Comparison of standard versus high-dose ibuprofen for the treatment of hemodynamically significant patent ductus arteriosus in preterm infants

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.

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

Journal of Comparative Effectiveness Research ◽

10.2217/cer-2020-0235 ◽

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.

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

Medicni perspektivi (Medical perspectives) ◽

10.26641/2307-0404.2021.1.227960 ◽

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.

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