Paracetamol vs Ibuprofen in Hemodynamically Significant Patent Ductus Arteriosus (HsPDA) in Preterms: A Randomized Controlled Trial

Background and Objective: Hemodynamically significant patent ductus arteriosus (HsPDA) is a common cause of morbidity in preterm infants. Indomethacin and Ibuprofen, which are cyclo-oxygenase (COX) 1, 2 inhibitors are commonly used drugs for closure of HsPDA. As, Ibuprofen has several contraindications, we designed study using oral paracetamol (a peroxidase inhibitor) and compared with oral ibuprofen, for efficacy and safety in relation to closure of HsPDA in preterm infants. Methods: 140 preterm infants (gestational age less than 32 weeks) with HsPDA (confirmed by 2D Echo) were randomly assigned in two groups and received first course of either oral paracetamol (70) or ibuprofen (70). The need for a second course was determined by 2D Echo evaluation. Parameters studied were rate of ductal closure, any adverse effects and discharge rate. Results: Both groups were similar in term of ductal closure after first course (p=0.46) and second course (p=0.59). However, 22 from Ibuprofen group and only 2 from PCM group developed adverse effects (p<0.001). From paracetamol group 58 were discharged, and 12 died; while from ibuprofen group 46 discharged, 24 died (p=0.03). Conclusion: Paracetamol for HsPDA in preterm neonates was associated with good efficacy and better safety; and less deaths, as compared to ibuprofen.

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ORAL VERSUS INTRAVENOUS IBUPROFEN FOR THE EARLY CLOSURE OF PATENT DUCTUS ARTERIOSUS IN LOW BIRTH WEIGHT PRETERM INFANTS

European Medical Health and Pharmaceutical Journal ◽

10.12955/emhpj.v6i0.388 ◽

2013 ◽

Vol 6 ◽

Cited By ~ 4

Author(s):

Alketa Hoxha ◽

Ermira Kola ◽

Numila Kuneshka ◽

Eduard Tushe

Keyword(s):

Birth Weight ◽

Adverse Effects ◽

Preterm Infants ◽

Premature Infants ◽

Ductus Arteriosus ◽

Ductal Closure ◽

Oral Ibuprofen ◽

Intravenous Ibuprofen ◽

Ibuprofen Group ◽

Patent Ductus

Background Patent ductus arteriosus (PDA) is common in very premature infants. Pharmacological closure of PDA with indomethacin, a prostaglandin inhibitor, has remained the mainstay of treatment in premature infants over the last three decades. Intravenous ibuprofen was recently shown to be as effective and to have fewer adverse reaction in preterm infants. If equally effective, then oral ibuprofen for PDA closure would have several important advantages over the intravenous route.This study was designed to assess the efficacy and safety of oral ibuprofen and intravenous ibuprofen for the early pharmacological treatment of PDA in LBW preterm infants with respiratory distress syndrome.MethodsA randomized, single-blinded, controlled study was performed on premature neonates at the neonatal care unit of the University Hospital for Obstetrics and Gynecology”Koco Gliozheni”, Tirana, Albania, from January 2010 to December 2012. The study enrolled 68 preterm infants with gestational age between 28-32 weeks, birth weight ≤ 2000 g, postnatal age 48-96 h, and had echocardiographically confirmed significant PDA. The preterm infants received either intravenous or oral ibuprofen randomly as an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 h. After the first dose of treatment in both groups, echocardiographic evaluation was performed, to determine the need for a second or third dose. The rate of ductal closure, adverse effects, complications, and the patient’s clinical course were recorded.Results All patients were born after 28 until 32 weeks’ gestation. 36 patients were treated with oral ibuprofen and 32 with intravenous ibuprofen in this period. After the first course of the treatment, the PDA closed in 30 (83.3%) of the patients assigned to the oral ibuprofen group versus 23 (71.8%) of those enrolled in the intravenous ibuprofen group (p = 0.355). There was no difference between treatment groups in demographics or baseline renal function. In the evaluation of renal tolerance, none of the patients had oliguria. There were no significant differences with respect to complications during the stay.Conclusions In low birth weight infants, the rate of early ductal closure with oral ibuprofen is at least as good as with the intravenous route. Oral ibuprofen is associated with fewer adverse effects

