Paracetamol-induced ductal closure in a 5-month-old infant

Abstract

To the Editor, Recently, we cared for a 5-month-old baby boy born at 28 weeks gestation with a 1.9-mm patent ductus arteriosus (Fig 1). The parents were counselled regarding the plan for percutaneous device closure and asked to return 2 weeks later. Surprisingly, on repeat echocardiogram, the ductus arteriosus had closed. As spontaneous ductal closure is unusual past the newborn period, we questioned the parents about the events in the preceding 2 weeks. The parents reported administering paracetamol 12 mg/kg/dose twice daily for 4 days because of fussiness and nasal congestion. In premature infants during the newborn period, indomethacin or ibuprofen are first-line agents utilised for ductal closure. In patients with contraindications to non-steroidal anti-inflammatory drugs, paracetamol at 15 mg/kg/dose every 6 hours for 48 hours has been used effectively as a second-line agent. 1,2 Previous authors have suggested that paracetamol works by acting at the peroxidase segment of prostaglandin synthetase and inhibits activity. 3 To the best of our knowledge, our case is the first reported case of ductal closure associated with paracetamol outside of the newborn period. Further studies are needed to elucidate the role of paracetamol for ductal closure beyond the neonatal period.

The strategy of paracetamol (acetaminophen) use in closing patent ductus arteriosus in premature neonates.

“…Is the next coming question. None of the reviewed papers showed that paracetamol therapy has been initiated before the age of 48 hours, this is going with the idea of high percentage of spontaneous closure of PDA in premature neonates by 48 hours of life as stated by Koch J et al (38), but it seems that there is no clear cut-off about the maximal postnatal age suitable for this therapy because a wide range of postnatal ages up to 47 days by Ozmert M. et al (27) have been included in the reviewed articles, however restricting this therapy to the neonatal period appears more logical although success outside this period has been reported by Cynthia H et al (18). Gestational age appears to be important among the treated patients because in 3 series with patients GA 23-27.9 weeks the success rates were the lowest ranging between 18.18-27.77% compared to the general success rate of 70-100 % for other more mature groups (24, 25, and 26).…”

“…Patients underwent daily evaluation using the same pretreatment parameters with daily echocardiographic evaluation. If the patient didn't show complete closure or significant ductal constriction a second course were given with the same evaluation method for the next 4-5 days regardless weather the patient already received one of the NSAIDs or not.The intended primary outcome of all reviewed papers were complete ductal closure or the development of significant ductal constriction (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34) which is defined by the absence of shunt or diameter < 0.5 mm without any other hemodynamic implications at echocardiographic examination performed daily during the study period as described by Terrin G et al (22) .Secondary outcome of treated patients can be summarized as the need for surgical ligation of the PDA , mode and duration of ventilation; increase in blood urea nitrogen, serum creatinine, bilirubin, AST, or ALT levels after treatment, rates of ductal reopening, surfactant treatment, pneumothorax, pulmonary hemorrhage, Chronic lung disease, IVH, necrotizing enterocollitis (NEC), gastrointestinal bleeding, retinopathy of prematurity, definite sepsis, and death. It seems that the drug is a safe and none of the papers showed increase in the incidence of the complications when compared to the other NSAIDs.…”

“…Four case report articles were evaluated (15)(16)(17)(18), with the first one has been published in 2011 as shown in table (1).Only Hammerman c et al (15) gave clear definition of hds PDA which was a ductus with internal diameter more than 2 mm, left atrium to aortic ratio more than 1.48 and ductal internal diameter to aortic ratio more than 0.5 (15), while Alan S et al (16) considered left atrium to aortic ratio (LA/AO) of >1,57 as hds PDA and Cynthia H et al considered a PDA with an internal diameter of 1,9 mm as hds PDA. In all cases paracetamol was given in a dose of 15mg/kg/dose /6 hours for 48 hours regardless to the rout of administration except for Pérez Dominguez ME et al (17) who gave IV paracetamol in a dose of 7.5 mg/kg/6 hours to a premature neonate when it was necessary to give a second course of paracetamol and 12mg/kg/12 hours for 4 days given for a different purpose to the child as reported by Cynthia H et al (18) and all patients followed by echocardiographic evaluation for up to 1 week to give the final decision about ductal closure. Paracetamol was started at a wide range of postnatal ages from 2-35 days (15-17) with successful closure as primary outcome, even surprisingly Cynthia H et al (18) reported this successful approach accidentally in a 5 months old infant, however Alan S et al reported therapy failure for 3 neonates without reasonable explanation (16).…”

“…In all cases paracetamol was given in a dose of 15mg/kg/dose /6 hours for 48 hours regardless to the rout of administration except for Pérez Dominguez ME et al (17) who gave IV paracetamol in a dose of 7.5 mg/kg/6 hours to a premature neonate when it was necessary to give a second course of paracetamol and 12mg/kg/12 hours for 4 days given for a different purpose to the child as reported by Cynthia H et al (18) and all patients followed by echocardiographic evaluation for up to 1 week to give the final decision about ductal closure. Paracetamol was started at a wide range of postnatal ages from 2-35 days (15-17) with successful closure as primary outcome, even surprisingly Cynthia H et al (18) reported this successful approach accidentally in a 5 months old infant, however Alan S et al reported therapy failure for 3 neonates without reasonable explanation (16). Four premature neonate among all the reported babies had unsuccessful approach and as a secondary outcome one of them died due to sepsis after surgical ligation of his PDA.…”

The strategy of paracetamol (acetaminophen) use in closing patent ductus arteriosus in premature neonates.

“…N (number), GA (gestational age), PDA (patent ductus arteriosus), LA (left atrium), Ao (aortic), h (hour), NSAID (non-steroidal anti-inflammatory drugs), d (days), I.V (intravenous). Four case report articles were evaluated (15)(16)(17)(18), with the first one has been published in 2011 as shown in table (1).Only Hammerman c et al (15) gave clear definition of hds PDA which was a ductus with internal diameter more than 2 mm, left atrium to aortic ratio more than 1.48 and ductal internal diameter to aortic ratio more than 0.5 (15), while Alan S et al (16) considered left atrium to aortic ratio (LA/AO) of >1,57 as hds PDA and Cynthia H et al considered a PDA with an internal diameter of 1,9 mm as hds PDA. In all cases paracetamol was given in a dose of 15mg/kg/dose /6 hours for 48 hours regardless to the rout of administration except for Pérez Dominguez ME et al (17) who gave IV paracetamol in a dose of 7.5 mg/kg/6 hours to a premature neonate when it was necessary to give a second course of paracetamol and 12mg/kg/12 hours for 4 days given for a different purpose to the child as reported by Cynthia H et al (18) and all patients followed by echocardiographic evaluation for up to 1 week to give the final decision about ductal closure.…”