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

Department of Pediatrics, University of California, San Francisco 94143, USA.
PEDIATRICS (Impact Factor: 5.3). 09/2003; 112(3 Pt 1):583-7. DOI: 10.1542/peds.112.3.583
Source: PubMed

ABSTRACT 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.
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 chi(2) analysis, Fisher's exact test, and the Mann-Whitney rank sum test.
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.
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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Indomethacin has been the mainstay for medical closure of patent ductus arteriosus. With its discontinuation, many units shifted to the use ibuprofen. We compared the therapeutic efficacy (successful closure, a priori defined as complete closure or >50 % reduction in size) and the impact of the two drugs on neonatal morbidities. Two time epochs were analysed (IV indomethacin, January 2008 to November 2010, and IV ibuprofen lysine, November 2010 to September 2013). Demographic, clinical and echocardiographic data was compared. A total of 101 infants formed the study population, 58 (57.4 %, indomethacin epoch) and 43 (42.6 %, ibuprofen epoch). The gestational age, birth weight and postnatal age at initial treatment respectively were comparable [26 ± 1.8 vs 26.5 ± 1.9 weeks, 806 ± 183 vs 862 ± 234 g and median 12 (6, 17) vs 11 days (8, 18)]. Successful closure was significantly higher in the indomethacin group [26 (45 %) vs 6 (14 %), p < 0.01]. The incidence of bronchopulmonary dysplasia (BPD) and discharge in oxygen was comparable. Four infants (all in the ibuprofen group) developed pulmonary hypertension; one required pulmonary vasodilator therapy. Posttreatment serum creatinine was significantly lower in the ibuprofen group. Mortality was higher during the indomethacin epoch. On univariate analysis, the choice of the drug and higher gestational age were associated with successful closure. Conclusion: Indomethacin was more efficacious for ductal closure although did not impact outcomes. Use of staging schema may help understand 'need to treat' and refine therapy.
    European Journal of Pediatrics 10/2014; · 1.98 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Debate about the importance of the preterm patent ductus arteriosus (PDA) remains unresolved. Ultrasound studies of PDA have suggested that the haemodynamic impact may be much earlier after birth than previously thought, but we still do not know when to treat a PDA. Studies that have tested symptomatic or pre-symptomatic treatment are mainly historical and have not tested the effect of no treatment. Prophylactic treatment is the best studied regimen, but improvements in some short-term outcomes do not translate to any difference in longer term outcomes. Neonatologists have been reluctant to engage in trials that test treatment against not treating at all or very rarely. Targeting treatment on the basis of the early post-natal constrictive response of the duct is currently being tested as a possible strategy.
    Journal of Paediatrics and Child Health 09/2012; 48(9):753-8. · 1.19 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Patent ductus arteriosus (PDA) is a common clinical condition in preterm infants. Preterm newborns with PDA are at greater risk for several morbidities, including higher rates of bronchopulmonary dysplasia (BPD), decreased perfusion of vital organs, and mortality. Therefore, cyclooxygenase (COX) inhibitors and surgical interventions for ligation of PDA are widely used. However, these interventions were reported to be associated with side effects. In the absence of clear restricted rules for application of these interventions, different strategies are adopted by neonatologists. Three different approaches have been investigated including prophylactic treatment shortly after birth irrespective of the state of PDA, presymptomatic treatment using echocardiography at variable postnatal ages to select infants for treatment prior to the duct becoming clinically significant, and symptomatic treatment once PDA becomes clinically apparent or hemodynamically significant. Future appropriately designed randomized controlled trials (RCTs) to refine selection of patients for medical and surgical treatments should be conducted. Waiting for new evidence, it seems wise to employ available clinical and echocardiographic parameters of a hemodynamically significant (HS) PDA to select patients who are candidates for medical treatment. Surgical ligation of PDA could be used as a back-up tool for those patients who failed medical treatment and continued to have hemodynamic compromise.
    BioMed research international. 01/2013; 2013:676192.


Available from