- Meeting abstracts
- Open Access
38th International Symposium on Intensive Care and Emergency Medicine
© The Author(s). 2018
- Published: 29 March 2018
V Herwanto1, Y Wang1, M Shojaei1, B Tang2, AS McLean2
1University of Sydney, Westmead, Australia; 2Nepean Hospital University of Sydney, Nepean Clinical School, Kingswood, Australia
Introduction: Leukocyte dysfunction may play a role in sepsis pathogenesis. Established evidence showed that leukocyte dysfunction leads to reduced immune response and consequently an increased sepsis-related mortality. Impaired metabolism has been recently proposed as one possible mechanisms underpinning leukocyte dysfunction in sepsis. In this study, we investigated the global changes in leukocyte metabolism in sepsis, using an established in vitro model of lipopolysaccharide (LPS) stimulation.
Methods: Peripheral blood mononuclear cells (PBMC) were isolated from healthy volunteers (n=4) and incubated with 62.5 ng/mL LPS. Mitochondrial respiration was measured using Agilent Seahorse XF Analyzer (Cell Mito Stress Test Kit). Total cellular oxidative stress was measured using DCFDA Cellular Reactive Oxygen Species (ROS) Detection Assay Kit (Abcam) and mitochondrial superoxide was measured using MitoSOXTM (Life Technology). Apoptosis was measured by Annexin V-FITC Apoptosis Detection Kit (Abcam). Evaluation of oxidative stress and apoptosis were performed using BD FACSCanto flow cytometer and flow cytometry data was analyzed using FlowJo Software V10.
Results: LPS stimulation of PBMC from healthy volunteers showed a trend of decrease in both oxidative phosphorylation and cellular respiration (Fig. 1). This decrease in cellular metabolism was accompanied by a trend towards an increase in cell death in the stimulated leukocytes (Fig. 2). The increase in cell death was associated with an increase in oxidative stress (total and mitochondria) (Fig. 2), suggesting that the adverse effect of LPS on cellular metabolism may be mediated by an imbalance in redox potential.
Conclusions: The LPS stimulation model could provide a useful approach to study the effect of sepsis on leukocyte metabolism. Further study is required to better understand the mechanism of reduced leukocyte metabolism, including the possible role of oxidative stress in reducing cellular respiration and causing leukocyte cell death.
T Shimazui1, T Nakada1, L Fujimura2, A Sakamoto2, M Hatano2, S Oda1
1Chiba University Hospital, Chiba; Japan, 2Chiba University, Chiba, Japan
Introduction: Conventional assay technique to quantify vascular permeability in animal studies requires sacrifice animals; this becomes a barrier to evaluate of temporal changes or responses to therapeutic approaches in a single individual. In vivo fluorescence imaging potentially quantifies vascular permeability without sacrifice animals. However, the use of this noninvasive approach for the assessment of vascular permeability in remote organ injury caused by systemic inflammatory disease such as sepsis has not been reported.
Methods: Cecal ligation and puncture (CLP)-induced septic mouse model was compared to sham and hydrocortisone pretreated (CLP + HC) mouse models. The lung was assumed as an injured remote organ and the footpad was assumed as a noninvasive observational site. The mixture of Evans blue (EB) and fluorescent dye of Genhance 750 were injected into mice, and the extraction of EB in harvested lung was assessed as a conventional indicator of vascular permeability. Fluorescent intensities in the harvested lung or footpad were assessed and their correlation was analyzed to investigate this novel, noninvasive approach to estimation of lung vascular permeability.
Results: EB extraction in the harvested lung in the CLP group was significantly higher than in the other groups (CLP vs. sham, P=0.0012; CLP vs. CLP + HC, P=0.011). Fluorescent intensity in the footpad and harvested lung in the CLP group was also significantly higher than in the other groups (footpad, CLP vs. sham, P<0.0001; CLP vs. CLP + HC, P=0.0004; lung, CLP vs. sham, P<0.0001; CLP vs. CLP + HC, P<0.0001). The fluorescent intensity of the footpad was strongly correlated with that of the lung (r=0.95).
Conclusions: The fluorescence imaging technique may be useful for assessment of vascular permeability based on EB quantification. The footpad fluorescent intensity was strongly correlated with that of the lung, and may be a suitable indicator in noninvasive estimation of lung vascular permeability.
P003 Correlation of systemic and regional glycocalyx injury parameters in non-septic critically ill patients
T Tamosuitis1, A Pranskunas1, N Balciuniene1, D Damanskyte1, E Sirvinskas1, A Vitkauskiene1, E Sneideris1, C Boerma2
1Lithuanian University of Health Sciences, Kaunas, Lithuania, 2Medical Center Leeuwarden, Leeuwarden, Netherlands
Introduction: The relationship between systemic glycocalyx degradation markers and regional glycocalyx thickness in non-septic critically ill patients is unclear. Conjunctival sidestream dark field-imaging for the purpose of glycocalyx thickness estimation has never been performed. We aimed to investigate whether changes in glycocalyx thickness in conjunctival and sublingual mucosa are associated with global glycocalyx shedding markers.
Methods: In this single-centre prospective observational study, using techniques for direct in-vivo observation of the microcirculation, we performed a single measurement of glycocalyx thickness in both ocular conjunctiva and sublingual mucosa in mixed cardio surgical (n=18) and neurocritical patients (n=27) and compared these data with age-matched healthy controls (n=20). In addition we measured systemic syndecan-1 levels
Results: In the sublingual and conjunctival region we observed a significant increase of the perfused boundary region (PBR) in both neuro critical and cardiac surgical ICU patients, compared to controls (2.20[2.04-2.42] vs 1.76[1.63-2.08] and 2.19[2.01-2.36] vs. 1.70[1.61-2.00], p<0,05).There was a significant increase of syndecan-1 in ICU patients comparing with controls and in cardiac patients comparing with neurological (120.0[71.0-189.6] vs. 18.0[7.2-40.7], p<0,05). We detected a weak correlation between syndecan-1 and sublingual PBR(r=0.40, p=0.002) but no correlations between global glycocalyx damage markers and conjuctival glycocalyx thickness.
Conclusions: Conjunctival glycocalyx thickness evaluation using SDF videomicroscopy is suitable and is impaired in non-septic ICU patients but only measurements in sublingual mucosa are correlating with systemic glycocalyx shedding markers. Global glycocalyx damage is more severe in cardiac comparing to neuro critical patients.
D Beurskens1, M Bol2, B Broddin2, C Reutelingsperger1, T Delhaas1, M Poll2, G Nicolaes2, J Sels2
1Maastricht University, Maastricht, Netherlands; 2MUMC, Maastricht, Netherlands
Introduction: The purpose of this study is to investigate the endothelial glycocalyx at the onset of sepsis. We hypothesize that the perfused boundary region (PBR) in microvessels (5-25μm) measured by side stream darkfield imaging (SDF) and plasma markers of glycocalyx shedding is increased in non-survivors.
Methods: We studied 31 sepsis patients and divided them into survivors (n=17) and non-survivors (n=14) (30-day mortality). SDF measurements and blood sampling were performed within 24h of ICU-admission. ELISAs were used to quantify syndecan-1, angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2). Non-parametric tests (Spearman for correlations, Mann Whitney for group comparison) were used to assess statistical significance. A p<0.05 was considered significant. Results are presented as median (25th-75th percentile).
Results: Syndecan-1 levels were higher in non-survivors compared to survivors (519.2 (255.6-1056.7) vs. 178.0 (58.1-298.2) ng/ml, p=0.005) (Fig. 1). PBR tended to be higher in non-survivors (2.0 (1.9-2.2)μM) than in survivors (1.9 (1.7-2.1)μM) (p=0.05) (Fig. 2). Syndecan-1 correlated positively with APACHE II (ρ =0.60; p=0.02) and Ang-2/Ang-1 ratio (ρ =0.59; p=0.004), but not with PBR.
Conclusions: Plasma markers of glycocalyx shedding at ICU admission are predictors of 30-day mortality and correlate with APACHE II score. However, there is no correlation between these plasma markers and glycocalyx thickness measured by SDF imaging on ICU admission. Further studies should address the cause of this apparent discrepancy to define the role of SDF imaging in the assessment of glycocalyx shedding in sepsis.
P005 The role of glycocalyx shedding and platelet adhesion in sepsis-induced microvascular dysfunction
CL Manrique-Caballero, CJ Baty, MH Oberbarnscheidt, A Frank, FG Lakkis, BS Zuckerbraun, MR Pinsky, JA Kellum, H Gomez
University of Pittsburgh, Pittsburgh, PA, USA
Introduction: Sepsis is associated with endothelial activation leading to alterations in global microcirculatory blood flow distribution. These effects might constitute key mechanisms leading to organ dysfunction. The aim of this study was to investigate the role of glycocalyx shedding and platelet adhesion on the development of microvascular dysfunction in the renal peritubular capillary system, and its association to the development of acute kidney injury (AKI).
Methods: C57BL/6 (n=6-8/group) mice received vehicle (control), hyaluronidase (140 IU IA q8h during 24 hours) or underwent cecal ligation and puncture (CLP). Platelet adhesion and rolling in renal peritubular capillaries were assessed and quantified using multiphoton IVM in five different areas . Plasma syndecan (SDC-1) and hyaluronan were measured to assess glycocalyx shedding. Neutrophil Gelatinase-Associated Lipocaline (NGAL) and creatinine levels were used as markers of AKI and measured using commercially available assays.
Results: Hyaluronidase and CLP resulted in shedding of the glycocalyx (Fig. 1A) and increased platelet adhesion and rolling as compared to control (Fig. 2). Enzymatic-induced shedding did not involve a systemic inflammatory response, as shown by IL-6 levels (Fig. 1B). Irrespective of a systemic inflammatory response, shedding of the glycocalyx and increased platelet adhesion and rolling was associated with increased markers of AKI (Fig. 1C, D).
Conclusions: Shedding of the glycocalyx increases platelet adhesion and rolling, resulting in AKI, suggesting this as a potential mechanism of organ injury. The increase in AKI markers in the noninfectious hyaluronidase model without IL-6 elevation indicate that glycocalyx denudation and secondary platelet adhesion may be mechanisms of organ injury independent from sepsis-induced systemic inflammation.
1. Singer, G., et al. Microcirculation 13(2):89-97, 2006.
M Angé1, L Bertrand1, C Beauloye1, S Horman1, D Castanares-Zapatero2
1Institut de Recherche Experimentale et Clinique - Pôle de Recherche Cardiovasculaire, Brussels, Belgium; 2Cliniques Universitaires Saint Luc - Intensive Care Unit, Brussels, Belgium
Introduction: Endothelial dysfunction plays a major role in the sepsis related organ dysfunction, and is featured by vascular leakage. AMP-activated protein kinase (AMPK) is known to regulate actin cytoskeleton organization and interendothelial junctions (IEJs), contributing to endothelial barrier integrity. We have already demonstrated its role in defence against sepsis induced hyperpermeability , but the underlying mechanisms remain unknown. This project aims to identify molecular targets involved in the beneficial action of AMPK against endothelial barrier dysfunction.
Methods: Experiments have been performed in human microvascular dermal endothelial cells. α1AMPK activity has been modulated via the use of a specific siRNA or treatment by two pharmacological AMPK activators (AICAr, 991). We have investigated the effect of this modulation on the expression/phosphorylation of Connexin 43 (Cx43) and Heat shock protein 27 (HSP27), two proteins playing a key role in maintenance of IEJs and actin dynamics respectively.
Results: We show that α1AMPK is required to sustain the level of Cx43 expression as it was drastically reduced in cells transfected with a siRNA targeting specifically α1AMPK. Regarding HSP27, its expression level was not affected by α1AMPK deletion. However, both AMPK activators increased its phosphorylation on Ser82, in a α1AMPKdependent manner, while they had no effect on Cx43. Our results also reveal that HSP27 phosphorylation concurred with the appearance of actin stress fibers at the periphery of cells, suggesting a beneficial role for pHSP27 as well as F-actin stress fibers in vascular barrier function through reinforcing the endothelial tethering.
Conclusions: Our work identifies the regulation of Cx43 expression and HSP27 phosphorylation as potential protective responses underlying the beneficial action of AMPK against endothelial barrier dysfunction. AMPK could consequently represent a new therapeutic target during sepsis.
1. Castanares D et al. Crit Care Med. 41(12):e411-e422, 2013
P007 Melusin protects from LPS-induced cardiomyopathy through modulation of calcium channel signalling
P Arina1, A Costamagna1, L Brazzi1, M Brancaccio2, R Giuseppe1, N Vitale2, L Del Sorbo1, P Capello3, A Mazzeo4, L Mascia5, VM Ranieri6, M Sorge2, V Fanelli4
1Università di Torino, Dipartimento di Anestesia e Rianimazione, Torino, Italy; 2Università di Torino, Molecular Biotechnology Center - Torino, Torino, Italy; 3Università di Torino, Department of Molecular Biotechnology and Health Sciences, Torino, Italy; 4Università di Torino, Dipartimento di Scienze Chirurgiche, Torino, Italy; 5Università degli Studi di ROMA "La Sapienza", Dipartimento di Scienze E Biotecnologie Medico-Chirurgiche, Roma, Italy; 6Università degli Studi di ROMA "La Sapienza", Dipartimento di Scienze Cardiovascolari, Respiratorie, Nefrologiche, Anestesiologiche E Geriatriche, Roma, Italy
Introduction: Sepsis Induced Cardiomyopathy (SIC) is a serious condition during sepsis with a mortality rate up to 70% (1). SIC is clinically manifested with left ventricle impaired contractility (2). Melusin is a muscle-specific protein involved in sustaining cardiomyocyte survival thorough the activation of AKT signaling pathways (3). PI3K– AKT signaling pathway plays a pivotal role in regulating calcium channel activity (4). We hypothesized that Melusin overexpression could exert a protective effect on cardiac function during septic injury.
Methods: Animals were treated with an intraperitoneal injection of lipopolysaccharide (LPS) at 12 mg/kg. SV129 strain Knockout mice (KO) for Melusin gene and FVB strain with cardiac-specific overexpression (OV) of Melusin were compared. Each group was studied together with a control group (WT). Hemocardiac parameters were studied at 0 hour and 6 hours through echocardiography. Another cohort of animals was sacrificed 6 hours after 20 mg/kg LPS treatment and cardiac tissues and blood sample were harvested for Wb analysis to quantify the expression of AKT, P-AKT and CACNA1C and Elisa analysis for Troponin levels.
Results: SV129 WT, KO Melusin and FVB WT mice groups, fractional shortening (FS) was significantly impaired after LPS challenge and was associated with compensatory tachycardia (Fig. 1). FVB OV mice group didn’t show decrease in FS. Consistent with the increased AKT phosphorylation observed in OV mice, the expression of CACNA1C was also significantly higher both at basal levels and after LPS treatment in OV mice compared to WT mice (Fig. 2). Troponin levels didn’t differ between mice groups after LPS treatment
Conclusion: Melusin has protective role in LPS induced cardiomyopathy, likely through Akt phosphorylation controlling the CACNA1C protein density.
1. Neri M et al. Mediators Inflamm. 2016:3423450, 2016
2. Sato R et al. J Intensive Care. 3:48, 2015
3. De Acetis M et al. Circ Res. 96(10):1087–94, 2005
4. Catalucci D et al. J Cell Biol. 184(6):923–33, 2009.
P008 Hepatic function is impaired after abdominal surgery and prolonged sedation and mechanical ventilation
S Liu1, M Jakob2, A Kohler2, D Berger1, S Jakob1
1Inselspital, Bern University Hospital, University of Bern, Department of Intensive Care Medicine, Bern, Switzerland; 2Inselspital, Bern University Hospital, University of Bern, Department of Visceral Surgery and Medicine, Bern, Switzerland
Introduction: Liver dysfunction is frequent in sepsis, but its pathophysiology remains incompletely understood. Since altered liver function has also been described in ICU patients without sepsis [1,2], the influence of sepsis may be overestimated. We hypothesized that sedation and prolonged mechanical ventilation after abdominal surgery is associated with impaired liver function independent of sepsis.
Methods: Sedated and mechanically ventilated pigs underwent abdominal surgery for regional hemodynamic monitoring and were subsequently randomized to fecal peritonitis and controls, respectively (n=4, each), followed by 80 h observation. Indocyanine green (ICG) retention rate 15 minutes after injection of 0.25mg/kg ICG (ICG R15) was determined at baseline, and 11, 32 and 80 h after sepsis induction (SI), and at the same time points in controls. Concurrent with ICG R15, plasma volume, total hepatic perfusion (ultrasound transit time), and bilirubin and liver enzymes were measured. ANOVA for non-parametric repeated measurements was performed in both groups separately.
Results: ICG R15 increased over time without significant differences between groups (Table 1). There was a parallel increase in bilirubin in septic but not control animals. The other measured parameters were similar in both groups at the end of the experiment.
Conclusion: Liver function was impaired under sedation and prolonged mechanical ventilation after abdominal surgery, even in animals without sepsis. The underlying reasons should be further explored.
1. Koch A, et al. Crit Care 15:R266, 2011.
2. Sander M, et al. Crit Care 13:R149, 2009.
Friedman test was used to evaluate the time effect on parameters in each time point, but only Baseline and SI + 80h were shown in this table. No differences between groups. SI, sepsis induction; PV, plasma volume; HF, hepatic blood flow; ALT, Alanine amino transferase; AST, Aspartate amino transferase; PT, prothrombin time
Baseline [Median, (quartile)]
SI + 80h [Median, (quartile)]
P value (Friedman)
ICG R15 (%)
Sepsis (n=4)/Control (n=4)
6.2 (5.3, 19.3)/4.3 (3.3, 19.5)
35.4 (18.7, 47.5)/20.2 (17.4, 33.8)
Sepsis (n=4)/Control (n=4)
2.8 (2.5, 3.1)/2.5 (2.4, 2.7)
3.0 (2.3, 3.7)/3.2 (3.0, 3.5)
Sepsis (n=4)/Control (n=4)
819 (634, 1054)/1319 (1036, 1969)
890 (631, 1062)/1058 (814, 1265)
Bilirubin (μ mol/L)
Sepsis (n=4)/Control (n=4)
0.7 (0.4, 1.0)/1.6 (1.0, 1.9)
4.6 (0.8, 16.3)/0.9 (0.4, 1.8)
Sepsis (n=4)/Control (n=4)
38.5 (27.0, 49.3)/30.5 (17.2, 36.3)
29.0 (22.5, 40.8)/22.0 (18.8, 24.5)
Sepsis (n=4)/Control (n=4)
60.5 (41.3, 67.0)/68.5 (31.8, 116.5)
60.5 (35.8, 78.5)/39.0 (25.5, 41.3)
Sepsis (n=4)/Control (n=4)
13.6 (13.2, 14.5)/13.3 (12.7, 13.8)
14.3 (13.9, 14.7)/13.4 (12.9, 14.2)
P009 Preclinical evaluation of non-anticoagulant heparin in mouse models of inflammation and sepsis.
GA Nicolaes1, DM Beurskens1, P Garcia de Frutos2, J Van Daal3, R Schrijver3, B Kool3, C Aresté2, S De Kimpe3, CP Reutelingsperger1
1Cardiovascular Research Institute Maastricht, Maastricht, Netherlands; 2Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona, Barcelona, Spain; 3Matisse Pharmaceuticals BV, Geleen, Netherlands
Introduction: Previous work has shown the cytoprotective properties of antithrombin-affinity depleted heparin (AADH), by neutralization of cytotoxic extracellular histones , major mediators of death in sepsis [2,3]. AADH was produced from clinical grade heparin, resulting in preparations that have lost >99,5% of their anticoagulant activity. To gain insight into the mechanisms and the basic pharmacological aspects of AADH protective properties, we performed a systematic analysis of how AADH is tolerated in mice and ascertained its effects in three different in vivo models of inflammation and infection.
Methods: Dose ranging studies, short term and medium term, were performed in C57BL/6 mice. The effects of i.v. administration of extracellular histones in the presence or absence of AADH were assessed in mice. We further analysed the effect of AADH in models of Concanavalin A- and MRSA-mediated lethality. In all studies we assessed clinical signs, lab parameters and histology.
Results: AADH was well tolerated in both short term and intermediate term (till 7 days) experiments in mice, in the absence of any signs of tissue bleeding. AADH was able to revert the cytotoxic properties of i.v. administered histones.
In a Concanavalin A mediated model of sterile inflammation, we confirmed that AADH has protective properties that counteract the cytotoxic effects of extracellular histones. In an in vivo lethal MRSA model, for the first time, AADH was shown to induce a survival-benefit.
Conclusions: We conclude that AADH contributes to the overall increased survival by means of neutralization of extracellular histones and represents a promising product for further development into a drug for the treatment of inflammatory diseases and sepsis.
 Wilhagen et al, Blood 123:1098-1101, 2014
 Xu et al, Nat Med 15:1318-1321, 2009
 Thromb Res 136:542-7, 2015
P010 Differential modulation of plasminogen activator mediated thrombolysis by recombinant thrombomodulin and activated protein c
Z Siddiqui1, S Raghuvir1, J Fareed1, R Wasmund1, O Iqbal1, W Jeske1, D Hoppensteadt1, K Tanaka2, K Tsuruta2
1Loyola University Medical Center, Maywood, IL, USA; 2Asahai Kasei Pharma America Corporation, Waltham, MA, USA
Introduction: Urokinase (UK) and tissue plasminogen activator (tPA) mediate thrombolytic actions by activating endogenous plasminogen. Thrombomodulin (TM) complexes with thrombin to activate Protein C and thrombin activatable fibrinolysis inhibitor (TAFI). Activated Protein C (APC) modulates coagulation by digesting factors V and VIII and activates fibrinolysis by decreasing PAI-1 functionality.
Methods: The purpose of this study is to compare the effects of rTM and APC on urokinase and tPA mediated thrombolysis utilizing thromboelastography.
Results: Native whole blood was activated using a diluted intrinsic activator (APTT reagent, Triniclot). The modulation of thrombolysis by tPA and UK (Abbott, Chicago, USA) was studied by supplementing these agents to whole blood and monitoring TEG profiles. APC (Haematologic Technologies, VT, USA) and rTM (Asahi Kasai Pharma, Tokyo, Japan) were supplemented to the activated blood at 0.02 – 3.0 ug/ml. The modulation of tPA and UK induced thrombolysis by APC and rTM was studied in terms of thromboelastograph patterns. The effect of both APC and rTM on plasma based systems supplemented with tPA was also investigated.
Conclusions: In comparison to rTM, APC produced a stronger anticoagulant effect in terms of r time, k time, angle and MA. 3.0ug/ml rTM and APC did not produce any direct fibrinolytic effects. APC also produced strong augmentation of the lytic of effects of tPA and urokinase. rTM at lower concentrations produced stabilization of clot resisting fibrinolysis.
P011 Anticoagulant actions of recombinant thrombomodulin and activated protein c and their neutralization by factor viii inhibitor bypass activity (FEIBA)
Z Siddiqui1, W Jeske1, M Lewis1, P Aggarwal1, O Iqbal1, D Hoppensteadt1, K Tsuruta2, J Fareed1, S Mehrota1, R Wahi1
1Loyola University Medical Center, Maywood, IL, USA; 2Asahai Kasei Pharma America Corporation, Waltham, MA, USA
Introduction: Thromboelastographic (TEG) analysis represents a global approach to monitor the clotability of the native whole blood. rTM (recombinant Thrombomodulin) is a mild anticoagulant with pleiotropic actions which are modulated through its complexation with thrombin. Activated protein C (APC) is a stronger anticoagulant which mediates its action via digestions of factor Va and VIIIa. FEIBA (Factor VII Inhibitor Bypass Activity) contains non activated factors II, IX and X and activated factor VII. The purpose of this study is to compare the relative anticoagulant effects of rTM and APC, employing the thromboelastographic analysis and their neutralization by graded amounts of FEIBA.
Methods: Citrated whole blood samples were supplemented with rTM and APC at a concentration of 3 ug/mL (n=20). TEG analysis was performed on a TEG 5000 system in which clotting was initiated by re-calcification of the whole blood and set parameters as R time, K time, MA and Angle were measured. The relative neutralization profiles of the APC and rTM by FEIBA at 1.0, 0.1, and 0.01 U/ml were investigated.
Results: At 3ug/ml rTM produced a mild anticoagulant effect as evident by its TEG profile in terms of prolongation of R and K times and marked decrease in angle and maximum amplitude. APC at 3 ug/mL produced a relatively stronger anticoagulant effects on all of the parameters in the TEG profile. The supplementation of FEIBA at 0.1 U/mL to the whole blood mixtures containing 3 ug/mL completely neutralized rTM and resulted in the partial neutralization of APC.
Conclusions: These results indicate APC is a stronger anticoagulant in comparison to rTM as measured by the TEG analysis. FEIBA is very effective in the neutralization of the anticoagulant effects of rTM and results in a weaker neutralization of APC. These results suggest that FEIBA can be used to neutralize rTM at much lower levels than the proposed dosing for the bleeding control of hemophilia.
P013 Acid-base profile of patients with infection during the first 24 hours of intensive care unit admission
RM Roepke, BA Besen, PV Mendes, LU Taniguchi, M Park
Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
Introduction: Acid-base disturbances are common in patients with infection admitted to the intensive care unit (ICU). More attention is given to hyperlactatemia in this patient population as a prognostic factor, although other acid-base disturbances may also have an impact on patient outcomes. Our objective is to describe the acid-base profile of this patient population and determine the association between different acid-base abnormalities and ICU mortality.
Methods: Retrospective cohort of patients admitted with infection to an intensive care unit. Patients were stratified according to pH (<7.35; 7.35 – 7.45; > 7.45) and, then, according to the standard base excess (SBE) (< -2; -2 – +2; > +2). In each of these strata and the whole population, the proportions of acid-base disturbances were quantified during the first 24 hours of ICU admission. To assess the association between acid-base disturbances and outcome, a logistic regression model was fit, adjusting for age, sex and SAPS 3 score.
Results: 605 patients were analysed. 304 (50%) patients were acidemic and 244 (40%) presented with a normal pH. Metabolic acidosis (as assessed by SBE) was observed in all subgroups, regardless of pH levels (pH < 7.35: 287/304 [94%]; pH 7.35 – 7.45: 184/244 [75%]; pH > 7.45: 34/57 [60%]). Lactic acidosis was observed in 71% of the whole population; SIG (Strong ion gap) acidosis, in 75%; SID (hyperchloremic) acidosis, in 58%; metabolic alkalosis, in 7%; and respiratory acidosis, in 13% of the patients. In multivariate analysis, lactic acidosis (OR 1.85 [95% CI 1.19 – 2.88]), albumin (OR 0.49 [95% CI 0.34 – 0.69]) and phosphate (OR 1.15 [95% CI 1.05 – 1.26]) were the acid-base variables independently associated with ICU mortality.
Conclusions: The most common form of acid-base disturbance in patients with infection is SIG acidosis, although only lactic acidosis is independently associated with worse outcomes among strong ions. Weak anions variations are also independently associated with worse outcomes.
Y Irie, H Ishikura, R Hokama, M Koie, K Muranishi, K Hoshino, R Yuge, T Kitamura, M Iwaasa
Fukuoka University Hospital, Fukuoka city, Japan
Introduction: Recently, it was clarified that zinc plays a pivotal role of inflammation and its deficiency resulted in deterioration of severe organ dysfunction including coagulopathy in patients with sepsis.
The purpose of present study is to clarify the relationship between serum zinc level and organ dysfunction especially sepsis-induced coagulopathy.
