M E E T I N G A B S T R A C T S Open Access
36th International Symposium on Intensive
Care and Emergency Medicine
Brussels, Belgium. 15-18 March 2016
Published: 20 April 2016
P001
Sepsis impairs the capillary response within hypoxic capillaries and
decreases erythrocyte oxygen-dependent ATP efflux
R. M. Bateman, M. D. Sharpe, J. E. Jagger, C. G. Ellis
University of Western Ontario, London, Canada
Critical Care 2016, 20(Suppl 2):P001
Introduction: A hallmark of sepsis is early onset microvascular dys-
function. However, the mechanism responsible for maldistribution of
capillary blood flow is not understood. Evidence suggests red blood
cells (RBC) can sense local oxygen (O2) conditions and signal the vas-
culature, via adenosine triphosphate (ATP), to increase capillary flow.
We hypothesized that sepsis impaired microvascular autoregulation
over the entire capillary network, within a capillary and within the
RBC. Study objectives were to: 1) measure capillary response time
within hypoxic capillaries (capillaries with RBC hemoglobin oxygen
saturation (SO2) < 20 %), 2) test the null hypothesis that sepsis had
no effect on RBC O2-dependent ATP efflux and 3) develop a patho-
physiological model.
Methods: Hypotensive sepsis was studied in male Sprague-Dawley
rats using cecal ligation and perforation, with a 6-hour end point. Rat
hindlimb skeletal muscle microcirculation was imaged using a dual
wavelength spectrophotometric intravital microscopy system, and ca-
pillary RBC supply rate (SR = RBC/s), RBC SO2 and oxygen supply rate
(qO2 = pLO2/s) were quantified. Arterial NOx (nitrite + nitrate) and
RBC O2-dependent ATP efflux were measured using a nitric oxide
(NO) analyzer and gas exchanger, respectively.
Results: Compared to control, sepsis increased capillary stopped flow
and plasma lactate (p < 0.05). Increased plasma NOx (p < 0.001) was
related to increased capillary RBC SR (p = 0.027). Analysis of 30-
second capillary SR-SO2-qO2 profiles, revealed a shift towards de-
creased (p < 0.05) oxygen supply rates in some capillaries. Moreover,
capillary response time within hypoxic capillaries (time to restore ca-
pillary RBC SO2 > 20 %) increased 3-4 fold (p < 0.05). And, consistent
with impaired microvascular autoregulation, the RBC’s response to a
hypoxic environment, measured as RBC O2-dependent ATP efflux,
decreased by 62.5 % (p < 0.001).
Conclusions: Sepsis impaired microvascular autoregulation at the ca-
pillary and erythrocyte level. Impaired autoregulation was manifested
by increased capillary stopped-flow, increased capillary response time
within hypoxic capillaries, decreased capillary oxygen supply rate
and decreased RBC O2-dependent ATP efflux. This loss of local micro-
vascular control was partially off-set by increased capillary RBC sup-
ply rate, which correlated with increased plasma NOx.
Reference
Bateman RM, Sharpe MD, Jagger JE, Ellis CG: Critical care 2015, 19(1):389.
P002
Lower serum immunoglobulin G2 level does not predispose to
severe flu
J. Solé-Violán
1
, M. López-Rodríguez
1
, E. Herrera-Ramos
1
, J. Ruíz-
Hernández
1
, L. Borderías
2
, J. Horcajada
3
, N. González-Quevedo
1
,
O. Rajas
4
, M. Briones
5
, F. Rodríguez de Castro
1
, C. Rodríguez Gallego
6
1
Hospital Dr Negrín, Las Palmas de GC, Spain;
2
Hospital San Jorge,
Huesca, Spain;
3
Hospital Universitari del Mar, Barcelona, Spain;
4
Hospital
Universitario de la Princesa, Madrid, Spain;
5
Hospital Clínico y
Universitario de Valencia, Valencia, Spain;
6
Hospital Universitari Son
Espases, Palma de Mallorca, Spain
Critical Care 2016, 20(Suppl 2):P002
Introduction: IgG2 deficiency has been suggested to predispose to
severe H1N1 infection (1). However, contradictory findings have been
reported (2) and, therefore, further replication of these findings in
different cohorts need to be performed. The purpose of this study is
to assess the immunoglobulins and IgG subclasses levels, in a cohort
of patients with influenza.
