Evaluation of presepsin and pro-adrenomedullin levels in diagnosis of sepsis and septic shock and prediction of prognosis

Objective: It is known that early diagnosis and appropriate management in the first hours after sepsis develops improves outcomes. Biomarkers that provide accurate and rapid results to support diagnosis are required. The aim is to demonstrate the effectiveness of these molecules, which are two alternative biomarkers that can be used to help detect sepsis early, screen for sepsis, start antibiotic therapy in appropriate patients in a short time, de-escalate treatment, and predict prognosis. Materials and Methods: A prospective case-control study was conducted, and patients who were followed up with sepsis/septic shock in our hospital's Internal Medicine Intensive Care Unit between October 27, 2023 and August 23, 2024 and who applied to our hospital's outpatient clinics for non-infectious reasons were included. Presepsin and pro-adrenomedullin, measured once on days 0, 3 and 7 in the case group and in the control group, were determined by the Enzyme-Linked ImmunoSorbent Assay method (ELK Biotechnology-PRC). These two markers were compared with other routine markers and in terms of mortality, and their role in diagnosis and follow-up was investigated. Results: The study included 99 people each in the case and control groups. The mean age was 60.7±15.4. 62.6% were male and 37.4% were female. No statistically significant difference was found between the two groups in age and gender (p>0.050). Significant differences were found in the two groups in terms of white blood cells, xvii lymphocytes, neutrophils, hemoglobin, platelets, C-reactive protein, erythrocyte sedimentation rate, creatinine, lactate, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio and presepsin (p<0.050). The cut-off point was determined as 0.701 ng/mL for presepsin, 209.3 for platelet/lymphocyte ratio and 4.95 for neutrophil/lymphocyte ratio. The time-dependent change in presepsin, CRP and procalcitonin levels in cases was found to be statistically significant (p<0.050). The time-dependent decrease in presepsin levels between day 0-day 3 and day 3-day 7 was found to be statistically significant (p<0.050). Presepsin and pro-adrenomedullin levels were not found to be statistically significant in the prediction of septic shock and mortality at the end of 7, 14 and 28 days in the distinction of two subgroups formed by accepting the age limit of 65 (p>0.050). A significant relationship was found between solid tumor and mortality (p=0.026). The relationship between SOFA, qSOFA, NEWS, MEWS, Charlson Comorbidity Index tools and mortality was found to be statistically significant (p<0.050). A significant relationship was found between blood pressure and Glasgow Coma Scale and mortality (p<0.005). Mortality was found to be statistically significantly higher in patients with septic shock (p<0.001) and in patients with ventilator-associated pneumonia (p=0.013). No statistically significant relationship was found between the factors detected in cultures and presepsin and pro-adrenomedullin, and also between bacteremia and mortality (p>0.050). In serial measurements, neutrophil levels on day 3, platelet, procalcitonin, direct bilirubin and pro-adrenomedullin levels on day 7, lactate and protein levels on days 3 and 7, aspartate aminotransferase levels on days 0 and 7, and albumin levels at all three points were found to be statistically significant in predicting mortality (p<0.050). It was observed that the presence of the new Coronavirus (COVID 19) disease increased mortality by approximately 13.69 times, the presence of septic shock by approximately 5.06 times, each point increase in the Charlson Comorbidity Index by approximately 1.22 times, each unit increase in potassium by approximately 1.85 times, each unit decrease in albumin by approximately 1.11 times, and a one °C decrease in body temperature by approximately 2.4 times (p<0.050). It was found that thrombocytopenia at presentation predicted mortality on the 7th day, and severe thrombocytopenia predicted mortality on the 7th and 14th days, which was statistically significant (p<0.050). Conclusion: Presepsin can be used for diagnosis, but it is insufficient to exclude patients without sepsis, which may lead to unnecessary antibiotic therapy. Presepsin is insufficient for prognosis even when used with other biomarkers. Measuring pro adrenomedullin at the time of admission is not cost-effective. There is no definitive finding regarding the effectiveness of pro-adrenomedullin in sepsis, and further studies are needed to show that it is predictive of septic shock and mortality. Key Words: sepsis, presepsin, pro-adrenomedullin, mortality