|
1
|
Zi-Yun X, Ruo-lin Z, Yue-wei X, Tao B. Efficacy and Safety of Oral Acetaminophen for Premature Infants With Patent Ductus Arteriosus: A Meta-Analysis. Front Pharmacol 2022; 12:696417. [PMID: 35115919 PMCID: PMC8804357 DOI: 10.3389/fphar.2021.696417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 12/22/2021] [Indexed: 11/13/2022] Open
Abstract
Objective: To systematically review the efficacy and safety of oral Acetaminophen for premature infants with patent ductus arteriosus (PDA). Methods: Databases including Ovid, EMbase, Pubmed, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINHAL), China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database (CBM), WanFang Data, China Science and Technology Journal Database were searched to collect the randomized controlled trials (RCTs) about Acetaminophen for premature infants with PDA from inception to January 1, 2021. Quality assessment was performed through bias risk evaluation according to the Cochrane Handbook 5.1.0, and then the homogeneous studies were analyzed using Revman 5.4 software. Results: A total of 16 RCTs were included, which were divided into for four subgroups: subgroup I (oral acetaminophen vs. oral ibuprofen, 13 RCTs), subgroup II (oral acetaminophen vs. intravenous indomethacin, 1 RCT), subgroup III (oral acetaminophen vs intravenous ibuprofen, 1 RCT), and subgroup IV (oral acetaminophen vs intravenous placebo, 1 RCT). In subgroup I, There was no significant difference in the ductal closure rate after the first course of drug administration [typical relative risk (RR) 0.97, 95% confidence interval (CI) 0.90 to 1.05], the accumulated ductal closure rate after two course of treatment (RR 0.96, 95% CI 0.91–1.02), and mortality (RR 1.06, 95% CI 0.75–1.49) between treatment with oral acetaminophen versus oral ibuprofen (p > 0.05); compared with oral ibuprofen, oral acetaminophen was associated with a significant reduction in the incidence of gastrointestinal bleeding/stool occult blood positive (RR 0.51, 95% CI 0.32 to 0.82)and oliguria (RR 0.62, 95% CI 0.42–0.91) (p < 0.05). Conclusion: The meta analysis approves the facts that there is no significant difference in the efficacity in premature infants with PDA between oral acetaminophen and buprofen or indometacin, but compared to ibuprofen, oral acetaminophen may decrease the incidence of oliguria and gastrointestinal bleeding. More reliable conclusions should be made through large-size, multi-center, well-designed RCTs.
Collapse
Affiliation(s)
- Xie Zi-Yun
- Department of Pediatrics, Division of Neonatology, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Zhang Ruo-lin
- Department of Neonatology, Nanshan Maternal and Child Health Care Hospital of Shengzhen, Shenzhen, China
| | - Xia Yue-wei
- Department of Neonatology, Changsha Maternal and Child Health Care Hospital, Changsha, China
| | - Bo Tao
- Department of Pediatrics, Division of Neonatology, The Third Xiangya Hospital, Central South University, Changsha, China
- *Correspondence: Bo Tao,
| |
Collapse
|
|
2
|
Godin R, Rodriguez JC, Kahn DJ. Oral Versus Intravenous Medications for Treatment of Patent Ductus Arteriosus in Preterm Neonates: A Cost-Saving Initiative. J Pediatr Pharmacol Ther 2021; 26:291-299. [PMID: 33833632 DOI: 10.5863/1551-6776-26.3.291] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Accepted: 10/18/2020] [Indexed: 01/27/2023]
Abstract
OBJECTIVE The purpose of the study was to quantify cost savings after promoting oral pharmacotherapy for the treatment of hemodynamically significant patent ductus arteriosus (hsPDA). METHODS This was a retrospective before-and-after time series quality improvement study. Oral ibuprofen and acetaminophen use criteria were developed and recommended, rather than the more costly intravenous equivalents. There were 24-month medication use reports generated for both the pre-criteria (Era-1) and the post-criteria (Era-2) implementation phases to identify neonates prescribed hsPDA medications in order to assess cost differences. RESULTS Era-1 had 190 treatment courses in 110 neonates for a total medication cost of $171,260.70. Era-2 had 210 courses in 109 patients for a total medication cost of $47,461.49, yielding savings of $123,799.21 ($61,899.61 annually) after criteria implementation. The reduction in intravenous ibuprofen use in Era-2 accounted for all the savings. CONCLUSION Preferentially prescribing lower-cost oral medications to treat hsPDA led to significant cost savings.
Collapse
|
|
3
|
Schindler T, Smyth J, Bolisetty S, Michalowski J, Lui K. Early PARacetamol (EPAR) trial: a study protocol for a randomised controlled trial of early paracetamol to promote closure of the ductus arteriosus in preterm infants. BMJ Open 2019; 9:e031428. [PMID: 31666270 PMCID: PMC6830666 DOI: 10.1136/bmjopen-2019-031428] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
INTRODUCTION The optimal management of patent ductus arteriosus (PDA) remains contentious. The medications used to treat PDA are often non-steroidal anti-inflammatory drugs, which are associated with a number of unwanted adverse effects. Paracetamol is a medication with an excellent safety profile in infants and has been suggested as a safe alternative medication in situations where other medications have failed or are contraindicated. There are limited data on the use of early, intravenous paracetamol in preterm infants. METHODS AND ANALYSIS This trial aims to address whether early treatment with paracetamol will reduce the number of infants requiring intervention for PDA. This is a randomised, double-blind, placebo-controlled trial in preterm infants <29 weeks' gestation. At 6 hours of life, infants with a ductus arteriosus >0.9 mm will be randomised to receive either (1) intravenous paracetamol at a dose of 15 mg/kg initially, followed by every 6 hours at a dose of 7.5 mg/kg for 5 days; or (2) intravenous 5% dextrose every 6 hours for 5 days. The primary outcome is the need for any intervention for management of PDA up to 5 days. Secondary outcomes include closure of the ductus arteriosus at 5 days, size of the ductus arteriosus, ductal reopening, systemic blood flow, mortality and significant morbidities. The target sample size of 100 infants yields >80% power, at the two-sided 5% level significance, to detect a 50% reduction in the need for intervention assuming that approximately 60% of infants in this study would otherwise have required intervention for PDA. ETHICS AND DISSEMINATION A report on the results of the planned analyses will be prepared. The results of the primary analysis of all end points will be presented at medical conferences and submitted for publication in peer-reviewed journals. Separate manuscripts pertaining to the second aim of the study may be written, and these will also be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER ACTRN12616001517460.
