biomarkers
Biomarkers and
diagnostic parameters
Biomarkers can aid and shorten the clinical decision process in sepsis
when the limitations of biomarkers are taken into account and procalcitonin
monitoring has now been integrated into treatment algorithms
Frank Bloos MD PhD
Department of
Anaesthesiology and
Intensive Care Medicine,
Centre for Sepsis Control
& Care, Jena University
Hospital, Germany
Sepsis is among the most common causes of
death in hospitalised patients and hospital
mortality ranges from 28.3% to 41.1%.
Management guidelines recommend that
antimicrobial therapy and surgical source control
should be initiated as soon as possible to optimise
outcomes. 1 However, sepsis often remains
unrecognised. Current data demonstrate that
initiation of adequate therapy is often delayed for
hours. Results from culture-based pathogen
detection methods are only available after
a number of days and cannot help the clinician in
first treatment decisions. Conventional diagnosis
relies on clinically suspected infection and the
new onset of organ dysfunction, but initial
symptoms are often unspecific and are not
recognised as a serious infection. In 2003, the
PIRO (Predisposition – Infection – Response
– Organ dysfunction) concept for improved
characterisation and staging of patients with
sepsis was developed. Although this concept did
not find its way in clinical practice, the authors
stated that new biomolecular methods and
biomarkers should be future tools to aid the
diagnosis of sepsis. In the last decade, many of
these methods have been developed and are
available for the clinician. 2 However, the
availability of clinical studies regarding the
impact of such techniques on the clinical course
of the patient is limited.
Biomarkers in the rapid diagnosis of sepsis
Biomarkers used as diagnostic parameters in
sepsis include C-reactive protein (CRP),
procalcitonin (PCT), lactate and others.
CRP
CRP is an acute phase protein and is released
from the liver four to six hours after stimulation
(predominantly of IL-6) and levels peak around
36 hours. CRP has been shown to aid in the
diagnosis of infections such as pneumonia, acute
appendicitis or infectious complications after
colorectal surgery. However, CRP demonstrates
slow kinetics after onset of infection, and is also
elevated in minor infections and many non-
infectious causes of inflammation such as trauma,
surgery or rheumatic disorders. Indeed, CRP was
unable to predict infectious complications after
gastro-oesophageal cancer surgery and pancreatic
surgery. No prospective randomised studies of the
impact of CRP-guided treatment algorithms on
the clinical course of patients with severe sepsis
or septic shock are available. Diagnostic accuracy
in differentiating bacterial- from non-infectious
causes of infection was only moderate (sensitivity
0.75; specificity 0.67). 3 Its performance in the
differentiation of patients with sepsis from
non-infectious causes of systemic inflammation is
even lower. In general, diagnostic accuracy for
sepsis is inferior to procalcitonin. These
properties make CRP only of limited use for the
application in emergency and critical care. CRP is
a poor predictor of mortality in this patient
population and therefore cannot identify
populations at high risk. CRP levels decrease over
the first 48 hours when successful antimicrobial
therapy is initiated. 4 Thus, CRP might be a good
marker to monitor success of antimicrobial
therapy.
PCT
PCT is the pro-hormone of calcitonin, which is
normally produced in the C-cells of the thyroid
glands. Whereas all PCT is cleaved to calcitonin
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