Acetaminophen in low doses for closure of the ductus arteriosus of the premature

Abstract

Objective: The objective of the study is to report the experience with acetaminophen in low doses as an alternative to the treatment of the ductus arteriosus of the preterm newborn. Materials and Methods: Retrospective study including preterm newborns with patent ductus arteriosus who received oral acetaminophen because treatment with indomethacin had failed or is contraindicated. A dosage consisted of a first dose of 25 mg/kg and maintenance doses of 30 mg/kg/day, for 3 to 7 days. A second cycle was administered in cases of reopening of the ductus arteriosus. The rates of ductal closure and surgery were calculated. Patients were categorized into responder and nonresponder groups for acetaminophen, and the average values of ductal diameter, weight, gestational age, and postnatal age were compared. Results: Eighty-seven preterm newborns, with a postnatal age from 3 to 27 days, with average values of ductus arteriosus equal to 2.5 ± 0.8 mm/kg, gestational age 27.2 ± 1.9 weeks, and birth weight 888.9 ± 241 g, received acetaminophen for 3 to 7 days. A second cycle was administered in 15 preterm newborns. The ductus closure rate, after one or two cycles, was 74.7%, and the recommendations for surgical closure were progressively reduced from 50% in the 1 st year to 6.2% in the past year. Lower ductal closure rate occurred in the group of newborns with the lowest average weight ( P = 0.018), the highest average ductal diameter ( P = 0.002), and the lowest average gestational age ( P = 0.09). Postnatal age at the start of acetaminophen use was shown to be irrelevant regarding the treatment ( P = 0.591). Conclusions: Acetaminophen in low doses showed to be an effective alternative for the closure of the ductus arteriosus for preterm newborns in whom treatment with indomethacin or ibuprofen failed or was contraindicated.

The efficacy and safety of oral paracetamol versus oral ibuprofen for patent ductus arteriosus closure in preterm neonates – A systematic review and meta-analysis

“…A study by Guimarães et al showed that low dose oral acetaminophen (25 mg/kg initial dose followed by 30 mg/kg/day, for 3–7 days) is an effective replacement if indomethacin or ibuprofen failed or contraindicated. 22 …”

Intravenous acetaminophen (at 15 mg/kg/dose every 6 hours) in critically ill preterm neonates with patent ductus arteriosus: A prospective study

“…We also observed that acetaminophen concentrations are more likely to be in the therapeutic range after first dose in late and very preterm neonates but not in the extreme preterm. Perhaps, a loading dose of acetaminophen at 20 mg/kg could possibly result in achieving the optimal therapeutic concentration as administered in some recent studies 30,31 . Intravenous acetaminophen at the dose administered in the present study is likely to result in a median exposure of 90 µmol/L as evident from one of the previous studies 32 .…”

An Observational Study on Use of Intravenous Paracetamol for Closure of Patent Ductus Arteriosus in Newborns

“…During the study, it was observed that some preterm newborns needed a longer treatment period to achieve ductal closure, which prompted a readjustment to the protocol, and treatment duration was extended to 7 days. 12 Another clinical trial by Dash et al, obtained a ductal closure rate of 100% with a 7 day treatment with paracetamol. 13 Also El-Khuffash et al, compared long (7 days) to short (2 days) courses of oral paracetamol and obtained a better results with longer duration of treatment.14 Above studies are complementing with our study where we prescribed paracetamol for minimal 3 days to maximum 7 days and achieved a ductal closure of 91.7%.…”