1.12 CME

Novel Biomarkers in Sepsis

Speaker: Dr. Adel Mohamed Yasin Al Sisi

Critical care Specialist,Prime Hospitals, Dubai

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Description

Elevated levels of PCT serve as a valuable biomarker in sepsis, aiding in the early diagnosis and monitoring of bacterial infections, and guiding therapeutic decisions. CRP is a commonly used biomarker for inflammation, and its levels are frequently elevated in sepsis, providing clinicians with an indication of the severity of the immune response. Elevated lactate levels are associated with tissue hypoxia and serve as a crucial biomarker in sepsis, aiding in the assessment of organ dysfunction and prognosis. Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1): Elevated sTREM-1 levels are indicative of bacterial infections, making it a promising biomarker for identifying sepsis of infectious origin. Endothelial Biomarkers (E-selectin, VCAM-1): Increased expression of endothelial biomarkers reflects endothelial dysfunction in sepsis, contributing to the understanding of the pathophysiology and progression of the condition.

Summary Listen

  • Sepsis definition has evolved, moving from SIRS criteria to a dysregulated immune response to infection leading to organ dysfunction. Early identification and immediate action are crucial, focusing on the first hour after suspected sepsis, emphasizing clinical assessment, blood tests, and organ support. Clinical evaluation remains critical, along with laboratory tests and organ function support, highlighting the importance of early management and risk stratification.
  • Biomarkers play a key role in diagnosing sepsis, recognizing organ dysfunction, and stratifying risk. Phenotypes of patients include hyperinflammation (overproduction of pro-inflammatory cytokines) and immunosuppression (overproduction of anti-inflammatory mediators). Biomarkers can also identify gut permeability and blood-brain barrier disruption.
  • Invading organisms release constituents (endotoxins, exotoxins, DNA) called pathogen-associated molecular patterns (PAMPs). Receptors, including pattern recognition receptors, identify these molecules, triggering an immune response. Cell injury from this immune response releases endogenous danger molecules (DAMPS).
  • Acute phase reactions in sepsis lead to the release of various chemokines, cytokines, mediators, and proteinaceous materials. These can originate from complex protein systems, immune cells (monocytes, neutrophils, lymphocytes), and endothelial cells. Divided into groups, these reactions include: pattern recognition molecules (CRP, serum amyloid B, pentraxin 3) and the complement system (C4D, complement 3A, complement 5A).
  • Damage-associated molecular patterns (DAMPs) are a key group, with examples like neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin. Endothelial cell mediators include occludin, claudin, zonulins, and calcium-binding protein B (S100B). Gut permeability markers consist of intestinal fatty acid-binding protein, plasma zonulin, and serum D-lactic acid.
  • Non-coding RNAs and micro RNAs, including long non-coding metastasis-associated lung adenocarcinoma transcript 1 (malat1) and maternally expressed gene 3 (MG3), correlate with poor outcomes. Other categories involve cell membranes, hormones (N-terminal brain naturetic peptide, mid-regional pro-adrenomedullin), and neutrophil-related biomarkers (resistine).
  • Challenges remain in sepsis treatment due to high mortality rates and long-term cognitive dysfunction, necessitating further research. Despite limitations, early intervention can reduce the risk of death. Biomarkers help in diagnosing and identifying sepsis.
  • The success of treatment is monitored by serial measurements and trend analysis. It is important to perform a trending evaluation by observing any improvement or worsening and interpreting along with clinical evaluation and other information, such as blood culture results. Although biomarkers can be a helping tool to observe any success of the treatment, it should not be the sole assessment.

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