Ulinastatin is effective in reducing mortality for critically ill patients with sepsis: a causal mediation analysis

Ulinastatin has been found to have anti-inflammatory effect for patients with sepsis. However, its clinical effects were conflicting. The study aimed to investigate the cost-effectiveness of ulinastatin and to perform mediation analysis to explore the proportion of the total effects that can be explained by inflammatory responses. This is a retrospective study involving critically ill patients with sepsis from January 2014 to July 2017. A total of 263 patients were included in the study, involving 179 patients in the ulinastatin group and 84 in the control group. Ulinastatin group showed significantly lower 28-day mortality rate than that in the control group (31% vs. 55%; p < 0.001). Both total (46330 [26000,83500] vs. 19870 [8747,41140] RMB; p < 0.01) and drug cost (18210 [9492,31920] vs. 7230 [2675,19270] RMB; p < 0.01) were significantly higher in the ulinastatin group than the control group. In multivariable model, the adjusted odds ratio for ulinastatin was 0.304 (95% CI: 0.152 to 0.592; p = 0.001). The mediation analysis showed that the use of ulinastatin was able to reduce the probability of death by 23.5%. The average causal mediation effect of delta C-reactive protein (CRP) was 8%, accounting for 35% of the total effect.