The Role of Serum and Peritoneal Biomarkers in Predicting Sepsis and Septic Multiorgan Failure in Patients With Secondary Peritonitis

Abstract

Purpose Secondary peritonitis is still one of the most important causes of severe sepsis in the world; therefore, it is of utmost importance to identify biomarkers that could be employed for the purpose of selecting patients at high risk for developing life-threatening complications after emergency surgery. In view of this quest, our study seeks to reveal the possible role for serum and peritoneal concentrations of selected biomarkers, specifically presepsin, procalcitonin, monocyte chemoattractant protein-1 (MCP-1), high mobility group box 1 protein (HMGB-1) and interleukins (IL-6, -8, -10), in early prediction of sepsis and septic multiorgan failure for patients with secondary peritonitis. Methods We prospectively observed 32 selected patients with secondary peritonitis that underwent emergency surgery. Blood and peritoneal fluid samples were drawn at the time of surgery (T0), and after that, blood samples were taken at 24 (T1) and 48 (T2) hours postoperatively. Cytokines concentrations were determined using a sandwich enzyme-linked immunosorbent assay (ELISA), a non-competitive variant, both in peritoneal fluid and serum. For determining whole blood concentration of presepsin and procalcitonin, PATHFAST™ assays (Polymedco, Cortlandt, New York) were used, based on the principle of non-competitive chemiluminescent enzyme immune-assay (CLEIA). The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of University Emergency Hospital Bucharest (no. 40325/6 April 2023). Results We found significant elevations in the peritoneal concentrations of interleukins 6, 8, 10, HMGB-1, and MCP-1 in all patients with secondary peritonitis at the moment of surgery; however, no clear correlation could be made based on this data with patient evolution. With regards to blood concentrations of the aforementioned serum cytokines and presepsin, procalcitonin (as already established markers of sepsis), our results showed good predictive value of presepsin for developing sepsis and septic multiorgan failure from the first hours in this patient category. All other biomarkers, despite having higher concentrations than baseline, in particular at 24-48 hours after surgery, had unpredictable dynamics that couldn't be correlated with the severity of the disease. Conclusion Cytokine production is the mainstay in developing sepsis and septic multiorgan failure in patients with secondary peritonitis; therefore, studying the dynamics of said cytokines seems of interest in finding tools to predict the development of sepsis or sepsis-related mortality. However, at the time, there seemed to be no clear correlation between the values of these cytokines and the development of complications.

Keywords: cytokine storm; peritoneal cytokines; secondary peritonitis; sepsis; syndrome.

Figure 1. Patients with sepsis and sepsis-induced MODS had higher WBC count at T0, with peak levels at T1 for patients with sepsis-induced MODS and peak levels at T2 for patients in the sepsis group

MODS - multiple organ dysfunction syndrome

Figure 2. Presepsin levels were higher in the sepsis and sepsis-induced MODS groups (median value 1316 pg/ml and 2100 pg/ml, respectively)

MODS - multiple organ dysfunction syndrome

Figure 3. Peritoneal fluid samples were taken intraoperatively (T0), and the concentrations of IL-6 was determined

Figure 4. Peritoneal fluid samples were taken intraoperatively (T0), and the concentrations of IL-8 were determined

Figure 5. Peritoneal fluid samples were taken intraoperatively (T0), and the concentrations of IL-10 were determined

Figure 6. Peritoneal fluid samples were taken intraoperatively (T0), and the concentrations of HMGB-1 were determined

HMGB-1 - high mobility group box 1 protein

Figure 7. Peritoneal fluid samples were taken intraoperatively (T0), and the concentrations of MCP-1 were determined

MCP-1 - monocyte chemoattractant protein-1

Figure 8. IL-6 plasma concentrations at T0 were highest in the septic group, but from T1 until T2, the sepsis-induced MODS group of patients presented the highest concentrations

MODS - multiple organ dysfunction syndrome

Figure 9. IL-8 concentrations were highest in the sepsis-induced MODS group at all moments, from T0 to T2

MODS - multiple organ dysfunction syndrome

Figure 10. IL-10 concentrations was highest in the sepsis-induced MODS group at all moments, from T0 to T2

MODS - multiple organ dysfunction syndrome

Figure 11. MCP-1 plasma concentrations at T0 were highest in the non-septic group, but from T1 until T2 the sepsis-induced MODS group of patients presented the highest concentrations

MCP-1 - monocyte chemoattractant protein-1, MODS - multiple organ dysfunction syndrome

Figure 12. HMGB-1 plasma concentrations at T0 were highest in the septic group, but from T1 until T2, the sepsis-induced MODS group of patients presented the highest concentrations

HMGB-1 - high mobility group box 1 protein, MODS - MODS - multiple organ dysfunction syndrome