Postoperative Nonsteroidal Anti-inflammatory Drug Use and Intestinal Anastomotic Dehiscence: A Systematic Review and Meta-Analysis.

BACKGROUND: Nonsteroidal anti-inflammatory drugs are commonly used analgesics in colorectal surgery. Controversy exists regarding the potential association between these drugs and anastomotic dehiscence. OBJECTIVE: This study aimed to determine whether postoperative nonsteroidal anti-inflammatory drug use is associated with intestinal anastomotic dehiscence. DATA SOURCES: PubMed, EMBASE, CENTRAL, and references of included articles were searched without date or language restriction. STUDY SELECTION: Randomized controlled trials and observational studies that compared postoperative nonsteroidal anti-inflammatory drug use with nonuse and reported on intestinal anastomotic dehiscence were selected. INTERVENTION: The use of postoperative nonsteroidal anti-inflammatory drugs relative to placebo or nonuse was investigated. MAIN OUTCOME MEASURES: Risk ratios and adjusted or unadjusted odds ratios for anastomotic dehiscence were pooled across randomized controlled trials and observational studies using DerSimonian and Laird random-effects models. RESULTS: Among 4395 citations identified, 6 randomized controlled trials (n = 473 patients) and 11 observational studies (n > 20,184 patients) were included. Pooled analyses revealed that nonsteroidal anti-inflammatory drug use was nonsignificantly associated with anastomotic dehiscence in randomized controlled trials (risk ratio, 1.96; 95% CI, 0.74–5.16; I2 = 0%) and significantly associated with anastomotic dehiscence in observational studies (OR, 1.46; 95% CI, 1.14–1.86; I2 = 54%). In stratified analyses of observational study data, the pooled OR for anastomotic dehiscence was statistically significant for studies of nonselective nonsteroidal anti-inflammatory drug use (6 studies; > 4900 patients; OR, 2.09; 95% CI, 1.65–2.64; I2 = 0%), but was not statistically significant for studies of cyclooxygenase-2 selective nonsteroidal anti-inflammatory drug use (3 studies; >697 patients; OR, 1.34; 95% CI, 0.78–2.31; I2 = 0%). LIMITATIONS: Studies varied by patient selection criteria, drug exposures, and definitions of anastomotic dehiscence. Analyses of randomized controlled trials and cyclooxygenase-2 selective nonsteroidal anti-inflammatory drugs were potentially underpowered. CONCLUSIONS: Pooled observational data suggest an association between postoperative nonsteroidal anti-inflammatory drug use and intestinal anastomotic dehiscence. Caution may be warranted in using these medications in patients at risk for this complication.