Methods: We studied 137 Spanish patients who developed flu (80.3 %
by H1N1pdm virus). Diagnosis was confirmed by the detection of Influ-
enza virus in nasopharyngeal swabs using the Real-Time polymerase
chain reaction. Immmunoglobulins and IgG subclasses (Binding Site Hu-
man IgG Subclass kits) were measured in both acute and convalescent
phase and their correlation with severity was examined. We analyzed
genetic variants at IGHG2 in order to evaluated their role in the IgG2
levels. Clinical and immunological characteristics were compared using
the Chi-squared test or Fisher’s exact test when needed.
Results: Ninety-three patients were hospitalized and 49 required ad-
mission to intensive care unit. Sixty-four patients developed viral
pneumonia and 26 acute respiratory distress syndrome. No differ-
ences in the serum levels of IgG, IgA, IgM or IgG subclasses were ob-
served in the different subgroups according to severity of disease.
Genotype G2m n-/n- was associated with lower serum IgG2 levels in
the convalescent phase. Patients homozygous for the G2m(n-) allele
had significantly lower serum IgG2 levels (256.7 +/- 121.3 mg/dL, N =
16) than individuals carrying the G2m(n-) allele (n+/n- and n-/n- ge-
notypes, 334,5 +/- 120,4 mg/dL, N = 31) (p = 0.042). However no asso-
ciation of IgG2m genotypes and severity of flu was observed.
Conclusions: In our study we have not been able to replicate previ-
ously reported observations. IgG2 deficiency does not appear to be a
significant risk factor for severity of flu.
References
1. Gordon C. et al. Association between severe pandemic 2009 influenza A
(H1N1) virus infection and immunoglobulin G(2) subclass deficiency. Clin
Infect Dis. 2010;50(5):672-8.
Critical Care 2016, Volume 20 Suppl 2
DOI 10.1186/s13054-016-1208-6
© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative C ommons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
2. Chan JF et al. The lower serum immunoglobulin G2 level in severe cases
than in mild cases of pandemic H1N1 2009 influenza is associated with
cytokine dysregulation. Clin Vaccine Immunol 2011; 18:305-10.
P003
Brain protective effects of intravenous immunoglobulin through
inhibition of complement activation and apoptosis in a rat model
of sepsis
F. Esen
1
, G. Orhun
1
, P. Ergin Ozcan
1
, E. Senturk
1
, C. Ugur Yilmaz
2
,
N. Orhan
3
, N. Arican
4
, M. Kaya
2
, M. Kucukerden
3
, M. Giris
3
, U. Akcan
3
,
S. Bilgic Gazioglu
5
, E. Tuzun
3
1
Istanbul University; Medical Faculty of Istanbul, Anesthesiology and
Intensive Care, Istanbul, Turkey;
2
Istanbul University; Medical Faculty of
Istanbul, Physiology, Istanbul, Turkey;
3
Istanbul University; Institute of
Experimental Medicine, Neuroscience, Istanbul, Turkey;
4
Istanbul
University; Medical Faculty of Istanbul, Forensic Medicine, Istanbul,
Turkey;
5
Istanbul University; Institute of Experimental Medicine,
Immunology, Istanbul, Turkey
Critical Care 2016, 20(Suppl 2):P003
Introduction: Intravenous(IV) immunoglobulin(Ig) treatment is known
to alleviate behavioral deficits in the experimentally induced model
of sepsis. To delineate the mechanisms by which IVIg treatment pre-
vents neuronal dysfunction, an array of immunological and apoptosis
markers was investigated.
Methods: Sepsis was induced by cecal ligation perforation(CLP) in
rats. The animals were divided into five groups; sham, control, CLP +
saline, CLP + immunoglobulin G IgG(250 mg/kg,iv), and CLP + immu-
noglobulins enriched with immunoglobulin M- IgGAM(250 mg/kg,iv).
Blood and brain samples were taken in two sets of experiments after
CLP to see the early(24 hrs) and late(10 days) effects of treatment.