Collapse
Affiliation(s)
- Tim Schindler
- Newborn Care, Royal Hospital for Women, Randwick, New South Wales, Australia
- School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia
| | - John Smyth
- Newborn Care, Royal Hospital for Women, Randwick, New South Wales, Australia
- School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia
| | - Srinivas Bolisetty
- Newborn Care, Royal Hospital for Women, Randwick, New South Wales, Australia
- School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia
| | - Joanna Michalowski
- Newborn Care, Royal Hospital for Women, Randwick, New South Wales, Australia
| | - Kei Lui
- Newborn Care, Royal Hospital for Women, Randwick, New South Wales, Australia
- School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia
| |
Collapse
|
|
4
|
Karabulut B, Paytoncu S. Efficacy and Safety of Oral Paracetamol vs. Oral Ibuprofen in the Treatment of Symptomatic Patent Ductus Arteriosus in Premature Infants. Paediatr Drugs 2019; 21:113-121. [PMID: 31025304 DOI: 10.1007/s40272-019-00331-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND The ductus arteriosus (DA) is situated between the aortic arch and the pulmonary artery in fetal circulation, and its closure is one of the most important changes required for the transition to extrauterine life. Prolonged duration of patent DA (PDA) impairs hemodynamics and contributes both to morbidity associated with prematurity and to mortality. Therefore, when best to initiate treatment and what drug to use as first-line treatment to close the ductus is important. OBJECTIVE The aim of this study was to compare the efficacy and side effects of the oral forms of ibuprofen and paracetamol and to contribute to the literature investigating the first drug to be selected in the medical treatment of PDA. METHODS This observational, retrospective cohort study was conducted in infants born at ≤ 28 weeks' gestation and admitted to our Neonatal Intensive Care Unit (Manisa Merkezefendi State Hospital, Manisa, Turkey) between February 2015 and April 2018. Included infants were born at ≤ 28 weeks' gestation, had PDA-related clinical findings and hemodynamically significant PDA on echocardiography, and received oral ibuprofen or oral paracetamol therapy as the closure treatment. RESULTS The most common clinical findings for the diagnosis of PDA were hyperdynamic circulation, tachycardia, and increased oxygen requirement. In total, 43 of the 51 (84.3%) premature infants in the ibuprofen group and 32 of the 36 (88.8%) in the paracetamol group achieved PDA closure after the first treatment cycle. There was no statistically significant difference between the two groups in terms of respiratory morbidity, renal and liver function, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, length of hospital stay, and mortality. CONCLUSIONS Our results indicate that oral paracetamol was as effective as oral ibuprofen in the medical treatment of PDA. In addition, both drugs were considered well-tolerated in terms of effects on kidney, liver, and intestinal functions. Our results demonstrate that oral paracetamol can be used effectively and safely as the first-line treatment of PDA.
Collapse
Affiliation(s)
- Birol Karabulut
- Pediatrics, Division of Neonatology, Izmir Katip Celebi University Ataturk Training and Research Hospital, Izmir, Turkey.
| | - Sebnem Paytoncu
- Pediatrics, Division of Pediatric Cardiology, Manisa Merkezefendi State Hospital, Manisa, Turkey
| |
Collapse
|
|
5
|
Guimarães AFM, Araújo FDR, Meira ZMA, Tonelli HAF, Duarte GG, Ribeiro LC, Rezende GQM, Castilho SRT. Acetaminophen in low doses for closure of the ductus arteriosus of the premature. Ann Pediatr Cardiol 2019; 12:97-102. [PMID: 31143033 PMCID: PMC6521660 DOI: 10.4103/apc.apc_42_18] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Objective The objective of the study is to report the experience with acetaminophen in low doses as an alternative to the treatment of the ductus arteriosus of the preterm newborn. Materials and Methods Retrospective study including preterm newborns with patent ductus arteriosus who received oral acetaminophen because treatment with indomethacin had failed or is contraindicated. A dosage consisted of a first dose of 25 mg/kg and maintenance doses of 30 mg/kg/day, for 3 to 7 days. A second cycle was administered in cases of reopening of the ductus arteriosus. The rates of ductal closure and surgery were calculated. Patients were categorized into responder and nonresponder groups for acetaminophen, and the average values of ductal diameter, weight, gestational age, and postnatal age were compared. Results Eighty-seven preterm newborns, with a postnatal age from 3 to 27 days, with average values of ductus arteriosus equal to 2.5 ± 0.8 mm/kg, gestational age 27.2 ± 1.9 weeks, and birth weight 888.9 ± 241 g, received acetaminophen for 3 to 7 days. A second cycle was administered in 15 preterm newborns. The ductus closure rate, after one or two cycles, was 74.7%, and the recommendations for surgical closure were progressively reduced from 50% in the 1st year to 6.2% in the past year. Lower ductal closure rate occurred in the group of newborns with the lowest average weight (P = 0.018), the highest average ductal diameter (P = 0.002), and the lowest average gestational age (P = 0.09). Postnatal age at the start of acetaminophen use was shown to be irrelevant regarding the treatment (P = 0.591). Conclusions Acetaminophen in low doses showed to be an effective alternative for the closure of the ductus arteriosus for preterm newborns in whom treatment with indomethacin or ibuprofen failed or was contraindicated.
