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Am J Perinatol 2022; 39(12): 1326-1333
DOI: 10.1055/s-0040-1722329
Original Article

Effectiveness of Dual Medication Therapy (Oral Acetaminophen and Oral Ibuprofen) for the Management of Patent Ductus Arteriosus in Extremely Premature Infants: A Feasibility Trial

Sanket D. Shah 
1   Department of Pediatrics, Division of Neonatology, University of Florida College of Medicine, Jacksonville, Florida
,
Kartikeya Makker
2   Department of Pediatrics, Division of Neonatology, Johns Hopkins Children's Center, John Hopkins University, Baltimore, Maryland
,
Padma Nandula
1   Department of Pediatrics, Division of Neonatology, University of Florida College of Medicine, Jacksonville, Florida
,
Carmen Smotherman
3   Center for Data Solutions, University of Florida College of Medicine, Jacksonville, Florida
,
Andrea Kropf
4   Department of Pediatrics, Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida
,
Mark L. Hudak
1   Department of Pediatrics, Division of Neonatology, University of Florida College of Medicine, Jacksonville, Florida
› Author Affiliations Funding None.
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Abstract

Objective The study aimed to evaluate the efficacy of dual medication therapy (DMT) with oral acetaminophen and oral ibuprofen for the closure of a hemodynamically significant patent ductus arteriosus (hsPDA).

Study Design In a prospective case–control cohort study (July 2017–May 2019), infants <29 weeks' gestational age and birth weight <1,000 g at ≤14 postnatal days with hsPDA and ratio of the smallest ductal diameter to the ostium of the left pulmonary artery diameter >0.5 were eligible. Infants received 10 mg/kg oral ibuprofen followed by two additional doses of 5 mg/kg at 24 and 48 hours after the initial ibuprofen dose and concomitant treatment with 15 mg/kg oral acetaminophen every 6 hours for 3 days (12 doses). Success of PDA treatment was defined as a small or absent PDA as ascertained by echocardiographic measurements. The p-values of comparisons were adjusted for multiple comparisons to preserve an error rate of 5%.

Results Overall, 20 infants received oral DMT and 11 infants received intravenous single medication therapy (SMT) with ibuprofen. The rates of successful PDA treatment following the first treatment in DMT and SMT groups were not statistically different (11/20 [55%] vs. 4/11 [36%], p = 0.46). However, DMT significantly decreased PDA size (mean difference = 0.54 mm, 95% confidence interval [CI]: 0.21–0.96, adjusted p-value = 0.0002) and PDA/LPA ratio (mean difference = 0.27, 95% CI: 0.10–0.47, adjusted p-value = 0.0004). We observed no evidence of hematologic, hepatic, or renal impairment.

Conclusion DMT achieved a greater degree of PDA closure than SMT and did not result in abnormalities in hepatic and renal profile.

Key Points

  • No consensus on optimal medication for PDA treatment is available.

  • Dual oral medication therapy (ibuprofen and acetaminophen) could be an effective alternative treatment for PDA.

  • Dual oral medication therapy (ibuprofen and acetaminophen) may have a better safety profile than currently approved medications such as intravenous indomethacin and intravenous ibuprofen.

Keywords

patent ductus arteriosus - acetaminophen - ibuprofen - extremely premature infants

Note

The portion of the study was presented at the Pediatric Academic Societies meeting from April 24 to May 1, 2019 at Baltimore, MD.




Publication History

Received: 11 June 2020

Accepted: 20 November 2020

Article published online:
17 January 2021

© 2021. Thieme. All rights reserved.

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