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Closure of a Patent Foramen Ovale (PFO): An Intervention Sequence
Published on: December 23, 2022
Increased indomethacin dosing for persistent patent ductus arteriosus in preterm infants: a multicenter, randomized,
Priya Jegatheesan1, Vlad Ianus, Basharat Buchh
1Cardiovascular Research Institute and Department of Pediatrics, University of California, San Francisco, California 94143-0544, USA.
Insights
Higher doses of indomethacin did not improve patent ductus arteriosus (PDA) closure rates in premature infants. This approach increased risks of retinopathy of prematurity (ROP) and kidney problems.
Area of Science:
- Neonatal Medicine
- Pediatric Cardiology
- Pharmacology
Background:
- Patent ductus arteriosus (PDA) is common in premature infants.
- Conventional indomethacin doses may not always achieve ductal closure.
- Optimizing indomethacin therapy is crucial for neonatal outcomes.
Purpose of the Study:
- To evaluate if higher-dose indomethacin improves PDA closure rates.
- To assess the safety and efficacy of escalated indomethacin dosing in neonates.
Main Methods:
- A multicenter, randomized controlled trial was conducted.
- 105 infants (<28 weeks gestation) with persistent PDA received either low-dose or higher-dose indomethacin.
- Echocardiograms assessed ductal patency before and after treatment.
Main Results:
- Higher indomethacin doses did not significantly increase PDA closure rates (52% vs. 45%).
- The higher-dose group showed increased rates of renal compromise (serum creatinine >2 mg/100 mL).
- Moderate/severe retinopathy of prematurity (ROP) was significantly higher in the higher-dose group (15% vs. 36%).
Conclusions:
- Elevated indomethacin concentrations offer minimal benefit for PDA closure.
- Higher doses are linked to increased risks of ROP and renal dysfunction in premature infants.
- Conventional indomethacin dosing appears safer for managing PDA in this population.
Objective:
We conducted a multicenter, randomized, controlled trial to determine whether higher doses of indomethacin would improve the rate of patent ductus arteriosus (PDA) closure.
Study Design:
Infants (<28 weeks gestation) who received a conventional, prophylactic 3-dose course of indomethacin were eligible if they had continued evidence of persistent ductus patency on an echocardiogram obtained before the third prophylactic indomethacin dose. Infants (n = 105) were randomized to receive an extended 3-day course of either low-dose (0.1 mg/kg/d) or higher-dose (0.2 or 0.5 mg/kg/d) indomethacin. An echocardiogram was obtained 24 hours after the last dose of study drug.
Results:
Despite increasing serum indomethacin concentrations by 2.9-fold in the higher-dose group, we failed to detect a significant decrease in the rate of persistent PDA (low = 52%; higher = 45%, P = .50). The higher-dose group had a significantly higher occurrence of serum creatinine >2 mg/100 mL (low = 6%, higher = 19%, P < .05) and moderate/severe retinopathy of prematurity (ROP) (low = 15%, higher = 36%, P < .025). The incidence of moderate/severe ROP was directly related to the poststudy indomethacin concentrations (odds ratio = 1.75, confidence interval: 1.15-2.68, P < .01).
Conclusion:
Increasing indomethacin concentrations above the levels achieved with a conventional dosing regimen had little effect on the rate of PDA closure but was associated with higher rates of moderate/severe ROP and renal compromise.
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