Collapse
Affiliation(s)
- Adriana Furletti Machado Guimarães
- Department of Pediatrics, Division of Neonatology, Hospital Foundation of Minas Gerais State, Minas Gerais, Brazil.,Department of Pediatrics, Division of Pediatric Cardiology, Clinics Hospital of the Federal University of Minas Gerais, Minas Gerais, Brazil
| | - Fátima Derlene Rocha Araújo
- Department of Pediatrics, Division of Pediatric Cardiology, Clinics Hospital of the Federal University of Minas Gerais, Minas Gerais, Brazil
| | - Zilda Maria Alves Meira
- Department of Pediatrics, Division of Pediatric Cardiology, Clinics Hospital of the Federal University of Minas Gerais, Minas Gerais, Brazil.,Department of Pediatrics, Division of Pediatric Cardiology, School of Medicine, Federal University of Minas Gerais, Minas Gerais, Brazil
| | - Henrique Assis Fonseca Tonelli
- Department of Pediatrics, Division of Pediatric Cardiology, Clinics Hospital of the Federal University of Minas Gerais, Minas Gerais, Brazil
| | - Guilherme Gomes Duarte
- Department of Pediatrics, Division of Pediatric Cardiology, Clinics Hospital of the Federal University of Minas Gerais, Minas Gerais, Brazil
| | - Lívia Castro Ribeiro
- Department of Pediatrics, Division of Pediatric Cardiology, Clinics Hospital of the Federal University of Minas Gerais, Minas Gerais, Brazil
| | - Gabriele Queiroz Monteiro Rezende
- Department of Pediatrics, Division of Neonatology, Hospital Foundation of Minas Gerais State, Minas Gerais, Brazil.,Department of Pediatrics, Division of Pediatric Cardiology, Clinics Hospital of the Federal University of Minas Gerais, Minas Gerais, Brazil
| | - Sandra Regina Tolentino Castilho
- Department of Pediatrics, Division of Pediatric Cardiology, Clinics Hospital of the Federal University of Minas Gerais, Minas Gerais, Brazil
| |
Collapse
|
|
6
|
Cuzzolin L, Bardanzellu F, Fanos V. The dark side of ibuprofen in the treatment of patent ductus arteriosus: could paracetamol be the solution? Expert Opin Drug Metab Toxicol 2018; 14:855-868. [PMID: 29938546 DOI: 10.1080/17425255.2018.1492550] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
INTRODUCTION Patent ductus arteriosus (PDA) persistence is associated, in prematures, to several complications. The optimal PDA management is still under debate, especially regarding the best therapeutic approach and the time to treat. The available drugs are not exempt from contraindications and side effects; ibuprofen itself, although representing the first-choice therapy, can show nephrotoxicity and other complications. Paracetamol seems a valid alternative to classic nonsteroidal anti-inflammatory Drugs, with a lower toxicity. Areas covered: Through an analysis of the published literature on ibuprofen and paracetamol effects in preterm neonates, this review compares the available treatments for PDA, analyzing the mechanisms underlining ibuprofen-associated nephrotoxicity and the eventual paracetamol-induced hepatic damage, also providing an update of what has been yet demonstrated and a clear description of the still open issues. Expert Opinion: Paracetamol is an acceptable alternative in case of contraindication to ibuprofen; its toxicity, in this setting, is very low. Lower doses may be effective, with even fewer risks. In the future, paracetamol could represent an efficacious first-line therapy, although its safety, optimal dosage, and global impact have to be fully clarified through long-term trials, also in the perspective of an individualized and person-based therapy taking into account the extraordinary individual variability.
Collapse
Affiliation(s)
- Laura Cuzzolin
- a Department of Diagnostics & Public Health-Section of Pharmacology , University of Verona , Verona , Italy
| | - Flamina Bardanzellu
- b Neonatal Intensive Care Unit, Neonatal Pathology and Neonatal Section , AOU and University of Cagliari , Cagliari , Italy
| | - Vassilios Fanos
- b Neonatal Intensive Care Unit, Neonatal Pathology and Neonatal Section , AOU and University of Cagliari , Cagliari , Italy
| |
Collapse
|
|
7
|
El-Farrash RA, El Shimy MS, El-Sakka AS, Ahmed MG, Abdel-Moez DG. Efficacy and safety of oral paracetamol versus oral ibuprofen for closure of patent ductus arteriosus in preterm infants: a randomized controlled trial. J Matern Fetal Neonatal Med 2018; 32:3647-3654. [PMID: 29695206 DOI: 10.1080/14767058.2018.1470235] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Objective: The objective of this study is to evaluate the efficacy and safety of oral paracetamol versus oral ibuprofen in the treatment of hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. Study design: An interventional randomized case-control study, registered in ClinicalTrials.gov (NCT03265782), was conducted on 60 preterm infants with gestational age ≤34 weeks, postnatal age of 2-7 d and color Doppler echocardiographic evidence of hsPDA. Neonates were randomly assigned to two groups: 30 received oral ibuprofen and 30 received oral paracetamol. With failure of ductal closure, a second course of ibuprofen or paracetamol was given. The included newborns were subjected to detailed history, clinical examination, laboratory investigations that included complete blood count, renal, and liver function tests and echocardiographic evaluation. Results: Oral paracetamol was as effective as ibuprofen for the closure of patent ductus arteriosus (PDA) with one course of treatment (p > .05). Moreover, oral paracetamol was superior to ibuprofen among neonates who needed second course of treatment with significant decrease in end diastolic flow velocity in the left pulmonary artery (0.35 ± 0.09 versus 0.19 ± 0.06, p = .014), right ventricular systolic pressure (40.50 ± 12.91 versus 20.50 ± 0.58, p = .016) and left atrium to aortic root ratio (1.23 ± 0.14 versus 1.07 ± 0.04, p = .046) when compared to ibuprofen group. Furthermore, the mean difference between pre- and post-treatment PDA size was significantly higher in the paracetamol group compared with ibuprofen group after the second course of treatment (1.07 ± 0.32 versus 0.73 ± 0.38, p = .024). Oral paracetamol was comparable with ibuprofen in terms of the rate of non-surgical ductal closure [28 (93.3%) versus 24 (80%), p = .591]. In addition, oral paracetamol was as safe as oral ibuprofen in terms of gastrointestinal perforation or bleeding, necrotizing enterocolitis, bronchopulmonary dysplasia, intraventricular hemorrhage, thrombocytopenia, hepatic or renal dysfunction. Conclusions: Oral paracetamol is an effective and well-tolerated first-line drug treatment for PDA in premature infants.
