Biomarkers for Predicting the Use of Selective Hemosorption of Lipopolysaccharides in Sepsis and Septic Shock

Abstract. Sepsis and septic shock are one of the most life-threatening complications with high mortality, reaching 70% in the presence of endotoxemia. Extracorporeal removal of lipopolysaccharides (LPS) can improve treatment outcomes. Aim. To evaluate the effectiveness of a group of biomarkers for predicting the use of selective hemosorption of lipopolysaccharides in patients with sepsis and septic shock. Material and Methods. The study included 22 patients (12 men and 10 women) who were treated at the N.V. Sklifosovsky Research Institute for Emergency Medicine from April 2022 to November 2023. Patients were examined within 72 hours after the development of sepsis. In the case of sepsis or septic shock, with an endotoxin activity assay ( EAA ) ≥0.6, 11 patients underwent LPS-selective hemoperfusion ( LPS-HP ) procedures. The values before hemoperfusion were analyzed in Group 1 (11 points), if LPS-HP was not used — in Group 2 (22 points). Results. The concentration of β-hydroxymyristic acid (β- HMA ) in healthy volunteers was 2.95 (1.52; 5.08) ng/ml, and in patients with sepsis and septic shock 7.44 (4.50; 15.68) ng/ml ( p =0.0001). The level of EAA was higher in Group 1 (0.780) compared to Group 2 (0.425), p =0.019. Differences were found between Groups 1 and 2 in the level of CRP: 290.0 and 166.5 mg/l, respectively ( p =0.016). The percentage of lymphocytes ( CD95 +) was lower in Group 1 compared to Group 2: 24.8 and 44.2%, respectively ( p =0.04). The SOFA score significantly correlated with the β- HMA level, the Spearman correlation coefficient r was 0.386, a moderate correlation was found between the β- HMA level and IL-6 ( r =0.638), EAA and CRP ( r =0.485), a negative correlation of CD 95+ lymphocytes with the level of IL-6 and CRP. Conclusion. 1. The β- HMA level in patients with sepsis and septic shock is 2.5 times higher than the values in healthy volunteers ( p =0.0001). In the ROC analysis, AUC was 0.817 (95% CI 0.702; 0.933, p=0.0001), the cutoff point was 3.26 ng/ml. 2. Using the threshold values EAA ≥0.6 c.u. allowed us to identify patients requiring LPS -selective hemoperfusion with statistically significant differences in the level of endotoxin activity (p=0.019) and CRP (p=0.016). At the same time, in the high EAA group, there was a tendency for an increase in the absolute value of the LPS level tested by β-HMA, the SOFA score was 13 points, compared with 9.5 points in the low EAA group. 3. In the high EAA group, a decrease in CD 95+ lymphocytes was established (p=0.033), which, together with a tendency towards lower values of HLA -DR expression on monocytes, may indicate the development of immunoparalysis and immune system dysregulation in these patients. 4. The β- HMA level correlated with the severity of organ dysfunction according to the SOFA score and IL-6 levels. EAA positively correlates with the level of CRP, and negatively correlates with IL-6. A positive correlation of IL-6 with CRP and a negative correlation with the level of CD 95+ lymphocytes were established. CRP negatively correlated with CD 95+ lymphocytes.