Effect of postoperative non-steroidal anti-inflammatory drugs on anastomotic leakage after pancreaticoduodenectomy

Background: Although the association between an increase in anastomotic leakage (AL) and non-steroidal anti-inflammatory drugs (NSAIDs) has been reported in gastrointestinal surgeries, this issue has rarely been addressed for pancreaticoduodenectomy (PD). We aimed to investigate the association between postoperative NSAIDs administration and clinically relevant AL (CR-AL) following PD.

Methods: We retrospectively evaluated 2,163 consecutive patients who underwent PD between 2007 and 2019. The patients were divided into two groups; patients who received and did not receive NSAIDs by postoperative day (POD) 5. We conducted a propensity score analysis using inverse probability of treatment weighting (IPTW) to adjust the baseline differences between both groups. We compared the occurrence of CR-AL and other postoperative outcomes before and after IPTW. Further, we used the multivariable binary logistic regression method for a sensitivity analysis for CR-AL.

Results: A total of 2,136 patients were included in the analysis. Of these, 222 (10.4%) received NSAIDs by POD 5. The overall occurrence rate of CR-AL was 14.9%. After IPTW, postoperative NSAIDs were significantly associated with CR-AL (odds ratio [OR]: 1.24, 95% CI [1.05, 1.47], P = 0.012), prolonged postoperative hospitalization (OR: 1.31, 95% CI [1.14, 1.50], P < 0.001), and unplanned readmission within 30 days postoperatively (OR 1.48: 95% CI [1.15, 1.91], P = 0.002). However, this association was not consistent in the sensitivity analysis.

Conclusions: Postoperative NSAIDs use was significantly associated with an increase in CR-AL incidence following PD. However, sensitivity analysis failed to show its association, which precludes a firm conclusion of its detrimental effect.