Collapse
Affiliation(s)
- Rania A El-Farrash
- a Department of Pediatrics, Faculty of Medicine , Ain Shams University , Cairo , Egypt
| | - Mohammed S El Shimy
- a Department of Pediatrics, Faculty of Medicine , Ain Shams University , Cairo , Egypt
| | - Abeer S El-Sakka
- a Department of Pediatrics, Faculty of Medicine , Ain Shams University , Cairo , Egypt
| | - Manal G Ahmed
- b Neonatal Intensive Care Unit at the Maternity Hospital , Ain Shams University , Cairo , Egypt
| | - Dina G Abdel-Moez
- b Neonatal Intensive Care Unit at the Maternity Hospital , Ain Shams University , Cairo , Egypt
| |
Collapse
|
|
8
|
Dowd LA, Wheeler BJ, Al-Sallami HS, Broadbent RS, Edmonds LK, Medlicott NJ. Paracetamol treatment for patent ductus arteriosus: practice and attitudes in Australia and New Zealand. J Matern Fetal Neonatal Med 2018; 32:3039-3044. [PMID: 29562792 DOI: 10.1080/14767058.2018.1456520] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Affiliation(s)
- L. A. Dowd
- Otago School of Pharmacy, Otago, New Zealand
| | - B. J. Wheeler
- Department of Women’s and Children’s Health, Dunedin School of Medicine, University of Otago, Otago, New Zealand
| | | | - R. S. Broadbent
- Department of Women’s and Children’s Health, Dunedin School of Medicine, University of Otago, Otago, New Zealand
| | - L. K. Edmonds
- Department of Women’s and Children’s Health, Dunedin School of Medicine, University of Otago, Otago, New Zealand
| | | |
Collapse
|
|
9
|
Valerio E, Valente MR, Salvadori S, Frigo AC, Baraldi E, Lago P. Intravenous paracetamol for PDA closure in the preterm: a single-center experience. Eur J Pediatr 2016; 175:953-66. [PMID: 27146832 DOI: 10.1007/s00431-016-2731-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2015] [Revised: 04/23/2016] [Accepted: 04/28/2016] [Indexed: 12/12/2022]
Abstract
UNLABELLED Increasing recent evidence favors paracetamol use for patent ductus arteriosus (PDA) closure in preterms. Our study aims were (1) to assess efficacy and safety of intravenous (i.v.) paracetamol for PDA closure in a 23-32-week preterm population, as "first-line" (when traditional ibuprofen treatment was contraindicated) or "rescue" treatment (after ibuprofen failed), and (2) to identify predictors of PDA closure. The cumulative efficacy of consecutive cycles of i.v. paracetamol on PDA closure was confirmed after both "first-line" and "rescue" treatment, the overall PDA closure rates being, respectively, 56.7 and 61.1 % (p = 0.7624) after two cycles and 63.3 and 77.8 % (p = 0.2959) after three cycles. No toxicity was apparent after either "first-line" or "rescue" i.v. paracetamol treatment. On multivariate analysis, gestational age (GA) emerged as an independent predictor of PDA closure in the "first-line" i.v. paracetamol treatment group, while clinical risk index for babies (CRIB) score (a patient risk index based on birth weight, GA at birth, sex, patient's temperature on admission, and maximum base excess in first 12 h of life) was an independent predictor of PDA closure failure in the "rescue" group. CONCLUSION I.V. paracetamol proved effective in our study population. Randomized control trials (RCTs) are warranted to further investigate the efficacy and safety of i.v. paracetamol for PDA closure in preterms. WHAT IS KNOWN • Oral paracetamol has been judged as effective as oral ibuprofen for PDA closure in the preterm. • To date, only a handful of non-randomized studies exist to support the effectiveness of i.v. paracetamol in PDA closure. What is New: • Our observations confirm the clinical efficacy of i.v. paracetamol for PDA closure in a very low birth weight (VLBW)/extremely low birth weight (ELBW) preterm population. • Gestational age and CRIB score emerge as independent predictors of PDA closure.
Collapse
Affiliation(s)
- Enrico Valerio
- Neonatal Intensive Care Unit, Department of Woman and Child's Health, University of Padua, Medical School, Via Giustiniani, 3, 35128, Padova, Italy.