Methods: The present study was conducted a single-center retrospective observational study from June 2016 to September 2017. Blood samples were collected on ICU admission.
Results: 128 patients were enrolled. Of the 108 patients, 100 patients were sepsis and 8 patients were non-sepsis. The serum zinc levels were significantly lower in the sepsis group than in the non-sepsis group (33.5±19.2 vs 66.5±14.2μ g/dL, p<0.01). Next, we divided sepsis group into two groups using SOFA score (SOFA≧8 and SOFA <8). Zinc level was significantly lower in group of SOFA>8 group than in group of SOFA <8. However, there were no significant between two groups such as calcium, phosphorus and magnesium. We analyzed the relationships between zinc and each factor of SOFA score. There was the most significant correlation between zinc level and Coagulation (r=-0.49, p<0.001). We performed ROC analysis to predict of DIC. The area under the curve of serum zinc level was 0.700, and cut off value of zinc was 25μ g/dL (sensitivity 0.629 and specificity 0.783, p<0.001). Using this zinc cutoff value, the sepsis group was divided into two groups. The 28-day mortality rate of zinc<25μ g/dL group was significantly higher than that of zinc>25 μ g/dL group.
Conclusions: Our result suspected that zinc levels are closely related to sepsis induced coagulopathy.
P015 Association between inflammatory markers and cognitive outcome in patients with acute brain dysfunction due to sepsis
G Orhun1, E Tuzun2, P Ergin Ozcan1, C Ulusoy2, E Yildirim2, M Kucukerden2, H Gurvit3, F Esen1
1Istanbul University; Medical Faculty of Istanbul, Anesthesiology and Intensive Care, Istanbul, Turkey,2Istanbul University, Institute of Experimental Medicine, Neuroscience, Istanbul, Turkey,3Istanbul University; Medical Faculty of Istanbul, Department of Neurology, Behavioral Neurology and Movement Disorders Unit, Istanbul, Turkey
Introduction: Sepsis-induced brain dysfunction has been neglected until recently due to the absence of specific clinical or biological markers. There is increasing evidence that sepsis may pose substantial risks for long term cognitive impairment.
Methods: To find out clinical and inflammatory factors associated with acute sepsis-induced brain dysfunction (SIBD) serum levels of cytokines, complement breakdown products and neurodegeneration markers were measured by ELISA in sera of 86 SIBD patients and 33 healthy controls. Association between these biological markers and cognitive test results was investigated.
Results: SIBD patients showed significantly increased IL-6, IL-8, IL-10 and C4d levels and decreased TNF-α, IL-12, C5a and iC3b levels than healthy controls. No significant alteration was observed in neuronal loss and neurodegeneration marker (neuron specific enolase (NSE), amyloid β, tau) levels. Increased IL-1β, IL-6, IL-8, IL-10, TNF-α and decreased C4d, C5a and iC3b levels were associated with septic shock, coma and mortality. Transient mild cognitive impairment was observed in 7 of 21 patients who underwent neuropsychological assessment. Cognitive dysfunction and neuronal loss were associated with increased duration of septic shock and delirium but not baseline serum levels of inflammation and neurodegeneration markers.
Conclusions: Increased cytokine levels, decreased complement activity and increased neuronal loss are indicators of poor prognosis and adverse events in SIBD. Cognitive dysfunction and neuronal destruction in SIBD do not seem to be associated with systemic inflammation factors and Alzheimer disease-type neurodegeneration but rather with increased duration of neuronal dysfunction and enhanced exposure of the brain to sepsis-inducing pathogens.
P016 Altered serum profile of aromatic metabolites reflects the biodiversity reduction of gut microbiota in critically ill patients
N Beloborodova, E Chernevskaya, A Pautova, A Bedova, A Sergeev
Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russia
Introduction: High levels of some aromatic microbial metabolites (AMM) in serum are related to the severity and mortality of critically ill patients . Several studies have discussed the imbalance and loss of the diversity of gut microbiota but there are practically no data on the gut microbial metabolites in critical conditions, only a little - in healthy people [2, 3]. The aim of this work is to analyze the connection between serum and fecal levels of AMM in ICU patients.
Methods: 13 simultaneously serum and fecal samples (SFS) from ICU patients with nosocomial pneumonia (group I), 21 SFS from ICU neurorehabilitation patients (group II) and 5 SFS from healthy people were taken for GC/MS analyses. The following AMM were measured: phenylpropionic (PhPA), phenyllactic (PhLA), p-hydroxybenzoic (p-HBA), p-hydroxyphenyllactic (p-HPhLA), p-hydroxyphenylacetic (HPhAA), p-hydroxyphenylpropionic (p-HPhPA) and homovanillic (HVA) acids. Data were presented as medians with interquartile range (IR, 25-75%) using STATISTICA 10.
Results: The sum of the level of 4 most relevant metabolites (4AMM) - PhLA, p-HPhLA, p-HPhAA, and HVA - in serum samples from group I and group II were equal to 0.9 (0.6-9.6) μ M and 0.7 (0.5-1.0) μ M, respectively, and were higher than in healthy people – 0.4 (0.4-0.6) μ M (p<0.05). We suppose the presence of the correlation of AMM profile in blood and intestine. Particularly, SFS of healthy people are characterized by the prevalence of PhPA; AMM are not detected in feces of non-survivors but only HVA dominates in their serum in the absence of other (Fig. 1).
Conclusions: The AMM profiles in gut and serum are interrelated; AMM in serum probably reflect the violation and loss of biodiversity of the gut microbiota in critically ill patients.
1. Beloborodova NV. Sepsis. Chapter 1. 2017. DOI: 10.5772/68046
2. McDonald D et al. mSphere 1(4): e00199-16, 2016
3. Jenner AM et al. Free Radic Biol Med 38:763–772, 2005
H Brodska 1, V Adamkova1, K Pelinkova1, A Studena1, J Zavora1, T Drabek2
1Charles University, Prague, Czech Republic,2University of Pittsburgh, Pittsburgh, PA, USA
Introduction: Sepsis is one of the most prevalent causes of morbidity and mortality in hospitalized patients worldwide. Early initiation of targeted antibiotic therapy is crucial. Blood stream infections are commonly divided to Gram positive (G+) or Gram negative (G-). However, blood cultures (BC) read-out may be delayed or cultures may be negative (NEG). Biomarkers may help to guide antibiotic therapy prior to BC results . We tested the hypotheses that 1) biomarkers will discriminate between BC- vs. BC+ patients; 2) biomarkers will discriminate between G+ and G- sepsis; 3) biomarkers will correlate with severity of illness.
Methods: With IRB approval, a patient cohort (n=60) admitted to mixed ICU for suspected sepsis were enrolled in a prospective observational study. BC and biomarkers of sepsis (C-reactive protein, CRP; procalcitonin, PCT; presepsin, PRE; leukocytes, LEU) were assessed and SOFA and qSOFA were determined on admission. Data are displayed as mean±SD or median [IQR]. One-way ANOVA with post-hoc Tukey’s test, Kruskal-Wallis test or Mann-Whitney test were used as appropriate. Pearson’s test was used to assess correlation between SOFA and biomarkers.
Results: CRP was the only biomarker different between BC- (33 [3, 64] mg/L) vs. BC+ (147 [51, 256] mg/L) patients (p=0.003). Numerically higher values were observed in G- patients. CRP was higher in G+ (p=0.006) and G- (p=0.023) vs. NEG. PCT was higher in G+ vs. NEG (p=0.037). LEU were higher in G- vs. NEG (p=0.044) and vs. G+ (p=0.015). PRE was not different between groups (Table 1). In BC- patients, SOFA score did not correlate with any biomarkers. In BC+ patients, SOFA correlated with CRP (p=0.005) and LEU (p=0.023). PRE correlated with SOFA in G+ patients (p=0.032).
Conclusions: In our limited sample-size pilot study, tested biomarkers showed limited capacity to identify BC+ patients and the type of infection. Higher values of biomarkers observed in G- sepsis warrant further study.
 Brodska H et al. Clin Exp Med 13(3):165-70, 2013.
P018 Clinical and diagnostic value of plasma concentration of nitrogen oxide in newborns with respiratory diseases
MG Pukhtinskaya, V Estrin
State Medical University, Rostov-on-Don, Russia
Introduction: Since nitrogen oxide (NO) is an essential component of the immune system, the dynamics of plasma NO concentration was studied in order to predict the development of sepsis [1, 2].
Methods: With the permission of the Ethics Committee included the 200 full-term newborns with respiratory diseases on a ventilator, retrospectively divided into two groups (I, n=46 - sepsis 4-5 days; II, n=154 without sepsis), at 1, 3-5, 20 days was studied by ELISA the plasma concentration of NO, NOS-2, NOS-3, ADMA (Multilabel Coulter Victor-21420, Finland). To select points "Cut-Off" used the method of ROC-Lines.
Results: The statistical power of the study was 86.7% (Î±<0.05). At admission in patients of groups I and II decrease the concentration of NO and increased ADMA in plasma (p<0.05) relative to healthy newborns. After 3-5 days, relatively in patients of groups I and II increased (p<0.05) plasma concentrations of NO, NOS-2, NOS-3, ADMA. NO concentration in patients with sepsis (I) was lower (p<0.05) compared to group II patients at all stages of observation.
NO concentration in plasma of less than 7.30 μmol/l at admission predicted the development of sepsis with a sensitivity of 88.00% and a specificity of 82.66%.
Conclusions: The significance of a low concentration of NO in the development of sepsis confirms the relevance of further study of the efficacy, safety and cost-effectiveness of prevention of sepsis, inhaled nitric oxide or other donators NO.
1. Ryazantseva NV. Cytology 54:105-111.105-111, 2012.
2. Puhtinskaya M. Critical Care 18:288, 2014.
P019 Plasma myeloperoxidase conjugated-DNA level as predictors of outcome and organ dysfunction in septic shock patients: possible therapeutic effect of hemoperfusion with a polymyxin B immobilized fiber column
N Takeyama, Y Maruchi, T Gocho, H Mori, N Takenaka, M Tsuda, H Noguchi
Aichi Medical University, Aichi, Japan
Introduction: We have previously reported that hemoperfusion with polymyxin B immobilized on polystyrene fibers in a cartridge (PMX-DHP) reduces endothelial damage by selective removal of activated neutrophils. Ex vivo perfusion experiments demonstrated that activated neutrophils adhered preferentially to PMX filters and that the remaining neutrophils caused less endothelial damage. There is, however, no report about the effect of PMX-DHP on neutrophil extracellular traps (NETs) formation. The objectives of this study were to investigate the correlations between plasma myeloperoxidase (MPO) conjugated-DNA level with degree of organ dysfunction, disease severity, and ICU mortality in septic shock patients. We also investigated the effect of PMX-DHP on MPO-DNA level.
Methods: Sixty-five septic shock patients admitted at the ICUs of 35 Japanese hospitals treated with PMX-DHP were enrolled. Septic shock was identified using old definition according to the ACCP/SCCM in 1997. Plasma MPO-DNA was measured by sandwich ELISA with anti-MPO and anti-DNA monoclonal antibodies.
Results: On day 1, septic shock patients displayed a marked increase of plasma MPO-DNA level compared with the healthy volunteers (p=0.008). Plasma MPO-DNA levels were significantly decreased on days 3 and 7 after PMX hemoperfusion. By correlation study, the MPO-DNA level on 7th day was inversely correlated with both the mean arterial pressure (p=0.048) and P/F ratio (p=0.003) at 7th day. Positive correlation was observed between plasma MPO-DNA level on 7th day and SOFA at 7th day (p=0.017). Using Wilcoxon signed-rank test the high MPO-DNA on 3rd day was found to be associated with the hospital mortality (p=0.019).
Conclusions: High MPO-DNA levels at 3rd and 7th days of septic shock patients are associated with the degree of organ dysfunction and hospital mortality. The beneficial effects of PMX-DHP may be at least partially due to the inhibition of excessive NETs formation.
M Ferrari, G Keegan, K Williams, ID Welters
Royal Liverpool University Hospital, Liverpool, UK
Introduction: Neutrophil-to-lymphocyte ratio (NLR) has been used to predict patient outcomes, with higher values linked to negative prognosis . However, most studies investigate NLR on admission to Critical Care only . In this study we analysed NLR values and trends over a 7-day observation period to define different time courses in survivors and non-survivors of critical illness.
Methods: This retrospective study included Intensive Care Unit (ICU) patients admitted to the Royal Liverpool University Hospital over a 4-year period. Age, gender, sepsis status (type of sepsis and date of sepsis), length of ICU stay, 28-day mortality and ICU outcome were collected. WCC, lymphocytes and neutrophils values were recorded for the first 7 days after ICU admission. NLR values were calculated for the first 7 days of intensive care admission. Patients with haematological malignancies and readmissions were excluded.
Results: Data were available for 542 patients. 28-day mortality was 20.3% and ICU mortality was 16.6%. Mean NLR in survivors decreased over the 7-day period, whereas mean NLR in non-survivors remained high throughout the 7-day period. Comparing the mean NLR value of the first 2 days (days 1 and 2) with the mean NLR value of the last 2 days (days 6 and 7), patients were divided into 3 groups: decreasing, stable and increasing NLR. The 28-day mortality was respectively 12,4%, 29,9% and 37,8% (P value < 0,01) and the ICU mortality was 9,7%, 24,8% and 32,4% (P-value < 0,01).
Conclusions: NLR trend over the first 7 days correlates with mortality in ICU, differing significantly between survivors and non-survivors, and could be used as an outcome predictor.
1. Hwang SY et al. Am J Emerg Med 35(2):234-239, 2017.
2. Salciccioli JD et al. Crit Care 19:13, 2015.
P021 The platelet, eosinophil, age, red cell distribution width (PEAR) score and out-of-hospital outcomes in critical illness survivors
L Maher1, L Roeker2, T Moromizato3, F Gibbons4, KB Christopher5
1The Lahey Hospital & Medical Center, Burlington, VT, USA,2Memorial Sloan Kettering Cancer Center, New York, NY, USA,3Okinawa Southern Medical Center and Children’s Hospital, Naha, Japan,4Massachusetts General Hospital, Boston, MA, USA,5Brigham and Women's Hospital, Boston, MA, USA
Introduction: Simple and accurate identification of high-risk critical illness survivors may allow for targeted monitoring and interventions that may improve outcomes. Our primary study objective was to determine if a risk prediction score based on demographics and surrogates for inflammation measured at ICU admission was predictive for post-hospital outcomes.
Methods: The PEAR score was previously derived and validated for mortality utilizing ICU admission data (age, gender, surgical vs. medical patient type, red cell distribution width, platelet count and peripheral blood eosinophil count). We performed a 2 center cohort study of 67,591 patients admitted to a MICU or SICU from 1997-2012, who survived to hospital discharge. The primary outcome was 90-day post-hospital discharge mortality. Adjusted odds ratios were estimated by logistic regression models including terms for the PEAR score, sepsis, number of acute organ failures, Deyo-Charlson comorbidity index, and the actual length of stay less the national geometric mean length of stay.
Results: The cohort was 58% male, 49% surgical ICU with a mean age of 62 years and a 90-day mortality rate of 7.8%. 10% were diagnosed with sepsis. Mean length of stay was 11.2 days. Unplanned 30-day readmission rate was 14%. Patients with the second highest and highest quartile of PEAR Score have an adjusted OR of 90-day post-discharge mortality of 3.95 (95%CI, 3.45-4.52; P< 0.001) and 8.21 (95%CI, 7.16-9.43; P< 0.001) respectively, relative to patients with the lowest quartile of PEAR Score. The AUC for the adjusted prediction model was 0.77. Further, patients with the second highest and highest quartile of PEAR Score have an adjusted OR of 30-day readmission of 1.38 (95%CI, 1.29-1.48; P< 0.001) and 1.64 (95%CI, 1.52-1.78; P< 0.001) respectively, relative to patients with the lowest quartile of PEAR Score.
Conclusions: Our simple PEAR score robustly predicts the risk of out of hospital outcomes in critical illness survivors.
P022 Validation of the neutrophil-lymphocyte count ratio and leukocyte score as prognostic markers in community acquired pneumonia
M Morales-Codina, R Subirana, A Pérez, N Bacelar, J Font, N Angrill, M Gallego, E Diaz, J Vallés
CSU Parc Tauli, Sabadell, Spain
Introduction: Some studies suggest the Neutrophil-Lymphocyte Count Ratio (NLCR) and Leukocyte Score (LS) are better in stratifying Community Acquired Pneumonia (CAP) severity than traditional methods. Both can be quickly performed with standard practice cost-effective exams but require further investigation [1, 2].
Methods: A retrospective analysis was performed on all ED adults with CAP from Oct. 2009 to Jan. 2011. Demographics, FINE, CURB-65, ATS criteria and initial blood tests were collected, admission to ICU and outcome at 30 days evaluated. The scoring systems prognostic value were compared through ROC curves. Cutoffs used were >=10:1 for NLCR and a score >=2 points for LS.
Results: 1059 patients were enrolled (mean age 65.3 ± 19.7 years, 61.7% male). The most prevalent comorbidities were COPD (18.2%), chronic renal disease (10.3) and solid neoplasm (7.2). ICU admission rate was 6.2% with an average APACHE II of 17.6 points. Overall mortality was 8.3%, 16.7% in ICU. The average CURB-65 scoring was 1.4 ± 1.2 points and FINE 92.6 ± 43.5. 21.3% met >=3 minor ATS criteria.
In our population the area under the ROC curve were, respectively for predicting admission to ICU and mortality at 30 days, 0.616 and 0.530 for NLCR, 0.559 and 0.615 for IS; versus 0.654 and 0.875 for FINE score, 0.756 and 0.739 for the ATS criteria, whereas 0.706 and 0.796 for the CURB-65.
Conclusions: The NLCR and LS showed a lower discriminative power compared to traditional FINE, ATS criteria and CURB-65 when applied in a much larger population than their original studies.
1. Cornelis PC et al. PLoS One 7:e46561, 2012
2. Blot M et al. Open Forum Infectious Diseases 1:ofu075, 2014
P023 Biomarkers of platelet activation and their prognostic value in patients in sepsis associated coagulopathy
D Hoppensteadt1, G Wegryzn1, A Walborn1, P Maia1, S Walborn1, R Green1, M Mosier1, M Rondina2, J Fareed1
1Loyola University Medical Center, Maywood, IL USA, 2University of Utah School of Medicine, Salt Lake City, UT, USA
Introduction: Sepsis-associated disseminated intravascular coagulation (SAC) is associated with decreased platelet counts and formation. The widespread activation of platelets contribute to vascular occlusions, fibrin deposition, multi-organ dysfunction, contributing to a two-fold increase in mortality. The purpose was to measure markers of platelet function in the plasma of patients with clinically established SAC and to determine association to disease severity and outcome.
Methods: Plasma samples from 103 adult intensive care unit (ICU) patients with sepsis and suspected SAC were collected at baseline and on days 4 and 8. DIC scores were calculated using platelet count, D-Dimer, INR, and fibrinogen. Patients were categorized as having no DIC, non-overt DIC, or overt DIC. Plasma levels of CD40L, von Willebrand Factor (vWF), platelet factor-4 (PF-4), and microparticles (MP) were quantified using commercially available ELISA methods.
Results: Markers of platelet activation were significantly elevated in patients with sepsis alone and with suspected DIC compared to normal healthy individuals on ICU day 0 (p<0.001). Levels of platelet-associated biomarkers were compared between survivors and non-survivors. PF-4 was significantly decreased in non-survivors compared to survivors (p = 0.0156). Patients were stratified based on platelet count and levels of markers were compared between groups. CD40L, vWF, PF4, and MP showed significant variation based on platelet count, with all markers exhibiting stepwise elevation with increasing platelet count.
Conclusions: Markers of platelet activation were significantly elevated in patients with SAC compared to healthy individuals. PF4 levels showed significant difference based on DIC score or mortality, and differentiated the non-survivors compared to survivors. CD40L, vWF, PF4, and MP showed significant association with platelet count, increasing in a stepwise manner with increases in platelet count (Table 1).
Markers of platelet activation on Day 0 vs. platelet count
127.0 ± 46.0
158.0 ± 42.0
274.0 ± 37.0
496.0 ± 94.0
218.0 ± 35.0
268.0 ± 18.0
274.0 ± 16.0
232.0 ± 8.6
46.0 ± 3.4
52.0 ± 5.6
81.0 ± 8.2
84.0 ± 4.6
20.0 ± 4.8
20.0 ± 5.5
29.0 ± 4.3
47.0 ± 4.0
King Hamad University Hospital, Bussaiteen, Bahrain
Introduction: Mean Platelet Volume (MPV) has been reported as a valuable marker of inflammatory diseases. The aim of the current study is to assess the prognostic value of MPV in septic patients.
Methods: Prospective study including all patients admitted to the intensive care unit (ICU) with sepsis or septic shock. Demographic, clinical and laboratory data were collected. The MPV was checked on admission and on day 3. Two groups were compared: Survivors and non-survivors.
Results: Thirty-four patients were included. Median age was 69[62-77] years. sex-ratio was 1.8. Median APACHEII score was 21[16-28]. Platelets count on admission was 264[177-391] with a MPV of 8.4[8-9.3] FL. On day3, platelets count was 183[101-265] with a MPV of 8.6[8-9.4] FL. MPV increased on day 3 in 19 patients (55.9 %). Mechanical ventilation was required for 20 (58.8 %) patients and CRRT was required for 14 (41.2 %) patients. The ICU length of stay was 7[3-12] days. Twelve patients died in the ICU (35.3 %).
Survivors were younger than non-survivors (66[60-76] versus 73[69-86] years; p = 0.016) and had lower APACHEII score (20[15.8-25.5] versus 27[20-33.5]; p = 0.04). MPV on admission and on day 3 were comparable between the two groups (respectively 8.3[8-9.5] versus 8.5[7.6-9.3] FL; p = 0.999 and 8.5[7.9-9.3] versus 9[8.2-9.6] FL; p = 0.369). However, the platelets count on D3 was significantly lower in the non-survivors (227[132-336] versus 113[44-231]; p = 0.049). The ICU length of stay was 7[3-12] days in survivors and 8.5[3.5-12] days in non-survivors (p=0.623).
Conclusions: The decrease of the platelet count but not the increase of the MPV was associated with increased mortality in critically-ill septic patients.
P025 Endotoxin activity assay levels measured within 24 hours after ICU admission affected patients’ severity assessments
A Kodaira1, T Ikeda2, S Ono2, S Suda2, T Nagura2
1Tokyo Medical University, Tokyo, Japan,2Tokyo Medical University, Hachioji Medical Center, Tokyo, Japan
Introduction: Endotoxin is a major component of the cell wall of Gram-negative bacteria and is the principal molecule responsible for the induction of septic shock. A prospective cohort study (MEDIC study) of 857 consecutive new ICU patients evaluated the usefulness of endotoxin activity assay (EAA) as a diagnostic tool in sepsis and septic shock.
Methods: This study was performed to classify EAA values measured within 24 hours of ICU admission into a high risk (H) group (EAA>0.6; N=154; mean age ± SD = 64±13; median 70) and a low risk (L) group (EAA<0.4; N=174; 68±16; 72), and then, to evaluate patient severities (APACHE 2 score, SOFA score) and sepsis-related biomarkers (procalcitonin, IL-6, angiopoietin 2), comparing groups. Results were expressed as the mean ± SD (median). The Mann-Whitney U-test and chi-square test or Fisher’s test were used for statistical analysis.
Results: The APACHE 2 score of the H-group was 26.5±9.5 (27.0), while that in the L-group was 19.9±9.1 (18.0), and the difference between the groups was statistically significant (p<0.05). The SOFA score of the H-group was 9.6±4.1 (10.0) and that of the L-group was 7.2±4.6 (6.5) (p<0.05).
PCT of the H-group was 37.8 ±58.5(11.7)and that in the L-group was 9.6±25.5 (1.6), but there was no significant difference between the groups. IL-6 of the H-group was 19,483±61,281 (1160) and that of the L-group was 6256±39,321 (144). Angiopoietin 2 of the H-group was 12,822±10,593 (10,100) and that in the L-group was 6004±4441 (4105). These two biomarkers indicated significant differences between the groups.
Survival rate of the H-group was 78.9% (153 survived, 41 died), and that of the L-group was 85.5% (147 survived, 25 died). Statistically, there was no significant difference between the groups.
Conclusions: These results indicate that the EAA value measured within 24 hours after ICU admission is a useful marker for a patient’s severity assessment, but not for outcome prediction.
P026 Interleukin 10 release after ex vivo stimulation of whole blood predicts clinical outcomes in sepsis
H Perrichet1, C Martin-Chouly2, JT Ross3, C Rousseau2, P Seguin1, N Nesseler1
1University Hospital Pontchaillou, Rennes, France,2Rennes 1 University, Rennes, France,3University of California, San Francisco, CA, USA
Introduction: Sepsis profoundly alters immune homeostasis by inducing first a systemic pro-inflammatory, then an anti-inflammatory state. We evaluate the prognostic value of ex vivo lipopolysaccharide (LPS) stimulation of whole blood in septic patients, at day 1 and 7 after intensive care unit (ICU) admission.
Methods: This prospective cohort study included patients with severe sepsis or septic shock admitted to a surgical ICU of a university hospital. Blood was drawn on day 1 and day 7, and stimulated ex vivo with LPS for 24 hours. Tumor necrosis factor alpha (TNF), interleukin (IL) 1, IL6 and IL10 were measured. Twenty-three healthy adults served as controls. Outcomes were ventilator and ICU-free days, SOFA score at day 1 and 7, and need for dialysis during the course of sepsis.
Results: Forty-nine patients were included (mean age 62 ± 15 years). The blood of septic patients was less responsive to ex vivo stimulation with LPS than that of healthy controls, as demonstrated by lower TNF, IL1, IL6 and IL10 release (Fig. 1). At day 1, patients above the 50th percentile of IL10 release had significantly fewer ventilator and ICU-free days than those in the lower 50th percentile (Fig. 2). In contrast, patients in whom IL10 release increased between day 1 and day 7 had significantly lower SOFA scores at day 1 and 7 and need for dialysis, and more ICU-free days than patients in whom IL10 release decreased (Table 1).
Conclusions: Greater LPS-stimulated IL10 release in septic patients at day 1 was associated with poorer clinical outcomes and may reflect the severity of the forthcoming immunoparalysis. However, an increase in IL10 release between day 1 and day 7 was associated with favorable outcomes, perhaps signaling immune restoration.
Clinical outcomes of septic patients according to interleukin 10 release evolution between day 1 and 7 after ICU admission
Patients who decrease IL10 release (n=11)
Patients who increase IL10 release (n=24)
Age (years, mean ± SD)
58 ± 17
61 ± 15
SOFA score at day 1 (mean ± SD)
9 ± 4
6 ± 3
SOFA score at day 7 (mean ± SD)
5 ± 5
2 ± 2
ICU free-days (days, mean ± SD)
12 ± 10
20 ± 6
Ventilation free-days (days, mean ± SD)
20 ± 9
25 ± 4
Dialysis (n, %)
3-month mortality (n, %)
P027 Is serum procalcitonin a reliable marker of bacterial sepsis after hyperthermic intraperitoneal chemotherapy with cytoreductive surgery (HIPEC-CRS)?
