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

Pranata, Raymond; Yonas, Emir; Vania, Rachel; Prakoso, Radityo

doi:10.1016/j.ihj.2020.05.012

Cited by 10 publications

(16 citation statements)

References 21 publications

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“…Acetaminophen has been also shown to be effective in closing the ductus within 48 hours that was refractory to ibuprofen 21 . A recent meta‐analysis revealed that oral acetaminophen to be superior to oral ibuprofen in neonates <34 weeks of gestational age (OR: 1.73; 95% CI: 1.01, 2.94) 22 . We did not observe any significant association between post‐natal days of treatment while a recent study, although not statistically significant, observed that 80% success rate for ≤7 days compared to 68% afterwards 23 .…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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What is known and objectives Acetaminophen has been increasingly used in treating patent ductus arteriosus (PDA) in preterm neonates. Variations were observed in the dosing regimen of acetaminophen across the studies. There is hardly any data available for a relatively higher dose of intravenous acetaminophen (15 mg/kg/dose every 6 hours) in the preterm population. We present here the results of a prospective study with this dose of intravenous acetaminophen for treating PDA in critically ill preterm neonates. Methods Preterm neonates (≤37 weeks of gestational age) with haemodynamically significant PDA were enrolled. Intravenous acetaminophen at 15 mg/kg/dose every 6 hours was administered. Echocardiographic monitoring, liver and renal function tests were carried out. Standard definitions were adhered for defining acute kidney injury (AKI) and hepatotoxicity. Results Fifty‐five neonates were recruited. Following the first dose, less than half had their serum acetaminophen concentrations in the therapeutic range. Extreme preterm neonates were less likely to have a sustained therapeutic acetaminophen concentration after the first dose. Following multiple doses and at steady state, 97.2% and 98.8% respectively were in the therapeutic range. Forty‐three (78.2%) neonates had successful closure of the ductus arteriosus of which 22 were extreme preterm, 17 were very preterm and 4 were late preterm neonates; and considering their birthweights, 21 were extremely low, 16 were very low and 6 were low birthweight categories. Ten neonates had elevated alanine aminotransferase levels with three in the low‐to‐moderate risk of hepatotoxicity category. Eight neonates had altered renal function tests indicating AKI. What is new and conclusion Intravenous acetaminophen at 15 mg/kg/dose every 6 hours was efficacious in 78.2% of the preterm neonates with PDA. We observed a lower incidence of hepatotoxicity, and AKI in the study population. No association was observed between the serum acetaminophen concentrations and PDA closure.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…In addition, it could be argued that this knowledge gap has allowed us to perform and publish clinical studies without including relevant short-and long-term pulmonary outcomes while planning and publishing systematic reviews without considering relevant pulmonary outcomes. 90,91 Clinical Studies: Potential Signals for Harm APAP use during pregnancy is considered safe due to a lack of reported adverse effects, rather than data from preclinical models and clinical trials demonstrating safety. 92 Safety during pregnancy is so accepted that exposures now occur in 50%-60% of pregnancies in the US, Europe, and Australia.…”

Section: Pulmonary Cyp2e1 Expression: Developmentally Regulated and Clinically Relevantmentioning

confidence: 99%

“…Five meta-analyses have been published. 14,91,[130][131][132] The most recent meta-analysis, comparing oral (PO) APAP with PO ibuprofen, did not report BPD in their outcomes. 91 In the remaining 4 studies, there was no signal for increased BPD in subjects exposed to APAP.…”

Section: Nicu Exposures: Underpowered To Determine Safety and Detect Harm Not Reassuringmentioning

confidence: 99%

“…14,91,[130][131][132] The most recent meta-analysis, comparing oral (PO) APAP with PO ibuprofen, did not report BPD in their outcomes. 91 In the remaining 4 studies, there was no signal for increased BPD in subjects exposed to APAP. 14,[130][131][132] Necessarily, the confidence in this conclusion is limited by the heterogeneity of the definition of BPD in the original trials.…”

Section: Nicu Exposures: Underpowered To Determine Safety and Detect Harm Not Reassuringmentioning

confidence: 99%

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Acetaminophen and the Developing Lung: Could There Be Lifelong Consequences?

