Sepsis is one of the most common causes of significant morbidity and mortality in hospitalized patients as well as the most common cause of death in ICU patients. In addition, the earlier sepsis is identified and treated, the better the prognosis for the patient. We actually do not have a biochemical marker which can be used to effectively diagnose sepsis. Sepsis diagnosis depends on finding microbial infection by culture, and while PCR methods do exist to quickly identify bacteremia, in most institutions cultures take at least 24 hours to grow. To aid in the diagnosis, clinicians can check three biomarkers commonly considered “sepsis” markers: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and procalcitonin (PCT).
Despite being very different tests, these three assays are ultimately indicators of inflammation or the inflammatory response. ESR is a simple manual test that measures how far red cells sediment out of a blood sample in one hour. It is used as a marker of inflammation but is quite unspecific; several conditions can cause inflammation. The ESR can tell a clinician that inflammation exists but not the cause of that inflammation CRP is an acute phase reactant protein. Its production by the liver increases in acute inflammation. However, its levels will be affected by liver dysfunction. PCT is a pro-hormone produced by extra-thyroidal immune cells within 2-4 hours of a bacterial insult or an inflammatory response.
Deciding whether a biomarker is a good indicator of sepsis is made difficult by its complex pathology. Studies that show one marker performs better are contradicted by other studies that show it does not. The utility of PCT for predicting sepsis remains controversial for this reason. However PCT has shown to be useful for predicting prognosis in sepsis. Increasing PCT concentrations correlate with increasing severity and a poor prognosis. Decreasing or low concentrations indicate a good prognosis. PCT is also being used to guide antibiotic therapy, although this use should be limited to non-surgical/trauma ICU patients, which is where the studies have been done. Thus although PCT proponents consider it to be the best available biomarker indicator of sepsis, none of the three tests have been shown to be good at diagnosing sepsis. Unfortunately, all three of these biomarkers are indicative of an inflammatory response and not specific for sepsis itself. However, once sepsis is known, all three biomarkers can be used to monitor its progression and response to therapy.
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-Patti Jones PhD, DABCC, FACB, is the Clinical Director of the Chemistry and Metabolic Disease Laboratories at Children’s Medical Center in Dallas, TX and a Professor of Pathology at University of Texas Southwestern Medical Center in Dallas.