Y Al Drees, A Alrbiaan, A Elhazmi, T Amin, N Salahuddin
King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
Introduction: Hyperthermic Intraperitoneal Chemotherapy with Cytoreductive Surgery (HIPEC-CRS) is a curative treatment modality for peritoneal carcinomatosis. Extensive debulking surgery, peritoneal stripping and multiple visceral resections followed by intraperitoneal installation of heated high-dose chemotherapeutic agents, a process leads to a ‘high-inflammatory’ syndrome. Serum procalcitonin (PCT), a biomarker for bacterial sepsis, in the heightened inflammatory state after HIPEC-CRS might be of limited utility. Our aim is to determine the trends of PCT in the early postoperative phase of HIPEC-CRS and to identify trends in patients with and without bacterial sepsis
Methods: In a case-control design, we reviewed all patients undergoing HIPEC-CRS over a 24-month period (2015-2017). Patients were divided into 2 groups based on whether they developed bacterial sepsis in the first 5 days after surgery (infected v/s non-infected). Summary data are expressed as medians and ranges. Two-tailed nonparametric tests were performed and considered significant at p values of less than 0.05
Results: 82 patients’ data was analyzed. Infections developed in 16% (13 patients) with Escherichia coli as the predominant pathogen isolated (36% isolates). PCT levels (ngm/ml) were elevated postoperatively in both infected and non-infected patients; Day 1 infected 0.97 (IQR 0.5, 3.2) v/s non-infected 0.68 (0.2, 1.6) p=not significant (ns), Day 2 infected 1.14 (0.8,4.2) v/s 1.2 (0.5, 3.4) p=ns, Day 3 infected 1.82 (0.6, 11.5) v/s 0.73 (0.3, 2.2) p=0.05. The differences became statistically significant only by the 4th day (Fig. 1); Day 4 infected 1.32 (0.4, 8.2) v/s 0.53 (0.19, 1.1) p=0.012, Day 5 infected 0.85 (0.09, 3.9) v/s 0.28 (0, 0.7) p=0.047
Conclusions: HIPEC-CRS is associated with an early postoperative increase in PCT levels, independent of the presence of bacterial sepsis. The study demonstrate that HIPEC-CRS is a stimulus for PCT release and that decisions for antimicrobial therapy should not be based solely on elevated PCT values
S Sudarsanan, A Pattath, A Omar, P Sivadasan, S Aboulnaga, F Hamwi, A Al Khulaifi
Heart Hospital, Hamad Medical Corporation, Doha, Qatar
Introduction: Early outcome in cardiac surgery has been an area of growing interest where the given risks raise several predictive models for assessment of postoperative outcome . Procacitonin (PCT) emerges as a possible predictive tool in cardiothoracic intensive care unit (CTICU).We aim at testing the predictive power of PCT for early morbidity, prolonged ventilation, ICU and hospital stay, in patients developing early fever after cardiac surgery
Methods: A retrospective descriptive study done in tertiary cardiac center, enrolling patients who stayed for more than 24 hours post-operatively in the CTICU Risk stratification included additive Euro score and PCT immunoluminometricaly prior to surgery and every 48 hours in response to onset of fever.
Results: We screened 501 consecutive patients who underwent open heart cardiac, of which 119 patients were enrolled in the study. Patients were divided into two groups based on the level of PCT, those with value > 2 ng/ml (Group 1) and those with level < 2 ng/ml (Group 2). Patients in group 1 as compared to Group 2, over the postoperative course was associated with prolonged ICU stay (P=0.04), length of mechanical ventilation (P=0.05), length of hospitalization (p=0.05), acute kidney injury (P=0.04) and culture positivity (P=0.02). Multivariate analysis showed that PCT >2ng/ml was was significantly associated with positive cultures. (p=0.023)
Conclusions: A rise of serum PCT carries the signals of early ICU morbidity and lengths of ventilation, ICU stay and hospital stay
1. Iyem H. Cardiovasc J Afr 20(6):340-3, 2009.
S Sudarsanan, A Pattath, A Omar, P Sivadasan, S Aboulnaga, F Hamwi, A Al Khulaifi
Heart Hospital, Hamad Medical Corporation, Doha, Qatar
Introduction: The diagnostic utility of procacitonin (PCT) in cardiac surgery remains controversial  where the systemic inflammatory response (SIRS) induced by the cardiopulmonary bypass is claimed to be associated with elevated levels of PCT . We aim to find a correlation between the level of PCT and the yield of positive blood culture in post operative fever in patients with intensive care unit (ICU) stay more than 24 hours post cardiac surgery.
Methods: Single center retrospective descriptive study over five years, enrolling patients who stayed for more than 24 hours post-operative, in the cardiothoracic ICU. PCT was assayed immunoluminometricaly prior to surgery and every 48 hours in response to onset of fever
Results: We screened 501 patients, of which 119 were enrolled in our study.Patients were divided into two groups according to the presence (Group 1), or absence of positive culture (Group 2).The mean PCT was significantly higher in Group 1 (19.0±4.6 versus 9.9±2.7, p=.033). Moreover, patients in Group 1 were associated with prolonged ICU stay,hospital stay and length of mechanical ventilation (p=0.00, 0.00, and 0.01 respectively)
Conclusions: The results showed that post cardiac surgery bacterial infections were associated with rise of PCT in contrast with patients who develop SIRS. The outcome measures were significantly worse in the culture positive group.
1. Boeken U, et al. Cardiovasc Surg 8(7):550-4, 2000.
2. Prat C, et al. J Cardiac Surg 23(6):627-32, 2008
P030 Prognostic value of procalcitonin, pro-adrenomedullin, copeptin and atrial natriuretic peptide as predictors of duration of artificial lung ventilation and length of stay in intensive care unit for newborns and children of the first year of life after cardiac surgery with cardiopulmonary bypass
A. Khrustalev, D. Popov, O. Stepanicheva
Bakoulev Scientific Center for Cardiovascular Surgery, Moscow, Russia
Introduction: Due to sequalae in the postoperative period children of the first year of life may require prolonged artificial lung ventilation (ALV) and prolonged length of stay (LOS) in the intensive care unit (ICU) after cardiac surgery. Procalcitonin (PCT), pro-adrenomedullin (MR-proADM), copeptin (CT-proAVP) and atrial natriuretic peptide (MR-proANP) can be predictors of duration of ALV and LOS in ICU.
Methods: 42 patients aged 153 (44-252) days (4-360 days) underwent cardiac surgery with cardiopulmonary bypass for severe congenital heart disease. In the dynamics levels of PCT, MR-proADM, CT-proAVP and MR-proANP were measured before surgery and on the 1, 2, 3 and 6 days after the operation with the Kryptor compact plus analyzer. Data are presented as medians with interquartile range. The Mann-Whitney U-test was used to compare the data. Values of p <0.05 were statistically significant.
Results: 24 patients (57%) required ALV for more than 72 hours. In this group statistically significant higher levels of PCT, MR-proADM and MR-proANP were found throughout the period (Table 1). The level of CT-proAVP had increased to statistical significance since the 3 day after the operation. 23 patients were in the ICU for more than 168 hours. In this group statistically significant higher levels of PCT, MR-proADM were found throughout the whole period (Table 2). The higher level of MR-proANP was statistically significant on the 1st and 6th days after surgery, MR-proANP had a tendency of increasing values on 2nd and 3rd days. CT-proAVP increased to statistical significance since the 2nd day after the operation and persisted throughout the studied period.
Conclusions: PCT, MR-proADM and MR-proANP can be used as predictors of prolonged ALV for children of the first year of life after cardiac surgery with cardiopulmonary bypass. The level of CT-proAVP can be considered since the 3 day after surgery. PCT and MR-proADM may be used to predict the LOS in the ICU. MR-proANP and CT-proAVP can be considered since the 1 and 2 days after surgery respectively.
P031 Association of inflammatory and hemostatic biomarkers with inflammasomes in septic patients at risk of developing coagulopathy
D Hoppensteadt, R Green, A Walborn, G Wegrzyn, S Walborn, M Mosier, J Fareed
Loyola University Medical Center, Maywood, IL, USA
Introduction: Inflammasome contributes to the innate immune response identification of pattern recognition receptors (PRRS) on pathogens including bacterial and viruses. The purpose of this study is to quantitate inflammasome levels in defined sepsis associated patients and to determine its potential relevance to various biomarkers of hemostatic dysregulation.
Methods: Plasma samples from 52 adults with sepsis and suspected coagulopathy were analyzed. Fibrinogen was measured using a clot based method on ACL-ELITE coagulation analyzer. Cortisol, D-dimer, PAI-1, NLRP-3 inflammasomes, MP-TF, Fibronectin, and CD40L were measured using commercially available ELISA assays.
Results: When comparing patients with sepsis and suspected DIC to the normal plasma samples, there was a significant elevation in NLRP-3 inflammasome levels in the sepsis cohort (p = < 0.0001) (Fig. 1). The NLRP-3 inflammasome concentration in the sepsis cohort did not correlate with other biomarkers. An elevated level of NLRP-3 inflammasomes was significantly associated with an increased levels of PAI-1 (p < 0.0004) (Table 1).
Conclusions: The current study shows a significant relationship between inflammasomes and PAI-1 levels in patients with sepsis associated coagulopathy. The positive correlation between NLRP-3 inflammasomes and PAI-1 shows that the activation of inflammasomes may have a role in the upregulation of PAI-1.
Inflammatory and hemostatic biomarkers correlated with NLRP-3 inflammasome levels in patients with sepsis and suspected DIC
NLRP-3 Inflammasome Correlation
T Gkavogianni, E Tzouveli, D Benas, G Papagiannopoulou, S Grigoropoulou, A Spanos, E Giamarellos-Bourboulis
ATTIKON University Hospital, Athens, Greece
Introduction: Easily measurable biomarkers to indicate the state of immune activation in sepsis remain an unmet need. HBP is secreted from neutrophils and it is increased in sepsis. However, its association with the innate immune function is poorly understood.
Methods: Plasma was isolated on three consecutive days from 30 patients with ventilator-associated pneumonia meeting the Sepsis-3 definitions. Monocytes were also isolated on day 1 and stimulated with lipopolysaccharide (LPS) for the production of tumour necrosis factor-alpha (TNFalpha). HBP, ferritin and TNFalpha were measured by an enzyme immunoassay. Over-time changes of HBP were associated with final outcome.
Results: A positive association was found between ferritin concentrations and circulating HBP on day 1 (rs: +0.371, p: 0.0002). The median value of HP on day 1 was 177 ng/ml. The stimulated production of TNFalpha in relation to the median HBP level is shown in Fig. 1. Among 20 survivors, mean change of HBP from the baseline was -12.2% +/- 20.2%; this was +146.8% +/- 89.4% among 10 non-survivors (p: 0.028). After ROC curve analysis it was found that more than 18% increase of HBP after 48 hours was associated with 81% specificity for 28-day mortality (odds ratio for unfavorable outcome 8.50; p: 0.017).
Conclusions: HBP seems to indicate patients who rely at the pro-inflammatory arm of sepsis since it correlates positively with ferritin and with the increased stimulated production of TNFα from circulating monocytes. Increases the first 48 hours by more than 18% indicate progression towards unfavorable outcome.
P033 Integration of heparin-binding protein (HBP) and one sign of quick SOFA score (qSOFA) to predict 30-day outcome.
E Kyriazopoulou, C Psarrakis, C Moschopoulos, I Christou, P Fragkou, T Marantos, E Karofyllakis, K Roussakis, E Giamarellos-Bourboulis
Attikon University Hospital, Athens, Greece
Introduction: Early prediction of the risk of death among patients admitted at the Emergency Department (ED) remains an unmet need. The prognostic performance of HBP that is secreted by neutrophils was prospectively validated in a series of sequential ED admissions.
Methods: HBP and elements of qSOFA were analyzed prospectively in 310 serial ED admissions (main reasons for admission: acute abdominal pain 28.4%; fever 24.5%; vomiting/diarrhea 23.9%; dyspnea 22.3%; neurologic signs 11.3%; non-specific complaints 38.1%; most patients admitted for more than one reasons). Upon ED admission patients were scored as low-risk, intermediate-risk and high-risk at the discretion of the physician. HBP was measured in blood samples upon admission by an enzyme immunosorbent assay.
Results: HBP was significantly greater among patients who died very early (Fig. 1). In five out of six of patients dying early HBP was greater than 15 ng/ml. We combined HBP more than 15 ng/ml and the presence of one sign of qSOFA into a new score; this had 82.4% sensitivity to predict 30-day mortality. The respective sensitivity of two signs of qSOFA was 23.5% (p: 0.002). The use of this new score allowed better stratification of patients originally considered at the triage as low-risk into high-risk (Fig. 2).
Conclusions: We propose HBP more than 15 ng/ml and one qSOFA sign as an early score for 30-day mortality at the ED.
C Balci, E Haftaci, B Koyun
Health Sciences University, Kocaeli Derince Traning Hospital, Kocaeli, Turkey
Introduction: Despite of our growing knowledge in pathophysiology of septic shock still remain one of the most important factors of hospital mortality. It is thought that early diagnosis and treatment at early stage of septic shock would decrease its mortality. There have been on-going studies in recent years which research the usability of Heparin Binding Protein (HBP) in early diagnosis of sepsis . To seek the usability of C- reactive protein (C-RP), procalcitonin (PCT) and HBP biomarker combination in early diagnosis of septic shock.
Methods: 30 patients, who have the diagnosis of septic shock, that are expected to stay in intensive care unit more than 24 hours, and aged between 22-75 are included in the study. Data are collected from the patients’ blood samples that are drawn on admission, on the 24th hour, and on the day of discharge or death.
Results: It has been found in our study that, best “cut-off” value 124 ng/mL, specificity 0.82 and sensitivity 0.77 for HBP. Compared with other biomarkers, HBP was the best predictor of progression to organ dysfunction (area under the receiver operating characteristic curve (AUC) = 0.801).
Conclusions: Although there have been many biomarkers for early diagnose of septic shock, C-RP and PCT are the most common used markers in nowadays’ clinical practice. The usability of HBP in early diagnosis of sepsis is still being researched. We concluded that PCT, C-RP and HBP biomarker combination is usable to diagnose septic shock at the end of our study.
1. Holub M, Beran O. Crit Care 16(3):133, 2012.
I Vasileiadis1, M Politou2, N Rovina1, S Dimopoulos2, E Tripodaki3, A Kyriakoudi1, E Ntouka1, E Stavrou1, A Koutsoukou1
1Sotiria Hospital, National and Kapodistrian University of Athens, Athens, Greece,2Onasseio Cardiac Surgery Center, Athens, Greece,3Agios Savvas Regional Cancer Hospital, Athens, Greece
Introduction: Reduced ADAMTS-13 and increased von Willebrand Factor (vWF)/ADAMTS-13 ratio have been observed in sepsis and are associated with the severity of the disease [1,2]. However, their change during the septic episode and in the event of a change in the clinical status of the septic patients has not been investigated. The aim of the study was to assess the variation of these hemostatic parameters in critically ill patients during the course of a septic episode.
Methods: We monitored 34 septic patients admitted in the Intensive Care Unit (ICU). 23 improved (group A) while 11 deteriorated (group B). We assessed vWF, ADAMTS-13 and the vWF/ADAMTS-13 ratio on admission in ICU (time point 0) and at the time of a change in patients’ clinical condition (remission or deterioration, time point 1).
Results: In group A, ADAMTS-13 and the vWF/ADAMTS-13 ratio did not significantly change (567.0±296.0 vs 670.7±534.5 ng/ml, p=0.238 and 0.709±0.588 vs 0.876±0.687, p=0.34 respectively) while vWF increased (326.2±122.7 vs 407.0±157.6 % of norm., p=0.028) at time point 1 compared to time point 0. In group B, ADAMTS-13 decreased (831.4±586.1 vs 482.0±277.8 ng/ml, p=0.026) while vWF and the vWF/ADAMTS-13 ratio increased (389.5±170.5 vs 525.3±141.0 % of norm., p=0.02 and 0.779±0.851 vs 1.490±1.060, p=0.002) at time point 1 compared to time point 0. There was a non-statistical greater increase (% change) of vWF (53±63 versus 35±63%, p=0.4) in group B patients compared to group A patients. ADAMTS-13 percentage difference (>or<= 22%) was associated with sepsis outcome (χ =8.7; HR:5.86; 95% CI:1.6-22.1; p=0.009).
Conclusions: Hemostatic disorders, as assessed by vWF and ADAMTS-13 levels were detected in septic patients, while their changes differed according to the evolution of the septic episode. ADAMTS-13 changes may be associated with outcome.
1. Fukushima H et al. Shock 39(5):409-14, 2013.
2. Azfar MF et al. Clin Invest Med 40(2):E49-E58, 2017.
L Lazaridis1, S Karatzas2, A Prekates3, K Toutouzas2, C Mathas4, J Popp5, J Olsen6, E Giamarellos-Bourboulis1
1Attikon University Hospital, Athens, Greece,2Ippokrateion General Hospital, Athens, Greece,3Tzaneion Hospital, Piraeus, Greece,4Aghia Olga Hospital, Athens, Greece,5Leibniz Instiute for Photonic Technology, Jena, Germany,6Virogates SA, Copenhagen, Denmark
Introduction: The Sepsis-3 Task Force has introduced quick sequential organ failure assessment (qSOFA) as a diagnostic tool for the early diagnosis of sepsis. However, the Sepsis-3 criteria and qSOFA have not yet been prospectively validated. INTELLIGENCE-1 (ClinicalTrials.gov NCT03306186) is aiming in this prospective validation through the integration of clinical signs and biomarkers.
Methods: 100 adult patients with at least one sign of qSOFA and infection or acute pancreatitis or after operation were prospectively followed-up. Blood was sampled the first 24 hours; those with HIV infection, neutropenia and multiple injuries were excluded. Sepsis was diagnosed using the Sepsis-3 criteria. Soluble urokinase plasminogen activator receptor (suPAR) was measured by an enzyme immunoassay.
Results: Sixty patients were classified with sepsis using the Sepsis-3 definitions. Presence of at least two signs of qSOFA had 56.7% sensitivity, 95.0% specificity, 92.8% positive predictive value and 38.0% negative predictive value for the diagnosis of sepsis. The integration of qSOFA signs and suPAR improved the diagnostic performance (Fig. 1).
Conclusions: Conclusions Two signs of qSOFA have significant positive prognostic value for sepsis but low sensitivity. This is improved after integration with suPAR.
The INTELLIGENCE-1 study is supported by the European Commission through the Seventh Framework Programme (FP7) HemoSpec.
P037 TRIAGE Study protocol: Assessment of biomarkers to predict clinical worsening of patients with sepsis admitted in the Emergency Department
T Lafon1, C Vallejo1, L Barbier2, MA Cazalis2, T Daix1, A Desachy1, V Gissot3, PF Laterre4, K Tazarourte5, B François1
1Centre Hospitalier Universitaire Dupuytren, Limoges, France,2bioMérieux SA, Marcy l’Etoile, France,3CHU de Tours/Université François Rabelais, Tours, France,4Cliniqies Saint-Luc, Brussels, Belgium,5Groupement Hospitalier Edouard Herriot - Hospices Civils de Lyon, Lyon, France
Introduction: Sepsis is a frequent reason for admission in the Emergency Department (ED) and its prognostic mainly relies on early diagnosis. In addition, no validated prognostic tool is currently available. Therefore, identification of patients at high risk of worsening in the ED is key. The TRIAGE objective was to assess the prognostic value of a blood marker panel to predict early clinical worsening of patients admitted in the ED with suspected sepsis.
Methods: TRIAGE was a prospective, multicenter (11 sites in France and Belgium) study on biological samples conducted in partnership with bioMerieux S.A. Patients admitted in the ED with suspected or confirmed community-acquired infection for less than 72h were included. Exclusion criteria were: admission in the ED for more than 12 hours, septic shock at admission, immunodepression, sepsis syndrome 30 days prior to admission. The protocol included 5 clinical and biological time points (H0, H6, H24, H72, D28). Patients were classified in 3 groups at admission (infection, sepsis, severe sepsis) and divided into 2 evolution/prognosis groups depending on worsening or not from their initial condition to severe sepsis or septic shock and SOFA score’s evolution. The evolution criteria were centrally evaluated by an independent adjudication committee of sepsis experts including emergency physicians and intensivists. Patients were followed up to day 28 for mortality.
Results: The study duration was 3 years with 600 patients included (102 excluded). The centralized analysis is in progress to select the combination of biomarkers with the best prognostic performance comparing both evolution/prognosis groups. Currently, 125 patients have been classified as worsening and some results will be available in 2018.
Conclusions: TRIAGE is the largest prospective multicenter study assessing the prognostic value of a panel of blood markers in EDs which could help identification of septic patient at risk of worsening at time of admission in the ED and develop specific management.
P038 Immune profiling of host response biomarkers through transcriptomic analysis using the FilmArray® system.
DM Tawfik1, L Ganee1, A Bocquet1, V Moucadel1, J Textoris1, T Rimmele2, G Monneret 2, S Blein 1, M Rol 3, J Montgomery4, F Mallet1, A Pachot 1, J Yugueros Marcos 1,.REALISM Study group5
1bioMerieux, Lyon, France,2Hospices Civils de Lyon, Lyon, France,3Bioaster Technology Research Institute, Lyon, France,4BioFire Diagnostics LLC Salt Lake City, UT, USA,5REALISM Study group, Lyon, France
Introduction: Immune status characterization in Intensive Care Unit (ICU) patients presents a major challenge due to the heterogeneity of response. In this study, the FilmArray® system was used with customized gene assays to assess the immune profile of critically-ill ICU patients compared to healthy volunteers; from within the REALISM cohort.
Methods: A customized FilmArray® pouch containing 24 assays was designed; 16 target and 8 reference genes. Detection and semi-quantification of assays from whole blood collected in PAXgene tubes occurs in the device within 1 hour. A total of 20 subjects from the REALISM cohort were tested in duplicates: 1 trauma, 5 septic shock and 5 surgery patients, along with 9 healthy volunteers. The patients’ selection was based on HLA-DR expression on monocytes, and PHA-(Phytohaemagglutinin) stimulated T-cell proliferation assay, to have various immune profiles.
Results: Quantification cycle values of the target genes were normalized by the geometrical mean of reference genes to account for the different cell counts among specimens. The number of the CD3+ cells and HLA-DR, determined by flow cytometry, showed good correlation to CD3D and CD74 gene expression, respectively. Seven genes showed significant differences in expression levels between the healthy volunteers and patient groups: CD3D, CD74, CTLA4 & CX3CR1 were down-regulated, while IL-10, IL1RN and S100A9 were up-regulated in the patient populations. The use of relative quantitative difference of some markers was able to distinguish and emphasize the variability between the patient groups while homogenizing the discrepancy among healthy volunteers.
Conclusions: The FilmArray® system was shown to allow host transcriptomics analysis of immune-relevant genes directly from PAXgene tubes, in only one hour. These results show great potential for the development of a fully automated immune profiling tool, enabling close monitoring of critically-ill patients.
P039 Rapid biophysical analysis of host immune cells enables diagnosis of sepsis in the emergency department
M Macdonald1, R Sheybani1, A DeWitt2, S Brierre3, T Caffery3, T Jagneaux3, C Thomas3, D Di Carlo4, H Tse1, A Shah1, H O’Neal3
1CytoVale, San Francisco, CA, USA,2Baton Rouge General Medical Center, Baton Rouge, LA, USA,3Louisiana State University Health Sciences Center, Baton Rouge, LA, USA,4University of California, Los Angeles, CA, USA
Introduction: Early, rapid diagnosis is integral to the efficient effective treatment of sepsis; however, there is no gold standard for diagnosis, and biochemical surrogates are of limited and controversial utility. The CytoVale system measures biophysical properties of cells by imaging thousands of single cells per second as they are hydrodynamically stretched in a microfluidic channel. This platform has been shown to measure dozens of mechanical, morphological, and cell surface biomarkers of WBC activation simultaneously [1,2]. In this study, we show the performance of the CytoVale system in measuring biophysical markers for sepsis detection in the emergency department (ED).
Methods: We conducted an IRB-approved prospective cohort study of Emergency Department (ED) patients with 2+ SIRS criteria and evidence of organ dysfunction. 307 patients were included for analysis. Blood samples for the Cytovale assay were collected in the ED, and the diagnosis of sepsis was adjudicated by blinded clinician review of the medical record. Captured imaging data were analyzed using computer vision to quantify mechanical parameters per cell, and a logistic model was trained to discriminate patients who had sepsis from those who did not.
Results: We found substantial biophysical differences between cells from septic and non-septic patients as observed at both the single cell level (Fig. 1) and when looking at the overall leukocyte populations (Fig. 2). A multiparameter classification algorithm to discriminate septic from non-septic patients based on biophysical markers currently yields a sensitivity of 88% with a negative predictive value of 95%.
Conclusions: In patients presenting to the ED with 2 of 4 SIRS criteria and evidence of organ dysfunction, the CytoVale system provides a potentially viable means for the early diagnosis of sepsis via the quantification of biophysical properties of leukocytes.
1. Gossett DR et al. PNAS 20:7630–5, 2012
2. Crawford K et al. AJRCCM, under review, 2017
V Tsolaki, M Karapetsa, G Ganeli, E Zakynthinos
ICU, Larissa, Greece
Introduction: Early identification of sepsis adds a survival benefit in ICU patients. Several biomarkers have been evaluated, yet an optimal marker is still lacking .
Methods: We prospectively determined oxidative status in patients admitted in a general Intensive Care Unit of the University Hospital of Larisa. Oxidative status was determined measuring the novel static (sORP) and capacity (cORP) oxidation-reduction potential markers. Other biomarkers (BNP, presepsin, CRP) were measured, and the discriminative properties for the detection of sepsis were evaluated.
Results: Oxidative status was evaluated in a hundred and fifty two consecutive patients. Patients with severe sepsis and septic shock had significantly higher sORP values than patients without sepsis (173.31± 20.44 vs 164.11±18.78, p=0.006), while cORP did not differ (0.34±0.31 vs 0.37±0.20, ns). Patients with cerebral damage had the lowest sORP on admission while surgical and medical patients had the highest sORP values (157.2 ±18.33 vs 174.04±18.1 respectively, p<0.001). sORP could predict the presence of sever sepsis (OR 1.107, p=0.009), along with presepsin (OR 1.002, p<0.0001), C-Reactive Protein values (OR 1.161, p=0.013) and Brain Natriuretic Peptide (OR 1.001, p=0.046). The best discriminating properties had presepsin (AUC 0.893, p<0.0001) and CRP (AUC 0.743 p<0.0001). The presence of a microorganism in blood or bronchial secretions could be predicted from the values sORP (AUC 0.633, p=0.042) and CRP (AUC 0.653, p=0.02).
Conclusions: Oxidative status differs between patients admitted in the ICU and could serve as a prognostic marker for the presence of sepsis.
1. Singer M, et al. JAMA 315(8):801-810, 2016
P041 Relationship between pre-operative C-reactive protein elevation and major cardiovascular events after vascular surgery
I Ben Naoui, A El Ghali, AG Ammous, I Nefzi, A Saidi, A Ammous, A Cherif
La Rabta Hospital, Tunis, Tunisia
Introduction: C-reactive protein (CRP), is reported to be an effective marker for the assessment of vascular inflammation activity and acute coronary events prediction .We hypothesized that preoperative CRP elevation is related to the occurrence of postoperative adverse cardiovascular outcomes.
Methods: We prospectively included patients scheduled to undergo different vascular surgeries from december 2016 to september 2017. we assessed demographic data, comorbidities, revised cardiac risk index (RCRI) and biomarkers (CRP, cardiac troponin high sensitive Ths, creatinine and urea) in the preoperative period. we also noted type and duration of surgery, intraoperative blood loss, ICU stay and mortality. we evaluated CRP as a predictive marker of major cardiovascular events defined as chest pain, Ths elevation, electrocardiogram changes, arrhythmia, pulmonary embolism, stroke occuring within postoperative 3 months.
