High Dose Indomethacin for Patent Ductus Arteriosus Closure Increases Neonatal Morbidity

2019 ◽  
Author(s):  
Salome Waldvogel ◽  
Andrew Atkinson ◽  
Mélanie Wilbeaux ◽  
Mathias Nelle ◽  
Markus R. Berger ◽  
...  
Keyword(s):  
Patent Ductus Arteriosus ◽  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Standard Dose ◽  
Ductus Arteriosus ◽  
Treatment Options ◽  
Univariate Analysis ◽  
High Dose ◽  
Closure Rate ◽  
Patent Ductus

Abstract Objective Symptomatic patent ductus arteriosus (sPDA) is the most common heart abnormality in preterm infants. Optimal duration and dose of medical treatment is still unclear. We assessed undesired effects and closure rate of high-dose indomethacin (HDI) for pharmacological closure of sPDA. Study Design Retrospective single center analysis of 248 preterm infants born between January 2006 and December 2015 with a birth weight <2,000 g and sPDA which was treated with indomethacin. Patients were treated with either standard dose indomethacin (SDI; n = 196) or HDI (n = 52). Undesired effects and PDA closure were compared between patients treated with SDI and HDI. Results In univariate analysis, patients receiving HDI had a significant increase in gastrointestinal hemorrhage (32.7 vs.11.7%, p = 0.001), bronchopulmonary dysplasia (BPD) (77.8 vs. 55.1%, p = 0.003), and retinopathy of prematurity (13.5 vs. 2.6%, p = 0.004). Moreover, HDI patients needed longer mechanical ventilation (2.5 vs. 1.0 days, p = 0.01). Multivariate analyses indicated that necrotizing enterocolitis (17 vs. 7%, p = 0.01) and BPD (79 vs. 55%, p = 0.02) were more frequent in HDI patients. PDA closure rate was 79.0% with HDI versus 65.3% with SDI. Conclusion HDI used for PDA closure is associated with an increase in necrotizing enterocolitis and BPD. Risks of HDI should be balanced against other treatment options.

scholarly journals Effect of ibuprofen for hemodynamically significant patent ductus arteriosus closure on the development of acute kidney injury in preterm infants

2021 ◽  
Vol 26 (1) ◽  
pp. 156-162
Author(s):  
T.P. Borysova ◽  
O.Yu. Obolonska
Keyword(s):  
Acute Kidney Injury ◽  
Patent Ductus Arteriosus ◽  
Preterm Infants ◽  
Standard Dose ◽  
Ductus Arteriosus ◽  
Kidney Injury ◽  
High Dose ◽  
The Third ◽  
Renal Hypoperfusion ◽  
Patent Ductus

Premature infants with hemodynamically significant patent ductus arteriosus (HSPDA) have a high risk of developing acute kidney injury (AKI) due to renal hypoperfusion and use of ibuprofen for duct closure. The aim of the study was to evaluate the effect of ibuprofen for the closure of HSPDA on the development of AKI in preterm infants depending on high dose of the drug on the first day of life. 40 preterm infants with HSPDA who were admitted for observation on the first day of life were examined. To close the ductus arteriosus, infants received restrictive therapy. In addition, 32 (80,0%) preterm infants on the first day of life were prescribed ibuprofen: 19 infants – in high dose (20 mg/kg), 13 infants – in standard dose (10 mg/kg). Clinical examination and treatment of preterm infants was carried out according to the generally accepted methods. Echocardiography with Doppler was performed at 5-11 hours of life and then daily to determine the size and hemodynamic significance of patent ductus arteriosus. Diagnosis and stratification of the severity of AKI were performed according to the criteria of neonatal modification of KDIGO, for which the concentration of serum creatinine and diuresis were studied. According to the results of the study, it was established that the frequency of AKI on the third and fifth days of life in preterm infants with HSPDA, who received ibuprofen in a high dose (20 mg/kg) on the first day, was 73.7% and 84.2%, respectively, which is 2.2 (OR=5.6; CI: 1,43-21,95; р<0.02) and 2.5 (OR=10.67; CI: 2.31-49.31; р<0.002) times, more often than in infants without such therapy. High dose of ibuprofen on the first day of life in preterm infants with HSPDA are most often associated with the development of stage I AKI on the third or fifth day of life, which was temporary in one third of patients. The use of a high-dose ibuprofen for HSPDA closure on the first day of life in preterm infants was significantly more often associated with foci of infection in the mother, large duct size and furosemide use.

scholarly journals Conservative Non-intervention Approach for Hemodynamically Significant Patent Ductus Arteriosus in Extremely Preterm Infants

