O3275: Histamine Receptor Blockers Are Associated with Increased Risk of Abscess Formation in Pediatric Perforated Appendicitis: A Multi-institutional Pediatric Database Confirmation of a Retrospective Clinical Observation

Background: Previous retrospective analysis of the results of a large cohort of patients at a single institution (St. Peter, et al. 2010) demonstrated that the administration of histamine blockade during the post operative period in children with perforated appendicitis resulted in a significantly increased risk of appendiceal abscess formation. Despite this compelling data, the concerns with histamine blockade in this population have not been widely disseminated in clinical practice. We sought to confirm this association between histamine blockade and intraperitoneal abscess formation in a large multi-institutional pediatrics database.

Methods: The Pediatric Health Information System database was queried for patients aged 5 and 18 years who were hospitalized with perforated appendicitis and underwent laparoscopic appendectomy within 48 hours of admission between 2018 and 2020. Exclusion criteria included mortality during index hospitalization. The primary outcome measure was diagnosis of an intraabdominal abscess during the index visit or a readmission visit within 30 days of discharge. Antihistamine exposure was defined as receipt of a histamine-receptor blocker within 48 hours of admission. Proton pump inhibitor (PPI) exposure, defined similarly, was included as a control. Antibiotic management strategy was per individual institutional protocol. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to compare likelihood of abscess formation.

Results: 9,862 patients from 49 hospitals satisfied inclusion criteria. The vast majority of the study sample (91%) did not receive an antihistamine or PPI within 48 hours of admission, and 34% developed an abscess. Patients who received an antihistamine were more likely to develop an abscess than patients who did not (38.8% OR 1.2; 95% CI 1.1 - 1.4). Patients who received both an H1 and and an H2 blocker had a cumulative affect with an abscess rate of 45.5% though this did not reach statistical significance (OR 1.6; 95% CI 0.7-3.8). PPI exposure alone did not alter abscess rate (OR 1.2; 95% CI 0.8, 1.6). However patients who received a PPI in conjunction with an antihistamine had nearly three times the likelihood of abscess formation (58.6% OR 2.8; 95% CI: 1.4, 5.6).

Conclusion: In a large multi-institution analysis, early receipt of antihistamines alone, but not PPI alone, after perforated appendicitis is associated with elevated risk of abscess formation in children, suggesting that the immunologic mechanism of action of antihistamine drugs underlines this observation. This confirms the previous single institution observations, and reinforces the hazards of these drugs in this population.