Total complement activity, complement 3(C3) and soluble comple-
ment C5b-9 levels were measured in sera of rats using ELISA-based
methods. Cerebral complement content was analyzed by Western
Blot. Immune cell infiltration and gliosis were examined by immuno-
histochemistry using cluster of differentiation 3, CD4, CD8, CD11b,
CD19 and glial fibrillary acidic protein antibodies. Apoptotic neuronal
death was investigated by TUNEL staining and Western Blot-based
semi-quantitative evaluation of brain homogenates by bax and bcl-2
antibodies.
Results: IV IgG and IgGAM administration significantly reduced sys-
temic complement activity but increased serum C3 and soluble C5b-
9 levels. Likewise, Western Blot data showed slightly increased C5b-9
expression and significantly reduced C1q expression in brain samples
of IgGAM-treated but not IgG-treated septic rats especially in the first
day of administration. No cerebral cellular infiltrates were observed
in treated and non-treated septic rats. By contrast, IV IgG and IgGAM
treatment induced considerable amelioration in glial cell proliferation
which was increased in non-treated rats. IgG and IgGAM treated rats
exhibited significantly reduced numbers of apoptotic neurons and
cerebral expression levels of bax and bcl-2 as compared to non-
treated rats.
Conclusions: We suggest that IV IgG and IgGAM administration ame-
liorates neuronal dysfunction and behavioral deficits by reducing
apoptotic cell death and glial cell proliferation. IgGAM treatment
might be suppressing classical complement pathway by reducing
C1q expression.
P004
Adenosine a1 receptor dysfunction is associated with leukopenia:
A possible mechanism for sepsis-induced leukopenia
R. Riff
1
, O. Naamani
1
, A. Douvdevani
2
1
Ben-Gurion University of the Negev, Beer-Sheva, Israel;
2
Soroka Medical
Center, Beer-Sheva, Israel
Critical Care 2016, 20(Suppl 2):P004
Introduction: Most patients survive the initial hyper-inflammatory
phase of severe sepsis and reach an intensive care unit with im-
munosuppression. Adenosine, a potent modulator of in fl;ammation
and immunity is strongly elevated in blood of septic patients. We
have previously shown that adenosine A1 receptor (A1R, Gi receptor)
dominates the pro-inflammatory phase of bacterial peritonitis and
that activation of this receptor by a specific agonist induces A2AR
(Gs) expression and dominance during the resolution phase of inflam-
mation. In this study we aimed to elucidate the role of adenosine and
its receptors in sepsis-associated leukopenia. We hypothesized that ele-
vated adenosine levels in sepsis affects the normal development of
lymphocytes through down-regulation of A1R.
Methods: Polymicrobial severe sepsis was induced in C57BL/6 mice
by cecal ligation and puncture (CLP) with an 18G needle. Blood and
bone marrow (BM) cell counts, as well as flow cytometry were per-
formed at 24 h post sepsis induction.
Results: CLP-treated mice exhibited significantly lower number of
WBC compared to sham controls (9.15 ± 2.65 vs. 3.21 ± 1.58 cells x
10^3/μl). Sham A1R-/- mice showed lower WBC counts compared to
sham WT littermate (4.5 ± 3.24 cells x10^3/μl, p < .05). No significant
difference was observed in WBC count between the sham A1R-/- and
CLP WT groups. Similarly, desensitization of A1R by agonist (CCPA) or
elimination of A1R with A1R antagonist (DCPCX) were associated
with leukopenia. The T-cell was the main cell population affected by
CLP and A1R elimination. Apoptotic rate of nucleated BM cells in
sham A1R-/- mice was similar to the rate observed in WT CLP mice,
and almost 2-fold greater than the early apoptosis rate (Annexin V+,
7-ADD-) shown in WT sham group (3.64 ± 1.23 % vs. 1.86 ± 0.59 %, re-
spectively, p < .05). Interestingly, CLP-A1R-/- mice were shown to pro-
duce less interleukin (IL)-15 in lavage fluid compared to CLP-WT mice
(8.8 ± 6.0 vs. 35.3 ± 9.8 pg/ml, respectively p < .001).
Conclusions: The similarities in the phenotype induced by sepsis and
suppression of A1R support our hypothesis that dysfunction/down-
regulation of the Gi-A1R at the onset of sepsis changes the effect of
adenosine towards Gs-A2AR/A2BR-mediated leukopenia and immune
paralysis. Suppression of IL-15 might be a part of the mechanism of
leukopenia observed in CLP-treated mice and A1R-/- mice.
