Oral paracetamol vs. oral ibuprofen in the treatment of symptomatic patent ductus arteriosus in premature infants: A randomized controlled trial

Abstract

The aim of the present study was to analyze the changes of plasma and urinary prostaglandin E2 (PGE2) levels in preterm infants with symptomatic patent ductus arteriosus (sPDA) treated with oral ibuprofen and acetaminophen. A total of 87 preterm infants with sPDA admitted to the Neonatal Ward of the Affiliated Xuzhou Hospital of Medical College of Southeast University from October, 2012 to June, 2015 were selected and randomly divided into the ibuprofen group (n=43, 10 mg/kg ibuprofen administered orally as initial dose, followed by 5 mg/kg during the first 24 and 48 h later) and acetaminophen group (n=44, 15 mg/kg acetaminophen administered orally once every 6 h for three days). The levels of plasma and urinary PGE2 in the two groups were estimated before and after treatment. The treatment of sPDA infants with ibuprofen (ibuprofen group) or acetaminophen (acetaminophen group) caused a significant decrease in the plasma and urinary PGE2 levels in comparison with plasma and urinary PGE2 levels before treatment (P<0.05). Furthermore, plasma and urinary PGE2 levels in the acetaminophen group (45.0±36.9 ng/l) were significantly lower than those in the ibuprofen group (73.5±44.8 ng/l, P=0.002). The arterial duct closure rate was similar between the acetaminophen [31 (70.5%)] and ibuprofen groups [33 (76.7%), P=0.506]. The incidence of oliguria was less among sPDA infants of the acetaminophen group [1 (2.3%)] than observed among the sPDA infants of the ibuprofen group [6 (14.0%)]; however, this difference was not statistically significant (P=0.108). Additionally, the incidences of fecal occult blood positive rate, intraventricular hemorrhage, neonatal necrotizing enterocolitis and bronchopulmonary dysplasia were distributed similarly in the ibuprofen and acetaminophen groups (P>0.05). The levels of platelet, serum creatinine and alanine transaminase showed no significant changes between the ibuprofen and acetaminophen groups (P>0.05). Following treatment with ibuprofen or acetaminophen, the extent of decrease of plasma and urinary PGE2 was significantly higher among sPDA infants with oliguria (135.0±38.0 ng/l) than that observed in sPDA infants without oliguria (52.5±37.0 ng/l) (P=0.01). The study also found a significant correlation between plasma and urinary PGE2 levels (r=0.648, P=0.01) and the coefficient of variation of urinary PGE2 (0.427) was less than that of plasma PGE2 (0.539). The clinical efficacy of oral ibuprofen and acetaminophen in the treatment of preterm infants with sPDA was similar with low adverse events, whereas acetaminophen-induced PGE2 levels were less than the levels observed in the ibuprofen-treated group. The incidence of oliguria was also lower in the acetaminophen group compared to the ibuprofen group. In addition, monitoring urinary PGE2 levels was more suitable because of its non-invasiveness in the clinical setting than monitoring of plasma PGE2 in preterm infants with sPDA.

Efficacy and Safety of Paracetamol for Patent Ductus Arteriosus Closure in Preterm Infants: An Updated Systematic Review and Meta-Analysis

“…This difference may allow POX inhibition to be optimally effective under conditions of low COX inhibitory activity (20). To date, although a number of correlative randomized controlled trials (RCTs) have compared the therapeutic efficacies of paracetamol and other drugs for PDA closure, most achieved insignificant results (21)(22)(23)(24)(25). Paracetamol's efficacy and safety for PDA closure in premature or low-birth-weight infants (or both) have not been fully determined.…”

Paracetamol in Patent Ductus Arteriosus Treatment: Efficacious and Safe?

“…At first, we report the results of five randomized controlled trials (RCTs) performed administering paracetamol and attesting its efficacy in PDA closure, comparable to ibuprofen and indomethacin. Paracetamol has also showed a safer profile, with less side effects than NSAIDs [ 18 , 55 , 85 , 88 , 108 ].…”

“…Yang et al [ 88 ] demonstrated a similar PDA closure rate between oral paracetamol and ibuprofen, but less adverse events were detected in newborns receiving paracetamol, with lower incidence of oliguria. In conclusion this study evidenced lower toxicity, also corresponding to lower plasma and urinary PGE2 levels, in paracetamol group.…”

“…Yang et al [ 88 ] demonstrated a probably higher renal safety of this drug describing a significantly lower reduction in PGE2 urinary excretion and minor incidence of oliguria comparing two groups of infants treated with paracetamol versus ibuprofen.…”

Pharmacological treatment strategies for neonates with patent ductus arteriosus: a systematic review

“…One study reported that paracetamol administration was associated with lower urinary PGE2 reduction and incidence of oliguria, indicating less nephrotoxicity. 7 This greater safety profile compared to classical NSAIDs may be attributed to paracetamol's different mechanism of action, which is in the perioxidase region of the COX enzyme. 8 Using an evidencebased case review, we aimed to compare the efficacy and safety of paracetamol to that of ibuprofen and indomethacin in treating PDA.…”