PDA in neonates: Please Doctor Act --- individually!
In his leading article Dr Benitz suggests to restrictively use interventions aimed at closing a patent ductus arteriosus (PDA) in preterm neonates (1); however, he scarcely provides the reader with specific recommendations in which clinical scenarios a closure of the PDA should be aimed for. Moreover, he outlines a somewhat black-and-white perspective on this issue by arguing along the line "to close or not to close a PDA". However, the real and clinically important question seems to be: How to change a hemodynamically relevant PDA into a PDA that does not compromise the infant?s circulation (either decreased in size or fully closed)? Also, it is very important to be aware of the fact that assessment of a PDA in a preterm constitutes a dynamic endeavour rather than a static process.
I do absolutely agree with Dr Benitz that indiscriminative efforts aimed at closing a PDA (be it pharmacologically or surgically) in very and extremely preterm infants should be abandoned, given the possible potent side affects associated with this approach. Based on my clinical experience, the decision to treat or not treat a PDA is made for each infant individually, based foremost on clinical grounds and on serial echocardiographic studies.
Clinical reasons that favour active treatment include: Low blood pressure requiring use of inotropes/vasopressors; oliguria requiring use of diuretics; respiratory failure secondary to pulmonary edema leading to increased oxygen requirements, and feeding intolerance requiring prolonged use of parenteral nutrition, given that these complications can be attributed to a hemodynamically relevant PDA (which I do admit can be a difficult task). These clinical findings are corroborated by serial echocardiographic studies demonstrating increased left atrium/aortic ratio, size of PDA, and hemodynamic compromise of the systemic circulation (pathological diastolic flow in middle cerebral artery, and mesenteric and renal artery). It is important to perform serial echocardiography to demonstrate changes over time as demonstrated by O?Rourke and colleagues (2).Of note, in their study serial echocardiographic assessment allowed significantly earlier identification and treatment of PDA versus awaiting the evolution of clinical signs. Moreover, and of importance severe intraventricular haemorrhage and ventilator days were significantly decreased after introduction of echocardiography (2). Moreover, the use of various biomarkers (BNP and N- terminal pro BNP) may be promising diagnostic tools in the assessment of the significance of PDA (3).
Notwithstanding the fact that infectious/inflammatory processes may be causative factors in keeping the PDA open, the suggested interventions by Dr Benitz (eg, immunomodulatory measures) are quite unlikely to close or keep the PDA closed in very preterm infants. Moreover, adopting a restrictive and possibly late approach will also lower the chances of successfully closing a PDA at a later stage (4).
Hence, it is prudent to reserve treatment of PDA to infants with clinically significant ductus on the basis of the clinical status complemented by serial echocardiography and to individualize the decision to treat. With this approach a closure rate of 70-80% can be achieved. If a randomized trial - as suggested by Dr Benitz - will be performed, it will be interesting to see how many infants in the "wait and see" group will require rescue interventions (pharmacological or surgical) for permanent ductal closure. Also, given the potential complications resulting from a hemodynamically relevant PDA (eg, NEC with a disproportionate increase in the relative risk of poor neurological outcome (5), it will be important to assess long-term neurodevelopmental outcome in these infants.
References 1. Benitz WE. Patent ductus arteriosus: to treat or not to treat? . Arch Dis Child Fetal Neonatal Ed. 2011 Dec 15. [Epub ahead of print 2. O'Rourke DJ, El-Khuffash A, Moody C, Walsh K, Molloy EJ. Patent ductus arteriosus evaluation by serial echocardiography in preterm infants. Acta Paediatr..2008 May;97(5):574-8. 3. Attridge JT, Kaufman DA, Lim DS. B-type natriuretic peptide concentrations to guide treatment of patent ductus arteriosus. Arch Dis Child Fetal Neonatal Ed. 2009 May;94(3):F178-82. Epub 2008 Nov 3. 4. Ohlsson A, Shah SS. Ibuprofen for the prevention of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst Rev. 2011 Jul 6;(7):CD004213. 5. Schulzke SM, Deshpande GC, Patole SK. Neurodevelopmental outcomes of very low-birth-weight infants with necrotizing enterocolitis: a systematic review of observational studies. Arch Pediatr Adolesc Med. 2007 Jun;161(6):583-90.
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