| | - Marta Rossella Valente
- Neonatal Intensive Care Unit, Department of Woman and Child's Health, University of Padua, Medical School, Via Giustiniani, 3, 35128, Padova, Italy
| | - Sabrina Salvadori
- Neonatal Intensive Care Unit, Department of Woman and Child's Health, University of Padua, Medical School, Via Giustiniani, 3, 35128, Padova, Italy
| | - Anna Chiara Frigo
- Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Medical School, Padova, Italy
| | - Eugenio Baraldi
- Neonatal Intensive Care Unit, Department of Woman and Child's Health, University of Padua, Medical School, Via Giustiniani, 3, 35128, Padova, Italy
| | - Paola Lago
- Neonatal Intensive Care Unit, Department of Woman and Child's Health, University of Padua, Medical School, Via Giustiniani, 3, 35128, Padova, Italy
| |
Collapse
|
|
10
|
Sivanandan S, Agarwal R. Pharmacological Closure of Patent Ductus Arteriosus: Selecting the Agent and Route of Administration. Paediatr Drugs 2016; 18:123-38. [PMID: 26951240 DOI: 10.1007/s40272-016-0165-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Opinions are divided regarding the management of a persistently patent ductus arteriosus (PDA). Some of the adverse effects associated with a large hemodynamically significant duct, including prolonged ventilation, pulmonary hemorrhage, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), and mortality, indicate that active management of infants with large ductal shunts may sometimes be necessary. Indomethacin and ibuprofen are the two US FDA-approved cyclooxygenase (COX) inhibitors used for the closure of a ductus in preterm babies. Both these drugs are effective in 70-80% of extremely low birthweight infants. Treatment with COX inhibitors may be associated with renal impairment, gastrointestinal hemorrhage, NEC, and spontaneous intestinal perforation when given concurrently with steroids, as well as changes in cerebrovascular auto-regulation. Ibuprofen appears to be a better choice for PDA closure, with a better side effect profile and efficacy that equals that of indomethacin. However, long-term outcome studies of ibuprofen are lacking, and prophylactic ibuprofen is ineffective in decreasing severe IVH. The choice of one drug over the other also depends on local availability of both drugs and the intravenous or enteral preparation. The oral preparation of ibuprofen appears as effective as the intravenous preparation. The use of paracetamol to close a hemodynamically significant PDA has increased in recent years. Paracetamol also decreases prostacyclin synthesis; however, unlike COX inhibitors, it does not have a peripheral vaso-constrictive effect and can be given to infants with contraindications to non-steroidal anti-inflammatory drugs. It appears to have similar efficacy based on limited data available from randomized trials. Until more data are available on efficacy, safety, and long-term outcomes, it cannot be recommended as the first choice.
Collapse
Affiliation(s)
- Sindhu Sivanandan
- Division of Neonatology, Department of Pediatrics (Newborn Health Knowledge Center (NHKC), ICMR Center for Advanced Research in Newborn Health and WHO Collaborating Centre for Newborn Training and Research, New Private Ward-1st Floor, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India
| | - Ramesh Agarwal
- Division of Neonatology, Department of Pediatrics (Newborn Health Knowledge Center (NHKC), ICMR Center for Advanced Research in Newborn Health and WHO Collaborating Centre for Newborn Training and Research, New Private Ward-1st Floor, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
| |
Collapse
|
|
11
|
Sallmon H, Koehne P, Hansmann G. Recent Advances in the Treatment of Preterm Newborn Infants with Patent Ductus Arteriosus. Clin Perinatol 2016; 43:113-29. [PMID: 26876125 DOI: 10.1016/j.clp.2015.11.008] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
A patent ductus arteriosus (PDA) is associated with several adverse clinical conditions. Several strategies for PDA treatment exist, although data regarding the benefits of PDA treatment on outcomes are sparse. Moreover, the optimal treatment strategy for preterm neonates with PDA remains subject to debate. It is still unknown whether and when PDA treatment should be initiated and which approach (conservative, pharmacologic, or surgical) is best for individual patients (tailored therapies). This article reviews the current strategies for PDA treatment with a special focus on recent developments such as oral ibuprofen, high-dose regimens, and the use of paracetamol (oral, intravenous).
Collapse
Affiliation(s)
- Hannes Sallmon
- Department of Neonatology, Charité University Medical Center, Augustenburger Platz 1, Berlin 13353, Germany
| | - Petra Koehne
- Department of Neonatology, Charité University Medical Center, Augustenburger Platz 1, Berlin 13353, Germany
| | - Georg Hansmann
- Department of Pediatric Cardiology and Critical Care, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
| |
Collapse
|
|
12
|
Oncel MY, Erdeve O. Oral medications regarding their safety and efficacy in the management of patent ductus arteriosus. World J Clin Pediatr 2016; 5:75-81. [PMID: 26862505 PMCID: PMC4737696 DOI: 10.5409/wjcp.v5.i1.75] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2015] [Revised: 11/22/2015] [Accepted: 01/07/2016] [Indexed: 02/05/2023] Open
Abstract
Patent ductus arteriosus (PDA) is a common clinical condition in preterm infants which is inversely related to birth weight and gestational age. Cyclooxygenase inhibitors such as indomethacin and ibuprofen which block the prostaglandin conversion from arachidonic acid are the most commonly used drugs for ductal closure. This review focuses on the safety and efficacy oral medications in the management of PDA in preterm infants. Ibuprofen seems to be the first choice due to its higher safety profile, as it is associated with fewer gastrointestinal and renal side effects when compared to indomethacin. PDA closure rates are better with oral than with intravenous ibuprofen probably due to the pharmacokinetic of the drug. However, these medications were reported to be associated with several adverse including transient renal failure, gastrointestinal bleeding and perforation, hyperbilirubinemia and platelet dysfunction. Paracetamol seems be an alternative to PDA therapy with lower adverse events and side effects.
Collapse
|
|
13
|
Intravenous paracetamol with a lower dose is also effective for the treatment of patent ductus arteriosus in pre-term infants. Cardiol Young 2015; 25:1060-4. [PMID: 25160728 DOI: 10.1017/s1047951114001577] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
INTRODUCTION Haemodynamically significant patent ductus arteriosus is a significant cause of morbidity and mortality in pre-term infants. This retrospective study was conducted to investigate the usefulness of lower-dose paracetamol for the treatment of patent ductus arteriosus in pre-term infants. MATERIALS AND METHODS A total of 13 pre-term infants who received intravenous paracetamol because of contrindications or side effects to oral ibuprofen were retrospectively enrolled. In the first patient, the dose regimen was 15 mg/kg/dose, every 6 hours. As the patient developed significant elevation in transaminase levels, the dose was decreased to 10 mg/kg/dose, every 8 hours in the following 12 patients. Echocardiographic examination was conducted daily. In case of closure, it was repeated after 2 days and when needed thereafter in terms of reopening. RESULTS A total of 13 patients received intravenous paracetamol. Median gestational age was 29 weeks ranging from 24 to 31 weeks and birth weight was 950 g ranging from 470 to 1390 g. The median postnatal age at the first intravenous paracetamol dose was 3 days ranging from 2 to 9 days. In 10 of the 13 patients (76.9%), patent ductus arteriosus was closed at the median 2nd day of intravenous paracetamol ranging from 1 to 4 days. When the patient who developed hepatotoxicity was eliminated, the closure rate was found to be 83.3% (10/12). CONCLUSION Intravenous paracetamol may be a useful treatment option for the treatment of patent ductus arteriosus in pre-term infants with contrindication to ibuprofen. In our experience, lower-dose paracetamol is effective in closing the patent ductus arteriosus in 83.3% of the cases.
