Treatment to prevent patency of the ductus arteriosus: beneficial or harmful?

摘要

Despite the strong association between the presence of a patent ductus arteriosus (PDA) and bronchopulmonary dysplasia (BPD), treatments that successfully close a PDA have not resulted in a reduction in the incidence of BPD. This apparent paradox has been observed with both of the cyclo-bxygenase (COX) inhibitors used to treat the PDA, indomethacin and ibuprofen. Treatments given either prophylactically, to promote early closure of the PDA, or for persistent patency of the ductus arteriosus have not decreased BPD. In the largest study to date of the use of prophylactic indomethacin, the Trial of Indomethacin Prophylaxis in Preterms (the TIPP Trial), Schmidt et al demonstrated this disconnect between successful prevention of persistent patency of the ductus arteriosus and a reduction in BPD.Despite - 50% reduction in the incidence of PDA in infants treated with prophylactic indomethacin, the incidence of BPD among treated infants and those in a placebo group was virtually identical.There are three possible explanations for the apparent lack of benefit of COX inhibitors in reducing BPD:(1) Prophylactic treatment -with COX inhibitors is effective in preventing BPD, but studies have not been designed to demonstrate this benefit. For decades, clinicians and investigators assumed that the short-term benefit of closing the ductus arteriosus would translate into a long-term benefit (eg, reduction in BPD) and designed studies to determine the most efficacious technique for closing the ductus. No study in the modern era has actually tested the hypothesis that PDA closure reduces BPD. All of these studies permitted treatment of infants in the placebo groups. Because of this crossover or "contamination" of the placebo group, one cannot draw conclusions about clinically meaningful benefits, such as a reduction in BPD, or risks of this therapy.