iinncciiddeennccee
Antenatal steroid administration
IUGR
Prolonged rupture of membranes

17. NNaattuurraall HHiissttoorryy
• 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.

18. RReeooppeenniinngg ooff aa CCoonnssttrriicctteedd DDuuccttuuss
• 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).

19. PPaatthhoopphhyyssiioollooggyy
 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)

20. CClliinniiccaall MMaanniiffeessttaattiioonnss
• 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.

21. CClliinniiccaall MMaanniiffeessttaattiioonnss
• 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

22. 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

23. What iiss tthhee iinniittiiaall ddiiffffeerreennttiiaall ffoorr
tthhiiss iinnffaanntt’’ss rreessppiirraattoorryy ddiissttrreessss??
• Respiratory:
o Respiratory Distress Syndrome
(RDS)
o Pneumothorax
o Pulmonary Hemorrhage
• Cardiac
o Persistent Ductus Arteriosus
(PDA)
o Ductal Dependent Heart Lesion
• Others
o Sepsis
o Pneumonia
• GI
o NEC
• Neuro:
o IVH
o Seizures

24. PPhhyyssiiccaall EExxaamm
• 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

25. WWhhaatt iiss tthhee lliikkeellyy ccaauussee ooff tthhiiss
iinnffaannttss rreessppiirraattoorryy ddiissttrreessss??
A. Respiratory Distress Syndrome
B. PDA
C. Sepsis
D. NEC

26. What is tthhee lliikkeellyy ccaauussee ooff tthhiiss
iinnffaannttss rreessppiirraattoorryy ddiissttrreessss??
A. Respiratory Distress Syndrome
B. PDA
C. Sepsis
D. NEC

27. WWhhaatt PPhhyyssiiccaall EExxaamm ffiinnddiinnggss
aarree ccoonnssiisstteenntt wwiitthh PPDDAA??
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

28. What ffuurrtthheerr ddiiaaggnnoossttiicc ssttuuddiieess
ccoouulldd bbee ddoonnee ttoo ccoonnffiirrmm tthhiiss??
• CXR
• Echocardiogram

29. WWhhaatt ffiinnddiinnggss oonn tthhiiss CCXXRR aarree
ssuuggggeessttiivvee ooff aa PPDDAA??
Increased
Pulmonary
vascular
makings Cardiomegaly
Uptodate.com

30. EEcchhooccaarrddiiooggrraamm
• Gold standard for diagnosing PDA
Taken from Neo Reviews

31. WWhhiicchh IInnffaannttss aarree aatt
ggrreeaatteesstt rriisskk??
• The Youngest: risk increases with decreasing
gestational age
• The Smallest: 80% of ELBW infants (BW <1000g) with a
murmur progress to large persistent PDAs

32. WWhhaatt aarree ccoommpplliiccaattiioonnss ooff hhaavviinngg
hheemmooddyynnaammiiccaallllyy ssiiggnniiffiiccaanntt PPDDAA??
• Pulmonary Edema
• Pulmonary Hemorrhage
• BPD
• NEC
• Heart Failure
• IVH
• Prolonged ventilator/O2 support
• Longer Duration of hospitalization.

33. WWhhaatt mmaakkeess aa PPDDAA
HHeemmooddyynnaammiiccaallllyy SSiiggnniiffiiccaanntt??
Pulmonary Overcirculation (↑ Qp) Systemic Hypoperfusion (↓ Qs)
Systemic Hypotension
End-Organ Hypoperfusion
Renal Insufficiency
NEC
IVH
Acidosis (metabolic, lactic)
Oxygenation failure
Increased Vent
Requirements
Pulmonary Edema
Cardiomegaly

34. WWhhaatt aarree tthhrreeee mmaaiinn
ooppttiioonnss ffoorr ttrreeaattmmeenntt??
1. Conservative/Supportive Management
2. Pharmacotherapy
3. Surgery

35. WWhhaatt SSuuppppoorrttiivvee MMeeaassuurreess ccaann yyoouu ttaakkee iinn
aann iinnffaanntt wwiitthh aa ssyymmppttoommaattiicc PPDDAA??
• Ventilator Strategies:
o Adequate Oxygenation
o Permissive Hypercapnea
o Use of PEEP
• Mild Fluid restriction: 110-130 ml/kg/day
• Heme: Maintenance of HCT 35-40%

36. PPhhaarrmmaaccootthheerraappyy
• What 2 agents are typically used?
o Indomethacin
o Ibuprofen

37. IInnddoommeetthhaacciinn • MOA:
o Cyclooxygenase inhibitor
o COX enzyme necessary for generating PGE2 (potent vasodilator)
• Adverse-Effects:
o reduces cerebral, gastrointestinal, and renal blood flow
o Decreased urine output
o 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

38. 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.

39. Dose of Indomethacin: O.2mg/kg stat followed by

40. IIbbuupprrooffeenn
Dose:
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.

41. WWhhaatt aarree ssoommee ccoonnttrraaiinnddiiccaattiioonnss ttoo
iinnddoommeetthhaacciinn??
 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

42. CCoommpplliiccaattiioonnss ttoo wwaattcchh ffoorr……
• 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 Changes
o Signs/Sx of bleeding
• Are there any labs you would like to check before/after
starting indomethacin?
o CBC: to check platelets
o BMP: to check BUN and Creatinine

43. After ttwwoo ttrriiaallss ooff iinnddoommeetthhaacciinn yyoouurr
ppaattiieenntt ssttiillll hhaass aa ssyymmppttoommaattiicc PPDDAA
wwhhaatt nneexxtt sstteeppss mmiigghhtt yyoouu ttaakkee??
• 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

44. SSuurrggiiccaall LLiiggaattiioonn • Indications?
o Persistent Symptomatic PDA after 1-2 trials of Indomethacin or Motrin
o Contraindication to Indomethacin or Motrin
• Complications?
o recurrent laryngeal nerve paralysis
o blood pressure fluctuations
o respiratory compromise
o infection
o intraventricular hemorrhage
o chylothorax
o BPD
o Death
• Timing: After 6months of age.
• Procedure: ligation and division of ductus via
thoracotomy.

45. SSuurrggiiccaall LLiiggaattiioonn
• Long Term Outcomes
o Current studies do not demonstrate that ligation
decreases incidence of BPD
o 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

46. RReeffeerreenncceess::
• 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