Comparison of carbamylated versus recombinant erythropoietin
during spinal cord ischemia/reperfusion injury
F Simon, A Scheuerle, A Soell, M Groeger, O McCook, P Radermacher,
M Georgieff , E Calzia, H Schelzig
Ulm University, Ulm, Germany
Critical Care 2010, 14(Suppl 1):P1 (doi: 10.1186/cc8233)
Introduction We previously showed that erythropoietin (EPO) attenuates
the morphological signs of spinal cord ischemia/reperfusion (I/R) injury
in swine  without, however, improving neurological function. The
clinical use of EPO has been cautioned most recently due to serious safety
concerns arising from an increased mortality in acute stroke patients
treated with EPO and simultaneously receiving systemic thrombolysis
. Carbamylated EPO (cEPO) is an EPO derivative without erythropoietic
activity and devoid of the EPO side eff ects, but with apparently well
maintained cytoprotective qualities . We therefore tested the hypothesis
whether cEPO may be equally effi cient as EPO in reducing morphological
as well as functional aortic occlusion-induced spinal cord I/R injury.
Methods In a randomized and blinded trial pigs received either vehicle
(control, n = 9), EPO or cEPO, respectively (n = 9 each; 5,000 IU/kg over
30 minutes before and during the fi rst 4 hours of reperfusion). Animals
underwent 30 minutes of thoracic aortic balloon occlusion with catheters
placed immediately downstream of the A. subclavia and upstream of the
aortic trifurcation. Spinal cord function was assessed by motor evoked
potentials (MEP as percentage of the amplitude before aortic occlusion)
and lower limb refl exes (assessed as the subjective strength of response)
for a period of 10 hours after reperfusion. Tissue damage was evaluated
using Nissl staining.
Results Both EPO-treated and cEPO-treated animals presented with
attenuated spinal cord injury in the Nissl staining (median (quartile)
percentage of damaged neurons in the thoracic segments: control 27
(25,44), cEPO 8 (4,10), and EPO 5 (5,7), P <0.001 vs control group; in the
lumbar segments: control 26 (19,32), cEPO 7 (5,13), EPO 8 (5,10), P <0.001
vs control group). However, while only cEPO treatment was associated
with recovery of the MEP amplitude to pre-occlusion values when
compared with the control group (P <0.05), lower limb refl ex response
was comparably restored stronger in both treatment groups (P <0.05 vs
Conclusions In a clinically relevant porcine model mimicking aortic cross-
clamping during vascular surgery repair of thoracic aortic aneurysm, cEPO
protected spinal cord function and integrity as eff ective as EPO when
applied at equipotent doses.
Acknowledgements Supported by the Deutsche Forschungs gemein-
schaft (SCHE 899/2-2).
Crit Care Med 2008, 36:2143-2150.
Stroke 2009. [Epub ahead of print]
J Int Med 2008, 264:405-432.
Sodium 4-phenylbutylate protects against myocardial
ischemia-reperfusion injury by reducing unfolded protein
response-mediated apoptosis in mice
M Okajima1, M Takamura2, S Usui2, T Taniguchi1, S Kaneko2
1Kanazawa University Hospital, Kanazawa, Japan; 2Kanazawa University
Graduate School of Medical Science, Kanazawa, Japan
Critical Care 2010, 14(Suppl 1):P2 (doi: 10.1186/cc8234)
Introduction Unfolded protein response (UPR)-mediated apoptosis plays a
pivotal role in ischemia-reperfusion injury. Sodium 4-phenylbutyrate (PBA)
has been reported to act as a chemical chaperone inhibiting UPR-mediated
apoptosis triggered by ischemia in various organs other than the heart.
Therefore we investigated whether PBA reduces UPR-mediated apoptosis
and protects against myocardial ischemia-reperfusion injury in mice.
Methods C57BL/6 mice were subjected to 30 minutes LAD ischemia
followed by reperfusion. PBA (100 mg/kg) or PBS (control) was adminis-
trated intraperitoneally just before ischemia. Apoptosis, infarct size and
tissue protein levels of Grp78 and caspase-12 (UPR-mediated apoptosis-
associated protein) were evaluated by TUNEL, TTC stain and western blot
analyses, respectively, at 48 hours after ischemia (n = 5 for each group).
Echocardiography was performed at 3 weeks after ischemia and the
survival ratio was observed (n = 9 for each group).
Results Compared with PBS, PBA reduced apoptotic cells (30.8 ± 0.2% vs
20.5 ± 0.5%, P <0.05) and infarct size (32.0 ± 3.8% vs 13.0 ± 2.1%, P <0.01)
after ischemia-reperfusion. Grp78 and caspase-12 were increased in
mice with PBS, but PBA attenuated the increase in Grp78 (P <0.05) and
caspase-12 (P <0.05). PBA inhibited the deterioration of cardiac parameters
including LVEDD (3.35 ± 0.08 mm vs 2.74 ± 0.11 mm, P <0.01), LVESD
(2.30 ± 0.08 mm vs 1.54 ± 0.12 mm, P <0.01), and %FS (31.3 ± 2.2% vs 39.4 ±
2.2%, P <0.05). All mice with PBA survived, but 33% animals with PBS died.
Conclusions PBA maintained cardiac function and improved survival
ratio after myocardial ischemia-reperfusion by reducing UPR-mediated
apoptosis in mice.
1. Qi X, et al.: Mol Pharmacol 2004, 66:899-908.
2. Vilatoba M, et al.: Surgery 2005, 138:342-351.
© 2010 BioMed Central Ltd
30th International Symposium on Intensive Care
and Emergency Medicine
Brussels, Belgium, 9-12 March 2010
Published: 1 March 2010
Figure 1 (abstract P2). Phenylbutyrate reduced the unfolded protein
Critical Care 2010, Volume 14 Suppl 1
© 2010 BioMed Central Ltd
Time-dependent eff ects of intravenous H2S during long-term,
resuscitated porcine hemorrhagic shock
H Bracht1, F Simon1, B Hauser1, M Groeger1, A Soell1, O McCook1,
M Georgieff 1, P Radermacher1, C Szabo2, E Calzia1
1Ulm University, Ulm, Germany; 2University of Texas Medical Branch,
Galveston, TX, USA
Critical Care 2010, 14(Suppl 1):P3 (doi: 10.1186/cc8235)
Introduction In awake, spontaneously breathing mice, inhaling hydrogen
sulfi de (H2S) induced a hibernation-like metabolic state characterised by
reduced energy expenditure and hypothermia , which protected against
otherwise lethal hypoxia  and hemorrhage . In contrast, other authors
reported that inhibition of endogenous H2S synthesis attenuated post-
hemorrhage organ dysfunction [4,5]. All these data originate, however,
from unresuscitated models using a pre-treatment design. Therefore we
investigated the time-dependent eff ect of intravenous H2S in a clinically
relevant, long-term model of porcine hemorrhage and resuscitation.
Methods After surgical instrumentation, pigs were subjected to 4 hours
of hemorrhagic shock induced by removal of 40% of the calculated blood
volume and thereafter by additional removal or retransfusion of blood boli
as needed to maintain MAP = 30 mmHg. Animals randomly received vehicle
(control, n = 14) or the intravenous H2S donor Na2S started 2 hours before
hemorrhage (pre-treatment, n = 11), at the beginning of blood removal
(early post-treatment, n = 10) or at the beginning of resuscitation (late
post-treatment, n = 10). In all groups the Na2S infusion was continued over
the fi rst 10 hours of reperfusion. Resuscitation comprised retransfusion of
shed blood, colloid volume expansion, and noradrenaline titrated to keep
MAP at pre-shock levels. Systemic, renal and liver perfusion, O2 exchange,
and organ function were assessed before and at the end of hemorrhage
as well as at 10 and 22 hours of resuscitation.
Results Survival (71% in the control vs 100, 91, and 90% in the pre-
treatment, early post-treatment and late post-treatment groups, respec-
tively) was signifi cantly improved in all treatment groups. The noradrenaline
infusion rate required to maintain hemodynamic targets was signifi cantly
reduced in the early post-treatment group only, which coincided with a
progressive drop in core temperature and attenuated kidney dysfunction
(blood creatinine levels, creatinine clearance) in these animals.
Conclusions Na2S application improved survival regardless of the drug
timing. The less benefi cial eff ect of pre-treatment on organ function may
be due to the higher total amount of drug infused, possibly suggesting
some toxicity at these doses.
Acknowledgements Supported by the German Ministry of Defence, and
Ikaria Inc., Seattle, WA, USA.
Science 2005, 308:518.
Shock 2007, 27:370-372.
J Trauma 2008, 65:183-187.
Br J Pharmacol 2004, 143:881-889.
Infl amm Res 2008, 57:512-518.
An ovine intensive care model of septic shock
M Chapman1, M Maiden1, J Fraser1, C Nash1, F Crichton1, P Sideris2,
1Royal Adelaide Hospital, Adelaide, Australia; 2IMVS, Adelaide, Australia
Critical Care 2010, 14(Suppl 1):P4 (doi: 10.1186/cc8236)
Introduction Translation of previous animal studies into human ICU
clinical trials has frequently produced negative results. Most of these
animal studies have had high baseline mortality and have not employed
standardised management of sepsis as usually provided in an ICU. The
aim of this study was to develop a large animal model of septic shock
receiving standardised intensive care management, thus replicating the
management of septic shock in humans.
Methods Eleven Marino ewes (weight 60 to 70 kg, hemiazygous vein
ligated) were anaesthetised and had radiological guided catheters
inserted into the iliac, renal, and hepatic veins, coronary sinus, and the
pulmonary and carotid arteries. Tracheostomy tubes were inserted and
the animals mechanically ventilated while supported in a sling. Six sheep
were administered intravenous E. coli (ATCC 25922) 1.0 x 108 orgs/kg over
1 hour (septic sheep), fi ve received placebo (nonseptic sheep). For 24 hours,
animals were monitored and received sedation (midazolam + ketamine),
ventilation, fl uids and inotropes according to a protocol. Primary end-point
was noradrenaline (NA) dose to maintain mean arterial pressure (MAP)
of 75 mmHg. Secondary end-points included haemodynamic variables,
respiratory, hepatic, and renal function, haematology, acid–base status and
global, hind-limb, renal, hepatic and coronary oxygen extraction ratio (OER).
Results Sheep were successfully instrumented, monitored and supported
for 24 hours. Septic sheep required NA (mean dose 0.28 μg/kg/min vs 0.00,
P <0.001), developed a higher cardiac index (6.6 l/m2 vs 4.3, P <0.05) and
lower SVRI (769 dynes/m2 vs 1,804, P <0.05). At 24 hours, septic sheep had
renal impairment (creatinine 286 mmol/l vs 76, P <0.05; urea 12 mmol/l vs
7, P <0.05), metabolic acidosis (pH 7.21 vs 7.39, P <0.05; lactate 10.9 mmol/l
vs 1.2, P <0.01; pCO2 32 vs 31, P = 0.63), coagulopathy (INR 5.9 vs 1.9,
P <0.05; fi brinogen 0.9 g/l vs 2.7, P <0.05) but preserved respiratory and
hepatic function. Global OER was lower in septic sheep (0.16 vs 0.29,
P <0.05) as was coronary OER (0.36 vs 0.68, P <0.05). OER did not change
with sepsis in the kidney (0.09 vs 0.11, P = 0.52), liver (0.24 vs 0.31, P = 0.48)
and hind-limb (0.31 vs 0.42, P = 0.23).
Conclusions We have developed a large animal model of septic shock
that receives intensive care support and standardised management. This
model replicates much of the pathophysiology and management that
occurs in human septic shock. It allows a large range of physiological
parameters to be assessed when investigating new therapies for sepsis.
Eff ects of temperature and H2S inhalation on glucose metabolism in
murine resuscitated septic shock
K Baumgart1, F Wagner1, V Hysa1, J Vogt1, U Wachter1, S Weber1,
M Georgieff 1, P Radermacher1, C Szabo2, E Calzia1
1Ulm University, Ulm, Germany; 2University of Texas Medical Branch,
Galveston, TX, USA
Critical Care 2010, 14(Suppl 1):P5 (doi: 10.1186/cc8237)
Introduction In awake, spontaneously breathing mice, inhaling hydrogen
sulfi de (H2S) induced a hibernation-like metabolic state characterised by
reduced energy expenditure and hypothermia , which protected against
otherwise lethal hypoxia  and hemorrhage  as a result of impaired
cellular energy metabolism . Therefore, we investigated the metabolic
eff ects of inhaled H2S in our model of resuscitated murine septic shock.
Methods Sixteen hours after induction of sepsis by cecal ligation and
puncture (CLP) or sham operation, anesthetized and mechanically ventilated
mice received 100 ppm H2S or vehicle over 5 hours at body temperatures
of 38 and 27°C, respectively. During the observation period, hyperdynamic
hemodynamics were maintained by colloid resuscitation and noradrenaline
infusion . Endogenous glucose production was calculated from blood
13C6-glucose isotope enrichment derived from the rate of appearance of
stable, non-radioactive labeled 1,2,3,4,5,6-13C6 glucose during continuous
isotope infusion . Whole-body glucose oxidation rate was derived from
the total CO2-production rate, the mixed expiratory 13CO2/12CO2 isotope ratio
and the 13 C6-glucose infusion rate after the steady state was achieved.
Results While endogenous glucose production was not aff ected by
hypothermia, it was signifi cantly higher in the septic animals when
compared with the corresponding sham operated groups, most likely
due to the ongoing noradrenaline infusion. In contrast, despite the
catecholamine infusion and higher glucose release, whole body glucose
oxidation was signifi cantly reduced in normothermic septic animals.
During hypothermia, H2S shifted substrate towards preferential glucose
utilisation, but this eff ect disappeared in the septic mice.
Conclusions H2S inhalation alone does not infl uence glucose metabolism
once temperature is maintained at normothermic levels in anesthetised
and mechanically ventilated mice. The H2S-related shift of energy meta-
bo lism towards preferential carbohydrate oxidation present during
hypothermia is blunted during sepsis, possibly as a result of the ongoing
Acknowledgements Supported by the Deutsche Sepsis Gesellschaft, the
DFG KFO 200, and Ikaria Inc., Seattle, WA, USA.
Critical Care 2010, Volume 14 Suppl 1
Science 2005, 308:518.
Shock 2007, 27:370-372.
J Trauma 2008, 65:183-187.
J Am Soc Nephrol 2009, 20:1901-1905.
Intensive Care Med 2009, 35:344-349.
Crit Care Med 2010, 38:in press.
Mitochondrial respiration and cytochrome c inhibition by sulfi de in
peritoneal macrophages in vitro: eff ects of temperature and pH
M Groeger1, F Wagner1, K Baumgart1, M Huber-Lang1, M Knoeferl1,
M Georgieff 1, P Radermacher1, C Szabo2, E Calzia1
1Ulm University, Ulm, Germany; 2University of Texas Medical Branch,
Galveston, TX, USA
Critical Care 2010, 14(Suppl 1):P6 (doi: 10.1186/cc8238)
Introduction Hydrogen sulfi de (H2S) is a potent inhibitor of cytochrome
c oxidase (COX) and, thus, of mitochondrial respiration . Since H2S was
reported to induce a suspended animation-like status characterized by
reduced energy expenditure and hypothermia , we sought to determine
the eff ect of hypothermia on mitochondrial respiratory capacity and H2S-
related COX inhibition. We further studied the infl uence of variations in pH
on both variables.
Methods All measurements were conducted in digitonin-permeabilised
cultured peritoneal macrophages using high-resolution respirometry 
(Oxygraph-2k, Oroboros, Austria). Maximum mitochondrial respiration (1
to 2 Mio cells/ml respiration medium) was achieved in the uncoupled
state by adding pyruvate, malate, glutamate and succinate as respiratory
substrates. Then, in one of the two chambers of the oxygraph, mitochondrial
respiration was inhibited stepwise by incremental concentrations of the
H2S donor Na2S (1 to 64 μM). In the parallel chamber, the identical inhibitor
titration sequence was preceded by the inhibition of the respiratory chain
by rotenone and antimycin A followed by the selective stimulation of the
COX after addition of ascorbate and TMPD. COX excess capacity (% of
OXPHOS) was calculated based on the ratio of inhibition of mitochondrial
respiration with full operating respiratory chain versus the COX-stimulated
condition. This experimental sequence was repeated at 37°C and 25°C
with a medium pH of 7.1 and then at 37°C with a pH of 6.8 and 7.7.
Results COX excess capacity (median (quartiles)) was signifi cantly higher
at 25°C than at 37°C (134 (113; 140) vs 61 (47; 79)), most likely due to the
almost halved mitochondrial respiratory capacity at hypothermia (50 (37;
63) vs 95 (81; 103) pmolO2/s x Mio cells). Changing the medium pH from
6.8 to 7.7 signifi cantly increased the COX excess capacity (91 (79; 103) vs 71
(64; 82) pmolO2/s x Mio cells), which again was related to the signifi cantly
lower mitochondrial respiratory capacity with more acidic conditions (80
(70; 89) vs 94 (85; 98)).
Conclusions Our results suggest that COX excess capacity is temperature
as well as pH dependent in peritoneal macrophages. This eff ect may
protect cells from H2S toxicity at low temperatures and high pH values.
Acknowledgements Supported by the Deutsche Forschungs ge mein-
schaft (KFO 200).
Science 2005, 308:518.
Toxicol Sci 2002, 65:18-25.
Biochim Biophys Acta 2006, S14:201-202.
Alterations of caspase 9 mRNA gene expression in survivors and
nonsurvivors of severe sepsis
M White1, D Doherty2, D Kelleher2, R McManus2, T Ryan1
1St James Hospital, Dublin, Ireland; 2Trinity College, Dublin, Ireland
Critical Care 2010, 14(Suppl 1):P7 (doi: 10.1186/cc8239)
Introduction Sepsis-induced lymphocyte apoptosis plays a fundamental
role in the pathophysiology of sepsis. Recent animal models of sepsis have
identifi ed anomalies in the extrinsic apoptotic pathway, a key pathological
occurrence in sepsis . Specifi cally apoptosis markers such as caspases
1, 3, 8, 9 and FADD have been shown to be signifi cant in animal models
of infection .We investigated mRNA transcription of these markers in a
human model of severe sepsis. We hypothesized that ICU mortality from
severe sepsis is associated with distinctive gene expression of extrinsic
Methods A prospective observational study of patients with severe sepsis
was performed. Mononuclear cells were isolated from 48 patients with
severe sepsis. Total RNA was extracted from samples for day 1 of admission
and again on day 7. FADD, caspase 1, 3, 8, and 9 mRNA was quantifi ed
with quantitative real-time polymerase chain reaction (qRT-PCR). Standard
demographic and outcome data were recorded. Between-group
comparisons were performed by Wilcoxon rank sum test. All values are
stated as median and interquartile range.
Results Sixteen of the 48 patients died in the ICU. Caspase 9 mRNA copy
numbers were signifi cantly increased on day 7 in the survivor group (5.4 x
106; 7.4 x 106 to 8.9 x 106) compared with death in the ICU group (1.9 x
106; 3.0 x 106 to 1.2 x 106) P = 0.001. FADD, caspase 1, 3 and 8 mRNA copy
numbers were not signifi cantly diff erent between patients who died and
those discharged from the ICU on either day 1 or day 7 of admission.
Conclusions Caspase 9 may be an important regulator of apoptotic
mechanisms in humans with late sepsis. Pro-apoptotic mechanisms may
have a role in the resolution of severe sepsis.
Acknowledgements This study is funded by the Association of Anaes-
thetists of Great Britain and Ireland and the Intensive Care Society Ireland.
1. Oberholzer C, et al.: Apoptosis in sepsis: a new target for therapeutic
exploration. FASEB J 2001, 15:879-892.
2. Hotchkiss R, et al.: Accelerated lymphocyte death in sepsis occurs by both
the death receptor and mitochrondrial pathways. J Immunol 2005,
The TLR4 antagonist CRX-526 reduces LPS-induced leukocyte
activation and improves capillary perfusion of the rat intestine
M Soltow1, K Zimmermann1, D Pavlovic1, J Zhou2, S Whynot2, O Hung2,
M Murphy2, B Johnston2, C Lehmann2
1Ernst Moritz Arndt University, Greifswald, Germany; 2Dalhousie University,
Critical Care 2010, 14(Suppl 1):P8 (doi: 10.1186/cc8240)
Introduction Toll-like receptor 4 (TLR4) represents an important mediator
of endotoxin-related signal transduction. The aim of our study was to
evaluate whether TLR4 inhibition after onset of experimental endotoxemia
is able to improve the intestinal microcirculation, which is crucial in the
pathogenesis of septic multiple organ failure.
Methods We studied four groups of animals (Lewis rats, n = 10 per
group): healthy controls (CON group), endotoxemic animals (15 mg/kg
lipopolysaccharide, LPS group), endotoxemic animals treated with TLR4
antagonist (1 mg/kg CRX-526, LPS + CRX group), and CRX-526 treated
controls (CRX group). Intravital microscopy of the intestinal microcirculation
was performed following 2 hours of observation in all animals. Blood samples
were taken for cytokine measurements at the end of the experiments.
Results Following 2 hours of endotoxemia we observed a signifi cant
increase of leukocyte adhesion in the intestinal submocosal venules
(for example, V1 venules: CON 20.4 ± 6.5 n/mm2, LPS 237.5 ± 36.2 n/
mm2, P <0.05). Capillary perfusion of the muscular and mucosal layers of
the intestinal wall was signifi cantly reduced (for example, longitudinal
muscular layer: CON 112.5 ± 5.9 cm/cm2, LPS 71.3 ± 11.0 cm/cm2). TLR4
inhibition reduced leukocyte activation (V1 venules: 104.3 ± 7.8 n/mm2)
and improved capillary perfusion (longitudinal muscular layer: 111.0 ±
12.3 cm/cm2) signifi cantly. Cytokine release was not aff ected.
Conclusions Administration of the TLR4 antagonist CRX-526 improved
intes tinal microcirculation in a post-treatment model of experimental endo-
toxemia. The TLR4 pathway may be a target in clinical Gram-negative sepsis.
1. Cristofaro et al.: Drugs 2006, 66:15.
2. Fort et al.: J Immunol 2005, 74:6416.
3. Moue et al.: Biochim Biophys Acta 2008, 1780:134.
4. Zanotti et al.: Am J Physiol Lung Cell Mol Physiol 2009, 297:L52.
Critical Care 2010, Volume 14 Suppl 1
Eff ects of lipopolysaccharide on isolated muscle mitochondrial
respiration are dose and time dependent
S Brandt1, S Djafarzadeh2, J Takala2, SM Jakob2
1University of Bern, Switzerland; 2Department of Intensive Care Medicine,
University of Bern, Switzerland
Critical Care 2010, 14(Suppl 1):P9 (doi: 10.1186/cc8241)
Introduction There is evidence that mitochondrial dysfunction plays a
role in sepsis-related tissue damage. Several studies described the uptake
and endocytosis of lipopolysaccharide (LPS) by various cells. LPS has been
localized in diff erent parts of the cytoplasm, including at close proximity
to or within mitochondria . Whether eff ects of LPS on mitochondrial
respiration are time and/or dose dependent is unknown.
Methods Quadriceps muscle biopsy was taken from seven anaesthetized
pigs. Mitochondria were isolated using diff erential centrifugation
and immediately incubated with 0.1, 1, 10, 50 and 100 μg LPS per mg
mito chondria protein on ice for 2 and 4 hours. Respiration rates were
determined polarographically using glutamate and succinate as substrates
to test the function of complex I and II. Respiration Control Ratio (State 3/
State 4) was derived for each substrate. Repeated-measures ANOVA was
used to analyze time and dose eff ect of LPS on respiration rates.
Results The results are shown in Figure 1.
Conclusions In vitro, LPS has time-dependent and dose-dependent
eff ects on muscle mitochondrial respiration. This has consequences for
design and interpretation of experimental studies.
1. Diaz-Laviada I, et al.: Histochem J 1991, 23:221-228.
Clinical severity and local infl ammatory responses in animal models
S Saeed, D Gilroy, M Singer
University College London, UK
Critical Care 2010, 14(Suppl 1):P10 (doi: 10.1186/cc8242)
Introduction Severe sepsis carries high morbidity and mortality. Pre clinical
research predominantly utilises animal models although their reproducibility
may vary, thus impairing understanding of disease. We sought to determine
the reproducibility of two murine models by assessing clinical severity and
local immune cell response 24 hours after septic insult.
Methods Intraperitoneal faecal slurry (FS) or zymosan was given to induce
acute peritonitis in 11 and 12 male C57/Bl mice (8 to 12 weeks, 18 to
32 g). A control group received saline only (n = 5). In surviving animals at
24 hours, clinical severity was scored as severe, moderate or mild according
to appearance and alertness. Peritoneal lavage was performed to obtain
immune cells. Analysis by antibody labelling (F4/80, GR-1, CD3 and CD19)
for fl uorescence-assisted cell sorting identifi ed numbers of macrophages,
neutrophils, T and B cells. Logistic regression (odds ratio, OR) was used to
determine the relationship of cell numbers with severity (reported if P <0.05).
Results Clinical severity varied markedly despite similar dosing (see Table 1).
At 24 hours, total intraperitoneal immune cells increased in both models and
with clinical severity (OR 0.83). Neutrophils predominated after septic insult
and also rose with severity (OR 0.75). Compared with control, macrophage
populations did not change in either model while B and T lymphocytes fell.
A cell population that expressed both F4/80 and GR-1 – that is, markers for
macrophages and neutrophils, respectively – occurred only in the FS model.
Table 1 (abstract P10). Number of animals according to clinical severity (with
Severe Moderate Mild
Conclusions Individual variability occurs in both faecal and zymosan
peritonitis models as shown by heterogeneous clinical responses and local
immune cell numbers to the same dose in similar animals. The cellular
immune response in both models is consistent with current understanding
of infection-induced infl ammation. Neutrophils, but not macrophages, rose
in proportion to worsening clinical severity. The signifi cance of F4/80+/GR-1+
cells in the FS model requires further evaluation.
Adenosine increases during human experimental endotoxemia, but
does not infl uence the immune response and subsequent organ injury
B Ramakers, N Riksen, B Franke, P Pickkers, H Van der Hoeven
Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
Critical Care 2010, 14(Suppl 1):P11 (doi: 10.1186/cc8243)
Introduction Although the innate immune response protects the
host from invading pathogens, an excessive response may also lead to
Critical Care 2010, Volume 14 Suppl 1
Figure 1 (abstract P9). Mean ± SD. Boxes: μg/mg LPS.
collateral damage to normal tissues. Adenosine has been proposed as an
immunomodulator capable of inhibiting infl ammation and preventing
tissue injury. The C34T nonsense mutation in the AMP deaminase 1
(AMPD1) gene is thought to increase the endogenous adenosine concen-
tration and has been associated with improved prognosis and survival in
ischemic heart disease. Caff eine on the other hand, acting as a nonselective
adenosine receptor antagonist, could diminish adenosine-mediated
eff ects. The present study evaluated the endotoxemia-induced adenosine
response, subclinical renal damage and endothelium dysfunction in
healthy male subjects. Furthermore, we investigated whether the LPS-
induced infl ammatory response is attenuated by AMPD1 and enhanced
by caff eine, as well as its eff ects on markers of endothelium activation
(plasma ICAM, VCAM) and renal damage (urinary excretion of GSTA1-1 and
Methods Thirty healthy male subjects received 2 ng/kg E. coli LPS. Three
groups were evaluated in a double-blind randomized controlled setting; a
LPS-placebo group (n = 10), LPS-placebo in AMPD1 subjects (n = 10), and
a LPS-caff eine group (4 mg/kg, n = 10).
Results During endotoxemia, the adenosine concentration increased from
10.0 ng/ml (9.0 to 15.3) at baseline to 15.5 ng/ml (13.0 to 22.3) 2 hours after
LPS infusion (P = 0.003; Friedman). The response was similar between LPS
groups. The increase in proinfl ammatory and anti-infl ammatory cytokines
(TNFα, IL-6, IL-10 and IL1RA) was similar in the three groups. Experimental
endotoxemia resulted in endothelial dysfunction, measured by an increase
in adhesion molecules and subclinical renal injury as measured by GSTA1-
1 and GSTP1-1. Infl ammation induced subclinical end-organ damage was
not infl uenced by either the AMPD1 SNP or treatment with caff eine.
Conclusions Human experimental endotoxemia induces an increase in
circulating cytokine levels and subclinical endothelial and renal damage.
Acute systemic infl ammation is also associated with an increase in
endogenous adenosine concentrations. Modulation of the adenosine
metabolism through the presence of the AMPD1 and administration of
caff eine does not aff ect the innate immune response and its subsequent
subclinical organ dysfunction.
Bacterial load plays a crucial role for survival in experimental
peritonitis and modulates immunoparalysis of monocytes
S Atmatzidis1, K Louis2, A Pistiki2, I Koutelidakis1, T Adamis2,
1Thessaloniki, Medical School, Thessaloniki, Greece; 2ATTIKON University
Hospital, Athens, Greece
Critical Care 2010, 14(Suppl 1):P12 (doi: 10.1186/cc8244)
Introduction Peritonitis is the prototype of polymicrobial sepsis with
kinetics of bacterial growth diff ering from those of other infections leading
to sepsis. The eff ect of the extent of leaking of gut content in the response
of the host was studied.
Methods A total of 21 rabbits were studied divided into two groups;
A: high-load peritonitis; and B: normal load peritonitis. After a midline
abdominal incision, the ileocecal calve was ligated. Three holes were
performed in the cecum wall of group A followed by masturbation to drain
cecal content in the peritoneal cavity. Two holes without masturbation
were performed in group B. After closure of the abdominal cavity, blood
was sampled at 2, 4, 24 and 48 hours. Peripheral blood mononuclear cells
(PBMCs) were isolated and stimulated in microplate wells with 10 ng/ml
LPS. Concentrations of TNFα were estimated in supernatants by a bioassay
in L929 fi brosarcoma cell line. In parallel, monocytes were separated from
lymphocytes by plastic adherence. Apoptosis was estimated after staining
with ANNEXIN-V and PI and fl ow cytometric analysis. Tissue bacterial
growth was estimated after death.
Results Mortality after 14 days was 84.6% in group A and 62.5% in
group B (log-rank: 3.83, P = 0.050). Mean respective rates of apoptosis
of lymhocytes of groups A and B were 32.2 and 44.5% at 2 hours; 33.5
and 51.9% at 4 hours (P = 0.028); 35.6 and 39.1% at 24 hours; and 28.5
and 43.7% at 48 hours (P = 0.029). Mean respective rates of apoptosis of
monocytes of groups A and B were 48.2 and 64.1% at 2 hours (P = 0.036);
57.9 and 66.3% at 4 hours; 47.3 and 69.9% at 24 hours (P = 0.041); and
60.5 and 73.5% at 48 hours. Respective TNFα released ex vivo from PBMCs
isolated at 24 hours from groups A and B after LPS stimulation was 2,579.1
and 31.3 pg/ml (P = 0.048). Mean respective log10 of enterobacteriaceae of
groups A and B were 6.52 and 1.39 cfu/ml in liver (P = 0.012); 7.79 and 1.43
cfu/ml in spleen (P = 0.012); and 7.98 and 1.79 cfu/ml in the right kidney
(P = 0.012).
Conclusions Experimental peritonitis with enormous bacterial leaking
from the gut is accompanied by reduced survival, increased tissue
bacterial growth and reduced apoptosis of lymphocytes and monocytes.
Peritonitis with low bacterial leaking is characterized by immunoparalysis
of PBMCs. These results may project in the effi cacy of immunotherapy in
Decreased whole blood TNFα production capacity after acute
alcohol exposure and LPS stimulation ex vivo
A Gavala1, K Venetsanou2, C Kittas3, E Manolis4, A Yiambides2,
P Myrianthefs2, G Baltopoulos2
1KAT, Kifi sia, Greece; 2ICU, KAT Hospital, School of Nursing, Athens University,
Athens, Greece; 3Medical School, Athens University, Athens, Greece; 4School of
Nursing, Athens University, Athens, Greece
Critical Care 2010, 14(Suppl 1):P13 (doi: 10.1186/cc8245)
Introduction Acute alcohol exposure is related to increased susceptibility
to infections . The purpose of the study was to investigate the eff ect of
acute exposure to diff erent alcohol concentrations in whole blood TNFα
production capacity after LPS stimulation ex vivo in healthy men.
Methods Whole blood was taken from healthy volunteers and was
placed in tubes containing EDTA and immediately transferred to the lab.
Heparinized blood samples diluted 1:10 in RPMI 1640 culture medium
(100 μl whole blood added in 900 μl RPMI 1640). Samples were pre-
incubated with 0‚ 5‚ 12.5‚ 25‚ 50‚ 100 and 200 mM alcohol (EtOH) for
10 minutes at room temperature. After incubation, 500 pg LPS was added
in each sample for 4 hours at 37°C. At the end of the process, samples
were centrifuged (1,800 rpm, 5 minutes, r.t.). Culture supernatants were
collected and stored at –70°C until measurements. TNFα levels were
determined in culture supernatant with ELISA .
Results We studied 17 healthy males volunteers aged 36.9 ± 1.6 (X ±
SEM). TNFα levels are shown in Figure 1. There was no TNFα production
detected in samples without alcohol in the absence of LPS stimulation
(control). TNFα production was signifi cantly decreased at a dose of alcohol
of 50 mM after LPS stimulation (P <0.05) but more apparently at doses of
100 and 200 mM alcohol (P <0.001) compared with LPS-induced samples.
Conclusions Alcohol is related to inhibition of TNFα production of
whole blood stimulated with LPS ex vivo . This eff ect occurred shortly
after alcohol exposure. Our observation indicates a suppression of
proinfl ammatory response during acute alcoholic intoxication which may
be related to increased susceptibility to infections.
1. Brown LA‚ et al.: Alcohol Clin Exp Res 2006, 30:1624-1631.
2. Myrianthefs P, et al.: Cytokine 2003, 24:286-292.
3. Nair M‚ et al.: Alcohol Clin Exp Res 1994, 18:602-607.
Figure 1 (abstract P13).
Critical Care 2010, Volume 14 Suppl 1
Leukocyte immunophenotyping: methodological aspects
J Jämsä, V Huotari, ER Savolainen, H Syrjälä, T Ala-Kokko
Oulu University Hospital, University of Oulu, Finland
Critical Care 2010, 14(Suppl 1):P14 (doi: 10.1186/cc8246)
Introduction Flow cytometric analysis of leukocyte surface receptors
has been performed and shown benefi cial, for example to characterize
infectious and septic patients [1,2]. For many surface antigens the results
may vary depending on the sampling temperature, the anticoagulant used
and the storage of the sample before analysis . In order to obtain reliable
data on leukocyte immunophenotyping for patient diagnostic purposes,
we wanted to carry out a thorough evaluation on these methodological
issues with a wide range of leukocyte surface antigens.
Methods Four blood samples, two using acid citrate dextrose (ACD) and
two using heparin as an anticoagulant, were taken from fi ve ICU patients
with severe sepsis and from fi ve healthy volunteers. The patients and the
healthy volunteers were combined into one study population (n = 10).
The samples were taken, processed and stored either at +4°C or at room
temperature. The surface antigen staining and fl ow cytometry were
performed immediately after sample collection or after 6 or 24 hours
at the above-mentioned temperatures. Antibodies of interest were for
monocytes and neutrophils CD11b and CD64, for monocytes CD14, CD40,
CD80, human leukocyte antigen (HLA)-DR, and for lymphocytes (CD4+ and
CD8+ T cells, B cells, and NK cells) CD69. The fl ow cytometry analysis was
done in three diff erent time points, after 1, 6 or 24 hours of sampling. Inter-
assay standardization and fl uorescence quantifi cations were performed
Results The fl uorescence intensities were higher at room temperature
compared with +4°C and they increased after storage (Figure 1). The eff ect
was observed especially for CD11b-antigen in monocytes and neutrophils
and for HLA-DR in monocytes.
Conclusions According to our results, fl ow cytometry leukocyte analysis
using CD antigens should be performed using +4°C temperature
throughout the measurement including sample collection, preparation
and storage, and the analysis should be performed within 6 hours.
1. Payden et al.: Minerva Anest 2009, 75:484-493.
2. Nuutila et al.: Hum Immunol 2009, 70:237-243.
3. Li et al.: Eur J Haematol 2000, 65:57-65.
Phenotypical analysis of peripheral human T lymphocytes in early
M Nalos, B Santner-Nanan, L Weisbrodt, AS Mclean, R Nanan
Sydney Medical School – Nepean, The University of Sydney, Penrith, Australia
Critical Care 2010, 14(Suppl 1):P15 (doi: 10.1186/cc8247)
Introduction T lymphocytes are crucial immune cells. We analysed T-cell
subsets phenotypes and tested, on a single cell level, their ability to
produce key cytokines in early human sepsis.
Methods Whole blood was collected from septic patients on ICU
admission. Peripheral blood mononuclear cells (PBMC) were isolated and
T-cell subsets analysed. To study cytokine production, PMBC were cultured
in the presence of PMA/ionomycin (50/750 ng/ml) in supplemented RPMI
1640 for 5 hours. Intracellular cytokines IL-4, IL-10, IL-17, IFNγ were stained
in CD3+/CD4+, CD3+/CD8+ cells using fl ow cytometry for both. The number
of cytokine producing cells was compared with age/sex-matched healthy
human volunteers. Data are expressed as mean ± SEM.
Results There were 12 patients (66 years old, six males, APACHE II-24,
eight survivors) and nine volunteers. We found a relative increase in
the frequency of Treg cells while the proportion of CD4+ cells remained
unchanged in septic patients. The PMA/ionomycin lead to maximal
T-cell stimulation, testing the ability of individual cell subsets to produce
cytokines. Septic patients displayed reduction of IFNγ (10.5 ± 0.8% vs
14.7 ± 1.9%, P <0.01) and a tendency to higher number of IL-10 (1.7 ±
0.3% vs 0.5 ± 0.1%, P = 0.10) producing CD4+ cells, while the proportion
of IFNγ-positive CD8+ cells increased (42.8 ± 5.8% vs 28.1 ± 4.9%, P = 0.03).
However, the overall CD8+ T-cell population was reduced (14.29 ± 1.6% vs
25 ± 1.2%) following ex vivo activation in patients. The number of IL-4 and
IL-17 staining cells was unchanged (Figure 1).
Conclusions Our results confi rm a relative increase of Treg  and a skew
towards Th2 lineage in the CD4+ cells. The highly activated CD8+ cells
appear to be more susceptible to activation-induced cell death.
1. Venet F et al.: Intensive Care Med 2009, 35:678-686.
Figure 1 (abstract P14). CD11b fl uorescence intensity for neutrophils
(n = 10).
Figure 1 (abstract P15).
Critical Care 2010, Volume 14 Suppl 1
CD64, a marker of leucocyte activation kinetics after uncomplicated
S Djebara, P Cauchie, A Alewaeters, A Daper, E Fosse, K Zouaoui Boujelta,
CHU Charleroi, Charleroi, Belgium
Critical Care 2010, 14(Suppl 1):P16 (doi: 10.1186/cc8248)
Introduction The aim of this study was to assess the CD64 kinetics after
normal cardiac surgery, an essential step to defi ne the potential use of
CD64 as an early and specifi c infectious marker in this postoperative
setting. CD64 is a high-affi nity receptor for the Fc portion of IgG. It is weakly
expressed on the polynuclear neutrophils (PMNs) at rest [1,2] but increases
specifi cally after bacterial stimulation. Thus, CD64 analysis is proposed as
an early infectious marker.
Methods Prospective study realised in the medico-surgical ICU of CHU
Charleroi (Belgium). Twenty-two patients (mean age 64 ± 13 years)
scheduled for cardiac surgery were included in the analysis. The CD64
expression on neutrophils was quantifi ed by the haematologic cell dyn
sapphire method (Abott, USA). C-reactive protein, leukocyte count, white
blood cells, platelets and temperature were also monitored. Values are
expressed as median (25th to 75th) percentile.
Results CD64 index (Figure 1) slightly rose from the day 0, median
value 0.86 units (1.06 to 1.38 units) to day 5 after the surgery, 1.01 (1.32
to 1.68 units). However, this increase was moderate, and the median
values did not exceed the usual threshold of 1.5 units. Conversely, CRP
showed a large increase from normal values on day 0 to 8, 67 mg/dl (6.64
to 13.56 mg/dl) on day 5. No signifi cant correlation (P >0.05) was found
between CD64 and the others parameters of infl ammation (CRP, leukocyte
count, PMNs, platelets and temperature).
Conclusions Our results show that the neutrophil CD64 expression after
cardiac surgery with ECC is only moderately increased. The role of this new
biomarker in the early diagnosis of infection (after major surgery) should
be assessed in prospective studies.
1. Loan-Facsinay A, de Kimpe SJ, Hellwig SMM, et al.: FcγRI(CD64) contributes
substantially to severities of arthritis, hypersensitivity responses, and
protection from bacterial infection. Immunity 2002, 16:391-402.
2. Harpaz Y, Chothia C: Many of the immunoglobulin superfamily domains in
cell adhesion molecules and surface receptors belong to a new structural
set which is close to that containing variable domains. J Mol Biol 1994,
Interferon-gamma reverses sepsis-induced immunoparalysis of
monocytes in vitro
M Mouktaroudi, A Savva, A Pistiki, M Raftogiannis, A Antonopoulou,
ATTIKON University Hospital, Athens, Greece
Critical Care 2010, 14(Suppl 1):P17 (doi: 10.1186/cc8249)
Introduction It is currently being understood that most of the agents
modulating host response in sepsis have failed because they act to
refrain an over-exaggerated immune response whereas immunoparalysis
takes place on the time of their administration. The eff ect of IFNγ on
immunoparalysis of monocytes in sepsis was assessed.
Figure 1 (abstract P16). CD64 kinetics (units).
Figure 1 (abstract P17). Eff ect of IFNγ on the release of TNFα.
Critical Care 2010, Volume 14 Suppl 1
Methods Blood was isolated within the fi rst 24 hours from the advent
of signs of sepsis from 10 healthy donors and from 33 patients; 14 with
sepsis and 19 with severe sepsis/shock. Peripheral blood mononuclear
cells (PBMCs) were isolated and stimulated with 10 ng/ml LPS; 5 μg/ml
Pam3Cys; and heat-killed isolates of Candida albicans, multidrug-resistant
Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus
(MRSA). Stimulations were done in the absence and presence of 10 ng/
ml IFNγ. Concentrations of cytokines were estimated in supernatants by
an enzyme immunoassay.
Results Eff ects of IFNγ on the release of TNFα are shown in Figure 1.
Open bars represent stimulation in the absence of IFNγ and solid bars
stimulation in the presence of IFNγ. Asterisks signify diff erences compared
with the absence of IFNγ. IL-6 and IL-1β had similar kinetics to TNFα.
Conclusions IFNγ reverses in vitro sepsis-induced immunoparalysis of
monocytes. The type of aff ected cytokine depends on the agonist and
probably refl ects the mechanism of action of IFNγ.
Early hydrocortisone treatment counteracts circulatory
derangement but not cytokine response in porcine endotoxemia
ES Söderberg1, ML Lipcsey1, JS Sjölin2, AL Larsson3, ME Eriksson1
1Section of Anaesthesiology and Intensive Care, Uppsala, Sweden; 2Section of
Infectious Diseases, Uppsala, Sweden; 3Section of Clinical Chemistry, Uppsala,
Critical Care 2010, 14(Suppl 1):P18 (doi: 10.1186/cc8250)
Introduction We evaluated whether treatment with hydrocortisone
administered just after establishment of endotoxin-mediated circulatory
dysfunction would have anti-infl ammatory and shock reversing eff ects.
Establishment of endotoxin-mediated circulatory dysfunction was
defi ned as the moment when the mean pulmonary arterial pressure
(MPAP) reached the double baseline value.
Methods All pigs were anesthetized and given endotoxin infusion
during the 6 hours of the experiment. Eight pigs were randomized to the
hydrocortisone group, receiving hydrocortisone at 5 mg/kg intravenously,
or to the control group, receiving a corresponding volume of saline, as
soon as the MPAP doubled the baseline value. P <0.05 was considered
Results No diff erence in baseline data was noted between the groups.
