Correspondence

Ibuprofen versus Indomethacin for Closure of Patent Ductus Arteriosus

N Engl J Med 2001; 344:457-458February 8, 2001

Article

To the Editor:

Van Overmeire et al. compared ibuprofen with indomethacin for closure of patent ductus arteriosus in premature neonates (Sept. 7 issue).1 They found that the rates of ductal closure were similar in the two treatment groups but that indomethacin was more likely to be associated with oliguria. However, the dosage of indomethacin in this study was 0.2 mg per kilogram of body weight given intravenously at 12-hour intervals for a total of three doses.

Rennie and Cooke2 compared a regimen of 0.2 mg per kilogram given at 12-hour intervals for a total of three doses with a regimen of 0.1 mg per kilogram given daily for a total of six doses. They reported an initial closure rate of 90 percent with the prolonged, lower-dose regimen, as compared with a rate of 77 percent for the higher-dose regimen. This 77 percent rate is similar to the closure rate reported by Van Overmeire et al. for their indomethacin group (66 percent). Relapse, or ductal reopening, occurred less frequently with the lower-dose regimen of indomethacin than with the higher-dose regimen in the study by Rennie and Cooke. Ductal reopening was not noted in either the ibuprofen group or the indomethacin group in the study by Van Overmeire and colleagues. In addition, Rennie and Cooke noted that significantly fewer infants had a rise in the serum creatinine concentration in the group receiving the lower-dose regimen.

Many neonatal units have accepted the findings of this study and use the lower-dose regimen of indomethacin to treat patent ductus arteriosus in premature neonates. On the basis of the information given, it would seem that the lower-dose regimen of indomethacin results in a higher ductal-closure rate and has less of an effect on renal function than either the higher-dose regimen of indomethacin or ibuprofen. Further information from studies comparing ibuprofen with a lower-dose regimen of indomethacin is needed, but on the basis of the available data, there seems to be little value in moving away from our current practice of using a low dose of indomethacin.

Dan Casalaz, M.B., B.S.
Mercy Hospital for Women, East Melbourne 3002, Australia

2 References

1. 1

   Van Overmeire B, Smets K, Lecoutere D, et al. A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus. N Engl J Med 2000;343:674-681
   Full Text | Web of Science | Medline

2. 2

   Rennie JM, Cooke RW. Prolonged low dose indomethacin for persistent ductus arteriosus of prematurity. Arch Dis Child 1991;66:55-58
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: We thank Dr. Casalaz for his comments. Before our study began, the five participating centers routinely used the regimen of 0.2 mg per kilogram given three times, making the comparison with ibuprofen clinically relevant. We agree that the study by Rennie and Cooke1 supports the use of the prolonged, lower-dose regimen of indomethacin because of the higher closure rates, fewer relapses, and lower incidence of renal side effects in the group of infants treated with that regimen. However, other studies have not confirmed these findings.2,3

In our study, the serum creatinine concentration was significantly lower from day 4 to day 8 in the ibuprofen group than in the indomethacin group, and urine output was higher in the ibuprofen group. No data on urine output were given by Rennie and Cooke.1 In their study, relapses of patent ductus were evaluated clinically. In our study, closure of the ductus arteriosus was confirmed by high-resolution echocardiography; we did not observe any relapses after the initial closure. On the basis of the information available, we cannot conclude that the prolonged, lower-dose regimen of indomethacin is superior to ibuprofen.

Bart Van Overmeire, M.D., Ph.D.
University Hospital Antwerp, B-2650 Edegem, Belgium

Koen Smets, M.D.
Ghent University Hospital, 9000 Ghent, Belgium

Jean-Paul Langhendries, M.D.
Clinique Saint Vincent, 4000 Rocourt, Belgium

3 References

1. 1

   Rennie JM, Cooke RW. Prolonged low dose indomethacin for persistent ductus arteriosus of prematurity. Arch Dis Child 1991;66:55-58
   CrossRef | Web of Science | Medline

2. 2

   Rhodes PG, Ferguson MG, Reddy NS, Joransen JA, Gibson J. Effects of prolonged versus acute indomethacin therapy in very low birth-weight infants with patent ductus arteriosus. Eur J Pediatr 1988;147:481-484
   CrossRef | Web of Science | Medline

3. 3

   Tammela O, Ojala R, Iivainen T, et al. Short versus prolonged indomethacin therapy for patent ductus arteriosus in preterm infants. J Pediatr 1999;134:552-557
   CrossRef | Web of Science | Medline

Citing Articles (2)

Citing Articles

1. 1

   Weir, E. Kenneth, López-Barneo, José, Buckler, Keith J., Archer, Stephen L., . (2005) Acute Oxygen-Sensing Mechanisms. New England Journal of Medicine 353:19, 2042-2055
   Full Text

2. 2

   S. L. Archer, X.-C. Wu, B. Thébaud, R. Moudgil, K. Hashimoto, E.D. Michelakis. (2004) O2 sensing in the human ductus arteriosus: redox-sensitive K+ channels are regulated by mitochondria-derived hydrogen peroxide. Biological Chemistry 385:3-4, 205-216
   CrossRef