Endotoxemia in patients with depressed cardiac function who develop septic shock after cardiac surgery. The role of immunomodulation strategies.

Introduction Sepsis is a potentially life-threatening condition caused by an infection and an inadequate dysregulation of host immune response. It is one of the leading causes of mortality despite the extensive efforts and many different types of treatments. The concepts of sepsis has changed over the time, from the "systemic inflammatory response syndrome triggered by infection" to "a severe, potentially fatal, organic dysfunction caused by an inadequate or dysregulated host response to infection". In cardiac surgery, the prevalence of sepsis is between 0.39% and 2.5%, with a mortality ranging from 65% up to 79%. Endotoxin, or more accurately termed bacterial lipopolysaccharide (LPS), is recognized as the most potent and common microbial mediator implicated in the pathogenesis of sepsis and septic shock. It is the most prominent “alarm molecule” and it is is able to trigger inflammation through both intracellular and extracellular pathways. Methods We conducted an observational study on 41 patients with depressed cardiac function who developed septic shock after cardiac surgery between November 2020 and August 2022. Septic shock was identified according to Surviving Sepsis Campaign 2021 criteria. Patients received a cycle of Levosimendan ic ev for 24/h and an extracorporeal blood purification therapy (EBPT) in combination with intravenous administration of IgM enriched immunoglobulin 5 mL/kg/die for at least three consecutive days. Data were compared with data already recorded from a population of patients with depressed cardiac function approach admitted between November 2019 and November 2020 (Control group). The primary endpoint of the study was to value Blood Endotoxin Activity with EAATM® test. The secondary endpoints were: assessment of multiorgan dysfunction (SOFA) and the dynamics of biochemical and biohumoral variables (PCT, IL-6, WBC, ESR, CRP, ESR, T) over time observed; the study of the performance indicators of the cardiovascular system advancement of hemodynamic dysfunction, such as EF (Ejection Fraction), SV (Stroke Volume), CO (Cardiac Output) and VIS (Vasoactive Inotropic score); hospital mortality, length of stay in the ICU and 30-day, 60-day, 90-day survival. All data were measured at baseline and at 24, 48, 72/h after start’s treatment. Results The two groups did not significantly differ in age and gender as well as in the prevalence of clinical history. Colonization was present in 14 patients (34,15%) in the active group compared to 13 patients (34,2%) in the control group. Multiple drug resistance (MDR) bacteria in the active group were 18 (44 %) compared to 16 (42,1%) in the control group. A significant greater reduction of EAA value was observed in the active group compared to the control group both at 48h. Median VIS significantly decreased and Median EF, SV, CO significantly increased at 72h in active group. A lower percentage of patients died in the active group at 30, 60 and 90 days and a greater survival of the active group compared to the control group is described. The data show that patients in the active group have a lower risk of dying from the start of the therapeutic strategy than in the control group. Conclusions. The difficulty in managing patients with septic shock has been to guarantee a correct timing of the start of treatment, which unfortunately cannot be the same for all patients, as it depends on a correct and fast diagnosis. The search for new and rapid biomarkers, such as LPS / Endotoxin, could be useful in improving the problem of the time, to confirm the diagnosis and speed up the initiation of multimodal treatments. Although difficult, further studies could support the role of these "tailored" therapeutic strategies in the patient with septic shock.