Results: During our study, 30 patients were scheduled to undergo vascular surgeries. From the 30 patients, 66% developed adverse cardiac events (Table 1). We showed the predictive value of CRP in major cardiovascular event in a ROC analysis (Fig. 1). The cuttoff value of CPR was 54 giving 85% of sensitivity and 82% of specificity.
Conclusions: Our study pointed out that CRP preoperative elevation could have a very strong predictive value of post-operative cardiovascular events in vascular surgery, this is in line with results showed by previous studies .
1. Yunxiang Li. Int J Clin Exp Pathol 9:11904-11910, 2016
Major cardiovascular events immediately after surgery
S Moreira1, J Baptista1, F Froes2, J Pereira3, J Gonçalves-Pereira4, C Dias5, J Paiva3
1Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal,2Hospital Pulido Valente, Centro Hospitalar Lisboa Norte, Lisboa, Portugal,3Centro Hospitalar São João, Porto, Portugal,4Hospital Vila Franca de Xira, Vila Franca de Xira, Portugal,5Centro de Investigação em Tecnologias e em Serviços de Saúde, Porto, Portugal
Introduction: Elderly are particularly susceptible to bacterial infections and sepsis, and they comprise an increasing proportion of intensive care unit (ICU) admissions. Our aim was to evaluate the impact of age on critically ill infected patients.
Methods: We performed a post-hoc analysis of all infected patients admitted to ICU enrolled in a 1-year prospective, observational, multicenter study involving 14 ICUs. Patients aged <65, 65-74 and >=75 years were compared (group A, B, and C). Multidrug-resistance (MDR) was defined as acquired non-susceptibility to at least one agent within three or more antimicrobial categories.
Results: Of the 3766 patients analyzed, 1652 (43.9%) were infected on ICU admission. Of these, 828 (50%) belonged to group A, 434 (23%) to group B and 440 (27%) to group C. Group C were more dependent, had higher SAPS II and Charlson scores (p<0.05). ICU and hospital length of stay did not differ between groups. Microorganism isolation and bacteremia were higher in group B (53% and 24%, respectively) than groups A (45% and 19%, respectively) and C (47% and 17%, respectively; p<0.05). Septic shock was present in 58% of patients and was more frequent in groups B (55%) and C (55%) than group A (48%). The most common sources of infections were respiratory and intra-abdominal. Isolation of gram-negative bacteria was significantly increased in group B and C (p=0.034). The most common isolated bacteria were Escherichia coli (17%), Staphylococcus aureus (15%) and Pseudomonas aeruginosa (8%) for all groups. In total, 151 isolates (22%) corresponded to MDR bacteria, of which 57% were Staphylococcus aureus. Age was not a risk factor for infection by MDR. All-cause mortality in ICU and hospital was: 23% and 30%; 29% and 40%; 36% and 53% - respectively for groups A, B, and C (p < 0.001).
Conclusions: Old patients (65-74 years) were more prone to present with bacteremia, which could account for the increased severity of sepsis and higher all-cause mortality. Age was not a risk factor for MDR infection.
AR Garg1, E Sherry1, L Verrinder1, JM Patel2
1University Hospital Birmingham, Birmingham, UK,2University of Birmingham, Birmingham, UK
Introduction: The rapid identification of pathogens using patient samples is crucial. Delays in this can potentially have serious implications for patients and infection prevention/control . The aim of this project was to identify the number of microbiology samples sent, the number rejected and reasons for rejection, with the intention to reduce such instances.
Methods: Data was collected retrospectively on ICU admissions from January-June 2017 to a university hospital in the UK. Patients were identified and data collected using the Intensive Care National Audit and Research Centre (ICNARC) database and from electronic patient records. Data collected included: demographics, length of stay, microbiology samples sent and details on the rejected samples.
Results: 530 patients were identified with a total of 4725 (median: 4 samples/patient) samples sent to microbiology. 144 were rejected (3%). 100 (18%) patients had at least 1 sample rejected. The median number of samples rejected per patient was 1 (Range: 1-10). The most common samples rejected were urine (22%), blood (20%), faeces (19%) and sputum (8%). 69 (48%) of the samples were resent for testing (median 1 day; range 0-20). Reasons for sample rejection are shown in Table 1. Most rejections occurred within 48-hours of admission (Fig. 1).
Conclusions: This study confirms a high number of samples are sent to microbiology. Although a few are rejected, overall this represents a large number, with most occurring during the first days of admission. Reasons for sample rejection are remedial through improved training and vigilance. A bespoke guide to sample collection for microbiology coupled with a training program for healthcare professionals has been introduced with the aim to reduce sample rejections from 3% to 0.5%.
1. Vincent JL et al. Crit Care Med 43:2283-2291, 2015
Reasons for sample rejection
Reason for rejection
Wrong sample type
Patient Identification error
Incorrect info on form
Others (Wrong lab, Test unavailable)
A Galazzi1, E Broggi1, A Grancini1, M Panigada1, I Zainaghi1, F Binda1, T Mauri2, G Grasselli2, I Adamini1, A Pesenti2
1Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milano, Italy,2Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, University of Milan, Milan, Italy
Introduction: Careful hand hygiene of health-care workers (HCWs) is recommended to reduce transmission of pathogenic microorganisms to patients . Mobile phones are commonly used during work shifts and may act as vehicles of pathogens [2,3]. The purpose of this study was to assess the colonization rate of ICU HCWs’ mobile phones before and after work shifts.
Methods: Prospective observational study conducted in an academic, tertiary-level ICU. HCWs (including medical and nursing staff) had their mobile phones sampled for microbiology before and after work shifts on 6 different days. Samples were taken with eSwab in a standardized modality and seeded on Columbia Agar plus 5% sheep blood. A semiquantitative growth evaluation was performed at 24 and 48 hours after incubation at 35°C.
Results: Fifty HCWs participated in the study (91% of department staff). One hundred swabs were taken from 50 mobile phones. Forty-three HCWs (86%) reported a habitual use of their phones during the work shift, and 38 of them (88.4%) usually kept their mobiles in the uniform pocket. All phones (100%) were positive for bacteria. The most frequently isolated bacteria were Coagulase Negative Staphylococcus, Bacillus sp. and MRSA (97%, 56%, 17%, respectively). No patient admitted to the ICU during the study period was positive for bacteria found of HCWs’ mobile phones. No difference in bacteria types and burden was found between the beginning and the end of work shifts.
Conclusions: HCWs’ mobile phones are always colonized mainly by flora resident on HCW’s hands, even before the work shift and irrespective of the microbiological patients’ flora. Further studies are warranted to investigate the role of mobile phones’ bacterial colonization in the ICU setting and to determine whether routine cleaning of HCWs’ mobile phones may reduce the rate of infection transmission in critical patients.
1. WHO Guidelines on Hand Hygiene in Health Care. 2009
2. Ulger F et al. Ann Clin Microbiol Antimicrob 8:7, 2009
3. Russotto V et al. J Intensive Care 3:54, 2015
P045 Microbiological contamination of mobile phones carried by health care workers in intensive care units and operating room
P Mogrovejo, S Castro, V Arízaga, E Guerrero, A Loja, L Tamayo, H Aguirre
Santa Inés Hospital, Cuenca, Ecuador
Introduction: Mobile phones (MP) of health care workers (HCWs) could be colonized by pathogenic bacteria. It can be a vector of drug resistant bacteria and could increase nosocomial infections. The aim of this study is to evaluate the prevalence of MP bacterial colonization in the adult intensive care unit (AICU), pediatric intensive care unit (PICU) and operating room (OR) in a tertiary level hospital.
Methods: Sixty samples were collected from AICU (n=25), PICU (n=15) and OR (n=20) during August to September 2017. Samples were randomly selected and taken at the end of the HCWs duty with a sterile swab covering all MP surfaces. The inoculation was made into blood sheep and eosyn methilene blue agar for culture. Isolated bacteria were identified according to standard microbiological techniques. Antibiotic sensitivity testing was performed using disc diffusion method.
Results: Overall MP bacterial colonization rate was 95%. Main results are detailed in Table 1. Most common non pathogenic bacteria was Staphylococcus epidermidis n=18 (90%). Isolated pathogenic bacteria were Meticilin-susceptible Staphylococcus aureus n=14 (38%), Methicillin-resistant Staphylococcus aureus n=10 (27%), resistant Staphylococcus epidermidis n=4 (11%), Acinetobacter baumanni n=4 (11%), Klebsiella pneumoniae n=4 (11%) and resistant Acinetobacter baumanni n=1 (2%). No significant difference was found in colonization rates of pathogenic bacteria between MP with case n=35 (59%) versus MP without case n=25 (41%) (p< .753).
Conclusions: We found high rates of MP colonization with pathogenic bacteria. An educational program is necessary to reduce the contamination and transmission of these high risk microorganisms.
Colonization rates per department and subtype of isolated bacteria
Non pathogenic bacteria
Non drug resistant
P046 Assessment of the variability of airborne contamination levels in an intensive care unit over a 24 hour period
M Booth1, L Dougall2, E Khoo3, H Hood3, S MacGregor2, M Maclean2
1Glasgow Royal Infirmary, Glasgow, UK,2University of Strathclyde, Glasgow, UK,3University of Glasgow, Glasgow, UK
Introduction: The objective of this study was to evaluate the variability in the dynamics and levels of airborne contamination within a hospital Intensive Care Unit in order to establish an improved understanding of the extent to which airborne bioburden contributes to cross-infection of patients. Microorganisms from the respiratory tract or skin can become airborne by coughing, sneezing and periods of increased activity such as bed changes and staff rounds. Current knowledge of the clinical microflora is limited however it is estimated that 10-33% of nosocomial infections are transmitted via air.
Methods: Environmental air monitoring was conducted in Glasgow Royal Infirmary ICU, in the open ward and in patient isolation rooms. A sieve impactor air sampler was used to collect 500 L air samples every 15 minutes over 10 hour (08:00-18:00 h) and 24 hour (08:00-08:00 h) periods. Samples were collected, room activity logged and the bacterial contamination levels were recorded as CFU/m3 of air.
Results: A high degree of variability in levels of airborne contamination was observed over the course of a 10 hour day and a 24 period in a hospital ICU. Counts ranged from 12-510 CFU/m3 over 24 hours in an isolation room occupied for 10 days by a patient with C. difficile infection. Contamination levels were found to be lowest during the night and in unoccupied rooms, with an average value of 20 CFU/m3. Peaks in airborne contamination showed a direct relation to increased room activity.
Conclusions: This study demonstrates the degree of airborne contamination that can occur in an ICU over a 24 hour period. Numerous factors were found to contribute to microbial air contamination and consideration should be given to potential improved infection control strategies and decontamination technologies which could be deployed within the clinical environment to reduce the airborne contamination levels, with the ultimate aim of reducing healthcare-associated infections from environmental sources.
P047 New practice of fixing the venous catheter of the jugular on the thorax and its impact on the infection
F Goldstein, C Carius, A Coscia
QuintaD’or, Rio de Janeiro, Brazil
Introduction: Central Line-associated Bloodstream Infection (CLABSI) is an important concern in the ICU, mainly in those with a high density of use of central venous catheter. Any measures that may have an impact on the reduction of CLABSI are important in reducing morbidity and mortality of hospitalized patients. Therefore we present a retrospective study comparing the fixation site (neck vs. thorax) of the catheters implanted in the jugular vein, guided by ultrasonography and evaluating its impact on the incidence of CLABSI. The purpose of our study was to identify if there is any positive impact on the reduction of CLABSI when the catheter is fixated on the thorax.
Methods: A retrospective unicentric study comparing the infection rates between the year of 2012, when the traditional technique of catheter fixation on the neck was used, and 2015, when 100% of the catheters were fixated on the thoracic region. The criteria for CLABSI were defined by the Infection Commission of QuintaD`or Hospital and the data on CLABSI were provided by the same commission. During this period there were no changes in the team of our unit and the patient's profile was the same. No deep vein catheter impregnated with antibiotics were used in the patients included in the study. The comparison used Fisher ́s test as a tool. All the patients hospitalized in the intensive care unit with indication of the central venous catheter of short permanence in the internal jugular vein were included. Patients with the central venous catheter of short permanence in other topographies, patients with hemodialysis catheter or with PICC were excluded.
Results: During the year of 2012, 98 internal jugular vein catheters were installed in our unit using the traditional technique, fixing the catheter on the neck. In this period, 6 cases of CLABSI were detected. On the other hand, in the year of 2015, 127 internal jugular vein catheters were installed in the same unit, all of them, using the thorax as the point of fixation. Although the number of catheters installed this year was higher, there was no case of CLABSI. It appears that this position, provides a better fixation of the catheter, avoiding that the bandage gets uncovered.
Conclusions: During the year of 2015, though there were more patients using deep vein catheters of short permanence, we had less CLABSI events on our unity compared to the year of 2012. Fisher's exact test identified a p-value of this association of 0.476. Fixation of the internal jugular vein catheter in the thorax seems to contribute to the prevention of CLABSI. Further prospective and randomized studies are required to evaluate the contribution of fixation of the jugular vein catheter in the thorax in the CLABSI prevention.
R Marinho1, J Marinho1, A Marinho1, J Frias-Bulhosa2
1Centro Hospitalar do Porto, Porto, Portugal,2Universidade Fernando Pessoa, Porto, Portugal
Introduction: The oral cavity of a patient who has been hospitalized presents a different flora from normal healthy people. After 48h hours of hospital stay, the flora presents a bigger number of microorganisms that can be responsible for secondary infections, like pneumonia, because of their growth and proliferation. The objective of our study was to assess the dental plaque index on patients on admission to an Intensive Care Unit, and reassess 7 days later, to evaluate the efficacy of oral hygiene.
Methods: Prospective, descriptive and observational study in an Intensive Care Unit of the CHP. Demographic, admission motive, hospital length of stay, feeding protocol, respiratory support need and oral hygiene protocol data was collected. The Greene & Vermillion Simplified Oral Hygiene Index (IHO-S) was used as the assessment tool on the first 24h and on 7th day.
Results: 74 patients were evaluated, 42 of which were excluded for not meeting the minimal dentition. 32 patients had a mean age of 60,53 ± 14,44 years, 53,1% were males and most of medical and surgical scope (37,5% each). Mean hospital length of stay was 15,69±6,69 days. The majority of patients were sedated (75%), under ventilator support (81,3%) and with enteric nutritional support, under nasogastric tube feeding. Initial IHO-S score was 0,67±0,45, rising to 1,04±0,51 (p<0,05) 7 days later.
Conclusions: Various studies have proven the importance of a good oral hygiene to avoid bacterial growth and reduce the risk for nosocomial infections. In this study, we’ve observed a significant worsening of oral hygiene one week after admission. Although this could be unimportant for a one week staying patient, it could indicate an increased risk for nosocomial infections for longer staying patients, which could benefit from a more efficient oral hygiene protocol.
P049 Positive pocket cultures and infection risk after cardiac electronic device implantation-a retrospective observational single-center cohort study
P Pekić1, M Bura2, N Marić1
1University Hospital "Sveti Duh", Zagreb, Croatia,2Neuropsychiatric hospital "dr. Ivan Barbot", Popovača, Croatia
Introduction: Positive pocket cultures after implantation of cardiac implantable electronic devices (CIEDs) are often found without clinically apparent infection. Infections related to CIEDs are a serious complication requiring complete device removal, prolonged antimicrobial therapy and can have an adverse patient outcome.
Methods: We performed a retrospective observational single-center cohort study on 251 patients who received de novo implantation of pacemaker, cardioverter-defibrillator or cardiac resynchronization therapy device in a two-year period. Each patient was implanted using standard aseptic procedure according to local protocol and antibiotic (cefazolin) prophylaxis before the procedure. Pocket aspirate was taken after irrigating the wound with normal saline just before device placement.
Results: We analyzed 251 patients (58.6% male, 41.4% female). The most often implanted device was a DDD pacemaker followed by a VVI pacemaker. Mean length of hospital stay was 12.02±8.34 days. There were 54 (21.5%) positive cultures with overall 3 (1.19%) clinically apparent infections which required prolonged iv antibiotics, removal of device and reimplantation after infection resolution. In regard to microbiology, S. epidermidis (48.2%) and coagulase negative Staphylococcus (29.6%) were the most often finding which is in contrast to the cultures described in the literature. The only statistically significant risk factor for positive pocket culture was male sex and presence of a urinary catheter. Invasive vascular devices, previous intrahospital infection, and diabetes were not found to increase the likelihood of positive pocket culture.
Conclusions: Positive pocket cultures after CIED implant are a frequent finding mostly due to contamination and colonisation. The risk factors for such a finding differ from the usual and expected clinical circumstances. Our results are consistent with those in the literature. It turns out that the most important preventive measure in CIED implantation is strict aseptic procedure.
W Yacov, Y Polishuk, A Geal-dor, G Yosef- hay
Kaplan Medical Center, Rehovot, Israel
Introduction: Intensive care patients are in constant risk of contamination due to suppression of their immune system, use of invasive procedures and medical equipment and health associated infections (HAI). Chlorhexidine Gluconate (CHG) is an antiseptic and disinfectant product. In medical research it has been found that daily CHG bathing is affective in reducing levels of skin and central line related infections (Climo, 2013). It is also referred to in the recommendations of the ministry of health "prevention of septicemia due to central lines" (2011).
Methods: Unit guide lines for patient Dry Bathing were written in May 2015 and thereafter began the implementation and instruction of nursing staff. Quality control was inspected by observation. There was a 15 phase questioner that included several categories such as: preparation of the CHG solution, staff protection actions, infusions and surgical wound dressings, bathing performance and documentation.
Results: A gradual rise of 97%was observed in theperformance ofdry bathing according to the unit guidelines
Conclusions: 97% of observed dry baths where performed according to the guide lines. Points for improvement: Correct care of infusions and surgical wound dressing and verify use of separate wipes for each body part. Next we will examine the correlation between the use of dry baths and theextent of infections in the unit. Dry Baths are nowconsidered an integralpart of the daily nursing routine. They have no substantial costs, help prevent complications from infection and add to the patient’s safety.
P051 Pragmatic selective digestive decontamination (SDD): ventilator-associated pneumonia (VAP) rates & local antibiotic resistance
J Highgate1, A Rashid2, J Kilic1, F Baldwin1
1Brighton and Sussex University Hospitals NHS Trust, Brighton, UK,2University of Brighton, Brighton, UK
Introduction: Despite reductions in mortality reported with SDD, concerns about bacterial resistance and alteration of microbiome limit use. A retrospective observational study was conducted into the effect of local SDD protocols on VAP rates and resistance patterns. Over a 2-year period, 2 regimens were used dependent on drug availability and hospital antibiotic stewardship concerns. The study was designed to review practice and identify any risks of partial implementation.
Methods: Patients ventilated on a general intensive care were identified via clinical information systems. Three periods were reviewed for adherence to SDD protocols, Pre SDD (Jan - Feb 14), Full (July - Sept 15) and Partial (July - Sept 16). High-risk patients during both SDD periods also received IV antibiotics for 96 hours. Patients admitted with pneumonia or tuberculosis were excluded from VAP analysis. Remaining patients’ records were reviewed and the Clinical Pulmonary Infection Score (CPIS) calculated for each ventilated day to identify VAP rates. Positive respiratory microbiological results for all patients admitted to the ICU during each time period were reviewed to assess for wider changes in local resistance patterns.
Results: Protocol adherence was assessed in 71 patients during the full SDD period and 70 during the partial (Table 1). The number of patients included for analysis of VAP rates during each period was 38 pre SDD, 50 during full SDD and 37 during partial SDD. There were no significant changes in resistance patterns or Clostridium difficule rates (Table 2).
Conclusions: Compliance with the available enteral antibiotics was reasonable but with IV antibiotics was poor. It is accepted that alterations and non-adherence to protocols risk development of resistant bacterial strains. Within our unit no decrease in VAP rates was seen but reassuringly no increased rates of extended bacterial resistance were identified during the treatment periods.
SDD Protocol adherence & VAP rates
Adherence % NG Gentamicin
Adherence % IV antibiotics
VAP cases per 1000 ventilator days (P=0.8)
Oropharyngeal SDD paste & NG gentamicin/nystatin
Number of resistant organisms isolated
Organism & resistance
P053 A multimodality approach to decreasing ICU infections by hydrogen peroxide, silver cations and compartmentalization and applying acinetobacter as infection marker
A Al Bshabshe1, M Hamid 1, A Assiri2, M Joseph1
1King Khalid University, Abha, Saudi Arabia, 2Aseer Central Hospital, Abha, Saudi Arabia
Introduction: Nosocomial infections at the intensive care unit (ICU) represent a substantial health threat [1, 2]. ICU infections are mainly attributed to the extended hospital delay which results in high morbidities and mortalities.
Methods: A cross sectional study was conducted at the Intensive Care Unit, Aseer Central Hospital, Saudi Arabia over 13 months period (2014-2015). The intervention program included the application of mist of hydrogen peroxide and silver cations, physical separation and compartmentalization of the intensive care unit. The GLOSAIR™ 400 System was used to deliver a mist of hydrogen peroxide and silver cations. Hydrogen peroxide is an oxidizing agent, which kills microorganisms.
Results: A total of 103 strains of Acinetobacter species were identified from the patients over the 13 months period (Fig. 1). The mean infection rates decreased from 14.3 in the first three months of the program to 4 in the last three month after continuous.
Conclusions: The program using the three procedures offered a significant decrease in infections at the ICU as measured by Acinetobacter count, which is one of the most hazardous nosocomial pathogens.
1. Burgmann H et al. Intensive Care Med 36:1597-1601, 2010.
2. Boncagni F et al. Minerva Anestesiol 81:765-775.3, 2015.
P054 A review of current practice of continuous antibiotic infusions on intensive care units in England
G Page, E Turner, C Day
Royal Devon and Exeter Hospital, Exeter, UK
Introduction: The efficacy of ß lactam antibiotics is related to the time above MIC. Continuous or extended infusions can be used to increase the time above MIC, especially in patients with normal or increased drug clearance. Administering antibiotics by continuous infusion is not a new concept. A review in 1992 looks at the outcomes of continuous infusions . More recently an improvement in mortality has been demonstrated . Our perception was that uptake of this low cost intervention was not common, so we undertook a survey to determine how commonly continuous infusions are used in England.
Are you using continuous or extended antibiotic infusions?
Which antibiotics are you using for continuous or extended infusions?
If not currently using has it been considered?
Data was collected over a week in June 2017.
Results: There was an 87% response rate. 73 (44.5%) of the units continuously infuse some antibiotics, however 71.2% of those only infuse vancomycin and not ß lactams. Only 21 of the total responders (12.8%) infuse antibiotics other than vancomycin (i.e. ß lactams).
Conclusions: The theoretical advantage of continuous infusion of ß lactam antibiotics has been described for over 20 years. There is now evidence that this may improve survival. Despite this, uptake in England has been slow.
1. Craig WA et al. Antimicrob Agents Chemotherap 36(12):2577-83, 1992
2. Roberts JA et al. Am J Respir Crit Care Med 194(6):681-91, 2016
J Mvukiyehe1, P Banguti1, R Elisabeth2, J Richard3, E Tuyishime1
1University of Rwanda, Kigali, Rwanda,2Harvard University, Boston, MA, USA,3Minnesota University, Minneapolis, MN, USA
Introduction: Infections contribute to a significant proportion of morbidity and mortality worldwide. While many infections are successfully managed with antimicrobial therapy, rates of antimicrobial resistance (AMR) are increasing. Certain patient populations such as those admitted to intensive care units (ICU) are at high risk.
Methods: We conducted a retrospective, observational study of all ICU patients at a tertiary referral hospital in Rwanda from January 2015 through December 2016 We collected data on diagnosis, ICU length of stay, mortality and hospital length of stay, as well as microorganism, site of culture, AMR and antibiotics prescribe.
Results: Overall, 331 patients were admitted to the ICU. Most patients were admitted from the main operating theater (n=150, 45%).The most common admitting diagnoses were sepsis (n=113, 34%), head trauma (n= 90, 27%). A total of 268 samples were collected from 331 patients. The samples were from blood (n=110, 33%), tracheal aspirate (n=22, 7%),. The most common organisms isolated were Klebsiella (n=30, 29%), Acinetobacter (n=20, 19%), E.coli (n=16, 15%), Proteus (n=15, 14%), Citrobacter (n=8, 8%), S aureus (n=7, 7%), Pseudomonas (n=5, 5%), and other (n=9, 9%). Of Klebsiella isolates, 100% and 76% were resistant to ceftriaxone and cefotaxime, respectively. Of E.coli isolates, 86% and 71% were resistant to ceftriaxone and cefotaxime, respectively. All Acinetobacter isolates were resistant to ceftriaxone and cefotaxime.
Conclusions: There is an alarming rate of antimicrobial resistance to commonly used antibiotics in the ICU. Expanding antibiotic options and strengthening antimicrobial stewardship are critical for patient care.
G Latten1, P Stassen2
1Zuyderland MC, Sittard-Geleen, Netherlands,2Maastricht UMC+, Maastricht, Netherlands
Introduction: This study provides an overview of the prehospital course of patients with a (suspected) infection in the emergency department (ED). Most research on serious infections and sepsis has focused on the hospital environment, while potentially most delay, and therefore possibly the best opportunity to improve treatment, lies in the prehospital setting.
Methods: Patients were included in this prospective observational study during a 4 week period in 2017. All patients aged 18 years or older with a suspected or proven infection were included. Prehospital, ED and outcomes were registered.
Results: In total, 2452 patients visited the ED during the study period, of whom 440 (17.9%) patients had a (suspected) infection. (Fig. 1) Median duration of symptoms before ED visit was 3 days (IQR 1-7 days), with 23.9% of patients using antibiotics before arrival in the ED. Most patients (83%) had been referred by a general practicioner (GP), while 41.1% of patients had visited their GP previously during the current disease episode. Twenty-two patients (5.0%) experienced an adverse outcome (ICU admission and/or 30-day all- cause mortality): these patients were less often referred by a general practicioner (GP) (59.1 vs. 84.2%, p=0.001) and were considered more urgent both by EMS and in the ED.
Conclusions: The prehospital phase of patients with an infection provides a window of opportunity for improvement of care. Patients become ill 3 days before the ED visit and 41.1% already visited their GP previously during the current disease episode, while 23.9% is currently using antibiotics. Future research should focus on quality improvement programs in the prehospital setting, targeting patients and/or primary care professionals.
H Ezzouine, Z Sghier, Y Hafiani, K Mediouni, A Benslama
Faculty of medicine and pharmacy.University Hassan II.Casablanca, Casablanca, Morocco
Introduction: Worldwide, the prevalence of tetanus has decreased.However, even if progress has been made in the combat to eradicate tetanus it may be a cause of admission to intensive care.The objectives of our study are to determine epidemiological,clinical and prognostic characteristics for severe tetanus in our unit.
Methods: We conducted a retrospective study in the medical intensive care unit of Ibn Rushd hospital in Casablanca in Morocco from 2010 to 2016.We studied the epidemiological,clinical and prognostic characteristics of the patients who were admitted for severe tetanus.
