Persistent Doppler flow predicts lack of response to multiple courses of indomethacin in premature infants with recurrent patent ductus arteriosus

7Objective. Although indomethacin produces ductus arteriosus constriction in extremely premature newborns, a recurrent symptomatic patent ductus arteriosus (PDA) frequently develops after the initial course of indomethacin. Currently, there is little information available to determine the effectiveness of a second course of indomethacin in producing permanent ductus closure. The objective of this study was to determine the rate of permanent ductus closure after a second course of indomethacin for a recurrent, symptomatic PDA and to identify the factors associated with permanent ductus closure. Methods. We identified 32 infants (< 28 weeks' gestational age) 1) whose ductus was considered to be clinically closed after an initial course of indomethacin and 2) who subsequently developed a symptomatic PDA and received a second course of indomethacin. Clinical variables were evaluated for their association with failure of the second course (defined as surgical ligation after the second course for recurrence of a hemodynamically significant PDA). Data were analyzed by χ(2) analysis, Fisher's exact test, and the Mann-Whitney rank sum test. Results. After the second course of indomethacin, 56% (18 of 32) of the infants had persistent or recurrent PDA-related symptoms that were considered to be hemodynamically significant. The only significant predictor of failure of the second indomethacin course was the demonstration (by Doppler echocardiogram) of persistent ductus flow within 24 hours of completing the initial indomethacin course. All of the 9 newborns with persistent Doppler ductus flow after the initial indomethacin course failed the second course of indomethacin. In contrast, only 39% (9 of 23) of newborns with absent Doppler flow after the initial indomethacin course failed the second course of indomethacin. Conclusions. Newborns who are <28 weeks' gestational age and develop a recurrent, symptomatic PDA after completion of an initial indomethacin course rarely respond to multiple courses of indomethacin if there was persistent Doppler evidence of ductus flow after completion of the initial course. Additional indomethacin treatment is unlikely to produce permanent ductus closure.