Is paracetamol as effective as indomethacin or ibuprofen in closing a hemodynamically significant patent ductus arteriosus in preterm infants?

Abstract

Commentary on: El-Mashad AE, El-Mahdy H, El Amrousy D, Elgendy M. Comparative study of the efficacy and safety of paracetamol, ibuprofen, and indomethacin in closure of patent ductus arteriosus in preterm neonates. Eur J Pediatr 2017; 176:233-240. PMID 28004188. This study was a prospective, randomised trial comparing paracetamol to indomethacin and ibuprofen for closing a hemodynamically significant patent ductus arteriosus (hs-PDA) in premature neonates (<28 weeks GA or <1500 grams). Currently available treatments to close the PDA include indomethacin and ibuprofen, but these treatments have been associated with transient reduction in kidney function 1, 2, and they are contraindicated in patients with active bleeding or renal dysfunction. Surgical ligation of the PDA has been associated with worse neurodevelopmental outcomes and BPD 3, although there may be no difference in outcomes after correcting for perinatal confounders 4. The search for safe pharmacologic treatments to close the hs-PDA continues. In this study, echocardiogram was performed in all infants by 48 hours of age. The severity of PDA-related symptomatology that led to treatment is not well-defined. It is not clear how many echocardiographic and/or clinical criteria were necessary to qualify a hs-PDA. The authors state that PDA closure occurs in 70% of cases following a course of either indomethacin or ibuprofen. However, the spontaneous ductal closure rate in this population is 73% 5. This trial found slightly higher closure rates of 80%, 77% and 81% in the paracetamol, ibuprofen and indomethacin groups, respectively. Thus, paracetamol may be as effective as indomethacin or ibuprofen for ductal closure, but the benefit of medical versus spontaneous ductal closure remains unknown. Ongoing studies, such as the Baby-OSCAR trial (ISRCTN84264977) 6, which is investigating ibuprofen versus placebo, are attempting to evaluate outcomes after early medical closure of the PDA. In this study, infants receiving paracetamol had less gastrointestinal bleeding, lower BUN/creatinine, higher platelet counts and higher urine output when compared to the indomethacin and ibuprofen groups. The definition of gastrointestinal bleeding was not specified. The clinical significance of these statistically significant changes remains uncertain. The overall complication rate was low; a larger sample size is necessary to truly estimate the risk of adverse events. Further, the duration of follow up was not specified, so whether these results are inclusive or important in hospital and post-discharge morbidities is unknown. Larger studies are necessary to evaluate whether paracetamol – when used to close the PDA - will be associated with a lower rate of adverse events compared to currently available pharmacologic treatment and morbidities including BPD and neurodevelopmental outcomes. In general, the ability to interpret the trial is limited. CONSORT guidelines have been developed for transparent reporting of clinical trials (http://www.consort-statement.org/checklists/view/32-consort-2010/66-title). In this study, a CONSORT flow diagram was not provided; thus, it is difficult to determine how many studied infants were ultimately included in the trial. Furthermore, it is not clear whether this trial was registered in ClinicalTrials.gov. Following CONSORT, guidelines in the reporting of clinical trials allow providers the opportunity to critically appraise and interpret trial results. We advocate that trials adhere to these guidelines and that Journals request that they be reported. Uniformly adopting this practice will facilitate data interpretation and implementation of practice change at the bedside. https://ebneo.org/2018/06/is-paracetamol-as-effective-as-indomethacin-or-ibuprofen None. None.