Results: The incidence of severe tetanus was 2.04% affecting male in 100%.41.9% were aged between 31 and 40 years old. In 85.7% there were a integumentary portal of entry. Contractures were present in 69%of the cases. At intensive care unit admission, 21.4% of the patients were sedated. The anti-tetanus vaccination was never updated. According to the Dakar score 28.6% of the patients were listed Dakar 1, 54.8% Dakar 2 and 16.6% Dakar 3. For the Mollaret score, the crude form was found in 44.2%, the acute generalized form was found in 32.6% and the severe form in 20.9% of the cases.Mechanical ventilation was necessary in 83.3%. Diazepam and baclofen were used in 92.9%, phenobarbital in76.2% and propofol in 42.85%. A serotherapy was used for all the patients and a preliminary vaccination dose for 26.9%. All the patients received antibiotics, penicillin G 33.33% and metronidazole 76.2%. The mortality was 61.9%. The length of intensive care stay was significantly higher. The need for an intubation,its duration and the occurrence of autonomic dysfunction have significantly influenced the mortality.
Conclusions: To improve the prognosis in these serious forms of tetanus,it is highly important to identify the warning signs and refer patients in intensive care for early and appropriate management in intensive care.
T Melissopoulou, S Kolovou, M Panoutsopoulou, T Kypraiou, M Papadimitriou, O Apostolou, J Deliolanis, A Pantazatou, A Skiada, J Pavleas, J Floros
Laiko Hospital, Athens, Greece
Introduction: Bloodstream infections (BSIs) are associated with increased mortality in the ICU. The aim of the study was to evaluate the epidemiology and resistance patterns during the period 2013 to 2017.
Methods: Bacteria and fungi isolated from the blood of patients hospitalized in a mixed ICU during the study period were retrospectively analyzed. Sensitivity testing was performed with disk diffusion (Kirby-Bauer) and Microscan Walkaway 96 plus for minimal inhibitory concentrations.
Results: During the study period 1198 patients were hospitalized in the ICU. BSIs were diagnosed in 284 cases (23.7%). The isolated microorganisms were Acinetobacter baumannii (29%), Klebsiella pneumoniae (15%), other Enterobacteriaceae (8%), Pseudomonas aeruginosa (6%), Stenotrophomonas maltophilia (1%), enterococci (20%), staphylococci (8%) and Candida spp. (13%). Of the A. baumannii isolates, 97% were resistant to carbapenems, 9.6% to colistin, and 31% to tigecycline. Of the K. pneumoniae isolates 80% were resistant to carbapenems, 70% to colistin, and 4.5% to tigecycline. Of the P. aeruginosa species 44% were resistant to carbapenems and they were all susceptible to colistin. The rate of resistance to vancomycin was 56% for the E. faecium isolates, 5.5% for the E. faecalis, while the resistance to methicillin of the coagulase negative staphylococci was 90%. The most commonly isolate species of Candida was C. albicans.
Conclusions: Multi-drug resistant isolates, especially A. baumannii and Enterobacteriaceae, are a serious problem in our ICU. Gram positive bacteria are less common, but the resistance of enterococci to vancomycin is significant. Antibiotic stewardship and infection control measures should be applied in a more strict way.
I Titov 1, S Melnyk2, M Grynovska1
1Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine,2Ivano-Frankivsk Regional Clinical Hospital, Ivano-Frankivsk, Ukraine
Introduction: Nosocomial sinusitis (NS) is a complication of critically ill patients which develops 48-72 h after admission and is mostly linked but not limited to such invasive procedures as nasotracheal intubation and nasogastric tube placement. NS is often overlooked as a source of pyrexia of unknown origin, meningeal manifestations, sepsis and ventilator associated pneumonia in ICU patients. CT scanning and sinus puncture are used to confirm the inflammatory process and identify the pathogen behind it.
Methods: A retrospective case study of 6.479 ICU patients for a period of 2012-2016 was performed. We have analysed data from the CT scans of paranasal sinuses and bacteriological findings of samples obtained from sinus puncture.
Results: 644 (9.9%) patients were suspected of NS on the 5-7th day of stay in the ICU. The CT scan confirmed pathological changes in 464 patients (7.1%). Hemisinusitis was detected in 422 patients (90.9%) and pansinusitis in 41 patients (8.8%). There was also an isolated case of maxillary sinusitis in 1 patient (0.2%). The pathogenic culture was identified only in 297 (64%) samples, 34.6% of which revealed isolated bacteria and 65.4% a polymicrobial association. Gram positive bacteria were detected in 16.1% of cases and Gram negative in 49.5%. Most cases revealed multiple antibiotic resistance.
Conclusions: 1. NS has proved to be largely caused by Gram negative bacteria and polymicrobial associations. The use of broad spectrum antibiotics in ICU may justify the presence of sterile cultures.
2.Early identification of risk patients in ICU as well as the use of screening CT scan may benefit timely diagnosis and adequate treatment of patients.
3.Preventive considerations include: patient’s bed head elevation, the use of oral gastric tube in sedated and coma patients on ventilation, nasotracheal intubation only if indicated, removal of nasogastric tube at night, proper hygiene.
J Barrett1, A Keeley1, D Keane1, L John1, W Lynn2, N Sabir1
1Northwick Park Hospital, London, UK,2Ealing Hospital, London, UK
Introduction: Despite wide availability of effective treatment a minority of patients with TB will become critically ill. Here we describe the presentation, demographics and outcomes of patients with TB admitted to ICU in our trust which is based in an area of high TB incidence in London (incidence >50/100000).
Methods: The London TB register was cross-referenced against ICU records from 01.01.07 to 31.12.2016. Clinical data were collected for matched patients.
Results: 78 patients identified; 50% of South Asian origin, 29.5% of African origin, 12% UK born 31% of patients had multifocal TB. TB sensitivities: 89% fully sensitive, 7% mono-drug resistance, 4% multi-drug resistant TB. Median length of ICU stay was 5 days (IQR 2-14). 6 patients were readmitted. 23 patients died on ICU (29.5%), 10 patients died prior to hospital discharge. Median time to death following ICU admission: 15 days (IQR 5-35).
Conclusions: Only 78 of 4,011 TB patients (2%) required critical care intervention (Table 1). Those admitted to ICU were older and more likely to have pulmonary, CNS, miliary or abdominal TB (Table 2). Mortality was high despite critical care input in a unit familiar with managing TB, and 24 hour access to Infectious Diseases advice within the trust, likely due to overwhelming organ dysfunction, patient frailty and advanced TB infection. Rates of drug resistant TB were low and comparable to UK-wide rates over that period (5% mono-drug resistant, 2% MDR) thus less likely a contributory factor to the majority of deaths.
Reasons for ICU admission
Reason for admission
Type 1 respiratory failure
Type 2 respiratory failure
>1 reason for admission
Characteristics of ICU TB patients vs non-ICU TB patients
ICU TB patients (n=78)
Non-ICU TB patients (n=3933)
56 (range 17-84)
28 (range 0-96)
TB smear +/culture +
P061 Short term antibiotics prevent early VAP in patients treated with mild therapeutic hypothermia after cardiac arrest
T Daix1, A Cariou2, F Meziani3, PF Dequin4, C Guitton5, N Deye6, G Plantefève7, JP Quenot8, A Desachy9, T Kamel10, S Bedon-Carte11, JL Diehl12, N Chudeau13, E Karam14, F Renon-Carron1, A Hernandez Padilla 1, P Vignon1, A Le Gouge4, B François1
1Centre Hospitalier Universitaire Dupuytren, Limoges, France,2hôpital Cochin (APHP) et université Paris Descartes, Paris, France,3Université de Strasbourg (UNISTRA), Faculté de Médecine, Hôpitaux universitaires de Strasbourg/Nouvel hôpital civil, Strasbourg, France,4CHU Bretonneau, Tours, France,5CHU de Nantes, Nantes, France,6CHU Lariboisière, APHP, Paris, France,7CH Victor Dupouy, Argenteuil, France,8CHU François Mitterrand, Dijon, France,9Centre Hospitalier d’Angoulême, Angoulême, France,10CHR d’Orléans, Orléans, France,11Centre Hospitalier de Périgueux, Périgueux, France,12HEGP, AP-HP, Paris, France,13Centre hospitalier du Mans, Le Mans, France,14Centre hospitalier général, Brive la Gaillarde, France
Introduction: Patients treated with mild therapeutic hypothermia after cardiac arrests with shockable rhythm are at high risk of ventilator-associated pneumonia (VAP) . Despite retrospective trials suggesting a benefit of short-term (48h) antibiotics in this setting , it is not recommended. The primary objective was to demonstrate that systematic antibiotic prophylaxis can reduce incidence of early VAP (<7 days). The impact on incidence of late VAP and on Day 28 mortality was also assessed.
Methods: Multicenter, placebo-controlled, double-blinded, randomized trial. ICU patients >18 years, mechanically ventilated after out-of-hospital resuscitated cardiac arrest related to initial shockable rhythm and treated with mild therapeutic hypothermia were included. Moribund patients and those requiring extracorporeal life supports, with ongoing antibiotic therapy, known chronic colonization with multiresistant bacteria or known allergy to beta-lactam antibiotics were excluded. Either IV injection of amoxicillin-clavulanic acid (1g/200mg) or placebo was administered 3 times a day for 2 days. All pulmonary infections were recorded and blindly confirmed by an adjudication committee.
Results: In intention to treat analysis, 196 patients were analyzed, (treatment group n=99; mean age 60.5±14.4 years, sex ratio=4, SOFA score 8.7±3.1). Global characteristics of cardiac arrest were similar (no flow= 3.5min vs 3.8min, low-flow= 21.8min vs 18.2min). 60 VAP were confirmed incl. 51 early VAP, 19 in treatment group vs 32 in placebo group (HR=0.546; IC 95%=[0.315; 0.946]) (Fig. 1). Occurrence of late VAP (4% vs 5.1%) and Day 28 mortality (41.4% vs 37.5%) was not affected by the study procedure.
Conclusions: Short-term antibiotic prophylaxis significantly decreases incidence of early VAP in patients treated with mild therapeutic hypothermia after out-of-hospital cardiac arrest related to shockable rhythm and should be recommended.
1. Mongardon N et al Crit Care Med 39:1359-64, 2011.
2. Davies KJ et al Resuscitation 84:616-9, 2013
P063 Clinical burden of inappropriate empirical antimicrobial therapy of in-hospital complicated intra-abdominal infections
S Carelli, T Taccheri, MS Vallecoccia, SL Cutuli, V Di Gravio, G De Pascale, M Antonelli
Fondaz. Policlinico A. Gemelli, Rome, Italy
Introduction: Complicated intra-abdominal infections (cIAIs) remain a common cause of morbidity and mortality among ICU patients and therapeutic failure still occurs. This study aimed to assess the clinical impact of an initial inappropriate empirical therapy of cIAIs.
Methods: This retrospective study enrolled patients admitted to the ICU of the Fondaz. Pol. A. Gemelli in Rome, between February 2010 and February 2017 with a diagnosis of in hospital cIAI. Comparisons between patients receiving initial inappropriate antimicrobial therapy (IIAT) and initial appropriate antimcrobial therapy (IAAT) were performed.
Results: A total of 137 patients were included (IIAT=44 and IAAT=93). Baseline characteristics were comparable, with the exception of SOFA score at infection which was higher in IAAT (p=0.04). Secondary peritonitis was the main type of cIAI (45.5% in IIAT and 40.9% in IAAT) followed by abdominal abscess and biliary tract infection. Secondary bacteraemia was significantly higher in IIAT (p=0.03). Conversely, IAAT had an higher rate of adequate source control (p=0.01). Empirical therapy of IAAT patients included more frequently anti gram-positive (p=0.016) and carbapenems (p=0.01), while empirical dual anti gram negative and antifungal coverages rate were not different (Fig. 1). MDR and polimicrobial infections rate was significantly higher in IIAT when associated with septic shock at occurrence of infection (p=0.03; Fig. 2). IAAT showed significantly lower mortality at 28 and 90 days (p<0.01) as well as higher rate of clinical cure and microbiological eradication than IIAT (p<0.01). At the multivariate analysis, adequate source control [p=0.04, OR 0.25 (0.09-0.65)] and IIAT [(p<0.01, OR 11.4 (4.02-32.3)] turned out to be independently related with 28 days mortality.
Conclusions: In cIAIs an appropriate empirical antibiotic therapy and an early infection source control are closely associated with better outcomes.
P064 Prospective observational study evaluating antibiotic prescription pattern and microbial isolates and their correlation with hemodynamic stability in icu patients
M Bhattacharyya 1, A Saha2, T Chatterjee2, S Todi1
1AMRI Hospitals, Kolkata, India,2Jadavpur University, Kolkata, India
Introduction: Antibiotics are the most commonly prescribed drugs in ICU.In the era of antibiotic resistance it is difficult to choose antibiotics during septic episode.The choice antibiotics mainly depends on clinical diagnosis,culture sensitivity and local flora. Whether severity of illness really maters is not well known. To study antibiotic prescription pattern and whether the choice of antibiotic varies according to hemodynamic stability in patients admitted in ICU.To study of microbiological isolates and their variability according to hamodynamic stability in ICU patients.
Methods: All ICU patients of more than 18 years age who received antibiotics and where cultures had been sent were included in the study.Patients discharged against medical advice and where treatment had been withdrawn were excluded in this study. This prospective observational study was conducted between July 2016 to March 2017.Patients were divided into stable and unstable group according to hemodynamic parameter and usage of antibiotics and microbiological isolated were correlated. ICU mortality and length of stay were correlated between hemodynamically stable and unstable group.
Results: 786 sepsis episode were analysed. Mean age was 65 years, male predominant, and average APACHE IV score was 58(SD25). We had 444 patients in unstable group of which 71% patients got discharged and 86% of patients got discharged in stable group. Antibiotic combination therapy was used more in hemodynamically unstsble patients(p 0.3). BLBLI was used more in stable group. Drug resistance in microbiological isolates did not reveal any statistically significant difference among stable or unstable group.
Conclusions: There is a tendency to administer combination antibiotics in sicker group of patients with hemodynamic instability. Prevalence of microbial flora did not show any statistical difference. outcome is worse in hemodynamically unstable patients.
H Al-Dorzi1, R Khan1, T Aldabbagh1, A Toledo1, S Al Johani1, A Almutairi2, S Khalil2, F Siddiqui2, Y Arabi3
1King Abdulaziz Medical City, Riyadh, Saudi Arabia,2MSD, Riyadh, Saudi Arabia,3King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
Introduction: Candida score (CS) is used to identify patients with invasive candidiasis in the ICU, but its clinical use has not become widespread. Our objective was to evaluate the clinical significance of CS in a mixed population of ICU patients.
Methods: This was a prospective observational study of critically ill patients who had Candida species growth during their stay in any of six different ICUs of a tertiary-care center. Two intensivists classified patients as having Candida colonization or invasive candidiasis according to predefined criteria. CS was calculated for each patient on the day of Candida species growth as follows: 1 point for parenteral nutrition + 1 point for surgery + 1 point for multifocal Candida colonization + 2 points for severe sepsis. The Receiver Operating Characteristic (ROC) curve was plotted to assess CS ability to discriminate between invasive candidiasis and Candida colonization.
Results: CS was 1.6±0.9 in patients with Candida colonization (N=261) and 2.4±0.9 in those with invasive candidiasis (N=120) (p<0.001). However, only 38.7% of invasive candidiasis cases had CS >= 3 (compared with 8.0% of Candida colonization cases; p<0.001). The ROC curve (Fig. 1) showed that CS had fair ability to discriminate between invasive candidiasis and Candida colonization (area under the curve 0.71, 95% confidence interval 0.65 to 0.77; p<0.001). In patients with invasive candidiasis, CS was similar in hospital survivors and nonsurvivors (2.2±0.9 and 2.5±0.8, respectively; p=0.13). CS did not discriminate between survivors and nonsurvivors (area under the ROC curve 0.61, 95% confidence interval 0.46 to 0.75; p<0.15).
Conclusions: CS was higher in patients with invasive candidiasis than those with Candida Colonization. However, its ability to discriminate between these patients was only fair. CS was not associated with hospital mortality.
P066 Poor reliability of creatinine clearance estimates in predicting fluconazole exposure in liver transplant patients
M Lugano, P Cojutti, F Pea
ASUIUD, Udine, Italy
Introduction: Invasive candidiasis (IC) is a frequent complication in liver transplant (LT) recipients, especially during the first 1-3 months after LT. Fluconazole is a triazole antifungal used for prophylaxis and treatment of IC. Due to its renal elimination, dose adjustments are usually based on estimated creatinine clearance (eCrCL). However, the reliability of eCrCL in predicting fluconazole clearance has never been investigated in this population. The aim of this study was to conduct a population pharmacokinetic (popPK) analysis in a cohort of LT patients who underwent therapeutic drug monitoring (TDM) in order to find out which covariates may influence fluconazole pharmacokinetics (PKs).
Methods: This retrospective study included LT patients who were admitted to the intensive care unit of our University Hospital between December 2007 and May 2016, and who were treated with intravenous fluconazole in the first months after LT. TDM of fluconazole was performed with the intent of attaining the efficacy pharmacodynamic target (AUC24h/MIC > 55.2). The tested covariates were: age, gender, CKD-EPI eCrCL, time from LT, serum albumin and transaminases, SAPS II score. PopPK was carried out with Pmetrics software.
Results: Nineteen patients (mean±SD age, weight and serum creatinine of 60±8.4 years, 75±16.8 kg, 1.0±0.62 mg/dL, respectively) with a total of 89 fluconazole trough plasma concentrations were included in the popPK analysis. Mean±SD fluconazole distribution volume (Vd) and clearance (CL) were 27.02±10.78 L and 0.55±0.19 L/h. Age and time from LT were the only clinical covariates significantly correlated with fluconazole Vd and CL, respectively. Conversely, CKD-EPI eCLCr was unable to predict fluconazole CL.
Conclusions: CKD-EPI eCLCr is unreliable in predicting fluconazole exposure in LT recipients. Consistently, in this population adaptation of fluconazole dose should be based on measured CrCL, and TDM may be helpful in optimizing drug exposure.
M Boujelbèn1, I Fathallah1, H Kallel1, D Sakis1, M Tobich1, S Habacha1, N Ben Salah1, M Bouchekoua2, S Trabelsi2, S Khaled2, N Kouraichi1
1Hôpital Régional Yasminette, Ben Arous, Tunisia, 2Hôpital Charles Nicolle, Tunis, Tunisia
Introduction: The aim is to determine the incidence, characteristics and risk factors of invasive candidiasis (IC) in critically ill patients by using a weekly screening protocol.
Methods: A 9 months’ prospective study was conducted in a 6-bed MICU. The candidiasis screening consisted of the culture of plastic swabs (from different body sites), urine and respiratory tract samples.It was conducted upon admission and on weekly basis for all the patients. Decision to treat was based on clinical and microbiological features.
Results: 97 patients were included. The colonization rate with Candida spp was 28.8%(n=28). 415 screening samples were collected with a positivity rate at 27.9%(n=118). Table 1 describes the isolated Candida species by site. Antifungal resistance was tested in 72(62%) species. The resistance rate to fluconazole was 13.8%(n=10). The antifungal resistance of Candida albicans is detailed in Table 2. 14(14.4%) patients presented an IC with a mean age and mean SAPS II at 54.3 ± 18 years and 48±18.7 respectively. 7(50%) presented acute renal failure upon admission. 85.7% (n=12) of the patients needed mechanical ventilation. The median length of stay was 29 days [18.5-62.5] and the mortality rate was 42.9%(n=6). The mean SOFA score upon infection was 8.5±2.79. The candida score was >= 2.5 and the colonization index was >= 0.5 in 92.8%(n=13) and 78.5%(n=11) of the patients respectively. Only one patient had a positive blood culture. Mannan antigen and anti-mannan antibodies were screened only in five patients with a positivity rate at 100%(n=5). The most isolated species was: Candida albicans 64.3%(n=9). Multivariate analysis showed that prior use of Imipinem more than 6 days was a risk factor for IC (OR=9.37, CI95[1.15 ; 75.8], p=0.03).
Conclusions: This study showed the ecology and epidemiology of Candida species in our MICU with an increased IC rate and high mortality. Prior Imipinem use was a risk factor for IC.
Isolated Candida species by site
Unidentified Candida spp
Candida albicans’ antifungal resistance
Resistant n(%) n(%)
Y Mehta1, O Shrivastav2, K Bajan3, A Khurana4, A Qamra4
1Medanta The Medicity, Gurgaon, India,2Jaslok Hospital, Mumbai, India,3PD Hinduja Hospital, Mumbai, India,4Wockhardt, Mumbai, India
Introduction: ICU-acquired infection is as high as 42.7 episodes per 1000 patient-days in lower-middle income countries like India (WHO). Almost three times higher than in high-income countries . Candida Infection is the 3rd most commonly acquired nosocomial infection in India burdening the debilitated patient with longer ICU stay . There are no definite guidelines on whether & when to start anti-fungal treatment, specific to India where IFI risk is high and diagnostic facilities are limited. Currently, the Intensivists across India are using antifungals, according to their clinical experience and selective application of international guidelines leading to non-uniformity of patient outcomes.
Methods: In an endeavour to synchronize anti-fungal therapy and educate intensivists from small cities of India, 2 Intensivists and 1 Infectious Disease specialist of international repute were approached to design a module on ‘Invasive Fungal Infections – When to Start Anti-fungals in ICU [Fig. 1]. The IFI in India was summarised into a compact 1 hour session for dissemination of knowledge using IDSA 2016 as a reference guideline. 12 Intensivists from across India were trained on the module by our faculty. The module was rolled out to Intensivists and Pulmonologists focussing particularly on the tier-2 & tier -3 cities where avenues for learning are limited [Fig. 2].
Results: The module covered epidemiology, diagnostic challenges & anti-fungal therapies in Candidemia. It also included Candiduria, Aspergillosis & Mucormycosis that intensivists infrequently encounter. 4 meetings have been conducted and over 150 intensivists have been trained so far and more such trainings are planned in near future.
Conclusions: This module serves as a good academic tool to create awareness, education and harmonisation of anti-fungal treatment amongst HCPs across India.
1. WHO Report Burden of Endemic HCI, 2011
2. Oberoi JK JIMSA 23 No. 1, January - March 2010
E Belesiotou, C Routsi, C Vrettou, E Magira, E Douka, P Kaltsas, M Nepka, E Perivolioti, E Kraniotaki, S Zakinthinos
Evaggelismos General HOSPITAL, Athens, Greece
Introduction: Trichosporon species are fungi found in nature and human normal flora but they can be an opportunistic pathogen, associated with medical devices (biofilm formation), especially in intensive care unit(ICU) patients.
Methods: After cultivation of urine samples, the identification was based on system Vitek 2, API 20C AUX, API ID 32C(bioMérieux@) and the susceptibility test on Vitek 2 and E test.
Results: During the last two years, 1/10/2015-30/9/2017, in 2359 ICU patients, 27884 patient days, we detected Trichosporon spp in 31patients. The minimum stay was 28 days. 24(77,4%) men and 7(22,6%) women. 27/31(87%) strains were T. Asahii and 4(13%) T. mucoides. All patients were exposed to antibiotics, had medical devices and other infections with other multi drug resistant strains. In 10 patients the infection persisted over one month, and 2 patients died during Trichosporon spp. funguria. According to the antifungal susceptibility testing, 3 strains T. Asahii had intermediate sensitivity (MIC:16:I) and 3 strains were resistant (MIC:16:R) to Fluconazole.. All strains T. Asahii were sensitive to Amphotericin-B. All T. mucoides were sensitive to Flucytosine. 2/4 (50%). T. mucoides were resistant to voriconazole(MIC:4 R), 2/4(50% R) to Amphotericin-B (MIC:8-16 R), and 1/4(25%) to Fluconazole (MIC:32 R). The echinocandins are not active against Trichosporon spp.. In most patients treatment was administration of voriconazole.
Conclusions: The Trichosporon spp after 28 days in ICU percentage is 31/2359(1,31%) and the incidence is 31/2788(1.11%). The majority were men. The azole drugs and Amphotericin-B showed activity against Trichosporon spp but recommendations must be based on in vitro susceptibility data and clinical experience and features.
P071 Acinetobacter baumannii ventilator-associated pneumonia epidemiology, risk and prognosis factors
W Sellami, W Essmat, I Ben mrad, Z Hajjej, H Gharssallah, I Labbene, M Ferjani
Military Hospital, Tunis, Tunisia
Introduction: Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in critically ill patients, reaching up to 30 to 50%, with a high mortality rate. Acinetobacter baumannii (AB) has emerged as a pathogen frequently incriminated in VAP’s in Tunisia. The aim of this study was to describe the epidemiological characteristics of Acinetobacter baumannii VAP, to identify the risk factors and the predictors of poor outcome of VAP with AB.
Methods: A retrospective study was conducted in the intensive care unit of the Military Hospital of Tunis, from January 2015 to December 2016. All patients with VAP’s documented infection were included. VAP’s patients with AB vs VAP’s patients due to other pathogens.
Results: Seventy patients (10%) developed VAP. The incidence of VAP with AB was 6.28%. Previous antibiotic therapy was identified as a risk factor for Acinetobacter baumanii-induced pneumonia, unlike the underlying disease. AB was resistant to ceftazidime in 100%, imipenem in 97.5% with sensitivity to colistin in 100% of cases. Multidrug-resistant AB accounted for 22.5% and highly resistant AB accounted for 77.5%. Patients with AB pneumonia were more frequently complicated by acute respiratory distress syndrome compared to other patients (37.5% versus 8.9%, p = 0.02), leading to higher mortality (52.5% versus 20%, p = 0.02).
Conclusions: The increasing incidence of VAP in multidrug-resistant and highly resistant AB predicts a high morbidity and mortality. Hence, the risk factors related to poor outcome in VAP’s need to be identified. The implementation of infection-control measures, mainly the cross-transmission, may be needed to improve outcome.
S Chatterjee 1, A Bhakta1, J Basak2, S Todi1
1AMRI Hospitals, Kolkata, India,2Jadavpore University, Kolkata, India
Introduction: This study assessed whether empiric combination antibiotic therapy directed against Gram-negative bacteria is associated with lower intensive care unit (ICU) mortality compared to single antibiotic therapy.
Methods: Retrospective cohort study on prospectively collected data conducted in the ICU of a tertiary care hospital in India between July2016 to March2017. All consecutive infection episodes treated with empiric antibiotic therapy and with subsequent positive culture for Gram-negative bacteria were included. Primary and secondary outcomes were all cause ICU mortality and ICU length of stay (LOS). Outcomes were compared between infection episodes treated with single vs.combination antibiotic therapy.
Results: Of total 214 episodes of gram-negative infections 66.4% received combination-antibiotic therapy. Baseline demographic and clinical characteristics between single vs. combination therapy groups were similar (mean age: p=0.07; sex: p=0.3; mean APACHE IV score: p=0.07). Overall ICU mortality did not significantly differ between single and combination antibiotic groups (30.2% vs. 27%; p=0.7). In single antibiotic group, ICU mortality was significantly higher for antibiotic-resistant compared to antibiotic-sensitive bacteria (77.8% vs. 18.5%, p=0.0002). In combination group, significantly lower ICU mortality was noted if bacteria was sensitive to even one antibiotic compared to pan-resistant bacteria (21.4% vs. 63.6%, p=0.0001). ICU LOS was similar between antibiotic-sensitive bacteria and antibiotic-resistant bacteria, both in single and combination therapy groups (single, antibiotic-sensitive vs. antibiotic-resistant: mean LOS±SD 14.6±12.7 vs.12.8±11days; p=0.6; combination, antibiotic-sensitive vs. antibiotic-resistant: 15.5±13.3 vs.11.2 days; p=0.1).