Collapse
|
|
14
|
Memisoglu A, Alp Ünkar Z, Cetiner N, Akalın F, Ozdemir H, Bilgen HS, Ozek E. Ductal closure with intravenous paracetamol: a new approach to patent ductus arteriosus treatment. J Matern Fetal Neonatal Med 2015; 29:987-90. [PMID: 25781500 DOI: 10.3109/14767058.2015.1029912] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
OBJECTIVES Indomethacin and ibuprofen are commonly used in the treatment of hemodynamically significant patent ductus arteriosus (hsPDA). These drugs are associated with serious adverse events, including gastrointestinal perforation, renal failure and bleeding. The role of paracetamol has been proposed for the treatment of PDA. METHODS We report a series of 11 neonates (birth weight: 415-1580 g; gestational age: 23-30.3 weeks) who were treated with paracetamol for a hsPDA. Neonates with hsPDA were treated with paracetamol in the presence of contraindications to ibuprofen or indomethacin. The condition of significant PDA was defined by the presence of at least one of the following criteria: internal ductal diameter # 1.4 mm/kg body weight, left atrium (LA)-to-aortic (Ao) root ratio > 1.4, unrestrictive pulsatile transductal flow, reverse or absent diastolic flow in the descending aorta along with clinical findings. Intravenous (IV) paracetamol was given at doses 15 mg/kg every 6 h for three days. RESULTS Successful ductal closure was achieved in 10 out of 11 babies (90.9%). No adverse or side effects were observed during the treatment. CONCLUSIONS On the basis of these results, paracetamol could be considered as a promising and safe therapy for the treatment of PDA in preterm infants.
Collapse
Affiliation(s)
| | | | - Nilufer Cetiner
- b Division of Pediatric Cardiology, Department of Pediatrics, Faculty of Medicine , Marmara University , Istanbul , Turkey
| | - Figen Akalın
- b Division of Pediatric Cardiology, Department of Pediatrics, Faculty of Medicine , Marmara University , Istanbul , Turkey
| | | | | | | |
Collapse
|
|
15
|
Limited effects of intravenous paracetamol on patent ductus arteriosus in very low birth weight infants with contraindications for ibuprofen or after ibuprofen failure. Eur J Pediatr 2015; 174:1433-40. [PMID: 25922139 PMCID: PMC4623081 DOI: 10.1007/s00431-015-2541-5] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2015] [Revised: 04/04/2015] [Accepted: 04/08/2015] [Indexed: 11/28/2022]
Abstract
UNLABELLED Finding the optimal pharmacological treatment of a patent ductus arteriosus (PDA) in preterm neonates remains challenging. There is a growing interest in paracetamol as a new drug for PDA closure. In this prospective observational cohort study, we evaluated the effectiveness of intravenous paracetamol in closing a PDA in very low birth weight infants with a hemodynamically significant PDA who either did not respond to ibuprofen or had a contraindication for ibuprofen. They received high-dose paracetamol therapy (15 mg/kg/6 h intravenous) for 3-7 days. Cardiac ultrasounds were performed before and 3 and 7 days after treatment. Thirty-three patients were included with a median gestational age of 25(1/7) weeks (IQR 1.66), a median birth weight of 750 g (IQR 327), and a median postnatal age of 14 days (IQR 12). Paracetamol was ineffective in 27/33 patients (82 %). Even more, after previous exposure to ibuprofen, this was even 100 %. CONCLUSION In this study, paracetamol after ibuprofen treatment failure was not effective for PDA closure in VLBW infants. From the findings of this study, paracetamol treatment for PDA closure cannot be recommended for infants with a postnatal age >2 weeks. Earlier treatment with paracetamol for PDA might be more effective.
Collapse
|
|
16
|
Sancak S, Gokmen Yildirim T, Topcuoglu S, Yavuz T, Karatekin G, Ovali F. Oral versus intravenous paracetamol: which is better in closure of patent ductus arteriosus in very low birth weight infants? J Matern Fetal Neonatal Med 2014; 29:135-9. [PMID: 25471090 DOI: 10.3109/14767058.2014.989829] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
OBJECTIVES To compare the efficacy of oral and intravenous paracetamol for closure of hemodynamically significant patent ductus arteriosus (HSPDA) in very low birth weight (VLBW) preterm infants. METHODS Eighteen VLBW infants with HSPDA treated with either intravenous (n = 10) or oral (n = 8) paracetamol at 60 mg/kg/d for three consecutive days were analysed retrospectively. Ductal closure rate and evaluation of liver function tests were the major outcomes. RESULTS After two courses of treatment, HSPDA closure rate was higher in oral paracetamol group than that in the intravenous paracetamol group (88% versus 70%), but it was not statistically significant (p = 0.588). Liver function tests were normal after the treatment. CONCLUSION Although it was not statistically significant, the cumulative closure rates were higher in oral paracetamol group than those in the intravenous group. Larger trials are needed to confirm these data.
