A brief overview of the potential for biomarkers to impact on sepsis diagnosis and management, looking at recent meta-analysis data on procalcitonin and exploring future options for prognostic and diagnosis markers including metabolomics.
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Biomarkers in sepsis
1. Biomarkers in Sepsis
Utility or Futility?
Dr Andrew Ferguson
Consultant in Intensive Care Medicine and Anaesthesia
Craigavon Area Hospital
2. Why give this your attention?
• Microbes – the WMDs in your ICU
• Sepsis is the main killer of general ICU patients
• Anything that helps you beat it is good news
• We need better diagnostic & prognostic tools
3. The clock is ticking - the first 12 hours…
Funk and Kumar, Crit Care Clinics 2011; 53-76.
For first 12 hours, 1% mortality per 5
minute delay
4. Early antibiotics
Szczepura A, Osipenko L. Point of Care Diagnostics for Sepsis: Health Economic Considerations. Available at https://connect.innovateuk.org/documents/3187680/3710018/Sepsis-TSB-27-07-12-Economic-slides.pdf/d805c6a6-ecdf-
43c7-ac60-9e4da9d046fd;jsessionid=481FF37BC0ECFA0D6D41EC7474D20822.2
6. Conventional detection of sepsis
• 2 main strategies…
• Detection of bacterial pathogen
– Slow and all too often negative
• Detection of host response
– NEWS for fever, tachycardia, tachypnoea
– “Conventional” lab tests (WBC, CRP etc)
– The ICU eyeball test
1
2
7. What’s wrong with that?
• Physiological reserve determines presentation
• Physiological reserve determines trajectory
• Misdiagnosis in patients with comorbidity
• Recognition of severity is biased
• Prognostication is weakened
• There might not be an ICU eyeball
10. The biomarker paradigm…
• Sepsis leads to
– Inflammation
– Coagulation
– Tissue damage and repair
• The sicker you are, the greater the changes
• We can identify biomarkers for these processes
• We can measure these biomarkers
• We can stratify severity based on biomarker levels
• We can prognosticate based on biomarker levels
13. Biomarker Candidates
• Multiple, and growing all the time
• Some more common in the literature
• Linked to the main underlying processes
– Inflammation
– Coagulation
– Tissue damage
– Tissue repair
15. Questions to be answered
• Does the biomarker aid diagnosis?
• Does it provide additional prognostic info?
– For outcome
– For progression/decline
• Better than the ICU eye?
• Better than scoring systems?
16. Procalcitonin
• Bacterial infections
– > ubiqitous CALC-1 gene expression
– > release of PCT from all parenchymal tissues
– Procalcitonin (PCT) increases after 2-3 hours after
induction e.g. by endotoxin
– Falls with successful treatment
26. Cytokines - IL-6
• Can be reliably measured
• Not specific for sepsis (hence not diagnostic)
• PROGNOSTIC tool
– Increased mortality as level rises
– Increased risk of progression to severe sepsis/shock
27. Chemokines
• IL-8
• MCP-1 (monocyte chemoattractant protein 1)
• IL-8 can be used as diagnostic tool in sepsis
• MCP-1 can be used as PROGNOSTIC tool
– Mortality risk
38. Fatty acid 2 oxidation issue in non-survivors v survivors related to carnitine shuttle
(defective fatty acid transfer into mitochondria). Detectable at presentation.
39. Microparticles?
• Small vesicles shed from membranes of
apoptotic and stress-activated cells
– Endothelial cells, RBCs, monocytes, platelets
40. Conclusion
• Biomarkers have utility and potential
• Earlier detection of disease
• Earlier detection of high risk sub-groups
• Earlier recognition of treatment success
• Earlier de-escalation
• Adjunctive prognostication