Role of Biomarkers in Sepsis in ICU: An Interim Analysis of Cross-sectional Study in a Tertiary Care Hospital ABS0130)

ABSTRACT

Introduction: Sepsis is a common cause of morbidity and mortality with no gold standard diagnostic test for detecting sepsis. Blood cultures are a frequent diagnostic step but the results take at least 48 hours and timely recognition of infection and initiation of appropriate antibiotics remain crucial in the treatment of sepsis. Biomarkers thus come in handy for rapid diagnosis and risk stratification. Objectives: Primary objective: To assess the diagnostic and prognostic value of procalcitonin (PCT), interleukin-6 (IL-6), ferritin, and C-reactive protein (CRP) levels in differentiating between Gram-negative and Gram-positive sepsis patients. Secondary objective: To determine the relationship between serum PCT, IL-6, ferritin, and CRP levels and isolated sepsis pathogens. Materials and methods: We are conducting a cross-sectional study for a period of 2 years on 360 adult patients admitted in an intensive care unit (ICU) of a tertiary care hospital with sepsis or septic shock. Our exclusion criteria are patients with burns, suspected or documented non-bacterial infections, viral hepatitis, iron overload states, and active COVID-19 infection. We are using convenience sampling. Demographic details of patients are collected. Blood is drawn for estimation of the four aforementioned biomarkers as well as body fluids of the patient based on clinical suspicion are sent for microbiological evaluation on admission to ICU before administration of antibiotics. Based on the culture reports, patients are classified as culture-positive or culture-negative sepsis and the biomarkers in each group are analyzed for diagnostic and prognostic accuracy. The primary outcome of the study is the survival or death of the patient while the secondary outcome is the number of days of ICU stay. During the time of submission, only 25 patients had been recruited and an interim analysis is being conducted. Results: During the time of submission, only 25 patients had been recruited and an interim analysis is being conducted. The mean age of our patients was 57.16 years. The study population was predominantly males (20 subjects) with ten subjects of urosepsis, three with pancreatitis, two with pneumonia, and the remaining ten had a miscellaneous diagnosis. The mean values of the inflammatory markers were as follows PCT = 16.672 (±24.3495), CRP = 85.8428 (±62.1224), IL-6 = 610.268 (±723.3846), and ferritin = 625.0832 (±628.5289). The p value of the biomarkers is <0.00001 and is significant at p < 0.05. The following combinations of biomarkers were found to be statistically significant - PCT with IL-6 (p = 0.00018), PCT with ferritin (p = 0.00012), CRP with IL-6 (p = 0.00116), and CRP with ferritin (p = 0.00079). The sensitivity of CRP and IL-6 was 100% while specificity was highest for PCT at 50%. Eight of the subjects had Gram-negative sepsis. The mean days of hospitalization were 19.92 days. Eight of the subjects died contributing to a mortality rate of 3.2 per 10 subjects. Conclusion: The combination of biomarkers reflects different aspects of sepsis pathophysiology and would be feasible to incorporate as a point of care testing. The biomarker panel that would provide diagnostic information for the investigation of a patient with suspected sepsis earlier than cultures is PCT with IL-6 and ferritin.