Chronic Nonsteroidal Anti-inflammatory Drugs Use Associated With 4 Times Higher Risk of Gastrointestinal Perforation in Meckel's Diverticulum: A Nationwide Analysis

Introduction: Meckel’s diverticulum (MD) is a common gastrointestinal (GI) anomaly which can present with various complications. NSAIDs are known for adverse gastrointestinal effects however the effect of their use in patients with MD is not well known. This study aims to evaluate inpatient outcomes of chronic NSAIDs use in patients with MD. Methods: We performed a nationwide analysis of MD-related hospitalizations in the US using the National Inpatient Sample (NIS) database 2016-2020. We used International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes to identify the population of interest, and stratified the patients based on their NSAIDs use status. We used chi-square test for categorical variables and student’s t-test for continuous variables. Univariate and multivariate linear and logistic regression models were built, and variables included in multivariate analysis were either known confounders or had P< 0.2 on univariate analysis. A P-value of ≤0.05 was considered statistically significant. Results: We identified 24,280 patients with MD and 200 (0.82%) were active chronic NSAIDs users. NSAIDs users were older (54.07 vs 58.83, P< 0.001) than those not using NSAIDs. Most patients had significant comorbidities (Elixhauser Comorbidity Index (ECI) ≥3) and were hospitalized in large hospitals in the southern US. There was no statistically significant difference in mortality (1.54% vs 0%, P=0.079), bowel obstruction (adjusted odds ratio(aOR)=0.88(0.46-1.67), P=0.700), GI bleeding (aOR=0.76(0.31-1.87), P=0.554), or volvulus (1.31% vs 0%, P= 0.100), however, NSAIDs use with MD was associated with a 4-fold higher risk of intestinal perforation (aOR=4.09(2.12-7.89), P=0.000) (Table 1). Conclusion: NSAIDs inhibit COX enzymes, leading to low-grade inflammation and alteration of the GI barrier, primarily in the stomach and duodenum. However, with the use of slow-release and enteric coated NSAIDs, there may be an increase in damage to the distal small intestine and colon, causing erosions and ulcers with complications such as perforation, as observed here. Notably, there was no increased risk of GI bleeding seen in those with MD taking NSAIDs, but this may be due to MD being an independent risk for bleeding, possibly masking the effect of NSAID-induced bleeding, and it is also likely that traditional methods of verifying bleeding, such as endoscopy, are not applicable for intestinal bleeding and may be altering the verity of this result. Table 1. - Patient and hospital characteristics of Meckel's Diverticulum related hospitalizations in the US in 2016-2020 stratified by NSAIDs use status Meckel's Diverticulum related hospitalizations No NSAIDs use Active NSAIDs use Number of hospitalizations (n) 24,080 200 Mean age in years (SE) 54.07 (19.07) 58.83 (17.14) < 0.001 Age 18-30 years 3,350 (13.91%) 10 ( 5.00%) 0.001 30-40 years 2,950 (12.25%) 20 (10.00%) 40-50 years 3,150 (13.08%) 30 (15.00%) 50-60 years 4,875 (20.25%) 35 (17.50%) 60-70 years 4,290 (17.82%) 50 (25.00%) 70-80 years 3,295 (13.68%) 35 (17.50%) >80 years 2,170 ( 9.01%) 20 (10.00%) Gender Male 14,650 (60.85%) 135 (67.50%) 0.050 Female 9,425 (39.15%) 65 (32.50%) Race White 18,925 (81.56%) 180 (92.31%) < 0.001 Black 1,075 ( 4.63%) 0 ( 0.00%) Hispanic 1,835 ( 7.91%) 10 ( 5.13%) Asian or Pacific Islander 595 ( 2.56%) 0 ( 0.00%) Others 775 ( 3.34%) 5 ( 2.56%) Median household income national quartile for patient ZIP Code $1-$43,999 5,585 (23.52%) 55 (27.50%) < 0.001 $44,000-$55,999 6,045 (25.46%) 65 (32.50%) $56,000-$73,999 6,585 (27.73%) 60 (30.00%) $74,000 or more 5,530 (23.29%) 20 (10.00%) Insurance type Medicare 8,345 (35.77%) 80 (42.11%) 0.180 Medicaid 2,890 (12.39%) 20 (10.53%) Private including HMO 10,930 (46.85%) 85 (44.74%) Others 1,165 ( 4.99%) 5 ( 2.63%) Elixhauser Comorbidity Index (ECI) 0 5,120 (21.26%) 25 (12.50%) 0.003 1 4,775 (19.83%) 40 (20.00%) 2 4,285 (17.79%) 30 (15.00%) ≥ 3 9,900 (41.11%) 105 (52.50%) Bed size of hospital Small 5,015 (20.83%) 55 (27.50%) < 0.001 Medium 6,770 (28.11%) 70 (35.00%) Large 12,295 (51.06%) 75 (37.50%) Hospital teaching status Non-Teaching Hospital 7,795 (32.37%) 75 (37.50%) 0.120 Teaching Hospital 16,285 (67.63%) 125 (62.50%) Region of hospital Northeast 4,050 (16.82%) 15 (7.50%) < 0.001 Midwest 6,550 (27.20%) 65 (32.50%) South 8,390 (34.84%) 85 (42.50%) West 5,090 (21.14%) 35 (17.50%) Outcomes Adjusted outcomes AOR (95%CI) P-value Inpatient mortality 365 (1.54%) 0 (0%) 0.079 - - Intestinal Perforation 310 (1.29%) 10 (5.00%) < 0.001 4.34 (2.24-8.44) 0.000 Bowel obstruction 1,395 (5.79%) 10 (5.00%) 0.630 0.86 (0.46-1.67) 0.7 Gastrointestinal bleeding 755 (3.14%) 5 (2.5%) 0.610 0.76 (0.31-1.87) 0.554 Volvulus 315 (1.31%) 0 (0.00%) - - - NSAIDs; non-steroidal anti-inflammatory drugs, AOR; adjusted odds ratio.