Prophylactic sivelestat for esophagectomy and in-hospital mortality: a propensity score-matched analysis of claims database

Purpose: Transthoracic esophagectomy is an invasive surgery, and the excessive surgical stress produces inflammatory cytokines, which provoke acute respiratory distress syndrome (ARDS). Sivelestat sodium hydrate—a selective neutrophil elastase inhibitor—is used to treat or prevent ARDS in patients undergoing esophagectomy, although clear evidence is lacking. We investigated the benefits and risk of prophylactic sivelestat. Methods: This retrospective study used an administrative claims database in Japan. Adult patients who underwent transthoracic esophagectomy from 2010 to 2016 were identified and divided into a prophylactic sivelestat use group and a non-prophylactic use group that included both non-users and therapeutic users. The primary outcome was all-cause in-hospital mortality, and a secondary outcome included the proportion of ARDS. We used 1:1 propensity score matching. For sensitivity analyses, we conducted a 1:2 propensity score matching analysis and several analyses with various patient inclusion criteria. Results: Of the 3391 patients with esophagectomy, 621 received prophylactic sivelestat. On unadjusted analysis, the sivelestat group had a higher proportion of in-hospital mortality (5.3% vs. 2.9%) compared with the control group. We created a matched cohort of 615 pairs, whose baseline characteristics were well balanced. On adjusted analysis using propensity score matching, prophylactic sivelestat administration was not associated with decreased in-hospital mortality [adjusted odds ratio (aOR) 1.65; 95% confidence interval (CI) 0.95–2.88], ARDS rate (aOR 1.25; 95% CI 0.49–3.17). The findings were also consistent with other sensitivity analyses. Conclusion: Because mortality and postoperative complications were similar, our findings do not support prophylactic sivelestat administration for patients undergoing esophagectomy.