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

Abstract

BackgroundSearching 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 acetaminophen has generated interest, with speculations that this approach may be more effective than standard single-agent therapy. ObjectivesOur 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. MethodsThis 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 infants 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. ResultsDuring 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. ConclusionPrimary combination therapy with ibuprofen and acetaminophen resulted in considerable improvements 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.