No diff erences in TNFα (Figure 1), IL-6 and core temperature were seen
between the groups. Pigs in the hydrocortisone group had signifi cantly
higher mean arterial pressure and systemic vascular resistance index
during the 6-hour experimental period than pigs in the control group,
while heart rate was signifi cantly lower in the hydrocortisone group at 1 to
6 hours as compared with controls.
Conclusions Early treatment with hydrocortisone, administered after the
onset of endotoxemia, counteracted circulatory deterioration, but did not
aff ect the plasma levels of proinfl ammatory cytokines in this model. Thus,
TNFα and IL-6 might not be involved in the development of circulatory
dysfunction during the early phase of experimental endotoxemia.
CD40L is selectively expressed on platelets from thrombocytopenic
AM Montalbano1, F Turani2, EC Ciotti1, MF Fede1, MP Piperno1, PD David1,
DF Fiume1, GC Caiazza1, SN Natoli1, FL Leonardis1, AB Bergamini1
1University Tor Vergata, Rome, Italy; 2European Aurelia Hospital, Rome, Italy
Critical Care 2010, 14(Suppl 1):P19 (doi: 10.1186/cc8251)
Introduction It has been recently hypothesized that septic microangio-
pathy is caused or at least promoted by the interaction between endo-
thelial surface receptor CD40 and its ligand CD40L, expressed by activated
platelets. This interaction produces procoagulative changes in endothelial
cells, endothelial apoptosis, subendothelial matrix exposition and
microthrombi formation. Since virtually all septic patients show a certain
degree of coagulation abnormalities, we hypothesized that low platelet
count is associated with a diff erent degree of CD40L expression and that
this could correlate with the severity of disease.
Methods To determine the infl uence of sepsis on levels of platelet-derived
CD40L expression, we performed a prospective observational study in a
polyvalent university hospital ICU. Eighteen consecutively septic patients
were enrolled in the study, independently of the platelet count and the
severity of disease (SOFA score). Flow cytometry of fresh blood from septic
patients (n = 18) and age-matched controls (n = 8) was performed for
membrane-bound CD40L and CD62P on circulating platelets.
Results Flow cytometry demonstrated low levels of CD62P in controls
while the levels in patients were high. CD40L+ platelets were selectively
found from patients with thrombocytopenia (platelet count ≤60,000/
mm3). Furthermore a direct correlation between CD40L expression and
the SOFA score was found in patients with sepsis and thrombocytopenia
compared to patients with sepsis without thrombocytopenia.
Conclusions These results suggest that CD40L expression on platelets is
somehow related to the degree of thrombocytopenia and possibly can
be a marker of the severity of sepsis. Although the role of endothelial-
derived CD40/platelet-derived CD40L interaction is not fully understood
during sepsis, the expression of CD40L on platelets could be related to
the severity of organ disease due to the possible bursting of endothelial
damage through this pathway. Further investigation is needed to
determine whether platelets CD40L contributes to endothelial and
subsequent organ damage, its role in thrombocytopenia and its
correlation with the outcome of sepsis. The microvascular injury seems
to be a central event in sepsis, so understanding the mechanisms
underlying its development is crucial for the individuation of new and
specifi c therapeutic strategies.
Neuronal NOS-inhibition in the setting of septic cardiomyopathy
A Van de Sandt1, R Windler1, A Gödecke2, J Ohlig3, S Becher1, T Rassaf1,
J Schrader2, M Kelm1, M Merx1
1Department of Cardiology, Pulmonology and Vascular Medicine, University
Hospital Düsseldorf, Germany; 2Department of Cardiovascular Physiology,
Heinrich-Heine-University, Düsseldorf, Germany; 3RWTH, Aachen, Germany
Critical Care 2010, 14(Suppl 1):P20 (doi: 10.1186/cc8252)
Introduction Nitric oxide (NO) plays a central role in the pathogenesis
of sepsis. Recently, we demonstrated that endothelial NOS (eNOS)
contributes to endogenous NO-production and modulates infl ammation,
associated with preserved cardiac function resulting in prolonged survival
of eNOS–/– compared with wild-type (WT) mice. The role of neuronal NOS
(nNOS) in septic cardiomyopathy remains unclear. This study’s aim is to
elucidate the infl uence of nNOS in the presence/absence of eNOS on
cardiac function and survival in a clinically relevant model of sepsis.
Methods Inhibition of nNOS was achieved via continuous application of
the selective nNOS-inhibitor Vinyl-L-NIO (VL-NIO) (0.02 mg/kg BW/hour)
using an osmotic mini pump. B6/c57 WT and eNOS–/– mice were rendered
septic by cecum ligation and puncture (CLP). After 12 hours heart function
was analyzed using a pressure–volume catheter placed in the left ventricle.
For catecholamine responsiveness, norepinephrine was applied (0.4 μg/kg
BW/minute, intraperitoneally). NOx-levels in plasma were measured using
high-pressure performing liquid chromatography.
Results Inhibition of nNOS via VL-NIO application resulted in signifi cantly
reduced nitrate plasma levels and prolonged survival (WT CLP + VL-NIO = 38
Figure 1 (abstract P18). TNFα over time (mean ± SEM).
Critical Care 2010, Volume 14 Suppl 1
hours vs WT CLP = 29 hours). However, cardiac function and norepinephrine
responsiveness were not improved compared with untreated septic WT.
In contrast to WT, application of VL-NIO in eNOS–/– had no infl uence on
plasma nitrate levels, while cardiac function and survival were signifi cantly
impaired compared with untreated septic eNOS–/–. Impaired cardiac
function was accompanied by decreased survival time (eNOS–/– CLP +
VL-NIO = 29.5 hours vs eNOS–/– CLP = 69.5 hours).
Conclusions Pharmacologic inhibition of nNOS result in signifi cant
reduction of plasma nitrate levels and prolonged survival compared
with untreated septic WT despite unimproved septic cardiomyopathy.
In contrast, the signifi cant survival benefi t of septic eNOS–/– compared
with septic WT was abrogated by pharmacologic nNOS inhibition.
Furthermore, the latter developed severe septic cardiomyopathy.
Whether eNOS acts as modulator of nNOS in this setting remains to be
clarifi ed by further studies.
Urinary albumin excretion is elevated in sepsis, but does not
correlate with circulating VEGF-A levels
S Basu1, M Bhattacharyya1, T Chatterjee2, S Todi1, A Majumdar1
1AMRI Hospitals, Kolkata, India; 2Jadavpur University, Kolkata, India
Critical Care 2010, 14(Suppl 1):P21 (doi: 10.1186/cc8253)
Introduction In critically ill patients admitted with SIRS, endothelial
dysfunction leads to increased capillary permeability. In the glomerulus,
it manifests as increased albumin excretion. Microalbuminuria is a
common fi nding in various acute conditions like sepsis, trauma and
surgery. Studies have shown increased levels of vascular endothelial
growth factor-A (VEGF-A), a potent vascular permeability inducing
agent, in LPS-induced endotoxemia, severe sepsis and septic shock.
The pathogenic mechanism of the glomerular leakage of albumin in
acute infl ammatory conditions remains to be clarifi ed. We wished to
investigate the causative role of VEGF-A, in this regard which might have
Methods Prospective study in the 43-bed ICU of a tertiary care hospital. Of
the consecutive patients admitted to the ICUs between September 2008
and January 2009, 597 patients were included, after excluding patients
with ICU stay <24 hours, pregnancy, menstruation, anuria, hematuria and
proteinuria due to renal and post- renal diseases. Of these, 30 consecutive
patients with sepsis, severe sepsis and septic shock (sepsis group) and 30
randomly chosen patients without sepsis were recruited for the VEGF-A
study. Spot urine samples for the albumin–creatinine ratio (ACR, mg/g)
and serum for VEGF-A (ELISA) were collected on ICU admission. Correlation
was analyzed using Spearman’s correlation coeffi cient.
Results Sixty critically ill patients, with a median age (IQR) of 60 years (48
to 72), 39:21 male:female ratio, median APACHE II score (IQR) of 16 (7 to
23), and 3 median days of ICU stay, had a median ACR (IQR) of 125 mg/g
(51.6 to 239.1) and a median VEGF-A (IQR) of 111 pg/ml (54.3 to 286.9) on
ICU admission. The median ACR on admission in the sepsis group (n = 30)
of 161.8 mg/g was signifi cantly higher than the median ACR (78.3 mg/g)
of the group without sepsis (n = 30) (P = 0.011). On statistical analysis, no
signifi cant correlation was obtained between levels of urinary ACR and
serum VEGF-A (P = 0.327) in the entire group. Analysis for correlation
between ACR and VEGF-A in the sepsis patients (P = 0.396) and in the
group without sepsis (P = 0.518) yielded similar results.
Conclusions Despite a strong physiologic rationale, our pilot study did not
show an association between microalbuminuria and VEGF-A in critically ill
patients. Larger studies are needed to come to a defi nitive conclusion.
High mobility group box protein-1 preconditions isolated rat hearts
and protects human pulmonary and renal cells against hypoxic injury
CM Walshe, D O’Toole, B Higgins, JG Laff ey, LG Kevin
National University of Ireland, Galway, Ireland
Critical Care 2010, 14(Suppl 1):P22 (doi: 10.1186/cc8254)
Introduction High mobility group box protein-1 (HMGB) is released by
activated monocytes/macrophages during sepsis. Levels correlated with
mortality in patients and anti-HMGB antibodies prevented endotoxin-
induced death in animal models . In marked contrast to these fi ndings
are reports of cytoprotective eff ects because HMGB protected liver from
ischemia/reperfusion (IR)  and HMGB-transgenic mice were resistant to
myocardial infarction . Despite these reports, little is known of the role
or mechanism of HMGB. We aimed to further evaluate HMGB in rat hearts
and in pulmonary and renal cell cultures.
Methods Isolated hearts received HMGB/vehicle before 30 minutes
ischemia and 120 minutes reperfusion. In separate studies, rats were
rendered septic by caecal ligation and puncture (CLP) prior to IR. Left
ventricular (LV) function was measured with a latex LV balloon. Infarct
size was measured by TTC staining. For human cell culture studies, A549
alveolar cells or HK-2 renal tubular cells were treated with HMGB/vehicle
before incubation in normoxia or hypoxia. Fluorimetric caspase-3 activity
was used as measure of apoptosis. Cytochrome C was measured by ELISA.
For HK-2 cells, the MTT assay was used to test viability.
Results HMGB, prior to cardiac IR, preserved developed (d) LVP at
120 minutes reperfusion compared with controls (44 mmHg vs 27 mmHg,
P <0.05) and infarct size, expressed as %V weight ± SEM, was reduced (31
± 5.4 vs 44 ± 4.2, P <0.05), n = 6/group. Hearts from CLP rats had reduced
baseline dLVP (59 mmHg ± 5.1 vs 97 ± 5.3, P <0.05) but infarct sizes after IR
were signifi cantly reduced (27 ± 8.8, P <0.05 vs 44 ± 6.2, P <0.05). In A549
cells, HMGB inhibited apoptosis (49% reduced caspase-3 activity (8.6 vs
17.1 a.u., P <0.01)). This was associated with reduced cytochrome C release
(250 vs 389 pg/ml, P <0.05). Using MTT assay, HMGB protected against
hypoxia-induced cell death vs controls (viability 75% vs 61%, P <0.05).
Conclusions HMGB, or sepsis, similarly precondition the heart against IR
injury. HMGB has anti-apoptotic eff ects that protect against hypoxic renal
and alveolar cell injury. We conclude that HMGB has potent anti-ischemic
eff ects in multiple organs and may function as an innate cytoprotective
mediator in sepsis.
1. Wang H, et al.: Science 1999, 285:248-251.
2. Tsung A, et al.: J Exp Med 2005, 201:1135-1143.
3. Kitahara T, et al.: Cardiovasc Res 2008, 80:40-46.
Early persisting elevation of plasma Pentraxin 3 is associated with
mortality and with coagulation impairment in severe sepsis and
A Coppadoro1, T Mauri1, G Bellani1, N Patroniti1, M Cugno2, A Grassi1,
G Iapichino2, L Gattinoni2, A Mantovani2, A Pesenti1
1Universita’ degli Studi di Milano-Bicocca, Monza, Italy; 2Universita’ degli Studi
di Milano, Italy
Critical Care 2010, 14(Suppl 1):P23 (doi: 10.1186/cc8255)
Introduction Pentraxin 3 (PTX3) is an infl ammatory mediator produced by
a variety of tissue cells, like neutrophils, macrophages, myeloid dendritic,
endothelial and epithelial cells . During sepsis a massive infl ammatory
activation occurs, which often leads to an important coagulation system
dysfunction. PTX3 upregulates coagulation promoters in vitro . PTX3
may represent an early marker of severity and outcome and may be
related to coagulation impairment in septic patients.
Methods We studied 90 patients aff ected by severe sepsis or septic
shock previously enrolled in a prospective trial regarding the impact of
glycemic control on infl ammation and coagulation. At enrollment we
recorded sepsis signs, plasminogen activator inhibitor 1 (PAI-1, an inhibitor
of fi brinolysis) activity and concentration, prothrombin fragments 1 + 2
(F1+2) concentration (a marker of coagulation activation), disease severity
and organ dysfunctions. We measured plasma PTX3 levels at enrollment
and everyday until day 7. Mortality was recorded at day 90.
Results Although not diff erent on day 1, PTX3 remained signifi cantly
higher in nonsurvivors than in survivors over the fi rst 5 days (P = 0.002 by
general linear model). On day 1, septic shock patients had higher PTX3
levels than patients with severe sepsis (274.41 ± 321.92 vs 114.95 ± 129.93
ng/ml, P = 0.029, t test). Day 1 PTX3 was signifi cantly correlated with SAPS
II score (R2 = 0.08, P = 0.006, linear regression), platelets count (R2 = 0.14,
P <0.001) and SOFA score (R2 = 0.16, P <0.001). Day 1 PTX3 was correlated
with PAI-1 concentration (R2 = 0.211, P <0.001) and activity (R2 = 0.231,
P <0.001) and with F1+2 concentration (R2 = 0.09, P = 0.045).
Conclusions Persisting high levels of circulating PTX3 over the fi rst days
from sepsis onset may be associated with mortality. PTX3 correlates with
severity of sepsis and with sepsis-associated coagulation dysfunction.
Critical Care 2010, Volume 14 Suppl 1
1. Mauri T, et al.: Crit Care Med 2008, 36:2302-2308.
2. Napoleone E, et al.: J Leukoc Biol 2004, 76:203-209.
Intravenous immunoglobulins prevent breakdown of the
blood–brain barrier in experimental sepsis
F Esen1, E Senturk1, P Ergin Ozcan1, B Ahishali1, N Arıcan1, N Orhan1,
O Ekizoğlu2, D Ustek1, M Kucuk1, M Kaya1
1Istanbul University Istanbul Medical Faculty, Istanbul, Turkey; 2Sadi Konuk
Training and Research Hospital, Istanbul, Turkey
Critical Care 2010, 14(Suppl 1):P24 (doi: 10.1186/cc8256)
Introduction The eff ect of intravenous immunoglobulin preparations –
immunoglobulin G (IgG), immunoglobulin G enriched with IgA and IgM
(IgGAM) – on blood–brain barrier (BBB) integrity and survival rate was
comparatively investigated in septic rats.
Methods Sepsis was induced by cecal ligation and perforation (CLP)
in Sprague–Dawley rats. The animals received either IgG (250 mg/kg,
intravenously) or IgGAM (250 mg/kg, intravenously) 5 minutes before CLP
surgery. All rats were observed for behavioral changes for 24 hours after CLP
operation. To show the alterations in BBB integrity, Evans blue (EB; 69 kDa)
dye extravasation was determined for quantitative measurement of BBB
permeability, and horseradish peroxidase (HRP; 40 kDa) extravasation was
evaluated to provide ultrastructural evidence for the transport pathways
involved in BBB permeability. Immunohistochemistry was performed
to show the alterations in immunoreactivity for tight junction protein
Results A high mortality rate (34%) was noted in septic animals and
the mortality rate was decreased to 15% and 3% by IgG and IgGAM,
respectively. Both IgG and IgGAM alleviated the sickness behavior in
septic rats and the animals were observed to be healthy and active.
Increased extravasation of EB dye into brain tissue of septic animals was
markedly decreased by both IgG and IgGAM. Occludin immunoreactivity
remained essentially unchanged in all groups including CLP. In addition,
strong staining for HRP was seen around vessels located in the cerebral
cortex and the hippocampus in septic animals. Increased luminal and
abluminal vesicles containing electron-dense HRP reaction product were
noted in the cytoplasm of endothelial cells in the cerebral cortex and
hippocampus of septic rats, emphasizing an increased BBB permeability
predominantly by transendothelial route. In these animals, tight junctions
were ultrastructurally intact suggesting that paracellular pathway of BBB is
not responsible for the BBB breakdown in sepsis. Following IgG or IgGAM
treatment, no ultrastructural evidence of leaky capillaries in brain was
observed in septic animals indicating the blockade of the transcellular
Conclusions The present study indicates that IgG and IgGAM improve the
integrity of the BBB and inhibit CLP-induced sickness behavior in rats.
Early use of immunoglobulin in septic shock
IC Cavazzuti, LR Rinaldi, LD Donno, SB Braccini, SB Busani, MG Girardis
Policlinico di Modena, Italy
Critical Care 2010, 14(Suppl 1):P25 (doi: 10.1186/cc8257)
Introduction In addition to the interventions suggested by the guidelines
of the Surviving Sepsis Campaign, in the recent years other therapeutic
options have been proposed and tested for patients with severe sepsis
and septic shock. Polyclonal intravenous immunoglobulins seem to be
an interesting and useful option because of its activity in neutralizing
endotoxin and in modulating the host immune response. In this retro-
spective study we assessed the eff ects of the early use of polyclonal
intravenous immunoglobulins enriched with IgA-M (IgGAM) in addition
to standard therapies on clinical outcome of patients with septic shock.
Methods In January 2008, IgGAM was introduced into our ICU protocol
for the management of septic shock patients (within 24 hours after shock
appearance and at the dosage of 5 ml/kg for 3 days). From January 2008
to September 2009, we studied 52 consecutive patients with septic shock
admitted to our ICU. In each patient we recorded the SAPS II and SOFA
scores, the compliance to the 6-hour and the 24-hour sepsis bundles, the
compliance to IgGAM use, the length of stay in the ICU and the 30-day
Results Due to low compliance of medical staff to protocol application,
IgGAM has been used only in 27 patients (IgGAM group). At ICU admission,
the severity scores were similar in patients with and without (Control
group) IgGAM therapy (SAPS II: control 54 (22 to 99), IgGAM: 59 (39 to
101); P >0.05 and SOFA: control 9 (2 to 17); IgGAM 9 (4 to 15); P >0.05).
The compliance to 6-hour and 24-hour bundles was also similar in the
two groups, apart from compliance to fl uid therapy that was larger in the
IgGAM group (85% vs 56% in Control group). The length of stay in the ICU
was 15 ± 9 days in the IgGAM group and 18 ± 31 days in the Control group
(P >0.05); the 30-day mortality was lower (P <0.05) in the IgGAM group
(25%) than in the Control group (52%).
Conclusions These preliminary data indicate that the early use of IgGAM,
associated with interventions proposed by the SSC guidelines, reduces
mortality of patients with septic shock.
1. Ballow M: Mechanism of action of intravenous immune serum globulin in
autoimmune and infl ammatory diseases. J Allergy Clin Immunol 1997,
2. Werdan K: Mirror, mirror on the wall, which is the fairest meta-analysis of
all? Crit Care Med 2007, 35:2852-2854.
Low levels of immunoglobulin G in patients with sepsis or septic
shock: a signum mali ominis?
S Dietz, C Lautenschlaeger, U Mueller-Werdan, K Werdan
University Clinics of the Martin-Luther-University Halle-Wittenberg, Halle
Critical Care 2010, 14(Suppl 1):P26 (doi: 10.1186/cc8258)
Introduction The role of intravenous immunoglobulin therapy in patients
with sepsis and septic shock is still controversially discussed. In a retro-
spective analysis of the data from the SBITS-trial  we investigated
whether the initial level of serum IgG on admission to the hospital in
patients with sepsis and septic shock (before the fi rst administration of the
fi rst dose of intravenous immunoglobulins) could be seen as a prognostic
parameter for the primary outcome, lethality on day 28, or the secondary
endpoints, lethality on day 7 or on the ICU.
Methods A total of 543 were included in the trial: the patients were
divided into four groups (quartiles) based on the 25th, 50th and 75th
percentiles of their initial level of IgG on admission to the hospital. The
fi rst group contained 140 patients with a range in the IgG serum level up
to 6.1 g/dl. The second and third groups contained 134 patients and 136
patients, respectively, the immunoglobulin G levels were greater than
6.1 g/dl to 8.4 g/dl and greater than 8.4 g/dl to 11.9 g/dl. The fourth group
containing 133 patients had IgG levels higher than 11.9 g/dl. In a logistic
regression model we adjusted for potential confounders (that is, sex, age,
APACHE II score, presence of shock on admission).
Results On basis of this model we could show that lethality between the
fi rst and second groups did not diff er signifi cantly with the lethality in the
third (reference) group with physiologic levels of IgG on day 0. Surprisingly
the lethality of the fourth group, with IgG levels higher than 11.9 g/dl, was
signifi cantly higher compared with the reference quartile (OR 1.69, CI 1.01
to 2.81, P = 0.047).
Conclusions Our post-hoc analysis did show no prognostic relevance of
a low level of serum IgG on admission to hospital for the 543 patients
with sepsis and septic shock. Thus the initial serum level of IgG seems to
be of no aid in making the decision to initiate therapy with intravenous
immunoglobulins for these patients. Whether a high level of serum IgG
on admission is an independent risk factor for an increased lethality in
critically ill patients, as shown in our analysis, needs to be investigated in
1. Werdan K, et al.: Score-based immunoglobulin G therapy of patients with
sepsis: the SBITS study. Crit Care Med 2007, 35:2693-2701.
Critical Care 2010, Volume 14 Suppl 1
Background factors in patients receiving immunoglobulin
administration and changes in sepsis markers
T Ikeda1, K Ikeda1, H Taniuchi1, S Suda1, Y Takahashi2
1Tokyo Medical University, Hachioji Medical Center, Tokyo, Japan; 2Sannoudai
Hospital, Ibaraki, Japan
Critical Care 2010, 14(Suppl 1):P27 (doi: 10.1186/cc8259)
Introduction The potentially envisaged actions of intravenous immuno-
globulin (IVIg) on severe infectious disease include virus or toxin neutralizing
action, opsonic eff ect, complement bacteriolytic activity, and enhancement
of sensitivity to antibiotics. In the case of severe infectious disease, antibiotics
are often supplemented with administration of IVIg. The aim of this study
is that the changes in sepsis markers followed by IVIg administration are
investigated with severe sepsis or severe septic shock patients.
Methods The subjects were 52 patients admitted to an ICU with a diagnosis
of severe sepsis or septic shock and from whom informed consent had been
obtained for the present study. IVIg was administered intravenously for 3 days
(5.0 g/day) and measurements were undertaken before administration (Day
1), on the day after completion of administration (Day 4), and on Day 7. The
items measured were IL-6, C-reactive protein (CRP) and, as indices of vascular
endothelial cell activation, plasminogen activator inhibitor-1 (PAI-1) and
adhesion molecules (endothelial leukocyte adhesion molecule-1 (ELAM-1));
the eff ect of IVIg administration on these markers was then studied. The IVIg
studied was polyethylene glycol-treated human immunoglobulin injection
fl uid (2.5 g, 50 ml, one vial).
Results The APACHE II score was 25.3 ± 7.8, the SOFA score 9.5 ± 3.5, and
the survival rate after 28 days 76.9%. The values before IVIg administration
were: procalcitonin 28.8 ± 44.5 (median value 13.6) ng/ml, CRP 16.3 ± 8.3
(median value 16.0) mg/dl, IL-6 8,873 ± 19,362 (median value 744) pg/ml,
PAI-1 374 ± 428 (median value 178) ng/ml, and ELAM-1 198 ± 359 (median
value 61) ng/ml. All values were thus elevated. After the completion of IVIg
administration, the level of mediators other than ELAM-1 (procalcitonin,
CRP, IL-6, PAI-1) decreased signifi cantly.
Conclusions The results of the present study found signifi cant decreases
of IL-6 and PAI-1 resulting from immunoglobulin administration, but did
not indicate a protective eff ect on vascular endothelial cell function.
C1-esterase inhibitor (C1INH) implication in systemic infl ammation
A Igonin, N Lazareva, VY Uvarov
BioGenius Research Centre, Moscow, Russia Federation
Critical Care 2010, 14(Suppl 1):P28 (doi: 10.1186/cc8260)
Introduction C1INH is the most potent endogenous regulator of compli ment
as well as intrinsic coagulation pathways and the kallekrein–kinin system.
Methods C1INH systemic activity was studied in patients who were
enrolled within 48 hours after onset of sepsis (ACCP, 1992). The analysis of
C1INH activity in quartiles (Q) was conducted in terms of RCT of human
purifi ed C1INH (Bicizar, Russia).
Results Sepsis patients (n = 40) responded with an increase of C1INH
activity in comparison with healthy individuals (Figure 1). Thirty percent of
Q1 patients had ARDS and septic shock whereas in Q4 everyone showed
only signs of sepsis. The CRP level was higher in Q1 patients (243.4 ±
39.9 mg/l) than in Q4 (144.0 ± 20.07 mg/l; P = 0.04), whereas the C4 subunit
was lower in Q1 (0.19 ± 0.04 g/l) than in Q4 (0.32 ± 0.04 g/l; P = 0.05).
Conclusions Inability to upregulate C1INH activity in sepsis was associated
with enhanced systemic infl ammation, higher number of ARDS and septic
Prognostic value of B-type natriuretic peptide in critically ill
patients with new onset of fever: preliminary study
V Soulountsi1, V Voutsas1, P Kontou1, A Giakamozis1, K Hatzimanolis2,
T Lazaridis1, V Hatsiou2, M Mpitzani1
1ICU, G. Papanicolaou, Thessaloniki, Greece; 2Microbiology Laboratory,
G. Papanicolaou Hospital, Thessaloniki, Greece
Critical Care 2010, 14(Suppl 1):P29 (doi: 10.1186/cc8261)
Introduction The purpose of the study is the evaluation of B-type
natriuretic peptide (BNP) as a predictor of septic complications and ICU
mortality in patients with a new onset of fever during the fi rst 3 days of
hospitalization in the ICU.
Methods Thirty-one ICU patients (21 males and 10 females) with new
onset of fever and leukocytosis within the fi rst 3 days of ICU admission
were prospectively included in the study. Exclusion criteria were heart or
renal failure, chronic obstructive pulmonary disease and head trauma.
Serial plasma samples were taken on days 1, 2 and 4 after the onset of
fever for BNP level measurement. BNP values were correlated with severity
scores (Acute Physiology and Chronic Health Evaluation (APACHE II) and
Sequential Organ Failure Assessment (SOFA)), the progression to septic
shock and the fi nal outcome.
Results According to the clinical and laboratory fi ndings within the fi rst
3 days of hospitalization, the patients included in the study were divided
into three groups: Group A = systemic infl ammatory response syndrome
(SIRS) (seven patients), Group B = sepsis (14 patients) and Group C =
septic shock (10 patients). The BNP value on days 1 and 2 was signifi cantly
associated with the SOFA Max value (P <0.001). The BNP value on day 4
was signifi cantly associated with ICU mortality (P = 0.006). The optimal
cutoff BNP value for diff erentiating between nonsurvivors and survivors
was estimated to be 203.55 pg/ml (sensitivity = 100%, specifi city = 61.1%).
In Group B patients, BNP value on day 2 was signifi cantly higher in patients
who fi nally progressed to septic shock (P = 0.001). The optimal cutoff BNP
value for identifying these patients was estimated to be 212.45 pg/ml
(sensitivity = 85.7%, specifi city = 64.3%).
Conclusions In ICU patients with new onset of fever during the fi rst
3 days of ICU hospitalization, the BNP value on day 4 seems to be a good
predictor of ICU mortality. In patients with sepsis, a cut-off BNP value of
212.45 pg/ml on day 2 could be a predictor of progression to septic shock.
Due to the small number of patients included in our study, further studies
are needed to confi rm these fi ndings.
Microalbuminuria evaluated as a biomarker in patients with septic
C Grion, L Cardoso, C Carrilho, J Altafi n, S Barros, L Carvalho, J Festti,
F Mansano, T Okamoto, K Uehara, J Dias, GC Silva
Hospital Universitário de Londrina, Brazil
Critical Care 2010, 14(Suppl 1):P30 (doi: 10.1186/cc8262)
Introduction The level of microalbuminuria is thought to refl ect the
severity of infl ammation during acute phase response and may have
prognostic value with regard to survival. This study aimed to describe
urinary albumin excretion in patients with septic shock and changes in
microalbuminuria levels in the fi rst 3 days of treatment.
Figure 1 (abstract P28). C1INH activity in patients with sepsis analyzed in
quartiles (Q1, Q2, Q3, Q4) in comparison with healthy individuals.
Critical Care 2010, Volume 14 Suppl 1
Methods Prospective observational study of 49 consecutive patients with
septic shock admitted to a general ICU. During the fi rst 24 hours after severe
sepsis was diagnosed, we collected data to calculate APACHE II and SOFA
scores and urinary sample to measure urinary albumin. Another sample of
urine was collected on the third day of septic shock. Microalbuminuria was
measured by immunoturbidimetry with a limit of detection of 3.5 mg/l.
The study was approved by the local Ethic Committee.
Results The mean age was 65.8 ± 15 years and male sex was more frequent
(63.3%). Pneumonia (59.2%) was the most common source of sepsis. Mean
APACHE II and SOFA scores on the fi rst day of sepsis were 24.4 ± 7.7 and
8.7 ± 3.7, respectively. Observed mortality was 71.4%. Median urinary
albumin was 7.0 mg/l (IQT: 4.7 to 60.3 mg/l) for survivors and 15.5 mg/l
(IQT: 7.9 to 77.1 mg/l) for nonsurvivors on the fi rst day of septic shock.
Urinary albumin decreased from 7.0 mg/l (IQT: 4.7 to 60.3 mg/l) to 3.9 mg/l
(IQT: 3.6 to 44.1 mg/l) in survivors during the fi rst 3 days of septic shock,
and in nonsurvivors remained at the same level from 15.5 mg/l (IQT: 7.9 to
77.1 mg/l) to 14.5 mg/l (IQT: 3.9 to 45.3 mg/l) in the period of observation.
Conclusions Patients with septic shock showed high frequency of
microalbuminuria. Levels of urinary albumin showed a tendency to
decrease in survivors, suggesting prognostic signifi cance.
1. Thorevska N, et al.: Crit Care Med 2003, 31:1075-1081.
2. Abid O, et al.: Chest 2001, 120:1984-1988.
Evaluation of automated hematologic VCS parameters in severe
sepsis and septic shock: a case–control study
A Cortegiani1, A Di Benedetto1, L Marino1, G Virga1, R Chiaramonte1,
C Sarno2, SM Raineri1, A Giarratano1
1University of Palermo, Italy; 2Fondazione Istituto S. Raff aele, Cefalù (PA), Italy
Critical Care 2010, 14(Suppl 1):P31 (doi: 10.1186/cc8263)
Introduction A cheap and quick hematologic diagnostic parameter for
detection of sepsis would have both economic and therapeutic benefi ts.
The Coulter LH series hematology analyzer uses the VCS technology
(Volume, Conductivity, Laser Scatter) providing information about cell
volume, size, internal structure, and surface morphology. Many authors
analyzed the clinical usefulness of VCS parameters in reactive neutrophils
for detection of sepsis. An increase in mean cell volume and a decrease in
mean light scatter in septic patients have been described. Our aim is to
verify the correlation between VCS parameters and sepsis.
Methods We enrolled 92 patients admitted in our ICU and divided them
into two groups: Controls (48) and Sepsis (44). We collected blood samples
immediately after making the diagnosis. All samples were analyzed by
Coulter LH 500 hematology analyzer. We realized ROC curves for each V,
C, S parameter.
Results The AUC was 0.816 (95% CI, 0.722 to 0.889) for mean-V value; 0.546
(95% CI, 0.439 to 0.650) for mean-C value; 0.604 (95% CI, 0.497 to 0.704) for
mean S value (Figure 1). The correlation with sepsis was a linear positive
one for mean-V (strong) and mean-C (weak) instead of a linear negative
one for mean-S. The best cut-off value for mean-V was >163 (Sens: 84.09%;
Spec: 68.75%); >137 for mean-C (Sens: 72.73%; Spec: 41.67%); <134 for
mean-S (Sens: 56.82%; Spec: 64.58%).
Conclusions Our study shows the high diagnostic performance of mean-V
and the weak one of mean-C and mean-S in septic patients. The clinical
usefulness of mean-V is strengthened by the quickness and cheapness of
its analysis. It could be tested daily or more as a valid laboratorial help for
critical patient’s clinical assessment.
Use of CD64 for the diagnosis of sepsis: a case–control study
A Cortegiani1, L Marino1, A Di Benedetto1, G Virga1, G Evangelico1,
C Sarno2, SM Raineri1
1University of Palermo, Italy; 2Fondazione Istituto S. Raff aele, Cefalù (PA), Italy
Critical Care 2010, 14(Suppl 1):P32 (doi: 10.1186/cc8264)
Introduction CD64 is the high-affi nity receptor of IgG. It is upregulated by
infl ammatory cytokines on neutrophils. The upregulation of CD64 is linked
with PMN activation in SIRS or sepsis. Our aim is to verify these correlations.
Methods We enrolled 48 ICU critical patients and three groups were
created: SIRS– (17), SIRS+ (13), Sepsis (17). We evaluated CD64 X-mean
values among the three groups as shown in Figure 1. We used a t test to
check the correlation between uprising CD64 and diff erent groups. We
verifi ed the correlation CD64/SOFA (Figure 2), WBC, NE, and patients’ age
Results We found a CD64 higher level in sepsis compared with SIRS– (t =
8.095; P <0.001) and with SIRS+ (t = 4.938; P <0.001). There were a high
positive linear correlation between CD64 and SOFA score (r = 0.806;
Figure 1 (abstract P31).
Figure 1 (abstract P32).
Figure 2 (abstract P32).
Critical Care 2010, Volume 14 Suppl 1
P <0.0001), a weak linear positive one with WBC count, a weak linear
positive correlation with NE count; no correlation with age.
Conclusions Our study shows that CD64 can identify SIRS/sepsis. We
found a correlation between CD64/SOFA; no infl uence of WBC, NE and
age was detected.
Endotoxin assay with endotoxin scattering photometry is one of the
diagnostic markers of sepsis
Y Kase1, T Obata2
1Jikei University School of Medicine, Tokyo, Japan; 2Microbial Chemistry
Research Foundation, Tokyo, Japan
Critical Care 2010, 14(Suppl 1):P33 (doi: 10.1186/cc8265)
Introduction Endotoxin scattering photometry (ESP) is one of a newly
developed clinically applicable method for endotoxin assay. Although ESP
is an analogous assay of turbidimetric method, it enables one to detect very
small amounts of endotoxin within 1 hour. This is because ESP can directly
detect clotting enzyme product, coagulin, which is the fi rst appearance of
Limulus amebocyte lysate (LAL) cascade and the precursor of gel clots.
Methods To study the correlates and prognostic signifi cance of the
endotoxin assay with ESP, we enrolled a total of 80 people consisting of
three groups which were normal healthy volunteers (n = 35), patients
admitted to the emergency department (ED) (n = 21) and patients
admitted to the ICU (n = 24). To examine whether endotoxin is infl uencing
in the severity of disease, we used sepsis/SIRS stratifi cation which was
defi ned by the American College of Chest Physicians/Society of Critical
Care Medicine (ACCP/SCCM).
Results Of all 80 people, 33.7% (n = 27) was sepsis. The levels of endotoxin
were signifi cantly higher in the patients with sepsis (median, 18.4 pg/ml;
interquartile range, 3 to 54.1 pg/ml) than in the people without sepsis
(0.227 pg/ml; 0.031 to 0.493 pg/ml). The area under the receiver operating
characteristic curve was 0.951 in the patients with sepsis. Cut-off
concentrations for optimum prediction of sepsis with ESP were endotoxin
>7.06 pg/ml (diagnostic effi ciency: 92.6%).
Conclusions Endotoxin assay with ESP is one of the diagnostic markers
of sepsis because the levels of endotoxin in patient with sepsis are clearly
high. Endotoxin assay with ESP concentration higher than 7.06 pg/ml
1. Obata T, Nomura M, Kase Y, Sasaki H, Shirasawa Y: Early detection of the
Limulus amebocyte lysate reaction evoked by endotoxins. Anal Biochem
Immature platelet fraction as predictive index of sepsis
C Scaramucci, R De Blasi, S Tribuzi, A Carlini
II Faculty of Medicine – University of Rome ‘La Sapienza’ S. Andrea, Rome, Italy
Critical Care 2010, 14(Suppl 1):P34 (doi: 10.1186/cc8266)
Introduction The incidence of sepsis is reported around 37% in European
ICUs . The mortality rate depends on the severity of organ failure, up to
65% if four or more organs are involved. Multiple organ failure (MOF) is
due to microcirculatory dysfunction with microthrombosis resulting from
coagulation disorders including platelets’ activation. An early diagnosis
should identify the microcirculatory dysfunction before MOF became
clinically evident. The diagnosis of sepsis is commonly based on clinical
criteria, pathogen identifi cation and use of markers like procalcitonin
(PCT) and C-reactive protein (PCR) associated with infection. The aim of
our study is to evaluate whether the routine measurement of immature
platelet fraction (IPF), considered a precocious marker of platelet
production, is associated with sepsis and its severity and/or whether it
could be used as a predicting marker of sepsis.
Methods We enrolled 66 consecutive patients admitted to the ICU,
dividing them into two groups: septic (n = 44) and no septic (n = 22). The
severity of sepsis was evaluated. The exclusion criterion was a platelet
count <150,000/mm3. Blood count, coagulation, PCR, PCT, and IPF were
collected every day.
Results The IPF values between septic (4.6 ± 3.1) and no septic patients
(3.3 ± 1.5) did not diff er (P = 0.16). No correlation was found between IPF
values and the severity of septic condition (no sepsis 11.7 ± 10.1; sepsis
14.3 ± 10.5; severe sepsis 10.5 ± 9.1; septic shock 19.5 ± 12.4; P = 0.3). When
we considered only subjects who did not have sepsis at the ICU admission
we found that patients who developed sepsis during the recovery had IPF
values higher than patients who did not develop sepsis (Table 1).
Conclusions From our results IPF cannot be considered a marker of sepsis.
Conversely it could be used as predictive index of sepsis because it can
identify patients who will develop sepsis.
1. Vincent et al.: Sepsis in European intensive care units: results of the SOAP
study. Intensive Care Med 2006, 34:344-353.
Serial estimation of cytokine markers and their correlation with
mortality in elderly patients with sepsis
R Bhanot, J Kaur, M Rao, T Ramachandran, K George, D Veliath
Pondicherry Institute of Medical Sciences, Pondicherry, India
Critical Care 2010, 14(Suppl 1):P35 (doi: 10.1186/cc8267)
Introduction Sepsis is a serious health problem in the elderly with a high
degree of mortality. The study of pathophysiology of sepsis has lead to the
development of cytokine markers which help in establishing diagnosis,
quantifying the severity and assessing the response to therapy. TNFα and IL-6,
a pleotropic cytokine, are among the most well-studied proinfl ammatory
cytokines in sepsis. However, very limited data are available in elderly
subjects regarding the markers for sepsis. The present study was undertaken
to establish the cytokine profi le in sepsis in the elderly and develop markers
for prediction. The infl uence of gender on cytokine production and mortality
in elderly patients with sepsis was considered in particular.
Methods In this prospective study, 50 elderly patients, age above 65 years,
satisfying the systemic infl ammatory response syndrome (SIRS) criteria
were included. Serial estimations of TNFα and IL-6 were done on days 1,
3 and 7 of ICU admission.
Results The results were drawn on the basis of gender and survival. A
correlation of APACHE score, TNFα values and IL-6 values on day 1, day
3 and day 7 between survivors and nonsurvivors was also documented,
which showed reducing levels of IL-6 levels from days 1 to 7 in the survivor
group (P <0.01). The TNFα level was signifi cantly low on day 1 in the
nonsurvivor female group (P <0.00001).
Conclusions Cytokine profi ling for TNFαand IL-6 level in elderly patients
with sepsis helps in prognosticating the outcome. Female gender was an
independent predictor of increased morality in critically ill patients with
1. Martin GS, et al.: Crit Care Med 2006, 34:15-21.
2. Ulloa L, et al.: Trends Mol Med 2005, 11:56-63.
3. Oberholzer A, et al.: Shock 2005, 23:488-493.
Infl uence of TIMP-1/MMP-9 ratio on the severity and mortality in sepsis
L Lorente1, M Martín2, J Solé-Violán3, J Blanquer4, L Labarta5, C Díaz6,
J Borreguero1, J Páramo7
1Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain; 2Hospital
Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain;
3Hospital Universitario Dr Negrín, Las Palmas de Gran Canaria, Spain;
4Hospital Clínico Universitario de Valencia, Spain; 5Hospital San Jorge
de Huesca, Spain; 6Hospital Insular, Las Palmas de Gran Canaria, Spain;
7CIMA-University of Navarra, Pamplona, Spain
Critical Care 2010, 14(Suppl 1):P36 (doi: 10.1186/cc8268)
Introduction The role of matrix metalloproteinases (MMPs) and tissue
inhibitors of matrix metalloproteinases (TIMPs) in sepsis remains unclear.
Table 1 (abstract P34)
No sepsis Sepsis Mann–Whitney
5.4 ± 2.9
0.68 ± 1.1
9.57 ± 10.2
3.3 ± 1.5
0.57 ± 1.3
11.7 ± 10
P = 0.04
P = 0.4
P = 0.46
Critical Care 2010, Volume 14 Suppl 1
Previously reported have been higher circulating levels of TIMP-1 in septic
patients than in controls , higher PAI-1 levels in nonsurviving than in
surviving septic patients , and a positive correlation between TIMP-1 and
PAI-1 in apparently healthy adult individuals . The objective of this study
was to determine the association between TIMP-1/MMP-9 ratio and PAI-1,
and its infl uence on the severity and mortality of patients with sepsis.
Methods This was a multicenter, observational and prospective study
carried out in six Spanish ICUs. We included 192 (125 surviving and 67
nonsurviving) patients with severe sepsis. Serum levels of MMP-9, TIMP-1
and plasma levels of PAI-1 were measured at the time of diagnosis.
Results Nonsurviving septic patients presented higher levels of TIMP-1
(P <0.001), higher TIMP-1/MMP-9 ratio (P <0.001), higher levels of PAI-1
(P <0.001), higher SOFA score (P <0.001), higher lactic acid levels (P <0.001)
and lower platelet count (P <0.001) than surviving ones. TIMP-1/MMP-9
ratio positively correlated with PAI-1(P <0.001), lactic acid levels (P <0.001),
SOFA score (P <0.001), INR ratio (P <0.001), aPTT (P <0.001), and negatively
with platelet count (P <0.001). The mortality prediction by TIMP-1/MMP-9 ratio
(AUC = 0.66; 95% CI = 0.58 to 0.74; P <0.001) was similar to that provided by
other markers of severity such as lactic acid (AUC = 0.67; 95% CI = 0.58 to
0.75; P <0.001) and SOFA score (AUC = 0.71; 95% CI = 0.64 to 0.79; P <0.001).
Conclusions The TIMP-1/MMP-9 ratio may be of great pathophysiological
signifi cance in terms of severity and mortality in sepsis, and may represent
a biomarker to predict the clinical outcome of septic patients. The novel
fi nding of our study is the association between TIMP-1/MMP-9 ratio and
PAI-1 levels in sepsis, which can contribute in the organ dysfunction and
mortality of sepsis.
Acknowledgements Study supported, in part, by the grants FUNCIS-
PI-42/07 and GTEI-SEMICYUC-2009.
