EAPS Congress 2016

Abstract

Patent ductus arteriosus (PDA) management changed dramatically in recent years ("to treat or not"). The current approach has shifted from aggressively closing any PDA using NDSAIDS (ibuprofen, indomethacin) to careful watching of ductal shunting, virtually withholding any intervention in neonates with a PDA except in the few neonates that are hemodynamically severely jeopardized. This change is based on a lack of evidence to continue the practice of early aggressive pharmacologic closure in combination with side effects of these compounds. It was clearly only a matter of time before intravenous paracetamol was going to be used for PDA closure with the idea that if effective, this drug might be having less side effects although the effect of paracetamol on peripheral prostaglandin synthesis is much lower. Moreover, a recent systemic review has made clear that studies on paracetamol in neonates should include long term follow up. Other steps to be taken relate to the dose or doing regimen to treat PDA. To illustrate the complexity, a paracetamol concentration-dependent constriction was observed in term mouse ductus arteriosus, with a much weaker response in the preterm. The doses suggested (60 mg/ kg/day) are higher than the doses evaluated in neonates from 28 weeks onwards. In the presence of a labelled alternative and in the absence of safety data or target concentrations, we recommend that this practice can only be part of prospective studies, with focus on PK, PD and safety. These trials should subsequently be used to document long-term safety (immunologic, neurologic issues).