Oral COX inhibitors for closure of hemodynamically significant Patent Ductus Arteriosus in Neonates : A retrospective analysis at a tertiary center in central India

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.

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

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-12.3.171 ◽

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.

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PO-0487 Constraining The Need For Ligating A Significant Patent Ductus Arteriosus After Ibuprofen Therapy In Preterms. A Retrospective Analysis From 10/2009–12/2013

Archives of Disease in Childhood ◽

10.1136/archdischild-2014-307384.1132 ◽

2014 ◽

Vol 99 (Suppl 2) ◽

pp. A407.2-A407

Author(s):

S Baumgartner ◽

U Salzer-Muhar ◽

M Steiner ◽

A Berger ◽

M Wald ◽

...

Keyword(s):

Patent Ductus Arteriosus ◽

Retrospective Analysis ◽

Ductus Arteriosus ◽

Patent Ductus

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Clinical Considerations for the Pharmacologic Management of Patent Ductus Arteriosus with Cyclooxygenase Inhibitors in Premature Infants

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-12.3.147 ◽

2007 ◽

Vol 12 (3) ◽

pp. 147-157

Author(s):

Karen E. Corff ◽

Kris C. Sekar

Keyword(s):

Clinical Trials ◽

Blood Flow ◽

Patent Ductus Arteriosus ◽

Premature Infants ◽

Ductus Arteriosus ◽

Arterial Blood Flow ◽

Medical Decision ◽

Cox Inhibitors ◽

Clinical Considerations ◽

Patent Ductus

When medical management is warranted for closure of a persistent patent ductus arteriosus (PDA) in premature infants, treatment with a cyclooxygenase (COX) inhibitor is indicated. Indomethacin, available since 1976, has been the conventional pharmacologic treatment for PDA, but its use is associated with vasoconstrictive effects that impair renal, mesenteric and cerebral blood flow. Intravenous (IV) ibuprofen lysine, approved in the United States in 2006, has less severe vasoconstrictive effects on these vital organs than IV indomethacin. Clinical trials have shown both of these COX inhibitors to be equally effective in closing the PDA in approximately 70%–80% of treated infants, with less vasoconstrictive and adverse renal effects occurring with IV ibuprofen lysine.12 Several clinical considerations are important in the process of medical decision-making when faced with the need for PDA treatment with one of these pharmacologic agents in the premature infant. This paper focuses on these clinical considerations, including cerebral, renal and mesenteric blood flow, renal function, pulmonary effects, protein-binding capacity as it relates to hyperbilirubinemia, and platelet aggregation. No differences in chronic lung disease, pulmonary hypertension, hyperbilirubinemia and coagulopathy were observed in clinical trials when comparing these 2 COX inhibitors; however, significant differences have been observed in arterial blood flow to the cerebral, renal and mesenteric organs, suggesting that IV ibuprofen lysine may be the more favorable agent.

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Pharmacoeconomics of Surgical Interventions vs. Cyclooxygenase Inhibitors for the Treatment of Patent Ductus Arteriosus

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-12.3.183 ◽

2007 ◽

Vol 12 (3) ◽

pp. 183-193

Author(s):

Charles J Turck ◽

Wallace Marsh ◽

James G. Stevenson ◽

John M. York ◽

Henry Miller ◽

...

Keyword(s):

Patent Ductus Arteriosus ◽

Medical Therapy ◽

Resource Use ◽

Ductus Arteriosus ◽

The United States ◽

Best Interests ◽

Cyclooxygenase Inhibitors ◽

Fluid Restriction ◽

Cox Inhibitors ◽

Patent Ductus

Management of neonatal patent ductus arteriosus (PDA) often is resource-intensive and costly. Therefore, it is in hospitals' best interests to ensure the most cost-efficient use of associated resources. Clinical status, comorbidities, and response to prior therapy are considered in selecting the most appropriate intervention for PDA management. Currently, supportive measures (e.g., fluid restriction), surgical ligation, and pharmacologically based medical therapy are the primary treatment modalities for correcting PDA. Medical therapy, which comprises a small percentage (2.0%–5.0%)1 of overall PDA treatment expenses in the United States, consists of either of the 2 intravenous (IV) cyclooxygenase (COX) inhibitors: IV indomethacin and the newly available IV ibuprofen lysine. Although IV COX inhibitors represent a small portion of medical expenses, their benefits appear to be considerable. Pharmacoeconomic studies have evaluated indomethacin's beneficial impact on cost-effectiveness per quality-adjusted life year in PDA prophylaxis; however, no analysis to date prospectively assesses the effect of COX inhibitors on resource use or expenses in treating PDA. Such analysis is desirable and should consider efficacy and safety outcomes, impact on health care resource use and length of stay (LOS), and any differential effects of the agents' safety profiles; notably, IV indomethacin adversely affects renal and mesenteric blood flow and increases serum creatinine and oliguria significantly more than IV ibuprofen. These observations lay the foundation to conduct studies assessing the influence of these differences on resource use, LOS and expenses associated with PDA management.

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Comparison of intravenous Paracetamol with oral Ibuprofen for medical closure of PDA (patent ductus arteriosus) in preterm newborns – can it be an effective, safe and preferable choice?

Pediatric Review International Journal of Pediatric Research ◽

10.17511/ijpr.2021.i01.05 ◽

2021 ◽

Vol 8 (1) ◽

pp. 29-38

Author(s):

Dr. Santosh Kumar Rathia ◽

◽

Dr. Virendra Kumar Kurrey ◽

Dr. Smit Shrivastava ◽

Dr. Ankit Kumar Gupta ◽

...

Keyword(s):

Patent Ductus Arteriosus ◽

Ductus Arteriosus ◽

Central India ◽

Preterm Neonates ◽

Intravenous Route ◽

Closure Rate ◽

Surgical Closure ◽

2D Echocardiography ◽

Oral Ibuprofen ◽

Patent Ductus

Introduction: In prematurely born newborns, the ductus arteriosus frequently fails to close and more than half of preterms might have Patent Ductus Arteriosus (PDA) after birth during the first 24hours. About 70% of infants born before 28 weeks may require medical or surgical closure of PDA. Objectives: To compare the effect of i/v PCM and oral Ibuprofen on PDA closure rate in preterm neonates with a gestational age of > 37 weeks and evaluate the side effect profile of both drugs. Material and Methods: This time-bound prospective observational study for comparison of the efficacy of the two drugs on the closure of PDA in preterms admitted during 1.5 years of the study period in a neonatal ICU caring for inborn as well as outborn neonates in central India. After approval of the institutional ethics committee, initial clinical screening included all preterms but only those with PDA (open ductus arteriosus) confirmed by 2D-echocardiography were allocated to receive either of two treatment regimens (3-day courses of each oral Ibuprofen and i/v PCM) which already exist as evidence-based therapeutic practice options. Result: Out of a total of 43 cases clinically suspected on initial screening, 30 preterm babies confirmed by 2D-Echo to have PDA were finally enrolled and analysed. Twenty-one patients received i/v PCM with a resultant PDA closure rate of 85.7 % (n = 18/21), while nine cases could be allocated oral Ibuprofen arm and ductus closure was obtained in seven patients (77.78%). Although the PDA closure rate between two drug regimens was not statistically significant (p=0.593), i/v PCM resulted in slightly higher efficacy and fewer adverse effects. Conclusion: Paracetamol, preferably by the intravenous route, seems to be an effective, cheap, easily available and safe first-line alternative to oral Ibuprofen for the closure of PDA, especially in newborns with extreme prematurity, who are initially intolerant to oral feeds or drugs.

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