The role of immune and metabolic biomarkers for improved management of sepsis patients

Abstract

Sepsis, the body`s overwhelming response to systemic infections, is responsible for significant morbidity, mortality, and financial burden. Pathogens and their antigens stimulate pro- and anti-inflammatory mediators and immune markers which characterize the host defense and orchestrate leukocyte recruitment to the acute site of infection. Different immune and metabolic biomarkers have been studied in relation to sepsis for their diagnostic and/or prognostic aid. Recent studies have provided abundant evidence that specific immune and metabolic biomarkers improve a physician`s ability to guide early sepsis recognition, severity assessment and therapeutic decisions in individual patients. This may allow for a transition from bundled sepsis care (protocols combining several medical practices) to more individualized management. First, lactate has now been widely used for risk stratification and guidance of fluid resuscitation. Second, procalcitonin correlates with risks of bacterial infections and helps guide therapeutic decisions about initiation and withdrawal of anti-microbial therapy. Third, prognostic markers such as pro-adrenomedullin improve early mortality prediction and thereby site-of-care decisions in respiratory infections. For these markers interventional trials have documented their value when integrated in clinical protocols.

Keywords::

• adrenomedullin
• antibiotic guidance
• biomarker
• lactate
• pro-ADM
• procalcitonin
• sepsis

Financial & competing interests disclosure

P Schuetz and B Mueller received support from B.R.A.H.M.S/Thermofisher and bioMérieux to attend meetings, fulfill speaking engagements and for unrestricted research grants. P Schuetz is supported by the Swiss National Science Foundation (SNSF Professorship, PP00P3_150531/1). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The authors wish to thank D Bielawski (Wayne State University, Detroit, MI, USA) for language editing of the manuscript, which was funded by University of Basel (Switzerland) without external support.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Every medical therapy has potential adverse effects, and selection of patients most likely to benefit is crucial, making more personalized approaches necessary.

• Immune biomarkers measured on admission and during follow-up can guide/support the clinician’s early recognition of sepsis, severity assessment and therapeutic decisions in individual patients.

• Biomarkers may allow transition from generalizing sepsis care bundles to a more tailored management in individual patients thereby reducing the risk for adverse treatment outcomes in patients who – based on their biomarker levels – do not likely benefit from therapy.

• Lactate improves initial risk stratification and prompts early fluid resuscitation.

• Lactate clearance may be used for assessing a patient’s response to fluids.

• Procalcitonin facilitates assessment of bacterial infection risk.

• Procalcitonin algorithms for guiding therapeutic decisions about initiation and duration of antimicrobial therapy have shown strong effects in regard to lower antibiotic consumption and appear to be safe regarding the results from interventional trials.

• Proadrenomedullin is an inflammatory prognostic immune marker that improves early mortality prediction and might improve site-of-care decisions in patients with respiratory infections.

Notes