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Indomethacin-associated bowel perforations: a study of possible risk factors
N A Shorter1, J Y Liu, D P Mooney
1Department of Surgery, Children's Hospital at Dartmouth, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.
Insights
Early indomethacin use in premature infants increases bowel perforation risk. This risk may be linked to the drug or an underlying condition, with potential infectious agents also implicated.
Area of Science:
- Neonatal Medicine
- Pediatric Surgery
- Pharmacology
Background:
- Indomethacin administration is a known risk factor for bowel perforation in premature infants.
- This study aimed to identify specific risk factors contributing to this serious complication.
Purpose of the Study:
- To investigate risk factors associated with indomethacin-induced bowel perforation in very low birth weight infants.
- To differentiate between types of perforations and their outcomes.
Main Methods:
- A case-control study comparing 15 infants with indomethacin-associated bowel perforation to 51 control infants receiving indomethacin.
- Infants in both groups had a birth weight less than or equal to 1,100 grams.
Main Results:
- Survival rates were significantly lower in the perforation group (53%) compared to controls (96%).
- Two perforation types were identified: necrotizing enterocolitis-associated and simple bowel perforation, with the latter having an 86% survival rate.
- Earlier indomethacin administration was associated with simple perforations; a potential infectious agent was suggested by seasonal clustering.
Conclusions:
- Earlier indomethacin administration correlates with an increased risk of focal bowel perforation in premature infants.
- The increased risk may be due to indomethacin itself or the underlying condition necessitating its early use.
- Further investigation into potential infectious agents is warranted.
Background:
The association between indomethacin administration and bowel perforation in premature infants is well known. The goal of this study was to examine possible risk factors for this complication.
Methods:
Fifteen cases of indomethacin-associated bowel perforation occurred from 1993 to 1996. All had a birth weight < or = 1,100 g. These patients were compared with a control group of 51 infants who were cared for contemporaneously, had birth weights < or = 1,100 g and received indomethacin.
Results:
Survival rate in the control group was 96%. For the group with perforations, it was 53%. Two types of perforation were seen, one occurring in the setting of necrotizing enterocolitis, and the other, a simple perforation in an otherwise normal-appearing bowel. For the latter group, the survival rate was 86%, and, when possible, primary repair was the procedure of choice. Use of aminophylline was greater in the control group. Otherwise, there were no significant differences between the two groups in any of the variables observed. However, when the simple perforations were observed separately, these patients had, on average, received indomethacin at a younger age than the controls (P < .05). The clustering of perforation cases from May through August suggests an infectious agent might be involved.
Conclusions:
Earlier administration of indomethacin correlates with an increased risk of focal perforation. It is unclear, however, whether the risk factor is the drug itself or the earlier need for it. Aminophylline use was somewhat more in the control group, but this is not likely to reflect a protective role for that drug. The possible involvement of an infectious agent should be considered.
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