Conclusions: Irrespective of the number of antibiotics prescribed as empiric therapy, outcome of patients solely depends on the sensitivity pattern of the bacteria isolated.
P073 Pharmacokinetics of trimethoprim and sulfametrole in critically ill patients on continuous haemofiltration
R Welte1, J Hotter1, T Gasperetti1, R Beyer1, R Bellmann-Weiler1, S Eschertzhuber1, M Zaruba1, I Lorenz1, M Ströhle2, M Joannidis1, R Bellmann1
1Medical University of Innsbruck, Innsbruck, Austria,2General Hospital of Innsbruck, Innsbruck, Austria
Introduction: The combination of trimethoprim and sulfametrole (TMP-SMT, Rokiprim®) is active against multi-drug resistant bacteria and Pneumocystis jirovecii. In critically ill patients undergoing continuous veno-venous haemofiltration (CVVH), however, its use is limited because of lacking pharmacokinetic data.
Methods: Pharmacokinetics of both drugs were determined after standard doses in patients on CVVH and in critically ill patients with approximately normal renal function. Quantification of TMP and SMT was done by high pressure liquid chromatography (HPLC) and UV detection after pre-purification by solid phase extraction. The total clearance (CLtot) was estimated from arterial plasma levels and the haemofilter clearance (CLHF) from plasma and ultrafiltrate concentrations.
Results: Six patients on CVVH (3 after the first dose, 3 at steady state) and nine patients off CVVH have been enrolled (4 after first dose, 7 at steady state). After a single dose, CLtot of SMT was 3.5 (1.8-3.8, median [range]) and 1.7 (1.1-2.7) L/h on and off CVVH, respectively. At steady state, we observed a CLtot of 1.0 (0.5-1.0) and 0.3 (0.2-0.9) L/h, respectively, on and off CVVH. Steady state trough levels (Cmin) of SMT amounted to 52-113 mg/L in patients on CVVH and 18-145 in patients off CVVH. CLtot of TMP was 4.4 (2.5-5.3) L/h on CVVH and 5.4 (3.2-9.9) L/h off CVVH after the first dose. At steady state, its CLtot amounted to 0.8 (0.4-0.8) and 1.0 (0.6-1.9) L/h on and off CVVH, respectively. Cmin was 4-12 mg/L on CVVH and 3-9 mg/L in patients off CVVH. CLHF accounted for 22-68% of CLtot of SMT and 28-72% of CLtot TMP.
Conclusions: Exposure to both antimicrobial agents is highly variable, but comparable in patients on and off CVVH. As considerable amounts of SMT and TMP are eliminated by CVVH, no excessive accumulation appears to take place during treatment with standard doses.
W Freitas1, M Davi1, L Souza1, M Couto1, L Lourenço1, R Eiras1, H Primo1, J Páramo1, J Garcia1, M Alves2
1Hospital Casa de Portugal, Rio de Janeiro, Brazil,2Universidade Federal de Juiz de Fora, Juiz de Fora, Brazil
Introduction: This study aimed to evolutionary analyze the decrease of the Meropenem Defined Daily Doses (DDD), at a Brazilian Intensity Care Unity (ICU) before and after six months of the antimicrobial stewardship intervention.
Methods: From June to November 2017, the meropenem use to treat inpatients at the Hospital Casa de Portugal ICU, Rio de Janeiro, Brazil, was reduced to seven days and Meropenem DDD, CRE ID, consumption of saline 100 mL for dilution, equipment for infusion of antibiotics, and global mortality values and BSI deaths were noted. Same data were retrospectively collected from December 2016 to May 2017. Results of both periods were analyzed by Student’s T Test.
Results: Meropenem DDD values ranged from 143.01 to 187.70 and 22.87 to 160.76, from December 2016 to May 2017 and June to November 2017, respectively, with average of 174.7 and 101.6 in this order, with T(10) of 3.60 (p = 0.005). CRE ID also decreased, with values ranging from 9.6 to 34.9 (December 2016 to May 2017) and 1 to 18.1 (June to November 2017), with average of 16.2 and 7.2, respectively. A decrease in the use of saline for dilution by 1000 patients-day with values from 2930 to 4436 and 2619 to 2980 from December 2016 to May 2017 and from June to November 2017 respectively, with 3310 and 2868 (average) in this order was detected. We have observed concomitant decrease in equipment for infusion by 1000 patients-day with values from 995 to 2116 and from 918 to 1054, from December 2016 to May 2017 and from June to November 2017, respectively, with average values of 1236 and 967, in this order. The global mortality values varied of 17.41 to 22.96 (December 2016 to May 2017) and 11.61 to 17.9 (June to November 2017), with average of 19.5 and 14.5 respectively, with T(10) of 3.78 (p = 0.004). A drop in the mean number of BSI deaths from December 2016 to May 2017 and June to November 2017 of 2.6 to < 1, in this order, was also observed.
Conclusions: Meropenem stewardship intervention had a positive impact in the Intensive Care Unity evaluated.
P075 Colistin ‘MIC’ creep, a harbinger for resistance? Study for monitoring antimicrobial resistance trends (SMART) - South Africa 2015-2016
B Magazi, R Holl
MSD, Midrand, South Africa
Introduction: Loss of colistin as a clinical option has profound public health implications. Widespread use of colistin in agriculture and humans has seen the emergence of Mcr-1 mediated resistance amongst South African patients . We sought to describe the trends of colistin minimum inhibitory concentrations (MIC) over two years using data collected by SMART.
Methods: SMART monitors the in vitro susceptibility of clinical aerobic and facultative gram-negative bacterial isolates to selected antimicrobials of importance, enabling longitudinal analyses to determine changes over time. The dataset comprised bacterial isolates from four different South African private pathology laboratories and one public sector pathology laboratory from 2015 - 2016. The methods used in the study have been described elsewhere . Isolate proportions between years were compared using the chi-squared test with Yates’ continuity correction.
Results: 146 and 198 Pseudomonas aeruginosa isolates were called in 2015 and 2016 respectively. Isolates with MICs=2 increased from 4.8% to 14.6 % between 2015 and 2016 (p=0.00278) (Table 1). In both years none of the isolates had an MIC>2. Non-significant changes were observed in Klebsiella pneumoniae and Escherichia coli.
Conclusions: While the clinical and public health significance of this MIC creep amongst P. aeruginosa is unknown, it is disconcerting. Could this be similar to the precipice witnessed in the hVISA phenotype in Staphylococcus aureus ? Further studies are required to elucidate this. Meanwhile, we call for more prudent use of this agent and the development of colistin sparing treatment options for P. aeruginosa.
1. Coetzee J et al. 106:449-450, 2016
2. Morrissey I et al. Pharmaceuticals. 6(11):1335-1346, 2013
3. McGuinness WA et al. Yale Bio Med 90(2):269-281, 2017
P076 Ceftazidime/avibactam for treating severe infections in the critically ill due to carbapenemases producing Klebsiella pneumoniae
A Corona, A Veronese, S Antinori, S Santini, C Soru, M Corbellino, F Cantarero, E Catena
ASST Fatebenefratelli Sacco, PO SACCO - Milano, Milano, Italy
Introduction: Carbapenemases producing (cp) Klebsiella pneumoniae (KP) infection rate ranges between 5-50% and is associated with a high mortality (19-51%). The use of ceftazidime-avibactam - a 3-generation cephalosporin plus a new inhibitor of class A (KPC), C (AmpC) and D (OXA48) ESBL, may resolve life-threatening conditions.
Methods: Case-report of 14 patients undergoing compassionate treatment.
Results: From April to November 2017, 14 patients (10 M and 4 F), median age 57 (IQR = 42.5-70.5) were given ceftazidime/avibactam for major KP-cp (meropenem MIC > 16) infections: (i.e. 9 bacteramia 3 secondary peritonitis and 2 UTI. 10/14 (71.5%) patients, developed a septic shock [median (IQR) SOFA score 10 (8-17)) and needed mechanical ventilation [median (IQR) 8 (4-17) days], norepinephrine infusion [median (IQR) 3 (2-5) days]; 4 patients underwent renal replacement therapy. The median treatment duration (IQR) was 14 (13-14) days. In 41.6% of cases, antibiotic-therapy therapy combination (phosphomycin and colistin) was chosen. All the patients experienced a clinical response by 72/96 hours from the ceftazidime/avibactam commencing. In 8/9 bacteraemic patients negativization of blood culture occurred by 96 hours as well as of the rectal swab in 5/14 patients. A (B) recurred and a second treatment was given. 11/14 (78.5%) patients survived, whereas death was caused by multi-organ failure. The susceptibility test of strains showed sensitivity to ceftazidime/avibactam, whereas 100% of resistance to carbapenems, quinolones and III/IV generation cephalosporin, tigecycline and piperacillin/tazobactam; 62.5% of susceptibility to fosfomycin and colistin; (v) less than 50% of suceptibility to aminoglicosides.
Conclusions: The 14 strains of KP-cp were susceptible to ceftazidime-avibactam despite the high carbapenem-resistance recorded in our ICU, because od rare identification of KP-cp VIM/NDL +. The preliminary data seems to confirm the efficacy and clinical utility of this antibiotic for the critically ill patients.
SM Wienhold1, MC Brack1, C Rohde2, G Nouailles1, C Seitz3, A Ross3, H Ziehr3, K Dietert4, C Gurtner4, O Kershaw4, AD Gruber4, M Rohde5, N Suttorp1, M Witzenrath1
1Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany,2Leibniz Institute DSMZ - German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany,3Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Braunschweig, Germany,4Freie Universität Berlin, Berlin, Germany,5Helmholtz Centre for Infection Research, Braunschweig, Germany
Introduction: Multidrug resistant bacteria (MDR) are an increasing problem on intensive care units. Lung infections caused by Acinetobacter baumannii are frequently difficult to treat. Phages have regained attention as treatment option for bacterial infections due to their specificity and effectivity in lysis. The aim of this preclinical study was to determine efficacy and safety of a novel phage preparation in mice.
Methods: Mice were transnasally infected with a MDR A. baumannii strain  and 12 hours later treated intratracheally with a specific phage or solvent. Phage Acibel004  was produced as suspension including efficient depletion of endotoxins. At defined time points, clinical parameters, bacterial burden in lung and bronchoalveolar lavage fluid (BALF) and cell influx were determined. Further, lung permeability and cytokine release were quantified and histopathological examination was performed.
Results: Mice treated with phages recovered faster from infection-associated hypothermia. 48 hours after infection, phage treatment led to a reduction in bacterial loads in lungs and BALF. In addition, lung permeability and cytokine production were reduced in phage-treated mice. Histopathological examination of the lungs showed less spreading of bacteria to the periphery in phage-treated mice, whereas cellular recruitment into the lung was unaffected. No adverse effects were observed.
Conclusions: For the first time a highly purified phage against A. baumannii was successfully used in vivo. The current preclinical data support the concept of a phage-based therapy against pulmonary A. baumannii infections.
1. Knapp S, et al. Am J Respir Crit Care Med. 1;173(1):122-9, 2006
2. Merabishvili M, et al. PLoS One. 11;9(8):e104853, 2014
P078 Efficacy of phage therapy against lethal methicillin resistant Staphylococcus aureus (MRSA) ventilator associated pneumonia in rats (VAP)
J Prazak1, P Reichlin2, D Grandgirard1, G Resch3, M Qiao1, S Nansoz1, Y Que1, M Haenggi1
1Inselspital, University Of Bern, Bern, Switzerland,2Medical School, University of Bern, Bern, Switzerland,3University of Lausanne, Lausanne, Switzerland
Introduction: VAP is common in critically ill patients and associated with high morbidity and mortality, especially when caused by antibiotic resistant bacteria. Recently, phage therapy has emerged as a promising non-antibiotic based treatment of antibiotic resistant bacterial infections. However, proof-of-concept experimental and clinical studies are missing before its wider use in clinical medicine. The goal of this experimental study was to compare the efficacy of phage therapy versus antibiotics for the treatment of MRSA in a rat model of VAP.
Methods: Four hours after intubation and protective ventilation, rats were inoculated via the endotracheal tube with 6-9 x 109 CFU (LD100) of the MRSA clinical isolate AW7. The animals were subsequently extubated. Two hours after bacterial challenge, rats were randomised to receive intravenously either teicoplanin (n= 8), a cocktail of 4 lytic anti-S. aureus bacteriophages (n=9) or combination of both (n=6). 5 animals served as control (no treatment). Survival by 96 hours was the primary outcome. Secondary outcomes were bacterial count in lungs, spleen and blood. Kaplan-Meier estimates of survival were done and multiple comparisons of survival rates performed using the Holm-Sidak method.
Results: Treatment with either phages, antibiotics or combination of both significantly increased survival (66%, 50%, 50% respectively, compared to 0% survival for controls, p<0.05). There were no statistical differences in survival rates between either forms of treatment (Fig. 1). Treatments hinder the systemic extension of the infection into the blood and spleen without impacting bacterial counts within the lungs, but the numbers are too small to perform statistical tests (Table 1).
Conclusions: Phage therapy performed as well as teicoplanin for the treatment of MRSA VAP when administered intravenously. Further experiments are needed to investigate whether phage administered via aerosols could heal infection within the lungs.
Bacterial count in lung, spleen and blood at euthanasia. Median [IQR]
cfu lung (log10 cfu/g tissue)
cfu spleen (log10 cfu/g tissue)
cfu blood (log10 cfu/ml blood)
4.05 [3.58 - 5.03] n: 8
0 [0 - 1.81] n: 8
6.51 [0 - 44.64] n: 6
antibiotic + phages
4.94 [4.31 - 6.91] n: 6
0 [0 - 0] n: 6
0 [0 - 0] n: 3
5.88 [3.84 - 7.01] n: 9
0 [0 - 3.52] n: 9
0 [0 – 41.76] n: 7
4.26 [3.76 - 4.80] n: 5
4.51 [0 - 5.19] n: 5
34.77 [34.77 - 34.77] n: 2
P079 Influence of amikacin inhalation on the efficacy of ventilation-associated pneumonia and ventilation-associated tracheobronchitis treatment caused by multi-drug resistant gram-negative bacteria: comparative study
A Yaroshetskiy1, N Rezepov2, I Mandel3, V Khodak4, V Konanykhin3
1Pirogov Russian National Research Medical University, Moscow, Russia,2City Clinical Hospital 1 67, Moscow, Russia,3Sechenov University, Moscow, Russia,4City Hospital 135, Nigniy Novgorod, Russia
Introduction: The aim of the study was comparative evaluation of the clinical and microbiological efficacy of combination of amikacin thru nebuliser Aeroneb Pro and standard antimicrobal therapy (AMTcomb) with standard antimicrobal therapy (AMTst) in treatment of ventilator-associated pneumonia (VAP) and ventilator-associated tracheobronchitis (VAT) caused by multi-drug resistant gram-negative bacteria.
Methods: In prospective two-center study with retrospective control included patients with VAP and VAT. In AMTst group (retrospective, n=25) we used combination of meropenem 1 g every 8h iv as continuous infusion, cefoperazon/sulbactam 4 g every 12 h iv as continuous infusion and amikacin 1 g iv every 24 h. In AMTcomb group (prospective, n=25) we used combination of AMTst and amikacin inhalation 500 mg every 12 h thru nebuliser Aeroneb Pro.
Results: In AMTcomb clinical cure rate was 84%, while in AMTst 29.2% (p<0.001), Clinical Pulmonary Infection Score (CPIS) on day 7 was 6 (4-7) points in AMTst and 2 (0-4) points in AMTcomb (p<0.001). Recurrence of VAP/VAT was 29.2% in AMTst and 12.5% in AMTcomb (p=0.008). On day 7 infectious agent titer in tracheal aspirate was 107 (103-108) CFU/ml in AMTst group, while 103 (no growth-106) CFU/ml in AMTcomb (p=0.016). Microbiological eradication observed in 13 patients in AMTcomb vs in 1 patient in AMTst and microbiological persistance observed in 6 patients in AMTcomb vs 17 patients in AMTst (p=0.002). In AMTcomb on 3rd day sputum was less purulent (p=0.016). Amikacin nebulisation didn’t led to deterioration of organ dysfunction: on day 7 there was no difference in platelet count, creatinine and bilirubin levels as compared to day 0 (p=0.102; p=0.297, p=0.532, respectively).
Conclusions: Addition of amikacin inhalation 500 mg every 12 h thru Aeroneb Pro nebuliser in patients with VAP and VAT was more efficacious than intravenous standard antimicrobal treatment with comparable safety profile.
P080 Aerozolized colistin is an effective adjunct to systemic antibiotics in ventilator-associated pneumonia
A Kuzovlev, A Shabanov, A Goloubev, V Moroz, A Grechko
Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, V.A. Negovsky research institute of general reanimatology, Moscow, Russia
Introduction: The aim of the study was to assess the effectiveness of inhaled colistin (IC) as an adjunct to systemic antibiotics in the treatment of ventilator-associated pneumonia (VAP).
Methods: 110 ICU patients with VAP were enrolled in this observational study. Resolution of VAP was assessed as primary endpoint; eradication of pathogens in sputum, weaning time, duration of ICU stay and mortality were assessed as secondary outcomes. Patients were split into 2 groups: Gr.1 (n = 60) - addition of IC to systemic antibiotics without changing the basic regimen; Gr. 2 (n = 50) - change in systemic antibiotics according to sensitivity. Groups were comparable. IC was administered in a dose of 2 million IU TID (Xselia Pharmaceuticals ApS, Denmark). Statistical analysis was performed using Statistica 7.0 (M, σ, Newman-Keuls test; p <0.05).
Results: VAP resolution rate was 77% in Gr.1 (vs. 50% in Gr. 2, p = 0.0295); eradication of pathogens from sputum by the 7th day. treatment was achieved in 80% of Gr. 1 and 60% in the Gr. 2 (n = 12) (p> 0.05); in Gr. 1 weaning from ventilation was possible earlier than in Gr. 2 - 7.8±1.3 days. in Gr. 1 vs. 10.9±4.5 days. in Gr. 2 (p = 0.0000); in Gr. 1 duration of ICU stay was shorter than in Gr. 2 - 11.5±3.2 days vs. 17.1±2.3 days. in Gr. 2 (p = 0.0000). No mortality differences were detected.
Conclusions: Administration of inhaled colistin 2 million IU TID is effective as an adjunct to systemic antibiotics in the treatment of VAP. This modified treatment promotes a more rapid resolution of VAP, earlier weaning from ventilator, reduction of the duration of ICU stay, with no impact on mortality. The addition of IC to systemic antibiotics should be considered as second-line regimen in VAP patients.
P081 Factors associated with no de-escalation of empirical antimicrobial therapy in ICU settings with high rate of multi-drug resistant bacteria
C Routsi 1, K Arvaniti1, G Poulakou1, A Tourtoglou1, A Goufa1, A Vemvetsou1, A Kanavou1, E Hasou1, E Antoniadou1, C Nikolaou1, K Ntorlis1, S Kokkoris1, V Theodorou1, S Vasilliagkou2, H Giamarellou2
1National and Kapodistrian University of Athens, Athens, Greece,2Hellenic Society of Chemotherapy Study Group, Athens, Greece
Introduction: De-escalation is recommended in the management of antimicrobial therapy in ICU patients . However, this strategy has not been adequately evaluated in the presence of increased prevalence of multidrug-resistant (MDR) bacteria. The aim of this study was to identify factors associated with no de-escalation in ICUs with high rate of MDR bacteria .
Methods: Prospective, multicenter study conducted in 12 Greek ICUs over a 1-year period. Patients with laboratory confirmed infections were included. SOFA score on admission, on septic episode and thereafter every 24 h over 14 days, infection site(s), culture results, antimicrobial therapy, and mortality were recorded. Only the first septic episode was analyzed. In order to assess the factors associated with no de-escalation, a multivariate analysis was performed.
Results: A total of 211 patients (admission SOFA score 10±3) were analyzed. 43% of those had septic episode on ICU admission; 57% patients had an ICU-acquired. De-escalation was applied to 44 (21%) patients whereas it was not feasible in 75 patients (44 %) due to the recovery of MDR pathogens or it was not applied, although the microbiology results allowed it, in 92 patients (56 %). Septic shock on the day of septic episode was present in 67% and 79% of patients with and without de-escalation, respectively, p=0.072). Compared to no de-escalation, de-escalation strategy was associated with a shorter duration of shock (4±5 vs. 9±7 days, p<0.001) and all-cause mortality (15.4% vs. 46.4%, p<0.001). Multivariate analysis showed that the variables associated with no de-escalation were: a deteriorating clinical course as indicated by an increasing SOFA score (OR 14.7, p<0.001) and a lack of de-escalation possibility due to recovery of MDR pathogens (OR 27.3, p=0.008).
Conclusions: Deteriorating clinical course and MDR pathogens are independently associated with no de-escalation strategy in critically ill patients.
1. Rhodes A et al. Intensive Care Med 43:304, 2017
2. Dimopoulos G et al. Minerva Anestesiol 81:405, 2015
P082 Corticosteroid treatment in patients with severe influenza pneumonia: a propensity score matching analysis.
G Moreno1, A Rodríguez1, LF Reyes2, J Sole-Violan3, E Díaz4, M Bodí1, S Trefler1, J Guardiola5, JC Yébenes6, A Soriano7, I Martín-Loeches8, MI Restrepo2
1Hospital Universitari Joan XXIII, Tarragona, Spain,2University of Texas Health at San Antonio, San Antonio, TX, USA, 3Hospital Dr. Negrín, Gran Canaria, Gran Canaria, Spain,4Hospital Parc Tauli, Sabadell, Spain,5University of Louisville and Robley Rex VA Medical Center, Louisville, Kentucky, USA,6Hospital de Mataró, Mataró, Spain,7Hospital Clinic, Barcelona, Spain,8Multidisciplinary Intensive Care Research Organization (MICRO). St James’s University Hospital. Trinity Centre for Health Sciences, Dublin, Ireland
Introduction: Patients with influenza infection could develop acute respiratory failure and ultimately ARDS. Corticosteroids have been broadly used as immunomodulatory despite lack of evidence supporting its effect in patients with influenza infection. Therefore, our aim was to determine the clinical predictors associated with corticosteroid administration and its association with ICU mortality.
Methods: This is a secondary analysis of a prospective cohort study of critically ill patients with confirmed influenza pneumonia admitted to 148 ICUs in Spain, between June 2009 and April 2014. Patients were stratified according to treatment with systemic corticosteroids when administrated within the first 24-hours of hospital admission. We use a propensity-score matching (PSM) analysis to reduce confounding factors and association of the administration of corticosteroids. Primary outcome was ICU mortality. Cox proportional hazard analysis was performed to investigate the association between baseline characteristics and steroid use and used ICU mortality as the dependent variable.
Results: The total population comprised 1,846 patients with H1N1 pneumonia, corticosteroids were administered in 604(32.7%) patients, being methylprednisolone the most frequently used medication(578/604 [95.7%]). The median daily dose was equivalent to 80 mg(IQR60-120) for a median duration of 7 days(IQR 5-10). Asthma, COPD, hematological disease and requirement of mechanical ventilation were independently associated with corticosteroid use(p<0.05). After adjusting with PSM, patients with H1N1 pneumonia who received corticosteroids had a higher ICU mortality(27.5%vs.18.8%, HR 1.44,1.18-1.76, p=0.005) compared to patients not treated with corticosteroids (Fig. 1).
Conclusions: Administration of corticosteroids in patients with severe influenza pneumonia was associated with an increased ICU mortality. Thus, we advocate caution to physician using these medications for influenza pneumonia.
Díaz E et al. J Infect 64(3):311-8, 2012
P083 Tracheostomy dependence increases the risk of medical emergency team activation in pediatric patients
B McKelvie1, A Lobos2, J Chan2, F Momoli2, J McNally2
1London Health Sciences Centre - Children’s Hospital, London, Canada,2Children’s Hospital of Eastern Ontario, Ottawa, Canada
Introduction: The purpose of this study was to determine if pediatric inpatients with tracheostomies (PTIs) were at increased risk of medical emergency team (MET) activation compared to other ward patients. The requirement for a tracheostomy confers a significant risk for morbidity and mortality . METs have been implemented to improve the detection and management of patients at risk for clinical deterioration. Based on their risk factors, we hypothesized that PTIs would be at higher risk of clinical deterioration than other patients and so would have higher MET activation rates.
Methods: This retrospective cohort study was conducted at a tertiary pediatric hospital, Children’s Hospital of Eastern Ontario (CHEO), in Ottawa, Canada. PTIs were identified using lists from subspecialty services, decision support and the operating room. MET activation data was obtained from a prospectively maintained database.
Results: From 2008 to 2014 there were 42,041 admissions, including 264 involving PTIs. MET activations occurred in 1260 distinct admissions, including 33 PTI admissions. In the PTI group, the MET activation rate was significantly higher when compared to other ward patients (14 vs 2.9 per 100 admissions, p<0.001) and they had a 5.7 times increased odds of MET activation (OR 5.7, CI: 95% CI 3.6 to 9.1). Almost all PTI patients required intervention during the MET activation (94.6%) and 21.6% were admitted to PICU.
Conclusions: PTIs are at significantly higher risk for MET activation. After MET activation, almost 80% of PTIs remained on the wards, which suggests that the MET helped manage deterioration in these patients. Targeted strategies need to be developed to reduce the risk of PTIs on the wards, and based on our results the MET may play a central role in improving care for these patients.
1. Watters K et al. Laryngoscope 126:2611–2617, 2016
P084 qSOFA versus SIRS versus SOFA for predicting sepsis and adverse outcomes of patients in the intensive care unit. Preliminary report of Russian national study
M Astafeva1, V Rudnov1, V Kulabukhov2, V Bagin1
1City Clinical hospital №40, Yekaterinburg, Russia,2AV Vishnevsky Institute of Surgery, Moscow, Russia
Introduction: In 2016 sepsis is defined as a life-threatening organ dysfunction caused by infection. This concept, called Sepsis 3 [Singer M at al], define only two stages – sepsis and septic shock. In addition, it is defined that quick SOFA (qSOFA) may be a better predictor of in-hospital mortality than the SOFA score [Seymour CW et al]. However, the possibility of application of the Sepsis-3 and qSOFA conception for use in low/middle-income countries is still unknown.
Methods: The aim of our study was to define the role of qSOFA, SIRS and SOFA for predicting sepsis and adverse outcomes of patients in the ICUs in Russia. Design: prospective observational multicenter study. We made ROC-analysis to estimate sensitivity, specificity, and predictive value of SIRS, qSOFA, and SOFA to identify sepsis and predict ICU-mortality.
Results: The study included 335 patients from 22 ICUs in Russia. Sepsis, according to the Sepsis 3 criteria, was identified in 179 (53%) patients, and septic shock – in 82 (24%) patients. 102 (30%) patients died within ICU stay. In the prognosis of sepsis the qSOFA scale, SIRS and SOFA demonstrated the following AUCROCs: 0.683 (95% CI 0.626-0.736); 0.719 (95% CI 0.674 to 0.764); 0.763 (95% CI 0.711 - 0.816) respectively (only the AUCROCs of qSOFA vs SOFA differ significantly, p<0.01). In the prognosis of mortality the qSOFA scale, SIRS and SOFA demonstrated the following AUCROCs: 0.736 (95% CI 0.682-0.791); 0.594 (95% CI 0.546-0.642); 0.843 (95% CI 0.798-0.889) respectively (all AUCROCs significantly differ from each other, p<0.01). For the break-point of the qSOFA score >1 in the prognosis of mortality, the specificity was 65.2%; the sensitivity was 70.6%.