Wright

2021

The Journal of Pediatrics

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he use of acetaminophen (paracetamol, APAP) in the neonatal intensive care unit (NICU) has become ubiquitous. Between 2005 and 2010, APAP was the 15th most common pharmacologic exposure among infants admitted to the Pediatrix-affiliated NICUs in the US. 1 Over nearly the same period of time, a significant increase in the use of APAP was reported in German NICUs, occurring in 8.1% of all infants with very low birth weights by 2010. 2 Since 2010, multiple reports indicate increasing APAP use in NI-CUs around the world. Data gathered in 2017-2018 from nearly 30 000 French infants showed that APAP was the third most commonly administered medication behind vitamin K and vitamin D and was given to >65% of all infants born at less than 27 weeks of gestation. 3 It is likely that this rapid increase in APAP exposure is primarily driven by the desire to provide analgesia and limit opioid exposure. In fact, one French NICU reported that by 2012-2013, nearly 95% of patients in the NICU postsurgery were administered APAP. 4 These data have been interpreted as demonstrating that "paracetamol is somehow a 'rising star' in NICU pain management." 5 The introduction of APAP into the NICU led to the chance observation that administration was temporally associated with closure of the patent ductus arteriosus (PDA). 6 In the time since this case series was published in 2011, the rise in annual publications in PubMed.gov demonstrate the rapidly growing interest in this pharmacologic approach to PDA treatment (Figure 1). Multiple case series, cohort studies, and ultimately randomized controlled trials (RCTs) evaluating APAP for PDA followed, and these have been summarized in a number of comprehensive reviews. [7][8][9][10][11][12][13] Based on the available data, a 2020 Cochrane review by Ohlsson and Shah concluded that moderate-quality evidence demonstrated that APAP is as effective as ibuprofen to treat PDA. 14 However, this review also noted that the results from the more than 19 registered and ongoing trials are necessary before any "recommendations for the possible routine use of paracetamol in the newborn population can be made." Specifically, the paucity of data

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“…8,9 The last decade there has been a great interest in the use of paracetamol as an alternative pharmacological agent, which is a less potent inhibitor of the peripheral cyclo-oxygenase cycle and seems to exerts its mode of action mainly through central nervous system receptors and, therefore has a better safety profile when compared to NSAIDs. 6,10 We conducted a systematic review and meta-analysis (SRMA) of randomized controlled trials (RCTs) to investigate the safety and efficacy of paracetamol versus NSAIDs in neonates with PDA. We included RCTs only in an attempt to strengthen the level of evidence of the results.…”

mentioning

confidence: 99%

Comparative safety and efficacy of paracetamol versus non‐steroidal anti‐inflammatory agents in neonates with patent ductus arteriosus: A systematic review and meta‐analysis of randomized controlled trials

Katsaras

Chatziravdeli

et al. 2022

Brit J Clinical Pharma

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Aim Ibuprofen and indomethacin are the preferred drug treatment for patent ductus arteriosus (PDA) in preterm neonates. The comparative safety and efficacy of paracetamol as an alternative has not yet been well established. The aim of our study was to define the comparative efficacy and safety of paracetamol versus ibuprofen and indomethacin for PDA. Methods We performed a systematic literature search in PubMed, Scopus and Cochrane databases on randomized controlled trials comparing the efficacy and/or the safety of paracetamol versus ibuprofen and/or indomethacin and meta‐analysed the available data. Results There were 1718 neonates from 20 eligible studies. Paracetamol did not differ from ibuprofen or indomethacin regarding the primary (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.69–1.26, P‐value: 0.650, when compared to ibuprofen, and OR: 0.78; 95% CI: 0.20–3.02, P‐value: 0.716, when compared to indomethacin) and overall (OR: 1.17; 95% CI: 0.82–1.66, P‐value: 0.394, when compared to ibuprofen, and OR: 1.12; 95% CI: 0.58–2.15, P‐value: 0.733, when compared to indomethacin) PDA closure rates. Paracetamol resulted in significantly reduced risk of oliguria and a tendency towards less gastrointestinal bleeding. Conclusion There was no significant difference between paracetamol and ibuprofen or indomethacin in the PDA closure rates. However, paracetamol caused fewer adverse effects.

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

Cited by 10 publications

References 21 publications

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

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

Acetaminophen and the Developing Lung: Could There Be Lifelong Consequences?

Comparative safety and efficacy of paracetamol versus non‐steroidal anti‐inflammatory agents in neonates with patent ductus arteriosus: A systematic review and meta‐analysis of randomized controlled trials

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