Collapse
Affiliation(s)
| | | | | | - Taner Yavuz
- b Department of Pediatric Cardiology , Zeynep Kamil Maternity and Children's Training and Research Hospital , Istanbul , Turkey
| | | | | |
Collapse
|
|
17
|
Abstract
Objective: To evaluate the literature describing acetaminophen use in treatment of patent ductus arteriosus (PDA). Data Sources: Searches were conducted in MEDLINE with full text (EBSCOhost; 1946 to September 2014) using the search terms acetaminophen, paracetamol, and patent ductus arteriosus. The references of identified articles were reviewed to identify other relevant articles. Study Selection and Data Extraction: Human clinical trials and case reports limited to the English language were reviewed. In all, 12 case reports and 2 randomized, controlled clinical trials explored the use of acetaminophen in treating PDA. Data Synthesis: The case reports described the use of oral or intravenous acetaminophen in patients with contraindications to or who had previously failed nonsteroidal anti-inflammatory drug therapy for PDA. More than 76% of patients achieved successful PDA closure in reported cases. The clinical trials compared the efficacy of oral acetaminophen versus oral ibuprofen in preterm infants. Acetaminophen was noninferior to ibuprofen, with closure rates from 72.5% to 81.2%. The acetaminophen dose used in most case series and trials was 15 mg/kg dose every 6 hours for 3 days. Acetaminophen therapy was well tolerated, with only a few incidents of elevated liver enzymes being reported. Conclusion: Oral acetaminophen is an alternative to PDA therapy in preterm infants when indomethacin/ibuprofen is not effective or is contraindicated, and it may be considered before surgical ligation.
Collapse
Affiliation(s)
- Jennifer Le
- Southwestern Oklahoma State University College of Pharmacy, Weatherford, OK, USA
| | - Mark A. Gales
- Southwestern Oklahoma State University College of Pharmacy, Weatherford, OK, USA
- Integris Baptist Medical Center, Oklahoma City, OK, USA
| | - Barry J. Gales
- Southwestern Oklahoma State University College of Pharmacy, Weatherford, OK, USA
- Integris Baptist Medical Center, Oklahoma City, OK, USA
| |
Collapse
|
|
18
|
El-Khuffash A, Jain A, Corcoran D, Shah PS, Hooper CW, Brown N, Poole SD, Shelton EL, Milne GL, Reese J, McNamara PJ. Efficacy of paracetamol on patent ductus arteriosus closure may be dose dependent: evidence from human and murine studies. Pediatr Res 2014; 76:238-44. [PMID: 24941212 PMCID: PMC4321957 DOI: 10.1038/pr.2014.82] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2013] [Accepted: 02/19/2014] [Indexed: 01/14/2023]
Abstract
BACKGROUND We evaluated the clinical effectiveness of variable courses of paracetamol on patent ductus arteriosus (PDA) closure and examined its effect on the in vitro term and preterm murine ductus arteriosus (DA). METHODS Neonates received one of the following three paracetamol regimens: short course of oral paracetamol (SCOP), long course of oral paracetamol (LCOP), and intravenous paracetamol (IVP) for 2-6 d. Pressure myography was used to examine changes in vasomotor tone of the preterm and term mouse DA in response to paracetamol or indomethacin. Their effect on prostaglandin synthesis by DA explants was measured by mass spectroscopy. RESULTS Twenty-one preterm infants were included. No changes in PDA hemodynamics were seen in SCOP infants (n = 5). The PDA became less significant and eventually closed in six LCOP infants (n = 7). PDA closure was achieved in eight IVP infants (n = 9). On pressure myograph, paracetamol induced a concentration-dependent constriction of the term mouse DA, up to 30% of baseline (P < 0.01), but required >1 µmol/l. Indomethacin induced greater DA constriction and suppression of prostaglandin synthesis (P < 0.05). CONCLUSION The clinical efficacy of paracetamol on PDA closure may depend on the duration of treatment and the mode of administration. Paracetamol is less potent than indomethacin for constriction of the mouse DA in vitro.
Collapse
Affiliation(s)
| | - Amish Jain
- Department of Pediatrics, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - David Corcoran
- Department of Pediatrics, The Rotunda Hospital, Dublin, Ireland
| | - Prakesh S. Shah
- Department of Pediatrics, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Christopher W. Hooper
- Division of Neonatology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Naoko Brown
- Division of Neonatology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Stanley D. Poole
- Division of Neonatology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Elaine L. Shelton
- Division of Neonatology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Ginger L. Milne
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Jeff Reese
- Division of Neonatology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Patrick J. McNamara
- Department of Neonatology, The Hospital for Sick Children, Toronto, Ontario, Canada,Department of Physiology and Experimental Medicine, Hospital for Sick Children, Toronto, Ontario, Canada
| |
Collapse
|
|
19
|
Oral paracetamol versus oral ibuprofen in the management of patent ductus arteriosus in preterm infants: a randomized controlled trial. J Pediatr 2014; 164:510-4.e1. [PMID: 24359938 DOI: 10.1016/j.jpeds.2013.11.008] [Citation(s) in RCA: 133] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2013] [Revised: 10/11/2013] [Accepted: 11/05/2013] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To compare the efficacy and safety of oral paracetamol and oral ibuprofen for the pharmacological closure of patent ductus arteriosus (PDA) in preterm infants. STUDY DESIGN This prospective, randomized, controlled study enrolled 90 preterm infants with gestational age ≤ 30 weeks, birthweight ≤ 1250 g, and postnatal age 48 to 96 hours who had echocardiographically confirmed significant PDA. Each enrolled patient received either oral paracetamol (15 mg/kg every 6 hours for 3 days) or oral ibuprofen (initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 hours). RESULTS Spontaneous closure rate for the entire study group was 54%. After the first course of treatment, the PDA closed in 31 (77.5%) of the patients assigned to the oral ibuprofen group vs 29 (72.5%) of those enrolled in the oral paracetamol group (P = .6). The reopening rate was higher in the paracetamol group than in the ibuprofen group, but the reopening rates were not statistically different (24.1% [7 of 29] vs 16.1% [5 of 31]; P = .43). The cumulative closure rates after the second course of drugs were high in both groups. Only 2 patient (2.5%) in the paracetamol group and 3 patients (5%) in the ibuprofen group required surgical ligation. CONCLUSION This randomized, controlled clinical study compared oral paracetamol with ibuprofen in preterm infants and demonstrated that paracetamol may be a medical alternative in the management of PDA.
