Clinical Pediatrics

Biography

Biography: Fazal-e-Rabi Subhani

Abstract

Introduction:

Hemodynamically significant patent ductus arteriosus (PDA) in preterm infants is known to be associated with greater mortality and substantial morbidity in the form of pulmonary oedema/haemorrhage, bronchopulmonary dysplasia (BPD) and potential end-organ ischaemic injury. Considerable practice variability exists regarding different PDA management approaches from supportive care alone to pharmacological closure to surgical ligation.

Method:

A comprehensive search of PubMed & EMBASE from their inceptions to October 2019 was made using 3 search items: patent ductus arteriosus, preterm infants, & management approaches. The search items were combined using the Boolean operator. A further search was made of the Cochrane Central Register of Controlled Trials, & ClinicalTrials.gov with no language restriction.

Results:

Literature review suggests that the most appropriate management approach is a step-wise strategy beginning with supportive care provided to all preterm infants including a neutral thermal environment, moderate fluid restriction (110-130 mL/kg/day) & adequate respiratory support (target SpO₂ 90-95%, PaCO₂ 55-65 mmHg, pH 7.3-7.4, & haematocrit above 35%). The next step is pharmacological closure attempted in infants who remain ventilator-dependent after one week. It is done in the form a course of non-selective COX inhibitors therapy (indomethacin, ibuprofen), or paracetamol. Latter is generally considered if COX inhibitor therapy is considered contraindicated (untreated infection, NEC, active bleeding, thrombocytopenia, significant renal impairment, concomitant congenital heart disease like pulmonary atresia, severe tetralogy of Fallot, severe coarctation of aorta). An echocardiogram is performed 1-2 days after completion of drug course. If it shows PDA closure, a positive response to therapy is confirmed. Unfortunately, a significant proportion of infants fail to respond to the initial course as evidenced by visualization of persistent PDA on follow-up echocardiogram & infants remaining ventilator-dependent. Limited date suggests that a second course of COX inhibitor is associated with 40% rate of ductal closure in such instances. Infants who fail to respond to even the second course & remain ventilator-dependent on maximum settings are unlikely to respond to drug treatment & therefore no further medical therapy is considered appropriate in such instances. Although rarely necessary in real life, surgical ligation should be considered in these cases.

Conclusion:

Head-to-head comparison of different drugs used to attempt pharmacological closure of PDA (indomethacin, ibuprofen, & paracetamol) is particularly tricky due to variations of criteria used to define hemodynamically significant PDA and multiple treatment protocols used with variations in dosing & route of administration (enteral vs IV bolus vs IV continuous) across different studies. A recent meta-analysis however concluded that high-dose oral ibuprofen was the most efficacious regimen for pharmacological closure of PDA. Because surgical ligation has become increasingly uncommon & published data is observational, it remains uncertain whether infants who fail pharmacological closure are more severely compromised to begin with, or in fact surgical intervention contributes to increased morbidity & mortality seen in such cases.