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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…
For first 12 hours, 1% mortality per 5
minute delay
Funk and Kumar, Crit Care Clinics 2011; 53-76.
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-ecdf43c7-ac60-9e4da9d046fd;jsessionid=481FF37BC0ECFA0D6D41EC7474D20822.2
6. Conventional detection of sepsis
• 2 main strategies…
1
• Detection of bacterial pathogen
– Slow and all too often negative
2
• Detection of host response
– NEWS for fever, tachycardia, tachypnoea
– “Conventional” lab tests (WBC, CRP etc)
– The ICU eyeball test
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
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•
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•
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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
38. Fatty acid b2 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