Effects of meropenem plus ulinastatin on inflammatory response and complications in patients with severe septic shock

To evaluate whether receipt of ulinastatin in addition to meropenem-based standard care was associated with inflammatory, coagulation, perfusion, and clinical outcomes in patients with severe septic shock.

This single-center retrospective, non-randomized comparative cohort study included 106 consecutive patients with severe septic shock treated between January 2023 and November 2025. Patients were classified according to treatment received in routine clinical practice: meropenem-based standard care plus ulinastatin (observation group, n = 53) or meropenem-based standard care alone (control group, n = 53). Twenty-eight-day all-cause mortality was presented as the principal objective patient-centered clinical outcome, whereas the total effective rate was reported only as an exploratory secondary outcome.

The overall response rate in the observation group presented higher at 90.6% (48/53) versus 73.6% (39/53) in the control group (p < 0.05). Post-treatment, the observation group presented lower levels of CRP, PCT, IL-6, IL-8, along with TNF-α (p < 0.05). For coagulation, post-treatment Fib levels were lower in the observation group compared to the control group, while PT and APTT were markedly shortened in the observation group (p < 0.05). Hemodynamic parameters-heart rate (HR), mean arterial pressure (MAP), along with cardiac index (CI)-showed greater improvement in the observation group (p < 0.05). Regarding immunity, the observation group presented higher CD4⁺ T cell counts and CD4⁺/CD8⁺ ratios, as well as significantly lower CD8⁺ T cell counts versus the control group (p < 0.05). The 6-h and 24-h lactate clearance rates were significantly higher in the observation group (p < 0.001 for both). ICU stay and mechanical ventilation duration were shorter in the observation group (p < 0.001 for both). The complication rate was 9.4% (5/53) in the observation group, which was lower than the 24.5% (13/53) seen in the control group (p < 0.05).

In this single-center retrospective cohort, receipt of ulinastatin in addition to meropenem-based standard care was associated with more favorable inflammatory, coagulation, lactate-clearance, hemodynamic, immune, and resource-use outcomes. Because treatment was not randomized and residual confounding cannot be excluded, these findings should not be interpreted as proof of causality or synergy.