Prophylaxis of patent ductus arteriosus with ibuprofen in preterm infants

Abstract

The aim of our study was to evaluate whether the prophylactic use of ibuprofen would reduce the incidence of significant patent ductus arteriosus (PDA) and to confirm the effectiveness of ibuprofen as rescue treatment in closing PDA. Eighty preterm infants with gestational age less than 34 wk with infant respiratory distress syndrome (iRDS) were randomized to receive intravenous ibuprofen lysine (10 mg/kg, followed by 5 mg/kg after 24 and 48 h) either within 24 h of life (group A) or after echocardiographic diagnosis of PDA (group B). To evaluate the severity of RDS in each patient, we calculated the initial and highest values of Oxygenation Index (O.I. =mean airway pressure × FiO2 × 100 / PaO2) and Ventilatory Index (V.I. = O.I. × mechanical respiratory rate). Other studied variables were ventilatory support, renal function, biochemical and haematological profiles, frequency of bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP). On the 3rd day of life, 8% (3/40) of patients of group A and 53% of patients (21/40) of group B (p < 0.0001) developed a significant PDA. Between patients of group B who presented PDA at 3 d of life 90% (19/21) had a closure of ductus arteriosus after ibuprofen treatment. Initial and highest values of O.I. and V.I. were similar in both groups A and B. No significant differences between the groups were observed in regard to respiratory support, renal function and frequency of BPD, IVH, NEC and ROP. Ibuprofen was not associated with adverse effects. Conclusion: Prophylactic treatment with ibuprofen reduces PDA occurrence in preterm infants with iRDS at 3 d of life in comparison with rescue treatment, but both modes are effective in closing the ductus without significant adverse effects.

The fate of ductus arteriosus in infants at 23–27 weeks of gestation: from spontaneous closure to ibuprofen resistance

“…This fact together with the consideration that prophylactic treatment of PDA does not improve the outcome of preterm infants in comparison with rescue treatment (11,12,24), suggests that early treatment of PDA could be more beneficial than prophylaxis in these patients because it allows to avoid them unnecessary therapy. An important issue may rise if delayed ibuprofen treatment is less effective in closing PDA than prophylactic treatment, but previous studies did not find any difference in closing PDA between ibuprofen therapy started in the first or third day of life, and seem to exclude this hypothesis (11,15,24).…”

“…The medication was continuously infused over a period of 15 min. The doses and dosing intervals were the same used in newborn infants in previous studies (10,14,15).…”

Ibuprofen Lysine for the Prevention and Treatment of Patent Ductus Arteriosus

“…The effect of prophylactic ibuprofen lysine in reducing the frequency of PDA and the effectiveness of this drug as rescue treatment were studied in 80 preterm infants less than 34 weeks' gestational age who had RDS. 65 Preterm newborns with a platelet count of 75 x 10 3 /mm 3 or lower, serum creatinine concentration of 1.5 mg/dl or higher, clinically normal clotting function, absence of grades 3-4 IVH before randomization, and requiring nasal continuous positive airway pressure or mechanical ventilation to maintain a FiO 2 of greater than 30% were enrolled. Neonates with major congenital malformations, congenital heart defects, persistent pulmonary hypertension, or hydrops fetalis were excluded.…”

The definition of a haemodynamic significant duct in randomized controlled trials: a systematic literature review

“…A Cochrane systematic review suggests that asymptomatic treatment after 24 h of life does not improve major clinical outcomes, and other evidence shows that early treatment does not provide better clinical outcomes if compared with later treatment (3,12,19,20). This effect is most likely due to the high rate of spontaneous closure during this period, and it seems questionable whether new trials randomizing infants without significant clinical signs at this point in time could prove beneficial.…”