Prophylactic indomethacin: factors determining permanent ductus arteriosus closure

Permanent closure of the ductus arteriosus (DA) requires both effective muscular constriction to block luminal blood flow and anatomic remodeling to prevent later reopening.

We examined the role of prophylactic indomethacin in producing permanent DA closure and the mechanism by which this occurs.

We studied 2 separate approaches to managing a patent DA in 257 preterm infants (gestation 24 to 27 weeks): (1) prophylactic indomethacin (all infants treated during the first 15 hours after birth) or (2) symptomatic treatment (infants in this group received indomethacin only if clinical symptoms appeared; infants whose ductus closed spontaneously and never received indomethacin were included in this group). Echocardiography was performed 24 to 36 hours after the last dose of indomethacin was administered or by age 5 days if spontaneous closure occurred. Infants were monitored for the development of ductus reopening.

The prophylactic treatment group had a greater degree of initial ductus constriction, a higher rate of permanent anatomic closure, and a decreased need for surgical ligation than did the symptomatic treatment group. The degree of initial ductus constriction was the most important factor determining the rate of ductus reopening. Post-treatment echocardiography proved to be the best test for predicting eventual reopening.

Prophylactic indomethacin improved the rate of permanent ductus closure by increasing the degree of initial constriction. Prophylactic indomethacin did not affect the remodeling process, nor did it alter the inverse relationship between infant maturity and subsequent reopening. Even when managed with prophylactic indomethacin, the rate of ductus reopening remained unacceptably high in the most immature infants.