Published online May 1, 2006
PEDIATRICS Vol. 117 No. 5 May 2006, pp. 1863-1864 (doi:10.1542/peds.2006-0133)
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High-Dose Indomethacin for Patent Ductus Arteriosus Closure: How Strong Is the Evidence?: In Reply

Markus Sperandio, MD
Bernd Beedgen, MD
Otwin Linderkamp, MD
Division of Neonatal Medicine
Department of Pediatrics
University of Heidelberg
69120 Heidelberg, Germany

In Reply.—

We appreciate Dr Manzar's comments on our high-dose indomethacin treatment strategy for the closure of symptomatic patent ductus arteriosus (sPDA) in premature infants1 and thank the editor for the opportunity to reply. Our initial rationale for treating infants suffering from sPDA with high doses of indomethacin was based less on reports that overdosages of indomethacin did not lead to severe adverse effects and more on the opportunity to closely follow-up on adverse effects and on the treatment success (measured by daily echocardiography). In addition, it has to be emphasized that our strategy does not consist of a high-dose approach per se. High doses of the drug were used only in those infants who had insufficient closure of the duct during standard treatment. This resulted in a surprisingly low number of infants who actually received high doses of the drug. We have to admit (having the Western Australian report on spontaneous ductal closure in mind2) that our approach may include indomethacin-treated infants who otherwise would have recovered by spontaneous closure of the ductus. However, in view of the serious complications that may develop in infants with untreated sPDA, we prefer to start early treatment in all premature infants suffering from sPDA. We do not treat prophylactically.

From the nonresponders we have learned that a prolonged low-dose indomethacin treatment strategy did not lead to appreciable echocardiographic changes, which we attribute to an insufficient rise in serum indomethacin levels, which most likely does not exceed the threshold level necessary to induce ductal closure.

We agree with Dr Manzar that close monitoring of indomethacin serum levels (in conjunction with daily echocardiography) would be the best approach for monitoring indomethacin therapy. We are currently investigating an association between low serum indomethacin levels and nonresponders, because we have found inadequately low indomethacin serum levels in several infants (some are included in the high-dose study group) who received high doses of indomethacin. This led us to speculate that indomethacin is handled differently in responders and nonresponders.

Concerning concomitant use of other drugs during indomethacin treatment, we did not give dexamethasone or dopamine to premature infants during indomethacin treatment. However, we treated those infants with furosemide (0.5 mg/kg per hour) when their urine output decreased below 1 mL/kg per hour.

Using the escalating, stepwise indomethacin-treatment strategy, we have treated >200 premature infants under 33 weeks of gestation suffering from sPDA. Only 3 of them had to undergo surgical closure of the PDA. It will be of great interest to exclude any long-term effects caused by this therapeutic approach. This prompted us to initiate a follow-up study on the neurodevelopmental outcome of our study groups, which is currently ongoing.

REFERENCES

  1. Sperandio M, Beedgen B, Feneberg R, et al. Effectiveness and side effects of an escalating, stepwise approach to indomethacin treatment for symptomatic patent ductus arteriosus in premature infants below 33 weeks of gestation. Pediatrics. 2005;116 :1361 –1366[Abstract/Free Full Text]
  2. Brooks JM, Travadi JN, Patole SK, Doherty DA, Simmer K. Is surgical ligation of patent ductus arteriosus necessary? The Western Australian experience of conservative management. Arch Dis Child Fetal Neonatal Ed. 2005;90 :F235 –F239[Abstract/Free Full Text]
PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics

Related articles in Pediatrics:

High-Dose Indomethacin for Patent Ductus Arteriosus Closure: How Strong Is the Evidence?
Shabih Manzar
Pediatrics 2006 117: 1863. [Extract] [Full Text]  




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