Indomethacin and NEC

Indomethacin and NEC

Necrotizing Enterocolitis and Gastrointestinal Complications after Indomethacin Therapy and Surgical Ligation in Premature Infants with Patent Ductus Arteriosus. O'Donovan DJ, Baetiong A,, Adams K, et al. Journal of Perinatology (June 2003);23:286-290.

Background: Indomethacin is the most frequently used pharmacological agent for closure of a patent ductus arteriosus (PDA) in premature infants. However, reports of complications, particularly, necrotizing enterocolitis (NEC) and isolated gastrointestinal perforation have generated concerns about the use of this medication.

Objectives: A retrospective study to compare the incidence of NEC, NEC-related gastrointestinal complications and isolated gastrointestinal perforation among premature infants treated for a PDA with either, indomethacin alone (I), surgical ligation alone (L), or indomethacin followed by surgical ligation (I-L).

Methods: The medical records of 224 infants that underwent treatment, either pharmacological or surgical, for a PDA, confirmed by echocardiography, over a 4-year period (1995 to 1998) were analyzed. Treatment history and gastrointestinal complications were reviewed.

Results: Of the 224 infants, 108 (48.2%) were treated with I, 50 (22.3%) by L, 66 (29.5%) with I-L. The clinical characteristics of the three treatment groups were similar and no differences in the incidence of NEC were observed between groups. NEC occurred in 14 (13%) of the I group, seven (14%) of the L group, and eight (12%) of the I-L group. The rate of NEC-related gastrointestinal complications and isolated gastrointestinal perforation were also similar among groups.

Conclusion: In this large retrospective study, indomethacin treatment for a significant PDA in premature infants was not associated with a greater risk for NEC or NEC-related gastrointestinal complications than surgical ligation.

Comments: Despite theoretical concerns, it appears that using IV indomethacin to treat PDA in preterm infants does NOT increase their risk of NEC. The risk of isolated small bowel perforations was also not increased in patients treated with indomethacin for PDA. This is in contrast to other studies that demonstrated an increased risk of small bowel perforations with prophylactic use of indomethacin to prevent IVH. This difference may be related to the timing of the indomethacin use, or to the concomitant use of dexamethasone and indomethacin in many of the babies who had intestinal perforation. For further discussion indomethacin and bowel perforation or NEC, see 1-002, 2-007, 2-036, and 3-047. ABK.

Date: 15 Jul 2003
Time: 08:27:22

We should be very careful not to rely upon RETROSPECTIVE studies to determine treatment outcomes, whether positive or adverse, especially when there ARE randomized controlled trials which demonstrate a different result. There are RCT's which have demonstrated an increase in isolated GI perforation with Indomethacin use for PDA. (See the Cochrane Review and the Prophylactic Indomethacin trials).
By the way, the reviewers conclusion is NOT what this paper states. The paper states that there does not appear to be an increase in NEC or GI perf with use of Indocin for PDA closure when compared to surgical ligation.

What would be a more interesting question to answer is: In what population does the "Number Needed to Harm" with Indocin therapy justify NOT using this medication and going directly to surgical ligation (or doing nothing)?

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