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Is indomethacin or ibuprofen better for medical closure of the patent ductus arteriosus?
  1. Erik N Swartz
  1. Assistant Professor, Department of Pediatrics, University of Alberta, Edmonton, Canada; erikswartzcha.ak.ca

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A preterm baby of 28 weeks gestation with respiratory distress syndrome is admitted to the neonatal intensive care unit. On day 2 of life, the characteristic murmur of a patent ductus arteriosus (PDA) is heard, with the diagnosis confirmed by Doppler echocardiography. The attending neonatologist orders a course of indomethacin in an attempt to treat the PDA. The astute paediatric resident has just taken two tablets of ibuprofen to treat his post-call headache, and wonders whether this alternative non-steroidal anti-inflammatory drug might be just as efficacious, with less side effects.

Structured clinical question

In a preterm baby of gestational age less than or equal to 34 weeks [patient] is ibuprofen [intervention] compared with indomethacin [comparison intervention] equally efficacious at treating echocardiographically proven patent ductus arteriosus and have fewer side effects [outcomes]?

Search strategy and outcome

Search engine—Cochrane library: “ductus arteriosus, patent” and “indomethacin” and “ibuprofen” (MeSH-Terms); PubMed: “ductus arteriosus, patent” and “indomethacin” and “ibuprofen” (MeSH-Terms) limit to clinical trial.

Search results—two systematic reviews: nil relevant. Two protocols for a Cochrane review: one relevant. Nine clinical studies found, four of which were relevant. See table 1.

Table 1

Ibuprofen versus indomethacin in the treatment of patent ductus arteriosus (PDA)

Commentary

All four studies were randomised, controlled trials; however, the methods of randomisation were not reported. All used cards in sealed envelopes as the system of allocation concealment. Furthermore, there is no evidence that neonatologists, nurses, or pharmacists were blinded in any study. Echocardiographers were blinded in two of the studies.

Each study clearly shows the equivalence of ibuprofen and indomethacin in the treatment of patent ductus arteriosus. In addition, three studies showed a significant increase in oliguria among patients treated with intravenous indomethacin, and two studies showed a significant increase in serum creatinine. No study showed a difference in death, necrotising enterocolitis, or progression of intracranial haemorrhage between the two groups. All trials used a “high” dose of 0.2 mg/kg every 12 hours for three days, as opposed to the “low” dose of 0.1 mg/kg daily for six days.

Clinical bottom line

  • Intravenous ibuprofen is equivalent to intravenous indomethacin in the treatment of PDA in neonates.

  • Patients receiving intravenous ibuprofen have a smaller rise in serum creatinine, and are less likely to develop oliguria (NNT  =  6) than those receiving intravenous indomethacin.

The recent Thai study attempts to compare oral ibuprofen with indomethacin; however, analysis is very difficult as patients in the indomethacin group received the drug by different routes of administration (some oral, some intravenous). Further trials with oral ibuprofen would be very helpful, especially for clinicians in countries where this is the only form of the drug available. Unfortunately, the intravenous preparation of ibuprofen is not easily available in North America.

REFERENCES

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  • Publisher Correction

    Please note that the email address for the author is publisher incorrectly in the online Full text and abstract pages.

    The correct email address is shown here:
    erikswartz{at}cha.ab.ca

    The error is much regretted.

    Footnotes

    • Bob Phillips

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