Indomethacin-associated bowel perforations: A study of possible risk factors

• Published in: Journal of pediatric surgery Vol. 34; no. 3; pp. 442 - 444
• Main Authors: Shorter, Nicholas A, Liu, Jean Y, Mooney, David P, Harmon, Bethany J
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Elsevier Inc 01.03.1999; Elsevier
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Biological and medical sciences; Birth Weight; Case-Control Studies; Drug toxicity and drugs side effects treatment; Female; Humans; Indomethacin - adverse effects; Indomethacin - therapeutic use; Infant, Newborn; Infant, Premature, Diseases - chemically induced; Infant, Premature, Diseases - epidemiology; Intestinal Perforation - chemically induced; Intestinal Perforation - epidemiology; Male; Medical sciences; Pharmacology. Drug treatments; Risk Factors; Survival Rate; Time Factors; Toxicity: digestive system; bowel perforation; prematurity; Indomethacin; Human; Endoperoxide; Premature; Prostaglandin; Enzyme; Perforation; Toxicity; Indometacin; Gut; Enzyme inhibitor; Synthase; Survival; Tocolytic; Non steroidal antiinflammatory agent; Newborn diseases; Chemotherapy; Newborn; Treatment; Indoleacetic acid derivatives; Digestive diseases; Intestinal disease; Evolution
• ISSN: 0022-3468; 1531-5037
• DOI: 10.1016/S0022-3468(99)90495-5

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 ≤1,100 g. These patients were compared with a control group of 51 infants who were cared for contemporaneously, had birth weights ≤ 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.