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High Dose Indomethacin for Patent Ductus Arteriosus Closure Increases Neonatal Morbidity
Salome Waldvogel1,2, Andrew Atkinson3,4, Mélanie Wilbeaux3
1Department of Neonatology, University Children's Hospital Basel UKBB, University of Basel, Basel, Switzerland.
Insights
High-dose indomethacin (HDI) for symptomatic patent ductus arteriosus (sPDA) in preterm infants increased risks of necrotizing enterocolitis and bronchopulmonary dysplasia. These risks must be weighed against potential benefits when considering treatment options.
Area of Science:
- Neonatal Medicine
- Pediatric Cardiology
- Pharmacology
Background:
- Symptomatic patent ductus arteriosus (sPDA) is a common heart issue in preterm infants.
- The optimal medical treatment for sPDA, including dose and duration, remains unclear.
- Indomethacin is a common pharmacological agent used for sPDA closure.
Purpose of the Study:
- To assess the closure rate and undesired effects of high-dose indomethacin (HDI) compared to standard-dose indomethacin (SDI) for the pharmacological closure of sPDA in preterm infants.
Main Methods:
- A retrospective single-center analysis was conducted on 248 preterm infants with sPDA.
- Infants were treated with either SDI (n=196) or HDI (n=52).
- Outcomes, including undesired effects and PDA closure rates, were compared between the two treatment groups.
Main Results:
- Patients receiving HDI showed significantly higher rates of gastrointestinal hemorrhage, bronchopulmonary dysplasia (BPD), and retinopathy of prematurity.
- HDI treatment was associated with longer durations of mechanical ventilation.
- Multivariate analyses confirmed increased risks of necrotizing enterocolitis and BPD in the HDI group, despite a higher PDA closure rate (79.0% with HDI vs. 65.3% with SDI).
Conclusions:
- High-dose indomethacin (HDI) for sPDA closure is linked to increased incidences of necrotizing enterocolitis and BPD in preterm infants.
- The potential risks associated with HDI should be carefully considered and balanced against alternative treatment strategies for sPDA.
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.