P005
Analysis of neutrophil by hyper spectral imaging - A preliminary
report
R. Takegawa
1
, H. Yoshida
1
, T. Hirose
1
, N. Yamamoto
1
, H. Hagiya
1
,
M. Ojima
1
, Y. Akeda
1
, O. Tasaki
2
, K. Tomono
1
, T. Shimazu
1
1
Osaka University Graduate School of Medicine, Suita, Japan;
2
Nagasaki
University Graduate School of Biomedical Sciences, Nagasaki, Japan
Critical Care 2016, 20(Suppl 2):P005
Introduction: Neutrophil play an important role as the first line of
innate immune defense. Activated neutrophils become segmented
and cytoplasm grows larger including granules. However, some-
times it is difficult to diffentiate whether the segmented neutro-
phils are on the process to grow up or not, and to decide to stop
antibiotics or not. There are some reports that hyper spectral im-
aging (HSI) is available for analysis including diagnosis of malaria
infected cells and distinction o f the cells to produce antibody. In
this study, we evaluated serial changes of HSI spectrum in patients
with infection, and examined wh ether we could distinguish acti-
vated neutrophils or not.
Methods: Sputum and urine samples were collected from the clin-
ically ill three patients with pulmonary infection(n = 2) and urinary
tra ct infection( UTI; n = 1). These samples were smeared on glass
slides and gram stain was conducted. We observed the slides with
HSI to get the hyper spectral data 10 times from each cytoplasm
of neutrophil, and analyzed hyper spectral data with the software
system, MultiSpec®.
Results: We could find that neutrophils have different spectrum in
each infectious stage, especially during from 400 to 700 nm wave-
length. Representative image of a patient with UTI was shown in
Fig.
1. When the neutrophils became segmented and had phagocyt-
osis, the cytoplasm of neutrophil enlarged and showed strong inten-
sity (black lines) compared to when microorganism disappeared and
the size of cytoplasm decreased (blue and red lines).
Conclusions: We could find the serial changes of spectrum of neutro-
phils during each infectious stage. HSI may be available to decide
start or termination of antibiotics. Further study is required to estab-
lish the cut off intensity level of the activated neutrophils.
Critical Care 2016, Volume 20 Suppl 2 Page 14 of 182
P006
Chemiluminescent intensity assessed by eaa predicts the incidence
of postoperative infectious complications following
gastrointestinal surgery
S. Ono
1
, T. Kubo
2
, S. Suda
1
, T. Ueno
1
, T. Ikeda
1
1
Tokyo Medical University Hachioji Medical Center, Hachioji, Tokyo,
Japan;
2
National Defense Medical College, Tokorozawa, Saitama, Japan
Critical Care 2016, 20(Suppl 2):P006
Introduction: Recent studies have demonstrated that the endotoxin
activity levels, which were analyzed using the Endotoxin Activity
Assay (EAA), correlated with the severity of sepsis in patients ad-
mitted to the ICU. On the other hand, there are several reports that
they dispute the c linical utility of the EAA. We focused on chemilu-
minescent intensity (CI) in response to lipopolysaccharide (LPS) by
EAA and evaluated the predictive value for the incidence of post-
operative infectious complications following elective gastroentero-
logical surgery.
Methods: Forty eight patients who underwent elective surgery for
gastrointestinal cancer were enrolled in this study. Blood samples
were taken on the previous day (before surgery), and on the first
(POD1) and third postoperative days (POD3). All blood samples were
analyzed using the EAA system. We focused on CI max, which is max-
imally stimulated with LPS and the minimum CI, which is only stimu-
lated with opsonized zymosan.
Results: Postoperative infectious complications occurred in 23 of
the 48 pat ients. There were significant differences in the E A levels
between patients who developed postoperative infectious com-
plications and patients who did not o n POD3. Minim um CI was
significantly higher in the patients who developed postoperative
infectious complications at all points compared to those from the
patients who did not. In addition, the ratio of maximal CI to mini-
mum CI, which reflects the neutrophil function against maximal
LPS, was significantly lower before surgery and on POD1 in patients
who developed postoperative infectious complications. Although a
significant positive correlation was observed between the neutro-
phi l counts and maximal CI or minimum CI, no correlation was ob-
served between the neutrophil counts and the ratio of maximal CI
to minimum CI.
