Effectiveness of Injectable Ibuprofen Salts and Indomethacin to Treat Patent Ductus Arteriosus in Preterm Infants: Observational Cohort Study

ABSTRACTBackground: There is no injectable ibuprofen product marketed to treat patent ductus arteriosus (PDA) in newborns in Canada. The authors’ institution has used ibuprofen arginine in the past. In the absence of published evidence supporting use of this salt form of ibuprofen for neonatal PDA, a retrospective analysis was undertaken.Objective: To compare the effectiveness and adverse effects of ibuprofen arginine, ibuprofen tromethamine, and indomethacin in the treatment of PDA.Methods: This retrospective observational cohort study, for patients admitted between 2009 and 2015, included preterm infants with symptomatic PDA who received at least one dose of injectable indomethacin, ibuprofen tromethamine, or ibuprofen arginine. Three effectiveness end points were analyzed: closure after one course of treatment, repeat medical treatment, and surgical ligation. The secondary end points included acute kidney injury, necrotizing enterocolitis, chronic lung disease, and time to full enteral feeding.Results: A total of 179 infants were included. There were no differences among groups in terms of closure after one course of treatment (37/54 [69%] with indomethacin, 42/70 [60%] with ibuprofen tromethamine, and 28/55 [51%] with ibuprofen arginine; p = 0.21) or surgical ligation (10/54 [19%] with indomethacin, 13/70 [19%] with ibuprofen tromethamine, and 12/55 [22%] with ibuprofen arginine; p = 0.88). However, there was a difference regarding use of a repeat course of treatment, ibuprofen arginine having the highest rate (8/54 [15%] with indomethacin, 18/70 [26%] with ibuprofen tromethamine, and 20/55 [36%] with ibuprofen arginine; p = 0.04). After adjustment for gestational age, the association between ibuprofen arginine and increased use of a repeat course of treatment remained significant. The groups did not differ with respect to adverse effects.Conclusion: These results highlight the potential for differences in effectiveness among various salt forms of injectable ibuprofen and indomethacin. Because of the small sample size and retrospective methodology, confirmation of the present results through a larger prospective study is needed.RÉSUMÉContexte : Il n’y a pas sur le marché de produit injectable à base d’ibuprofène pour traiter la persistance du canal artériel (PCA) chez le nouveau-né au Canada. L’ibuprofène arginine a été utilisé auparavant dans l’établissement de santé des auteurs. En l’absence de données publiées appuyant l’utilisation de ce médicament sous forme de ce sel pour traiter la PCA chez le nouveau-né, une analyse rétrospective a été réalisée.Objectif : Comparer l’efficacité et les effets indésirables de l’ibuprofène arginine, de l’ibuprofène trométhamine et de l’indométhacine dans le traitement de la PCA.Méthodes : Cette étude de cohorte observationnelle rétrospective, au sujet de patients hospitalisés entre 2009 et 2015, incluait des nourrissons prématurés atteints d’une PCA symptomatique ayant reçu par injection au moins une dose d’indométhacine, d’ibuprofène trométhamine ou d’ibuprofène arginine. Trois paramètres d’évaluation de l’efficacité ont été analysés : la fermeture après un seul traitement, la répétition du traitement médical et la ligature chirurgicale. Les paramètres d’évaluation secondaires étaient les cas d’insuffisance rénale aiguë, d’entérocolite nécrosante et de maladie pulmonaire chronique ainsi que le temps pour atteindre l’alimentation entérale complète.Résultats : Au total, 179 nourrissons ont été admis à l’étude. Aucune différence n’a été relevée entre les groupes en ce qui touche à la fermeture après un seul traitement (37/54 [69 %] pour l’indométhacine, 42/70 [60 %] pour l’ibuprofène trométhamine et 28/55 [51 %] pour l’ibuprofène arginine; p = 0,21) ou à la ligature chirurgicale (10/54 [19 %] pour l’indométhacine, 13/70 [19 %] pour l’ibuprofène trométhamine et 12/55 [22 %] pour l’ibuprofène arginine; p = 0,88). Cependant, une différence a été observée pour ce qui est de la répétition du traitement et l’ibuprofène arginine a obtenu le taux le plus élevé (8/54 [15 %] pour l’indométhacine, 18/70 [26 %] pour l’ibuprofène trométhamine et 20/55 [36 %] pour l’ibuprofène arginine; p = 0,04). Après ajustement pour l’âge gestationnel, l’association entre l’utilisation de l’ibuprofène arginine et une augmentation du recours à un second traitement demeurait significative. Il n’y avait pas de différence entre les groupes en ce qui touche aux effets indésirables.Conclusion : Ces résultats soulignent la possible différence d’efficacité parmi les divers sels d’ibuprofène injectable et l’indométhacine. Cependant, en raison de la petite taille de l’échantillon et de l’emploi d’une méthodologie rétrospective, une étude prospective plus importante doit être menée pour confirmer les résultats de la présente étude

Effectiveness of Alberta Family Integrated Care on infant length of stay in level II neonatal intensive care units: a cluster randomized controlled trial.

BackgroundParents of infants in neonatal intensive care units (NICUs) are often unintentionally marginalized in pursuit of optimal clinical care. Family Integrated Care (FICare) was developed to support families as part of their infants' care team in level III NICUs. We adapted the model for level II NICUs in Alberta, Canada, and evaluated whether the new Alberta FICare™ model decreased hospital length of stay (LOS) in preterm infants without concomitant increases in readmissions and emergency department visits.MethodsIn this pragmatic cluster randomized controlled trial conducted between December 15, 2015 and July 28, 2018, 10 level II NICUs were randomized to provide Alberta FICare™ (n = 5) or standard care (n = 5). Alberta FICare™ is a psychoeducational intervention with 3 components: Relational Communication, Parent Education, and Parent Support. We enrolled mothers and their singleton or twin infants born between 32 0/7 and 34 6/7 weeks gestation. The primary outcome was infant hospital LOS. We used a linear regression model to conduct weighted site-level analysis comparing adjusted mean LOS between groups, accounting for site geographic area (urban/regional) and infant risk factors. Secondary outcomes included proportions of infants with readmissions and emergency department visits to 2 months corrected age, type of feeding at discharge, and maternal psychosocial distress and parenting self-efficacy at discharge.ResultsWe enrolled 654 mothers and 765 infants (543 singletons/111 twin cases). Intention to treat analysis included 353 infants/308 mothers in the Alberta FICare™ group and 365 infants/306 mothers in the standard care group. The unadjusted difference between groups in infant hospital LOS (1.96 days) was not statistically significant. Accounting for site geographic area and infant risk factors, infant hospital LOS was 2.55 days shorter (95% CI, - 4.44 to - 0.66) in the Alberta FICare™ group than standard care group, P = .02. Secondary outcomes were not significantly different between groups.ConclusionsAlberta FICare™ is effective in reducing preterm infant LOS in level II NICUs, without concomitant increases in readmissions or emergency department visits. A small number of sites in a single jurisdiction and select group infants limit generalizability of findings.Trial registrationClinicalTrials.gov Identifier NCT02879799 , retrospectively registered August 26, 2016