2020 ◽  
Vol 8 ◽  
Author(s):  
Se In Sung ◽  
Yun Sil Chang ◽  
So Yoon Ahn ◽  
Heui Seung Jo ◽  
Misun Yang ◽  
...  
Keyword(s):  
Patent Ductus Arteriosus ◽  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Ductus Arteriosus ◽  
Intervention Approach ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Surgical Treatments ◽  
Minimal Evidence ◽  
Patent Ductus

While persistent patent ductus arteriosus (PDA) in preterm infants has been known to be associated with increased mortality and morbidities including bronchopulmonary dysplasia, and necrotizing enterocolitis, there is minimal evidence supporting their causal relationships, and most traditional medical and/or surgical treatments have failed to show improvements in these outcomes. As such, the pendulum has swung toward the conservative non-intervention approach for the management of persistent PDA during the last decade; however, the benefits and risks of this approach are unclear. In this mini review, we focused on whom, when, and how to apply the conservative non-intervention approach for persistent PDA, especially in extremely preterm infants.

Clinical Pharmacology of Ibuprofen and Indomethacin in Preterm Infants with Patent Ductus Arteriosus

2014 ◽  
Vol 10 (3) ◽  
pp. 216-237 ◽  
Author(s):  
Gian Maria Pacifici
Keyword(s):  
Patent Ductus Arteriosus ◽  
Serum Creatinine ◽  
Prostaglandin E2 ◽  
Preterm Infants ◽  
Gestational Age ◽  
Urine Output ◽  
Ductus Arteriosus ◽  
Closure Rate ◽  
Term Infants ◽  
Patent Ductus

Background: Ibuprofen and indomethacin are potent non-selective cyclo-oxygenase inhibitors and inhibit prostaglandin E2 synthesis. The patent ductus arteriosus (PDA) occurs in more than 70% of preterm infants weighing <1500 g. Prostaglandin E2 relaxes smooth muscle, tends to inhibit the closure of PDA, yields vasodilatation of the afferent renal arterioles and maintains glomerular filtration rate (GFR). Ibuprofen and indomethacin inhibiting prostaglandin E2 synthesis close PDA and reduce GFR with consequent decrease of urine output and increase of serum creatinine concentrations. Aims: The aims of this study are to give the definitive estimates of PDA closure rate following ibuprofen or indomethacin treatment and to evaluate the extent of renal side effects following the administration of these drugs to preterm infants. Other aims are to review the metabolism and the pharmacokinetics of ibuprofen and indomethacin in preterm infants with PDA. Methods: The bibliographic search was performed using PubMed and EMBASE databases as search engines, January 2013 was the cutoff point. Results: The %PDA closed by ibuprofen (n=24) and indomethacin (n=24) is 77.7±14.1 and 77.3±11.0, respectively. For ibuprofen, the gestational age of the infants included in the study ranged from 25.0 to 39.0 weeks (mean±SD=29.3±3.1 weeks). The %PDA did not correlate with the gestational age (p=0.2516). For indomethacin, the gestational age of infants included in the study ranged from 25.0 and 39.0 weeks (mean±SD=29.4±2.9 weeks). The %PDA did not correlate with the gestational age (p=0.3742). The treatment with ibuprofen reduces the urine output and increases the serum creatinine concentrations less extensively than indomethacin. The half-life (t1/2) of ibuprofen and indomethacin is lengthened and the clearance is reduced in preterm infants as compared with fullterm infants. Conclusions. Ibuprofen and indomethacin are equally effective in closing PDA. Treatment with ibuprofen decreases the risk of renal failure. Ibuprofen has the most favourable risk/benefit ratio. The rate of metabolism is reduced and t1/2 is lengthened in prematures as compared with term infants.

scholarly journals Clinical Experience with Intravenous Ibuprofen Lysine in the Pharmacologic Closure of Patent Ductus Arteriosus

2007 ◽  
Vol 12 (3) ◽  
pp. 171-182
Author(s):  
Evelyn R. Hermes-DeSantis ◽  
Jacob V. Aranda
Keyword(s):  
Clinical Trials ◽  
Patent Ductus Arteriosus ◽  
Ductus Arteriosus ◽  
Treatment Options ◽  
Pharmacologic Therapy ◽  
Low Birth Weight Infants ◽  
Closure Rate ◽  
Cox Inhibitors ◽  
Negative Side Effects ◽  
Patent Ductus