Conclusions: The qSOFA scale in the prognosis of sepsis does not differ significantly from the SIRS criteria, but in the prognosis of mortality is significantly better than SIRS. qSOFA significantly worse in the prognosis of sepsis and death than the SOFA scale.
J Luo, W Jiang, L Weng, J Peng, X Hu, C Wang, G Liu, H Huang, B Du
Peking Union Medical College Hospital, Beijing, China
Introduction: The international task force of Sepsis-3 introduced the quick Sequential Failure Assessment (qSOFA) score to supersede the systemic inflammatory response syndrome (SIRS) score as the screen tool for sepsis. The objective of this study is to prospectively access the diagnostic value of qSOFA and SIRS among patients with infection in general wards.
Methods: A prospective cohort study conducted in ten general wards of a tertiary teaching hospital. For a half-year period, consecutive patients who were admitted with infection or developed infection during hospital stay were included. Demographic data and all variables for qSOFA, SIRS and SOFA scores were collected. We recorded daily qSOFA, SIRS and SOFA scores until hospital discharge, death, or day 28, whichever occurred earlier. The primary outcome was sepsis at 28 days. Discrimination was assessed using the area under the receiver operating characteristic curve (AUROC) and sensitivities or specificities with a conventional cutoff value of 2.
Results: Of 409 patients (median age, 55 years [IQR, 40-67]; male, 225[55%]; most common diagnosis pneumonia, 234[57%]) who were identified with infection in general wards, 229(56%) developed sepsis at a median of 0 (IQR, 0-1) day, 146 patients (36%) and 371 patients (91%) met qSOFA and SIRS criteria at a median of 1 (IQR, 0-5) and 0 (IQR, 0-0) day, respectively. The qSOFA performed better than SIRS in diagnosing sepsis, with an AUROC of 0.75 (95% CI, 0.71-0.79) vs 0.69(95% CI, 0.64-0.74). With a conventional cutoff value of 2, qSOFA had lower sensitivity (53% [95% CI, 47%-60%] vs. 98% [95% CI, 95%-99%], p < 0.001) and higher specificity (87% [95% CI, 81%-91%] vs. 18% [95% CI, 13%-23%], p < 0.001) than SIRS (Table 1).
Conclusions: Among patients with infection in general wards, the use of qSOFA resulted in greater diagnostic accuracy for sepsis than SIRS during hospitalization. qSOFA and SIRS scores can predict the occurrence of sepsis with high specificity and high sensitivity, respectively.
Diagnostic performance of qSOFA and SIRS scores for sepsis-3
Sensitivity, % (95% CI)
Specificity, % (95% CI)
Positive Predictive value, % (95% CI)
Negative Predictive value, % (95% CI)
Positive Likelihood ratio (95% CI)
Negative Likelihood ratio (95% CI)
P086 Prognostic accuracy of quick sequential organ failure assessment (qSOFA) score for mortality: systematic review and meta-analysis
B Brandao Barreto1, M Luz2, D Gusmao-Flores1
1Pós-graduação em Medicina e Saúde, Salvador, Brazil,2Hospital da Mulher, Salvador, Brazil
Introduction: The purpose of this study was to summarize the evidence assessing the qSOFA , calculated in admission of the patient in emergency department (ED) or intensive care unit (ICU), as a predictor of mortality. The hypothesis was that this tool had a good prediction performance.
Methods: Systematic review and meta-analysis of studies assessing qSOFA as prediction tool for mortality found on PubMed, OVID, EMBASE, SCOPUS and EBSCO database from inception until November 2017. The primary outcomes were mortality (ICU mortality, in-hospital mortality, 30 and 90-day mortality). Studies reporting sensitivity and specificity of the qSOFA making it possible to create a 2x2 table were included. The diagnostic odds ratio (LnDOR) was summarized following the approach of DerSimonian and Laird using the software R (‘mada’ package). The summary ROC curve was created using the Reistma model (bivariate model). The RevMan 5 software was used to organize the data.
Results: The search strategy yielded 266 citations. Of 134 unique citations, 48 met the inclusion criteria (426,618 patients). The sensitivity and specificity from each study are shown in Fig. 1. The meta–analysis of the DOR was 4.838 (95% confidence interval (CI): 3.808 - 6.146) and of the LnDOR was 1.576 (95% IC: 1.337 - 1.816) (Fig. 2). The pooled area under the summary receiver operating characteristic (SROC) curve was 0.717. The summary estimative of the sensitivity was 0.55 and the false positive rate was 0.209, by bivariate diagnostic random-effects meta-analysis. The Chi-square goodness of fit test rejects the assumption of homogeneity, and the fit of the model for heterogeneity was better (p-value = 0.3661).
Conclusions: The qSOFA has a poor performance to predict mortality in patients admitted to the ED or ICU.
 Singer M et al. JAMA 315(8):801-10, 2016.
E Karakike1, I Tsangaris1, A Savva1, C Routsi1, K Leventogiannis1, M Tsilika1, V Apollonatou1, I Tomos1, JL Vincent2, EJ Giamarellos-Bourboulis1
1National and Kapodistrian University of Athens, Athens, Greece,2Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
Introduction: Based on the new Sepsis-3 definitions, it may be hypothesized that changes of baseline SOFA (Sequential Organ Failure Assessment score, δ SOFA) may become a measure of treatment efficacy. To this end, the earliest time-point over the sepsis course where these changes are seen should be specified. This was attempted in the present study through test and validation cohorts.
Methods: We used clinical data coming from two randomized clinical trials where intravenous clarithromycin was compared to placebo in patients with Gram-negative infections, meeting the 1991 sepsis definitions [1, 2]. We depicted those patients who retrospectively met Sepsis-3 definitions; 449 patients were in the test cohort  and 199 in the validation cohort . δ SOFA on days 2, 3, 5, 7, 14 and 28 were calculated. The areas under the curves (AUC) of ROCs were designed to define association with 28-day mortality.
Results: The AUCs on follow-up days (Table 1) indicated earliest changes on day 7 to detect outcome. On that day, less than 25% decrease of SOFA was associated with 87.1% sensitivity for 28-day mortality (odds ratio 14.44; p=3.13 x10-22). This was 94.9% in the validation cohort (odds ratio 6.95; p=2.1 x10-4).
Conclusions: 25% decrease of SOFA by day 7 is associated with 28-day mortality and could guide decision-making in future sepsis trials.
The study was supported by the Horizon 2020 Marie-Curie Grant European Sepsis Academy
1. Giamarellos-Bourboulis EJ et al. J Antimicrob Chemother 69: 1111-8, 2014
2. Giamarellos-Bourboulis EJ et al. Clin Infect Dis 46: 1157-64, 2008
Change of SOFA to discriminate final outcome over-follow-up
Area Under the Curve (95% CI)
P vs day 2
T Lertwattanachai1, P Dilokpattanamongkol1, V Tangsujaritvijit2
1Faculty of Pharmacy, Mahidol University, Bangkok, Thailand,2Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
Introduction: Sepsis and septic shock patients are the most common cause of death in intensive care units. The aim of this study is to quantify the relationship between 72 hours sequential organ failure assessment (SOFA) scores change and in-hospital mortality as a treatment outcome in sepsis and septic shock patients.
Methods: A retrospective cohort study in tertiary hospital, Thailand was conducted. Sepsis or septic shock patients receiving carbapenems in medical intensive care unit during April to September 2017 were recruited. Delta SOFA scores, calculated by SOFA day 4 – SOFA day 1 after receiving the first dose of carbapenem, and in-hospital mortality were collected.
Results: There were 86 adult patients (54.70% men, mean age 66 + 17 years, and 70.90% septic shock) during the study period. In-hospital mortality rate was 43%. Mean delta SOFA scores were -0.060 + 3.572 points. Comparing between two groups, the mean delta SOFA scores were significant lower in survivor group than in non-survivor group (-1.140 + 3.116 vs. 1.380 + 3.669; P < 0.001).
Conclusions: The delta SOFA scores during the first few days were a useful predictor of in-hospital mortality in critically ill patients with sepsis and septic shock. An increase in delta SOFA score in the first 72 hours of treatment should be reassess for evaluate an adequacy of antibiotic therapy.
1. Bassetti M et al. Intensive Care Med. 44:73-75, 2017
H Tan, J Teh, F Lee, G Soo, N Horsahamay, S Tan, Y Lee, F Khan
Ng Teng Fong General Hospital, Singapore, Singapore
Introduction: An Outreach Team, akin to a Rapid Response Team, is made up of healthcare professionals assembled together for quick and effective reviews in managing of rapidly deteriorating or gravely deteriorated patients . This study aimed to look at the variety of patient referrals in terms of their severity, patient dynamics, reasons for referral and their subsequent dispositions.
Methods: 258 patient records were randomly reviewed retrospectively from July to October 2017. Data were collated in an excel spreadsheet for comparison and then sorted in accordance with the clinical questions and percentages calculated.
Results: From the 258 referrals, the severity criteria was done by calculating the National Early Warning Score (NEWS). It was found that 51% patients had a score of 0-4, 23% had a score of 5-6, and 26% scored more or equal to 7. 50% of patients were in the age range 61-70 years old. 78% referrals came from the Emergency Department (ED) where a consultant was involved in the decision of the referral; of this, 46% were referred during office hours of 8AM to 5PM where there was greater manpower to aid management. 19% referrals came from inpatients on the General Wards; 32% were done during office hours. 65% of referrals were transferred to IC/HD upon review; 35% were not, from whom 9 died and 7 were later admitted after procedures (2%) or because they deteriorated further (1%). For reasons for referrals and disposition decisions, see Fig. 1.
Conclusions: Despite having no set criteria for Outreach Team referrals, the accuracy rate was nearly 65% admissions to IC/HD based on clinician concerns. There was only 1% re-admission rate having been re-reviewed when the patients had not been deemed suitable for IC/HD admission initially. Therefore referrals were done accurately and safely with the protocol of clinician referral openness directly to IC consultants.
DeVita MA et al. BMJ Quality & Safety 13: 251-254, 2004.
Y Lichter1, D Stavi1, U Keler2, IM Pessach3, H Artsi1, N Adi1, I Matot1
1Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel,2Intensix, Netanya, Israel,3Sheba Medical Center, Safra Children’s Hospital, Tel-Hashomer, Israel
Introduction: Prompt recognition of patient deterioration allows early initiation of medical intervention with reduction in morbidity and mortality. This digital era provides an opportunity to harness the power of machine learning algorithms to process and analyze big data, automatically acquired from the electronic medical records. The results can be implemented in real-time. Intensix (Netanya, Israel) has developed a novel predictive model that detects early signs of patient deterioration and alerts physicians. In this study we prospectively validated the ability of the model to detect patient deterioration in real time.
Methods: The model was developed and validated using a retrospective cohort of 9246 consecutive patients admitted to the Intensive Care Unit in the Tel-Aviv Sourasky medical center – a tertiary care facility in Israel, between January 2007 and December 2015. In this study, we tested model performance in real time, on a cohort of 333 patients admitted to the same ICU between June 2016 and August 2017. Significant events that lead to major interventions (e.g. intubation, initiation of treatment for sepsis or shock, etc.) were tagged upon medical case review by a senior intensivist, blinded to model alerts. These tags were then compared with model alerts.
Results: A total of 136 patients suffered major events during study period, out of which 109 were detected by the model, resulting in a sensitivity of 0.80, specificity of 0.93 and a PPV of 0.89. The model AUC-ROC was 0.86.
System operation and algorithm execution were fluent and reliable.
Conclusions: We developed a machine-learning model that can reliably recognize patient deterioration in real time. Ongoing research aims at showing improved model validity and verifying its ability to precede clinical detection. Future research is needed to demonstrate positive effect on patient outcome.
T Buttle, P Parulekar, G Glover
Guys and St Thomas’ NHS Foundation Trust, London, UK
Introduction: The UK National Early Warning Score (NEWS) is advocated to detect acute deterioration in hospital , however NEWS may lack sensitivity to detect all patients requiring Critical Care (CC) admission.
Methods: An analysis of the Rapid Response Team (RRT) database for a university hospital; all acute reviews/emergency calls, 1st March – 31st May 2017. Protocolised RRT calling criteria are NEWS >=5/single parameter score 3. For patients reviewed by RRT, probability of CC admission was calculated at each NEWS level. For admissions not meeting calling criteria (‘low NEWS’), reason for admission was investigated. Data is shown as median [IQR] or count (%).
Results: There were 2742 acute RRT reviews for 1009 patients; median [IQR] NEWS 4 [3-6]. 1240 reviews occurred despite ‘low NEWS’ (Fig. 1). RRT review led to CC admission in 315 (31.2%) cases; median [IQR] NEWS 5 [3-8]. Probability of admission increased with higher NEWS (Fig. 1), however 82 admissions had ‘low NEWS’. Of these 51 were excluded due to high NEWS trigger in the preceding 24hrs or post-operative status. The remaining 31 (9.8%) represented genuine low NEWS cases; age 54 [36-64], 50% male, admission APACHE II 12 [8-17] and day 1 SOFA 2 [1-5]. Admission source was emergency department 29%, medical 42%, surgical 29%. Diagnoses are shown in Table 1. No low NEWS patients with sepsis were qSOFA positive. CC length of stay was 2 [1-4] days and ICU mortality was 9.6%.
Conclusions: A high proportion of RRT activity occurs at low levels of abnormal physiology. Despite an association between NEWS and CC admission, NEWS fails to trigger for approximately one in ten admitted cases. Clinical concern remains an important component of the escalation of acutely ill patients. Meanwhile, novel markers of deterioration should be sought and validated.
1. Smith GB et al. Resuscitation 84:465-70, 2013
Acute Kidney Injury (inc. hyperkalaemia)
J Silvestre, N Candeias, A Ricardo, R Marques, F Brás, J Nunes
Hospital dos Lusiadas, Lisbon, Portugal
Introduction: Although rapid response systems are known to reduce in-hospital cardiac arrest rate, their effect on mortality remains debated. The Rapid Response Call (RRC) is a system designed to escalate care to a specialised team in response to the detection of patient deterioration. There are diurnal variations in hospital staffing levels that can influence the performance of rapid response systems and patient outcomes. The objective of this study was to examine the relationship between the time of RRC activations and patient outcome.
Methods: Review of retrospectively collected, linked clinical and administrative datasets, at a private hospital during a 34-month period. All patients with medical emergency team activation were included. Rapid response calls occurring between 18:00-07:59 were defined as ‘out of hours’.
Results: Between January 2015 and October 2017 there were 209 RRC. The trigger for RRCs activation was nurse concern (101; 38.3%), modified early warning score (80; 28.3%) and cardiac arrest (28; 13.4%). 44 RRCs were “out of hours” being the main activation trigger a modified warning score > 5. “Out of hours” patients had higher ICU admissions (31.7% versus 20%) and were more likely to have an in-hospital cardiopulmonary arrest (OR=1.4, p<0.002).
Conclusions: The diurnal timing of RRCs appears to have significant implications for patient outcomes. Out of hours calls are associated to a poorer outcome. This finding has implications for staffing and resource allocation.
G Zani, F Di Antonio, M Pichetti, A Garelli, C Gecele, F Menchise, M Valbonetti, S Mescolini, E Graziani, C Nencini, FD Baccarini, M Fusari
Santa Maria delle Croci Hospital, Ravenna, Italy
Introduction: Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection [1, 2]. We compared organ failure incidence and evolution in medical versus surgical septic patients in ICU.
Methods: Septic patients admitted to a general ICU were retrospectively analyzed from 2012 to 2017 for: SAPSII, SOFA score at ICU admission and worst value during ICU stay, site of infection and severity, duration of MV, need and timing for tracheotomy, need and duration of vasoactive drugs, need for RRT, ICU-acquired infections, ICU and post-ICU LOS and outcome. Traumatic and neurological patients were excluded. P value <0.05 was considered significant.
Results: 956 septic patients were enrolled: 56% medical and 44% surgical. Medical patients were younger (66vs70yy, p<0.05) and with worst SAPSII (53vs49, p<0.05). At ICU admission SOFA score was higher in medical patients (9vs7, p<0.05), due primary to neurological and renal dysfunction. During ICU stay, medical patients revealed an haemodynamic worsening (8% shock increase, p<0.05). Moderate ARF was prevalent in both groups; surgical patients had a higher need of MV (96%vs83%, p<0.05), but with a shorter duration than medical ones that were mostly treated with tracheotomy (26vs15%, p<0.05). AKI was more severe in medical patients and worsened in both groups without differences on need of RRT. Targeted antibiotic therapy was higher in medical patients (63vs35%, p<0.05), but no differences emerged for duration and superinfections. Medical patients had a longer ICU LOS (8vs6dd, p<0.05), with a higher ICU mortality rate (26vs17%, p<0.05); they showed a shorter post-ICU LOS (11vs16dd, p<0.05) with a higher but not significant inhospital mortality rate (37vs33%).
Conclusions: Septic medical patients had a worst outcome in comparison to surgical ones, probably related to a more severe clinical state at ICU admission and a worsening in organ function.
 Rhodes A et al. Intensive Care Med 43:304-377,2017
 Michael D et al. JAMA 317:847-848,2017
P094 The use of the medication based disease burden index and drug counts to quantify comorbidity during intensive care and to predict long term mortality
C McMechan1, M Booth2, J Kinsella1
1University of Glasgow, Glasgow, UK,2Glasgow Royal Infirmary, Glasgow, UK
Introduction: The aims of the project were to use the Medication based Disease Burden Index (MDBI) and drug counts to quantify comorbidity at ICU admission and assess how levels of comorbidity change during a stay in ICU and to assess how comorbidity affects long term survival after a stay in ICU. Pharmacy data offers an alternative method of quantifying comorbidity and the MDBI is one method of doing this that can predict mortality.
Methods: Data was collected from patients admitted to Glasgow Royal Infirmary ICU between 01/01/14 to 31/12/15. Ethical approval was sought. This data was used to produce an MDBI score and a drug count before and after an ICU stay. Information on long term mortality was also collected. T tests were used to determine the difference in comorbidity levels pre and post ICU. Kaplan Meier curves were used to establish if comorbidity affects long term mortality. Logistic regression was used to determine which method of measuring comorbidity was better at predicting mortality.
Results: A paired t test was performed on 437 patients that showed comorbidity increases after a stay in ICU, as measured by the MDBI and drug counts. Kaplan Meier curves demonstrated that as comorbidity increases, long term survival decreases. Survival time was calculated as time from ICU discharge date to the date of death or end of study (31/01/17). The hazard ratio for the high MDBI group was 1.89 when compared to the zero MDBI group. The hazard ratio for the high drug count group was 1.81 when compared to the zero drug count group. Cox proportional hazard models were performed and results remained significant after adjusting for age. Logistic regression showed that the MDBI was better at predicting long term mortality than drug counts.
Conclusions: This study increases the ever-growing evidence that the MDBI is a useful predictive tool for quantifying comorbidity and predicting long term mortality. Further research is required to replicate its use in other populations, and potentially other specialities.
P095 Adverse events among those admitted to the ICU: a retrospective cohort study using administrative data
KM Sauro, A Soo, HT Stelfox
University of Calgary, Calgary, Canada
Introduction: The objective of this study is to estimate the frequency and type of, and factors associated with adverse events (AEs) among those with an intensive care unit (ICU) admission. AEs are unintended, negative consequences of care that compromise patients’ health and are costly to the healthcare system. In Canada, an estimated 7.5 per 100 hospital admissions are associated with an AE, but evidence suggests that the rate of AEs varies by hospital unit and by patient population. However, few studies examine AEs in the ICU.
Methods: This retrospective cohort study included patients admitted to 30 adult ICUs & CCUs in Alberta, Canada (n=30) between May 2014 and April 2017. Validated ICD-10CA algorithms for 18 patient safety indicators were used to estimate the frequency of any AE and each type of AE. Regression analysis was used to examine factors associated with AEs.
Results: Of 49,447 admissions, the typical admission was a 62 (IQR=21) year old male (64%), admitted for a non-surgical cardiac reason (35%). At least 1 AE was experienced by 12,549 (25%) ICU patients during their hospital admission. The most common AEs were respiratory complications (10%) and hospital acquired infections (9%). Those who were re-admitted to ICU (OR=4.83, 95% CI=4.48, 5.20), admitted for a general surgical vs. non-surgical cardiac reason (OR=9.49, 95% CI=8.84, 10.20) and had >=2 comorbidities (OR=1.82, 95% CI=1.73, 1.92) had increased odds of an AE, while those who spent >50% of their hospital admission in ICU (OR=0.42, 95% CI=0.41, 0.44) had decreased odds of an AE. Those who experienced an AE stayed 5.8 days longer in ICU and 23.5 days longer in hospital, and had increased risk of hospital mortality (OR=2.41, 95% CI=2.27, 2.55) than those who did not experience an AE.
Conclusions: AEs are common among patients admitted to ICU, highlighting the need for ongoing quality improvement initiatives to improve the safety of care.
P096 Clinical characteristics and outcomes of toxic epidermal necrolysis in a Tunisian tertiary critical care unit (icu)
I Ben Saida, W Zarrougui, E Ennouri, N Sma, N Fraj, S Kortli, N Fathallah, M Boussarsar
Farhat Hached Teaching hospital, Sousse, Tunisia
Introduction: Toxic epidermal necrolysis (TEN) is a rare, potentially life threatening mucocutaneous disease. The aim of the study was to determine clinical characteristics and outcomes of patients admitted to ICU with a diagnosis of TEN.
Methods: A retrospective study was performed in the ICU of Farhat Hached hospital of Sousse between January 1995 and September 2017. Data were collected by reviewing the medical patients’ charts. A multivariate regression analysis was used to identify risk factors for ICU mortality in those patients.
Results: A total of 27 patients were recorded. Mean age was 43 years (range, 17 to 76). 19(70.4%) were male. Median of CHARLSON index was 1 [0-4]. Mean SAPS II was 29.59±16. The average affected skin area was 50.5 ± 28.95% of total body surface area. Mucous membrane involvement was seen in the mouth or pharynx (21, 77.8%), eye (18, 66.7%) and genital area (15, 55.6%). NIKOLSKY sign was positive in 25 patients. The most common drugs that triggered TEN were antibiotics (8/27, 29.62%), allopurinol (6/27, 22.22%), anticonvulsants (5/27, 18.51 %), non-steroidal anti-inflammatory drugs (3/27, 11.11%), and antipsychotic drugs (1/27, 3.7%). 6 patients (22.2%) required mechanical ventilation, 7 (25.9%) vasoactive drugs and 2 (7.4%) renal replacement therapy. The major complications were acute renal failure (51.9%) and sepsis (29.6 %). The mortality rate was 40.6%. This rate was much higher than predicted mortality according to a severity-of-illness scoring system for TEN prognosis (SCORTEN) score. In univariate analysis, predictors of fatal outcome were: invasive mechanical ventilation (p=0.0.27), vasoactive drugs (p=0.026), acute renal failure (p=0,012), age (p=0.042) and CHARLSON index (p=0.01). Acute renal failure was the only independent factor of ICU mortality (OR, 19.8 ; 95%CI, [1.94- 201.62] ; p=0.012).
Conclusions: The present study demonstrated a severe prognosis in TEN patients. Acute renal failure was identified as the sole independent factor associated to mortality.
P097 D-dimer and the national early warning score: identifying medical patients at low risk of 30-day mortality in a Danish emergency department
H Lyngholm1, C Nickel2, J Kellett1, S Chang1, M Brabrand1
1Hospital of South West Jutland, Esbjerg, Denmark,2University Hospital Basel, Emergency Department, Basel, Switzerland
Introduction: The aim of this study was to prospectively validate the use of low D-dimer levels in combination with a low National Early Warning Score (NEWS) to identify medical patients at low risk of 30-day mortality in an unselected cohort representative of acutely ill patients normally seen in an emergency department (ED).
Methods: In this prospective observational study, plasma D-dimer levels and NEWS of all acute adult consenting medical patients presenting to the ED at the Hospital of South West Jutland were assessed at arrival. 30-day survival status was extracted from the Danish Civil Registration System which ensured complete follow-up. Patients were sorted by high and low d-dimer with a cut-off value of 0.50 mg/L and additionally by high and low NEWS with a cut-off score of 2.
Results: The final study population consisted of 1516 patients with a median (25-75 percentile) age 66 years (52-77) of which 49.4% were female. 791 (52.2%) patients had a low D-dimer (<0.50 mg/L) of which 3 (0.38%, 95%CI 0.12-1.17%) died within 30 days; all of these patients had a low NEWS (<2). 725 (47.8%) patients had a high d-dimer (>=0.50 mg/L) of which 32 (4.4%, 95%CI 3.14-6.18) died; 12 (37.5%) of these had a low NEWS (<2). Comparing 30-day mortality for patients with high and low D-dimer, the odds ratio is 12.3 (95%CI 3.7-40.3). 14 of the 35 patients (40.0%) who died had a low NEWS at presentation to the ED.
Conclusions: Low D-dimer levels appear to identify patients at low risk of 30-day mortality. The addition of NEWS does not appear to increase this ability. Further validation is needed.
P098 Comparison of severity score models based on different sepsis definitions for predicting in-hospital mortality of sepsis patients in medical intensive care unit
T Songsangjinda, B Khwannimit
Prince of Songkla University, Hat Yai, Thailand
Introduction: There are three generations of sepsis definition concepts: Systemic Inflammatory Response Syndrome (SIRS), Predisposition, Insult, Response, Organ dysfunction (PIRO), and Sequential Organ Failure Assessment (SOFA). However, the performance between these concepts had not been compared. The aim of our study to evaluate and compare the performance between severity score models based on different sepsis definitions in order to predict outcomes among sepsis patients.
Methods: A retrospective analysis over a 10-year period. The primary outcome was in-hospital mortality and the secondary outcome was the composite of hospital death and ICU stay of more than 72 hours.
Results: A total of 2,152 sepsis patients were enrolled. The hospital mortality was 45.9%. Mean APACHE-II score was 23.9. The SOFA score had the highest performance for predicting hospital mortality with an area under the receiver operating characteristic curve (AUC) of 0.86. The AUC of SOFA score was statistically greater than the other scores (p<0.001, Fig. 1). Also, the SOFA and qSOFA presented good discrimination for secondary outcome. The AUC of SOFA (0.76) and qSOFA (0.76) for predicting secondary outcome was statistically greater than those of SIRS (0.59, p<0.001) and the PIRO models (Howell 0.72, Robulotta 0.71, p=0.01). In the subgroup analysis (n=1,239), serum lactate value (>2 mmol/L) was shown to improve qSOFA specificity from 32.4% to 54.1% with comparable sensitivity (96.9% and 94.7%). Howell’s PIRO performance was not significantly changed.
Conclusions: The SOFA score had the best performance for predicting hospital mortality among ICU sepsis patients. Our findings support the Sepsis-3 using SOFA in an ICU setting.
Jena University Hospital, Jena, Germany
Introduction: Sepsis is one of the most prevalent diseases among hospitalized patients and an important contributor to hospital mortality. The study aims to assess trends in infection and sepsis incidence and mortality between 2010-2015 in Germany.
Methods: We analyzed hospital discharge data from the years 2010-2015 by using the Diagnosis-related Groups Statistics of the German Federal Statistical Office, which contains nearly complete data of all inpatient hospital treatments in Germany. We identified cases of infection, infection and organ dysfunction, sepsis (incl. severe sepsis and septic shock) and severe sepsis (incl. septic shock) using ICD-10 codes coded as primary and secondary discharge diagnoses and procedural OPS codes. We assessed incidences and discharge disposition incl. mortality.
