Should heparin-binding protein levels be routinely monitored in patients with severe sepsis and septic shock?
Michal Holub
0
1
Ondej Beran
0
1
0
Department of Infectious and Tropical Diseases, First Faculty of Medicine, Charles University in Prague and Na Bulovce Hospital
,
Budinova 2, 180 81 Praha 8
,
Czech Republic
1
Abbreviations HBP
,
heparin-binding protein; IL, interleukin
-
Heparin-binding protein (HBP), also known as
azurocidin, has multiple functions in the inflammatory
process, especially during severe infections. Beside
its antimicrobial properties, HBP may induce vascular
leakage leading to extravascular efflux, which is an
important pathophysiologic event in the development
of septic shock. Not surprisingly, high HBP plasma levels
are found in severe sepsis patients and in septic shock
patients as well as in serious infections associated with
endothelial damage. In the present issue of Critical
Care, Linder and colleagues demonstrate new aspects
of HBP daily monitoring in ICU patients. The authors
observed that high HBP plasma levels are associated
with an increased mortality rate in both septic and
nonseptic critically ill patients, indicating that HBP
may be a reliable prognostic biomarker. However,
there are some limitations hindering rapid translation
of these interesting findings into the daily routine.
First, the group of nonseptic critically ill patients
(n=28) enrolled in the study was rather small as
compared with the septic group (n=151). Moreover,
50% of nonseptic patients developed infection
while hospitalized in the ICU, and to classify them
as truly nonseptic patients is problematic. Second,
there is a lack of a routine diagnostic method for HBP
analysis. Nevertheless, if the results of the present
study are validated in large clinical trials in different
ICU populations and cost-effectiveness data become
available, the serial HBP measurements will have a
promising future.
In the present issue of Critical Care, Linder and colleagues
present a new study in which they assess the clinical
importance of serial measurements of heparin-binding
protein (HBP) plasma levels in critically ill septic and
nonseptic patients [1]. They found that HBP plasma
levels are significantly higher in patients with severe
sepsis and septic shock in comparison with patients with
a nonseptic critical condition. The authors also
demonstrated that HBP plasma levels obtained at admission to
the ICU and during the last individual sampling are
higher in nonsurvivors as compared with survivors in
both the septic group and the whole study group.
Moreover, the high baseline HBP plasma levels in septic
patients were associated with an increased 28-day
mortality rate. Altogether, these results indicate that serial
HBP measurements might be very helpful in stratification
of ICU patients. However, there are some issues that
should be raised before the study results can be translated
into the daily routine.
The study was designed to compare HBP plasma levels
in patients with severe sepsis and septic shock with levels
in patients with noninfectious critical illness. However,
these two groups of patients were not equal in size. Also,
a significant proportion of patients from the nonseptic
group developed infection and was treated with
antibiotics. This raises the question of whether the
comparison between septic and nonseptic ICU patients is hindered
by this treatment. Nevertheless, the study design is
logical because finding a biomarker that would predict
development of any shock state is highly desirable.
Previous studies have demonstrated significant predictive
values of elevated levels of lactate, cortisol and IL-6 in the
blood of patients with different etiologies of shock [2-4].
However, these biomarkers have some limitations: lactate
levels are less influenced by arterial sampling,
endogenous cortisol levels are downregulated by
corticosteroids used in the treatment of septic shock or by
relative adrenal insufficiency, and IL-6 analysis is not
generally available in regular hospital laboratories [5].
Other routinely measured biomarkers such as
procalcitonin, C-reactive protein, neutrophil and lymphocyte
counts have only a limited value in prognostic scoring
of the critically ill patients and are mostly used in the
early diagnostics of bacterial etiology of critical illness
[6-8].
It is worth noting that HBP mediates multiple actions
during the infectious process. Notably, HBP has
antibacterial activity, which includes a direct microbicidal
effect, and also helps neutrophils to migrate into the focus
of infection. Similarly to HBP, C-reactive protein and IL-6
play an active role during the immune responses against
infections: C-reactive protein is an inflammation opsonin,
and the major function of IL-6 is amplification as well as
downregulation of inflammatory reactions, depending on
the concentrations [9,10]. Regarding procalcitonin, there
are only limited data from animal studies which
demonstrate that immunoneutralization of procalcitonin
improved survival in experimental porcine sepsis [11].
Additionally, elevate (...truncated)