Acetaminophen for Patent Ductus Arteriosus in Extremely Low-Birth-Weight Neonates

Luecke, Caitlyn M; Liviskie, Caren; Zeller, Brandy; Vesoulis, Zachary A.; McPherson, Christopher

doi:10.5863/1551-6776-22.6.461

Cited by 8 publications

(8 citation statements)

References 27 publications

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“…The clinical characteristics and outcomes of the entire cohort have been reported previously. 6 Of the 41 infants in the overall cohort, 36 received acetaminophen courses that were exclusively intravenous and were included in this study. Demographics of study infants are presented in the Table.…”

Section: Resultsmentioning

confidence: 99%

“…Our previous report of this cohort suggests the potential for a lower rate of complete ductal closure in extremely preterm infants treated at relatively late postnatal ages. 6 A recent publication suggests these clinical findings may arise partially from an association between lower acetaminophen concentrations and higher postnatal ages. 2 However, we failed to detect an association between postnatal age and acetaminophen concentration (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

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Acetaminophen Serum Concentrations in Infants Treated Intravenously for Patent Ductus Arteriosus

McPherson¹,

Luecke²,

Liviskie³

et al. 2019

The Journal of Pediatric Pharmacology and Therapeutics

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OBJECTIVE Although acetaminophen has emerged as a therapeutic option for treating hemodynamically significant patent ductus arteriosus (PDA) in preterm infants, limited data exist on pharmacodynamics. The objective of this research is to report serum acetaminophen concentrations at steady state in infants treated with intravenous acetaminophen for PDA and to examine associations with clinical outcomes. METHODS This retrospective study evaluated all infants admitted during the study period who received intravenous acetaminophen for the treatment of PDA. Acetaminophen dosing was 15 mg/kg every 6 hours. A serum acetaminophen concentration was obtained 4 hours after the eighth dose. Associations between serum concentrations and efficacy, assessed by ductal constriction on echocardiogram, and safety, assessed by serum creatinine and hepatic transaminases, were explored using simple linear regression. RESULTS A total of 36 infants were included, with a median birth weight of 720 g (IQR 585–895 g) and a median gestational age of 25 weeks (IQR 24–26 weeks). The median acetaminophen concentration in the cohort was 12.3 mg/L (IQR 6.7–16.5 mg/L; range, 1.1–29.0 mg/L). Serum acetaminophen concentrations did not correlate with infant demographics, hepatic transaminases during treatment, or duct size at treatment completion. We observed ductal closure across a wide range of serum acetaminophen concentrations. CONCLUSIONS We did not identify an association between acetaminophen serum concentrations following intravenous therapy and ductal response or hepatic toxicity.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Acetaminophen Serum Concentrations in Infants Treated Intravenously for Patent Ductus Arteriosus

McPherson¹,

Luecke²,

Liviskie³

et al. 2019

The Journal of Pediatric Pharmacology and Therapeutics

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“…A case series in nine neonates revealed acetaminophen concentrations in the range between 10 and 20 mg/L to be therapeutically effective in PDA closure 28 . Extreme preterm neonates have been shown to poorly respond to acetaminophen therapy in a previous study 29 . 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.…”

Section: Discussionmentioning

confidence: 51%

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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“…[178][179][180][181][182] One additional retrospective cohort study with an average gestational age of $25 weeks reported BPD in 61% of APAP exposed subjects and commented that "notably, BPD rates in our cohort were dramatically greater, likely attributable to patient selection, but requiring attention in ongoing controlled trials of acetaminophen therapy." 183 The numbers of high-risk infants born preterm included in these reports greatly exceed those from the RCTs, making this finding particularly concerning. Although data from cohort studies and case series are often considered "lower quality" than those gathered in RCTs, here they are a vitally important adjunct potentially revealing a signal demonstrating unanticipated harm.…”

Section: Difference In Bpd Incidencementioning

confidence: 99%

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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Acetaminophen for Patent Ductus Arteriosus in Extremely Low-Birth-Weight Neonates

Cited by 8 publications

References 27 publications

Acetaminophen Serum Concentrations in Infants Treated Intravenously for Patent Ductus Arteriosus

Acetaminophen Serum Concentrations in Infants Treated Intravenously for Patent Ductus Arteriosus

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?

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