Conclusions: Chemiluminescent intensities, especially the ratio of
maximal CI to minimum CI, could be an early predictive marker for
the development of postoperative infectious complications.
P007
Serial change of c1 inhibitor in patients with sepsis – Aprospective
observational study
T. Hirose, H Ogura, H Takahashi, M Ojima, J Kang, Y Nakamura, T Kojima,
T Shimazu
Osaka University Graduate School of Medicine, Suita, Japan
Critical Care 2016, 20(Suppl 2):P007
Introduction: C1 inhibitor (C1INH), belonging to the superfamily of
serin protease inhibitors, regulates not only complement system, but
also plasma kallikrein-kinin system, fibrinolytic system and coagula-
tion system. The biologic activities of C1INH can be divided into the
regulation of vascular permeability and anti-inflammatory functions.
The objective of this study was to clarify the serial change in C1INH
in patients with sepsis and evaluate the impact of C1INH on their
clinical course.
Methods: This study was a single center prospective observational
study. We serially examined C1INH activity values (normal range 70-
130 %) in patients with sepsis admitted into the intensive care unit
of the Trauma and Acute Critical Care Center at Osaka University
Hospital (Osaka, Japan) during the period between January 2014 and
August 2015. We defined refractory shock as septic shock unrespon-
sive to the conventional therapy such as adequate fluid resuscitation
and vasopressor therapy to maintain hemodynamics.
Results: The serial change of C1INH was evaluated in 40 patients with
sepsis (30 male and 10 female; 30 survivors and 10 non-survivor; mean
age, 70+/-13.5 years). We divided patients into three groups such
as (i) non-shock group (n = 14), (ii) non-refractory shock group
(n = 13), (iii) refractory shock group (n = 13, survivors; n = 3, non
sur vivors; n = 10). In no n-sh ock group , C1INH were 107.3+/-26.5 %
at admission and 104.2+/-22.3 % at day1, and it increased after
day1 (128.1+/-2 6.4 % at day3, 138.3+/-21.2 % at day 7, 140.3+/-
12.5 % at day 14)(p = 0.0040). In non-refractory shock group,
C1INH were 113.9+/-19.2 % at admission and it increased after admis-
sion (120.2+/-23.0 % at day1, 135.7+/-19.9 % at day3, 138.8+/-17.2 % at
day 7, 137.7+/-10.7 % at day 14)(p = 0.0029). In refractory shock group,
C1INH were 96.7+/-15.9 % at admission and 88.9+/-22.3 % at day1 and
it increased after day1 (119.8+/-39.6 % at day3, 144.4+/-21.1 % at day 7,
140.5+/-24.5 % at day 14)(p < 0.0001). The difference between these
three groups was statistically significant (p = 0.0039). C 1INH in non-
survivors did not increase significantly during their clinical course
(p = 0.0773).
Conclusions: In refractory shock patients with sepsis, the values of
C1INH were low (especially in non survivors) at admission and day 1.
The validity of C1INH replacement therapy in patients with septic
shock may lead to a new strategy for management in sepsis.
Fig. 1 (Abstract P005).
Critical Care 2016, Volume 20 Suppl 2 Page 15 of 182
P008
Comparison of bacteremia and sepsis on sepsis related biomarkers
T. Ikeda, S. Suda, Y. Izutani, T. Ueno, S. Ono
Hachiouji medical center, Tokyo medical university, Tokyo, Japan
Critical Care 2016, 20(Suppl 2):P008
Introduction: When septic patients progress to endotoxin shock,
they become subject to high mortality rate. The mortality rate of sep-
tic patients with multiple organ failure has been reported to be 30-
80 %. Recently, much sepsis related biomarkers have been measured
for diagnosis of sepsis.