1. Hoff mann U, et al.: Scand J Infect 2006, 38:867-872.
2. Hermans PW, et al.: Lancet 1999, 354:556-560.
3. Aznaouridis K, et al.: Atherosclerosis 2007, 195:212-215.
Cytokine response in severe sepsis: predicting and modelling the
course of illness
J Malaska1, M Kratochvil2, M Kyr2, P Jabandziev2, F Otevrel2, K Muriova2,
M Fedora2, V Sramek3, J Michalek2, P Sevcik2
1University Hospital Brno, Czech Republic; 2University Hospital Brno and
Faculty of Medicine Masaryk University, Brno, Czech Republic; 3St Anne’s
University Hospital Brno and Faculty of Medicine Masaryk University, Brno,
Critical Care 2010, 14(Suppl 1):P37 (doi: 10.1186/cc8269)
Introduction Severe sepsis remains one of the most threatening
conditions in intensive care. During the progression of sepsis from
early hit to multiorgan failure proinfl ammatory and anti-infl ammatory
cytokines are released. Cytokines can be used as biomarkers to determine
the specifi c patterns of sepsis progression and association with mortality
. These biomarkers were successfully used as predictors in animal
studies . Data from humans, especially comparison between children
and adults, are limited. Hence, in this study we widely describe systemic
cytokine response in this type of patient population.
Methods Prospective study of 37 subjects (20 children, 17 adults)
hospitalized with severe sepsis in intensive care. We measured CRP,
procalcitonin, TNF, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12, TREM-1. ANOVA models
were specifi ed using Proc Mixed. Study was fully approved by an ethics
Results We identifi ed a correlation of CRP levels with mortality or
presence of shock (Figure 1). We found a distinct feature of CRP in adults
with pronounced dynamic dichotomy in these subjects. Levels of IL-6
were signifi cantly diff erent in adult patients in the context of shock states.
High IL-6 levels in the beginning of sepsis were associated with shock
during progression of illness. Highest risk of death was in adult patients
associated with TREM-1 sustained high after 48 hours after sepsis onset
(Figure 2). Otherwise, there was no correlation with death, shock states
and SOFA score for PCT, TNF, IL-1β, IL-4, IL-8, IL-10, and IL-12.
Conclusions Response of circulating factors in patients with severe sepsis
is heterogeneous in the adult and children population and has some
distinct features according to the dynamics of CRP, IL-6 and TREM-1.
Acknowledgements Supported in part by the Internal Grant Agency of
the Ministry of Health NR 9297-3 and NR 9894-4.
1. Kellum JA, et al.: Arch Int Med 2007, 167:1655-1663.
2. Osuchowski et al.: Crit Care Med 2009, 37:1567-1573.
Time course of IL-6 and LBP, candidate biomarkers of sepsis in
surgical critical care
E Kipnis, L Ogé, B Soudan, B Leroy, B Vallet, G Lebuff e
Centre Hospitalier Régional Universitaire de Lille, France
Critical Care 2010, 14(Suppl 1):P38 (doi: 10.1186/cc8270)
Introduction The outcome of sepsis in critically ill patients relies on
rapid identifi cation and therapy. However, identifi cation of sepsis in these
patients is challenging, and focus has shifted towards biological surrogates
as diagnostic/therapeutic biomarkers. IL-6 and lipopolysaccharide binding
protein (LBP) may have such a potential.
Methods Retrospective analysis of daily IL-6 and LBP serum levels
over the course of a 3-month laboratory feasibility study of large-scale
chemiluminescent immunometric assays on unused residuals of routine
patient blood samples from the surgical critical care unit. We determined
the time course of IL-6 and LBP over septic events defi ned as 4 days
before and after the initiation of antimicrobial therapy as day 0 (n = 40).
Variations over time of IL-6 and LBP in both absolute values and amplitude
were measured between day –4 to day 0 and day 0 to day +4. Candidate
biomarker variations were assessed for coherence with clinical evolution
of sepsis to determine biomarker-like behavior.
Figure 1 (abstract P37). SOFA adults. Solid line, SOFA 0 to 12; dashed line,
SOFA 13 to 24.
Figure 2 (abstract P37). Adults. Solid line, exitus; dashed line, survived.
Critical Care 2010, Volume 14 Suppl 1
Results Only amplitudes of variation were coherent with clinical evolution
of sepsis rather than variations in absolute values or values relative
to published thresholds. Coherence between patient evolution and
biomarker time course was 93% for IL-6 and 85% for LBP. IL-6 levels always
increased to over at least 50% of baseline (51 to 2,523%) before initiation
of antibiotics. IL-6 decreased by at least 45% (45 to 98%) of the maximal
value when sepsis resolved successfully with antimicrobial therapy in 92%
of the cases. Stagnating IL-6 levels always paralleled absence of resolution
of sepsis. No pre-antimicrobial initiation increase of LBP was observed.
LBP always decreased by at least 16% (16 to 85%) of the maximal value
when sepsis resolved successfully with antimicrobial therapy. LBP increase
after initiation of antimicrobials or LBP stagnation paralleled absence of
clinical resolution. Concordant patterns of both IL-6 and LBP were always
coherent with clinical evolution but only concerned 35% of the cases.
Conclusions IL-6 and LBP behave as biomarkers over the course of sepsis
in surgical critical care patients. Only dynamic monitoring may yield any
information relevant to diagnosis or treatment follow-up. It remains to be
shown how well these biomarkers perform through other study designs.
Prognostic value of melatonin in patients with sepsis: a comparison
of survivors and nonsurvivors
K Alan, D Memis, G Altun, N Sut
Trakya University, Edirne, Turkey
Critical Care 2010, 14(Suppl 1):P39 (doi: 10.1186/cc8271)
Introduction Our objective was to investigate the plasma levels of
melatonin and the prognostic value of these markers in patients with
sepsis. This is a prospective study of 131 patients over 22 years old with
sepsis in the ICU.
Methods The patients were divided into two groups containing 72
patients as survivors (Group I) and 59 patients as nonsurvivors (Group II).
The blood collection was performed in the night (02.00 to 04.00 hours)
and the Acute Physiologic and Chronic Health Evaluation II (APACHE II)
score calculated on the day of hospitalisation, second day and the last
day (discharge or death). The samples were centrifuged methodically
and plasma samples were preserved at –200°C. After reaching the target
quantity, all plasma samples were studied with RIA method at room
Results Statistically signifi cant high APACHE II values were determined
in Group II compared with Group I on the all days (P <0.05). Statistically
signifi cant low nocturnal plasma melatonin values were determined
in Group II compared with Group I on the last day (P <0.05). In Group II,
duration of mechanical ventilation and stay of ICU are longer, and at the
last days of biochemistry parameters failed (elevation of urea, creatinine,
serum glutamic oxaloacetic transaminase and serum glutamic pyruvic
transaminase) (P <0.05).
Conclusions We conclude that from plasma melatonin values it is
impossible to predict the prognosis but during the follow-up these values
can demonstrate the status of prognosis in septic patients. There are
several factors aff ecting these melatonin values; thereby we propose that
further research should be performed.
Serum C-reactive protein as a prognostic variable in elective
surgery ICU patients: especially valuable following esophagectomy
M Van Genderen, H De Geus, D Gommers, J Van Bommel
Erasmus MC, Rotterdam, the Netherlands
Critical Care 2010, 14(Suppl 1):P40 (doi: 10.1186/cc8272)
Introduction Serum C-reactive protein (CRP) is synthesized in response to
infl ammatory status. Elevated CRP levels are associated with an increased
risk of multiorgan failure in ICU patients. Preoperative elevation of serum
CRP is a prognostic indicator in gastric and colorectal surgery. The aim of
this study was to determine serum CRP as prognostic variable in patients
undergoing esophagectomy with gastric tube reconstruction in contrast
to other ICU admitted patients.
Methods Data were collected retrospectively for a total of 208 patients
admitted to the ICU following elective surgery from October 2007 to
December 2008. Patients included underwent esophagectomy with
gastric tube reconstruction, liver transplantation, hemihepatectomy,
neuro- and abdominal aneurysm surgery. Postoperative serum markers
were measured and the relation between the course of postoperative
serum CRP, development of complications and prognosis of the patients
Results Postoperative serum CRP was signifi cantly higher at T24 in
patients undergoing esophagectomy with gastric tube reconstruction,
compared with all other patients. Higher serum CRP levels correlated with
the occurrence of complications in the heterogeneous ICU population
but especially in the esophagectomy patients. Within this group, serum
CRP levels at T24 and T48 were signifi cantly higher in patients with a
postoperative pneumonia, which in itself was associated with increased
Conclusions Postoperative serum CRP levels can easily be monitored
in the ICU in order to identify patients at risk for the development of
postoperative complications. Especially in the esophagectomy patients,
the occurrence of postoperative complications is associated with reduced
Role of procalcitonin as a diagnostic and prognostic marker of
infectious diseases in the emergency department: preliminary data
L Magrini, V Mura, F Travaglino, O Piras, E Ferri, S Di Somma
A. O. S.Andrea, Rome, Italy
Critical Care 2010, 14(Suppl 1):P41 (doi: 10.1186/cc8273)
Introduction An observational study was conducted in a teaching hospital
to evaluate the diagnostic and prognostic value of procalcitonin together
with C-reactive protein (CRP) in assessing the presence of infection/sepsis
in patients arriving in the emergency department (ED). The objective
was to improve diagnostic and therapeutic time to intervention by the
Methods Three hundred and fi ve patients were studied (145 male, 160
female, mean age 67.2 years). Vital parameters were recorded during
patient’s stay in the ED. Hemocultures and biological fl uids cultures
were performed before antibiotic therapy. CRP and procalcitonin were
performed at arrival in the ED, and after 5 days of antibiotic therapy.
Results Median PCT and CRP values at arrival in the ED were 0.3 ng/ml
and 12.9 mg/dl, after 5 days they were 0.09 ng/ml and 4.2 mg/dl with a
signifi cant statistical diff erence in both markers (P <0.001). PCT was higher
in sepsis vs infections (respiratory, urinary, gut or skin infections) (3.1 vs
0.2 ng/ml, P <0.001). PCT pre-therapy was signifi cantly higher in septic
nonsurvivors vs septic survivors (1.0 vs 0.2 ng/ml, P <0.001), and there was
a signifi cant PCT increase after 5 days in nonsurvivors vs survivors (3.6 vs
0.07 ng/ml) (P <0.001). CRP results did not show a statistical signifi cance,
except for CRP measured after 5 days (3 mg/dl) vs CRP pre-therapy in
survivors (12 mg/dl, P <0.001). PCT (cut-off 0.5 ng/ml) ROC curve showed
an AUC 0.72 (P <0.001), with a sensitivity 75% as a diagnostic marker for
Figure 1 (abstract P40). CRP and complications in all groups.
Critical Care 2010, Volume 14 Suppl 1
infection. In septic patients, PCT ROC curve had an AUC 0.70 (P <0.001)
if considered as a prognostic factor of death (cut-off 1 ng/ml). Although
pre-therapy PCT values were not particularly sensitive, nor specifi c for
predicting deaths, PCT in therapy (cut-off 0.5 ng/ml) had an AUC 0.79
(sensitivity 75%, specifi city 76% in predicting events) (P <0.0001). This was
higher than CRP (AUC 0.73, P <0.0004).
Conclusions PCT, with CRP, is useful to make an initial rapid infection
diagnosis for patients presenting to the ED, and also to discriminate it from
sepsis. Our results are in agreement with other authors [1,2]. A PCT cut-off
value of 0.5 ng/ml shows high sensitivity as a diagnostic infection marker,
but also as a prognostic marker for outcomes. PCT with CRP are useful
tools to assess a fast empiric therapy, and to ameliorate the prognosis of
infectious/septic in ED patients.
1. Hausfater P, et al.: Clin Infect Dis 2002, 34:895-901.
2. Balci C, et al.: Crit Care 2003, 7:85-90.
Evaluation of procalcitonin at James Paget Intensive Care Unit
A Brodbeck, N Elumogo, G Rajendran
James Paget University Hospital NHS Foundation Trust, Great Yarmouth, UK
Critical Care 2010, 14(Suppl 1):P42 (doi: 10.1186/cc8274)
Introduction Procalcitonin (PCT) off ers the possibility of diff erentiating
bacterial infection from viral or non-infectious reactions. PCT can be used
to support decision-making on initiation or discontinuation or change of
antibiotic therapy. Our aim was to determine the usefulness of PCT in our ICU.
Methods PCT was measured once daily for all patients admitted to the
ICU. Results were reviewed daily by intensivists and microbiologists and an
appropriate decision about antibiotic therapy was made. We considered to
stop antibiotics if the PCT was <0.5 ng/ml or had decreased to 80% of the
peak value. CRP and clinical progression were also taken into consideration.
Results One hundred and fourteen PCT values were obtained from 27
patients over 18 ICU days. PCT concentrations were lower than 0.5 ng/ml
in 49 samples whilst CRP values were higher with a median of 107.5 mg/l.
Antibiotics were discontinued or not initiated following low PCT values in
38 of these samples despite high CRP. For two patients who were already
on antibiotics, a rise in PCT was noticed which prompted us to change
the antibiotics. No new microbiologically proven systemic infection was
identifi ed in any of the patients with low PCT values. See Figure 1.
Conclusions Frequently, discrepancy between PCT and other
infl ammatory markers were noticed, suggesting an infl ammatory response
or nonbacterial infection and not necessarily an indication for antibiotics.
Regular assessment of PCT, when interpreted with clinical context, was
helpful not only to decrease the duration of antibiotics but also to change
the antibiotic regimen.
1. Shehabi Y, et al.: Crit Care 2008, 12:211.
2. Hochreiter M, et al.: Crit Care 2009, 13:R83.
Procalcitonin facing the postoperative culture results after liver
J Fazakas1, E Papp1, G Ther1, Z Gallfy1, B Fule1, M Varga1, T Mandli1, S Toth1,
J Fazakas2, L Kobori1, M Arkosy3
1Semmelweis University, Budapest, Hungary; 2Bajcsy Zsilinszky Hospital,
Budapest, Hungary; 3Soprponi Erzsébet Oktató Kórház, Sopron, Hungary
Critical Care 2010, 14(Suppl 1):P43 (doi: 10.1186/cc8275)
Introduction The early infl ammatory response after liver transplantation
(LTx) could be diagnosed by the simultaneous interpretation of
procalcitonin (PCT) levels and culture results. The aim of this prospective,
non-interventional study was to evaluate the prognostic signifi cance of
the PCT levels in the term of etiology (infection, colonization and non-
infectious infl ammatory states).
Methods The PCT measurements and cultures were performed before
surgery and on the fi rst fi ve postoperative days in 114 liver transplanted
patients. The relationship between the absolute PCT levels (n = 762) and
culture results (n = 474) was studied. The patients were divided into two
groups according to the infection or colonization with Gram-positive (GP)
or Gram-negative (GN) bacteria. Statistical analysis was done with the SPSS
Results In 21 patients negative cultures were associated with PCT
elevation (PCT: 3.77 ± 3.22 ng/ml), positive cultures were found in 107
patients, in 58 patients this was colonization (PCT <0.5 ng/ml). There
signifi cant diff erences between the PCT elevation according to the
etiology culture (GN, n = 36, PCT: 17.55 ± 11.3 ng/ml; GP, n = 222, PCT:
16.54 ± 6.58 ng/ml; P <0.02).
Conclusions In the early phase after liver transplantation, the GP culture
occurred more frequently; the GN culture could be associated with higher
PCT elevation than those found in case of GP culture.
Can follow-up procalcitonin measurements shorten the periods of
antibiotic administrations for septic patients?
T Wada, A Hagiwara, R Sasaki, T Sato, K Kobayashi, A Inaka, T Sakamoto,
Y Hagiwara, T Inagaki, K Katsuno, R Takegawa, A Kimura
International Medical Center of Japan, Sinjyuku Tokyo, Japan
Critical Care 2010, 14(Suppl 1):P44 (doi: 10.1186/cc8276)
Introduction To examine whether we can safely shorten the periods
of antibiotic administration for septic patients with procalcitonin (PCT)
measurements compared with no PCT measurements.
Methods The participants were septic patients including (1) hospitalized
to our ICU from February 2009 to November 2009, (2) administered
antibiotics for 4 days and over, and (3) stopped the antibiotics during their
ICU stays. We treated the patients from February to June without PCT
measurements (Group A). On the other hand, we treated the patients from
July to November referring to serum PCT level (Group B). In group B, when
Figure 1 (abstract P42). Example 1 (left): sepsis secondary to hydronephrosis. This graph clearly shows the rise in procalcitonin (PCT) during early onset
of sepsis and its fall during antibiotic treatment. Antibiotics were discontinued when the PCT level fell to 80% of its peak value on day 8. Example 2 (right):
laparoscopic cholecystectomy complicated by bile peritonitis. Good response to antibiotics initially, but PCT started to rise on day 12 which prompted us to
change antibiotics. Serial PCT is useful to assess the response to treatment.
Critical Care 2010, Volume 14 Suppl 1
the serum PCT level decreases under 0.5 ng/ml, we stopped the antibiotic
administrations if their systemic conditions were getting better.
Results Twelve patients were in Group A, and 15 patients were in Group
B. The ages were 65 ± 18 in Group A, and 64 ± 23 in Group B. The APACHE
II scores were 20.4 ± 6.3 in Group A, and 18.5 ± 7.5 in Group B. There were
no signifi cant diff erences. The periods of antibiotic administrations were
14.1 ± 7.7 days in Group A, and 9.7 ± 6.0 days in Group B. The periods in
Group B tended to be signifi cantly shorter than in Group A (P = 0.049).
The C-reactive protein (CRP) levels were 3.5 ± 4.2 mg/dl in Group A, and
6.5 ± 4.1 in Group B when the antibiotic administrations were stopped.
The CRP levels in Group B were higher than in Group A (P = 0.071). Two
patients in Group B were repeated antibiotic administrations, while they
were discharged without any complications.
Conclusions The follow-up PCT measurements safely shorten the periods
of antibiotic administrations for septic patients. We believe that PCT has
good cost–benefi t eff ects for critically ill patients.
Effi ciency diagnostic and advantages of procalcitonin and
C-reactive protein in the early diagnosis of sepsis
M De la Torre-Prados, A García-de la Torre, A García-Alcántara,
C Ortíz-García, A Enguix-Armada
Hospital Virgen de la Victoria, Málaga, Spain
Critical Care 2010, 14(Suppl 1):P45 (doi: 10.1186/cc8277)
Introduction The goal of our study is to assess the diagnostic profi tability
of procalcitonin (PCT) in septic shock and another biomarker as C-reactive
Methods Case–control study. During 2009 we proceeded to select the
sample: 54 patients (ICU) and 61 controls. PCT and CRP were set in the
fi rst 24 hours besides the diagnosis and other analytical (glucose, lactate,
leukocytes, platelets, white blood cells, LIC cells and ALY cells) and
clinical parameters. There were realized diagnostic output curves (ROC),
area under the curve (AUC), confi dence interval (95%), cut-off and the
comparison between AUC.
Results Fifty-four septic patients were assessed, 66% were males; mean
age, 63 years. Eighty-eight percent was diagnosed as septic shock and
11% severe sepsis. Seventy-six percent were medical patients. Positive
blood cultures in 42.5%. Sepsis origin: respiratory 46%, neurological 5%,
digestive 37% and urinary 3%. Average SOFA score was 10.4.
Conclusions PCT and CRP have the same effi ciency in early sepsis
diagnosis. The PCT and CRP effi ciency diagnostic together is signifi cant
but small. We suggest using both with the doubt of sepsis.
Biomarkers of sepsis in burn patients
H Oueslati1, K Bousselmi1, I Rahmani1, A Mokline1, J Haddad1, Y Yahyia1,
R Ghanem2, A Messadi1
1Burn and Trauma Center, Tunis, Tunisia; 2Microbiology Department, Tunis,
Critical Care 2010, 14(Suppl 1):P46 (doi: 10.1186/cc8278)
Introduction Sepsis is still the major cause of death in the late post-
traumatic period in patients with major burns. Diagnosis of sepsis remains
diffi cult in these patients where signs of sepsis may be present in the
absence of real infection. This study attempted to assess whether the
plasma procalcitonin (PCT) level was related to sepsis in burned patients.
Methods PCT was measured over the entire course of stay in patients with
predictive signs of sepsis according to Burn French Society Criteria (SFETB)
for the presence of infection. The patients were assigned to two groups
depending on the clinical course and outcome: A = no septic patients, B =
septic patients. Optimum sensitivity, predictive values, and area under the
receiver operating characteristic (ROC) curve were evaluated.
Results Over a 6-month period starting from 1 July 2008 to 31 December
2008, 157 patients were admitted. Sixty-two were investigated, 40 in group
A and 22 in group B. Procalcitonin was signifi cantly higher in the septic
group (7.26 ± 7 ng/ml) compared with the no septic group (0.25 ± 0.32 ng/
ml). Area under the curve was 0.94 on the day of sepsis diagnosis. A PCT
cut-off value of 0.75 ng/ml was associated with the optimal combination
of sensitivity (85%), specifi city (87%), positive predictive value (91%), and
negative predictive value (73%). In surviving septic patients the PCT value
was signifi cantly lower than in deceased septic patients (3.5 ± 0.87 ng/
ml vs 10.18 ± 9.6 ng/ml). The PCT cut-off value for optimum prediction
of outcome in septic patients was 3.66 ng/ml with sensitivity (91%),
specifi city (75%), positive predictive value (78%), and negative predictive
Conclusions Procalcitonin appears to be a powerful marker of sepsis in
burn patients. It is sensitive, specifi c, reliable and easy to measure. A high
PCT concentration (>3.66 ng/ml) would indicate poor outcome in septic
1. Gramm HJ, et al.: A biological marker of the infl ammatory response with
prognostic properties. Clin Intens Care 1995, 6(Suppl):71.
2. Zeni F, et al.: Procalcitonin serum concentrations and severity of sepsis. Clin
Intens Care 1994, 5(Suppl):2.
Age-related diff erences of outcomes in patients hospitalized with
community-acquired pneumonia are not explained by diff erences
in immune response
S Kale, S Yende, L Kong, A Perkins, JA Kellum, AN Vallejo, AB Newman,
University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Critical Care 2010, 14(Suppl 1):P47 (doi: 10.1186/cc8279)
Introduction We hypothesized that the higher risk of severe sepsis and
mortality observed after infection in prior epidemiologic studies are due
to age-related diff erences in immune response.
Methods We analyzed 2,183 subjects from a multicenter observational
cohort of patients hospitalized with community-acquired pneumonia
(CAP). We divided subjects into fi ve age groups (<50, 50 to 64, 65 to 74,
74 to 84, ≥85). To compare immune response, we measured circulating
infl ammatory (IL-6 and IL-10), coagulation-fi brinolysis (D-dimer, factor
IX (F-IX), thrombin–antithrombin complex (TAT), antithrombin (AT) and
plasminogen-activator inhibitor (PAI)), and cell surface markers (TLR2,
Figure 1 (abstract P45). Comparison between AUC not signifi cantly
diff erent for PCT and CRP (P = 0.445).
Table 1 (abstract P45). Output curve results: PCT/CRP, sensitivity, specifi city
Mean 24 ng/ml 227 mg/day
AUC 0.983 0.965
95% CI 0.93 to 0.99 0.91 to 0.99
Sensitivity 92.6% 91.1%
Specifi city 93.1% 100%
Critical Care 2010, Volume 14 Suppl 1
TLR4, HLADR) on emergency department (ED) presentation and during
the fi rst week of hospitalization.
Results Older subjects had higher rates of severe sepsis (14.8%, 23.0%,
26.3%, 34.0%, 42.3%) and 90-day mortality (1.8%, 3.8%, 9.2%, 18.2%, 19.8%,
per age group (P <0.001)). However, there were no age-related diff erences
in infl ammatory or cell surface markers and only modest diff erences in
coagulation-fi brinolysis abnormalities on ED presentation and over the
fi rst week (P <0.05) (Figure 1).
Conclusions Despite large diff erences in outcomes, patients hospitalized
with CAP displayed no age-related diff erences in circulating infl ammatory
or cell surface markers and modest diff erences in circulating coagulation-
fi brinolysis markers.
Cost-eff ectiveness of a rapid and accurate test for diagnosing
infection in severe sepsis and septic shock patients
T Walke1, D Chalfi n2, J Lee1, E Rivers3
1Altarum Institute, Ann Arbor, MI, USA; 2Abbott Diagnostics, Abbott Park, IL,
USA; 3Henry Ford Hospital, Detroit, MI, USA
Critical Care 2010, 14(Suppl 1):P48 (doi: 10.1186/cc8280)
Introduction Prompt and accurate pathogen identifi cation is crucial
for treatment of severe sepsis and septic shock (SS/SS). Blood cultures
(BC) require 24 to 48 hours and often yield inaccurate results. Eff ective
pathogen identifi cation allows for timely, targeted antimicrobial therapy.
Methods A SS/SS Markov model  was developed to assess the cost-
eff ectiveness (CE) of a rapid and accurate diagnostic test compared with
the current standard. In the model, patients can transition between no SIRS,
SIRS, sepsis, severe sepsis and septic shock or exit the model via discharge
or death. Key literature assumptions are as follows: 91% eff ectiveness of
empiric therapy, 70% BC eff ectiveness, 90% new test eff ectiveness, $750
cost/test, 9.5 years average life expectancy of sepsis survivor, 0.69 quality-
adjusted life-year (QALY) for survivors, and turnaround times of 24 hours
for the new test and 48 hours for standard BC.
Results The model shows that the new test would be cost-eff ective
when compared with current BC, at a cost of $32,939 per QALY (day 28).
These results are compelling across a range of assumptions and almost
all estimates fall below the US CE threshold of $50,000 to $100,000/QALY
(Figure 1). Varying most assumed values by up to 25% had a moderate
impact on CE. CE is sensitive to empiric test eff ectiveness >95%. More
rapid diagnostic information lowered the cost/QALY.
Conclusions Preliminary results show that a rapid and accurate test would
be considered cost-eff ective across many assumptions and would reduce
the mortality associated with delayed diagnosis.
1. Rangel-Frausto et al.: Clin Infect Dis 1998, 27:185.
A multicentre study of bacteraemia using a new commercial
universal 16S rDNA PCR test
S Sakka1, N Wellinghausen2, A Kochem1, C Disque3, H Mühl3, S Gebert2,
J Winter2, J Matten4
1Medical Center Cologne-Merheim, Cologne, Germany; 2Universitätsklinikum
Ulm, Germany; 3Hochschule Bremerhaven, Germany; 4MVZ Leverkusen,
Critical Care 2010, 14(Suppl 1):P49 (doi: 10.1186/cc8281)
Introduction Bloodstream infection is a life-threatening condition
with a high mortality rate, especially in intensive care and neutropenic
patients. Standard diagnostics is based on blood culturing (BC). However,
limitations of BC include relatively low sensitivities and a long time-to-
result for the identifi cation of the pathogen, generally over 2 days and
more. On the grounds of data from a multicentre study using a universal
16S rRNA gene PCR assay, SepsiTest™, molecular diagnosis is discussed as
a rapid and sensitive tool for the detection and identifi cation of pathogens
supportive of BC. A new commercial PCR test, SepsiTest™, for direct
detection of bacteria in whole blood was compared with BC in terms
of sensitivity, specifi city, predictive values and time to positivity (TTP) of
bacterial infections of the bloodstream of critically ill patients.
Methods The test, SepsiTest™ (Molzym, Bremen), comprises the extraction
and 16S rRNA gene PCR detection of bacterial DNA in whole blood
samples. Bacteria in positive samples were identifi ed by sequence analysis
of the amplicon. In a prospective multicentre study, 342 blood samples
from 187 patients with systemic infl ammatory response syndrome (SIRS),
sepsis, or neutropenic fever were included.
Results Compared with BC, the diagnostic sensitivity and specifi city
of PCR/sequencing was 87.0% and 85.8%, respectively. The positivity
rate of PCR/sequencing (25.7%) was higher than BC (15.8%). Of 31 PCR/
sequencing-positive, BC-negative patients, most of whom received
antibiotics, the PCR results of 25 were judged as true or possible to
bacteraemia. Using a routine testing workfl ow, time to positivity of the
PCR test was on average decreased by 40 hours for anaerobe/fastidious
infections and by 54 hours for yeast infections.
Figure 1 (abstract P47). Modest diff erences in circulating concentration
of coagulation-fi brinolysis markers on ED presentation (day 1) and over
the fi rst 7 days. P1, day 1 P value from ANOVA model adjusted for sex, race,
co-morbidity, and smoking status; Tobit models used for censored data.
P2, day 1 to 7 P value from mixed eff ects model adjusted for sex, race, co-
morbidity, and smoking status; Tobmit models used for censored data.
Figure 1 (abstract P48). Sensitivity analysis on CE (Base Case CE =
Critical Care 2010, Volume 14 Suppl 1
Conclusions The PCR approach enables the detection and identifi cation
of bacteraemia in blood samples within a few hours. Despite the
indispensability of BC diagnostics, the rapid detection of bacteria by
SepsiTest™ appears to be a valuable tool, allowing earlier pathogen-
adapted antimicrobial therapy in critically ill patients.
Time to antibiotics in sepsis
R Appelboam, R Tilley, J Blackburn
Royal Devon and Exeter Hospital, Exeter, UK
Critical Care 2010, 14(Suppl 1):P50 (doi: 10.1186/cc8282)
Introduction Mortality from sepsis increases with delay in administration
of antibiotics. The Surviving Sepsis Guidelines suggest that antibiotics are
administered within 1 hour of diagnosis of severe sepsis and septic shock.
This retrospective study investigated the time to appropriate antibiotics in
patients with sepsis and identifi es reasons for delay where possible.
Methods All adult patients in our institution who had positive blood
cultures in 2008 were identifi ed. Included were patients with sepsis, severe
sepsis, or septic shock. Excluded were the isolation of low-pathogenicity
organisms from blood culture (for example, coagulase-negative Staphylo-
coccus). Case notes were reviewed to identify the time between diagnosis
of sepsis and administration of antibiotics. Time zero was taken as the
time recorded in the notes by the doctor that the patient was seen. Times
of prescription and administration of antibiotics were taken from the
Results There were 1,477 sets of positive blood cultures in 1,098 patients.
Following exclusions there were 503 episodes of positive blood cultures
in 494 patients. Three hundred and seventy-fi ve fulfi lled the criteria
and were analysed: 52 did not fulfi l entry criteria, in 16 cases sepsis was
not suspected, and 60 sets of notes were incomplete or unavailable.
Average age was 69 years. Mean time between diagnosis and antibiotic
administration was 8.1 hours, median 4 hours. A delay of 3 hours or more
between diagnosis and administration of antibiotics occurred in 218 cases
(58%). The 28-day mortality for all patients overall was 21%; 19% in the
no-delay group compared with 24% in the delayed group. The 1-year
mortality was 35% for both groups. Causes of delay in administration
included prescription error, awaiting senior review, and patient movement
Conclusions These retrospective data demonstrate that there is a delay in
administering antibiotics patients with sepsis. These data are likely to be
an underestimation as an accurate time zero is diffi cult to ascertain.
1. Kumar A, Roberts D, Wood KE, et al.: Crit Care Med 2006, 34:1589-1596
2. Dellinger RP, Levy MM, Carlet JM, et al.: Crit Care Med 2008, 36:296-327.
3. Bone RC, Sibbald WJ, Sprung CL: Chest 1992, 101:1481-1483.
Utility of an antibiotic guideline in hospital-associated infections
M Shankar-Hari, D Wyncoll
Guy’s and St Thomas’ NHS Foundation Trust, London, UK
Critical Care 2010, 14(Suppl 1):P51 (doi: 10.1186/cc8283)
Introduction Prompt initiation of appropriate antibiotic therapy improves
outcome in critically ill patients . In a tertiary-level ICU, we evaluated
the appropriateness of, and adherence to an antibiotic guideline (based
on local bacterial epidemiology) in CDC-defi ned hospital-associated
Methods We conducted a 6-month prospective observational study (April
2008 to October 2008) in consecutive ICU admissions of patients who
satisfi ed investigator-adjudicated classifi cation of ICU-acquired infections
according to CDC criteria . We assessed patient characteristics including
severity of illness at admission, ICU length of stay (LOS), appropriateness
of initial antibiotic choice as judged by in vitro sensitivity results and
appropriateness of the current guideline. Results are presented as mean
(SD) or median as appropriate.
Results During the study period there were 101 antibiotic starts in 65
patients with sepsis secondary to ICU-acquired infections. Medical patients
formed 44% of the study cohort; whilst 23% of patients were general
surgical and the remaining 33% were post cardiothoracic surgery. The age
and admission APACHE II score of the study cohort was 61.8 (16.3) years
and 18.4 (5.6). The median LOS and ICU mortality of the cohort was 24 days
and 27.6%. The most common CDC reportable diagnosis was clinical or
microbiological confi rmed pneumonia (PNU1/PNU2/LRI) (n = 57), followed
by intra-abdominal infection (SSI-GIT) (n = 10) and urinary tract infection
(SUTI) (n = 8). The culture positivity rate was 71.2%. The appropriateness of
the ICU antibiotic guideline is summarised in Table 1. Monotherapy was
used in 52.5% of episodes. The median length of antibiotic treatment with
positive cultures was 7 days, and 5 days for culture negative episodes. In
sepsis episodes with negative culture, antibiotics were stopped within
3 days in 17% of the episodes.
Table 1 (abstract P51). Appropriateness of guideline-based antibiotic therapy
(n = 35)
(n = 30)
(n = 36)
Positive cultures 23 (66%) 25 (83%) 24 (67%)
Appropriateness 18/23 (78%) 21/25 (84%) 14/24 (58%)
Conclusions The study cohort had a high culture positivity rate (71%) in
ICU-acquired sepsis. Our antibiotic guidelines gave an optimal empiric
initial therapy in over 74% of episodes, with more than 50% of antibiotics
started being monotherapy.
1. Kumar et al.: Crit Care Med 2006, 34:1589-1596.
2. Horan et al.: Am J Infect Control 2008, 36:309-332.
Assessment of antibiotic prescriptions in two French intensive care
MP Parisot1, CT Tassin2, AL Lepape2, RG Gauzit1
1Hotel Dieu, Paris, France; 2CHU Lyon Sud, Lyon, France
Critical Care 2010, 14(Suppl 1):P52 (doi: 10.1186/cc8284)
Introduction In the setting of antimicrobial policy, the French authorities
recommend assessing the quality of antibiotic therapy . The aim of this
study is to assess the adequacy of antibiotic therapy in the ICU, to good
practice guidelines and unit protocols. The three steps of prescription are
analysed: choice of treatment, modalities of prescription and treatment
Methods This preliminary observational trial was conducted in two ICUs
(October 2005 to August 2006 and March to August 2009). All patients with
curative antibiotherapy were prospectively included. For each patient, we
collected individual data of treatment and we evaluated them according
to the recommendations of good use published in the literature [1,2].
Results One hundred and thirteen patients were included. Infections
were community-acquired infection in 30% of the cases. Respiratory
tract infections were the most frequently encountered, followed by intra-
abdominal infections. The three most frequently isolated pathogens were
P. aeruginosa, E. coli and S. aureus.
Initial antibiotic therapy, n = 113: lack of sample 14%, inadequacy with unit
protocol 13%, too broad spectrum 7%, not justifi ed association 8%, wrong
posology 20%, incorrect route of administration 1%, wrong interval 6%,
lack of plasmatic dosage (n = 46) 7%.
Treatment follow-up, n = 108: wrong delay of reappraisal 14%, no adap-
tation to microbiological results 10%, lack of de-escalation 5%, no
reassessment of posology 3%, wrong posology (if change of treatment)
2%, wrong interval (if change of treatment) 3%, unjustifi ed duration 10%.
Conclusions The rate of prescriptions that did not conform to at least
one criterion in this study was over 70%. This high rate is partly explained
by the high number of assessment criterions (n = 15). The most frequent
criterion of inadequacy was a wrong initial dosage, followed by the
initiation of an antibiotherapy without a microbiologic sample, a wrong
delay of reassessment, and a nonconformity of treatment to unit protocols.
That last criterion must be assessed in a more qualitative way, as some
transgressions could be justifi ed.
Stratégie d’antibiothérapie et prévention des résistances bactériennes en
établissement de santé [www.has-sante.fr]
2. Van der Meer JW, et al.: Clin Microbiol Infect 2001, 7(Suppl 6):12.
Critical Care 2010, Volume 14 Suppl 1
Occurrence of alert pathogens in the clinical materials and
consumption of antibiotics in the ICU, in the years 2007 and 2008
K Wawrzyniak, A Mikucka, A Deptuła, E Gospodarek, K Kusza
Nicolaus Copernicus University in Toruń, Collegium Medicum, Bydgoszcz,
Critical Care 2010, 14(Suppl 1):P53 (doi: 10.1186/cc8285)
Introduction A continuous pressure of antibiotics and chemotherapeutics
in ICU patients promotes isolation of multidrug-resistant (MDR) strains.
Treatment of infections caused by microorganisms resistant to available
drugs often results in a therapeutic failure. The purpose of this work was
a retrospective comparison of the rates of isolation of particular MDR
pathogen groups in 2007 vs 2008 in ICU patients hospitalised in a university
hospital 11-bed reference department, and of antibiotic consumption in
the analysed years.
Methods Data concerning microbiological testing were analysed based
on the WHONET software, version 5.4. The analysis rejected repeated
identical culture results that did not refl ect a subsequent case of infection
with a given MDR pathogen, but only persistence of the same strain in a
Results MDR pathogen stains most frequently were isolated from the
bronchoalveolar lavage (BAL) material. Carbapenem-resistant Gram-
negative rods represented the highest rate (62% in 2007 and 64% in
2008); these included Pseudomonas aeruginosa strains (57% and 35%,
respectively). Escherichia coli (11% in 2007), Klebsiella pneumoniae (12%
in 2008) and Enterobacter cloacae (9% in 2008) predominated among
ESBL-producing intestinal rods. A minor increase of the rate of the
ESBL(+) strains was found in 2008. Single MRSA strains were isolated in
the analysis period, no VRE were cultured. The highest antimicrobial drug
consumption (DDD/100 person-days) in 2007 pertained to meropenem
(20.6), piperacillin/tazobactam (20.0), cephazolin and vancomycin
(11.6 and 11.1). The respective values for the year 2008 were as follows:
piperacillin/tazobactam (20.8), voriconazole (19.7), meropenem (14.6).
Conclusions A 47% increase in the MDR pathogen isolation rate
was found in the year 2008. MDR nonfermenting rods represent the
largest therapeutic and epidemiological challenge among the isolated
MDR pathogens. In the subsequent analysed year, fi rst emergence of
carbapenem-resistant Acinetobacter baumanii strains was noted.
1. Rossolini GM, Mantengoli E: Antimicrobial resistance in Europe and its
potential impact on empirical therapy. Clin Microbiol Infect 2008, 14:2-8.
Treatment cost of secondary peritonitis in Germany: a comparative
study of medical cost incurred for tigecycline therapy and standard
J Kresimon1, U Theidel2, C Runge2, R Rychlik1, W Krueger3
1Institute of Empirical Health Economic, Burscheid, Germany; 2Wyeth Pharma
GmbH, Muenster, Germany; 3Clinics of Constance, Germany
Critical Care 2010, 14(Suppl 1):P54 (doi: 10.1186/cc8286)
Introduction Secondary peritonitis is the most frequent form of peritonitis,
characterized by a high disease burden and a high mortality rate. Choice of
adequate antibiotics is an independent factor for survival. The aim of this
study was to compare treatment of secondary peritonitis with tigecycline
(TG) with standard regimens (SR) from an economical standpoint.
Methods After ethics committee approval, the study was performed
as prospective, non-interventional cohort trial in 23 medical centers in
Germany. Patients could be included if suff ering from severe secondary
peritonitis treated in an ICU. Patients with pregnancy, aged below 18 years
and milder forms of diseases (APACHE II score <15) were not eligible. In
order to compare treatment with TG with SR, the following data were
documented: demographic data, disease severity scores, causing micro-
organisms, laboratory parameters, and length of stay (LOS). Patients were
analysed according to initial antibiotic choice except for perioperative
prophylaxis. In order to balance for diff erences in co-morbidities and
severity of disease, a matched-pairs analysis was performed based on
logistic regression analysis.
Results A total of 178 patients were enrolled (49 TG/129 SR). After logistic
regression analysis and matching for gender, age ± 3 years, APACHE
II score ± 1 and (non)existence of liver cirrhosis, arterial sclerosis and
coronary heart disease, 15 matched pairs were built. Compared with the
SR group, in the TG group was a tendency for higher creatinine, urea and
glucose levels, higher number of co-morbidities (3.3 vs 3.0, NS) and higher
number of pathogens isolated on initial surgery (2.2 vs 1.6, NS). There was
a higher number of discharges 9/15 in the TG group (vs 7/15 SR, NS) and
6/15 patients died (vs 4/15 SR, NS). Considering these factors, there was
a trend for shorter LOS in patients treated with TG (11 days vs 18 days
and 8 days vs 16 days for survivors and nonsurvivors, respectively, NS) and
total costs of ICU stay were signifi cantly lower in the TG group (€8,832 vs
€15,482, P = 0.023).
Conclusions In our non-interventional study, tigecycline tended to be
used in patients with more severe co-morbidities. In spite of this, there was
a trend for shorter LOS and treatment costs were signifi cantly lower, which
make tigecycline an attractive treatment, also from a pharmacoeconomical
Colistin monotherapy versus therapy combination
B Charra, A Benslama, H Ezzouine, S Motaouakkil
CHU Ibn Rochd, Casablanca, Morocco
Critical Care 2010, 14(Suppl 1):P55 (doi: 10.1186/cc8287)
Introduction The purpose of our study was to compare the eff ectiveness
of colistin monotherapy and colistin combination in the treatment of
nosocomial infections with multi-resistant germs.
Methods Retrospective study including 63 patients realized during 3 years
from January 2006 to December 2008 in the medical ICU of University
Hospital Ibn Rochd, Casablanca, Morocco. The study includes only the
patients who suff er from nosocomial infection with multi-resistant
germs, all of the sites are concerned. The patients have been divided into
groups: group 1 including 30 patients treated by colistin only, and group
2 including 33 patients treated by the association colistin–rifampicin. The
colistin has been administered intravenously and/or in nebulization and/
or in an intrathecal way according to the considered infectious site. The
main criterion of judgment was the rate of mortality in the resuscitation
unit, the second criteria of judgment were the ventilator weaning, the
introduction of the vasoactive drugs and the supervening of side eff ects.
Results Sixty-three patients judged as appropriate, have been included.
The mean age of the patients was about 43.62 ± 17.34 years and APACHE
2 score at the admission was about 15 ± 5.69. The total mortality caused
by infection was about 41.27%. The basic characteristics of the two groups
were similar. The mortality in group 1 was about 36.66%, and about
69.69% in group 2 (P = 0.001), the rate of introduction of vasoactive drugs
was about 23.33% in group 1 versus 48.48% in group 2 (P = 0.03). In group
1, 6,66% of the patients developed renal failure, against 12.12% of the
patients in group 2 (P = 0,46). With the rifampicin, 27.27% of the patients
of group 2 presented cytolysis.
Conclusions This study suggests that colistin represents a good
therapeutic alternative for the treatment of nosocomial infection with
multi-resistant germs. However, our study is not without limits; it is a
retrospective study, absence of randomization and the control group of
Effi cacy and safety of once daily dosing of colistin to critically ill
A Skiada1, J Pavleas2, T Topalis2, K Georgiou2, D Siggouna2,
G Thomopoulos2, GL Daikos1, G Floros2
1University of Athens, Greece; 2Laiko General Hospital, Athens, Greece
Critical Care 2010, 14(Suppl 1):P56 (doi: 10.1186/cc8288)
Introduction Although colistin has been used extensively in critically
ill patients infected with multidrug-resistant (MDR) organisms, our
knowledge about the pharmacokinetic and pharmacodynamic para-
meters correlating with effi cacy is very limited and little consensus exists
on the optimum dosing regimen of this agent. In our center, during the
past 2 years several patients treated with colistin were given the total daily
dose once every 24 hours. The aim of this study was to analyze the effi cacy
and safety of this dosing regimen in critically ill patients.
Critical Care 2010, Volume 14 Suppl 1
Methods The medical fi les of all patients who were admitted to the ICU
in 2008 and who received colistin for an infection due to MDR bacteria
were retrospectively analyzed. Criteria for inclusion were: dosing regimen
of colistin 9 million units (MU) every 24 hours (colistin methanesulphonate
– CMS, Norma, 1 vial = 1 MU, 1 mg = 13,300 U), administration of CMS for at
least 7 days and normal renal function at initiation of treatment with CMS
(serum creatinine ≤1 mg/dl or creatinine clearance >80 ml/min). Mortality
was evaluated at 28 days.