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Use of combination therapy with acetaminophen and ibuprofen for closure of the patent ductus arteriosus in preterm neonates

Paediatrics & Child Health ◽

10.1093/pch/pxaa057 ◽

2020 ◽

Author(s):

Susan Kimani ◽

Aimann Surak ◽

Michael Miller ◽

Soume Bhattacharya

Keyword(s):

Adverse Effects ◽

Combination Therapy ◽

Patent Ductus Arteriosus ◽

Neonatal Intensive Care ◽

Ductus Arteriosus ◽

Combination Group ◽

Preterm Neonates ◽

Primary Therapy ◽

Ductal Closure ◽

Patent Ductus

Abstract Objective To compare effectiveness and safety of combination therapy (acetaminophen and ibuprofen) to monotherapy (ibuprofen, indomethacin, or acetaminophen alone) in treatment of the patent ductus arteriosus (PDA) in premature neonates. Methods This was a retrospective cohort study of neonates admitted to a tertiary-level neonatal intensive care unit. Included neonates were born at <32 weeks gestation and received pharmacotherapy for PDA closure. Based on the primary therapy received, our cohort was divided into the following four groups: indomethacin alone, ibuprofen alone, acetaminophen alone, and ibuprofen and acetaminophen (in combination). Baseline characteristics, effectiveness, safety, neonatal mortality, and morbidities rates between these groups were compared. Results One hundred and forty neonates were analyzed; 17 received combination therapy, and 123 neonates received monotherapy: 22 (17.9%) ibuprofen, 29 (23.6%) acetaminophen, and 72 (58.5%) indomethacin. The PDA closure rates were 41.7% for indomethacin, 41.2% for combination therapy, 37.9% for acetaminophen, and 31.8% for ibuprofen (P=0.100). Rates of adverse effects were comparable between the groups. Conclusion The rate of ductal closure was not different between combination therapy and monotherapy. The study did not demonstrate any increased adverse effects in the combination group. Future well-designed prospective clinical trials are needed to guide clinical practice.

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Patent ductus arteriosus, systemic NT-proBNP concentrations and development of bronchopulmonary dysplasia in very preterm infants: retrospective data analysis from a randomized controlled trial

BMC Pediatrics ◽

10.1186/s12887-021-02750-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Solomiia Potsiurko ◽

Dmytro Dobryanskyy ◽

Lesya Sekretar

Keyword(s):