Methods: We would like to clarify the difference of patient fs back-
ground and various biomarkers (Procalcitonin:, Presepsin., Interleukin-6,
Endotoxin activity assay:EAA,Angiopoietin-2) and 28-days mortality
rate in sepsis and bacteremia. Patients were classified as a g roup in
which blood culture was positive (BC-positive group: N = 31) or a
group in which blood culture was negative (BC-negative group:
N = 31).Blood cultures (blood samples were drown from different
two sites) were performed immediately after ICU admission due to
sepsis or septic shock. Results were expressed as mean+/-SD (median).
Statistical analysis was used with Mann-Whitney U-test and Chi square
test or Fisher’s test.
Results: Procalcitonin of BC-positive and BC-negative patients were
35.9}75.3 (7.8) and 17.1}30.9 (2.0) respectively. There are no signifi-
cant differences between the patients. Presepsin of BC-positive and
BC-negative patients were 2726}3208 i2147 jand 2733}2558 i2281 jre-
spectively, also, no significant difference between the groups.
EAA level of BC-positive patients was 0.54}0.20 (0.58), while that in
BC-negative patients was 0.37}0.26 (0.36), and the difference be-
tween the groups was statistically significant (p < 0.05). Angiopoietin-
2 of BC-positive and BC-negative patients were 16943}22793 i12000
jand 7457}7068 i5080 jrespectively. There is also a significant difference
(p < 0.05) between the groups. IL-6 of BC-positive and BC-negative pa-
tients were 2988}10602 i212 jand 516}1703 i107 jrespectively, but, no
difference between the groups. 28-days survival rate was 90.9 % in BC-
positive patient and 87.1 % in BC- negative patient. There were no sig-
nificant data in the two groups.
Conclusions: The values of EAA and Angiopooitin-2 of BC-positive
patients were significant higher than BC-negative patients. But, no
significant differences on 28-days mortality between the groups were
existed. These results showed discrepancy to our previous report1).
We shold be more evaluating about the patient’s basic disease.
Reference
1) T. Ikeda, K. Ikeda, S. Suda, et al.: Usefulness of the endotoxin activity assay
as a biomarker to assess the severity of endotoxemia in crit ically ill
patients. Innate immunity, 2014, DOI: 10.1177/1753425913516885
P009
The changes of procalcitonin levels in critical patients with
abdominal septic shock during blood purification
T. Taniguchi
1
, M. Okajima
2
1
Kanazawa University, Kanazawa, Japan;
2
Kanazawa University Hospital,
Kanazawa, Japan
Critical Care 2016, 20(Suppl 2):P009
Introduction: Procalcitonin (PCT) is an early, sensitive and accurate
marker for sepsis. Especially, several studies indicated that PCT is an
important indicator to diagnose infection, predict outcomes or guide
treatment of abdominal sepsis. Recently, blood purification (BF) such
as endotoxin absorption therapy (polymyxin B [PMX] hemoperfusion)
and continuous renal replacement therapy (CRRT) has been carried
out for abdominal septic shock. However, there are few studies about
the changes of PCT levels in abdominal septic shock during BF.
Therefore, we retrospectively evaluated the changes of PCT levels in
critical patients with abdominal septic shock during BF.
Methods: Twenty-four patients (M/F 17/7, mean age 61 years) with
abdominal septic shock underwent BF (PMX and CRRT). PMX was
undergone twice and CRRT was undergone for 5 days. The changes
of PCT levels and other inflammatory mediators such as blood WBC
counts, CRP levels and lactate levels during BF were measured for
5 days. Moreover, SOFA and survival rate 14 days after ICU admitted
were measured.
Results: Hemodynamics in all patients improved at 8 hrs after BF.
The PCT levels were improved (66.0 to 12.7 ng/mL; p < 0.05), but
WBC counts (8,420 to 10,380 /uL) and CRP levels (9.3 to 9.0 mg/dL)
were not improved 5 days after BF. SOFA scores decreased (12.5 to
7.0; p < 0.05) at 5 days after BF. All patients recovered and discharged
in ICU. There was significantly correlation between PCT and SOFA
scores (Y = 9.04 + 0.02X; R2 = 0.112, p < 0.0001), but there were no
correlation between PCT and other mediators.
Conclusions: In the present study, the PCT levels in critical patients
with abdominal septic shock improved after BF and there was signifi-
cantly correlation between PCT and SOFA scores.