Results Thirteen patients were included in the study (69% male, median
age 71 years). The underlying diseases were surgical in seven patients and
medical in six patients. The median APACHE and SOFA scores on the fi rst
day of CMS administration were 15 and 10, respectively. Eleven patients
had nosocomial pneumonia, two had peritonitis and one osteomyelitis.
Causative bacteria were isolated in 10 patients (six Acinetobacter baumanii,
three Pseudomonas aeruginosa and one Klebsiella pneumonia) and
were all MDR. Of the 10 isolated bacteria, six were susceptible only to
colistin, while the other four were also susceptible either to aztreonam
or sulbactam. In cases of susceptibility of the isolate only to colistin, it
was given in combination with a carbapenem, while in the other cases
either aztreonam or sulbactam was added. The median length of CMS
administration was 11 days (mean 19; range 7 to 79 days). Median serum
creatinine on initiation and completion of treatment with CMS was 0.7 and
0.9 mg/dl, respectively (P = 0.357). No cases of neurotoxicity were found.
Mortality at 28 days was 15%.
Conclusions The total daily dose of 9 MU of CMS, given as one dose
every 24 hours in critically ill patients, seems to be effi cient and safe,
without resulting in increased nephrotoxicity or other adverse events.
A prospective study should be done to confi rm the fi ndings we have
A comparison of the eff ect on renal function of fl ucloxacillin and
vancomycin antibiotic prophylaxis in cardiac surgery patients
TO Brougham, K Giraud, A Vuylsteke
Critical Care Unit, Cambridge, UK
Critical Care 2010, 14(Suppl 1):P57 (doi: 10.1186/cc8289)
Introduction This study compared the eff ect on renal function of
fl ucloxacillin and vancomycin antibiotic prophylaxis for elective fi rst-
time coronary artery bypass grafting (CABG) surgery, using both direct
biochemical markers and indirect clinical outcome measures. Recent
evidence has suggested that vancomycin may be nephrotoxic in patients
undergoing cardiac surgery.
Methods A retrospective observational study of patients undergoing
elective fi rst-time CABG was performed, covering a 13-month period. All
patients received prophylactic antibiotics: fl ucloxacillin 1 g pre-operatively
and three 1 g doses post-operatively. Patients who were MRSA-positive,
MRSA unknown or penicillin allergic received an alternative regimen:
vancomycin 1 g pre-operatively and 1 g post-operatively. Exclusion criteria: pre-
operative creatinine >133mmol/l, any antibiotics other than prophylaxis
and haemodynamic support except <5 μg/kg/hour dopamine.
Results Of 1,413 patients in the study period, 415 met the study criteria:
360 patients received fl ucloxacillin and 55 patients received vancomycin.
There were no signifi cant diff erences between the two groups in sex,
age, BMI, euroSCORE, diabetes status, ejection fraction, pre-operative
creatinine, eGFR, sodium, or potassium. Comparing change in renal
function pre-operatively to post-operatively, there were no signifi cant
group diff erences in change in: creatinine (mmol/l; VAN median 0 (IQR
11); FLU –2 (19); P = 0.22), eGFR (ml/min; VAN 0 (14); FLU 2.4 (19.3); P =
0.22), sodium (mmol/l; VAN 1 (4); FLU 1 (4); P = 0.28). Change in potassium
diff ered signifi cantly (mmol/l; VAN 0.7 (0.9); FLU 0.5 (0.7); P <0.05). In clinical
outcome measures, the groups were similar. Most patients in both groups
stayed in ITU for 1 day and there was no signifi cant diff erence in the
number of patients staying for longer than 1 day (VAN 7/55 (13%); FLU
29/360 (8%); P = 0.30). There was no diff erence in hospital length of stay
(days; VAN 7 (4); FLU 6 (3); P = 0.19).
Conclusions In elective fi rst-time CABG patients, there is no signifi cant
diff erence in change in renal function between those given vancomycin
antibiotic prophylaxis and those given fl ucloxacillin prophylaxis, as
assessed by creatinine, eGFR and sodium levels, and indirect clinical
outcome measures. Potassium increased more in the vancomycin
group but the clinical signifi cance of this is unclear. Our data suggest
that prophylactic vancomycin does not impair renal function relative to
Microdialysis study of meropenem cerebral distribution in patients
with acute brain injury
C Dahyot-Fizelier1, I Timofeev2, S Marchand1, W Couet1, P Hutchinson2,
B Debaene1, D Menon2, O Mimoz1, A Gupta2
1University Hospital, Poitiers, France; 2Addenbrooke’s Hospital, Cambridge, UK
Critical Care 2010, 14(Suppl 1):P58 (doi: 10.1186/cc8290)
Introduction Antibiotic dosing recommendations are usually based
on plasma or cerebral spinal fl uid pharmacokinetic (PK) studies.
However, as infections mainly occur in extracellular tissue fl uid (ECF),
corresponding unbound ECF antibiotic concentrations are responsible
for the antimicrobial eff ect. Because of the blood–brain barrier, the
cerebral antibiotic distribution is thought to be reduced compared with
tissues without any physiological barrier. This study aims to determine
meropenem (MPM) unbound concentrations in the brain and compare
them with MPM concentrations in plasma to explore cerebral distribution
of MPM in patients with acute brain injury.
Methods After local ethic approval and written informed consent, two
brain-injured patients, sedated, mechanically ventilated, receiving MPM for
an infection and monitored by cerebral microdialysis (CMA 71, membrane
length 10 mm, membrane diameter 0.6 mm, molecular cut-off 100 kDa;
CMA, Stockholm, Sweden) were enrolled. The PK study succeeded to 1 g
meropenem over 30 minutes and brain dialysates and blood samples were
collected over 420 minutes. Probe recoveries were evaluated individually
by retrodialysis. MPM was assayed by HPLC coupled with tandem mass
Results For each of the two patients, the MPM brain AUC is much
lower than plasma AUC and accordingly brain to serum AUC ratios
are respectively 0.73 for Patient 1 (P1) and 0.14 for Patient 2 (P2). MPM
concentration versus time curves in brain are delayed (time-to-peak
in P1 = 100 minutes, in P2 = 80 minutes) and present a smooth peak
compared with the corresponding curves in plasma (Figure 1). Mean
probe recoveries are respectively 19 ± 7% for P1 and 29 ± 7% for P2.
Conclusions The MPM brain AUC is much lower than plasma AUC for
the two patients enrolled, consistent with the PK theory in the presence
of tissue with effl ux transporters. More patients are needed to better
understand MPM brain distribution characteristics.
Eff ects of two regimens of antibiotic prophylaxis on colonizing fl ora
of the respiratory tract in patients with cardiovascular surgery
EM Berg, R Wesselink, M Tersmette
Sint Antonius Hospital, Nieuwegein, the Netherlands
Critical Care 2010, 14(Suppl 1):P59 (doi: 10.1186/cc8291)
Introduction Antibiotic prophylaxis in cardiovascular (CV) surgery has
greatly reduced the rate of postoperative infections. First-generation or
second-generation cefalosporines are used for this purpose. Our hospital
changed its antibiotic prophylaxis protocol for elective CV surgery in June
2007 from cefuroxime to cefazolin in accordance with national guidelines
Figure 1 (abstract P58). Individual MPM plasma (?) and brain (?)
concentrations versus time in P1 and P2.
Critical Care 2010, Volume 14 Suppl 1
. The aim of this study was to explore the eff ect of changing this
antibiotic prophylaxis protocol on microbial fl ora in sputum.
Methods Retrospective study. All patients admitted >10 days on the ICU
after elective CV surgery between 1 June 2006 and 1 June 2007 (Group
1) were compared with the same group of patients between 1 July 2007
and 1 August 2008 (Group 2). Patients received single-dose prophylaxis
(bypass surgery), or 2 days of prophylaxis (cardiac prosthetic surgery).
Group 1 received cefuroxime and Group 2 received cefazolin. Patients
did not receive selective digestive tract decontamination. Isolated
pathogens from elective sputum cultures of all patients were registered
and compared between groups after dividing pathogens into six classes
based on the profi le of intrinsic antibiotic susceptibility. Comparative data
between groups were analyzed with Pearson’s Χ test.
Results One hundred and fi fty-eight patients had positive sputum cultures.
Comparing total amounts of positive cultures, there was no signifi cant
diff erence between colonization with pathogenic micro-organisms
between Group 1 (n = 77 patients) and Group 2 (n = 76 patients). In Group
1 more colonization with pathogens from class 4 (β-lactamase-producing
Enterobacteriaceae and Pseudomonas aeruginosa) was observed compared
with Group 2 (45% vs 34%, P = 0.079). This nonsignifi cant diff erence
between groups was mainly attributable to a diff erence in colonization
with Pseudomonas. In the other classes of pathogens, no diff erences were
observed. No diff erence in postoperative wound infections was noted
Conclusions Prophylactic use of cefazolin instead of cefuroxime after
CV surgery resulted in a trend towards reduction of colonization of the
respiratory tract with intrinsic β-lactam-resistant microbial fl ora in patients
with prolonged ICU stay, without adverse eff ects on the incidence of
postoperative wound infection.
1. van Kasteren MEE, et al.: Ned Tijdschr Geneeskd 2000, 144:2049-2055.
Prevalence of infections among patients admitted to ICUs in Nordic
countries and the Netherlands in comparison with Mediterranean
countries: a report from the EPIC II study
H Hanberger1, H Gill1, H Njimi2, S Walther1, JL Vincent2
1Antibiotic Research Unit, Linkoping, Sweden; 2Erasme Hospital, Brussels,
Critical Care 2010, 14(Suppl 1):P60 (doi: 10.1186/cc8292)
Introduction The prevalence of infection is high among patients
admitted to the ICU and one of the main causes of mortality. The aim of
this study was to determine the burden of infectious diseases in patients
admitted to ICUs in Nordic countries and the Netherlands in comparison
with Mediterranean countries.
Methods The EPIC II 1-day point prevalence study of infections and
demographics of critically ill patients was performed on 8 May 2007. A
comparison of severity score, source of infection, co-morbidity and
patient outcome was done for patients admitted to ICUs in low antibiotic
resistance countries (LARC) (Denmark, Finland, the Netherlands, Norway,
Sweden) and high antibiotic resistance countries (HARC) (Greece, Israel,
Italy, Malta, Portugal, Spain, Turkey).
Results The number of patients included was 2,270 in HARC and 581 in
LARC. On the day of the study, 45.3% of patients in LARC were considered
as infected compared with 51.6% in HARC (P = 0.007). The mean SAPS
II scores were (95% CI) 32.7 (31.6 to 33.8) in LARC and 35.6 (35 to 36.2)
in HARC (P <0.001). Of all patients in LARC/HARC, 27.0%/33.9% (P =
0.002) had a respiratory infection, 10.8%/9.8% (P = 0.45) an abdominal
infection, 7.2%/10.4% (P = 0.023) a blood infection, 2.8%/3.2% (P = 0.60)
a skin infection, 2.1%/3.4% (P = 0.09) a catheter infection, 3.8%/6.6% (P =
0.012) a genitourinary infection and 0.7%/1.7% (P = 0.08) a CNS infection.
Chronic renal failure was seen in 2.6% of patients in LARC and 7.3% in
HARC (P <0.001) and the corresponding prevalence of chronic obstructive
disease was 13.4% and 20.2%, respectively (P <0.001). Admissions were
more often seen from OR/monitoring and less often from emergency
rooms among patients admitted to ICUs in LARC compared with HARC.
Median ICU length of stay (LOS) in LARC (IQR) was 5 days (1 to 19) and
in HARC was 12 days (3 to 31) (P <0.001). The corresponding hospital
LOS was 16 days (7 to 38) and 24 days (10 to 54), respectively (P <0.001).
The ICU mortality rates in LARC/HARC were 14.9%/19.9% (P = 0.008) for
all patients and for infected patients 21.2%/25.4% (P = 0.17), whereas the
corresponding hospital mortality rates were 20.8%/26.7% (P = 0.005) for all
patients and for infected patients 29.6%/34.3% (P = 0.16). The prevalence
of MRSA was 0.8% among patients in LARC (5.8% in HARC) (P <0.001) and
the prevalence of P. aeruginosa was 9.9% and 14.0% (P = 0.07), respectively.
Conclusions Infections and serious co-morbidities were more prevalent
among patients admitted to ICUs in HARC than in LARC. This was
associated with a longer stay and greater mortality in the ICU.
1. Vincent JL, et al.: JAMA 1995, 274:639-644.
Risk factors for the development of carbapenem-resistant Klebsiella
pneumoniae infections in critically ill patients
KZ Vardakas, DK Matthaiou, E Antypa, A Grammatikos, E Chasou,
G. Gennimatas, Thessaloniki, Greece
Critical Care 2010, 14(Suppl 1):P61 (doi: 10.1186/cc8293)
Introduction We sought to study the characteristics and outcomes of ICU
patients with carbapenem-resistant (CRKp) and carbapenem-sensitive
(CSKp) K. pneumoniae infections.
Methods A retrospective cohort of patients requiring ICU treatment. The
study was conducted in an eight-bed ICU between January 2006 and
Results During the study period, 104 patients were diagnosed with
K. pneumoniae infection. The mean age of patients was 66.3 ± 14.3 years.
Fifty-one (49%) were males. The mean APACHE II score was 17.9 ± 6.9. The
median duration of hospital stay until the infection was 28 days. Forty-
eight patients (46.2%) had bacteremia, 27 (30%) urinary tract infections, 15
(14.4%) pneumonia, seven (6.7%) peritonitis and seven (6.7%) skin and soft
tissue infections. Fifty-eight (56.9%) and 39 (39%) patients had previous
and concurrent infections, respectively. Seventy-six patients (73.1%)
died. The univariate analysis showed that prior hospitalization (P = 0.049),
dialysis (P = 0.034), and history of urologic neoplasia (P = 0.041) were
associated with the development of carbapenem-resistant infections. No
independent risk factors were found in the multivariate analysis. APACHE
II score (P = 0.003), need for dialysis (P = 0.034), shock prior and after the
infection (P = 0.006 and P <0.001, respectively), respiratory distress prior
and after the infection (P = 0.021 and P = 0.032, respectively), multiorgan
failure prior and after the infection (P = 0.02 and P = 0.003, respectively),
treatment failure (P <0.001), and acidosis after the development of
infection (P = 0.003) were associated with death in the univariate analysis.
Shock after the infection (P = 0.016) and treatment failure (P = 0.001)
were independent predictors of mortality in the multivariate analysis. No
diff erence in mortality was found between patients with CRKp and CSKp
Conclusions Infection due to K. pneumoniae in the ICU is associated with
high mortality. Infection treatment and hemodynamic support of the
patient may be important determinants of the clinical course in critically ill
patients with such infections.
1. Falagas ME, et al.: Risk factors of carbapenem-resistant Klebsiella
pneumoniae infections: a matched case control study. J Antimicrob
Chemother 2007, 6:1124-1130.
Outcome of unimicrobial versus polymicrobial sepsis
N Abed1, A Hussein1, S Salaheldine1, A Hassan2, M Mahfouz1,
H Khaled Nagi1, H Khaled Nagi1
1Cairo University, Cairo, Egypt; 2National Heart Institute, Cairo, Egypt
Critical Care 2010, 14(Suppl 1):P62 (doi: 10.1186/cc8294)
Introduction Polymicrobial sepsis is associated with immunosuppression
caused by the predominance of anti-infl ammatory mediators and
profound loss of lymphocytes through apoptosis, and so deaths directly
related to sepsis are twofold higher in polymycrobial sepsis. The aim of
study is to compare unimicrobial versus polymicrobial sepsis as regards
microbiology, complications, length of stay, mortality, factor aff ecting
Critical Care 2010, Volume 14 Suppl 1
Methods One hundred and one patients with sepsis were studied and
divided into two groups. The fi rst group: unimicrobial, where one organism
was isolated from cultures; and the second group: polymicrobial, where
more than one organism was isolated from the cultures.
Results The fi rst group (unimicrobial) was 48 cases (47.5%) and the second
group (polymicrobial) was 53 cases (52.47%). Both groups has similar
positive sputum cultures (32/48 (66%) versus 38/53 (71%), P value 0.6), but
positive blood culture was signifi cantly higher in the second group (27/53
(51%) vs 7/48 (14%), P value 0.0001). There was also a signifi cantly higher
incidence of UTI and wound infection in the second group (49.7% vs 6.3%
for UTI, P value 0.0001 and 20.7% vs 2.1%, P value 0.004 for wound infection,
respectively). The commonest detected organisms were Staphylococci
and Klebsiella (48, 22 out of 101 patients); 16/48 (33%) in unimicrobial vs
32/53 (60%) in polymicrobial (P value 0.007) for staph, and 7/48 (14.5%) in
unimicrobial vs 15/53 (28%) in polymicrobial for Klebsiella (P value 0.09).
Incidence of Acinetobacter, Candida and E. coli in the second group were
signifi cantly higher 10/53 in poly vs 2/48 in unimicrobial (P value 0.032), and
10/53 vs 0/48 (P value 0.002 ) and 6/53 vs 0/48 (P value 0.016), respectively.
Need for mechanical ventilation in the second group was signifi cantly
higher than the fi rst group (46/53 (86%) vs 31/48 (64%), P value 0.009). The
mean hospital stay was longer in the second group (26.9 ± 15.4 vs 17.4 ±
9.3, P value 0.001). Mortality was signifi cantly higher in the second group
(P value 0.012). Factors increasing mortality in both groups were DCL
(P value 0.007 in unimicrobial and 0.036 in polymicrobial); vasopressors
(P value 0.001 and 0.002, respectively); mechanical ventilation (P value 0.00
and 0.00, respectively), and severe sepsis and septic shock with signifi cant
P value (0.019) and (0.008), respectively, for the fi rst group and (0.003) and
(0.002), respectively, for the second group.
Conclusions Polymicrobial sepsis shows higher risk for complication,
length of stay and mortality than unimicrobial.
1. Aliaga et al.: Eur J Clin Microbiol Infect Dis 2000, 19:871-874.
De-escalation practice pattern in an Indian intensive care unit
A Bhakta, M Bhattacharyya, S Todi
AMRI Hospitals, Kolkata, India
Critical Care 2010, 14(Suppl 1):P63 (doi: 10.1186/cc8295)
Introduction Antibiotic de-escalation is thought to be benefi cial by
reducing the selection pressure for resistance. This study was carried out
to identify variables that infl uence de-escalation practices.
Methods Prospective observational study during a 1-year period (July
2008 to June 2009) in a 50-bed ICU in a tertiary care hospital. Any patient
admitted to the ICU during this period in whom at least one specimen
was sent for microbiological culture at or before starting antibiotics was
included in the study and subsequently followed up for antibiotic change
according to the culture sensitivity report. Antibiotics covering Gram-
negative organisms were ranked as per Figure 1.
Results Seven hundred and seventy-eight patients were included, of
whom cultures were positive in 551 (70.8%) and negative in 227 (29.2%)
cases. In 350 (44.9%) patients, neither escalation nor de-escalation of
therapy was done. Overall escalation of therapy occurred in 192 (24.7%)
patients and de-escalation in 236 (30.3%). The mortality rate was lowest
among patients in whom therapy was de-escalated (8.9%) compared
with categories of no change (14.2%) or escalation (23.4%). De-escalation
occurred more frequently among patients in whom no pathogen was
isolated (45.8%) compared with culture-positive cases (23.9%) and in
18.3% of patients with growth of drug-resistant pathogens, compared with
38.9% of patients with susceptible pathogens. De-escalation occurred
most frequently where an antibiotic having only Gram-positive coverage
was included in the initial empiric therapy (60.3%), and in cases where
third-generation cephalosporin was the initial empiric therapy (54.4%).
Conclusions This study highlights no change of therapy as the most
prevalent practice pattern of antibiotic use. Mortality remained low
in patients in whom therapy was de-escalated. Variables favoring de-
escalation practices were non-isolation of pathogen, growth of susceptible
organisms, and stopping of Gram-positive coverage.
Incidence, identifi cation of multidrug-resistant pathogens and
impact on the outcome after cardiac surgery
A Tasouli, K Papadopoulos, G Stravopodis, C Panagiotou, J Kriaras,
S Geroulanos, G Saroglou
Onassis Cardiac Surgery Center, Athens, Greece
Critical Care 2010, 14(Suppl 1):P64 (doi: 10.1186/cc8296)
Introduction Multidrug-resistant (MDR) pathogens constitute an emerg-
ing threat with increasing incidence and uncertain outcome. On the other
hand, patients undergoing open heart surgery represent a vulnerable
Methods Evaluation of the incidence and identifi cation of MDR pathogens
after cardiac surgery in 2,803 patients for a 2-year period. Examination of
the clinical features of patients with MDR infection. Elucidation of the
impact on the outcome.
Results In 18 patients (0.64%) consisting of 12 males and six females, at least
one MDR pathogen was isolated. Gram-positive pathogen was certifi ed in
fi ve patients (27.8%) and Gram-negative in 13 patients (72.2%). Specifi cally,
four patients were infected with vancomycin-resistant enterococcus (VRE),
six with Klebsiella pneumoniae, three with Acinetobacter spp., one with VRE
and Acinetobacter spp., four with Acinetobacter and K. pneumoniae. Low
output syndrome (CI <2.0l/min/m2) was common in all these patients
and essentially contributed to the deterioration of clinical situation with
dependence on inotropic support, prolonged mechanical ventilation
(>10 days), acute renal failure and need for haemodilution (66.6%).
Therefore, the ICU and hospital stay is prolonged (>20 days and >30 days,
accordingly) and pathogenesis of MDR infection is provoked after 20 days
of ICU stay. Consequently, nine patients with MDR infection (50%) died.
All were critically ill patients with multiple organ dysfunction syndrome
under broad-spectrum antimicrobials with hospital-acquired bloodstream
Conclusions Infection with MDR pathogens, while rare, constitutes a
notable prognostic marker of increased mortality after cardiac surgery.
It is worth noting that the higher mortality rate is mainly attributable to
the severe co-morbidity in haemodynamically compromised patients.
Management must concentrate on the implementation of eff ective
Surveillance of ICU-acquired infections in Belgium: 2008 reference data
I Morales, B Catry, K Mertens
Scientifi c Institut of Public Health, Brussels, Belgium
Critical Care 2010, 14(Suppl 1):P65 (doi: 10.1186/cc8297)
Introduction This paper aims to provide reference data for pneumonia
(PN) and bloodstream infections (BSI) acquired in Belgian ICUs taking
patients’ characteristics into account. This information could enlighten
policy decisions. This 2008 set of indicators is the fi rst yielded by the ICU
Belgian surveillance (NSIH-ICU) since 2001.
Figure 1 (abstract P63). Antimicrobial therapy ranking.
Critical Care 2010, Volume 14 Suppl 1
Methods The NSIH-ICU is a voluntary, patient-based reporting system
set up in 1992 to follow ICU-acquired infections and guide prevention.
It establishes a national risk-adjusted benchmark for infection rates,
antibiotics use and invasive device-use ratios through uniform case
defi nitions, data-collection methods, data entry and analysis. Only patients
staying more than 2 days in the ICU are included. These aggregated
database means are derived from the NSIH-ICU 2008 report.
Results In 2008, 4,355 patients and 35,802 patient-days were reported
by 19 ICUs. The age mean was 67.2 years; mean length of stay 8.1 days;
mean SAPS II score 43.8; the proportion of patients with antibiotics at
admission was 47.1%; medical admissions represented 63.4%, 4.2% were
immunocompromised patients; trauma was reported in 6.7% of cases.
Overall ICU mortality was 8.5%. The proportion of intubated patients
was 44.4%, with central venous catheters (CVC) 68.3% and with urinary
catheters 58.3%. Invasive-device use rates were: 358.5 intubation-days,
746.5 CVC-days and 644.2 urinary catheter-days per 1,000 patient-days.
The ICU-acquired PN/100 patients was 9.8, 16.5/1,000 patient-days and the
intubation-associated PN was 11.1/1,000 intubation days. ICU-acquired BSI
was 3.6/100 patients, 5.3/1,000 patient-days and the catheter-related BSI
was 4.3/1,000 catheter-days.
Conclusions The 2008 report provided Belgian hospitals with comparative
ICU-acquired infection data adjusted for patients’ intrinsic and extrinsic
infection risks. The participation changed across time and could cause a
selection bias. Outlier verifi cation is ongoing and eff orts to increase the
participation are being made. Indicator rates could be related to protocol
modifi cation, demographic trends and changes in patient mix linked to
restructuration of medical services or in clinical practice patterns. Some
are vulnerable to continuous medical and nursing in-service training, for
example at surveying the antibiotics use and improving invasive devices
use. Further studies could assess to what extent modifi cations in clinical
practice and/or external interventions might cause changes in the
Risk of acquiring drug-resistant (MDR) Gram-negative isolates with
previous exposure to antibiotic
A Bhakta, M Bhattacharyya, S Todi
AMRI Hospitals, Kolkata, India
Critical Care 2010, 14(Suppl 1):P66 (doi: 10.1186/cc8298)
Introduction Prior antimicrobial therapy is one of the most important
factors leading to the acquisition of MDR organisms. Formulating
antibiotic policy and choice of empirical antibiotic selection will be helped
by knowing the association of MDR Gram-negative organisms with a
previous exposure of particular antibiotic.
Methods Prospective observational study during January 2008 to June
2009 in a 50-bed ICU in a tertiary care hospital. Specimens sent after
2 days of the start of the antibiotic and no more than 90 days from the
stop date have been included in the study. Analyses were based on those
specimens that resulted in detection of MDR Gram-negative organism.
Observed relative risk (RR) of an antibiotic class was computed with
respect to an MDR infection. RR was computed as the ratio of the risk of
the event (acquiring the infection) occurring in the exposed group vs
in the nonexposed group. A logistic regression model was used where
multiple antibiotics were applied.
Results A total of 1,072 specimens from 500 patients met the criteria as
specifi ed above. Of these, 423 (39.4%) specimens resulted in detection
of MDR bacteria, 186 (17.4%) resulted in detection of non-MDR bacteria
and no bacteria were detected in the remaining 463 (43.2%) specimens.
Of the total 423 cases of MDR acquisitions, ESBL Enterobacteriaceae (151
or 35%), MDR Acineto (89 or 21%) and MDR Pseudo (58 or 14%). Risk of
isolating ESBL Enterobacteriaceae was highly signifi cant with the prior
exposure to third-generation cephalosporin (RR = 5.8 and P <0.001).
Risk of isolating MDR Acinetobacter spp. was highly signifi cant with
the exposure to piperacillin-tazobactam (RR = 2.7 and P <0.001). Risk
of isolating MDR Pseudomonas spp. was signifi cant with the exposure
to Group 2 carbapenem (RR = 2.2 and P >0.001). Group 1 carbapenem,
aminoglycosides have not been found to have signifi cant association with
any individual MDR organisms.
Conclusions Previous exposure to antibiotics leads to increased
acquisition of MDR organisms. There is a signifi cant association of isolating
diff erent MDR organisms with previous exposure to a particular class of
Ozone fumigation successfully controlled and eradicated
multidrug-resistant Acinetobacter baumanii from an intensive care
R Stümpfl e, A Castello-Cortes, F Coogan, PB Nielsen
Northwick Park Hospital, London, UK
Critical Care 2010, 14(Suppl 1):P67 (doi: 10.1186/cc8299)
Introduction The emergence of multidrug-resistant Acinetobacter
baumanii (MDRAB) poses a serious threat to patients on the ICU. The
production of metallo-β-lactamase leaves colistin as the only therapeutic
option. Outbreaks due to MDRAB can persist for months. Traditional
decontamination methods fail to deal with this level of colonisation
and contamination eff ectively. We tackled a recent outbreak of MDRAB
eff ectively using gaseous ozone. To our knowledge it is the fi rst time ozone
has been used to control an outbreak of MDRAB.
Methods An external company (Hydrozone Environmental Ltd) was
hired to perform the fumigation. The ICU was divided into three
decontamination areas using heavy-duty polythene sheets. Patients were
in turn relocated from contaminated to clean areas before each area was
sealed and fumigated. Humidity levels within were raised to 70 to 80%
using a humidifi er. An Ozone Ultra Pro 16 g/hour ozone generator with
ozone destruct capability, operated remotely, delivered ozone to a target
concentration of >2.0 ppm for 15 minutes. A fan was used to achieve
even dispersal. For safety reasons perimeter ozone concentrations were
monitored with a UV photometer and kept below 0.05 ppm. The effi cacy
of the fumigation was measured by environmental microbiological
sampling before and after fumigation.
Results All fumigated areas received ozone concentrations of 4.62 to 5.66
ppm for 21 to 32 minutes. Ozone was not detected outside the treatment
areas. Prior to fumigation, 72 (38%) of 188 environmental samples were
MDRAB-positive. Following fumigation, nine (5%) of 158 samples were
positive. Most of these samples were from nontouch areas, for example
ceiling, above door frame with signifi cant dust collection and without
daily cleaning. Considering that dust may impede ozone penetration,
Figure 1 (abstract P66). Observed relative risk of MDR infections for
diff erent antibiotic classes.
Critical Care 2010, Volume 14 Suppl 1
basic cleaning was improved and duration of fumigation was increased
to 30 minutes. Subsequent samples all proved negative and no further
Conclusions This is the fi rst study using ozone fumigation as a disinfectant
to control an outbreak in an ICU. Ozone fumigation is an eff ective tool
for eradicating MDRAB from heavily contaminated clinical sites. Used in
conjunction with good infection control measures, ozone can be used to
control outbreaks such as MRSA, Clostridium diffi cile, Norovirus and swine fl u.
Viral infections in the ICU: should we search for them?
M Sousa, M Monteiro, V Alves, C Granja
Hospital Pedro Hispano, Matosinhos, Portugal
Critical Care 2010, 14(Suppl 1):P68 (doi: 10.1186/cc8300)
Introduction Respiratory viral infections are usually self-limited in adults
but 4 to 30% can be clinically severe and lead to intensive care needs.
The aim of this study was to determine the impact of viral respiratory
infections in an intensive care setting and the role of systematic viral
testing in patients admitted to an ICU.
Methods A retrospective analysis of all 114 viral tests of respiratory
samples of 98 patients admitted to the ICU for four consecutive years was
performed. Molecular biology test and immunofl uorescence assay for
adenovirus, infl uenza A and B, parainfl uenza 1 to 3, metapneumovirus and
syncytial respiratory virus (SRV) were performed in tracheal aspirate (TA)
(89%) and bronchoalveolar lavage (BAL) (11%). SAPS II was used as the
severity index. Patients were stratifi ed according to the primary diagnostic.
Results Viral tests were performed in 98 patients, 60% were male, mean
age 58 years old and 45% had previous respiratory disease. SAPS II was
48. Ninety-two percent need mechanical ventilation (MV) for 8.5 days.
Primary diagnostics were community-acquired pneumonia (CAP) (50%) or
tracheobronchitis (32%), chronic pulmonary disease exacerbations (6%),
aspiration pneumonia (3%), nosocomial infection (5%), septic shock (3%)
and meningitis (1%). Length of stay (LOS) was 11 days and ICU mortality was
17.5%. Virus identifi cation was positive in 13 (12.2%) respiratory samples of
12 patients, 12 in TA and one in BAL. Twelve were identifi ed in the winter.
Demographic variables, LOS, co-morbidities and severity index of patients
with viral infection were similar to the main group. Infl uenza A (in three
CAP, one tracheobronchitis, one nosocomial infection and one septic
shock), metapneumovirus (two tracheobronchitis and one CAP), infl uenza
B (one CAP), parainfl uenza 3 (one CAP) and SRV (one tracheobronchitis)
were identifi ed. In these patients, C-reactive protein was higher and
leucocytes were lower. Bacterial co-infection was identifi ed in 33% of the
patients, all of them with acquired community pneumonia. Antibiotic
step down was done in 62% of the patients with isolated viral infection.
In these patients LOS and days of mechanical ventilation were 9.6 and 6.2,
respectively, and invasive ventilation-associated pneumonia was reduced.
Conclusions Although viral tests should not be required for all ICU
patients, respiratory samples for viral tests should be performed in patients
with tracheobronchitis/pneumonia requiring intensive care, especially
in the winter. Positive identifi cation of viral agents could be useful in
Oseltamivir dosing with haemofi ltration
M Tomlin1, B Skinner1, J Fennell1, EP Pelosi1, SK Khoo2, NL Lindegardh3
1Southampton University Hospitals NHS Trust, Southampton, UK; 2University
of Liverpool, UK; 3Mahidol University, Bangkok, Thailand
Critical Care 2010, 14(Suppl 1):P69 (doi: 10.1186/cc8301)
Introduction In the current pandemic it is likely that some patients
will be admitted to hospital and require respiratory support including
mechanical ventilation. These patients are likely to have a profound
systemic infl ammatory response syndrome (SIRS); consequently they may
have multiorgan failure (MOF) requiring renal replacement therapy (RRT)
with haemofi ltration. Two questions then arise – what dose of oseltamivir
(Tamifl u) should we give these patients to shorten the duration of the
H1N1 infection? How should we modify the dose in response to altered
renal drug clearance and in those requiring RRT?
Methods A young adult female patient with H1N1 infection and MOF was
given oseltamivir 75 mg BD nasogastrically. Failure to respond changed
the risk: benefi t ratio and justifi ed doubling the dose despite uncertainties
over an overall reduced clearance. Enteral nutrition absorption was
uncertain, and thus we sampled her blood to ensure adequate oseltamivir
absorption and that activation of the pro-drug was not inhibited. We
undertook serial sampling for blood concentration assay to determine the
pharmacokinetic parameters in this diffi cult scenario. Blood samples were
collected in plain serum tubes (without sodium fl uoride). The samples
were spun and refrigerated within half an hour, then batched and shipped
to Bangkok for drug concentration measurement.
Results We report both the parent oseltamivir phosphate (OP) and that of
the active metabolite oseltamivir carboxylate (OC). OP levels were low at
10 to 77 ng/ml. but OC concentrations were high at 2,600 to 5,000 ng/ml.
Conclusions The population normal parameter for half-life OP is 1 hour
and for OC it is 3 to 5 hours. A single dose of 150 mg OP is expected
to achieve an OP level of 50 to 150 ng/ml and an OC level of 1,000 to
1,500 ng/ml. Our slightly low OP levels are likely to be due to ex vivo
hydrolysis in the collection tube due to a lack of esterase inhibitor. The
high OC levels are most probably due to reduced renal elimination despite
being on haemofi ltration. Our concerns were focused on the possibility
of viral mutation (subsequently shown to be negative) or poor enteral
absorption/activation. What we found was that 150 mg BD produces
more than adequate OC levels to treat H1N1 infection.
Effi cacy and utility of a protocol for pre-emptive antimycotic
SG Milanov, G Georgiev, V Todorova, L Kozarov, M Milanov
Pirogov Emergency Institute, Sofi a, Bulgaria
Critical Care 2010, 14(Suppl 1):P70 (doi: 10.1186/cc8302)
Introduction Invasive candidiasis (IC) is associated with increasing
morbidity and mortality in critically ill patients. This, in conjunction
with diffi culties in diagnosis, underscores the need for novel treatment
strategies based on the identifi cation of signifi cant risk factors for IC. The
aim of the study was to evaluate the effi cacy and safety of a protocol for
pre-emptive antimycotic treatment.
Methods A randomized prospective controlled trial was carried out in a
general ICU for 2 years. After the implication of the inclusion and exclusion
criteria, patients were submitted to block randomization and stratifi ed
on the basis of their initial SAPS II expanded score. We have developed
a protocol for pre-emptive antimycotic treatment. Having reviewed the
current literature, we combined the most signifi cant risk factors for IC with
tree major clinical criteria for persistent nonbacterial sepsis and assumed
this algorithm as an indication for starting pre-emptive therapy. According
to the protocol, antimycotic therapy was started on the day of inclusion
in the treatment group and only with proven IC in the control group.
Initial data were gathered on demographic characteristics of the patients,
proven risk factors for IC-related mortality (malnutrition, non-albicans
colonization, creatinine clearance) and severity of infl ammatory response
and organ dysfunction. Dynamics of SIRS and SOFA, subsequent Candida
isolates, ventilator-free days, length of ICU stay, outcome and eventual
adverse reactions were followed.
Results A total of 110 patients (equal in both groups) were enrolled.
No statistically signifi cant diff erences in the basal characteristics of the
patients, length of ICU stay and the number of ventilator-free days were
found. The delta SOFA score was signifi cantly lower in the treatment group
(P = 0.019).The in-hospital mortality was 38.2% in the treatment group vs
61.8% in the control group (P = 0.013). The associated with pre-emptive
therapy relative risk was 0.62 (95% CI = 0.4 to 0.94). Signifi cant diff erences
between the Kaplan–Meyer estimates of survival were found (log-rank test
P = 0.007). A total of 15 (13.6%) adverse reactions were observed among
treated patients in both groups which was not associated with higher
Conclusions The implementation of the developed protocol reduced the
degree of organ dysfunction severity and was associated with signifi cant
survival benefi t.
Critical Care 2010, Volume 14 Suppl 1
Amphotericin B used as a continuous infusion is safer
J Streefkerk, S Gijsberts, J Ros, J Rommes, P Spronk
Gelre Ziekenhuizen, DZ Apeldoorn, the Netherlands
Critical Care 2010, 14(Suppl 1):P71 (doi: 10.1186/cc8303)
Introduction Many patients in an ICU are intestinal carriers of yeasts with
an inherent risk of infections if bowel perforation occurs. Resistance to
azoles is increasing, while treatment with conventional amphotericin B
(AM-B) is associated with potential toxicity. AM-B given in a continuous 24-
hour infusion may be less toxic compared with the conventional 4-hour
to 6-hour infusion rate of AM-B [1,2]. AM-B given in a continuous 24-hour
infusion is only evaluated in a tertiary care setting, with a predominance of
immunocompromised patients. We evaluated the feasibility and safety of
continuous AM-B treatment in critically patients with suspected or proven
yeast or fungal infections.
Methods This is an observational retrospective analysis for the side
eff ects in consecutive patients treated with AM-B from January 2003 to
December 2008 in our ICU department. During the investigation period
patients received amphotericin B: 40 mg/24 hours or a lower dose if
the MDRD clearance was less than 60 ml/min. During the treatment the
dose was adjusted to the desired therapeutic range of 200 to 1,000 μg/l
according to measured plasma levels.
Results The mean treatment duration was 12.3 ± 6.3 days with a dose of
32.1 ± 12.2 mg/24 hours. Of the 10 patients who died, seven died after
the termination of the AM-B therapy, without signs of an active yeast
or fungal infection. Within the fi rst week three patients died, necropsy
was carried out in one case, demonstrating a PCP infection, and in two
patients a role of antibiotic failure cannot be ruled out. All other patients
with proven yeast or fungal infection demonstrated a clinical recovery
of their infection. The AM-B concentration was measured in 113 blood
samples, nine samples had a level <200 μg/l and 10 a level >1000 μg/l.
Renal impairment, defi ned as more than 1.5 times the creatinine at the
start of the treatment with AM-B, occurred in 9% and was not evaluable
in 6% due to unresolving renal replacement therapy dependency at the
start of AM-B. None of the evaluated patients developed a creatinine more
than 2.0 times the baseline value. Temporary elevation of liver enzymes
was seen in 23%, without the need for dose modifi cation. Hypokalemia (K+
<3.0 mmol/l) was observed in one patient.
Conclusions Compared with the conventional infusion rate of AM-B, we
conclude that continuous 24-hour infusion seems a feasible and safer
treatment alternative in patients with invasive yeast or fungal infections.
1. Walsch TJ, et al.: N Engl J Med 1999, 340:764-771.
2. Wingard JR, et al.: Clin Infect Dis 1999, 29:1402-1407.
Anidulafungin compared with fl uconazole therapy in critically ill
DH Kett1, AF Shorr2, AC Reboli3, AC Reisman4, P Biswas4, HT Schlamm4
1University of Miami/Jackson Memorial Hospital, Miami, FL, USA;
2Washington Hospital Center, Washington, DC, USA; 3University of Medicine
and Dentistry of New Jersey – Robert Wood Johnson Medical School,
Camden, NJ, USA; 4Pfi zer Inc., New York, USA
Critical Care 2010, 14(Suppl 1):P72 (doi: 10.1186/cc8304)
Introduction The 2009 IDSA Treatment Guidelines for Candidiasis favor
an echinocandin for initial treatment of candidemia in patients with
severe illness. In a prospective, randomized study anidulafungin resulted
in improved global response (GR) and a trend toward improved survival
compared with fl uconazole .
Methods Retrospective analysis in patients classifi ed as severely ill at study
entry: treatment initiated in an ICU (Group 1), APACHE II score ≥15 (Group
2) or presence of severe sepsis (Group 3). Within groups, anidulafungin
was compared with fl uconazole for GR rate at the end of intravenous
therapy and 14-day and 28-day mortality.
Results In Group 1 (n = 89), GR was 63.3% vs 45.0% (95% CI: –2.2 to
38.8); Group 2 (n = 113), GR was 68.3% vs 46.0% (95% CI: 4.3 to 40.2); and
Group 3 (n = 118), the GR was 67.7% vs 51.8% (95% CI: –1.6 to 33.5), in
patients with MOD (n = 45), the GR was 76.2% vs 29.2% (95% CI: 21.3
to 72.8) anidulafungin versus fl uconazole, respectively. Across groups,
an association with anidulafungin use and lower day 14 mortality was
suggested (12.2% to 14.3% for patients receiving anidulafungin vs 19.6%
to 28.0% for those receiving fl uconazole) (P = NS). See Figure 1.
Conclusions In patients with severe illness, anidulafungin was associated
with greater GR than fl uconazole, signifi cantly so for those with APACHE II
score ≥15 or with MOD, supporting the IDSA Guidelines.
1. Reboli AC, et al.: N Engl J Med 2007, 356:2472-2482.
Increase in systolic blood pressure and improvement in laboratory
parameters following polymyxin B-immobilized fi ber treatment in
Y Sakamoto1, K Mashiko1, T Obata2, H Matsumoto1, Y Hara1, N Kutsukata1,
1Chiba Hokusoh Hospital, Nippon Medical School, Chiba, Japan; 2Microbial
Chemistry Reaearch Foundation, Tokyo, Japan; 3Nippon Medical School,
Critical Care 2010, 14(Suppl 1):P73 (doi: 10.1186/cc8305)
Introduction Direct hemoperfusion using a polymyxin B-immobilized
fi ber column (DHP-PMX; Toray Industries Inc., Tokyo, Japan) was fi rst
developed in 1994 and has since been used for the treatment of septic
Methods A total of 47 patients with septic shock who received DHP-
PMX for 2 to 6 hours were retrospectively reviewed to examine any
improvement in sepsis-related factors after DHP-PMX and to analyze
the relationship between any such improvement and increase in SBP.
Figure 1 (abstract P72). Global response to treatment.
Figure 1 (abstract P73). Changes in systolic blood pressure in patients
treated with DHP-PMX in whom HMBG-1 level increased. P <0.0001.
Critical Care 2010, Volume 14 Suppl 1
In addition, we analyzed the eff ectiveness of long-term DHP-PMX (5 to
6 hours) with respect to improvement in sepsis-related factors.
Results N-arachidonoylethanolamine (AEA), 2-arachidonoyl glycerol
(2-AG), and plasminogen activator inhibitor-1 (PAI-1) were signifi cantly
improved after DHP-PMX treatment. SBP increased signifi cantly in the
group showing improved high mobility group box protein 1 (HMGB-1)
level (P <0.0122). AEA, 2-AG and HMGB-1 were improved in all four patients
who were treated with long-term DHP-PMX.
Conclusions We observed a relationship between hemodynamic
improve ment and a decrease in serum HMGB-1 level in septic shock
patients treated with DHP-PMX. We suggest that long-term DHP-PMX
improves sepsis-related factors.
