Patent Ductus Arteriosus in Prematurity

Patent ductus arteriosus in prematurity is persistence of the foetal vascular connection between the pulmonary artery and descending aorta after birth in a preterm infant. With the fall in pulmonary vascular resistance, flow reverses to left to right, causing pulmonary overcirculation and systemic steal.

Frequency increases as gestation falls, with persistence in the majority of infants under 28 weeks in the first week of life. Many close spontaneously by 2 to 3 weeks of age, but a haemodynamically significant duct is linked with bronchopulmonary dysplasia, necrotising enterocolitis, intraventricular haemorrhage and pulmonary haemorrhage.

The ductus of a preterm infant is less responsive to oxygen and more sensitive to prostaglandin E2 and nitric oxide, so closure is delayed.

Pathophysiology.

Left to right shunting increases pulmonary blood flow and left atrial and ventricular volume load. Pulmonary oedema, reduced lung compliance and higher ventilator requirements follow.

Diastolic steal from the aorta lowers systemic diastolic pressure and perfusion to the brain, gut and kidney, causing intestinal ischaemia, renal impairment and cerebral injury.

• Systolic or continuous murmur (at the left upper sternal border), bounding pulses, wide pulse pressure (diastolic pressure under 25 to 30 mmHg) and hyperdynamic precordium.
• Respiratory deterioration with increased oxygen or ventilator requirement, apnoea, pulmonary haemorrhage and difficulty weaning.
• Feeding intolerance, oliguria, metabolic acidosis, hypotension and heart failure.

Red flags.

• Pulmonary haemorrhage, gut ischaemia signs or oliguria.
• Duct dependent congenital heart disease (cyanosis, weak femoral pulses or hypotension): do not close the duct.

• Echocardiography is the diagnostic test. Haemodynamic significance is supported by ductal diameter over 1.5 mm, left atrium to aortic root ratio over 1.5, left to right or bidirectional flow with low flow velocity, diastolic flow reversal in the descending aorta or cerebral and mesenteric arteries, and a dilated left ventricle.
• NT-proBNP or BNP is raised in haemodynamically significant ducts.
• Chest X-ray (cardiomegaly, pulmonary plethora), urea, creatinine, electrolytes, platelets and cranial ultrasound.

Differential diagnosis. Congenital heart defects (ventricular septal defect, aorto pulmonary window, truncus), sepsis with hypotension, respiratory distress syndrome and pulmonary hypertension.

Conservative care.

• Many centres first observe, with careful fluid management (avoid overload), adequate positive end expiratory pressure, maintenance of haemoglobin, and monitoring, since many ducts close spontaneously.

Pharmacological closure for a haemodynamically significant duct with respiratory dependence, heart failure or end organ compromise.

• Ibuprofen IV 10 mg/kg, then 5 mg/kg at 24 and 48 hours. Oral ibuprofen 10 mg/kg then 5 mg/kg at 24 and 48 hours is an alternative.
• Paracetamol IV or oral 15 mg/kg every 6 hours for 3 to 7 days, when non-steroidal anti-inflammatory drugs are contraindicated or have failed. Monitor liver function.
• Indometacin IV 0.2 mg/kg every 12 hours for 3 doses is an alternative.
• Contraindications to NSAIDs: necrotising enterocolitis or spontaneous intestinal perforation, urine output under 1 mL/kg/h, creatinine rising or over 130 micromol/L, platelets under 50 x 10^9/L, active bleeding, severe intraventricular haemorrhage and duct dependent heart disease.
• A second course is given if the duct stays open. Avoid combining NSAIDs with corticosteroids.

Surgical or catheter closure. Surgical ligation or transcatheter closure for a significant duct that persists after medical treatment with continued respiratory dependence. Anticipate low cardiac output after ligation (hypotension 6 to 12 hours later) and treat with milrinone 0.33 to 0.75 micrograms/kg/min IV. Other risks are vocal cord palsy, pneumothorax and chylothorax.

Monitoring. Urine output, creatinine, electrolytes, platelets, bilirubin (ibuprofen displaces bilirubin from albumin), liver function and repeat echocardiography at 24 to 48 hours after treatment.

Referral and escalation. Refer to paediatric cardiology for a haemodynamically significant duct and for any suspected duct dependent lesion, and to cardiac surgery for failure of medical closure.

Special groups. Infants under 26 weeks have the highest incidence and are most likely to have prolonged symptomatic patency.