Reviewed and revised 20 December 2015
- At least 178 different sepsis biomarkers have been described in the published medical literature, reflecting the complex pathophysiology of sepsis
- e.g. coagulation, complement, contact system activation, inflammation, and apoptosis
- also biomarkers of complications, e.g. troponin for myocardial dysfunction
- None have well proven clinical utility
- Most used are procalcitonin and CRP despite their limited ability to distinguish between sepsis and SIRS or to predict outcome
- Only 5 biomarkers have studies reporting sensitivity and sensitivity >90% as diagnostic tests
- Biomarkers have uses other than diagnosis (e.g. prognosis)
POTENTIAL USES OF SEPSIS BIOMARKERS
- rule out sepsis
- provide early intervention
- guide antimicrobial therapy
- assess response to therapy
- differentiate gram positive and gram negative infection
- distinguish bacterial from viral or fungal infection
- predict outcome
- distinguish local from systemic infection
- predict multi-organ failure
TYPES OF SEPSIS BIOMARKERS
Acute Phase Reactants
- C-reactive peptide (CRP)
- Erythrocycte sedimentation rate (ESR)
- CD types
- toll-like receptors
- TNF receptors
- IL-2 receptors
- many others
- interleukins (e.g. IL-27)
- macrophage inflammatory proteins
- monocyte protein
- protein C and S
- vascular endothelial damage markers
- vasodilation markers
- organ dysfunction markers
- many others!
IMPORTANT SEPSIS BIOMARKERS
Table adapted from Deranged Physiology — Sepsis Biomarkers
|Erythrocyte sedimentation rate (ESR)|
Non-infectious causes of elevation:
|C-reactive protein (CRP)|
non-infectious causes of elevation:
Non-infective causes of elevation:
Non infectious causes of elevation:
|Soluble triggering receptor expressed on myeloid cell 1 (sTREM-1)|
Elevated in non-septic patients:
PROBLEMS WITH THE USE OF SEPSIS BIOMARKERS
- sepsis is a multisystem disease
- varying effects in different patients
- no gold standard to diagnose sepsis (cultures often negative)
- course of mediators released changes throughout disease process
- most biomarkers have not yet been tested properly to assess assess reliability and validity
Combinations of biomarkers (e.g. procalcitonin and APTT waveform) may hold more promise
References and Links
FOAM and web resources
- Deranged Physiology — Sepsis Biomarkers
- Biron BM, Ayala A, Lomas-Neira JL. Biomarkers for Sepsis: What Is and What Might Be? Biomarker insights. 10(Suppl 4):7-17. 2015. [pubmed]
- Cho SY, Choi JH. Biomarkers of sepsis. Infection & chemotherapy. 46(1):1-12. 2014. [pubmed]
- Faix JD. Biomarkers of sepsis. Crit Rev Clin Lab Sci. 2013 Jan;50(1):23-36. doi: 10.3109/10408363.2013.764490. PubMed PMID: 23480440; PubMed Central PMCID: PMC3613962.
- Kibe S, Adams K, Barlow G. Diagnostic and prognostic biomarkers of sepsis in critical care. J Antimicrob Chemother. 2011 Apr;66 Suppl 2:ii33-40. doi: 10.1093/jac/dkq523. Review. PubMed PMID: 21398306.
- Pierrakos C, Vincent JL. Sepsis biomarkers: a review. Crit Care. 2010;14(1):R15. doi: 10.1186/cc8872. Epub 2010 Feb 9. Review. PubMed PMID: 20144219; PubMed Central PMCID: PMC2875530.
- Póvoa P, Salluh JI. Biomarker-guided antibiotic therapy in adult critically ill patients: a critical review. Ann Intensive Care. 2012 Jul 23;2(1):32. doi: 10.1186/2110-5820-2-32. PubMed PMID: 22824162; PubMed Central PMCID: PMC3475044.
- Shankar-Hari M, Deutschman CS, Singer M. Do we need a new definition of sepsis? Intensive care medicine. 41(5):909-11. 2015. [pubmed] [free full text]
- Singer M. Biomarkers in sepsis. Current opinion in pulmonary medicine. 19(3):305-9. 2013. [pubmed] [free full text]
Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.
After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.
He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE. He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.
His one great achievement is being the father of three amazing children.
On Twitter, he is @precordialthump.