1. Sakamoto Y, et al.: ASAIO J 2007, 53:646-650.
Selection of acute blood purifi cation therapy according to lipid mediator
adsorption and blood purifi cation in patients with septic shock
Y Sakamoto1, K Mashiko1, T Obata2, H Yokota3
1Chiba Hokusoh Hospital, Nippon Medical School, Chiba, Japan; 2Microbial
Chemistry Research Foundation, Tokyo, Japan; 3Nippon Medical School,
Critical Care 2010, 14(Suppl 1):P74 (doi: 10.1186/cc8306)
Introduction Direct hemoperfusion using a polymyxin B-immobilized
fi ber column (DHP-PMX) has been used for the treatment of septic
shock. As an alternative method for acute blood purifi cation therapy,
continuous venovenous hemodiafi ltration (CVVHDF) has been reported
to be an eff ective clinical treatment for critically ill patients; however,
the optimal column for performing CVVHDF remains controversial. On
the other hand, recently, one of the lipid mediators, endocannabinoids
(N-arachidonoylethanolamine (AEA) and 2-arachidonoyl glycerol (2-AG))
have been reported with a blood pressure decreased eff ect.
Methods We investigated 14 polymethylmethacrylate (PMMA) membrane
hemofi lters and three polyacrylonitrile (PAN) membrane hemofi lters
after use in patients with septic shock. Therefore, in clinical study, we
used CVVHDF after DHP-PMX to treat 32 patients with septic shock. To
determine the optimal acute blood purifi cation therapy, we subsequently
divided the patients into two groups: group A underwent CVVHDF using
a PMMA membrane hemofi lter after undergoing DHP-PMX (n = 25);
group B underwent CVVHDF using a PAN membrane hemofi lter after
undergoing DHP-PMX (n = 7). In addition, the levels of endocannabinoids
(AEA, 2-AG) were measured. The severity scores and the improvement of
endocannabinoids were compared between the two groups.
Results Endocannabinoids (AEA, 2-AG) were adsorbed more in the PMMA
column (AEA; 506.3 ± 680.2 ng/column, 2-AG; 23.0 ± 38.5 μg/column) than
in the PAN column (AEA; 1.5 ± 0.7 ng/column, 2-AG; 0.1 ± 0.1 μg/column).
The average Acute Physiology and Chronic Health Evaluation (APACHE) II
score and the average sepsis-related organ failure assessment (SOFA) score
did not diff er signifi cantly between the two groups. Group A showed a better
outcome compared with Group B (P = 0.05). In addition, only group A showed
a signifi cant improvement in the blood AEA level on day 1 (P = 0.0185).
Conclusions Our study suggests that the PMMA column might be the
better column for performing CVVHDF after DHP-PMX treatment, as
suggested by the adsorption and blood purifi cation of endocannabinoids.
1. Sakamoto Y, et al.: ASAIO J 2008, 54:129-132.
Prognostic assessment in community-acquired pneumonia by
pneumonia severity scores and biomarkers
F Dusemund1, W Albrich1, P Schuetz2, B Müller1
1Kantonsspital Aarau, Switzerland; 2University Hospital Basel, Switzerland
Critical Care 2010, 14(Suppl 1):P75 (doi: 10.1186/cc8307)
Introduction Classical biomarkers like C-reactive protein (CRP) or the
leucocyte count are only inaccurate tools for predicting the severity of
community-acquired pneumonia (CAP). Procalcitonin (PCT) was found to
predict 28-day mortality in CAP (area under the curve (AUC) 0.8) similar to
the combination of PCT and CRB65 score (AUC 0.83) . Novel prognostic
biomarkers, such as Pro-ET1 and MR-ProADM, were shown to correlate
with CAP severity . We aimed to compare the diagnostic accuracy to
predict mortality and ICU admission of clinical severity scores, biomarkers
and their combination.
Methods Nine hundred and twenty-fi ve CAP patients enrolled in the
ProHOSP trial  were analyzed by assessing clinical severity scores (SMART-
COP, PSI, CURB65) and biomarker levels (PCT, MR-ProADM, Pro-ET1). Receiver
operating characteristic curves for 30-day mortality and ICU admission were
used to calculate and compare the diff erent predictive values.
Results The AUC for the prediction of 30-day mortality was 0.84 with
SMART-COP, 0.82 with PSI, 0.72 with CURB65, 0.59 with PCT, 0.75 with
MR-ProADM and 0.75 with ProET1. ICU admission was predicted best
by SMART-COP (AUC 0.83), compared with the other severity scores and
biomarkers (PSI: 0.68, CURB65: 0.65, PCT: 0.7, Pro-ET1: 0.73, ProADM: 0.72).
The combination of SMART-COP and MR-ProADM was superior to SMART-
COP alone (AUC 0.84, P = 0.04).
Conclusions The combination of MR-ProADM with SMART-COP
signifi cantly improved the prediction of ICU admission. Prognostic
biomarkers should complement the clinical assessment of patients with
LRTI to improve allocation of healthcare resources to high-risk patients.
1. Krüger S, et al.: Eur Respir J 2008, 31:349-355.
2. Schuetz P, et al.: BMC Inf Dis 2008, 8:22-30.
3. Schuetz P, et al.:: JAMA 2009, 302:1059-1066.
Current progress in pneumonia research
T Smelaya1, V Moroz1, A Goloubev1, L Salnikova2, A Rubanovich2
1V.A. Negovsky Research Institute of General Reanimatology RAMS, Moscow,
Russia Federation; 2N.I. Vavilov Research Institute of General Genetics,
Moscow, Russia Federation
Critical Care 2010, 14(Suppl 1):P76 (doi: 10.1186/cc8308)
Introduction Diagnosis and treatment of acute pneumonia (Pn) is a
problem of high signifi cance in modern medicine. The incidence of
complicated and lethal acute Pn has increased . Candidate genes are of
great importance in the course of acute diseases and their complications.
Cytokines and xenobiotic detoxication genes are the most investigated. The
aim of the investigation was to study genetic predisposition to acute Pn.
Methods Results of the associative DNA polymorphism studies in 243
patients with acute community-acquired Pn are presented; 178 healthy
individuals formed a control group. Genetic variability of the candidate
loci was studied: renin–angiotensin ACE system gene, chemokine receptor
CCR5 gene and four genes controlling xenobiotic detoxifi cation (CYP1A1,
GSTM1, GSTT1, GSTP1). Multiplex polymerase chain reaction was utilized
for genotyping of insertion–deletion polymorphism on loci ACE (287
nucleotide pairs) and CCR5 (deletion of 32 nucleotide pairs). The odds ratio
index was used to describe the degree of association of the genotypes
with the diseases. Statistical analysis was done by means of Fisher’s exact
test and the online program SNPStats (http://bioinfo.iconcologia.net).
Results An increased predisposition to Pn development was registered in
homozygotes in deletion at the ACE locus (OR = 1.8; P = 0.013), positive
genotypes of the GSTM1 locus (OR = 1.7; P = 0.010) and homozygotes in
allele 606T of the CYP1A1 gene (OR = 1.6; P = 0.020).
Conclusions A combination of positive genotypes of the GSTM1 locus and
homozygotes in allele 606T of the CYP1A1 gene (OR = 1.9, P = 0.006; incidence
in controls >20%) presented with a most eff ective prognostic power.
1. Sinopalnikov AI, et al.: Military Med J 1996, 2:30-33.
Bacterial colonization and infections of the lower respiratory tract
in an interdisciplinary ICU
M Sartzi, M Agrafi otis, P Peppa, F Nanu, M Charitidi, I Basiliadis, G Kallitsi,
M Michalia, P Clouva-Molyvdas
General Hospital Thriassio Elefsinas, Magoula, Greece
Critical Care 2010, 14(Suppl 1):P77 (doi: 10.1186/cc8309)
Introduction Tracheal intubation and mechanical ventilation are often
associated with infection of the lower respiratory tract (LRT). The morbidity
Critical Care 2010, Volume 14 Suppl 1
associated with the progression of airway colonization (AC) to ventilator-
associated tracheobronchitis (VAT) and from VAT to ventilator-associated
pneumonia (VAP) has been analyzed but not been fully elucidated. We
endeavored to study the relationship between AC and development of
infections (VAT and VAP) of the LRT in ICU patients.
Methods Retrospective study of 400 consecutive ICU patients ventilated
>48 hours in the past 4 years. Patients age, gender, APACHE II, prior illness,
cause of admittance, length of stay (LOS), time of mechanical ventilation
(MV), outcome, time of appearance of AC and infection of the LRT were
registered. MODS and CPIS were measured at onset of infection (VAT–
VAP) and 3 days after. MODS was also calculated on the day AC appeared.
Bronchial secretions were cultured at admission, at least once a week and
whenever there was a change in the amount and quality of bronchial
secretions or clinical infection was suspected. The Mann–Whitney test was
used for statistical analysis and statistical signifi cance was set at P <0.05.
Results From the 400 studied patients 68 (17%) were colonized and
153 (48.25%) developed infections: 54 (13.5%) VAT and 99 (24.7%) VAP.
Colonization appeared after 3.1 ± 0.8 days of ICU admission exclusively
with Gram-negative microorganisms. Twenty-fi ve (36.7%) of the colonized
patients developed infections of the LRT (with the same pathogen): 8
(11.7%) VAT after 4.6 ± 2.7 days and 17 (25%) were diagnosed with VAP
after 9.8 ± 1.8 days. From the eight VAT patients, four developed VAP (50%)
after 5.4 ± 0.4 days. None of the colonized patients died. The colonized
patients who developed infections were elderly (P <0.05), more severely ill
(P <0.04) and had at the time of infection a diagnosis higher temperature
(P <0.01), more severe leukocytosis (P <0.02) but not statistically signifi cant
organ dysfunction (P >0.3). The appearance of VAP caused more severe
organ dysfunction (P <0.002), longer MV duration (P <0.01) and longer
LOS (P <0.001) but did not infl uence mortality. On the day of AC detection
MODS was 2.4 ± 0.5, on VAT detection MODS was 4.8 ± 0.9 and on VAP
appearance MODS was 9.6 ± 0.7. CPIS at VAT detection was 3.9 ± 0.9 and at
VAP detection 6.1 ± 0.5 (day I) and 7.2 ± 0.8 (on day III).
Conclusions AC resulted in LRT infections in only one-third of our patients
and the majority of LRT infections are not preceded by AC.
Rehydration does not aff ect pulmonary immune responses to
infl uenza or susceptibility to secondary bacterial pneumonia
RD Sanders1, A Godlee1, JC Goulding1, M Maze2, T Hussell1
1Imperial College London, UK; 2UCSF, San Francisco, CA, USA
Critical Care 2010, 14(Suppl 1):P78 (doi: 10.1186/cc8310)
Introduction In our murine model of infl uenza, signifi cant weight loss
occurs up to day 7 post-infection . We sought to determine whether
weight loss from infl uenza could be altered by rehydration and whether
this aff ects pulmonary immune responses.
Methods Adult BALB/c mice were infected with X31 (H3N2) infl uenza (1:80)
via the intranasal route and randomized to intraperitoneal rehydration
with 20 ml/kg compound sodium lactate (CSL), normal saline (NS) or
no rehydration (NR) starting on day 3 following infection and continued
for 4 days (n = 5/group). On day 7, mice were challenged with 1 x 106
Streptococcus pneumoniae (serotype 2). Two further cohorts of mice were
challenged with diff erent doses of infl uenza and rehydrated from day 3 to
7 to investigate pulmonary immune responses in the absence of bacteria.
Mice were infected with 1:80 (n = 10/group) infl uenza and rehydrated
once daily or 1:60 (n = 5/group) infl uenza and rehydrated twice (1:60)
daily with 20 ml/kg CSL or not. Daily weight, survival following secondary
bacterial pneumonia, number of colony-forming units (48 hours after
bacterial challenge) from peripheral blood, lung, and nasal wash and
cellularity in lung compartments were measured.
Results Rehydration did not aff ect weight loss following 1:80 infl uenza
infection (naïve mice (+0.3 ± 0.4 g), infl uenza plus NR (–1.58 ± 0.4 g),
infl uenza plus CSL (–1.1 ± 0.7 g) and infl uenza with NS (–1.3 ± 0.4 g)). A
repeat experiment with CSL once daily or twice daily did not alter weight
loss compared with NR (P >0.05). Survival or CFU counts following bacterial
pneumonia did not diff er between the groups (P >0.05). The total number or
activational status of bronchoalveolar, lung macrophages/monocytes and
lymphocytes was not aff ected by rehydration following infl uenza infection
or 48 hours following bacterial pneumonia (P >0.05; P <0.05 vs naïve mice).
Conclusions Rehydration does not aff ect immunity or pathophysiology
in a murine infl uenza infection model. Assuming these results can be
extrapolated to the clinical setting, our fi ndings support the use of
conservative fl uid resuscitation strategies in patients with infl uenza.
1. Snelgrove et al.: Nat Immunol 2008, 9:1074-1083.
Bacteremic nosocomial pneumonia cases from the ATTAIN studies
E Rubinstein1, SL Barriere2, FC Genter2, GR Corey3, C Luna4, A Lentnek5,
1University of Manitoba, Winnipeg, Canada; 2Theravance, Inc., South San
Francisco, CA, USA; 3DCRI, Durham, NC, USA; 4University of Buenos Aires,
Argentina; 5Wellstar Infectious Disease, Marietta, GA, USA; 6CEMIC, Buenos
Critical Care 2010, 14(Suppl 1):P79 (doi: 10.1186/cc8311)
Introduction Bacteremic pneumonia is associated with worse outcome
including higher mortality. The ATTAIN program compared telavancin
(TLV), a lipoglycopeptide antibiotic, with vancomycin (VAN) for treatment
of nosocomial pneumonia (NP) due to Gram-positive pathogens including
MRSA. This subgroup analysis examined the baseline characteristics and
clinical outcomes in bacteremic HAP cases.
Methods ATTAIN 1 and 2 were methodologically identical, randomized,
double-blind, phase 3 studies. Adult patients with NP due to presumed or
confi rmed Gram-positive pathogens were randomized (1:1) to TLV 10 mg/
kg intravenously every 24 hours or VAN 1 g intravenously every 12 hours
(adjusted per site-specifi c guidelines) for 7 to 21 days. The modifi ed all-
treated (MAT) population consisted of patients who received ≥1 dose of
study medication and who had a respiratory pathogen recovered from
baseline cultures. Bacteremic NP was defi ned by the identifi cation of a
pneumonia-causing pathogen in the blood or of the same pathogen in
lung and blood with identical susceptibility profi les. Clinical outcomes
were assessed at test-of-cure (TOC) 7 to 14 days after end of study
Results All MAT patients with bacteremic NP (n = 73) were included in
this analysis. At baseline, more TLV patients than VAN patients were in the
ICU (TLV 74%, VAN 62%) and had ventilator-associated pneumonia (TLV
59%, VAN 44%); APACHE II scores were similar between groups (mean ±
SD, TLV 16 ± 6, VAN 17 ± 6). S. aureus was the most common pathogen
(TLV 76%, VAN 69%) and included MRSA (TLV 41%, VAN 49%). Cure rates for
TLV and VAN were 44% and 36%, respectively (diff erence TLV – VAN (95%
CI) = 7.3% (–15.9%, 30.5%)). On-study mortality was similar, 41% in each
treatment group. Incidences of adverse events (AE) were similar between
groups, except for nausea (TLV 21%, VAN 3%) and vomiting (TLV 15%, VAN,
0%). Proportions of patients who discontinued the study medication due
to AEs were similar (TLV 12%, VAN 13%).
Conclusions TLV and VAN had similar cure rates in a subgroup of ATTAIN
patients with bacteremic NP. The safety profi les of TLV and VAN were
mostly comparable in these patients.
Late ventilator-associated pneumonia: analysis of baseline
characteristics and clinical outcomes in the ATTAIN studies
E Rubinstein1, SL Barriere2, FC Genter2, GR Corey3, PC Lee4, T Lalani3
1University of Manitoba, Winnipeg, Canada; 2Theravance, Inc., South San
Francisco, CA, USA; 3DCRI, Durham, NC, USA; 4Baystate Medical Centre,
Springfi eld, MA, USA
Critical Care 2010, 14(Suppl 1):P80 (doi: 10.1186/cc8312)
Introduction Pneumonia is a leading cause of death associated with
hospital-acquired infections. Late ventilator-associated pneumonia
(VAP), defi ned as disease onset after ≥4 days of mechanical ventilation,
is associated with worse outcomes than other forms of hospital-acquired
Methods ATTAIN 1 and 2 were methodologically identical, randomized,
phase 3 studies of telavancin (TLV) 10 mg/kg intravenously every 24 hours
vs vancomycin (VAN) 1 g intravenously every 12 hours for treatment of
HAP, including VAP. VAN doses could be adjusted per investigative site
guidelines. Clinical outcome was assessed at the test-of-cure (TOC) visit
7 to 14 days after the end of study treatment. Baseline characteristics,
outcomes, and safety in the late VAP sub-group were analyzed in the
Critical Care 2010, Volume 14 Suppl 1
modifi ed all-treated population (MAT; patients with baseline respiratory
pathogen(s) who received ≥1 dose of study medication) and the
microbiologically evaluable population (ME; protocol adherent MAT
patients with baseline Gram-positive pathogen(s)). Patients with mixed
Gram-positive/Gram-negative infections were excluded in this analysis.
Results A total of 197 late VAP cases were analyzed. Baseline characteristics,
including the APACHE II scores, were balanced between the treatment
groups (Figure 1). At least one adverse event (AE) was reported by 95%
(106/112) and 93% (79/85) of MAT patients in the TLV and VAN groups,
respectively, and 21% (23/112) of the TLV group and 22% (19/85) of the
VAN group died during the study.
Conclusions In this exploratory sub-group analysis, numerically higher
cure rates were observed for TLV than for VAN in patients with late VAP.
Incidences of reported AEs and mortality rates were similar between the
TLV and VAN groups.
On the diagnosis of acute respiratory distress syndrome in
A Kuzovlev, VV Moroz, AM Goloubev
V.A. Negovsky Research Institute of General Reanimatology, Moscow, Russia
Critical Care 2010, 14(Suppl 1):P81 (doi: 10.1186/cc8313)
Introduction Clinical practice deals highly frequently with patients
presenting a concomitant occurrence of acute respiratory distress
syndrome (ARDS) and nosocomial pneumonia (NPn). Timely diagnosis
of ARDS and NPn in such circumstances is problematic, but it provides
a possibility of diff erential treatment. The aim of the investigation was to
elucidate the value of the oxygenation index (OI), extravascular lung water
index (EVLWI), pulmonary vascular permeability index (PVPI) and central
hemodynamics indexes in the diagnosis of ARDS in NPn.
Methods Thirty-eight cancer and severely traumatized patients were
enrolled in the prospective clinical investigation. The patients were split
into three groups according to the ARDS and NPn diagnostic criteria:
group 1 (ARDS + NPn), group 2 (NPn), group 3 (no ARDS, no NPn). ARDS
was diagnosed by means of the Lung Injury Score (LIS), the American–
European Consensus Conference on ARDS criteria (1992), and the criteria
of the V.A. Negovsky Research Institute of General Reanimatology (2006).
All patients were investigated with a complex protocol, key elements of
which were EVLWI, PVPI and central hemodynamics indexes measured by
the transpulmonary thermodilution (Pulsion PiCCO plus, Pulsion Medical
Systems, Germany). The data were analyzed by Statistica 7.0 (M ± SD,
Newman–Keuls test, correlations). P <0.05 was considered statistically
Results Patients of group 1 on the day of enrollment presented with a
signifi cantly lower OI (160.9 ± 51.7 mmHg vs 239.5 ± 96.7 mmHg) and static
pulmonary compliance (46.3 ± 13.7 ml/water cm vs 72.4 ± 23.1 ml/water
cm) and signifi cantly higher EVLWI (12.7 ± 4.7 ml/kg vs 7.6 ± 1.6 ml/mg)
and LIS (2.22 ± 0.67 scores vs 1.68 ± 0.58 scores) in comparison with group
2 patients. The patients of group 2 presented with an EVLWI within the
physiological limits over the whole investigation period. PVPI calculated
by three existing methods was available within the physiological limits
even in the patients with a profound pulmonary edema. There were no
signifi cant diff erences between the groups in central hemodynamics
Conclusions The OI, EVLWI, static pulmonary compliance and LIS made it
possible to timely diagnose ARDS in NPn. Patients with NPn without ARDS
presented with EVLWI within the physiological limits. A complex analysis of
these indexes must be performed to diagnose ARDS in NPn. Physiological
limits of the PVPI require an additional investigation due to an insuffi cient
diagnostic value. Volumetric indexes of central hemodynamics should be
measured to confi rm the noncardiogenic nature of pulmonary edema.
Genetic variability at the surfactant proteins A and D in
susceptibility and severity of pneumonia
J Solé-Violán1, M Garcia-Laorden1, F Rodriguez de Castro1,
O Rajas2, J Blanquer3, L Borderías4, P Saavedra5, J Aspa2, M Briones3,
J Marcos-Ramos6, E Herrera-Ramos1, J Ferrer1, I Sologuren1, J Rello7,
1Hospital Dr Negrín, Las Palmas de Gran Canaria, Spain; 2Hospital de la
Princesa, Madrid, Spain; 3Hospital Clínico, Valencia, Spain; 4Hospital San
Jorge, Huesca, Spain; 5University of Las Palmas de Gran Canaria, Las Palmas,
Spain; 6Hospital General de Lanzarote, Spain; 7Joan XXIII University Hospital,
Critical Care 2010, 14(Suppl 1):P82 (doi: 10.1186/cc8314)
Introduction Genetic variability of the pulmonary surfactant proteins
A and D may aff ect clearance of microorganisms and the extent of the
infl ammatory response. The genes of these collectins (SFTPA1, SFTPA2
and SFTPD) are located in a cluster at 10q21-24, near to the gene coding
for mannose-binding lectin (MBL2), another collectin involved in innate
immunity. The aim of this study was to evaluate the association of
variability at SFTPA1, SFTPA2 and SFTPD with susceptibility to and severity
of community-acquired pneumonia (CAP). Another objective was to
evaluate the existence of linkage disequilibrium among SFTPA1, SFTPA2,
SFTPD and MBL2.
Methods Nonsynonymous polymorphisms of SFTPA1, SFTPA2, SFTPD and
MBL2 were analysed in 682 CAP patients and 769 controls. Haplotypes
were inferred and linkage disequilibrium (LD) was characterized. The eff ect
of genetic variability on SP-A and SP-D serum levels was studied.
Results Haplotypes SFTPA1 6A2 (P = 0.0009), SFTPA2 1A0 (P = 0.0017), and
SFTPA1-SFTPA2 6A2-1A0 (P = 0.0005) were under-represented in patients,
whereas haplotypes SFTPA2 1A10 (P = 0.00007) and SFTPA1-SFTPA2
6A3-1A (P = 0.00065) were over-represented. We observed the existence of
LD among the studied genes. Chromosomes carrying the SFTP-D aa11-C
allele with 6A2-1A0 and the XA variant of MBL2 were found to be even
more under-represented in patients (P = 0.00008). 1A10 and 6A-1A were
associated with higher mortality, and also with multiorgan dysfunction
syndrome (MODS) and acute respiratory distress syndrome (ARDS),
respectively. SFTPD aa11-C allele was associated with development of
MODS and ARDS.
Conclusions We report for the fi rst time an association between genetic
variants of SFTPA1, SFTPA2 and SFTPD with the susceptibility, severity and
outcome of pneumonia.
Successful strategy to reduce ventilator-associated pneumonia
AL Manoel, Í Boszczowski, AH Andrade, L Bierrenbach, E Taira, AC Baruzzi
Hospital Municipal Dr. Moysés Deutsch, São Paulo, Brazil
Critical Care 2010, 14(Suppl 1):P83 (doi: 10.1186/cc8315)
Introduction VAP rates in Brazil are higher than those related in Europe
and USA. The study objective was to examine the eff ect of the Institute for
Healthcare Improvement’s ventilator bundle plus oral decontamination
with chlorhexidine (ODC) in the incidence of VAP in an ICU.
Methods The study was conducted in a 20-bed, medical-surgical ICU.
Criteria for nosocomial pneumonia are those from the CDC. Strategy
was to implement the IHI’s ventilator bundle plus ODC. The goals were
the ICU team adhesion of 80% achieved in the ninth month after bundle
implementation and 98% after 1 year of follow-up. These measures
included fi ve strategies to prevent ventilator-associated pneumonia: 30 to
45° elevation of the head of the bed, adequate sedation level (Ramsay 2 or
3), DVT/PE prevention, peptic ulcer prophylaxis and oral decontamination
with chlorhexidine 0.12%.
From February 2009 onwards, the ICU nursing staff and ICT performed a
daily checklist in order to observe the fi ve issues accomplishment. If any
item was found to be inadequate it was promptly corrected.
Figure 1 (abstract P80).
Critical Care 2010, Volume 14 Suppl 1
Results In February and September, adhesion to the whole bundle was 9%
and 86%, respectively (P <0.001) (Figure 1). VAP density was proportionally
lower to bundle adhesion in the same period, 20 per 1,000 ventilation/day
and 4.5, respectively.
Conclusions Initial VAP rates were extremely high even for Brazilian
benchmarks. Although we could not implement expensive technologies
like continuous aspiration of subglottic secretions, the ICU team and ICT
eff orts were crucial for satisfactory results, as well the administrative board
support, which turned this issue into an institutional priority. Our goals are
to reduce even more, implementing the ‘ventilator bundle – getting to
zero’ program, and maintaining a continued eff ort to sustain these results.
Ventilator-associated pneumonia rate and ventilator bundle
compliance in a district general hospital
E Winkley, E Sykes
Northumbria Healthcare NHS Trust, Ashington, UK
Critical Care 2010, 14(Suppl 1):P84 (doi: 10.1186/cc8316)
Introduction An observational study to establish the incidence of
ventilator-associated pneumonia (VAP), and ventilator care bundle (VCB)
compliance. Neither has previously been quantifi ed at our institution. VAP
is a nosocomial pneumonia presenting in patients mechanically ventilated
for ≥48 hours . Use of microbiological data in conjunction with the Clinical
Pulmonary Infection Score (CPIS) improves VAP diag nostic specifi city .
VCBs reduce VAP rates, in some cases to zero. The Department of Health VCB
is one such collection of evidence-based interventions .
Methods A 3-month (April 2009 to June 2009) prospective observational
study, in an eight-bed critical care unit in a district general hospital. All
mechanically ventilated patients, age ≥18, intubated >48 hours were
included. Pregnant or immunosuppressed patients were excluded. Patients
treated with antibiotics for suspected or confi rmed VAP were identifi ed.
CPIS was calculated on day 0 and day 3 of treatment. VCB compliance was
recorded weekly in all patients.
Results A total of 190 ventilator-days were identifi ed with no cases of
VAP. The VAP rate per 1,000 ventilator-days is 0. Sixty-nine percent of cases
achieved 100% VCB compliance. Four of the six VCB elements were 100%
compliant (Table 1). All incidents of noncompliance had valid clinical
Conclusions The VAP rate at Wansbeck General Hospital is zero.
Compliance with a recognised VCB is high. The previous VAP rate was
unknown. The impact of the VCB and the short study duration are unclear.
Continuous data collection has been implemented to establish whether
such results are representative and sustainable. Use of the CPIS to limit
inappropriate antibiotic in suspected VAP is planned.
1. Calandra T, et al.: Crit Care Med 2005, 33:1538-1548.
2. [http://www.clean-safe-care.nhs.uk/index.php?pid = 4]
Oral chlorhexidine to prevent nosocomial pneumonia in critically ill
patients: a systematic review and meta-analysis
RJ Pugh, P Rathbone
Glan Clwyd Hospital, Rhyl, UK
Critical Care 2010, 14(Suppl 1):P85 (doi: 10.1186/cc8317)
Introduction This systematic review aims to evaluate evidence from
randomised controlled trials (RCTs) for oral chlorhexidine in preventing
nosocomial pneumonia in intubated mechanically ventilated critically ill
adults. Use of oral chlorhexidine appeals since it should reduce bacterial
aspiration from the orophayrnx. A number of RCTs have recently been
published on this topic.
Methods Search of Medline, Embase, Cochrane library, grey literature
registers, conference proceedings and reference lists for RCTs comparing
chlorhexidine with placebo or standard care for prevention of pneumonia
in the critically ill. Outcomes: episode of nosocomial respiratory tract
infection (RTI), mortality, duration of mechanical ventilation (MV) and
length of ITU stay (ITU LOS). Review Manager 4.2 (Nordic Cochrane Centre)
was used for data synthesis. Eff ect estimates (odds ratio for dichotomous
and weighted mean diff erence for continuous data) were calculated using
a random eff ects model.
Results Fourteen studies were identifi ed, three involving patients
undergoing cardiac surgery (1,841 patients) and 11 involving patients
in noncardiothoracic ITUs (1,497 patients; see Table 1). Five studies
(including two cardiac studies) found a signifi cant reduction in episodes
of nosocomial RTI in the chlorhexidine-treated group versus placebo or
standard care. Pooled data indicated a signifi cant reduction in nosocomial
RTI in the treatment group among all patients, and among cardiac and
noncardiac sub-groups (odds ratio 0.57 (95% CI 0.42 to 0.77), 0.52 (0.37 to
0.75) and 0.6 (0.4 to 0.89), respectively). However, no signifi cant diff erences
in mortality, duration of mechanical ventilation or ITU stay were
demonstrated. Signifi cant heterogeneity (I2 statistic >40%) was detected
for all outcomes except mortality.
Table 1 (abstract P85). Eff ect estimates
Number of studies Participants Eff ect
RTI 14 3,338 OR 0.57
Mortality 11 3,233 OR 1.2
MV days 6 noncardiac 1,027 WMD +1.34
ITU LOS days 4 noncardiac 702 WMD –0.51
Conclusions Use of oral chlorhexidine is associated with reduction
in nosocomial respiratory tract infection in intubated mechanically
ventilated critically ill adults.
Impact of routine multiple site decontamination in intubated
patients on ICU-acquired infections
C Camus, S Lavoué, A Gacouin, S Marque, A Gros, Y Le Tulzo
Hôpital Pontchaillou, Rennes, France
Critical Care 2010, 14(Suppl 1):P86 (doi: 10.1186/cc8318)
Introduction We have shown that a the combination of selective digestive
decontamination with topical antibiotics (SDD) and a decontamination
regimen using nasal mupirocin with chlorhexidine bodywashing
(M/C) markedly reduced acquired infections (AI) in intubated patients
as compared with SDD alone, M/C alone or none . We report the
surveillance of AI in our ICU before and after the implementation of
multiple site decontamination (MSD) as a routine prevention procedure.
Figure 1 (abstract P83). Proportion of bundle adhesion and density of
incidence of ventilator-associated pneumonia.
Table 1 (abstract P84). Ventilator care bundle compliance
30 to 40°
DVT GI Tubing
prophylaxis prophylaxis Humidifi cation elements
Compliance (%) 100 88 81 100 100 100 69
Critical Care 2010, Volume 14 Suppl 1
Methods MSD was implemented in June 2007. We compared the
incidence rates of AI (expressed per 1,000 patient-days (‰) or per 1,000
device-days for device-related AI) between the last 1-year period before
(period A, 7,723 patient-days) and the fi rst 1-year period after (period B,
7,646 patient-days) MSD use was started.
Results In period B (MSD) versus period A (no MSD), there was a reduction
in the rates of total AI (9.4‰ vs 23.6‰), bloodstream infections (1.0‰ vs
4.0‰), ventilator-acquired pneumonia (5.6‰ vs 19.1‰) (all P <0.01), and to
a less extent catheter-related urinary tract infection (1.0‰ vs 2.2‰, P = 0.11).
Multivariate analysis with the Cox regression model showed that period A
(OR 2.34 (1.64 to 3.20)) and the presence of a central venous catheter (OR
2.07 (1.22 to 3.57)) were the two independent risk factors for AI. In period
B, there was a statistically signifi cant reduction in the rates of AI involving
S. aureus (1.0‰ vs 3.0‰), coagulase-negative staphylococci (0.4‰ vs
1.3‰), Candida (0.4‰ vs 1.3‰) and aerobic Gram-negative bacilli (5.0‰
vs 15.8‰), especially Enterobacteriaceae (3.4‰ vs 9.4‰), Pseudomonas
aeruginosa (1.4‰ vs 3.9‰), S. maltophilia (0 vs 1.7‰) and Acinetobacter sp.
(0 vs 0.8‰) (all P ≤0.05). MRSA AI rates were also lower (0.3‰ vs 0.9‰, NS)
and no AI due to VRE occurred during both period. The rates of AI involving
antimicrobial-resistant Enterobacteriaceae were lower in period B for 12
antimicrobials tested, especially for ticarcillin (2.1‰ vs 6.5‰), ticarcillin/
clavulanate (0.8‰ vs 4.0‰), cefotaxime (0.3‰ vs 2.2‰) and colistin (0.5‰
vs 1.8‰) (all P ≤0.02). Similar fi ndings were observed for antimicrobial-
resistant P. aeruginosa although diff erences were not signifi cant. Overall,
the rate of AI involving organisms defi ned as multidrug-resistant (MDROs)
markedly decreased in period B (2.5‰ vs 9.1‰, P <0.001).
Conclusions Routine use of MDS was associated with a strong reduction
in ICU AI. The reduction was consistently observed for all principal classes
of pathogens, including MDROs. No new MDRO emerged.
1. Camus C: Crit Care Med 2005, 33:307-314.
Ventilator-associated pneumonia caused by Pseudomonas
aeruginosa and respiratory colonization by Candida spp.
F Antonicelli, R Festa, F Idone, F Di Muzio, R Maviglia, M Antonelli
Università Cattolica del Sacro Cuore, Roma, Italy
Critical Care 2010, 14(Suppl 1):P87 (doi: 10.1186/cc8319)
Introduction This study aims to test the association of an increased
mortality in critically ill patients with ventilator-associated pneumonia
(VAP) caused by Pseudomonas aeruginosa in patients with a previous
respiratory tract colonization by Candida spp. compared with that of
patients with a VAP by P. aeruginosa without Candida spp. isolation.
Methods A retrospective study on all 5,236 critically ills patients admitted
to the ICU of a university hospital from 2001 to 2008, of which 1,097
received mechanical ventilation and in whom Pseudomonas and/or
Candida were isolated in quantitative cultures from the Mini-BAL .
Results P. aeruginosa and Candida spp. were present at the same time in
295 patients (P-C group), P. aeruginosa only in 92 patients (P group) and
Candida spp. only in the remaining 710 patients (C group). SAPS II was
44.27 ± 14.8 (mean ± SD), 39.07 ± 14.61 and 39.07 ± 14.61, respectively,
for P-C, P and C groups. The SAPS II score of the C group was signifi cantly
higher than the P group (P <0.05), the SAPS II score of the C group was
higher than the P-C group (P >0.05), and the SAPS II score of the P group
was lower than the P-C group (P >0.05). The population with Candida
spp. isolation alone was older (70.25 years vs 63.17 (group P-C) and 60.22
(group P), P <0.05). The group with Pseudomonas associated with Candida
spp. had a mortality rate higher than the P group (57.96% vs 6.05%,
P <0.05). The length of stay in the ICU of patients with Candida spp. and
P. aeruginosa was not diff erent from the group who had P. aeruginosa alone
(26.22 ± 31.80 vs 29.15 ± 25.66, P >0.05). Duration of hospitalization in the
group with only P. aeruginosa was longer than the other two groups (79.38
days vs 51.85 of the group P-C and 28.40 of group C, P <0.05).
Conclusions Candida colonization seems to increase the risk for
Pseudomonas infection . Patients who developed VAP due to
P. aeruginosa with previous colonization of the respiratory tract by Candida
spp. were older, with a higher SAPS II score and had a high mortality.
1. Koenig SM, Truwit JD: Clin Microbiol Rev 2006, 19:637-657.
2. Azoulay E, et al.: Chest 2006, 129:110-117.
Time course of RT-PCR positivity in H1N1-induced ARDS
E Mannelli1, M Murtigni1, M Andreani1, S Cianferoni1, D Colosimo1, G Zagli2,
M Bonizzoli2, A Azzi3, A Peris2
1Postgraduate School of Anesthesia and Intensive Care, University of Florence,
Italy; 2Careggi Teaching Hospital, Florence, Italy; 3University of Florence, Italy
Critical Care 2010, 14(Suppl 1):P88 (doi: 10.1186/cc8320)
Introduction The aim of this study was to analyze the correlation between
antiviral therapy effi cacy and the negative profi le of the RT-PCR made on
pharyngeal swab, subglottic aspiration, and bronchoalveolar lavage in
patient aff ected by ARDS caused by H1N1 infection.
Methods A prospective analysis was performed on 11 patients admitted
to the ICU of a tertiary referral center (Careggi Teaching Hospital, Florence,
Italy). All patients underwent daily RT-PCR monitoring on pharyngeal
swab, subglottic aspiration, and bronchoalveolar lavage. All patients were
treated with oral administration of oseltamivir (75 mg twice daily) and
inhaled zanamivir (10 mg twice daily) since ICU admission. Six patients
were treated with extracorporeal membrane oxygenation (ECMO) due to
their critical respiratory conditions. Two of them resulted co-infected by
Results As shown in Figure 1, RT-PCR from pharyngeal swab at ICU
admission failed to demonstrate the viral infection in four patients,
whereas RT-PCR from bronchoalveolar lavage had a sensibility of 100%.
Similarly, the time course showed that RT-PCR from pharyngeal swab
resulted negative in an average time of 3 days after therapy start, while
RT-PCRs from bronchoalveolar lavage continued to permit infection
monitoring and therapy regimen conduction. None of RT-PCRs on
subglottic aspiration samples resulted positive. All patients recovered and
were discharged alive from ICU in spontaneous breathing.
Conclusions In our experience, the most reliable method to diagnose
and monitor H1N1 infection was RT-PCR from bronchoalveolar lavage,
since pharyngeal swab do not off er enough sensibility, either for antiviral
therapy initiation or for antiviral therapy management. Samples from
subglottic aspiration can be avoided due to a low sensibility.
Novel swine infl uenza A: most frequent ultrasonographic lung
L Tutino1, F Barbani1, G Cianchi2, S Batacchi2, L Perretta2, R Cammelli2,
M Bonizzoli2, R Spina2, G Zagli2, A Peris2
1Postgraduate School of Anesthesia and Intensive Care, Faculty of Medicine,
Florence, Italy; 2Anaesthesia and Intensive Care Unit of Emergency
Department, Careggi Teaching Hospital, Florence, Italy
Critical Care 2010, 14(Suppl 1):P89 (doi: 10.1186/cc8321)
Introduction Bedside lung ultrasound is able to identify with high
sensibility and sensitivity most pulmonary pathological patterns and is
widely adopted in critically ill patients’ daily management. It is a feasible
Figure 1 (abstract P88). Time course of RT-PCR positivity for H1N1
Critical Care 2010, Volume 14 Suppl 1
and reliable method for the identifi cation of the lung pathological patterns
caused by H1N1 infl uenza infection.
Methods The study took place in the ICU of a regional referral center,
with ECMO availability, for respiratory failure (Careggi Teaching Hospital,
Florence, Italy). Eight patients admitted for H1N1-induced ARDS
(September to October 2009) underwent daily LU examination. The
examination was standardized with a procedure ad hoc in order to
achieve complete and comparable reports for every patient. Patients were
examined supine, taking lateral and anterior views and, if possible, on
one side. Intercostal spaces were used as acoustic windows. Every single
examination and its fi nding have been reported in our ICU database.
Results Pleural thickness was present in 100% of cases, mostly related
to little and multiple pleural consolidations. Anyway, pleural gliding was
present most of the time (87.5%), even if with a visible decrease of its
movement. This was replaced with the lung pulse only in the presence
of important lung consolidation. Alveolar interstitial syndrome (AIS) was
always present on the whole lung, ranging from moderate to severe (100%),
with high positivity at the base, posteriorly (100%). White lung appeared in
every patient, most at the lung base and in the middle fi elds, posteriorly.
As far as consolidation is concerned, its presence was confi rmed in 100%
of the patients, associated with satellite multiple subpleural consolidations
in 37.5% of patients. Basal lung was always involved (100%), followed
by middle (50%) and apical fi elds(25%). Bronchogram was present in
100% of patients in bigger consolidations. Their aspect was aerial and
only in one patient, with severe consolidations, turned into a fl uid one.
Anechoic pleural eff usions were found in 37.5% of patients. No cases of
pneumothorax were detected.
Conclusions In this group of patients, H1N1 infection shows diff erent
lung patterns altogether, where the most frequent seemed to be severe
basal posterior AIS, multiple subpleural lung consolidations, and multiple
parenchymal consolidation with bronchogram. The presence of spared
areas did not seem to belong to H1N1 LU patterns.
Outcome and prognostic factors in patients with HIV-negative
pneumocystis pneumonia requiring mechanical ventilation
Asan Medical Center, Seoul, Republic of Korea
Critical Care 2010, 14(Suppl 1):P90 (doi: 10.1186/cc8322)
Introduction Pneumocystis pneumonia (PCP) in HIV-negative patients
frequently presents as fulminant respiratory failure and is associated with a
high mortality rate when the patient requires mechanical ventilation. The
aims of this study were to evaluate the outcome and prognostic factors in
the patients with HIV-negative PCP requiring mechanical ventilation (MV).
Methods We retrospectively reviewed the medical records and collected
the HIV-negative patients who were microbiologically confi rmed as PCP
and required MV in ICU over a 10-year period in a tertiary care teaching
Results A total of 51 patients were identifi ed. Mean age was 55.4 ± 15.0
years. Mean APACHE II score at ICU admission was 25.7 ± 5.8. The 28-day
mortality and in-hospital mortality were 45.8% and 66.7%, respectively.
Between survivors and nonsurvivors, there were no signifi cant diff erences
in baseline characteristics, APACHE II score, PaO2/FiO2 ratio, and absolute
neutrophil counts on ICU admission day. Also the mortality was not
diff erent in relation to the presence of barotrauma, application of non-
invasive ventilation, timing of susceptible antibiotic administration,
changing or not to salvage regimens, presence of cytomegalovirus co-
infection and even the microbiologic persistency in follow-up specimens.
Based on the types and intensity of previous immunosuppressive therapy,
we classifi ed patients into three subgroups: patients receiving low-dose
steroid maintenance ± other immunosuppressive agents (LS), which
represent previously stable organ transplants; another group consisting
of patients receiving recent intensive chemotherapy (CTx); and the other
group refers to patients receiving high dose (defi ned as >2 weeks at
least 1 mg/kg dose) steroid therapy ± other immunosuppressive agents
(HS). Signifi cant diff erences of outcome were observed among the three
diff erent groups (28-day mortality: LS = 22.2%, CTx = 29.4%, HS = 71.4%,
P = 0.01; 60-day mortality: LS = 33.3%, CTx = 64.7%, HS = 81.0%, P = 0.04).
Conclusions Our data showed that the mortality of fulminant HIV-
negative PCP requiring MV was signifi cantly diff erent according to the
types and intensity of previous immunosuppressive treatment despite
similar clinical features on ICU admission.
Acute respiratory failure from pandemic infl uenza A (H1N1) in an
intensive care unit in southern Brazil
S Beduschi Filho, D Siqueira, SC Carvalho Flores, I Yoshiko Masukawa,
L Kretzer, AC Burigo Grumann, I Silva Maia, M Pimentel Pincelli
Hospital Nereu Ramos, Florianópolis, Brazil
Critical Care 2010, 14(Suppl 1):P91 (doi: 10.1186/cc8323)
Introduction In the winter of 2009 the infl uenza A (H1N1) pandemic
reached Brazil, aff ecting severely its southern states. A total 68,806 cases
of suspected pandemic infl uenza A infection had been reported in Brazil
and 91% of the specimens tested were positive. Incidence of pandemic
infl uenza A in southern Brazil was 137/100,000. In the southern Brazilian
state of Santa Catarina, Nereu Ramos Hospital is the referral center for the
treatment of infectious diseases, and it provided eight intensive care beds
for the management of acute respiratory failure from suspected cases of
infl uenza A during the 2009 pandemic.
Methods We collected retrospective data on the epidemiological features,
clinical course and ventilatory characteristics of patients with laboratory-
confi rmed infl uenza A (H1N1) infection who were admitted to our ICU
during the winter of 2009.
