Elsevier

The Journal of Pediatrics

Volume 155, Issue 6, December 2009, Pages 819-822.e1
The Journal of Pediatrics

Original Article
Duration of Indomethacin Treatment of the Preterm Patent Ductus Arteriosus as Directed by Echocardiography

https://doi.org/10.1016/j.jpeds.2009.06.013Get rights and content

Objective

To determine whether the duration of indomethacin administration could be shortened in infants with good early constrictive response of patent ductus arteriosus (PDA).

Study design

Infants born at < 30 weeks' gestational age were assessed with echocardiography in the first 12 hours of life and treated with indomethacin (0.1 mg/kg) if the PDA was > 2 mm in diameter. Randomization occurred before the second dose to either standard treatment (2 more doses of indomethacin at 0.1 mg/kg irrespective of echocardiographic findings) or to echocardiographically directed duration of indomethacin treatment (ECHO; further doses only if the PDA was >1.6 mm). Serial echocardiography was performed to day 28 of age. The primary outcome was failure of PDA closure.

Results

The infants were randomized to either the ECHO arm (n = 34) or the standard treatment arm (n = 40). No differences between the arms were seen in terms of failure of PDA closure, PDA reopening, need for further doses of indomethacin, or need for surgical ligation. More doses of indomethacin were given in the standard treatment arm (median, 3 doses [range, 1 to 12] vs 1 dose [range, 1 to 15]; P < .0001).

Conclusion

Echocardiographically directed duration of indomethacin treatment is effective in achieving PDA closure and offers the potential for dose minimization.

Section snippets

Methods

This study was conducted at a tertiary referral neonatal intensive care unit at Royal Prince Alfred Hospital, Sydney, Australia between 2003 and 2007. The study design was approved by the Human Research Ethics Committee of the Sydney South Area Health Service. Written informed parental consent was obtained before study commencement. Infants born before 30 weeks of gestational age (GA) and requiring respiratory support were eligible. In each infant, an echocardiogram was performed between 3 and

Results

We recruited 74 infants into the study between January 1, 2003 and June 30, 2007 (Figure 1; available at www.jpeds.com). Of 318 infants born before 30 weeks GA admitted to the nursery during this time period, 148 were eligible for the study, 138 either did not have a significant duct (< 2 mm) or had a closed duct, 72 were not approached, and 2 refused consent. During 2005, the study was suspended because there was no primary researcher on site. One infant was randomized to the standard treatment

Discussion

This study has shown that by tailoring the duration of indomethacin treatment to the ductal constrictive response 24hours after the first dose, it is possible to significantly reduce the exposure to the drug without affecting eventual successful closure rates. Empirically, this strategy for dose minimization would allow therapy for ductal closure to at a reduced risk of side effects. Our data are consistent with those reported by Su et al,6 who used the Doppler pattern of flow through the

References (7)

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Cited by (63)

  • Point of care ultrasound in the neonatal unit: Applications, training and accreditation

    2019, Early Human Development
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    Superiority of ultrasound when compared with clinical examination for PDA diagnosis is well established, with clinical parameters preceded by echocardiographic markers of haemodynamic significance by approximately 2 days [10]. More importantly, CPU is useful in identifying the subset of patients most likely to benefit from treatment, and has also been used serially to guide duration of treatment with indomethacin for hsPDA [11]. Assessment of the PDA using ultrasound includes: confirmation there are no overt signs of abnormal cardiac anatomy requiring cardiologist consultation, estimation of the size, shunt volume and direction and haemodynamic effects of the PDA (so-called ‘haemodynamic significance’) [12] as well as prediction of the likelihood of spontaneous closure.

  • Efficacy and safety of pharmacological treatments for patent ductus arteriosus closure: A systematic review and network meta-analysis of clinical trials and observational studies

    2019, Pharmacological Research
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    With respect to intervention, 8292 subjects received indomethacin, 4761 ibuprofen, 574 acetaminophen, and 941 control, including placebo or no intervention. 30 RCTs were judged at high risk of performance bias [15–18,20,21,25–28,30,31,35,39,42,44,45,47,48,53,57,59–62,64,70,73,74,77], 11 at high risk of attrition bias [15,22,23,31,35,44,54,56,60,62,69], 12 at high risk of detection bias [18,21,26–28,48,53,57,61,70,73,74], and three at high risk of selection bias (either considering randomization or allocation) [52,54,55] (Appendix 4 and Appendix 5). Nineteen studies were at high risk of bias in at least two items, 27 were at low/unclear risk of bias in all items, and two studies had low risk of bias in all items.

  • Role of neonatologist-performed echocardiography in the assessment and management of patent ductus arteriosus physiology in the newborn

    2018, Seminars in Fetal and Neonatal Medicine
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    Only those patients who remained with a ductal diameter of >1.6 mm received an additional dose. Adopting this policy, the exposure to indomethacin could be reduced from a median of three doses to only one dose, without any concomitant increase in the incidence of closure failure, ductal reopening, surgical ligation, or clinical outcomes, such as pulmonary haemorrhage, bronchopulmonary dysplasia, necrotising enterocolitis, or renal failure [27]. In another randomised controlled pilot study, the benefit of echocardiographically guided ibuprofen treatment was analysed in preterm neonates born at a gestational age between 24 and 34 weeks [28].

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The authors declare no conflicts of interest.

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