P010
Validation of a new sensitive point of care device for rapid
measurement of procalcitonin
C. Dinter
1
, J. Lotz
2
, B. Eilers
3
, C. Wissmann
1
, R. Lott
2
1
ThermoFisher, Hennigsdorf, Germany;
2
Institut für Klinische Chemie und
Laboratoriumsmedizin, Mainz, Germany;
3
MVZ Labor Limbach Gruppe,
Berlin, Germany
Critical Care 2016, 20(Suppl 2):P010
Introduction: Procalcitonin (PCT), a highly sensitive and specific bio-
marker for bacterial infections, is increasingly being used in the ED
and ICU for the diagnostic work up of patients with LRTI and sepsis.
Recently, Samsung IB BRAHMS PCT, a new point of care
(POC) test, has been developed for a fast PCT measurement of whole
blood and EDTA samples with a measuring range of 0.08 - 10 μg/L.
The objective of this evaluation study was to determine the correl-
ation of the Samsung IB BRAHMS PCT test to established reference
methods.
Methods: This study was conducted to examine the correlation of
the Samsung IB BRAHMS PCT to the established reference methods
BRAHMS PCT sensitive Kryptor and BRAHMS PCT Elecsys at two
German Laboratories. The design was based on the related CLSI
Guidelines EP09-A3 (Measurement Procedure Comparison and Bias
Estimation Using Patient Samples). The study compared PCT values
using EDTA plasma determined with reference methods with results
determined with Samsung IB BRAHMS PCT using EDTA whole blood
and EDTA plasma over the whole measuring range of the assay in
patients undergoing routine care PCT measurement.
Results: 256 patients were included over a 6 weeks period. The cor-
relation between EDTA whole blood or plasma and the reference
method was r- = 0.97, the correlation of plasma and whole blood
samples, both determined on the Samsung analyzer, was r = 0,98.
The clinical concordance was 94 % related to a 0.5 μg/L threshold in
whole blood. No significant bias was observed (0.033 and 0.034 for
venous whole blood and plasma respectively, compared to the refer-
ence method). No difference was observed comparing imprecision of
whole blood and plasma. The total CV was < 14.5 % for concentra-
tions between 0.45 and 4.54 μg/L. The time to result of the Samsung
IB BRAHMS PCT was 20 min.
Conclusions: This study found an excellent correlation and diagnostic
accuracy of the new, sensitive POC device for rapid measurement of
procalcitonin. The Samsung IB BRAHMS PCT test allows an accurate
measurement of PCT at a point of care, where near patient testing is
Fig. 2 (Abstract P009).
Critical Care 2016, Volume 20 Suppl 2 Page 16 of 182
practical, that is comparable to established lab based BRAHMS PCT
assays.
P011
Infection biomarkers in primary care patients with acute
respiratory tract infections – Comparison of procalcitonin and C-
reactive protein
M. M. Meili, P. S. Schuetz
Kantonsspital Aarau, Aarau, Switzerland
Critical Care 2016, 20(Suppl 2):P011
Introduction: There is a lack of studies comparing the utility of C-
reactive protein (CRP) with procalcitonin (PCT) for the management
of patients with acute respiratory tract infections (ARI) in primary
care. Our aim was to study first the correlation between these
markers, and second to compare their predictive accuracy in regard
to clinical outcome prediction.
Methods: This is a secondary analysis using clinical and biomarker
data of 458 primary care patients with pneumonic and non-
pneumonic ARI. We used correlation statistics (spearman’s rank test)
and multivariable regression models to assess association of markers
with adverse outcome, namely days with restricted activities and on-
going discomfort at day 14.
Results: At baseline, CRP and PCT did not correlate well in the overall
population (r2 = 0.16 and r2 = 0.04) and particularly in the subgroup
of patients with non-pneumonic ARI. Low correlations were also
found comparing cut-off ranges, day seven levels and biomarker
changes from baseline to day seven. High admission levels of CRP
(>100 mg/dL, regression coefficient 1.7, 95%CI 0.6 to 2.8) as well as
PCT (>0.5ug/L regression coefficient 2.3, 95%CI 0.3 to 4.3) were sig-
nificantly associated with days with restricted activities. There were
no associations of both markers regarding ongoing discomfort at day
14.
