PDA

Pathophysiology And Incidence

The ductus arteriosus connects the pulmonary artery to the descending aorta in fetal life.
It diverts a large portion of the ventricular output away from the unexpanded lungs.
In term neonates, the ductus constricts within 24 to 48 hours after birth.
This functional closure is aided by lung expansion, increased oxygenation, and a fall in vasodilatory prostaglandins.
Anatomical closure follows over the next three weeks through connective tissue proliferation and muscle atrophy.
In preterm infants, the ductus has lower intrinsic tone and less smooth muscle.
Preterm ductal tissue has fewer sub-endothelial cushions and high concentrations of vasodilatory prostaglandins.
These factors predispose the preterm neonate to a delay or complete failure of ductal closure.
The incidence of patent ductus arteriosus (PDA) is inversely related to gestational age.
It affects up to 70% to 80% of extremely preterm infants born before 28 weeks of gestation.

A hemodynamically significant PDA (HS PDA) causes blood to shunt from the left to the right circulation.
This shunting leads to pulmonary overcirculation and systemic hypoperfusion.
Pulmonary overcirculation reduces lung compliance and impairs gas exchange.
Alveolar flooding causes protein leakage and surfactant inactivation.
These pulmonary effects increase the duration of respiratory support and accelerate the development of bronchopulmonary dysplasia (BPD).
The left ventricle faces an increased volume load but is poorly compliant in preterm neonates.
The left ventricle compensates by increasing the heart rate and remodeling into a larger, spherical shape.
Systemic hypoperfusion is known as ductal steal.
A large ductus can steal up to 50% of the total aortic flow.
Ductal steal is best demonstrated during diastole as retrograde flow in the descending aorta.
It compromises perfusion to the renal, mesenteric, and coronary circulations.
A significant PDA increases the risk of necrotizing enterocolitis (NEC), acute kidney injury, intraventricular hemorrhage (IVH), and mortality.

Low blood pressure is the only consistently reported clinical sign of PDA in the first 24 hours of life.
Clinical signs of a hyperdynamic circulation typically appear on day 3 or 4 of life.
The neonate develops bounding peripheral pulses and an easily palpable dorsalis pedis pulse.
A wide pulse pressure greater than 25 mm Hg is frequently observed.
A hyperactive precordium with visible pulsations is a highly sensitive sign.
Auscultation may reveal a pansystolic or holosystolic murmur over the left parasternal region.
However, the absence of a murmur does not exclude a significant left-to-right shunt.
Ventilated neonates may present with increasing oxygen requirements, hypercarbia, metabolic acidosis, and recurrent apnea.
Echocardiographic signs of a hemodynamically significant PDA often precede these clinical signs by an average of 1.8 days.

Two-dimensional Doppler echocardiography is the gold standard for the early diagnosis of PDA.
A transductal diameter (TDD) of greater than 1.5 mm with reversed diastolic flow in the descending thoracic aorta strongly indicates an HS PDA.

Parameter Group	Echocardiographic Findings
Size Of PDA	Transductal diameter > 1.5 mm. LA:Aorta ratio > 1.5. LV:Aorta root width ratio > 2.2.
Pulmonary Blood Flow	Peak velocity across the ductus < 1.5 m/sec. Antegrade left pulmonary artery diastolic flow > 40 cm/sec.
Systemic Blood Flow	Descending aorta diastolic flow shows absence or reversal. Diastolic steal in celiac or superior mesenteric artery.
Ventricular Output	Left ventricular output > 320 mL/kg/min.

Brain-type natriuretic peptide (BNP) and N-terminal pro-BNP are released from a volume-loaded ventricle.
Biomarker levels increase with the emergence of an HS PDA and decline after therapeutic closure.
The assay becomes accurate only after day 3 of life.
Routine use of biomarkers to dictate treatment or to ascertain PDA closure is not recommended.
There is significant overlap in biomarker levels between neonates with no PDA, small PDA, and large PDA.

Prophylactic or early asymptomatic treatment of PDA is not recommended due to the lack of clear long-term benefits.
Prophylactic treatment exposes many neonates to medications unnecessarily, as up to 90% of PDAs close spontaneously in neonates above 30 weeks gestation.
Treating the PDA only when it becomes hemodynamically significant and symptomatic is the most practiced approach.
A wait-and-watch expectant management approach is reasonable in stable infants greater than 28 weeks gestation.

Fluid restriction is commonly utilized, limiting daily fluid intake to 120 to 130 mL/kg beyond day 3 of life.
Fluid restriction must be discontinued if serum sodium exceeds 147 mEq/L or increases rapidly.
Routine administration of diuretics like furosemide is not recommended.
Furosemide causes upregulation of prostaglandin receptors, which promotes PDA patency and delays closure.
Continuous positive airway pressure (CPAP) or optimal positive end-expiratory pressure (PEEP) should be utilized in babies with respiratory distress.
A modest increase in PEEP by 1 to 2 cm H2O may physically splint the alveoli and reduce the left-to-right shunt.
Liberal platelet transfusions do not promote ductal closure and should be avoided.

Drug	Dosage And Administration	Special Remarks And Adverse Effects
Ibuprofen	Oral high dose: 15-20 mg/kg initially, then 7.5-10 mg/kg 24 hours apart for two doses.	High-dose oral ibuprofen is the drug of choice for neonates >28 weeks. It offers the highest net clinical benefit with a better safety profile than indomethacin. Theoretical risk of bilirubin displacement.
Indomethacin	Loading dose: 0.2 mg/kg. Subsequent doses depend on postnatal age (0.1 to 0.25 mg/kg 12 hourly).	Associated with a higher risk of transient renal impairment and gastrointestinal perforation. Causes impairment of cerebral blood flow. Contraindicated in acute kidney injury or necrotizing enterocolitis.
Paracetamol (Acetaminophen)	15 mg/kg per dose given 6 hourly for 3 to 7 days.	The first choice for preterm babies <28 weeks gestation. Serves as an alternative when ibuprofen is contraindicated. Rare risk of hepatotoxicity at high doses.

If the PDA remains persistently open and symptomatic after the first course of oral ibuprofen, a second course of oral ibuprofen is recommended.
Enteral paracetamol may be considered as a third medical course in refractory cases while surgical management is being planned.
Enteral feeding with trophic feeds can be safely continued during pharmacological treatment without increasing the risk of necrotizing enterocolitis.

Surgical or catheter-based closure is indicated if medical therapy fails after two courses.
It is also indicated if pharmacological agents are contraindicated due to necrotizing enterocolitis, gastrointestinal perforation, or severe renal impairment.
Transcatheter device closure has a success rate of over 95% and carries a lower risk of hemodynamic complications compared to open surgery.
Surgical ligation carries specific complication risks, including diaphragmatic paralysis, vocal cord paresis, and chylothorax.
Post-PDA ligation cardiac syndrome (PLCS) occurs in up to one-third of extremely low birth weight neonates following surgical closure.
PLCS manifests 4 to 12 hours post-operatively as profound hypotension and low cardiac output.
It is caused by a sudden increase in left ventricular afterload coupled with a decreased preload from reduced pulmonary venous return.
Management of PLCS requires afterload-reducing agents like milrinone, dobutamine, or low-dose epinephrine, alongside careful ventilatory support and occasionally hydrocortisone.