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.
Biomarkers in Sepsis
Utility or Futility?
Dr Andrew Ferguson
Consultant in Intensive Care Medicine and Anaesthesia
Craigavon Area Hospital
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
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
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-
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
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
The biomarker paradigm…
• Sepsis leads to
– 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
• Multiple, and growing all the time
• Some more common in the literature
• Linked to the main underlying processes
– Tissue damage
– Tissue repair
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?
• 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
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
• 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