Results Thirty-four adult patients were admitted to our ICU with acute
respiratory failure and suspected pandemic infl uenza A infection. Of these,
14 cases tested positive for infl uenza A (H1N1). The majority of the patients
were male (61.5%) with median age of 27.5 years and interquartile range
(IR) of 26.5 to 48.5. The APACHE II median was 14.5 (IR 10.0 to 18.25) with
median predicted mortality of 20.0 (IR 10.73 to 27.7). Risk factors were:
obesity (23.1%), obstructive respiratory diseases (15.4%); pregnancy,
immunosuppressive and neuromuscular disorders were present in one
patient each. All 14 patients presented severe respiratory failure, with a
median lowest PaO2/IOF of 113.3 (IR 83.53 to 159.55) and 92.3% of them
requiring mechanical ventilation. The patients in mechanical ventilation
were all ventilated in pressured-controlled mode, demanded high PEEP
levels (mean of 18.5 ± 5.16 cmH2O), presented high peak inspiratory
pressure (mean of 37.83 ± 7.35 cmH2O) and required elevated IOF
(81.15 ± 20.83%). A total of 57.1% of the patients were submitted to lung
recruitment, while the prone position was used in 42.8% of them. The
median ICU stay was 13.0 days (IR 4.75 to 23.50) and the median hospital
stay was 16.5 days (IR 9.75 to 25.0). The ventilatory-associated pneumonia
(VAP) rate was unusually high (69.2%) as well as the mortality rate during
the intensive care stay (38.5%).
Conclusions Patients admitted to our ICU with confi rmed pandemic
infl uenza A infection presented severe acute respiratory failure and an
unusually high incidence of VAP and mortality rates.
1. Perez-Padilla R, et al.: Pneumonia and respiratory failure from swine-origin
infl uenza A (H1N1) in Mexico. N Engl J Med 2009, 361:680-689.
Extracorporeal membrane oxygenation for infl uenza A (H1N1):
experience in a regional referral center
A Pasquini1, S Di Valvasone2, S Biondi2, S Batacchi1, G Cianchi1, M Ciapetti1,
M Bonizzoli1, R Spina1, L Turrisi1, E Mascitelli3, M Bonacchi3, G Zagli1,
GF Gensini3, A Peris1
1Careggi Teaching Hospital, Florence, Italy; 2Postgraduate School of
Anesthesia and Intensive Care, Florence, Italy; 3University of Florence, Italy
Critical Care 2010, 14(Suppl 1):P92 (doi: 10.1186/cc8324)
Introduction The novel infl uenza A H1N1 virus can cause, in a restricted
subgroup of infected patients, an acute respiratory failure not responding
to conventional treatment. In selected cases, extracorporeal membrane
oxygenation (ECMO) has been applied with a 21% mortality rate. Here we
report the experience of the ICU of a regional referral center for ECMO
(Careggi Teaching Hospital, Florence, Italy).
Methods An Emergency Medical Service has been established for the
novel pandemic infl uenza to guarantee the possibility of ECMO initiation in
the peripheral hospitals by our ECMO Team and the subsequent transport
Critical Care 2010, Volume 14 Suppl 1
on extracorporeal circulation to our referral center. The ECMO Team is
composed of an intensivist, a cardiac surgeon, a cardiologist, a perfusionist
and a nurse. All of the diff erent fi gures were properly trained and formed
on ECMO treatment. According to our internal protocol, eligible patients
for ECMO treatment are aged 15 to 70 years old with acute respiratory
failure with one of the following conditions: a ratio PaO2/FiO2 <60 or
pH <7.20 under protective ventilation conditions. ECMO insertion was
achieved percutaneously and a high-fl ow approach (5 to 6 l/minute) was
initially established according to patient need. ECMO device is a Rotafl ow
Maquet Centrifugal Pump with a Quadrox-D oxygenator (Maquet, Rastatt,
Germany) and biocoated circuits. H1N1 infection was monitored by RT-
PCR examination on pharyngeal swab and bronchial aspirate. Antiviral
therapy was conducted by oral administration of oseltamivir (75 mg twice
daily), and inhaled zanamivir (10 mg twice daily).
Results From October 2009 to November 2009, six patients with infl uenza
A (H1N1) have been treated with ECMO support. Three patients were
cannulated in the district hospital and transported safety to our ICU by
our ECMO Team. Median SAPS II at admission, median age and sex were
as listed as follows: 46, 35 years old and fi ve males/one female. All patients
had an acute respiratory failure accompanied by a multiorgan dysfunction.
ECMO was established and maintained for 200 hours. All patients were
successfully weaned from ECMO support, extubated and discharged from
our ICU. No major procedure-related complications were observed.
Conclusions Well-timed ECMO use in cases of infl uenza A H1N1 acute
respiratory failure could improve overall the survival rate.
Budd–Chiari syndrome complicated by abdominal compartment
syndrome: evidence of central hypovolaemia?
D Joshi, S Saha, W Bernal, J Wendon, G Auzinger
King’s College Hospital, London, UK
Critical Care 2010, 14(Suppl 1):P93 (doi: 10.1186/cc8325)
Introduction Budd–Chiari syndrome (BCS) is characterised by hepatic
venous outfl ow obstruction (HVOO) leading to post-sinusoidal portal
hypertension, congestion of the liver with caudate lobe hypertrophy. In
addition to intra-abdominal hypertension (IAH), caused by severe ascites,
HVOO may aggravate the cardiovascular disturbances seen in patients
with decompensated disease. The aim was to study the haemodynamic
response to abdominal decompression in BCS compared with patients
with decompensated cirrhosis.
Methods Ten patients with BCS admitted to the Liver ICU, King’s
College Hospital were studied. Transpulmonary thermodilution cardiac
output monitoring and calculation of volumetric indices of preload was
performed with the PiCCO system. Haemodynamic variables and IAP
were analysed pre and post intervention. The control group comprised of
cirrhotic patients with IAH requiring abdominal paracentesis (PC).
Results Ten patients with BCS were studied, median age 39 years (range
(R) 20 to 52); eight had liver transplantation and two had a surgical shunt
procedure. Eight patients (PC), median age 59 (33 to 65), underwent
abdominal paracentesis for tense ascites. IAP was raised in both groups
pre intervention (23, R 17 to 40, BCS vs 26, R 20 to 40, PC). ITBVI remained
low in the BCS group (632, R 453 to 924) pre intervention despite
aggressive volume resuscitation (median positive FB10L, R 0.5 to 39). Post
intervention, a reduction in IAP was seen in both groups (BC P <0.001,
PC P <0.0001). ITBVI increased (633, R 453 to 924 vs 736, R 512 to 1,110,
P = 0.001) in BCS patients. No change in ITBVI was noted (pre 870, R 598
to 1,619 vs post 1,036, R 763 to 1,762) in the CP group despite albumin
replacement. An increase in CI and SVI was noted in both groups: BCS (CI
P = 0.003, SVI P = 0.007), CP (CI P = 0.005, SVI P = 0.02). There was an inverse
relationship between IAP, CI (P = 0.003), SVI (P = 0.004) and ITBVI (P = 0.01)
in BCS patients. In the CP group, IAP did not correlate with ITBVI.
Conclusions Compared with cirrhotic patients with ascites, patients with
BCS and IAH have evidence of central hypovolaemia. We postulate that
in addition to raised IAP, hepatic venous obstruction and caudate lobe
hypertrophy limit venous return in patients with BCS. Reduction in IAP
restores preload with improvement in cardiac output.
1. Cheatham et al.: Intensive Care Med 2007, 33:951-962.
2. Malbrain et al.: Intensive Care Med 2006, 32:1722-1732.
Adenosine signalling has a protective role in intestinal ischemia and
K Zimmermann1, T Krieg2, M Soltow1, D Pavlovic1, J Zhou3, S Whynot3,
O Hung3, M Murphy3, C Lehmann3
1Ernst Moritz Arndt University Greifswald, Germany; 2Department of
Cardiology, Cambridge, UK; 3Dalhousie University, Halifax, Canada
Critical Care 2010, 14(Suppl 1):P94 (doi: 10.1186/cc8326)
Introduction Gut ischemia and reperfusion (IR), for example in small
bowel transplantation or following resuscitation, may result in severe
impairment of the intestinal microcirculation. Potential sequelae are
mucosal damage, loss of barrier function, bacterial translocation, systemic
infl ammation, multiple organ failure and death. We hypothesized that
extracellular adenosine signalling has a protective role in intestinal IR
injury. Using intravital microscopy we investigated the eff ects of the
adenosine receptor agonist NECA (5΄-N-ethyl carboxamide adenosine) on
leukocyte–endothelial interactions and capillary perfusion in the intestinal
microcirculation following intestinal IR.
Methods Six groups of animals (n = 7 per group) were studied: control
(CON), NECA, IR (30 minutes of intestinal ischemia, 2 hours of reperfusion),
IR + NECA, IR + NECA + MRS1754 (adenosine A2B receptor antagonist), IR
+ NECA + DPCPX (adenosine A1 receptor antagonist). All substances were
administered immediately after declamping of the superior mesenteric
artery. Intravital microscopy was performed after 2 hours of reperfusion.
Leukocyte adhesion (rolling/fi rm adherence) and functional capillary
density (FCD) were measured offl ine by blinded investigators.
Results Following IR we observed a signifi cant increase of leukocyte
adherence in the intestinal submucosal venules (for example, V1 venules:
CON 20.1 ± 5.8 n/mm2, IR 237.8 ± 24.2 n/mm2, P <0.05). Capillary perfusion
of the muscular layers of the intestinal wall was reduced (for example,
longitudinal muscular layer: CON 112.3 ± 5.3 cm/cm2, IR 92.4 ± 8.4 cm/
cm2). NECA administration reduced signifi cantly leukocyte adherence
(V1 venules: 67.8 ± 6.8 n/mm2, P <0.05) and improved capillary perfusion
(longitudinal muscular layer: 113.9 ± 8.3 cm/cm2). Administration of the
adenosine A2B receptor antagonist completely reversed the NECA eff ects
(for example, leukocyte adherence V1 venules: 228.8 ± 33.2 n/mm2),
whereas A1 receptor inhibition only partially abolished the action of NECA
(for example, leukocyte adherence V1 venules 124.5 ± 14.5 n/mm2).
Conclusions The data support the hypothesis, that adenosine signalling
is involved in intestinal IR injury. The adenosine A2B receptors are more
important than adenosine A1 receptors since inhibition of A2B receptor
by MRS1754 completely reversed the eff ect of the adenosine receptor
1. Förster et al.: Basic Res Cardiol 2006, 101:319-326.
2. Solenkova et al.: Am J Physiol 2005, 290:H441-449.
3. Hart et al.: J Immunol 2009, 182:3965-3968.
Hemodynamic states during the course of norepinephrine weaning
E Kipnis, H Tytgat, N Bruneau, B Leroy, G Lebuff e, B Tavernier, B Vallet
Centre Hospitalier Régional Universitaire de Lille, France
Critical Care 2010, 14(Suppl 1):P95 (doi: 10.1186/cc8327)
Introduction Norepinephrine is a standard of care in the hemodynamic
management of septic shock concomitantly to fl uid administration.
However, no guidelines exist concerning norepinephrine weaning.
Further more, norepinephrine may rapidly restore macrocirculatory hemo-
dynamics through stressed volume without treating the underlying
volume defi cit, especially in the absence of optimal volume expansion.
Norepinephrine weaning may reveal latent/persisting need for volume
expansion in apparently stable patients.
Methods Observational study of norepinephrine weaning in seven
resuscitated SICU septic shock patients. Weaning was performed in 0.1 mg/
hour decrements every 5 to 15 minutes until hemodynamic instability,
defi ned as a mean arterial pressure (MAP) ≤70 mmHg, interrupted the
process, at which point pulse pressure variation (PPV) was measured
and transthoracic echocardiography (TTE) performed as per standard
procedures. Upon instability with PPV ≥13%, 250 ml fl uid challenge was
performed and the MAP increase allowed pursuit of weaning, whereas
Critical Care 2010, Volume 14 Suppl 1
instability with PPV <13% halted weaning. Nonparametric correlations
were sought between norepinephrine decrements and variations over
weaning (and fl uid challenge) in PPV, arterial compliance, and indexed
systolic ejection volume (iSEV). Global resuscitation endpoints (serum
lactate, ScvO2) were compared before and after the entire weaning
Results Two behaviors were observed. First, norepinephrine weaning
unmasked latent preload dependency in steps characterized by marked
PPV increase (16.5%, 8 to 36), correlated to norepinephrine decrements
(ρ = 0.971; r2 = 0.745; P = 0.005) resulting in PPV ≥13% and fl uid challenge
increasing the MAP and allowing pursuit of weaning. Second, weaning
revealed norepinephrine dependency in steps halted by instability and
characterized by slight PPV increases (3.9%, 0.3 to 8.4), resulting in PPV
<10%, and a decrease in iSEV that was correlated to norepinephrine
decrements (ρ = 0.943; r2 = 0.830; P = 0.001). Globally, weaning decreased
serum lactate to under 2 mmol/l with ScvO2 maintained above 70%.
Conclusions Hemodynamic stability through norepinephrine use in
septic shock might be at the cost of occulting residual fl uid requirements
which can be revealed during norepinephrine weaning.
Threshold levels of extreme body surface area that may cause a
misrepresentation of cardiac performance
WT McGee1, BH Nathanson2
1Baystate Medical Center, Springfi eld, MA, USA; 2OptiStatim, LLC,
Longmeadow, MA, USA
Critical Care 2010, 14(Suppl 1):P96 (doi: 10.1186/cc8328)
Introduction Stroke volume (SV) and cardiac output (CO) are standardized
into the stroke index (SI) and cardiac index (CI) by dividing by the patient’s
body surface area (BSA). Commonly used algorithms in hemodynamic
management suggest diverse therapeutic interventions based on low,
high, or normal SI or CI. Morbid obesity is increasingly common. When
morbidly obese patients have their SV or CO indexed, high absolute values
become low SI and CI, and may be misleadingly low. This would then
cause therapeutic interventions opposite to their needs.
Methods BSA was derived using the Mosteller formula on the metric
equivalent of simulated patients ranging from 5 ft to 7 ft and 100 lbs
to 700 lbs. A priori, we defi ned normal CO = 4 to 8, normal CI = 2.5 to
5.0, normal SV = 60 to 100 ml/beat, and normal SI = 33 to 47. Algebraic
analysis was used to determine BSA levels that would classify an SV or CO
Results Critical BSA thresholds (T) are presented in Table 1. For example,
at SV = 100, a BSA higher than 3.03 (to the second decimal place) would
classify the patient as having a low SI.
Table 1 (abstract P96)
SV T CO T
90 2.72 7 2.80
100 3.03 8 3.20
110 3.33 9 3.60
120 3.64 10 4.00
130 3.94 11 4.40
Conclusions Patients with extreme BSAs are increasingly encountered
in the ICU, especially larger BSAs related to obesity. We provide threshold
values where extreme BSAs will classify high SV or CO values as low indexed
values. The ranges considered normal for SI and CI may be inappropriate for
patients with extreme BSAs, particularly in the obese. We caution against
relying solely on the SI and CI to assess hemodynamic performance.
Instead, the SV and CO along with other physiological parameters should
also be considered before making therapeutic decisions.
Cardiac output measurement is feasible in the presence of
left-to-right shunt with ultrasound dilution method: a validation
study in lambs
S Vrancken, W De Boode, J Hopman, S Singh, K Liem
Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands
Critical Care 2010, 14(Suppl 1):P97 (doi: 10.1186/cc8329)
Introduction It remains a great challenge to measure systemic blood
fl ow in critically ill newborns, especially during the transitional period
with intracardiac and extracardiac shunts. Due to technical restraints, size
limitations, the necessity for a relatively large amount of blood withdrawn
and possible indicator toxicity, many methods of cardiac output
monitoring are not feasible, hence cardiac output is generally estimated
from indirect parameters of systemic blood fl ow. In a former study we
assessed the agreement for cardiac output using the ultrasound dilution
method (UDCO) and ultrasound transit time-based measurement of main
pulmonary blood fl ow in a juvenile piglet model without shunts . In the
present study we analyzed the infl uence of a left-to-right shunt on the
agreement between UDCO and ultrasonic transit time pulmonary blood
fl ow in a juvenile lamb model.
Methods In this prospective, experimental animal study, which
was approved by the Ethical Committee on Animal Research of the
Radboud University Nijmegen, we placed a Gore-Tex® shunt between
the left pulmonary artery and the descending aorta in eight random-
bred newborn lambs (3.5 to 8.3 kg). This aortopulmonary shunt was
intermittently opened and closed while cardiac output was manipulated
by creating hemorrhagic hypotension. Ultrasound dilution cardiac output
(Q-UDCO) – using repeated injection of 1.0 ml/kg isotonic saline at body
temperature – was compared with pulmonary blood fl ow (Q-MPA)
invasively measured by a perivascular fl ow probe around the main
Results A total of 220 measurements were performed. Bias, defi ned as
Q-UDCO minus Q-MPA, was calculated for each measurement. With an
open shunt there was a signifi cant left-to-right shunt (mean Qp-/Qs- ratio
1.8; range 1.6 to 2.6). Mean bias (SD) was 6.80 (18.0) ml/kg/minute with a
closed shunt and 11.1 (19.8) ml/kg/minute with an open shunt. Limits of
agreement (±1.96 SD) were ±35.2 ml/kg/minute and ±38.8 ml/kg/minute,
respectively. Percentage error was 22.0% and 24.2% for measurements
with a closed and open shunt, respectively.
Conclusions Cardiac output measurement with the UDCO method is
reliable and easily applicable in ventilated juvenile lambs, even in the
presence of a signifi cant left-to-right shunt.
1. de Boode WP, et al.: Pediatr Crit Care Med 2009, 9. [Epub ahead of print]
The PAPIKAS trial: a comparative clinical trial of pulmonary catheter
versus the PiCCO device during therapy of patients with acute heart
failure and cardiogenic shock
T Schwab, B Schmid, S Richter, C Bode, HJ Busch
University Hospital, Freiburg, Germany
Critical Care 2010, 14(Suppl 1):P98 (doi: 10.1186/cc8330)
Introduction Haemodynamic measurement plays an important role in
the treatment of patients with acute heart failure and cardiogenic shock
(CS). The pulmonary catheter (PAC) is a common device for enhanced
haemodynamic measurement. The aim of this study was to evaluate the
comparability of the PiCCO device with the PAC during the treatment of
patients with CS; for example, the use of intra-aortic counterpulsion (intra-
aortic balloon pumping (IABP)), and therapeutic hypothermia after cardiac
Methods Seventy-seven measurements were taken in 11 critically ill
patients during the therapy of cardiogenic shock. The cardiac index (CI),
stroke volume (SVI), and systemic vascular resistance (SVRI) were measured
by pulmonary catheter and PiCCO device, as well as the pulmonary aortic
occlusion pressure (PAWP) with a pulmonary catheter and the global
end-diastolic volume (GEDI) with the PiCCO device, and registered in a
commercially available computer system.
Results A good correlation between the two techniques in all data, as
well as during the use of IABP or during hypothermia was shown. The
Critical Care 2010, Volume 14 Suppl 1
mean bias between CIpa and CIart was 0.042. The calculated mean error
was 24.89%, 26.17% and 19.08%, respectively. There was also a good
convergence between the measurements of vascular resistance in overall
data and during IABP. Signifi cant correlations were found for SVIpa, SVIpi,
SVRIpa, SVRIpi to CIpa. For GEDI there was a signifi cant correlation with
CIpa for data collected during cooling. No signifi cant correlation between
PAWP und CIpa was found.
Conclusions The data show interchangeability for the two methods using
intermitting measurements during therapy of cardiogenic shock even
during intra-aortic counterpulsation and therapeutic hypothermia. The
cardiac output seems to be related to the GEDI as a preload parameter; no
relationship between PAOP and CI can be shown. The usability of the less
invasive PiCCO device for the enhanced hemodynamic measurement in
patients with acute heart failure and cardiogenic shock is ensured.
Bioreactance versus PICCOTD/PC in critically ill septic shock patients
G Monti1, G Pizzilli1, M Cecconi2, A Rhodes2, S Vesconi1, P Brioschi1,
M Pulici1, G Casella1
1Niguarda Hospital, Milan, Italy; 2St George’s Hospital, London, UK
Critical Care 2010, 14(Suppl 1):P99 (doi: 10.1186/cc8331)
Introduction We designed this study to compare the performance in
cardiac output (CO) monitoring capabilities of two devices in refractory
septic shock patients (RSS Pts): non-invasive transthoracic bioreactance
(NICOM) and pulse contour analysis (PICCO PC) coupled to transpulmonary
Methods We included RSS Pts in vasopressor/inotrope need monitored
with both devices. Triplicate measurements of CO by PICCOTD were
used to measure CO at baseline and to calibrate PulseCO. The CO values
recorded simultaneously minute-by-minute by the two systems were
compared at baseline (nonperturbated system), in response to a passive
leg-raising maneuver (PLR = leg elevation to 45° for 2 minutes starting from
a supine position) and PEEP test (10 and 15 cmH2O for 10 minutes each)
(perturbated system). We used PICCOTD/PC as the reference technology
evaluating the accuracy and estimating the precision of both devices.
Results Continuous CO recording with both devices was performed on 12
consecutive RSS Pts (Nep + Epi = 0.66 ± 0.15 μg/kg/minute, all ventilated
with TV <8 ml/kg). At baseline (nonperturbated system), correlation
analysis of NICOM vs PiCCOTD CO showed r2 of 0.78 (P <0.001). Bland–
Altman analysis evidenced a mean bias of 0.08 l/min (LOA –1.31 to 1.49).
The mean CO was 6.01 ± 1.48 l/min. In a perturbated system the bias of
NICOM vs PICCO PC was respectively–0.05 l/min (LOA –1.52 to 1.42) and
0.3 l/min (LOA –2 to 2.6) during PLR and PEEP test. The percentage error
was <30% in 92% of patients at baseline (nonperturbated system), in 92%
of patients during PLR and in 74% during PEEP test. In a nonperturbated
system the CO precision (calculated as 2 SD/mean over 10 consecutive
measurements) was 6.5 ± 6% and 6.7 ± 9% for NICOM and PiCCOTD,
respectively (NS). Precision for NICOM and PICCOPC was respectively 6.8
± 13% and 4.7 ± 10% during PLR and 7 ± 15% and 7.6 ± 15% during PEEP
Conclusions Although limited to a small number of patients, NICOM
and PICCO PC, calibrated by TD, seem to have comparable accuracy and
precision in CO monitoring in RSS Pts even in a perturbated system.
1. Squara P: Intensive Care Med 2007, 33:1191-1194.
2. Squara P: Crit Care 2009, 13:R125.
NICOM vs LiDCO™plus during changes in cardiac output in critically
M Cecconi1, G Monti2, S Vesconi2, M Hamilton1, M Grounds1, A Rhodes1
1St George ‘s Hospital, London, UK; 2Niguarda Hospital, Milan, Italy
Critical Care 2010, 14(Suppl 1):P100 (doi: 10.1186/cc8332)
Introduction NICOM (Cheetah) is a new non-invasive cardiac output
(CO) monitor based on bioreactance. We tested the agreement of NICOM
vs LiDCO™plus in terms of absolute CO values and of the ability to track
changes after therapeutic intervention in critically ill patients.
Methods Patients requiring haemodynamic monitoring were monitored
with LiDCO™plus and NICOM. Three measurements of CO by LiDCO
were used to measure CO at baseline and to calibrate PulseCO. After
fl uid challenges (FC = 250 ml colloid/5 minutes) or inotropic therapy
alterations, the change in stroke volume (SV) for PulseCO and NICOM CO
was recorded. Patients able to increase SV ≥10% as measured by PulseCO
were considered responders (R). Bland–Altman analysis was performed
for NICOM vs LiDCO CO at baseline. The coeffi cient of variation (CV) and
percentage error (PE) were calculated. ΔSV of NICOM vs PulseCO was
analysed with correlation analysis. In patients receiving FC, a ROC analysis
was performed to detect the sensitivity and specifi city of NICOM to track
ΔSV as measured by PulseCO CO.
Results Baseline haemodynamics in 30 patients enrolled: BA analysis for
NICOM vs LiDCO CO showed a mean bias of –0.18 l/minute (LOA –2.5 to
2.16). Mean CO was 5.8 l/minute, PE was 41%. Mean LiDCO CO CV was
6.8%. A total of 81 pairs of data were collected after FC or inotrope dose
change. Correlation analysis showed r2 of 0.55 (P <0.0001) for changes post
FC and r2 of 0.54 (P <0.006) post inotrope dose changes. ROC analysis for
NICOM CO in R and NR after a FC showed an area under the curve (AUC) of
0.8 (P <0.0001; Figure 1). An increase in NICOM SV >8% showed a sensitivity
of 76% and a specifi city of 75% to predict PulseCO changes >10%.
Conclusions NICOM demonstrated a moderate agreement with LiDCO
but showed excellent agreement with PulseCO in tracking CO changes
following therapeutic interventions.
Eff ect of cardiac arrhythmias on PulseCO calibration and
M Jonas1, E Mills2, C Wolff 2, T O’Brien2
1Southampton University Hospital, Southampton, UK; 2LiDCO Ltd, London, UK
Critical Care 2010, 14(Suppl 1):P101 (doi: 10.1186/cc8333)
Introduction Arrhythmias are common among high-risk surgical and
ICU patients. The PulseCO pressure waveform algorithm is used for
both LiDCO™plus and LiDCOrapid hemodynamic monitors, which are
frequently used to estimate cardiac output (CO) in critically ill patients.
Cardiac arrythmias could increase the variation of both the lithium dilution
(LiDCO) and/or the PulseCO measurement. At set-up the algorithm
is calibrated by comparing the PulseCO CO estimate, averaged over
30 seconds, with a known CO (normally LiDCO) to generate a calibration
factor (CF) . This study was designed to explore the eff ect of arrythmias
on the accuracy of CF generation in the PulseCO monitor.
Methods LiDCO™plus hemodynamic data fi les were obtained retro spectively
from a university hospital medical/surgical ICU. Files were separated into
those records with and without arrhythmia – defi ned as heart rate variation
>5% during at least one additional CF determination after monitor set-up.
Previous studies have established the coeffi cient of variation (CV) of a single
LiDCO determination at 8%  and the PulseCO measurement at 2.4% . A
combined CV, refl ecting the eff ect of calibration, is estimated at 8.5%, resulting
in an expected precision for the CF of 17%. Data were analysed for variation in
CF against HRV using linear regression and the Student’s t test.
Figure 1 (abstract P100). ROC analysis for NICOM CO in R and NR.
Critical Care 2010, Volume 14 Suppl 1
Results Twenty-eight records were collected and analysed. Twenty-one
records contained 32 post set-up calibration events. Of these 17 occurred
with HRV ≤5% (median = 1%, range: 0 to 5%) and 15 occurred while HRV
>5% (median: 19%, range: 7 to 26%). The average variation in CF during
HRV was 5.4 ± 4.0% and for high HRV was 8.9 ± 8.1% of the initial value.
The t test indicated no diff erence in the mean variation of CF (P = 0.162)
or median. There was no correlation between HRV and CF variation (r2 =
0.002). Ninety-one per cent (29/32) of the observed CF variation were less
than 17% of the initial CF value.
Conclusions CF determinations are not signifi cantly aff ected by HRV.
PulseCO estimates CO acceptably in the presence of arrhythmias.
Interpretation of the data is enhanced by using at least 30 second averaging.
1. Rhodes A, et al.: Functional Hemodynamic Monitoring Update in Intensive Care
and Emergency Medicine, volume 42, 2005:183-192.
2. Cecconi M, et al.: Intensive Care Med 2009, 35:498-504.
3. Kemps H, et al.: J Appl Physiol 2008, 105:1822-1829.
PulseCO consistency: variation in calibration factor over 24 and 48 hours
E Mills1, M Jonas2, C Wolff 1, T O’Brien1
1LiDCO Ltd, London, UK; 2Southampton University Hospital, Southampton, UK
Critical Care 2010, 14(Suppl 1):P102 (doi: 10.1186/cc8334)
Introduction The PulseCO pressure waveform algorithm is used for both
LiDCO™plus and LiDCOrapid hemodynamic monitors to estimate cardiac
output (CO). The accuracy of this CO estimate is achieved by comparing
(calibrating) the PulseCO with a known CO, for example from the lithium
dilution or LiDCO which scales the software algorithm and reduces the
bias to the actual CO . This calibration/scaling factor (CF) is patient
specifi c and should not signifi cantly change over a period of a few days as
it refl ects the patient’s aortic capacitance.
Methods LiDCO™plus hemodynamic data fi les were obtained
retrospectively from a university hospital medical/surgical ICU. Files
were screened to obtain records with at least 24 hours of continuous
hemodynamic data and at least one calibration at 24 hours following the
initial set-up calibration. Data were analysed for change in CF from initial
calibration over 24 and up to 48 hours. Relative change in CF was analyzed
for correlation with changes in SVR and CO.
Results Twenty-one records contained at least 24 hours of data with a
calibration at 24 hours. Eleven contained at least 48 hours of data and a further
calibration at 48 hours. The 32 calibrations were reviewed for consistency of
PulseCO and LiDCO results. The average variation in CF over 24 hours (7.4 ±
6.9% (mean ± SD)) and 48 hours (6.5 ± 6.2%) were similar (P = 0.362). Average
changes in SVR were 24.7 ± 27.4% (range: 0 to 130%); average CO changed by
21.4 ± 17% (range: 0 to 57%) over 24 hours. There was no correlation between
the variation in CF and changes in either CO or SVR.
Conclusions It is known that the estimated coeffi cient of variation of
a single measurement of LiDCO is 8%  and PulseCO is 2.4% . An
orthogonally combined CV, refl ecting the eff ects on CF, is estimated at
8.5%, or precision of 17%. Ninety-one per cent (29/32 ) of the observed
CF changes were less than 17% of the initial CF. The PulseCO CF remains
constant despite changes in SVR of up to 130% and CO of up to 57% over
periods of 24 to 48 hours.
1. Rhodes A, et al.: Functional Hemodynamic Monitoring Update in Intensive Care
and Emergency Medicine, volume 42, 2005:183-192.
2. Cecconi M, et al.: Intensive Care Med 2009, 35:498-504.
3. Kemps H, et al.: J Appl Physiol 2008, 105:1822-1829.
Performance of cardiac output measurement derived from arterial
pressure waveform analysis in patients undergoing triple-H-therapy
of cerebral vasospasms after subarachnoidal hemorrhage
SM Metzelder, R Kopp, M Fries, M Reinges, S Reich, R Rossaint, G Marx, S Rex
RWTH Aachen, Germany
Critical Care 2010, 14(Suppl 1):P103 (doi: 10.1186/cc8335)
Introduction The validity of an arterial waveform-based device for
measuring cardiac output (CO) without the need for invasive calibration
(FloTrac/Vigileo) in patients needing large doses of vasoactive medication
has not yet been thoroughly studied. We performed the present study
to assess the validity of both the second-generation and the third-
generation software compared with transpulmonary thermodilution
CO measurement using the PiCCO technology in patients undergoing
triple-H-therapy (hypertonia, hypervolemia, hemodilution) of cerebral
vasospasms after subarachnoidal hemorrhage.
Methods Twenty-three patients (18 females and fi ve males) were
included in this study. All of them were suff ering from a subarachnoidal
hemorrhage (Hunt&Hess grade I to V) due to rupture of a cerebral
aneurysm. Triple-H-therapy was initiated for the treatment of cerebral
vasospasm. Simultaneous CO measurements by bolus thermodilution and
the FloTrac/Vigileo device were obtained at baseline as well as 2 hours,
6 hours, 12 hours, 24 hours, 48 hours and 72 hours after inclusion. A
percentage error of 30% or less was established as the criterion for method
Results Patients received vasoactive support with 0.53 ± 0.46 μg/kg/
minute norepinephrine, resulting in a mean arterial pressure of 104 ±
13.6 mmHg and a systemic vascular resistance index of 1,741.17 ± 432.50
dyn·s/cm5/m2. One hundred and fi fty-one CO-data pairs were analyzed.
Transpulmonary thermodilution CO ranged from 5.18 to 14.28 l/minute
(mean 8.61 ± 1.93 l/minute) and FloTrac/Vigileo CO ranged from 4.1 to
13.7 l/minute (mean 7.62 ± 1.79 l/minute). Bias and precision (1.96SD of
the bias) were 0.99 l/minute and 2.46 l/minute, resulting in an overall
percentage error of 28.55%. Subgroup analysis revealed a percentage error
of 29.53% for 67 data pairs measured using the second-generation FloTrac
software and 26.44% for 84 data pairs analyzed by the third-generation
Conclusions In patients undergoing triple-H-therapy and needing
extensive vasoactive support, CO values obtained by arterial waveform
analysis showed good agreement with intermittent transpulmonary
thermodilution CO measurements, which was improved by the intro-
duction of a new software generation.
1. Mayer J, Boldt J, Wolf MW, Lang J, Suttner S: Cardiac output derived from
arterial pressure waveform analysis in patients undergoing cardiac
surgery: validity of a second generation device. Anesth Analg 2008,
Infl uence of systemic vascular resistance on cardiac output
measured by new non-invasive cardiac output monitor
K Yamashita, T Yamatabe, H Abe, M Yokoyama
Kochi Medical School, Kochi, Japan
Critical Care 2010, 14(Suppl 1):P104 (doi: 10.1186/cc8336)
Introduction Early manipulation of hemodynamic variables has
been reported to be able to improve the outcome of patients. Cardiac
output (CO) was an important parameter to understand the status of
hemodynamics. Recently, the pulse-contour method is widely used to
estimate CO, because it is non-invasive and easy to use. However, the
change in the systemic vascular resistance (SVR) aff ects CO measured
by the pulse-contour method. In this study, we evaluated the new non-
invasive cardiac output monitor  based on pulse pressure analysis
combined with pulse-wave transition time (estimated continuous CO;
esCCO) compared with the conventional thermodilution method under
a clinical setting.
Methods Twenty-fi ve surgical patients who underwent cardiac or
vascular surgery (ASA physical status 2) were enrolled in this study.
After anesthesia induction, radial arterial catheter and pulmonary artery
catheter were inserted. Intermittent cardiac output (ICO) was measured
by thermodilution method in triplicate and averaged (<5°C saline 10 ml
in each measurement) using Vigilance (Edwards Life Science, Irvine, CA,
USA). Echocardiogram, pulse oximetry and arterial blood pressure were
also monitored and connected to personal computer to calculate esCCO.
Bland and Altman plots were used to evaluate the percentage diff erence
in CO in relation to SVR.
Results One hundred matched sets of data were obtained. The limit of
agreement (bias ± 2SD of bias) was –2.9 ± 31.9%. Only fi ve measurements
were exceeded – 30% against ICO. Each SVR was 1,159, 1,376, 1,418, 2,567,
Critical Care 2010, Volume 14 Suppl 1
Conclusions The diff erence in most CO was within ±30% against the
reference values, although CO was underestimated by esCCO under
the relative high SVR. COs estimated by esCCO were acceptable under
the clinical setting. Therefore, we concluded that esCCO was a useful
algorithm to estimate CO.
J Clin Monit Comput 2004, 19:313-330.
Comparison of cardiac output values; pulse contour methods
against thermodilution technique
R De Wilde, B Geerts, P Van den Berg, J Jansen
Leiden University Medical Center, Leiden, the Netherlands
Critical Care 2010, 14(Suppl 1):P105 (doi: 10.1186/cc8337)
Introduction We evaluated the performance of the FloTrac/Vigileo system
(FCO) and simultaneously obtained cardiac output (CO) values with the
PiCCOplus (PCO), LiDCO™plus (LCO), Vigilance continuous pulmonary
artery thermodilution (CCO) against the intermittent pulmonary artery
thermodilution technique (ICO).
Methods Data were collected during standard postoperative care in
28 cardiac surgery patients. The cardiac output data were collected at
1 hour (T1), 2 hours (T2), 4 hours (T3), 8 hours (T4), 12 hours (T5), 24 hours
(T6), 36 hours (T7), and 48 hours (T8) after ICU admission. The number
of observations per patient varied between four and eight. Data were
analyzed with Bland–Altman statistics.
Results Reference cardiac output (ICO) ranged from 2.90 to 8.70 l/minute,
mean value of 5.12 (SD = 1.02) l/minute. Agreement between methods
against the reference method are also expressed in a percentage (LOA%);
that is, at low CO a small error and at high CO a higher error is observed.
The distribution of errors is diff erent among the methods (Figure 1). This is
confi rmed by Levine’s statistics, which showed signifi cant (F value = 20.5,
P <0.001) unequal homogeneity of the variances of the four methods. For
CCO bias and limits of agreement are 0.31 and –0.99 to 1.61. Bias and limits
of agreement of FCO, LCO and PCO are 0.59, –1.37 to 2.55; –0.05, –1.99 to
1.89 and –0.16, –2.60 to 2.28 l/minute, respectively.
Conclusions The performance of pulse contour methods has signifi cantly
increased in the past few years, which makes comparisons with older
publications invalid. The auto-calibrated FloTrac/Vigileo system can
replace the initially PAC-calibrated LiDCO and PiCCO system.
Continuous cardiac output measurement: eff ect of time
R De Wilde, B Geerts, P Van den Berg, J Jansen
Leiden University Medical Center, Leiden, the Netherlands
Critical Care 2010, 14(Suppl 1):P106 (doi: 10.1186/cc8338)
Introduction Calibration turns pulse contour methods of cardiac output
measurement from continuous to intermittent. We evaluated the necessity
to recalibrate pulse contour cardiac output methods; LiDCO™plus (LCO),
FloTrac/Vigileo (FCO), PiCCO (PCO) and continuous CO measurement with
pulmonary artery catheter (Vigilance) (CCO).
Methods In 28 cardiac surgery patients, data were collected at 1 hour
(T1), 2 hours (T2), 4 hours (T3), 8 hours (T4), 12 hours (T5), 24 hours (T6),
36 hours (T7), and 48 hours (T8) after ICU admission. Devices were only
calibrated at start of the investigation period. To compute eff ect against
time, at each time point, the CO values from LCO, FCO, PCO and CCO were
subtracted, and compared with COtd (ICO). Eff ect of time was quantifi ed
by calculating the slope values using linear regression. Slope values of the
regression line were tested against a horizontal line (no eff ect).
Results No change with time was found for CCO (slope = 0.02 l/minute/
hour, 95% CI –0.12 to 0.17, P = 0.763) nor for LCO (slope = 0.011 l/minute/
hour, 95% CI –0.11 to 0.03, P = 0.322). Time eff ect for PCO was (slope =
–0.017 l/minute/hour, 95% CI –0.032 to –0.001, P = 0.036) and for FCO
(slope = 0.029 l/minute/hour, 95% CI 0.003 to 0.055, P = 0.027). For the
LCO system, the data range indicated by the 95% CI crosses the threshold
value of 10% at 2, 12 and 24 hours, implying more than 2.5% of the data
points are outside the chosen 10% limits at these time points (Figure 1).
This occurs with PCO from 1 hour to 24 hours, with FCO at 4, 8, 12 and 24
hours, and with CCO at 4, 12 and 24 hours.
Conclusions PiCCO and FloTrac/Vigileo showed an eff ect with time. For
PiCCO, our fi ndings are in accordance with the publications of Boyle and
Figure 1 (abstract P105).
Critical Care 2010, Volume 14 Suppl 1
A comparison in cardiac output data: a random eff ects model for
R De Wilde, B Geerts, P Van den Berg, J Jansen
Leiden University Medical Center, Leiden, the Netherlands
Critical Care 2010, 14(Suppl 1):P107 (doi: 10.1186/cc8339)
Introduction A random eff ects model can be used to estimate the within-
subject variation after accounting for other observed and unobserved
variations, in which each subject has a diff erent intercept and slope over the
observation period. On the basis of the within-subject variance estimated
by the random eff ects model, Bland–Altman plots can be created.
Methods In 28 cardiac surgery patients, cardiac output data LiDCO™plus,
PICCO, FloTrac/Vigileo pulse contour and CCO (PAC-Vigilance) was
collected at 1 hour (T1), 2 hours (T2), 4 hours (T3), 8 hours (T4), 12 hours
(T5), 24 hours (T6), 36 hours (T7), and 48 hours (T8) after ICU admission and
compared against intermitted thermodilution COtd (ICO). Within patient
variation was calculated using Linear Mixed Models (SPSS). Percentage
error is calculated as: PE = [(2.SD of CO diff erence) / (COmean)] x 100%.
Results The results of the random eff ects model on continuous cardiac
output data are presented in Figure 1.
Conclusions The variation of the diff erences of the original measurement
will be underestimated by this practice because the measurement error is,
to some extent, removed. The bias between these two methods will not
be aff ected by averaging the repeated measurements.
1. Myles PS, Cui J: Br J Anaesthesia 2007, 99:309-311.
In vivo validation of a new transpulmonary thermodilution method
to assess global end-diastolic volume and extravascular lung water
K Bendjelid1, R Giraud1, N Siegenthaler1, F Michard2
1Geneva University Hospitals, Geneva, Switzerland; 2Edwards Lifesciences,
Critical Care 2010, 14(Suppl 1):P108 (doi: 10.1186/cc8340)
Introduction The downslope time (DSt) is part of the equation used
to derive global end-diastolic volume (GEDV) and extravascular lung
water (EVLW) from a transpulmonary thermodilution curve. DSt may
be aff ected by recirculation phenomena of the cold indicator, as those
observed in case of valvular regurgitation. Our goal was to validate a new
transpulmonary thermodilution method that does not depend on DSt.
Methods Eleven anesthetized and mechanically ventilated pigs (90 to
110 kg) were instrumented with a central venous catheter and a right
(PulsioCath; Pulsion, Munich, Germany) and a left (VolumeView; Edwards
Lifesciences, Irvine, CA, USA) thermodilution femoral arterial catheter. The
right femoral catheter was connected to a PiCCO2 monitor (Pulsion) and
used to measure COp (cardiac output), GEDVp and EVLWp using the method
based on the equation: GEDV = COp x (MTt – DSt). The left femoral catheter
was connected to the EV1000 monitor (Edwards) and used to measure COe,
GEDVe and EVLWe using the new method based on the equation: GEDVe =
f (S2/S1) x COe x MTt, where S1 and S2 are respectively the maximum up-
slopes and down-slopes of the dilution curve. One hundred and thirty-seven
measurements were done during inotropic stimulation (dobutamine),
during hypovolemia (bleeding), during hypervolemia (fl uid overload), and
after inducing acute lung injury (oleic acid).
Figure 1 (abstract P106). Stability range of ±10% indicated by dashed lines.
Figure 1 (abstract P107). Bland–Altman statistics from CO data: random
eff ects model (LMM).
Critical Care 2010, Volume 14 Suppl 1
Results COp and COe ranged from 3.1 to 15.4 and from 3.4 to 15.1 l/
minute, respectively. COp and COe were closely correlated (r2 = 0.99),
mean bias (± SD) was 0.18 ± 0.29 and percentage error was 7%. GEDVp
and GEDVe ranged from 701 to 1,629 and from 774 to 1,645 ml. GEDVp
and GEDVe were closely correlated (r2 = 0.79), mean bias was –11 ± 78 and
percentage error was 14%. EVLWp and EVLWe ranged from 507 to 2379
and from 495 to 2,222 ml. EVLWp and EVLWe were closely correlated (r2 =
0.97), mean bias was –5 ± 72 and percentage error was 15%.
Conclusions In animals, and over a very wide range of values, the new
transpulmonary thermodilution method is as reliable as the PiCCO
method to assess cardiac output, cardiac preload and lung water during
inotropic stimulation, bleeding, volume loading and lung injury.
Cardiac index derived from arterial pressure waveform:
uncalibrated analysis vs once-only calibrated analysis
H Einwaechter, S Hiemer, M Treiber, B Saugel, V Phillip, RM Schmid,
Klinikum rechts der Isar der TU München, Germany
Critical Care 2010, 14(Suppl 1):P109 (doi: 10.1186/cc8341)
Introduction As the need for recalibration and the best time point to
recalibrate has been a matter of debate since the introduction of the PiCCO
monitor (Pulsion, Germany), we set out to analyze the performance of its
pulse contour (PC) analysis without recalibration over a 24-hour period.
Methods We studied the cardiac index (CI) over a 24-hour period in
eight nonoperative patients admitted to our ICU. Seven CI measurements
(median number; every 4 hours) by thermodilution (TD) were performed
in each patient (in triplicate), PC-derived data were recorded continuously.