Collapse
|
|
20
|
Terrin G, Conte F, Scipione A, Bacchio E, Conti MG, Ferro R, Ventriglia F, De Curtis M. Efficacy of paracetamol for the treatment of patent ductus arteriosus in preterm neonates. Ital J Pediatr 2014; 40:21. [PMID: 24555510 PMCID: PMC3940001 DOI: 10.1186/1824-7288-40-21] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2013] [Accepted: 02/16/2014] [Indexed: 02/06/2023] Open
Abstract
Inhibitors of the cyclo-oxygenase component of prostaglandin-H2 synthetase, namely indomethacin and ibuprofen, are commonly used in the treatment of hemodynamically significant patent ductus arteriosus. These drugs are associated with serious adverse events, including gastrointestinal perforation, renal failure and bleeding. The role of paracetamol, an inhibitor of the peroxidase component of prostaglandin-H2 synthetase, has been proposed for the treatment of patent ductus arteriosus. We report a series of 8 neonates (birth weight: 724 ± 173 g; gestational age: 26 ± 2 weeks) treated with paracetamol for a hemodynamically significant patent ductus arteriosus, because of contraindications to ibuprofen or indomethacin. Successful closure was achieved in 6 out of 8 babies (75%). Median ductal diameter was significantly reduced after treatment (from 1.2 mm, range 1.0-2.5 mm to 0.6 mm, range 0.0-2.5 mm, p = 0.038). No adverse or side effects were observed during treatment. On the basis of these results, paracetamol could be considered a promising and safe therapy for the treatment of patent ductus arteriosus in neonates.
Collapse
Affiliation(s)
- Gianluca Terrin
- Department of Gynecology-Obstetrics and Perinatal Medicine, University "La Sapienza", Viale del Policlinico 155, 00161 Rome, Italy.
| | | | | | | | | | | | | | | |
Collapse
|
|
21
|
Paracetamol therapy for patent ductus arteriosus in premature infants: a chance before surgical ligation. Pediatr Cardiol 2014; 35:276-9. [PMID: 23942783 DOI: 10.1007/s00246-013-0770-9] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2013] [Accepted: 07/25/2013] [Indexed: 10/26/2022]
Abstract
Patent ductus arteriosus (PDA) remains a common problem in premature infants. Treatment options include pharmacologic therapy and surgical ligation, but these are associated with potentially significant adverse effects. This report describes the effect of administering oral paracetamol to premature neonates with PDA. The study enrolled seven premature neonates followed up with the diagnosis of hemodynamically significant PDA (hsPDA) between February and December 2012 and treated with oral paracetamol. Patients with hsPDA were given at least two or more courses of ibuprofen treatment. If this therapy failed to promote ductal closure, the patients with clinical symptoms who had hsPDA defined by echocardiography were treated with oral paracetamol (15 mg/kg every 6 h). If these patients did not respond to paracetamol therapy, the PDA was closed by surgical ligation. The mean gestational age of the seven patients in this study was 26.1 weeks, and their mean birth weight was 936 g. Paracetamol treatment was started at 36.2 ± 11.6 days. The mean internal ductal diameter was 2.0 ± 0.2 mm, and the left atrium-to-aorta ratio was 1.5 ± 0.2. All the patients were administered oral paracetamol because of no response to ibuprofen treatment. The hsPDA was successfully closed with oral paracetamol in five (71.4 %) of the seven patients. The remaining two patients had surgical ligation performed, but one of them died. No side effects related to paracetamol were observed. Oral paracetamol may be used as an alternative drug for the management of hsPDA in premature neonates when ibuprofen treatment is unsuccessful and the only other therapeutic option is surgery.
Collapse
|
|
22
|
Patent ductus arteriosus in preterm infants: do we have the right answers? BIOMED RESEARCH INTERNATIONAL 2013; 2013:676192. [PMID: 24455715 PMCID: PMC3885207 DOI: 10.1155/2013/676192] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/27/2013] [Revised: 09/13/2013] [Accepted: 10/04/2013] [Indexed: 12/20/2022]
Abstract
Patent ductus arteriosus (PDA) is a common clinical condition in preterm infants. Preterm newborns with PDA are at greater risk for several morbidities, including higher rates of bronchopulmonary dysplasia (BPD), decreased perfusion of vital organs, and mortality. Therefore, cyclooxygenase (COX) inhibitors and surgical interventions for ligation of PDA are widely used. However, these interventions were reported to be associated with side effects. In the absence of clear restricted rules for application of these interventions, different strategies are adopted by neonatologists. Three different approaches have been investigated including prophylactic treatment shortly after birth irrespective of the state of PDA, presymptomatic treatment using echocardiography at variable postnatal ages to select infants for treatment prior to the duct becoming clinically significant, and symptomatic treatment once PDA becomes clinically apparent or hemodynamically significant. Future appropriately designed randomized controlled trials (RCTs) to refine selection of patients for medical and surgical treatments should be conducted. Waiting for new evidence, it seems wise to employ available clinical and echocardiographic parameters of a hemodynamically significant (HS) PDA to select patients who are candidates for medical treatment. Surgical ligation of PDA could be used as a back-up tool for those patients who failed medical treatment and continued to have hemodynamic compromise.
Collapse
|
|
23
|
Alan S, Kahvecioglu D, Erdeve O, Atasay B, Arsan S. Is paracetamol a useful treatment for ibuprofen-resistant patent ductus arteriosus? Concerning the article by M.Y. Oncel et al: intravenous paracetamol treatment in the management of patent ductus arteriosus in extremely low birth weight infants [Neonatology 2013;103:166-169]. Neonatology 2013; 104:168-9. [PMID: 23921529 DOI: 10.1159/000352068] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2013] [Accepted: 05/16/2013] [Indexed: 12/20/2022]
Affiliation(s)
- Serdar Alan
- Division of Neonatology, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey
| | | | | | | | | |
Collapse
|