Patent ductus arteriosus (PDA) is the failure of the ductus that arises from the distal dorsal aortic arch to close during the first few days of life. The treatment options for PDA include “watchful waiting,” pharmacologic therapy with cyclooxygenase (COX) inhibitors (COX-1 and COX-2), such as indomethacin or intravenous (IV) ibuprofen lysine, and surgery when medical interventions have proved ineffective. The clinical trials evaluating the utilization of IV ibuprofen lysine focus on either preventing the persistence of a PDA or treating the PDA in premature infants in whom the ductus does not close within 48 hours of birth. Although the role of COX inhibitors in prophylaxis of PDA has been studied, it has not been clearly delineated. Treatment of PDA in preterm low birth weight infants from the second day of life on with IV ibuprofen lysine has been studied in 4 major and 3 smaller clinical trials. Overall, in 7 studies with 492 patients, the closure rate of PDA was 75.1% with IV ibuprofen lysine compared to 73.5% with indomethacin. In addition, neonates treated with IV ibuprofen lysine had significantly better creatinine clearance, urine output, serum creatinine, and blood urea nitrogen (BUN) profiles than indomethacin-treated patients. Overall, IV ibuprofen lysine is as effective as indomethacin for closure of PDA, yet is associated with a better safety profile with fewer negative side effects when compared to indomethacin.

Use of ibuprofen for the closure of patent ductus arteriosus in preterm infants: a systematic review of meta-analyses

2021 ◽  
Author(s):  
Samaher Al-Shaibi ◽  
Dina Abushanab ◽  
Eilan Alhersh ◽  
Rasha Kaddoura ◽  
Abdul Rouf Pallivalappila ◽  
...  
Keyword(s):  
Systematic Review ◽  
Patent Ductus Arteriosus ◽  
Preterm Infants ◽  
Ductus Arteriosus ◽  
Dosage Forms ◽  
Risk Of Bias ◽  
High Dose ◽  
Oral Ibuprofen ◽  
Meta Analyses ◽  
Patent Ductus

Aim: To systematically review ibuprofen, including versus indomethacin and paracetamol/acetaminophen, for the closure of patent ductus arteriosus (PDA). Methods: Pubmed, Embase, Cochrane and gray literature were searched to summarize ibuprofen outcomes in closure of PDA in published meta-analyses (MAs). Results: Seven MAs were included. Including high dose (HD) use, ibuprofen is equivalent/superior to indomethacin, and inferior/equivalent to paracetamol. Oral ibuprofen had higher efficacy than IV ibuprofen, including compared with indomethacin and paracetamol. Ibuprofen had safety advantages over indomethacin. Indomethacin and paracetamol had safety advantages over IV ibuprofen. HD of ibuprofen increases efficacy, but not toxicity. Conclusion: Evidence on ibuprofen effectiveness and safety, including the dosage forms, is limited by heterogeneity in doses and the levels of methods quality and risk of bias.

The Effect of Oral High-dose Ibuprofen on Patent Ductus Arteriosus Closure in Preterm Infants

2015 ◽  
Vol 32 (12) ◽  
pp. 1158-1163 ◽  
Author(s):  
Shahnaz Pourarian ◽  
Sirous Cheriki ◽  
Hamid Amoozgar ◽  
Faranak Takmil
Keyword(s):  
Patent Ductus Arteriosus ◽  
Preterm Infants ◽  
Ductus Arteriosus ◽  
High Dose ◽  
Patent Ductus Arteriosus Closure ◽  
Patent Ductus

Adding Paracetamol to Ibuprofen for the Treatment of Patent Ductus Arteriosus in Preterm Infants: A Double-Blind, Randomized, Placebo-Controlled Pilot Study

2018 ◽  
Vol 35 (13) ◽  
pp. 1319-1325 ◽  
Author(s):  
Gur Mainzer ◽  
Liron Borenstein-Levin ◽  
Huda Jubran ◽  
Gil Dinur ◽  
Meirav Zucker ◽  
...  
Keyword(s):  
Pilot Study ◽  
Patent Ductus Arteriosus ◽  
Preterm Infants ◽  
Ductus Arteriosus ◽  
Closure Rate ◽  
Double Blind ◽  
Positive Tendency ◽  
Postmenstrual Age ◽  
Intravenous Ibuprofen ◽  
Patent Ductus

Objective The objective of this study was to compare the closure rate of hemodynamically significant patent ductus arteriosus (hsPDA) of intravenous ibuprofen + paracetamol (acetaminophen) versus ibuprofen + placebo, in preterm infants of 24 to 316/7 weeks postmenstrual age. Study Design This is a single-center, double-blind, randomized controlled pilot study. Infants were assigned for treatment with either intravenous ibuprofen + paracetamol (n = 12) or ibuprofen + placebo (n = 12). Results There was no statistical difference in baseline characteristics of the two groups. Echocardiography parameters were comparable before treatment in both groups. There was a trend toward higher hsPDA closure rate in the paracetamol group in comparison to the placebo group (83 vs. 42%, p = 0.08). No adverse effects, clinical or laboratory, were associated with adding paracetamol. Conclusion Our pilot study was unable to detect a beneficial effect by adding intravenous paracetamol to ibuprofen for the treatment of hsPDA. Larger prospective studies are needed to explore the positive tendency suggested by our results and to assure safety.

Sign in / Sign up

Export Citation Format

Share Document