Conclusions: CRP and PCT levels do not well correlate and have both
have moderate prognostic accuracy in primary care patients with ARI
to predict clinical outcomes. The low correlation between both
markers calls for interventional research comparing these markers
head to head in regard to their ability to guide antibiotic decisions.
P012
Do we need a lower procalcitonin cut off?
H. Hawa, M. Sharshir, M. Aburageila, N. Salahuddin
King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
Critical Care 2016, 20(Suppl 2):P012
Introduction: Procalcitonin (PCT) has been proposed as a helpful tool
to guide treatment with antibiotics and to improve antibiotics stew-
ardship. [1,2,3] However the cut off for the PCT level has not been
agreed as different studies have suggested different thresholds to
predict the need for antibiotics, these cut off points ranged from
0.25 ng/mL – 1 ng/mL. In our hospital the reference range is set at
0.5 ng/mL. This study aimed at identifying the best PCT level to rule
out sepsis.
Methods: We have retrospectively reviewed 53 intensive care unit pa-
tients, who had serial PCT tests as part of their daily blood tests. Three
serial readings of PCT were collected in addition to microbiology cul-
ture results and whether the patient met the definition criteria for sep-
sis as set out in the 2001 International Sepsis Definition conference.
Results: Out of the 53 patients, 26 (49.05 %) patients had negative
microbiological cultures with no evidence of sepsis.
PCT test level of 0.13 ng/mL had 100 % sensitivity as no patient
below this cut off had evidence of sepsis or positive microbiology
culture. The Area under the ROC was 0.702 with 95 % Confidence
interval of 0.56-0.84 and a p value of 0.012 (Fig.
3).
Conclusions: Using lower PCT cut off would further enhance the abil-
ity of PCT to rule out sepsis in the critically ill patient.
References
1. Bouadma et al, Lancet. 2010 Feb 6;375(9713):463-74.
2. Burkhardt et al, Eur Respir J. 2010 Sep;36(3):601-7.
3. Hochreiter M, Critical care, 2009; 13(3): R83.
P013
The predictive role of C-reactive protein and procalcitonin
biomarkers in central nervous system infections with extensively
drug resistant bacteria
V. Chantziara, S. Georgiou, A. Tsimogianni, P. Alexandropoulos, A. Vassi,
F. Lagiou, M. Valta, G. Micha, E. Chinou, G. Michaloudis
Saint Savvas Hospital, Athens, Greece
Critical Care 2016, 20(Suppl 2):P013
Introduction: Central Nervous System (CNS) infections after neuro-
surgical procedures with extensively drug resistant bacteria (XDR), in
intensive care unit (ICU) patients, is a life threatening complication
requiring early identification and immediate action. Increased num-
ber of white blood cells (WBC), high temperature and circulating
acute phase proteins are common in those patients making timely
diagnosis challenging. We sought to investigate the reliability of
serum C-Reactive protein (CRP) and procalcitonin (PCT) to early iden-
tify and monitor CNS infections.
Methods: From January 2013 to November 2015 all cases with CNS
infections were recorded. Inclusion criteria were the presence of
fever > 38.5oC and compatible lumbar puncture findings (increased
number of polymorphonuclear leukocytes, increased protein and low
glucose compared to serum levels). The WBC, CRP and PCT levels be-
fore (when the inclusion criteria were met) and after the infection
(last intrathecal administration of Collistin 300.000 IU, Amikacin
25 mg and Vancomycin 25 mg) were compared.
Results: Twelve patients (mean age 45.7 ± 18.1) were studied. WBC
remained high before and after infection. Conversely, CRP values
were statistically different before and after the infection whereas the
PCT ones were not (Table
1).
Conclusions: Based on our findings CRP carries a better predictive
value than PCT as biomarker for early diagnosis and monitoring of
CNS infections in ICU. The small number of patients is a limitation for
these results.
Fig. 3 (Abstract P012).
Table 1 (Abstract P013).
Before CNS infection After CNS infection P value
WBC 13000 ± 6500 9700 ± 4200 0,12
CRP 18 ± 9.2 7.7 ± 4.7 0,06
PCT 13.4 ± 9.3 9 ± 2.2 0,2
Critical Care 2016, Volume 20 Suppl 2 Page 17 of 182