We used a special PiCCOplus monitor with a disabled auto-recalibrate
feature; that is, TD did not lead to an automatic calibration of the PC
analysis. Calibration was only performed manually once at the start of the
analysis for each patient. Later TD measurements were recorded but had
no eff ect on the CIPC. An additional comparison was performed using
the FloTrac/Vigileo System (Edwards, USA), which does not need manual
recalibration and instead recalibrates itself every 60 seconds based on
the arterial waveform. The FloTrac/Vigileo monitor used was a second-
generation device (software version 1.14). Both the pressure transducers
of the PiCCO and the FloTrac were connected in series to the same femoral
Results A total of 59 TD measurements of CI (CITD) were compared with
FloTrac CI measurements (CIFloTrac) and PC-derived CI measurements
(CIPC) from the PiCCO device. CITD ranged from 2.1 to 7.6 l/minute/m2
(mean 4.3 ± 1.39 l/minute/m2). PC (PiCCO) compared with TD: bias and
precision (1.96SD of the bias) were 0.18 l/minute/m2 and ±1.35 l/minute/
m2, the percentage error was 30.9%. FloTrac compared with TD: bias and
precision were –0.75 l/minute/m2 and ±1.79 l/minute/m2, the percentage
error was 46.2%. The mean absolute value of the diff erence |CITD – CIPC|
and |CITD – CIFloTrac| was 0.48 ± 0.49 l/minute/m2 for PiCCO pulse contour
values and 0.97 ± 0.76 l/minute/m2 for FloTrac/Vigileo values, respectively.
This higher diff erence of CIFloTrac from CITD was signifi cant (P = 0.0002)
and remained signifi cant even when only data from the last time point
(24 hours) was analyzed (P = 0.03).
Conclusions PC-derived CI values obtained over a 24-hour period from
the PiCCO device after only one manual calibration provide signifi cantly
better estimates of CI than measurements by the FloTrac/Vigileo device,
even after a calibration-free interval of 24 hours.
Cardiac output monitoring during abdominal aortic cross
clamping: a comparison between Vigileo/FloTrac system and
D Simion, M Lecca, M Dan, A Martini, N Menestrina, L Gottin
University of Verona, Verona, Italy
Critical Care 2010, 14(Suppl 1):P110 (doi: 10.1186/cc8342)
Introduction Cardiac output (CO) monitoring is one of the key points in
the hemodynamic evaluation of critically ill patients, and can be useful in
various settings of high-risk surgery. There is a lack of evidence that the
extensive use of invasive devices in the hemodynamic monitoring has a
good impact in terms of outcome , and less invasive systems have been
proposed. Our aim was to compare the CO estimated by Vigileo/FloTrac
with the blood fl ow in thoracic aorta as measured by transoesophageal
Doppler in patients undergoing open abdominal aortic aneurysm
repair, during the aortic cross-clamping (AoX) phase. We have measured
the Augmentation Index (AI), a parameter related to vascular stiff ness,
using the applanation tonometry method, in order to have a better
understanding of the eff ect of AoX on blood pressure waves.
Methods We enrolled 10 consecutive patients (10 men; age 66 ± 6 years)
undergoing elective open AAA repair (ASA II to III) under general
anesthesia. Radial arterial access was used for semi-invasive determination
of blood pressures and CO (APCO) with the Vigileo. An esophageal
Doppler was positioned after clinical stabilization. Applanation tonometry
was measured just before and after the aortic clamping.
Results We found a signifi cant (P <0.05) increase in CO reported by
Vigileo/FloTrac system in the post-clamping phase, when compared
with the pre-clamping and basal phases, while the blood fl ow in thoracic
aorta resulted decreased, according with the theory of redistribution of
fl uids in the splanchnic venous vasculature . There was an important
contribution of the wave refl ection to the aortic pulse pressure wave after
the AoX, as expressed by a signifi cant increase in the AI.
Conclusions The Vigileo/FloTrac system appears to overestimate CO after
AoX when compared with the measure of blood fl ow in thoracic aorta,
and this result could be infl uenced by the pulse pressure wave refl ection
occurring after clamping. In high-risk surgical settings, other situations of
rapid change of systemic resistance vessels could be similarly misread,
thus suggesting the necessity of a more tailored Vigileo algorithm.
1. Shah MR et al.: Impact of the pulmonary artery catheter in critically ill
patients: meta-analysis of randomized clinical trials. JAMA 2005,
2. Gelman S: The pathophysiology of aortic cross-clamping and unclamping.
Anesthesiology 1995, 82:1026-1060.
Stroke volume index assessment using two minimal invasive
devices during hemodynamic postoperative optimization
M Costa, T Cecconet, P Chiarandini, L Pompei, S Tomasino, S Buttera,
G Della Rocca
University of Udine, Italy
Critical Care 2010, 14(Suppl 1):P111 (doi: 10.1186/cc8343)
Introduction Postoperative hemodynamic optimization has been proved
to reduce morbidity in high-risk patients . Nowadays stroke volume
index (SVI) monitoring is available with diff erent less invasive techniques
that have shown diff erent levels of agreement and precision with the
pulmonary artery catheter . The aim of this study was to evaluate
agreement and precision between SVI obtained with a calibrated
(LiDCO™plus; LiDCO Ltd, Cambridge, UK) and an uncalibrated pulse
contour analysis device (FloTrac/Vigileo; Edwards Lifesciences, Irvine, CA,
USA), in patients undergoing postoperative hemodynamic optimization.
Methods Patients undergoing a hemodynamic optimization protocolized
care according to a previous published trial  to reach an oxygen delivery
Figure 1 (abstract P111). Bland and Altman analysis.
Critical Care 2010, Volume 14 Suppl 1
index >600 ml/minute/m2 after abdominal surgery were enrolled. After
calibration of the LiDCO™plus, SVI data obtained from LiDCO™plus, and
FloTrac/Vigileo (version 1.07) were recorded every 15 minutes for 6 hours.
Agreement and precision between SVI obtained with LiDCO (SVILI) and
SVI obtained with Vigileo (SVIFT) were evaluated with Bland and Altman
Results Thirteen patients (nine males, four females), mean age 68.5
(± 28.3) years were enrolled into the study. Two hundred and seventy SVI
data pairs were analyzed. Bias was 1.79 ml/m2, with a precision (1.96SD of
the bias) of 25.1 ml/m2 (Figure 1).
Conclusions SVI obtained from the uncalibrated low-invasive, pulse
contour analysis technique seems as accurate as the calibrated technique
in a clinical hemodynamic protocolized setting to increase oxygen delivery
in postoperative high-risk patients.
1. Pearse R, et al.: Crit Care 2005, 9:R687-R693.
2. Hofer CK, et al.: Curr Opin Crit Care 2007, 13:308-331.
Non-invasive cardiac output monitoring in children:
Y Vandormael, T Vu, M Gewillig, D Vlasselaers
University Hospitals Leuven, Belgium
Critical Care 2010, 14(Suppl 1):P112 (doi: 10.1186/cc8344)
Introduction Continuous noninvasive cardiac output (CO) provides
valuable information for patient management. Non-invasive cardiac
output monitoring (NICOM) measures CO based on chest bioreactance
and is validated in adults . Validated data in children are lacking. Our
objective was to evaluate NICOM in children with pulmonary artery
catheter thermodilution (PAC) as reference.
Methods Paired CO values using NICOM and TD were recorded during
cardiac catheterization in children with congenital heart disease. Children
with intracardiac or extracardiac shunts were excluded. PAC was inserted
through the femoral vein and CO was measured after bolus injection
of 5 ml iced saline. NICOM was connected in accordance with the
Results Nineteen pairs of CO measurements were collected in nine
patients. Mean age was 4.6 years (range: 0 to 12 years) and mean weight
16.8 kg (range: 4.8 to 34 kg). Cardiac diagnosis was dilated cardiomyopathy
or interventional procedures. Mean CO values were 2.18 l/minute (PAC)
and 1.88 l/minute (NICOM). Correlation between two methods was
signifi cant (r = 0.826; P = 0.0005). Bland–Altman analysis shows a mean
diff erence between the reference method and NICOM of +0.33 l/minute.
Ninety-fi ve percent of measurements were inside the limits of agreement
(±1.96SD) but these limits were broad (–1.24 to 1.96 l/minute) (Figure 1).
Conclusions CO measurements with NICOM and PAC show a signifi cant
correlation. Bland–Altman demonstrates an acceptable agreement;
however, the limits of agreement are broad. Depending on the CO range,
NICOM reveals a trend to systematically overestimate or underestimate
CO. Additional studies in larger and more heterogeneous pediatric patient
populations are warranted for further validation.
1. Squara P, et al.: Intensive Care Med 2007, 33:1191-1194.
Response of NICOM stroke volume to passive leg raising to predict
fl uid responsiveness in critically ill patients with spontaneous
B Lamia1, A Cuvelier1, PL Declercq1, LC Molano1, MR Pinsky2, JF Muir1
1Rouen University Hopsital, Rouen School of Medecine, Rouen, France;
2University of Pittsburgh Medical Center, Pittsburgh, PA, USA
Critical Care 2010, 14(Suppl 1):P113 (doi: 10.1186/cc8345)
Introduction Volume responsiveness cannot be predicted by the
respiratory variation in arterial pressure in hemodynamically unstable
patients with spontaneous breathing activity. The NICOM device (Reliant®;
Cheetah) (bioreactance technique) is a totally non-invasive hemodynamic
monitoring technique for the measurement of stroke volume. Our
objective was to test whether volume responsiveness could be predicted
by the response of stroke volume measured by the NCOM device to
passive leg raising (PLR) in patients with spontaneous breathing activity.
Methods Prospective study in the respiratory critical care of a university
hospital. Eleven patients with spontaneously breathing activity considered
for volume expansion. An increase in stroke volume index (SVi) of 15% or
more after volume expansion defi ned a responder patient. We measured
the response of the bioreactance stroke volume to PLR and to saline
infusion (500 ml over 15 minutes).
Results The proportional changes in NiCOM-SVi induced by PLR were
correlated with the proportional changes in NICOM-SVi induced by
volume expansion (r = 0.67, P = 0.02). The proportional changes in
NICOM-cardiac index (CI) induced by PLR were also correlated with the
proportional changes in NICOM-CI induced by volume expansion (r = 0.63,
P = 0.03). A PLR-induced increase in stroke volume of 9% or more predicted
an increase in stroke volume of 15% or more after volume expansion with
a sensitivity of 100% and a specifi city of 80%.
Conclusions The response of NICOM-stroke volume to PLR was a good
predictor of volume responsiveness. In our hemodynamically unstable
patients with spontaneous breathing activity, fl uid responsiveness can be
assessed totally non-invasively with a bioreactance device.
Global end-diastolic volume and its correlation to cardiac index
inside and outside normal values
W Huber, S Mair, B Saugel, V Phillip, H Einwaechter, R Schmid
Klinikum rechts der Isar der Technischen Universität München, Germany
Critical Care 2010, 14(Suppl 1):P114 (doi: 10.1186/cc8346)
Introduction Transpulmonary thermodilution (TPTD)-derived volumetric
parameters such as global end-diastolic volume (GEDI) and ELWI have
been established as hemodynamic cornerstones for assessment of
preload (GEDI) and pulmonary hydration. Normal values of GEDI have
been created more than a decade ago based on studies in pre-selected
patients. Therefore, it was the aim of our prospective study to investigate
the correlation of GEDI to cardiac index (CI) in clinical routine.
Methods Over a 6-month period all 1,574 routine TPTD measurements
in 78 consecutive patients (APACHE II: 23.5 ± 8.6) of an internal ICU with a
PiCCO catheter were prospectively documented and analysed: correlation
(Spearman) and multiple regression analysis; SPSS 17.0.
Results Including all 1,574 measurements, CI was univariately correlated
to GEDI (r = 0.251; P <0.001), dPmax (r = 0.221; P <0.001) and heart rate (r =
0.102; P <0.001), but not to CVP (r = 0.001; P = 0.962). The correlation of GEDI,
dPmax and heart rate to CI was confi rmed in multivariate analysis (P <0.001
for all three variables). Changes in CI (Delta-CI) were univariately correlated
to changes in GEDI (r = 0.414), dPmax (r = 0.240) and ELWI (r = 0.152; P <0.001
for all comparisons). In a multivariate analysis of all measurements, Delta-
CI was independently associated with changes in GEDI (P <0.001), dPmax
(P <0.001) and CVP (P = 0.017). Subgroup analysis of all measurements
Figure 1 (abstract P112). Bland–Altman analysis.
Critical Care 2010, Volume 14 Suppl 1
with GEDI below the lower normal level 680 ml/kg/m2 demonstrated an
independent association of CI to GEDI (P <0.001), dPmax (P <0.001) and ELWI
(P = 0.041) but not to CVP. Similarly, Delta-CI was independently associated
with changes in GEDI and dPmax (P <0.001). Similar results were found for
the measurements with GEDI within the normal range (680 to 800 ml/kg/
m2): signifi cant and independent correlation of CI to GEDI (P <0.017) and
dPmax (P <0.001). Changes in CI were independently correlated to changes
in GEDI (P <0.001), dPmax (P <0.001) and CVP (P = 0.035). Interestingly,
even in measurements with GEDI >800 ml/kg/m2, CI was independently
correlated to GEDI (P = 0.009) and dPmax (P <0.001). Changes in CI in this
group were independently associated with changes in dPmax and GEDI
(P <0.001).In the subgroup of measurements with GEDI >1,000 ml/kg/m2
there was no correlation of any parameter to CI, however changes in CI
were independently correlated to changes in GEDI (P <0.001) and dPmax
(P = 0.003).
Conclusions GEDI and dPmax and their changes have an independent and
positive correlation to CI and its changes even in patients with increased
Relationship of stroke volume variation, pulse pressure variation
and global end-diastolic volume in patients undergoing brain
A Rieß1, S Wolf2, C Lumenta2, L Schürer2, P Friederich1
1Klinikum Bogenhausen, Department of Anesthesiology, München, Germany;
2Department of Neurosurgery, München, Germany
Critical Care 2010, 14(Suppl 1):P115 (doi: 10.1186/cc8347)
Introduction Monitoring intravascular volume in patients with intra-
cranial pathology is often mandatory for maintaining hemodynamic
stability [1,2]. Cyclic changes in cardiac stroke volume [1,3] and pulse
pressure induced by positive pressure ventilation as well as target values
of global end-diastolic volume index (GEDVI) (ml/m2)  allow volume
therapy guidance. The relationship between stroke volume variation (SVV)
(%) and pulse pressure variation (PPV) (%), as well as between SVV or PPV
and values of GEDVI has not been established in patients with intracranial
Methods In this prospective investigation the correlation between
dynamic and static hemodynamic parameters of 38 patients undergoing
brain surgery was studied. Measurements were performed using the
PiCCO technology. For statistical analysis, nonparametric correlation
analysis and hypothesis testing were applied.
Results SVV correlated signifi cantly with PPV (r2 = 0.87, P <0.001). Neither
SVV (r2 = 0.14, P = 0.13) nor PPV (r2 = 0.07, P = 0.81) correlated with GEDVI.
Threshold values for SVV (9.5%, 11.6%) as well as for PPV (12.5%) allowed
discrimination between groups with signifi cantly diff erent values of
stroke volume index, while failing to discriminate between groups with
signifi cantly diff erent values of GEDVI. Dichotomizing the patients into
groups of GEDVI ≤680 ml/m2 and >680 ml/m2 resulted in groups with
signifi cantly diff erent values of stroke volume index as well while failing
to discriminate between groups with signifi cantly diff erent values of SVV
Conclusions Static (GEDVI) and dynamic (SVV, PPV) parameters of cardiac
preload may refl ect diff erent properties of the cardiovascular system. The
combination of SVV, PPV, and GEDVI may off er more precise information
on the cardiovascular system than either parameter alone.
1. Berkenstadt H, et al.: Anesth Analg 2001, 92:984-989.
2. Mutoh T, et al.: Stroke 2009, 40:2368-2374.
3. Marik PE, et al.: Crit Care Med 2009, 37:2642-2647.
The value of pulse pressure variation to predict volume response in
patients ventilated with low VT
GF Friedman, CD Costa, SR Vieira, L Fialkow
Hospital de Clínicas de Porto Alegre, Brazil
Critical Care 2010, 14(Suppl 1):P116 (doi: 10.1186/cc8348)
Introduction The prediction value of pulse pressure variation (ΔPP) in
patients ventilated with low VT is not well studied. A ΔPP of 12 to 13%
is validated as a predictor of volume response in several studies, but in
patients ventilated with VT >8 ml/kg. One study has shown that the ΔPP
of 12 to 13% does not predict volume response in patients ventilated with
a low VT. We hypothesized that a lower cut-off value for ΔPP can predict
volume response in patients with low VT.
Methods Thirty-seven adult patients mechanically ventilated with a tidal
volume <8 ml/kg (PBW), without cardiac arrhythmias, with a pulmonary
artery catheter and a peripheral arterial catheter were included. An
increase in cardiac index (thermodilution)) >15% output after a fl uid
challenge (Crystalloid 1,000 ml or Colloid 500 ml) was considered a
Results Seventeen patients were responders. The ROC curve showed that
the best cut-off value for ΔPP was 10% (ROC area = 0.74, 95% CI: 0.51 to 0.9;
sensitivity 53%, specifi city 95%, positive likelihood ratio 9.4 and negative
0.34).Twelve patients consisted of a heterogeneous group of patients
(liver transplant, acute pancreatitis, aortic surgery). Among 25 septic
shock patients, a ΔPP >10% showed a ROC area of 0.84 (sensitivity 78%,
specifi city 93%). In any case, the greater ΔPP, the greater the fl uid response.
ΔPP >10% was a better predictor than CVP or PAOP.
Conclusions ΔPP has a limited value in patients ventilated with low VT.
However, a ΔPP >10% may help identify septic shock patients that will
respond to a fl uid challenge.
1. Vincent JL, et al.: Pulse pressure variations to predict fl uid responsiveness:
Infl uence of tidal volume. Intensive Care Med 2005, 31:517-523.
Pre-ejection period is a reliable parameter to estimate cardiac
preload in a hemorrhagic shock
R Giraud, N Siegenthaler, JA Romand, K Bendjelid
Hôpitaux Universitaires de Genève, Switzerland
Critical Care 2010, 14(Suppl 1):P117 (doi: 10.1186/cc8349)
Introduction We have already demonstrated that in mechanically
ventilated patients, the respiratory change in the pre-ejection period
(ΔPEP) is a reliable dynamic index for the prediction of increase in cardiac
output after volume infusion . However, in an animal study, Kubitz and
colleagues showed that the pre-ejection period is not sensitive to the
changes in intravascular volume status .
Methods This study investigated the infl uence of changes in intravascular
volume status on ΔPEP. In 17 pigs, ECG, arterial pressure and cardiac output
derived from a Swan–Ganz catheter were recorded. Measurements were
performed during normovolaemic conditions, after haemorrhage (25 ml/
kg) and following re-transfusion (25 ml/kg) with constant tidal volume
(10 ml/kg) and respiration rate (15/minute).
Figure 1 (abstract P117). Box plot representing pulse pressure variations
(PPV) (%) and pre-ejection period variations (ΔPEP) (%) at the three times
of the protocol. §P <0.05, †P <0.05.
Critical Care 2010, Volume 14 Suppl 1
Results At baseline, respiratory changes in pulse pressure (PPV) and ΔPEP
were both <12%. PPV signifi cantly correlated with ΔPEP (r = 0.96, P <0.001).
Volume loss induced by haemorrhage increased PPV and ΔPEP. Moreover,
during this state, PPV correlated with ΔPEP with a signifi cant correlation
coeffi cient (r = 0.88, P <0.001). Retransfusion signifi cantly decreased PPV
and ΔPEP and PPV signifi cantly correlated with ΔPEP (r = 0.94, P <0.001)
Conclusions Available correlations between PPV and ΔPEP at each time
of the study were observed, meaning that ΔPEP is a reliable parameter to
estimate the changes in intravascular volume status.
1. Bendjelid K, Suter PM, Romand JA: The respiratory change in preejection
period: a new method to predict fl uid responsiveness. J Appl Physiol 2004,
2. Kubitz JC, Kemming GI, Schultheib G, Starke J, Podtschaske A, Goetz AE,
Reuter DA: The infl uence of cardiac preload and positive end-expiratory
pressure on the pre-ejection period. Physiol Meas 2005, 26:1033-1038
Predictive value of pulse pressure variation for fl uid responsiveness
after maneuver to change tidal volume in patients with protective
F Machado, F Freitas, M Assuncao, B Mazza, M Jackiu
Federal University of São Paulo, Brazil
Critical Care 2010, 14(Suppl 1):P118 (doi: 10.1186/cc8350)
Introduction After the early phase of sepsis, excessive fl uid administration
may worsen pulmonary edema and prolong mechanical ventilation .
Accurately predicting fl uid responsiveness obviates unnecessary fl uid
loading, and helps to detect patients who may benefi t from a volume
expansion. Pulse pressure variation (DPP) is a reliable predictor of fl uid
responsiveness in mechanically ventilated patients only when tidal volume
is at least 8 ml/kg . The aim of this study was to evaluate the predictive
value of DPP for fl uid responsiveness after a maneuver to change tidal
volume to 8 ml/kg in patients ventilated with 6 ml/kg.
Methods Prospective clinical study in 40 patients ventilated with 6 ml/kg
after resuscitation phase of severe sepsis and septic shock. Fluid challenge
was indicated by the attending physician (7 ml/kg of 6% hydroxyethyl
starch 130/0.4). Complete hemodynamic measurements including DPP
(DPP 6 ml/kg) were obtained at baseline. The tidal volume was then
changed to 8 ml/kg and the DPP (DPP 8 ml/kg) was measured after
5 minutes. The ventilatory settings were returned to 6 ml/kg before fl uid
challenge. Patients whose cardiac output (CO) increased by ≥15% were
considered to be fl uid responders. Receiver operating characteristic (ROC)
curve analysis was used to evaluate the predictive value of DPP.
Results In 19 patients (responders), CO increased by >15% after fl uid
infusion. Fluid responsiveness was better predicted with DPP 6 ml/kg (ROC
curve area 0.92 ± 0.05) than with pulmonary artery occluded pressure
(0.56 ± 0.09) and right atrial pressures (0.74 ± 0.08). Increasing tidal volume
to 8 ml/kg did not improved prediction as the ROC curve area with DPP
8 ml/kg was 0.94 ± 0.03. The best cut-off values defi ned by the ROC curve
analysis was 6.5% and 10.5% for DPP 6 ml/kg and DPP 8 ml/kg, respectively.
Conclusions The maneuver to change tidal volume to 8 ml/kg in
patients ventilated with protective ventilatory strategy to better predict
fl uid responsiveness is not useful. Fluid responsiveness can be correctly
predicted in patients ventilated with tidal volume of 6 ml/kg.
1. Wiedemann HP, et al.: N Engl J Med 2006, 354:2564-2575.
2. De Backer D, et al.: Intensive Care Med 2005, 31:517-523.
Does stroke volume increase after a fl uid challenge? A study on the
management of patients undergoing major head and neck free fl ap
surgery: preliminary data
L Wijayasiri, D Garewal, M Khpal, A Rhodes, A Dewhurst, M Cecconi
St George’s Hospital, London, UK
Critical Care 2010, 14(Suppl 1):P119 (doi: 10.1186/cc8351)
Introduction Major head and neck surgery involving reconstructive free
fl aps for oropharyngeal cancers are complex and prolonged operations
during which appropriate fl uid management can become diffi cult.
Potential adverse eff ects of fl uid mismanagement in this group of patients
include fl ap hypoperfusion related to hypovolaemia or fl ap oedema
and deterioration in alveolar–arterial gradients related to excessive
fl uid administration. This study looked at ongoing standard practice, to
determine whether the use of a cardiac output monitor could improve
fl uid management in this subset of patients.
Methods Single-blinded, prospective observational study conducted
on consecutive adult patients undergoing major head and neck
reconstructive free fl ap surgery. All patients were anaesthetised by the
same individual, using a standardised technique. Volume-controlled
positive pressure ventilation was initiated in all patients. Patients received
maintenance crystalloid fl uids at a rate of 5 ml/kg/hour. Additional
fl uid challenges (250 ml crystalloid boluses given over 5 minutes) were
administered at the discretion of the anaesthetist. A priori criterion of fl uid
responsiveness was defi ned as an increase in stroke volume (SV) >10%
as measured with the LiDCOrapid after a fl uid challenge. The anaesthetist
was blinded to the LiDCOrapid data and observations were made by an
independent investigator. Data were collected on: heart rate (HR), mean
arterial pressure (mAP) and central venous pressure (CVP).
Results Forty-seven fl uid boluses were assessed. The median age of the
patients was 72 years (range 68 to 81 years) and their median weight was
71.2 kg (range 63 to 88 kg). The ventilatory set-up used a median tidal
volume of 7 ml/kg (range 450 to 600 ml). Fifteen out of 47 (32%) of the
fl uid challenges were positive when assessed against the change in stroke
volume. When comparing the fl uid responders with the nonresponders,
there were no diff erences in HR (62 ± 10 bpm vs 62 ± 10 bpm), mAP (63 ±
6 mmHg vs 63 ± 7 mmHg) or CVP (8 ± 3 mmHg vs 10 ± 3 mmHg).
Conclusions This preliminary report suggests that only 32% of fl uid
challenges given in theatre were eff ective in increasing the SV >10% and
potentially two-thirds of the fl uid challenges may have been detrimental.
This can be seen only if SV is monitored continuously. If further data
confi rm this, LiDCOrapid may be useful to guide fl uid administration in
order to optimise the SV, thereby minimizing the risk of fl uid overload.
Optimizing stroke volume and oxygen delivery in elective
abdominal aortic surgery
J Bisgaard1, E Rønholm1, T Gilsaa1, P Toft2
1Kolding Hospital, Kolding, Denmark; 2Odense University Hospital, Odense,
Critical Care 2010, 14(Suppl 1):P120 (doi: 10.1186/cc8352)
Introduction Patients undergoing elective abdominal aortic surgery
(EAAS) are at risk of developing complications due to preoperative
co-morbidity, surgical trauma, blood loss and infl ammatory injury .
Individualized goal-directed therapy (IGDT) has been proposed to
improve outcome in patients undergoing high-risk surgery . The aim of
this study was to investigate whether IGDT, targeting stroke volume (SV)
and oxygen delivery (DO2), can be performed safely in EAAS.
Methods Sixty-three EAAS patients were randomized to IGDT or
conventional therapy. The LiDCO™plus system was used for SV and DO2
monitoring. SV was optimized by 250 ml fl uid challenges intraoperatively and
the fi rst 6 hours postoperatively. DO2 was optimized 6 hours postoperatively
targeting a DO2I level of 600 ml/min/m2, by infusion of dobutamine, if
necessary. Hemodynamic data were collected at baseline (t0) preoperatively
(t1), before aortic cross-clamping (t2), at the end of surgery (t3), and the fi rst
6 hours postoperatively (p1 to p6). All patients were monitored with fi ve-
lead ECG during dobutamine infusion and dosage was reduced at signs
of ischemia or heart rate >20% above baseline. Dobutamine dosage was
limited to a maximum of 10 μg/kg/minute.
Results The mean SVI level was 19.4% higher at p4 to p6 in the IGDT group
compared with the control group (P = 0.02), and 12.1% higher in the entire
intervention period (t1 to p6) (P = 0.07). The mean DO2I was 18.0% higher
at p4 to p6 (P = 0.01) and 12.9% higher in the entire intervention period (t1
to p6) in the IGDT group (P = 0.03). Mean arterial pressure and heart rate
did not diff er signifi cantly (P = 0.12 and P = 0.21). There was no diff erence in
the frequency of postoperative cardiac complications between the groups.
Conclusions The results of this study demonstrate that IGDT targeting SV
and DO2 can be performed safely in patients undergoing EAAS. Whether
this intervention is benefi cial is being evaluated in the current study.
Critical Care 2010, Volume 14 Suppl 1
1. Dardik et al.: Results of elective abdominal aortic aneurism repair in the 1990s:
A population-based analysis of 2335 cases. J Vasc Surg 1999, 30:985-995.
2. Bundgaard-Nielsen et al.: Monitoring of perioperative fl uid administration by
individualized goal-directed therapy. Acta Anaestesiol Scand 2007, 51:331-340.
Oxygen saturation determined from the mouth is an early indicator
of central hypovolemia in humans
A Lima, M Alamyar, C Ince, J Bakker
Erasmus MC University Medical Centre, Rotterdam, the Netherlands
Critical Care 2010, 14(Suppl 1):P121 (doi: 10.1186/cc8353)
Introduction Studies have suggested that tissue oxygenation (StO2)
measured on the thenar muscle is not sensitive to track acute changes
in hemodynamics due to reductions in central blood volume. We aimed
to investigate the feasibility of StO2 measurements in the mouth as a
quantitative indicator comparable with StO2 measurements obtained
from the thenar eminence during changes in central blood volume (CBV).
Methods We performed a head-up tilt (HUT) test in 10 healthy volunteers
as an experimental model to reduce CBV. StO2 was continuously measured
using two devices (InSpectra model 650): a multiple depth optical probe
was placed over the thenar eminence (15 and 25 mm) and a 1-mm probe
was placed in the mouth. Subjects were placed on an electrically driven
tilt table with a footboard. After 5 minute baseline measurements in the
supine position, the table was tilted up to 70° and returned to the supine
position after 10 minutes. StO2 readings were analyzed at the lowest stroke
Results All subjects (mean age: 23 ± 6; six males) tolerated well the supine
and head-up positions. Cardiac output signifi cantly decreased in the HUT
position; simultaneous decrease in StO2 was observed in the mouth, but
not in the thenar. The general results of the HUT test are shown in Tables
1 and 2.
Table 1 (abstract P121). Hemodynamics in the baseline and in the head-up
*P <0.05 vs baseline.
Table 2 (abstract P121). StO2 in the baseline and in the head-up tilt (HUT)
Baseline HUT Baseline 2 StO2 15 thenar
StO2 25 thenar
76 ± 6
76 ± 5
88 ± 3
75 ± 6
75 ± 6
78 ± 3*
78 ± 7
78 ± 8
87 ± 3
*P <0.05 vs baseline 1 and 2.
Conclusions Near-infrared spectroscopy can be used in the mouth to
track changes in central blood volume. Our results showed that buccal
StO2 is an earlier indicator of acute hemodynamic responses to the HUT-
induced central hypovolemia than thenar StO2.
Plethysmographic indices as predictors of fl uid responsiveness: a
CM Marano, FC Cavallaro, CS Sandroni, AD Dell’Anna, MA Antonelli
Catholic University School of Medicine, Rome, Italy
Critical Care 2010, 14(Suppl 1):P122 (doi: 10.1186/cc8354)
Introduction The aim of the study was to assess the ability of respiratory
variations in pulse oximetry plethysmographic waveform amplitude
(ΔPOP) to predict the increase of cardiac output (CO) after fl uid infusion
(fl uid responsiveness).
Methods Two authors independently performed a search iterated until
November 2009 in MEDLINE, Embase and Cochrane Database using
keywords: ‘fl uid OR preload OR volume responsiveness’, ‘cardiovascular
monitoring’, ‘fl uid challenge’, ‘functional hemodynamic monitoring’, ‘dynamic
indices OR indexes’, ‘delta POP’, ‘pleth index’, ‘plethysmographic waveform’.
Predictive value of ΔPOP was estimated by: diff erence in mean value of
ΔPOP between responders and nonresponders; correlation coeffi cient
between pre-infusion ΔPOP and CO increase after fl uids; and sensitivity,
specifi city and area under the ROC curve (AUC) for ΔPOP to predict a
responder state. A meta-analysis was performed using Comprehensive
Meta-Analysis v. 2.2. Pooled values of diagnostic odds ratio (DOR), sensitivity,
specifi city and summary ROC (SROC) curve were calculated using MetaDiSC
v. 1.4. Heterogeneity was evaluated with Q and I2 tests.
Results From the initial dataset of 839 records we identifi ed six articles
[1-6] on 135 patients to whom 195 fl uid boluses were administered. All
patients were in sinus rhythm and adapted to a ventilator. An increase
of cardiac index or stroke volume index >10 to 15% defi ned responders.
Mean responder rate was 58.9%. Pooled diff erence in mean was 10% (95%
CI 5.8 to 14.2), correlation coeffi cient 0.59 (0.41 to 0.73), AUC 0.85 (0.76 to
0.94), sensitivity 81.1% (72.5 to 87.9), specifi city 78.6% (68.3 to 86.8), DOR
21.7 (6.3 to 74.4), area under SROC 0.88 (0.80 to 0.96). The best threshold
value for identifi cation of responders was 9.5 to 15%. Heterogeneity was
signifi cant for all evaluations.
Conclusions ΔPOP is a non-invasive dynamic parameter able to predict
fl uid responsiveness with only a moderate level of accuracy. The main
limitation of this analysis is heterogeneity between included studies.
1. Cannesson M, et al.: Anesthesiology 2007, 106:1105-1111.
2. Cannesson M, et al.: Br J Anaesth 2008, 101:200-206.
3. Feissel M, et al.: Intensive Care Med 2007, 33:993-999.
4. Wyff els PA, et al.: Anesth Analg 2007, 105:448-452.
5. Natalini G, et al.: Anesth Analg 2006, 103:1478-1484.
6. Solus-Biguenet H, et al.: Br J Anaesth 2006, 97:808-816.
Maintenance of cardiac index within normal range is associated
with mortality reduction in patients undergoing major urological
PS Szturz, JM Maca, JT Tichy, PS Sukenik, VC Chylek, PS Sklienka, JJ Jahoda,
Faculty Hospital Ostrava, Czech Republic
Critical Care 2010, 14(Suppl 1):P123 (doi: 10.1186/cc8355)
Introduction Hemodynamic optimisation based on fl ow variables allows
an early detection and correction of possible occult organ hypoperfusion
in patients undergoing major surgery. Shoemaker described a markedly
decreased cardiac index (CI) in nonsurvivors, which remained signifi cantly
below the values compared with survivors during the surgery. The aim of
this study was to evaluate the length of ICU stay, overall in-hospital stay
and the postoperative outcome in a group of patients undergoing major
urological surgery, while the CI is maintained within the normal range
during intraoperative period.
Methods Patients were randomised into groups the day before surgery –
conventional management group (decision about fl uid therapy and
vasoactive support was based on internal guidelines to preserve normal
macrohemodynamic variables), and protocol group. Each patient in the
protocol group received an oesophageal Doppler probe (TED) (Hemosonic
100; Arrow International, USA) after the start of general anaesthesia and
then hemodynamic optimisation (fl uid management and vasoactive
drugs), according to TED variables, was performed to keep CI between 2.6
and 3.8 l/minute/m2.
Results We enrolled 230 patients. The control group: n = 115 and the
protocol group: n = 115. High-risk criteria surgery was fulfi lled in 43%
patients in protocol group and 45% in control group. There were no
signifi cant diff erences in baseline variables between both groups (age,
gender, length of surgical procedure, estimated blood loss and also in
intraoperative values of MAP and CVP). In the protocol group was observed
a high frequency of CI <2.6 l/minute/m2 after induction of anesthesia 75%
with fast recovery of CI. The volume of fl uids (Ringer’s solution and HES
6% 130/0.4) administered during surgery was lower in the control group
(medians: 2,800 ml vs 3,800 ml, P <0.05). Amount of used blood units (RBC
71 vs 133, P = 0.001; FFP 71 vs 142, P <0.001) was higher in control group.
Signifi cant diff erences have also been found in the use of vasoactive
Critical Care 2010, Volume 14 Suppl 1
agents. Total number of postoperative complications (P <0.001), the ICU
stay and overall in-hospital stay (medians: 2 vs 3 days, P = 0.041, and 9 vs
11 days, P = 0.014), in-hospital mortality (2.6% vs 10.4%, P = 0.029) were in
favour of the protocol group of patients.
Conclusions Hemodynamic optimisation guided by TED can improve
postoperative outcome in patients after major urological surgery.
Maintain ing normal values of CI is an applicable target of intraoperative
Eff ect of a preload challenge on peripheral perfusion in critically ill
E Klijn, S Niehof, J Bakker, C Ince, J Van Bommel
Erasmus Medical Center, Rotterdam, the Netherlands
Critical Care 2010, 14(Suppl 1):P124 (doi: 10.1186/cc8356)
Introduction Fluid therapy in ICU patients serves to maintain tissue
perfusion and is directed at increasing cardiac stroke volume (SV) through
an increase in preload: fl uid responsiveness. Although there is increasing
evidence that the regional blood fl ow cannot be predicted from global
hemodynamic measurements, the relation between SV and parameters
of peripheral perfusion is not clear. The aim of our study was to evaluate
the eff ect of an increase in preload on commonly used parameters of
Methods Hemodynamically unstable patients with clinically suspected fl uid
responsiveness underwent a passive leg raising (PLR) test, which consisted
of 5 minutes of rest in a semirecumbent position of 30°, followed by 5
minutes PLR (lower limbs elevated at 30° and trunk in supine position). SV
was measured continuously by pulse contour analysis using PiCCO (Pulsion).
Peripheral perfusion was measured continuously with sidestream dark fi eld
imaging (sublingual area) and laser Doppler fl owmetry (LDF) (fi nger).
Results Sixteen patients (age: 63 years (55 to 72), APACHE II: 25 (20 to 28),
SOFA: 10 (7 to 13)) were included in our study. Of these 16 patients, six (38%)
increased their SV by >10% in response to a PLR. Flow indices (LDF and
sublinguale microcirculatory fl ow) did not change. However, there was a trend
in increase of the functional capillary density in the responders (see Figure 1).
Conclusions These data suggest that increasing SV in hemodynamically
unstable patients might improve peripheral perfusion, however only in
the sublingual area and not in all patients. There was no relation between
systemic circulation and peripheral perfusion: it remains to be investigated
whether optimizing SV actually results in improved tissue perfusion.
Distensibility index of inferior vena cava diameter in ventilated
septic and trauma patients with shock
N Parenti1, D Sangiorgi2, A Pigna3, C Coniglio4, F Cancellieri4, G Gordini4,
R Melotti3, G Di Nino3
1Hospital Santa Maria della Scaletta Imola, Bologna, Italy; 2Università,
Bologna, Italy; 3Policlinico Sant’Orsola, Bologna, Italy; 4Ospedale Maggiore,
Critical Care 2010, 14(Suppl 1):P125 (doi: 10.1186/cc8357)
Introduction We evaluated the distensibility index of the inferior vena
cava (dIVC%) in ventilated septic and trauma patients with shock before
and after fl uid therapy. There are no data on this index in patients in shock
Methods This is a prospective study conducted in two ICUs between
September 2008 and May 2009. Inclusion criteria were: shock (systolic
arterial pressure below 90 mmHg and/or perfusion of vasopressor amines)
related to severe sepsis or to trauma. The inferior vena cava diameter at
end-expiration (IVCDmax) and at end-inspiration (IVCDmin) was measured by
echocardiography using a subcostal approach. The distensibility index of
the IVC was the ratio of IVCDmax – IVCDmin / IVCDmin expressed as a percentage
(dIVC%). Cardiac index (CI) was calculated by analysis of the arterial pressure
wave (FloTrac/Vigileo; Edwards). Measurements were performed at baseline
and after a volume expansion using 7 ml/kg colloid and 20 ml/kg crystalloid
for septic and trauma patients, respectively. Patients were separated into
responders (increase in CI ≥15%) and nonresponders (NR) after fl uid therapy.
The Wilcoxon and Mann–Whitney tests were used to compare paired values.
Statistical signifi cance was tested at an α level of 0.05.
Results Eleven patients in shock (fi ve septic, six trauma; six responder, fi ve
NR) were included. The median age was 62 years (range 28 to 78 years) and
mean SAPS II score was 52 ± 30 SD. There were no signifi cant diff erences
between responders (R) and NR regarding age, gender, and risk scores.
Among all patients, at baseline, median CI and dIVC% were 2.6 l/minute/
m2 and 29%, respectively. Volume expansion signifi cantly increased the
median CI from 2.6 (2 to 3.3) to 3 (2.1 to 4) l/minute/m2 (P = 0.005) and
decreased dIVC% from 29.4% to 12.6% (P = 0.003). The median dIVC% in R
was higher than NR: 31.3% vs 17% (P <0.05). Fluid therapy decreased more
dIVC% in R than in NR: R 31% to 12% (P = 0.03), NR 17% to 12% (P = 0.04).
The dIVC% showed similar trend in both groups of septic shock (SS) and
trauma shock (TS) patients before and after fl uid therapy: dIVC% 27% in SS
and 24% in TS before fl uid therapy; 15% in SS and 11% in TS after therapy.
Conclusions Our data suggest that dIVC% is a sensitive index of fl uid
responsive ness in septic and trauma patients in shock. Limitations: few
1. Barbier C, et al.: Respiratory changes in inferior vena cava diameter are
helpful in predicting fl uid responsiveness in ventilated septic patients.
Intensive Care Med 2004, 30:1740-1746.
Aortic dP/dtmax accurately refl ects left ventricular contractility when
eff ective preload independence is achieved
P Morimont1, B Lambermont1, T Desaive1, N Janssen1, G Chase2, V D’Orio1
1University of Liege, Belgium; 2University of Canterbury, New Zealand
Critical Care 2010, 14(Suppl 1):P126 (doi: 10.1186/cc8358)
Introduction Myocardial depression occurs in 40% of patients presenting
with sepsis. In critically ill patients, the peak fi rst derivative of aortic pressure
(Ao_dP/dtmax) derived from a fl uid-fi lled catheter has been commonly used
by clinicians for decades to assess directional change in left ventricular (LV)
contractility. However, this parameter remains questionable because of its
preload sensitivity. The aim of this study was to test whether Ao_dP/dtmax
represents an accurate method for assessing LV contractility when preload
independence, based on dynamic indices, is achieved.
Methods LV pressure–volume data obtained with a conductance
catheter and invasive aortic pressure obtained with a fl uid-fi lled catheter
were continuously recorded in six anaesthetized and mechanically
Figure 1 (abstract P124). Functional capillary density. Dotted line, median.
Critical Care 2010, Volume 14 Suppl 1
ventilated pigs. After a stabilization period, endotoxin was infused to
induce septic shock. Fluid administration was continuously controlled by
preload responsiveness by holding pulse pressure variation (PPV) <13%.
Catecholamines were transiently administrated during shock. Ao_dP/dtmax
was compared with end-systolic elastance (Ees), the gold standard method
for assessing LV contractility.
Results Endotoxin-induced septic shock and catecholamine infusion lead
to signifi cant variations in LV contractility. The best correlation (r2 = 0.76)
and agreement between Ao_dP/dTmax and Ees were obtained when PPV
<11% (Figure 1).
Conclusions Ao_dP/dTmax is a minimally invasive and accurate method for
assessing LV contractility when eff ective preload independence, defi ned
as PPV <11%, is achieved.
1. Sharma AC: Shock 2007, 28:265-269.
2. Pinsky MR, et al.: Curr Opin Crit Care 2005, 11:235-239.
Cardiac cycle effi ciency: a new index for cardiac work estimation
tested during aortic valve plasty
S Romagnoli, M Romano, C Lazzeri, G Santoro, F Meucci, D Quattrone,
D Dini, A De Gaudio
Careggi Hospital, Florence, Italy
Critical Care 2010, 14(Suppl 1):P127 (doi: 10.1186/cc8359)
Introduction The pressure recording analytical method (PRAM) is the
only pulse contour method that does not need any calibration since it
estimates in vivo, beat to beat, the impedance of the cardiovascular system
[1-3]. Cardiac cycle effi ciency (CCE) is a novel parameter that is directly
related to the cardiovascular impedance. Since the aortic valve contributes
to impedance, we hypothesized during an aortic valvuloplasty, performed
for severe aortic stenosis, the cardiovascular impedance may decrease by
the reduction of the transvalvular gradient.
Methods In a cath lab, fi ve consecutive patients undergoing aortic valve
plasty for severe aortic stenosis were monitored by means of PRAM during
the procedure. Systolic (SAP), diastolic, and mean (MAP) arterial pressures,
stroke volume (SV), heart rate (HR), cardiac output (SV x HR), CCE, and dP/
dtmax were continuously collected and afterwards analyzed. The stroke work
(SW = SV x MAP) and minute work (MW = SBP x CO) were also measured.
Results After the ballooning maneuver (valvuloplasty), the maximal
gradient measured with intraventricular and intraaortic catheters
signifi cantly decreased (146 (37) vs 43 (12) mmHg; P <0.0001). The
CCE signifi cantly improved from –0.72 (0.4) to 0.02 (0.19) U; P <0.0001.