Randomized Controlled Trial ◽

Patent Ductus Arteriosus ◽

Preterm Infants ◽

Roc Curve ◽

Controlled Trial ◽

Ductus Arteriosus ◽

Very Preterm Infants ◽

Very Preterm ◽

Randomized Controlled ◽

Patent Ductus

Abstract Background Patent ductus arteriosus (PDA) is a common complication in very preterm infants. It is known that there is an association between PDA and development of bronchopulmonary dysplasia (BPD) or death before the postmenstrual age (PMA) of 36 weeks, but this association remains one of the most controversial aspects of the problem. The study aimed to evaluate the relationship between PDA, serum NT-proBNP levels at 2–3 and 8–9 days of life, and BPD/death in very preterm infants. Methods Data of 52 preterm infants with a gestational age < 32 weeks, chronological age < 72 h, and PDA diameter > 1.5 mm, enrolled in a randomized controlled trial, were used for the retrospective analysis. All patients underwent daily echocardiographic and two serum NT-proBNP measurements within the first 10 days after birth. Two groups of infants were formed retrospectively at PMA of 36 weeks depending on the outcome, BPD (n = 18)/death (n = 7) or survival without BPD (n = 27). Receiver operator characteristic (ROC) curve was used to evaluate the predictive performance of serum NT-proBNP levels for BPD/death occurrence. Results The percentage of infants who received pharmacological treatment for PDA did not differ between the groups. Based on the area under the ROC curve, serum NT-proBNP levels on the 2–3 day of life (AUC = 0.71; 95% confidence interval (CI): 0.56–0.9; p = 0.014)) and on the 8–9 day of life (AUC = 0.76; 95% CI: 0.6–0.9; p = 0.002) could reliably predict BPD/death in very preterm infants who had PDA diameter > 1.5 mm in the first 72 h of life. Hemodynamically significant PDA (hsPDA) was significantly more often detected in newborns with BPD/death, however, treatment of infants with hsPDA did not reduce the incidence of BPD/death. Conclusions In very preterm infants with PDA > 1.5 mm at the age of 24–48 h, serum NT-proBNP concentration could reliably predict the development of BPD or death, regardless of the persistence of PDA, with the highest diagnostic value at 8–9 days. Trial registration This study is registered in ClinicalTrials.gov - NCT03860428 on March 4, 2019.

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Enteral paracetamol or intravenous indomethacin for closure of patent ductus arteriosus in preterm neonates: A randomized controlled trial

Indian Pediatrics ◽

10.1007/s13312-015-0677-z ◽

2015 ◽

Vol 52 (7) ◽

pp. 573-578 ◽

Cited By ~ 30

Author(s):

Swarup Kumar Dash ◽

Nandkishor S Kabra ◽

Bhupendra S Avasthi ◽

Shobha R Sharma ◽

Phalguni Padhi ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Patent Ductus Arteriosus ◽

Controlled Trial ◽

Ductus Arteriosus ◽

Preterm Neonates ◽

Randomized Controlled ◽

Patent Ductus

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CYP2C9*2 is associated with indomethacin treatment failure for patent ductus arteriosus

Pharmacogenomics ◽

10.2217/pgs-2019-0079 ◽

2019 ◽

Vol 20 (13) ◽

pp. 939-946

Author(s):

Sydney R Rooney ◽

Elaine L Shelton ◽

Ida Aka ◽

Christian M Shaffer ◽

Ronald I Clyman ◽

...

Keyword(s):

Patent Ductus Arteriosus ◽

Treatment Failure ◽

Preterm Infants ◽

Gestational Age ◽

Genetic Factors ◽

Ductus Arteriosus ◽

Preterm Neonates ◽

Multicenter Cohort Study ◽

Patent Ductus ◽

Indomethacin Treatment

Aims: To identify clinical andgenetic factors associated with indomethacin treatment failure in preterm neonates with patent ductus arteriosus (PDA). Patients & Methods: This is a multicenter cohort study of 144 preterm infants (22–32 weeks gestational age) at three centers who received at least one treatment course of indomethacin for PDA. Indomethacin failure was defined as requiring subsequent surgical intervention. Results: In multivariate analysis, gestational age (AOR 0.76, 95% CI 0.60–0.96), surfactant use (AOR 9.77, 95% CI 1.15–83.26), and CYP2C9*2 (AOR 3.74; 95% CI 1.34–10.44) were each associated with indomethacin failure. Conclusion: Age, surfactant use, and CYP2C9*2 influence indomethacin treatment outcome in preterm infants with PDA. This combination of clinical and genetic factors may facilitate targeted indomethacin use for PDA.

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Early prediction of spontaneous Patent Ductus Arteriosus (PDA) closure and PDA-associated outcomes: a prospective cohort investigation

BMC Pediatrics ◽

10.1186/s12887-019-1708-z ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 4

Author(s):

Jonathan L. Slaughter ◽

Clifford L. Cua ◽

Jennifer L. Notestine ◽

Brian K. Rivera ◽

Laura Marzec ◽

...

