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

Abstract

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.

Keywords: Administrative claims; Esophagectomy; Mortality; Propensity score; Sivelestat.