Peripheral dP/dtmax increased from 0.8 (0.27) to 1.16 (0.23) mmHg/ms; P =
0.001, while SW and MW did not show substantial modifi cations (4.06
(1.03) vs 4.02 (1.4) l x mmHg; NS, and 549.8 (111.5) vs 544.6 (153.4) l x
mmHg; NS, respectively).
Conclusions CCE demonstrated to be a very sensitive estimation of
cardiovascular impedance since it shows a signifi cant improvement after
the valvuloplasty in spite of unchanged values of both SW and MW. In
other words, the energy expenditure of the whole cardiovascular system
signifi cantly reduced after the aortic valve stenosis is corrected. Moreover,
our data strongly suggest that peripheral dP/dtmax is deeply aff ected by
aortic valve stenosis.
1. Romagnoli S, Romano SM: Estimation of hemodynamic parameters by
arterial waveform: available technologies. Anesth Analg in press.
2. Maus TM, Lee DE: Arterial pressure-based cardiac output assessment. J
Cardiothorac Vasc Anesth 2008, 22:468-473.
3. Romano SM, Pistolesi M: Assessment of cardiac output from systemic
arterial pressure in humans. Crit Care Med 2002, 30:1834-1841.
Nonocclusive mesenteric ischemia following cardiothoracic surgery
N Kiyonaga, T Yasuda, T Yonemitsu, M Nagaoka, T Oryoji, M Nakahara,
N Okayama, T Kikuchi, T Imabayashi, Y Kakihana, Y Kanmura
Kagoshima University Hospital, Kagoshima City, Japan
Critical Care 2010, 14(Suppl 1):P128 (doi: 10.1186/cc8360)
Introduction Nonocclusive mesenteric ischemia (NOMI) following cardiac
surgery carries a high mortality. This disease is diffi cult to diagnose. Early
diagnosis is thought to be of paramount importance as the only chance of
improving the survival rate in these patients. Therefore, we were retrospectively
studied all cases of NOMI to evaluate what were the sensitive markers and
what were the risk factors contributing to the occurrence of NOMI.
Methods We retrospectively reviewed 279 patients undergoing cardio-
thoracic surgery from August 2007 to July 2008. Six of these patients
(2.2%) developed NOMI postoperatively and the data for them were
retrospectively evaluated in detail.
Results In all cases of NOMI, they were diagnosed at laparotomy. The mean
age was 69.7 years (50 to 83 years old), and the male:female ratio was 1:1.
One patient received off -pump coronary artery bypass surgery, and fi ve
underwent thoracic aortic surgery. Hemodialysis was initiated in one of
six patients before operation, while the continuous hemodiafi ltration
was initiated in all patients postoperatively. After operation, high-dose
catecholamines were necessary in fi ve of six patients for long periods
because of severe hypotension. In four of six patients, abdominal pain
was the presenting symptom. The rest of two patients had a nonspecifi c
presentation because they were ventilated and sedated. All patients
presented abdominal distension and their abdominal X-rays showed
paralytic ileus features. The serum values of AST, LDH, CK, and lactate
were slightly elevated in most patients. Five of six patients died from
septic shock and multiple organ failures, and the mortality rate of patients
with NOMI was 83%. Potential risk factors contributing to the occurrence
of NOMI and sensitive markers might be the following: continuous
hemodiafi ltration (6/6); hypotension (5/6); high-dose catecholamines
(5/6); dehydration (6/6); abdominal pain (4/6); paralytic ileus patterns of
abdominal X-rays (6/6).
Conclusions The increase of NOMI incidence following cardiothoracic
surgery might be related to continuous hemodiafi ltration, hypotension,
dehydration, and uses of high-dose catecholamines. Identifi cation of
patients at NOMI risk and prevention of hypovolemic hypotension and use
of vasodilator may help to reduce the incidence of NOMI.
1. Klotz S, Vestring T, Rotker J, et al.: Dagnosis and treatment of nonocclusive
mesenteric ischemia after open heart surgery. Ann Thorac Surg 2001,
Etiology, comorbidity and prognosis of hospitalized patients with
congestive heart failure
Y Zhao, J Li, Q Xue, L Gao, Q Xu, X Wu
Institute of Geriatric Cardiology, Beijing, China
Critical Care 2010, 14(Suppl 1):P129 (doi: 10.1186/cc8361)
Introduction Congestive heart failure (CHF) is a growing public health
problem in China, mainly because of aging of the population and the
Figure 1 (abstract P126). Correlation between Ees and Ao_dP/dtmax when
PPV <11%. Incidence of ICR-BSI in WCNN intensive therapy unit.
Critical Care 2010, Volume 14 Suppl 1
increased prevalence of CHF in the elderly. The aim of present study was
to investigate the major causes, comorbidities and in-hospital mortality of
patients with CHF.
Methods A retrospective study was performed in 6,960 patients (4,352
males, 2,608 females) with a validated primary discharge diagnosis of CHF
hospitalized from 1 January 1993 through 31 December 2007, at Chinese
PLA General Hospital in Beijing. The patients were divided into fi ve groups
based on the number of etiologies and comorbidities from one to fi ve
or more than fi ve. A comparative analysis was performed to explore the
major causes, comorbidities and in-hospital mortality of patients among
Results The mean (± SD) age of patients was 53 ± 17 years in the one-
comorbidity group, 60 ± 16 years in the two-comorbidity group, 65 ±
14 years in the three-comorbidity group, 70 ± 13 years in the four-
comorbidity group and 72 ± 11 years in the fi ve-comorbidity group.
The major causes of hospitalized patients with CHF were coronary artery
disease (44.9%), vavular heart disease (27.5%), cor pulmonale (9.6%) and
cardiomyopathy (7.4%). The comorbidities of CHF were hypertension
(38.6%), atrial fi brillation (23.1%), diabetes mellitus (18.3%), pneumonia
(11.6%) and renal failure (7.1%). The single comorbidity was predominant
in younger patients while multiple comorbidity was predominant in the
elderly (P <0.001). The most common single etiology was vavular heart
disease, the most common triple etiology was coronary artery disease
complicated with hypertension and diabetes mellitus. Cox regression
analysis showed higher hospital mortality rates associated with increased
numbers of etiology and comorbidity (hazard ratio (HR) from 0.98, 95% CI
0.71 to 1.36 to HR 1.59, 95% CI 1.23 to 2.05, to HR 1.90, 95% CI 1.43 to 2.51,
to HR 2.47, 95% CI 1.81 to 3.35, P <0.001).
Conclusions This study demonstrates that the older a hospitalized
patient with CHF is, the more comorbidities they have. The major
causes and comorbidities of hospitalized patients with CHF are coronary
artery disease, vavular heart disease, cor pulmonale, cardiomyopathy,
hypertension, atrial fi brillation, diabetes mellitus, pneumonia and renal
failure. The single etiology or comorbidity is predominant in younger
patients, while multiple etiology or comorbidity is predominant in the
elderly. A higher in-hospital mortality rate of CHF is associated with an
increased number of etiologies and comorbidities.
Factors associated with intensive care morbidity following surgical
repair of tetralogy of fallot
A Aralihond, A Krishnaiah, B Mimic, K Brown
Great Ormond Street Hospital, London, UK
Critical Care 2010, 14(Suppl 1):P130 (doi: 10.1186/cc8362)
Introduction The outcome of surgical repair of tetralogy of fallot (TOF)
is a useful benchmark for the assessment of congenital cardiac surgical
programs. The aim of this study was to describe postoperative morbidity
following TOF repair and assess the factors linked to a longer duration of
Methods Retrospective study of all patients admitted to cardiac intensive
care between January 2003 and December 2008 following classic TOF
repair. More complex repairs were excluded. Factors were investigated
for a relationship with intubation hours using linear regression analysis.
Intubation hours were log transformed for the analysis since the data were
Results A total of 174 children were included, 97 (56%) male, of whom
31 (18%) had previous palliation with a BT shunt and 23 (13%) had extra
medical problems. The median age at repair was 8.9 (range 1.6 to 112.8)
months and the median weight was 8.2 (3.5 to 28.5) kg. The median
cardiopulmonary bypass (CPB) time was 101 (42 to 292) minutes and 94
(54%) required transannular patch. The median postoperative intubation
time was 23 (0 to 566) hours and 11 patients (6%) did not require
postoperative ventilation. The median ICU stay was 66 (13 to 791) hours
and there was one early death before hospital discharge. One hundred and
seventy (95%) patients received an inodilator. Postoperative complications
included renal failure and fl uid overload requiring peritoneal dialysis
(PD) in 31 (17%); junctional ectopic tachycardia (JET) in 29 (16%); other
arrhythmias in 10 (6%), delayed chest closure in six (3%) of which two had
emergency mediastinal exploration due to bleeding and ECMO in one
patient. A multiple regression model for the outcome measure intubation
hours indicated that younger age at repair (P = 0.03), associated medical
problems (P = 0.04), longer CPB time (P = 0.057), JET, PD, noradrenalin use
and adrenaline use (P <0.01 for all) were independently linked with longer
postoperative ventilation times.
Conclusions Younger children, those with extra medical problems and
children that required higher levels of inotropes (probably refl ecting low
cardiac output syndrome), had longer intubation times. The commonest
and most important complications that infl uenced duration of ventilation
were JET and PD. In our series, mortality and length of stay were
comparable with other published data.
Sildenafi l attenuates pulmonary vascular remodeling and
upregulates Kv1.5 mRNA expression in pulmonary hypertension
secondary to left-to-right shunt in rats
L Hu, LH Tan
Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
Critical Care 2010, 14(Suppl 1):P131 (doi: 10.1186/cc8363)
Introduction Sildenafi l is a phosphodiesterase-type-5 inhibitor and
selectively decreases pulmonary artery pressure. So far, the mechanism
underlying sildenafi l’s eff ects on pulmonary vascular remodeling and
potassium channel activity in pulmonary artery smooth muscle cells
(PASMCs) has not been clearly addressed in pulmonary hypertension
secondary to increased pulmonary blood fl ow.
Methods A total of 27 male SD rats were randomly divided into a sham
group (n = 9), a shunt group (n = 9) and a shunt + sildenafi l group (n = 9).
A left-to-right shunt was established by performing an abdominal aorta to
inferior vena cava fi stula both in the shunt group and the shunt + sildenafi l
group. Rats in the shunt + sildenafi l group received oral sildenafi l 10 mg/kg/
day, whereas the rats in the sham group and the shunt group were fed with
normal saline of the same volume. Eleven weeks later, mean pulmonary
artery pressure (mPAP) was measured. Meanwhile, the ratio of right
ventricular mass to left ventricular plus septal mass (RV/(LV+S)) was detected
as a marker of the degree of right ventricular hypertrophy. The relative medial
thickness (RMT) of middle and small pulmonary muscularized arteries was
calculated as a sign of pathological changes of pulmonary vasculature. The
voltage-gated potassium channel Kv1.5 mRNA expression of pulmonary
vasculature was detected using real-time PCR.
Results Eleven weeks later, the rats in the shunt group developed
pulmonary hypertension as evidenced by signifi cantly increased
mPAP, RV/(LV+S), as well as higher RMT of middle and small pulmonary
muscularized arteries (all P = 0.01). In addition, the rats in shunt group had
decreased Kv1.5 mRNA expression in pulmonary vasculature (P = 0.01).
The rats in the shunt + sildenafi l group had a signifi cantly decreased mPAP,
and RV/(LV+S) ratio, and a lower RMT as well (all P = 0.01), whereas the
levels of Kv1.5 mRNA expression were signifi cantly upregulated (P = 0.01).
Furthermore, there were no statistically signifi cant diff erence in mPAP, in
RV/(LV+S) ratio, RMT of middle and small pulmonary muscularized arteries
and Kv1.5 mRNA expression between the shunt + sildenafi l group and the
sham group (all P = NS).
Conclusions Oral sildenafi l attenuated pulmonary vascular remodeling
and upregulated Kv1.5 mRNA expression in the rats with pulmonary
hypertension secondary to left-to-right shunt.
Validation of echocardiographic indices of right ventricular
afterload: an experimental, open pericardium pig model
A Knook, D Reis Miranda, J Van Bommel, A Bogers, D Duncker,
D Gommers, J Bakker
Erasmus Medical Centre, Rotterdam, the Netherlands
Critical Care 2010, 14(Suppl 1):P132 (doi: 10.1186/cc8364)
Introduction Pulmonary vascular resistance (PVR) has been used to assess
right ventricular afterload; however, this is considered meaningless due to
several physiologic shortcomings. Echocardiography has often been used to
assess right ventricular (RV) afterload, but this has never been validated as an
index of RV afterload. The purpose of this study is to evaluate echocardiographic
indices of RV afterload in an experimental, open-pericardium pig model with
induced, variable main pulmonary artery stenosis.
Critical Care 2010, Volume 14 Suppl 1
Methods Eleven anesthesized pigs were instrumented for the measure-
ment of arterial blood pressure, central venous pressure, RV and pulmonary
pressure. An ultrasonic fl owprobe (MA14PAX; Transonic) was positioned on
the main pulmonary artery to obtain pulmonary fl ow. Distal to the fl owprobe,
a balloon-occluder was positioned facilitating gradual constriction of the
pulmonary artery. To obtain a stepwise pressure diff erence increment over the
banding of 10 mmHg at each measurement, we gradually infl ated the balloon-
occluder. After 10 minutes, all invasive hemodynamic data were registered
and an epicardial echocardiography was performed to obtain tricuspid fl ow
velocities, isovolumetric and isovolumetric relaxation time. To calculate the
TEI index during one heartbeat, echocardiographic measurements were
synchronized with fl owprobe measurements to obtain ejection time. The
E/E΄ ratio was obtained with tissue Doppler echocardiography of the lateral
tricuspid annulus. All echocardiographic measurements were performed in
triple and averaged. The ejection period and mean pulmonary acceleration
and cardiac output were calculated from the pulmonary fl ow curve derived
from the ultrasonic fl owprobe. Resistance over the pulmonary banding was
calculated by pressure gradient divided by cardiac output.
Results Of the 11 pigs, two pigs died prematurely, one inferior caval vein
rupture, and one due to asystole while inserting the pulmonary artery
catheter. After pulmonary banding, central venous pressure did not
increase signifi cantly. Mean acceleration correlated with the resistance
over the banding (r = 0.59, P <0.0001). The TEI index and E/E΄ neither
correlated with the pressure gradient over the banding nor fl ow.
Conclusions Mean acceleration correlated with RV afterload in this model.
Activation of apoptotic pathways in experimental acute
afterload-induced right ventricular failure
C Dewachter1, L Dewachter1, B Rondelet1, P Fesler2, S Brimioulle1,
F Kerbaul3, R Naeije1
1Faculty of Medicine, ULB, Brussels, Belgium; 2Lapeyronie Hospital, Montpellier,
France; 3La Timone University Hospital, Marseille, France
Critical Care 2010, 14(Suppl 1):P133 (doi: 10.1186/cc8365)
Introduction The pathobiology of persistent right ventricular (RV) failure
observed after an acute increase in pulmonary artery pressure (Ppa)
remains incompletely understood. We hypothesized that these severe
complications might be related to an activation of apoptotic pathways.
Methods Fourteen anesthetized dogs were randomised to a transient
90 minutes pulmonary artery constriction or to a SHAM operation,
followed 30 minutes later by hemodynamic measurements including
eff ective arterial elastance (Ea) to estimate RV afterload and end-systolic
elastance (Ees) to estimate RV contractility, and sampling of cardiac tissue
to assess apoptosis by real-time quantitative polymerase chain reaction,
enzyme-linked immunosorbent assay and immunohistochemistry.
Results Transient increase in Ppa persistently increased Ea from 0.75 ± 0.08
to 1.37 ± 0.18 mmHg/ml, and decreased Ees from 1.06 ± 0.09 to 0.49 ± 0.09
mmHg/ml, Ees/Ea from 1.44 ± 0.06 to 0.34 ± 0.03 and cardiac output from
3.78 ± 0.16 to 1.46 ± 0.10 l/minute, indicating RV failure. As compared with
the SHAM-operated group, and with left ventricular tissue in animals with
persistent RV failure, there were decreased gene expressions of RV and
septal Bcl-2, with no changes in the gene expressions of Bax and Bak, and
an increase in the Bax/Bcl-2 ratio. RV and septal Bcl-XL, and RV Bcl-w gene
expressions were decreased as compared with the SHAM-operated group.
There were activations of RV caspases 8 and 9, and of RV and septal caspase
3. Diff use RV and septal apoptosis was confi rmed by TUNEL staining. There
were also increased RV and septal protein expressions of TNFα.
Conclusions Acute afterload-induced persistent RV failure appears to be
related to an early activation of apoptotic pathways, and to a myocardial
increase of TNFα.
High incidence of severely prolonged QT interval after cardiac surgery
M Biry, U Schurr, S Ritter, K Baenziger, A Zollinger, M Genoni
Triemli City Hospital, Zurich, Switzerland
Critical Care 2010, 14(Suppl 1):P134 (doi: 10.1186/cc8366)
Introduction A prolonged QT interval may be associated with torsades
de pointes and lead to sudden cardiac death. The aim of this study was to
determine both the frequency of QT prolongation and administration of
QT prolonging drugs perioperatively in cardiac surgery.
Methods This prospective observational study included 82 patients
(mean age 67 years) undergoing elective cardiac surgery (coronary
bypass grafting 37, valve surgery 29, combination 16). The QT interval was
manually measured in lead II and V2 of a 12-lead electrocardiogram (ECG)
and corrected for heart rate (corrected QT interval, QTc, calculated from
Bazett’s formula) on the day before surgery, immediately after surgery,
daily until day 5 and before hospital discharge. A QTc interval >440 ms
in men and >460 ms in women in either ECG lead II or V2 was defi ned
as moderately prolonged. A QTc interval >500 ms was considered to be
moderately prolonged in patients showing complete left or right bundle
block, and severely prolonged in patients without complete bundle block.
All administered drugs that may prolong the QT interval were identifi ed
and classifi ed according to the QTdrugs.org Advisory Board: drugs with
a defi nite risk of torsades de pointes (class 1, for example amiodarone,
sotalol, haloperidol) or with a possible risk (class 2, for example granisetron,
Results A total of 489 ECG were analyzed (mean six ECG per patient).
The QTc interval was moderately prolonged in 40/82 patients before
surgery (48.8%). Five out of 40 patients (12.5%) had received drugs from
class 1 preoperatively and 1/40 (2.5%) from class 2. The QTc interval was
severely prolonged in 3/82 patients before surgery (3.7%), of which none
had received QT prolonging drugs preoperatively. In 38/82 patients
(46.3%) moderate QTc prolongation was newly discovered in at least
one postoperative ECG. Seventeen put of 38 patients (44.7%) received
drugs from class 1, and 3/38 (7.9%) from class 2 perioperatively. In 16/82
patients (19.5%) severe QTc prolongation newly appeared in at least one
postoperative ECG. Seven out of 16 patients (43.8%) received drugs from
class 1 and 1/16 (6.3%) from class 2 perioperatively.
Conclusions Severe QT interval prolongation >500 ms occurs in one-
quarter of cardiac surgical patients in the perioperative period while
moderate prolongation occurs in most of them. In nearly one-half of
these cases, QT prolonging drugs like amiodarone and haloperidol may
be involved. Before and during administration of such drugs in cardiac
surgical patients perioperatively, assessment of the QT interval from
routine ECG is recommended.
Endothelial protein C receptor expression after cardiopulmonary
bypass in adult cardiac surgical patients
R Hajek1, J Ruzickova2, L Slavik1, V Krcova1, M Simek1, I Fluger1
1University Hospital Olomouc, Czech Republic; 2Hospital Prerov, Czech
Critical Care 2010, 14(Suppl 1):P135 (doi: 10.1186/cc8367)
Introduction Endothelial protein C receptor (EPCR) is a transmembrane
glyco protein primarily localised on vessel endothelium. EPCR binds
protein C (PC) on the endothelial surface and presents it to the thrombin/
thrombomodulin complex. Thrombin activates PC to APC, which exerts
anticoagulant and anti-infl ammatory eff ect. Proteolysis of membrane-
bound EPCR releases soluble EPCR which can be detected in plasmatic
circulation. This reaction indirectly correlates with thrombin generation
and can be interpreted as marker of endothelial activation during
cardiopulmonary bypass (CPB).
Methods In a prospective study, the group of 35 adult patients (mean age
68 years) scheduled for cardiac surgery with standard cardiopulmonary
bypass (duration 80 ± 30 minutes, heparin dose 3 mg/kg, mild hypo-
thermia about 34°C) was evaluated. The markers of endothelial activation
and coagulation parameters (EPCR, PAI-1, antithrombin, tPA, PTT, aPTT,
fi brinogen, platelets and thromboelastography (TEG)) immediately
before and after surgery were recorded. We hypothesized that the
EPCR level (detected with ELISA monoclonal antibodies labeled with
myeloperoxidase, 450 nm reader – detection limit 10 ng/ml soluble
EPCR) increases after CPB and correlates with other markers of endothelial
Results The cut-off value of EPCR was set down 200 ng/ml. In 17% of
patients the value above the cut-off (366 ng/ml before, 209 ng/ml after CPB)
was detected. The EPCR value decreases after CPB (150.7 ± 124 vs 99.4 ±
70.6) whereas tPA increases (1.5 vs 9.3 ng/ml) and PAI-1 was unchangeable.
A trend to hypocoagulation after CPB was noticed (Δfi brinogen –1.04 g/l,
Critical Care 2010, Volume 14 Suppl 1
ΔaPTT +7.7 sec, Δplatelets –67 G/l) but no correlation between EPCR and
TEG parameters (coagulation index ΔCI –1.46, ΔR +0.22 minutes, Δα΄ –3.9°,
ΔMA –9.3 mm) was recorded. No correlation between EPCR and CPB
duration was recorded as well.
Conclusions CPB is not associated with increase of EPCR – a novel endothelial
marker – measured immediately after operation. We need further studies to
explain mechanisms of endothelial protection in this clinical setting.
1. Esmon CT: The endothelial protein C receptor. Curr Opin Hematol 2006,
2. Thiyagarajan M, Cheng T, Zlokovic V: Endothelial cell protein C receptor: role
beyond endothelium? Circ Res 2007, 100:155-157.
3. Lopez-Sagasetza J, Montes R, Puy C, et al.: Binding of factor VIIa to the
endothelial cell protein C receptor reduces its coagulant activity. J Thromb
Haemost 2007, 5:1813-1816.
Urapidyl for hypertension control in severe pre-eclampsia:
a comparative study with nicardipine
R Vizitiu1, M Krauss-Grignard2, V Garcia1, L Valentin2, E Samain2, P Diemunsch1
1Hôpitaux Universitaires de Strasbourg, France; 2Hôpital Saint Jacques,
Critical Care 2010, 14(Suppl 1):P136 (doi: 10.1186/cc8368)
Introduction During severe pre-eclampsia (PE), control of blood
pressure (BP) is crucial in order to prevent systemic complications.
Currently approved treatments such as nicardipine (N) and dihydralazine
have drawbacks. Since hypertension in PE is associated with increased
sympathetic activity, urapidil (U), a peripheral α1 antagonist, has potential
for BP control in PE, but no controlled comparison of U with N is available.
This preliminary randomized controlled trial aims to compare effi cacy and
safety of U and N to reduce BP in severe PE.
Methods After IRB approval and signed informed consent, 18 women with
severe PE without previous antihypertensive treatment were randomized
to U or N groups. The therapeutic goal was to achieve a mean BP (MBP)
between 105 and 125 mmHg. The U patients fi rst received U 6.25 mg
boluses every 5 minutes until the diastolic BP dropped below 105 mmHg,
followed by a 4 mg/hour infusion adjusted as needed. In the N group,
patients fi rst received a N 1 γ/kg/minute infusion until a 15% reduction in
mean BP, followed by a N 0.75 γ/kg/minute infusion adjusted as needed.
Non-invasive BP was assessed every 5 minutes during treatment titration
and then every 15 minutes. The time needed to reach the therapeutic
goal was registered. The main endpoint was the achievement of the BP
goal in 2 hours or less. Tolerance was assessed by the number of episodes
of hypotension (HO) (defi ned as MBP below 100 mmHg) and side eff ects.
Severe HO, defi ned as MBP below 80 mmHg or two episodes of HO, was
considered as treatment failure and led to exclusion. Further assessment
was limited to safety, amount of ocytocics used and neonatal evaluation by
ICU paediatricians until discharge from ICU. Results were compared using
analysis of variance. Side eff ects were compared with the chi-square test.
Results One U patient was excluded from the effi cacy assessment due to
a protocol violation. The main endpoint was reached in all 17 patients, after
50 minutes in both groups. During the fi rst 2 hours, the needed treatment
adjustment median value was 1 (0 to 10) in the U group and 1 (0 to 13) in
the N group. Side eff ects attributable to the study treatment were observed
in six of the nine cases in the N group and in one of the nine cases in the U
group (P <0.02). There were no severe side eff ects or neonatal side eff ects.
Conclusions No diff erence in effi cacy could be shown in this preliminary
series. Both treatments were easy to titrate. Fewer side eff ects were recorded
in the U group. Further studies are needed in order to compare U and N.
Comparison of the eff ects of furosemide, captopril and lorazepam on
noncomplicated hypertensive patients in the emergency department
A Uzun, L Yamanel, O Cinar, H Hasman, B Comert
Gulhane Military Medical Academy, Ankara, Turkey
Critical Care 2010, 14(Suppl 1):P137 (doi: 10.1186/cc8369)
Introduction Patients frequently refer to the emergency department with
hypertension and related disorders. If hypertensive crisis is not diagnosed
in these patients, urgent treatment is not necessary. However, taking
patient satisfaction into consideration, the emergency physicians usually
discharge these patients after lowering the blood pressure with various
medications . This prospective, randomized, placebo-controlled study
is designed in order to compare the eff ects of captopril, furosemide and
lorazepam on lowering blood pressure and increasing patient satisfaction.
Methods One hundred patients with uncomplicated hypertension were
included in the study. All were randomized into four groups: (1) captopril
group, (2) furosemide group, (3) lorazepam group, (4) placebo group. The
blood pressure was measured at baseline, 30th, 60th and 90th minute.
The patient satisfaction was assessed with a visual analog scale (VAS) at
baseline and 90th minute.
Results Captopril (23.64 mmHg), lorazepam (24.90 mmHg) and
furosemide (24.10 mmHg) were found similarly eff ective in lowering blood
pressure when we compare baseline and 90th minute, but all three drugs
were superior to placebo (15.94 mmHg) (P <0.05) (Table 1). When patient
satisfaction was assessed with the VAS, captopril (30.12 mm), furosemide
(28.04 mm) and lorazepam (32.88 mm) were statistically similar and all
three drugs were superior to placebo (22.76 mm).
Table 1 (abstract P137). Mean arterial pressure
Group MAP (mmHg) SD (mmHg) Level of signifi cance
Furosemide 24.1 10.7 19.9 to 28.5
Captopril 23.6 11.7 18.8 to 28.4
Lorazepam 24.9 10.1 20.7 to 29.1
Placebo 15.9 10.1 11.7 to 20.1
Total 22.1 11.1 19.9 to 24.3
Conclusions In conclusion, all three drugs can be used in subjects referred
to the emergency department with uncomplicated hypertension. They
are similarly eff ective in both lowering the blood pressure and increasing
1. Chiang WK: Asymptomatic hypertension in the ED. Am J Emergency Med
Incidence, risk factors and outcome of hypertensive crises in
critically ill patients: a retrospective survey
C Chelazzi, G Villa, V Selmi, AR De Gaudio
University of Florence, Italy
Critical Care 2010, 14(Suppl 1):P138 (doi: 10.1186/cc8370)
Introduction Hypertensive crises (HC) are common among patients
admitted to emergency rooms . However, data are lacking about
prevalence in the critically ill admitted to the ICU. The aim of the study
was to assess the rate of HC in a cohort of patients admitted to a medical–
surgical ICU, to look for risk factors for HC and to assess outcome of
patients with HC.
Methods Data have been collected from clinical charts of patients
consecutively admitted to a mixed ICU (1 January 2008 to 31 January
2009). HC diagnosis was made based on JNC defi nitions . Patients were
divided into two groups, the HC group and the control group. Diff erences
between groups were evaluated regarding age, gender distribution,
admission diagnosis, SAPS II score, ICU length of stay, ICU mortality, and in-
hospital mortality (P <0.05). Clinical and behavioural conditions associated
with HC were considered in the two groups and diff erences tested for
statistical signifi cance (P <0.05).
Results Of a total of 409 patients, 63 had one or more HC (15.4%).
Conditions signifi cantly associated with HC were age, cigarette smoking,
cancer surgery, vasculopathy, medical indication to ICU admission,
coronary artery disease, and chronic atrial fi brillation. HC patients showed
higher ICU length of stay and ICU mortality.
Conclusions HC were common among critically ill patients admitted
to the ICU, irrespective of their admission diagnosis. Conditions strongly
Critical Care 2010, Volume 14 Suppl 1
associated with HC included cigarette smoking, cancer and age. HC were
associated with worse outcomes.
1. Zampaglione B, Pascale C, Marchisio M, Cavallo-Perin P: Hypertensive
urgencies and emergencies. Prevalence and clinical presentation.
Hypertension 1996, 27:144-147.
2. Joint National Committee on Prevention, Detection, Evaluation, and
Treatment of High Blood Pressure; National Heart, Lung, and Blood Institute;
National High Blood Pressure Education Program Coordinating Committee:
Seventh report of the Joint National Committee on Prevention, Detection,
Evaluation and Treatment of High Blood Pressure. Hypertension 2003,
Comparative study to evaluate blood pressure levels measured by
an invasive method versus a non-invasive method in patients in an
intensive care unit
S Kiff er Macedo, T Bissoli, L Carvalho Dias, M Rodrigues Lacerda, R Paiva
Barbosa de Castro, D Leite Cordeiro, R Janetti Carrara, PV Falcão Duarte
Hospital Sao José do Avai, Itaperuna, Brazil
Critical Care 2010, 14(Suppl 1):P139 (doi: 10.1186/cc8371)
Introduction The blood pressure is an important variable in medical
practice. A mistaken measurement can change the management of some
diseases, modifying the patient’s prognosis. Therefore a correct defi nition
and control of blood pressure is an essential item in an ICU environment.
Methods A prospective and comparative study of the blood pressure
assessed by arterial catheterization (pressure referenced to atmospheric
pressure at mid-chest level and adequate curve in the monitor) and by
non-invasive blood pressure device (using the cuff of the monitor with
automatic oscillometric measurement) in the upper and lower limbs.
Results Included were 52 patients with average age of 54.7 years. In the
right arm (RA), a diff erence between IBP and NIBP larger than or equal
to 20 mmHg in systolic blood pressure (SBP) (plus or minus) occurred in
26.5% of the patients; 14.3% in diastolic blood pressure (DBP) and 8.7% in
mean blood pressure (MBP). In the left arm (LA), 30.6% for SBP; 4.1% for
DBP and 4.2% for MBP. In the left leg (LL), 40% for SBP, 17.8% for DBP and
17.8% for MBP. In the right leg (RL), 47.8% for SBP; 8.7% for DBP and 17.4%
Conclusions There were diff erences between BP measured by invasive
and non-invasive methods mainly in SBP. Lower limbs presented a larger
diff erence, which means that non-invasive methods in this place are not
reliable. The DBP in both methods presented less diff erence.
Crit Care 2006, 10:R64.
Chronic atrial fi brillation in intensive care unit treated with
electrical cardioversion: is it appropriate?
M Murtigni1, E Mannelli1, D Colosimo1, S Cianferoni1, S Degl’innocenti2,
J Parodo2, M Bonizzoli2, G Zagli2, A Peris2
1Postgraduate School of Anesthesia and Intensive Care, University of Florence,
Italy; 2Careggi Teaching Hospital, Florence, Italy
Critical Care 2010, 14(Suppl 1):P140 (doi: 10.1186/cc8372)
Introduction Chronic atrial fi brillation is known to be an important co-
morbidity factor in critically ill patients admitted to the ICU. The aim of
this study was to evaluate whether electrical cardioversion in the ICU can
reduce mortality of patients with chronic atrial fi brillation.
Methods From January 2005 to November 2009, 50 patients with history of
chronic atrial fi brillation admitted to the ICU were retrospectively studied.
Patients were divided into two groups: the fi rst group included patients
who underwent electrical cardioversion (CVE group, n = 10) and were
discharged in sinus rhythm; the second included patients who did not
undergo electrical cardioversion and were discharged with chronic atrial
fi brillation (CAF group, n = 40). In both groups, mortality, antiarrhythmic
drug therapy and oral anticoagulation regimen were monitored. The fi rst
group’s follow-up evaluated maintenance of sinus rhythm. The number of
DC shocks required for the maintenance of sinus rhythm in patients of the
CVE group was also collected. The main outcome parameter considered
was 28-day mortality.
Results Patients of both groups resulted in similar demographic and
clinical parameters. In patients included in the CVE group, the maintenance
of sinus rhythm was achieved with one DC shock in 66.6%, two DC shocks
in 22.2% and three DC shocks in 11.1% of cases. The mortality rate at 24
hours was 0% while at 28 days was 11.1%, whereas patients in the CAF
group had a 28-day mortality rate of 35%. See Figure 1.
Conclusions Our pilot study indicates that the improvement of ventricular
performance with the contribution of atrial systole might improve critically
ill patients’ outcome. Considering the small number of cases, a prospective
study, based on these preliminary results, is ongoing.
Applanation tonometry application in ICU patients with acute
N Menestrina1, A Martini1, D Simion1, M Dan2, L Gottin1
1University Hospital, Verona, Italy; 2Ospedale Civile, Verona, Italy
Critical Care 2010, 14(Suppl 1):P141 (doi: 10.1186/cc8373)
Introduction The incidence of acute cardiogenic pulmonary edema
(ACPE) is increasing and it is now one of the leading causes of morbidity
and mortality in our society. As the global population of European
countries is getting older, the impact of arterial stiff ness is becoming more
and more important in the pathophysiology of ACPE, besides coronary
vascular disease and valvular disease. The aim of the study was to evaluate
whether acute modifi cations in elastic artery distensibility can be involved
in the pathogenesis of ACPE.
Methods Six consecutive patients (four men and two women; age 76 ±
7.1 years) were admitted to our ICU with the clinical diagnosis of ACPE. All
patients were studied with transthoracic echocardiography (TTE) and by
evaluation of pulse wave analysis (PWA) and pulse wave velocity (PWV)
with the applanation tonometry method, performed at admission and
after clinical stabilization.
Results In all patients, left ventricular systolic function was not signifi cantly
reduced when evaluated with transthoracic echocardiography, while
a diastolic dysfunction was always demonstrated. We have recorded
a signifi cant (P <0.05) decrease in blood pressure values after clinical
stabilization. Estimation of the central aortic pressure waveform by
mathematical transformation of radial tonometry pressure was similarly
reduced. Other tonometric parameters, such as the Augmentation Index,
which represents the contribution of the wave refl ection to the global
pulse pressure wave, and PWV, which is inversely correlated to the arterial
compliance, were also signifi cantly decreased, when compared with the
values at the admission time. The subendocardial viability ratio (SEVR),
an indirect index of myocardial perfusion relative to cardiac workload,
increased after treatment with vasodilatators.
Conclusions Our data confi rm the determining role of the increased
arterial stiff ness in the pathogenesis of ACPE, and how a therapeutic
strategy able to ameliorate this target can be associated with a clinical
improvement for the patient. The applanation tonometry could be an
interesting method to evaluate these patients in the ICU setting.
1. Nichols WN, O’Rourke MF: McDonalds Blood Flow in Arteries: Theoretical,
Experimental and Clinical Principles. 4th edition. London: Hodder Arnold; 1998.
Figure 1 (abstract P140).
Critical Care 2010, Volume 14 Suppl 1
P142 Download full-text
A better prognosis for septic patients with left ventricular
P Carrilho-Ferreira, A Pais-de-Lacerda, H Côrte-Real, C França
Hospital de Santa Maria, Lisbon, Portugal
Critical Care 2010, 14(Suppl 1):P142 (doi: 10.1186/cc8374)
Introduction Several studies using angiographic or echocardiographic
methods have shown that in septic shock (SSh) or severe sepsis (SeS),
cardiac abnormalities, which are often documented , seem to have a
relevant prognostic signifi cance [2,3].
Methods A retrospective study was conduced during 6 months (April
to September 2009) in an ICU of a university tertiary hospital, identifying
all patients with SSh or SeS and reviewing their echocardiographic data.
All the patients with known or clinical/echocardiographic evidence of
signifi cant prior cardiac disease were excluded from this analysis.
Results Forty-nine patients were identifi ed with SSh or SeS from a total
of 211 ICU patients (23.2%). Among these, 26 had echocardiograms
done during their ICU stay (53.1%). We analyzed 19 echocardiograms
from 15 patients. The remaining 11 patients were excluded, having
ischemic heart disease (seven patients) and signifi cant valvular heart
disease (four patients). Within the SSh/SeS group of patients, those with
echocardiograms were younger (mean age 56.3 vs 64.4) and more often
women (53.3% vs 36.7%). The ICU mortality was nevertheless similar
in the two groups (46.7% vs 46.9%). The primary sites of infection were
the lungs and abdomen (26.7% each) or unknown (20%). The agents
most frequently isolated were Gram-negative bacilli (26.7%). In 53.3%
of cases there was no identifi ed agent. Echocardiographic evaluation
revealed signifi cant changes in 26.7% of the patients, with the remaining
being considered normal. Of those with signifi cant changes, 75% (n = 3)
showed impairment of left ventricular (LV) systolic function with global
hypokinesia simultaneously with diastolic dysfunction. Either abnormality
was not found in any other patients. The mortality rate during ICU stay was
lower in the group of patients with systolic and diastolic LV dysfunction
compared with those with no apparent modifi cation of LV function (0 vs
58.3%). The right ventricle was dilated and showed high systolic pressures
present in only one patient.
Conclusions This study reinforces the concept that changes in systolic
and diastolic functions are common in septic shock and severe septic
patients, and that the development of these changes (as an adaptation
mechanism) seems to correlate inversely with the acute mortality rate
during ICU stay [2,4].
1. Zanotti-Cavazzoni SL, et al.: Curr Opin Crit Care 2009, 15:392-397.
2. Parker MM, et al.: Ann Intern Med 1984, 100:483-490.
3. Poelaert J, et al.: Intensive Care Med 1997, 23:553-560.
4. Jardin F, et al.: Chest 1999, 116:1354-1359.
Microvascular eff ects of pulsatile versus nonpulsatile perfusion
during cardiopulmonary bypass
PW Elbers1, J Wijbenga2, F Solinger2, A Yilmaz2, M Van Iterson2,
E Van Dongen2, C Ince3
1OLVG, Amsterdam, the Netherlands; 2St Antonius Hospital, Nieuwegein, the
Netherlands; 3Academic Medical Center, Amsterdam, the Netherlands
Critical Care 2010, 14(Suppl 1):P143 (doi: 10.1186/cc8375)
Introduction While advantages of pulsatile perfusion (PP) during
cardiopulmonary bypass (CPB) in terms of clinical outcome remain the
subject of debate, possible benefi ts are generally thought to occur via
improvements in microvascular fl ow . However, this is currently not
supported by human clinical data. Therefore we used real-time human
microvascular imaging to test our hypothesis that pulsatile perfusion
would enhance microvascular perfusion.
Methods We used sidestream dark fi eld imaging to record video clips
of the human microcirculation in 16 patients undergoing routine CPB
for cardiac surgery. Following administration of cardioplegia, CPB was
continued in either pulsatile (PP, n = 8) or nonpulsatile (NP) mode. After
10 minutes, microvascular recordings were made. The perfusion mode was
then switched from PP to NP or vice versa. Ten minutes later, a second series
of microvascular video recordings were obtained. Global hemodynamic
and laboratory data were recorded and the energy equivalent pressure
(EEP) and pulse pressure (both mean ± SD) were calculated to quantify
PP generated surplus energy. Microvascular analysis was performed both
for smaller and larger microvessels with a diameter cut-off of 20 μm.
Assessments included perfused vessel density (PVD) (mean ± SD, 95%
confi dence intervals of the diff erence between NP and PP (95% CID)) and
the Microvascular Flow Index (MFI) (mean ± SD and interquartile range).
Results Pulsatile perfusion resulted in higher pulse pressure (27 ± 6 vs 7 ±
2 mmHg, P <0.0001) and CPB circuit EEP (184 ± 33 vs 150 ± 27 mmHg, P
<0.0001) as compared with NP while MAP was similar between these
perfusion modes (52 ± 11 vs 56 ± 13 mmHg, P = 0.09). Both for small and
larger microvessels, we found no diff erences in indices of microvascular
perfusion between PP and NP. Small microvessel PVD was similar between
PP and NP (6.65 ± 1.39 vs 6.83 ± 1.23/mm; 95% CID –0.50 to 0.87/mm, P =
0.58). The same was true for larger microvessel PVD (2.16 ± 0.64 vs 1.96 ±
0.48; 95% CID –0.50 to 0.11, P = 0.20). Similarly, the MFI did not diff er between
groups either for smaller (3.00 (2.83 to 3.00) vs 3.00 (2.75 to 3.0), P = 0.41) and
larger microvessels (3.00 (2.75 to 3.00) 3.00 (3.00 to 3.00), P = 0.50).
Conclusions PP during CPB does not alter human microvascular perfusion
using standard equipment in routine cardiac surgery despite yielding
higher CPB circuit energy equivalent pressure and patient pulse pressure.
1. Murphy GS, et al.: Anesth Analg 2009, 108:1394.
Microcirculation and intravascular coagulopathy in patients with
severe sepsis and septic shock
R Wimmer, S Franz, S Siebelist, M Uschner, C Seidelmann, H Ebelt,
S Hettwer, J Wilhelm, H Loppnow, K Werdan
Universitätsklinikum Halle (Saale), Halle, Germany
Critical Care 2010, 14(Suppl 1):P144 (doi: 10.1186/cc8376)
Introduction Sidestream darkfi eld imaging (SDF) technology is a new
method to visualize directly microcirculation. In this study we examined
the perfusion of the oral mucosa in patients with severe sepsis and
septic shock in order to evaluate the link between the severity of illness,
microcirculation and intravascular coagulopathy.
Methods Microcirculation was analysed in 46 ICU patients with clinical
suspicion for sepsis and procalcitonin >2 ng/ml. Microcirculation was
recorded daily over a 7-day period (d0 to d6). Each day, at least fi ve single
fi lm clips were taken by SDF and analysed with special software on a PC. We
used the functional vessel density and distribution of the vessel diameters
as well-established parameters to qualify microcirculation. Laboratory
parameters, hemodynamic data and vital signs were also registered. The
degree of disseminated intravascular coagulopathy was evaluated by
calculating the overt DIC score (according to ISTH), and severity of illness
was determined using SAPS II and the SOFA score.
Results During the stay in the ICU we observed a continuous descent of
the DIC score (1.82 ± 1.91 on d0 vs 1.3 ± 1.94 on d6) as well as a decline
of SAPS II (63.1 ± 14.1 on d0 vs 57.1 ± 18.4 on d6) and SOFA score (12.2 ±
3.9 on d0 vs 9.2 ± 5.8 on d6). The percentage of smallest vessels below
25 μm diameter decreased initially from 79.5 ± 21.9% (d1) to rise up then
persistently 86.2 ± 10.3% (d6). Nonsurvivors (n = 11) had, compared with
survivors (n = 35), a signifi cantly higher initial DIC score on day 0 (1.3 ± 1.6
vs 2.05 ± 4.1; P <0.05).
Conclusions Our data show a clear relation between the time courses of
DIC and microcirculation in patients with severe sepsis and septic shock.
This fi nding is in line with previous reports stating the profound impact of
DIC on microcirculation and fi nally on patient outcome.
Prevalence and prognostic signifi cance of cardiac abnormalities in
the ICU: an echocardiographic study
A Dell’Anna, C Sandroni, F Cavallaro, C Marano, M Antonelli
UCSC School of Medicine, Rome, Italy
Critical Care 2010, 14(Suppl 1):P145 (doi: 10.1186/cc8377)
Introduction The aim was to describe the prevalence and type of cardiac
abnormalities in ICU patients detected using echocardiography and to
assess whether those abnormalities are correlated with ICU survival.
Critical Care 2010, Volume 14 Suppl 1