Keyword(s):

Patent Ductus Arteriosus ◽

Brain Natriuretic Peptide ◽

Preterm Infants ◽

Prospective Cohort ◽

Ductus Arteriosus ◽

Neurodevelopmental Delay ◽

Ductal Closure ◽

Postmenstrual Age ◽

Patent Ductus

Abstract Background Patent ductus arteriosus (PDA), the most commonly diagnosed cardiovascular condition in preterm infants, is associated with increased mortality and harmful long-term outcomes (chronic lung disease, neurodevelopmental delay). Although pharmacologic and/or interventional treatments to close PDA likely benefit some infants, widespread routine treatment of all preterm infants with PDA may not improve outcomes. Most PDAs close spontaneously by 44-weeks postmenstrual age; treatment is increasingly controversial, varying markedly between institutions and providers. Because treatment detriments may outweigh benefits, especially in infants destined for early, spontaneous PDA closure, the relevant unanswered clinical question is not whether to treat all preterm infants with PDA, but whom to treat (and when). Clinicians cannot currently predict in the first month which infants are at highest risk for persistent PDA, nor which combination of clinical risk factors, echocardiographic measurements, and biomarkers best predict PDA-associated harm. Methods Prospective cohort of untreated infants with PDA (n=450) will be used to predict spontaneous ductal closure timing. Clinical measures, serum (brain natriuretic peptide, N-terminal pro-brain natriuretic peptide) and urine (neutrophil gelatinase-associated lipocalin, heart-type fatty acid-binding protein) biomarkers, and echocardiographic variables collected during each of first 4 postnatal weeks will be analyzed to identify those associated with long-term impairment. Myocardial deformation imaging and tissue Doppler imaging, innovative echocardiographic techniques, will facilitate quantitative evaluation of myocardial performance. Aim1 will estimate probability of spontaneous PDA closure and predict timing of ductal closure using echocardiographic, biomarker, and clinical predictors. Aim2 will specify which echocardiographic predictors and biomarkers are associated with mortality and respiratory illness severity at 36-weeks postmenstrual age. Aim3 will identify which echocardiographic predictors and biomarkers are associated with 22 to 26-month neurodevelopmental delay. Models will be validated in a separate cohort of infants (n=225) enrolled subsequent to primary study cohort. Discussion The current study will make significant contributions to scientific knowledge and effective PDA management. Study results will reduce unnecessary and harmful overtreatment of infants with a high probability of early spontaneous PDA closure and facilitate development of outcomes-focused trials to examine effectiveness of PDA closure in “high-risk” infants most likely to receive benefit. Trial registration ClinicalTrials.gov NCT03782610. Registered 20 December 2018.

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Abnormal Cerebral Hemodynamics in Preterm Infants with Patent Ductus Arteriosus

PEDIATRICS ◽

10.1542/peds.69.6.778 ◽

1982 ◽

Vol 69 (6) ◽

pp. 778-781

Author(s):

Brian Lipman ◽

Gerald A. Serwer ◽

Jane E. Brazy

Keyword(s):

Blood Flow ◽

Patent Ductus Arteriosus ◽

Preterm Infants ◽

Ductus Arteriosus ◽

Cerebral Arteries ◽

Flow Patterns ◽

Cerebral Hemodynamics ◽

Ductal Closure ◽

Blood Flow Patterns ◽

Patent Ductus

Blood flow patterns in the anterior cerebral arteries were studied in eight preterm infants with patent ductus arteriosus and left-to-right shunts. A noninvasive Doppler technique was used to obtain the blood flow patterns and to calculate a pulsatility index. Advancing diastolic blood flow was decreased in all eight infants, and two demonstrated retrograde anterior cerebral artery flow during diastole. Following ductal closure, the diastolic flow in the anterior cerebral arteries increased significantly, reaching levels seen in normal infants. These observations demonstrate that infants with patent ductus arteriosus and left-to-right shunts may have abnormal cerebral hemodynamics which return to normal following ductal closure.

