Let's not increase the indomethacin dose for PDA

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A major advance in neonatology was the demonstration in the late 1970s that indomethacin would close the PDA of the preterm infant. The problem in 2008 is that indomethacin is not as effective in the very preterm infants as in larger infants. A concern has been that the dose may be inadequate because of an increased volume for distribution of indomethacin in very preterm infants. Higher doses and longer durations of treatment are being used without validation. In this issue of The Journal, Jegatheesan et al report a careful study comparing the efficacy and safety of a higher dose of indomethacin for infants whose PDA did not close with conventional doses. The results of this study are definitive—a higher dose of indomethacin results in higher plasma indomethacin levels but no better closure of the PDA than continuing the standard dose. Further, the higher dose resulted in higher plasma creatinine levels (impaired kidney function) and an increased incidence of retinopathy of prematurity. Yet again, more is not better for the preterm infant.