Combination therapy for patent ductus arteriosus in preterm infants: Echocardiographic changes and clinical use

Background: Searching for the optimal therapeutic strategy for hemodynamically significant Patent Ductus Arteriosus in preterm infants is ongoing. A novel approach utilizing a combination of ibuprofen and acetamin-ophen has generated interest, with speculations that this approach may be more effective than standard single -agent therapy. Objectives: Our objectives were to compare the echocardiographic parameters before and after the combination therapy and to describe its use (primary vs. rescue), effectiveness, and side effects. Methods: This was a retrospective cohort review of preterm infants born <33 weeks gestation who were admitted to a tertiary-level neonatal intensive care unit between January 1, 2012, and December 31, 2020. Included in-fants received combination pharmacotherapy with ibuprofen and acetaminophen for ductal closure, either as a primary course (1st line use) or as a rescue (2nd or 3rd course), and had echocardiographic measurements pre -and post-therapy. Baseline characteristics, echocardiographic parameters of ductus arteriosus hemodynamics before and after combination therapy, the effectiveness of treatment, and adverse effects were examined. Results: During the study period, 32 infants received combination therapy, with 17 (53 %) receiving it as a primary course and 16 (47 %) receiving it as a rescue course after trying another pharmacological agent. Complete echocardiographic data were available for 17 infants included in the study (11 primary and 6 rescues). The overall treatment success rate was 41 %. The primary course had a better treatment success rate (55 %) than the rescue course (17 %). Echocardiographic analysis showed that the primary course treatment resulted in significantly lower ductal diameter (p = 0.013), higher ductal flow Doppler velocities (p = 0.037), more restrictive shunt pattern (p = 0.005), and decreasing ductus arteriosus significance score (p = 0.016). Such improvement in hemodynamic significance was not noted when combination therapy was used as rescue therapy. Conclusion: Primary combination therapy with ibuprofen and acetaminophen resulted in considerable im-provements in echocardiographic markers of hemodynamically significant ductus arteriosus. Future trials exploring the safety and efficacy of this treatment as a first-line option are required.