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Neurodevelopmental Outcomes of Preterm Infants Treated with Oral Paracetamol Versus Ibuprofen for Patent Ductus Arteriosus

American Journal of Perinatology ◽

10.1055/s-0037-1601564 ◽

2017 ◽

Vol 34 (12) ◽

pp. 1185-1189 ◽

Cited By ~ 11

Author(s):

Zeynep Eras ◽

Nurdan Uras ◽

Fuat Canpolat ◽

Omer Erdeve ◽

Serife Oguz ◽

...

Keyword(s):

Patent Ductus Arteriosus ◽

Preterm Infants ◽

Infant Development ◽

Controlled Trial ◽

Ductus Arteriosus ◽

Neurodevelopmental Outcomes ◽

Significant Difference ◽

Oral Ibuprofen ◽

Patent Ductus

Objective This study aims to determine the effects of paracetamol versus ibuprofen treatment given to preterm infants for the pharmacological closure of patent ductus arteriosus (PDA) on neurodevelopmental outcomes at 18 to 24 months' corrected age. Method A follow-up study was conducted to evaluate the neurodevelopmental outcomes of preterm infants (gestational age ≤ 30 weeks) enrolled in a randomized controlled trial comparing oral paracetamol versus oral ibuprofen for the closure of PDA. The developmental assessment was done by using “Bayley Scales of Infant Development, Second Edition” at 18 to 24 months' corrected age. Results A total of 80 infants completed the trial protocol. Of the 75 infants eligible for follow-up, 61 infants (30 in the paracetamol group and 31 in the ibuprofen group) were evaluated. There was no significant difference in neurodevelopmental outcomes between the two groups. Conclusion The neurodevelopmental outcomes did not differ among the preterm infants who receive either paracetamol or ibuprofen at 18 to 24 months' corrected age.

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Using benchmarking to identify inter-centre differences in persistent ductus arteriosus treatment: can we improve outcome?

Cardiology in the Young ◽

10.1017/s104795111700052x ◽

2017 ◽

Vol 27 (8) ◽

pp. 1488-1496 ◽

Cited By ~ 3

Author(s):

Esther J. S. Jansen ◽

Koen P. Dijkman ◽

Richard A. van Lingen ◽

Willem B. de Vries ◽

Daniel C. Vijlbrief ◽

...

Keyword(s):

Patent Ductus Arteriosus ◽

Preterm Infants ◽

Standard Procedure ◽

Ductus Arteriosus ◽

Short Term ◽

Surgical Ligation ◽

Persistent Ductus Arteriosus ◽

Ductal Closure ◽

Neonatal Icu ◽

Patent Ductus

AbstractObjectiveThe aim of this study was to identify inter-centre differences in persistent ductus arteriosus treatment and their related outcomes.Materials and methodsWe carried out a retrospective, multicentre study including infants between 24+0 and 27+6 weeks of gestation in the period between 2010 and 2011. In all centres, echocardiography was used as the standard procedure to diagnose a patent ductus arteriosus and to document ductal closure.ResultsIn total, 367 preterm infants were included. All four participating neonatal ICU had a comparable number of preterm infants; however, differences were observed in the incidence of treatment (33–63%), choice and dosing of medication (ibuprofen or indomethacin), number of pharmacological courses (1–4), and the need for surgical ligation after failure of pharmacological treatment (8–52%). Despite the differences in treatment, we found no difference in short-term morbidity between the centres. Adjusted mortality showed independent risk contribution of gestational age, birth weight, ductal ligation, and perinatal centre.ConclusionsUsing benchmarking as a tool identified inter-centre differences. In these four perinatal centres, the factors that explained the differences in patent ductus arteriosus treatment are quite complex. Timing, choice of medication, and dosing are probably important determinants for successful patent ductus arteriosus closure.

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