Results: Incidences, mortalities and discharge disposition comparing 2010 and 2015 and the mean annual increase in incidence rates are reported in Tables 1 and 2.
Conclusions: The annual increase in standardized sepsis incidence rates is greater than in infections, but similar to the increase in infectious disease patients with organ dysfunction, which are less prone to coding incentives than sepsis codes. An increasing number of patients is discharged to nursing homes and hospice. Given the alarming increase in sepsis cases and deaths, this analysis confirms sepsis as a key priority for health care systems.
Infections, 2010-2015 in Germany: Incidence, mortality and discharge disposition
Infection in 2010
Infection in 2015
Infection and organ dysfunction in 2010
Infection and organ dysfunction in 2015
Incidence/100.000 (age- and sex-standardized)
4,894 (mean annual increase +1.6%)
1,315 (mean annual increase +7.0%)
Discharge to hospice
Discharge to nursing home
Discharge to rehab
Sepsis, 2010-2015 in Germany: Incidence, mortality and discharge disposition
Sepsis in 2010
Sepsis in 2015
Severe sepsis in 2010
Severe sepsis in 2015
Incidence/100.000 (age- and sex-standardized)
371 (mean annual increase +5.8%)
158 (mean annual increase +7.9%)
Discharge to hospice
Discharge to nursing home
Discharge to rehab
W Angus1, P Turton2, E Nsutebu2, C McGrath1
1Wirral University Teaching Hospital NHS Foundation Trust, Wirral, UK,2Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
Introduction: The Advancing Quality Sepsis Programme is an established approach to reducing variation and improving outcomes in the North West of England. It aims to improve clinical care by producing and implementing evidence-based bundles of care across a collaborative network of hospitals. Data is collected, analysed and fed back enabling monitoring and comparison of quality of sepsis care in the form of an Appropriate Care Score (ACS), mortality rate and length of stay.
Methods: Between September 2014 and 2016 data from 25,358 patients who generated an inpatient sepsis code (ICD10) were collected. Of these 11,301 patients had confirmed sepsis (Sepsis 2 criteria) at presentation. 5207 patients were either hypotensive (SBP <90mmHg) or hyperlactataemic (Lactate >4mmol/L) at presentation. ACS, mean time to antibiotics, blood cultures and lactate measurement were calculated for each day of the week. Mortality and length of stay were measured, enabling comparison of weekday and weekend presentation. Data was analysed using SPSS software.
Results: Comparing weekend to weekday presentation did not reveal any significant differences in ACS, time to antibiotics, blood cultures or lactate measurement. Mortality rates and length of stay were not significantly different between the groups. There does not appear to be a weekend effect in sepsis care for this cohort of patients. There were more patients with hypotension and/or hyperlactaemia presenting on a Monday.
Conclusions: Quality of sepsis care was not significantly different between weekend and weekday presentation for patients in this cohort. There were no significant differences in mortality or length of stay when comparing weekday or weekend presentation. There were more septic patients with hyperlactataemia and/or hypotension presenting on a Monday, which may indicate a reluctance of septic patients to present over the weekend.
P101 Weekend effect is not associated with delays in antibiotic administration in septic patients in the emergency department
R Passos, J Ramos, B Fahel, C Starteri, G Silva, M Manciola, M Barbosa, J Caldas, S Farias, M Teixeira, A Gobatto, M Ribeiro, P Batista
Hospital Sao Rafael, Salvador, Brazil
Introduction: Patients with urgent admissions to the hospital on weekends may be subjected to a higher risk of worse outcomes, which may be due to differences in compliance to established processes. Because delays to antibiotic administration is an important measure of sepsis protocol efficiency and has been associated to worse outcomes, we aimed to assess the association of the weekend effect (admissions on weekend) with timing to antibiotic administration.
Methods: Patients included in the sepsis protocol in the emergency department (ED) of Hospital Sao Rafael, from January 2016 to July 2017 were retrospectively evaluated. Sepsis protocol is supposed to be activated to every patient with a suspected sepsis diagnosis in the ED. We evaluated the association of weekend (saturday or sunday) admission with timing to antibiotic administration.
Results: In the study period, 257 patients were evaluated, of which 121 (47%) were male, with a mean age of 59±23 years. Mortality was 27% (70 patients) and 113 (44%) were admitted to the ICU. Mean SOFA score was 2±1.8 and mean Charlson comorbidity index was 4±3.2. Sixty-eight (26%) patients were admitted during weekend. There was no difference in time to antibiotic administration between patients admitted during weekend (31±42 minutes) and patients admitted during weekdays (31±41 minutes). Also, mortality was similar for both groups of patients [OR(95%CI)=0.83(0.47-1.59)].
Conclusions: In this cohort of patients with a suspicion of sepsis in the ED, admission during weekend was not associated to worse outcomes.
P102 Relationship between intensive care unit hypotension and morbidity in patients diagnosed with sepsis
K Maheswari1, M Stevens2, S Munson3, B Nathanson4, S Hwang3, A Khanna1
1Cleveland Clinic, Cleveland, OH, USA,2Edwards Lifesciences, Irvine, CA, USA,3Boston Strategic Partners, Inc., Boston, MA, USA,4OptiStatim, LLC, Longmeadow, MA, USA
Introduction: Current sepsis guidelines emphasize resuscitation of hypotension to a mean arterial pressure (MAP) of at least 65 mmHg . A MAP less than 90 mmHg appears to be associated with poor outcomes in postoperative patients in the intensive care unit (ICU) . However, extent of hypotension in critically ill septic patients during ICU stay and its relationship with adverse outcomes is poorly defined. We determined the magnitude of hypotension in ICU patients with a diagnosis of sepsis and its association with major complications.
Methods: With IRB approval we evaluated records from a large US electronic health records database (Cerner HealthFacts®, Kansas City, MO) of adult patients with a diagnosis of sepsis and ICU stay >= 24 hours from Jan 2010 - Nov 2016. Patients with a history of acute myocardial infarction or acute kidney injury (AKI) for six months prior to ICU admission or < 5 MAP readings/ICU day were excluded. Hypotension exposure was defined and analyzed via three methods: total time spent below MAP <65 mmHg; time-weighted average (TWA) MAP <65 mmHg, and the number of MAP readings <65 mmHg. Analyses were repeated for different MAP thresholds (<55, <75, <85 mmHg). We estimated association between hypotension exposure and a major morbidity composite defined by mortality, myocardial injury and AKI using multivariable logistic regression models.
Results: 10,495 patients met all qualifying criteria. 74% of sepsis patients experienced ICU hypotensive events with MAP <65 mmHg; 40% with MAP <55 mmHg. The number of minutes the average patient spent with MAP < 65 mmHg per ICU day will be presented, as will unadjusted/adjusted rates for the morbidity outcome, and unadjusted rates for composite components for all MAP thresholds.
Conclusions: The result of this analysis will determine the amount and duration of ICU hypotension that is associated with major morbidity in patients with sepsis.
1. Rhodes et al. Crit Care Med 45:486-552, 2017
2. Khanna AK et al. SCCM 2018 (Abstract #177)
CV Cosgriff1, LA Celi2
1Harvard T.H. Chan School of Public Health, Boston, MA, USA,2Massachusetts Institute of Technology, Cambridge, MA, USA
Introduction: The role of hyperoxia during oxygen administration in sepsis mortality remains uncertain and controversial [1, 2]. We hypothesized that the duration of hyperoxia while ventilated in the ICU was associated with increased in-hospital expiration in septic patients.
Methods: The Medical Information Mart for Intensive Care database (MIMIC-III), containing data for ~60,000 ICU admissions at Beth Israel Deaconess Medical Center from 2001 to 2012, was used to derive a cohort of ventilated sepsis patients . Hyperoxia was defined as arterial oxygen saturation by pulse oximetry (SpO2) >98%. Extracted SpO2 were transformed to estimate time spent hyperoxic. Patients were grouped by hyperoxic duration into bins derived from quartiles of the hyperoxic duration. Group 1 (lowest quartile) was taken as the reference. The association between hyperoxic group and in-hospital mortality was examined by logistic regression.
Results: Of the 46,476 patients in MIMIC-III, 2,591 met criteria for inclusion. After adjustment for for age, gender, ethnicity, unit type, length of stay, duration of ventilation, disease severity, burden of comorbidity, and the use of vasopressors, hyperoxic group 4 was significantly associated with in-hospital mortality (OR = 2.47, p = 0.004, 95%CI: [1.35, 4.59]), as was group 3 (OR = 1.93, p = 0. 013, 95%CI: [1.16, 3.28]). Group 2 was not associated (OR = .84, p = 0. 564, 95%CI: [0.46, 1.53]). Figure 1 summarises these results.
Conclusions: Odds of in-hospital death were nearly double and more than double in group 3 and 4 respectively, and we conclude that longer durations of hyperoxia are associated with increased in-hospital mortality in sepsis patients.
 Vincent JL et al. Can Respir J 2017: 2834956, 2017
 Hafner S et al. 5:42. 2015
 Johnson AEW et al. Scientific Data 3:160035, 2016
ND Nielsen 1, F Zeng2, ME Gerbasi3, G Oster3, A Grossman3, NI Shapiro4
1Tulane School of Medicine, New Orleans, LA, USA,2LaJolla Pharmaceutical Company, San Diego, CA, USA,3Policy Analysis Inc, Brookline, MA, USA,4Beth Israel Deaconess Medical Center, Boston, MA, USA
Introduction: Consensus clinical guidelines recommend maintaining mean arterial pressure (MAP) >=65 mmHg for vasodilatory shock (VS) patients. This study uses the Medical Information Mart for Intensive Care (MIMIC-III) database to examine treatment and outcomes in patients with severe VS in a real-world setting.
Methods: We identified patients in the MIMIC-III database which contains information for 61,532 admissions to intensive care units (ICU) at Beth Israel Deaconess Medical Center (BIDMC) in Boston, Massachusetts between 2001 and 2012. Inclusion criteria: 1) aged >=18 years, 2) treated with vasopressors for >=6 hours. Exclusion criteria: cardiac surgery, vasoplegia, cardiogenic shock, intra-aortic balloon pump, extracorporeal membrane oxygenation, large amount of blood transfusion, cardiac tamponade or pulmonary embolism. The primary outcome was mortality.
Results: There were 5,922 ICU admissions. Among these patients, those who consistently maintained MAP above 65 mmHg (n=167, 3%), 60 mmHg (n=418, 7%), and 55 mmHg (n=949, 16%) while in ICU had lower mortality rates than patients with one or more MAP excursions below these thresholds (n=5755, n=5504, and n=4973, respectively): 11% vs 31% for MAP <65 (p<0.0001); 10% vs 32% for MAP <60 (p<0.0001); and 10% vs 34% for MAP <55 (p<0.0001). When assessing the exposure of hypotension for >=2 continuous hours, ICU mortality rates were 31% for 65 threshold (n=4741), 34% for 60 threshold (n=3498), and 41% for 55 threshold (n=2090). ICU mortality rates were 41%, 52% and 66% for patients with MAP below 65 (n=1686), 60 (n=746), and 55 (n=354), respectively, for >=8 continuous hours.
Conclusions: Most patients did not have MAP control based on current clinical guidelines, and not achieving the recommended target MAP was associated with worse outcomes. However, since association does not imply causation, trials aimed at more aggressively achieving a MAP >=65 are warranted, and quality of care initiatives aimed at improving MAP control for patients with VS may be helpful.
P105 Igm enriched immunoglobulins as adjunctive treatment to antimicrobial therapy for patient on septic shock
A Corona, A Veronese, C Soru, F Cantarero, S Santini, I Cigada, G Spagnolin, E Catena
ASST Fatebenefratelli Sacco, PO SACCO - Milano, Milano, Italy
Introduction: Sepsis is responsible of both an immune hyperactivity damage from inflammation and an immune suppression and paralysis. A few studies support the role of IgM enriched immunoglobulins G as adjunctive of antimicrobial treatment .
Methods: Case-control prospective study. Since 12/2016 to 11/2017, patients experiencing a septic shock - admitted with a first 24h SAPS II > 25, associated with a SOFA-score > 4 – underwent treatment with IgM-e-IG, given for three days at the total dosage of 500 mg/kg. The therapy response was based on clinical, microbiological and rheological data. All cases were 1:1 matched with analogous controls.
Results: Over the study period 17 patients [cases, median age 50 (49-62),] experiencing severe infection (peritonitis, meningitis, community acquired pneumonia and UTI) and in septic shock, were recruited and treated with IgM enriched IgG (Pentaglobin) and matched with specific controls. No differences were found in basic patients characteristics but in median (IQR) SAPS II, little bit higher in cases [56 (43-67) vs. 46 (35-61), p=0.464]. No differences were found in the trend of the 1st 72 hrs in WBC, PCT, CRP, Lactate and PLT, even though SOFA score decreased significantly more in cases [-4 (-5;-2) vs. -1.5 (-2;-0.5), p=0.015]. 28th day survival was 100% in cases and 75.5% in controls (Log Rank = 1.93, p=0.165. VLAD (variable life adjusted display) showed 4.48 more lives saved than those expected by SAPS II for cases than controls (0.77), despite a similar SMR (p=0.419).
Conclusions: Reduced mortality may be supposed to be correlated to a quicker recovery of organ damage sepsis related. PCRTs should be warranted in the future to corroborate these preliminary data.
1. Cavazzuti I et al. Intensive Care Med 40(12):1888-96, 2014
RS Hotchkiss1, E Colston2, S Yende3, DC Angus4, LL Moldawer5, ED Crouser6, GS Martin7, CM Coopersmith8, S Brakenridge5, FB Mayr3, PK Park9, K Zhu2, M Wind-Rotolo2, T Duan2, J Ye2, Y Luo2, IM Catlett2, K Rana2, DM Grasela2
1Washington University School of Medicine, St Louis, MO, USA,2Bristol-Myers Squibb, Inc., Lawrenceville, NJ, & Wallingford, CT, USA,3Veterans Affairs Pittsburgh Healthcare System and University of Pittsburgh, Pittsburgh, PA, USA,4University of Pittsburgh Critical Care Medicine CRISMA Laboratory, Pittsburgh, PA, USA,5University of Florida, Gainesville, FL, USA,6The Ohio State University, Columbus, OH, USA,7Dept. of Medicine, Division of Pulmonary, Allergy, Critical Care & Sleep Medicine, Emory University, Atlanta, GA, USA,8Dept. of Surgery, Emory University, Atlanta, GA, USA,9University of Michigan, Ann Arbor, MI, USA
Introduction: The PD-1/PD-L1 immune checkpoint pathway is involved in sepsis-associated immunopathy. We assessed the safety of anti-PD-L1 (BMS-936559, Bristol-Myers Squibb) and its effect on immune biomarkers and exploratory clinical outcomes in participants with sepsis-associated immunopathy.
Methods: Participants with sepsis/septic shock and absolute lymphocyte count <=1100 cells/μ L received BMS-936559 i.v. (10–900mg; n=20) or placebo (PBO; n=4) + standard of care and were followed for 90d. Primary endpoints were death and adverse events (AEs); secondary endpoints were monocyte (m)HLA-DR levels and clinical outcomes.
Results: Apart from the treated group being older (median 62y treated pooled vs 46y PBO) and sicker ([>=]3 organ dysfunctions: 55% treated pooled vs 25% PBO), baseline characteristics were comparable. 6/24 (25%) participants died (10mg: 2/4 [50%]; 30mg: 2/4 [50%]; 100mg: 1/4 [25%]; 300mg: 1/4 [25%] 900mg: 0/4; PBO: 0/4). All participants had AEs (grade 1–2: 75%), with one participant (30mg) having potentially drug-related AEs (grade 1–2 increases in amylase, lipase and LDH). 3/20 (15%) treated pooled and 1/4 (25%) PBO had a serious AE, with none deemed drug-related. AEs of special interest (AEOSI, i.e. potentially immune-related) occurred in [>=]1 participant per group, with diarrhea (33%) the most common. All but 3 AEOSI (1 lung infiltration, 2 diarrhea) were grade 1–2. At the two highest doses there was a trend toward an increase in mHLA-DR expression (>5000 mAb/cell) that persisted beyond 30d. No clear dose-relationship or between-group difference in clinical outcomes (duration of organ support, viral reactivation, ICU/hospital length of stay) was seen.
Conclusions: In this sick population, BMS-936559 was well tolerated. There were no AEs indicative of an excessive drug-induced pro-inflammatory state. At higher doses, a trend toward sustained restoration of mHLA-DR expression was seen. These findings justify further study of PD-1/PD-L1 inhibitors in sepsis.
P107 Effects of a non-neutralizing humanized monoclonal anti-adrenomedullin antibody in a porcine two-hit model of hemorrhage and septic shock
C Thiele1, TP Simon1, J Szymanski1, C Daniel2, C Golias1, J Struck3, G Marx1, T Schürholz4
1Uniklinik RWTH Aachen, Aachen, Germany,2Universität Erlangen-Nürnberg, Erlangen, Germany,3Adrenomed AG, Hennigsdorf, Germany,4Universitätsmedizin Rostock, Rostock, Germany
Introduction: Adrenomedullin (ADM) is a vasoactive peptide improving endothelial barrier function in sepsis, but may cause hypotension and organ failure. Treatment with an ADM monoclonal antibody (mAB) showed improvement in murine sepsis models. Here, we tested effects of the humanized anti-ADM mAB Adrecizumab (AC) in a porcine two hit model of hemorrhagic (HS) and septic shock (SSH).
Methods: In a randomized, blinded study 12 German Landrace pigs (31+/-2 kg) were bled to half of baseline MAP for 45 minutes (HS). SSH was induced using an E.coli clot (7-9x10^11CFU/kg BW) placed into the abdominal cavity 6 hours after HS. Animals received either 2 mg/kg BW Adrecizumab or vehicle (VH) immediately after SSH induction. After 4 hours, resuscitation was initiated using balanced crystalloids and noradrenalin to maintain a CVP of 8-12 mmHg, a MAP >65mmHg and a ScvO2 >70% for another 8 hours. Hemodynamics, laboratory parameters and kidney histology were assessed. General linear model, MWU or Chi2 test were used for statistics where appropriate. P<0.05 was considered significant.
Results: Volume resuscitation was significantly lower in the AC compared to VH group (5300 vs. 6654ml; p=0.036). Vasopressor therapy was necessary in significantly less animals in the AC group (33 vs. 100%; p=0.014). Horowitz index was higher in the AC group (375 vs 286mmHg, p=0.055). Kidney histology showed significantly lower granulocytes in both cortex (9.1 vs. 31.1 n/mm2; p=0.02) and medulla (19.3 vs 53.0 n/mm2; p=0.004) in AC treated animals. After induction of sepsis, plasma ADM increased immediately in both groups, but increased quicker and more pronounced in the AC group (p=0.003 for time*group effect).
Conclusions: In this two hit shock model treatment with Adrecizumab overproportionally increased plasma ADM levels. Hemodynamics and pulmonary function were improved and histological kidney damage was reduced. Thus, therapy with Adrecizumab may provide benefit in septic shock, and clinical investigation candidate is warranted.
P108 Prognosis of patients excluded by the definition of septic shock based on their lactate levels after initial fluid resuscitation: a prospective multi-center observational study
B Ko1, W Kim2, T Lim1
1Hanyang University Hospital, Seoul, Korea, Seoul, South Korea,2University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
Introduction: Lactate levels should be measured after volume resuscitation (as per the Sepsis-3 definition) . However, currently, no studies have evaluated patients who have been excluded by the new criteria for septic shock. The aim of this study was to determine the clinical characteristics and prognosis of these patients, based on their lactate levels after initial fluid resuscitation.
Methods: This observational study was performed using a prospective, multi-center registry of septic shock. We compared the 28-day mortality between patients who were excluded from the new definition (defined as <2 mmol/L after volume resuscitation) and those who were not (lactate level >=2 mmol/L after volume resuscitation), from among a cohort of patients with refractory hypotension, and requiring the use of vasopressors.
Results: Of 567 patients with refractory hypotension, requiring the use of vasopressors, 435 had elevated lactate levels, while 83 did not have elevated lactate levels (neither initially nor after volume resuscitation), and 49 (8.2%) had elevated lactate levels initially, which normalized after fluid resuscitation (Fig. 1). Thus, these 49 patients were excluded by the new definition of septic shock. Significantly lower 28-day mortality was observed in these patients than in those who had not been excluded (8.2% vs 25.5%, p=0.02).
Conclusions: It seems reasonable for septic shock to be defined by the lactate levels after volume resuscitation, however due to small sample size further large scale study is needed.
1. Shankar-Hari M et al. JAMA 315(8):775-787, 2016.
Comparison of outcomes between patients with restored perfusion and those compatible with the Sepsis-3 definition
Sepsis with restored perfusion (n=49)
Sepsis with restored perfusion (n=49)
Max SOFA score
ICU stay (day)
Hospital stay (day)
Hadassah-Hebrew University, Jerusalem, Israel
Introduction: Allocetra™, donor leukocytes containing early apoptotic cells and no necrotic cells, was shown as safe and potentially efficacious for the prevention of aGVHD(Mevorach et al. BBMT 2014). We tested the effects of early apoptotic cells on cytokines/chemokines of patients with aGVHD, and in mice treated with LPS and IFN-g.
Methods: LPS and IFN-g were used to trigger cytokine/chemokine release in vitro and in vivo in mice, and in patients treated for aGVHD. Cytokines/chemokines were evaluated in 13 patients. Mouse and human IL-1ß, IL-2 to 10, IL-12p70, IL-13, IL-15, IL-17A, IL-22, IL-27, Il-31, IL-32, IP-10, RANTES, GRO, IFN-g, GM-CSF, TNF-a, MIP-1a, MIP-1ß, MIP-2, MCP-1, MCP-3, MIG, ENA-78, were evaluated (Luminex technology, Merck Millipore). The IFN-g effect was evaluated by STAT1 phosphorylation.
Results: Significant downregulation (p<0.01) of about 30 pro- and anti-inflammatory cytokines, including IL-6, IP-10, TNF-a, MIP-1a, MIP-1ß, IL-10, was documented. IFN-g effect on macrophages and dendritic cells was inhibited at the level of phosphorylated STAT1. IFN-g-induced expression of CXCL10 and CXCL9 in macrophages was reduced. Patients treated in vivo with higher dosages of apoptotic cells had lower cytokine/chemokine levels compared to those treated with lower levels, and in inverse correlation to aGVHD staging. In vitro binding of apoptotic cells to LPS was documented.
Conclusions: The cytokine storm is significantly modified towards homeostasis following apoptotic cell treatment. The mechanism is multifactorial and was shown to include TAM receptor triggering, NFkb inhibition, and LPS binding. These results together with previous studies showing significantly higher murine survival in sepsis models of LPS and cecal ligation puncture suggest that apoptotic cells may be used to treat patients with sepsis. A multicenter clinical trial in septic patients is planned in 2018.
P110 Efficacy of continuous haemodiafiltration using a polymethylmethacrylate membrane haemofilter (PMMA-CHDF) in the treatment of sepsis and acute respiratory distress syndrome (ARDS)
12628 tomioka takeo-cho, Takeo, Japan
Introduction: CHDF using with a polymethymethacrylate membrane is currently widely applied for non-renal indications in Japan, this technique is used in the treatment not only of patients with sepsis but also of those with cytokine-induced critical illness such as ARDS and pancreatitis. This study aimed to investigate the clinical efficacy of PMMA-CHDF in the treatment of a patients with sepsis and ARDS.
Methods: Seventy- five patients diagnosed with sepsis (ARDS[n=30], Pyelonephritis [n=10], Cholangitisn [n=10], Tsutugamusi in Scrub typhus disease[n=1], Snake Mamushi biten[n=1], haemophagocytic syndrome[n=1],anti neutrophil cytoplasmic antibody(ANCA)lung disiese[n=1],beriberi heart disease[n=1] and unknown causes[n=18]) were enrolled in this study between August 2010 and March 2017. The common cause for ARDS in elderly patients aspiration pneumonia in elderly patients.
Results: Following initiation of PMMA-CHDF teatment, early improvement of haemodynamics was observed, along with an increase in the urine output. The average survival rates of patients were75.6%. The low survival rate among diseases 35% belonged to the Unknown group. The highest survival rate for patients with ARDS was 95%. Moreover, the urine output significantly increased in survival group.
Conclusions: The present study suggests that cytokine-oriented critical care using PMMA-CHDF might be effective the treatment of sepsis and ARDS, particularly,in the treatment of ARDS associated with aspiration pneumonia in elderly patients.
P111 The polymyxin b immobilized fiber column direct hemoperfusion has an effect for septic shock but has no effect on sepsis: a cohort study and propensity-matched analysis
K Hoshino1, H Ishikura1, Y Irie1, K Muranishi1, F Kiyomi1, M Hayakawa2, Y Kawano1, Y Nakamura1
1Fukuoka University Hospital, Fukuoka, Japan,2Hokkaido University Hospital, Sapporo, Japan
Introduction: Many patients with sepsis receive Polymyxin B immobilized fiber column direct hemoperfusion (PMX-HP) as a rescue therapy. Recently, we are reported that PMX-HP reduces all-cause hospital mortality in patients with septic shock . However, it is unclear that whether PMX-HP reduce not only septic shock patients but also sepsis patients. A purpose of this study is to clarify an effect of PMX-HP for the prognosis of patients with sepsis.
Methods: Data from patients admitted for severe sepsis (including septic shock) to Japanese ICUs were retrospectively collected from Jan 2011 to Dec 2013 through the Japan Septic Disseminated Intravascular Coagulation (J-SEPTIC DIC) study data base set. We analyzed the potential benefit of PMX-DHP using a propensity score–matched (1:1) cohort analysis in patients with sepsis.
Results: Of 2,952 eligible patients, 664 underwent PMX-HP. Propensity score matching created a matched cohort of 740 patients (370 pairs with and without PMX-HP). There was no significant difference between the two matched cohorts for the hospital and ICU mortality [Odds ratio (OR); 1.20, 95% confidence interval (CI), 0.93-1.52, p=0.150), OR; 0.98, 95%CI; 0.79-1.21, p=0.828, respectively].
Conclusions: In this demonstrated that PMX-HP had a no benefit on hospital and ICU survival when compared with conventional management (non-PMX-HP) in matched patients with sepsis. From this study we concluded that PMX-HP has an effect for septic shock but has no effect on sepsis.
1. Nakamura Y et al. Crit Care 21(1):134, 2017
P112 A real world experience of novel extracorporeal cytokine adsorption therapy (Cytosorb) to manage sepsis and septic shock patients at tertiary care hospital in India
SK Garg, D Juneja, O Singh
Max Hospital, New Delhi, India
Introduction: Sepsis and septic shock with very high mortality rate (30-50%) is associated with an inflammatory cascade and responsible for multiple organ dysfunction . Extracorporeal cytokine adsorption device (Cytosorb) is an adjunctive therapy to modulate systemic inflammation in Sepsis and Septic shock patients. This retrospective data analysis from real world provides more insight in management of septic shock, as they reflect the management of patients in heterogeneity routine clinical settings.
Methods: In this retrospective study, data of 30 septic shock patients with SOFA score >10 admitted in ICU treated with hemoadsorption (Cytosorb) therapy was collected and analysed.
Results: 30 patients (22 Male and 8 Females; mean age 59.33 yrs.) were administered cytosorb in addition to standard of care, an average of 1.1 cartridge was used for every patients for 4-6 hrs. Out of 30, 13 patients showed substantial reduction of 40% in SOFA score. 7 out of 30 patients had their MAP above 70mm hg after Cytosorb treatment and vasopressors were reduced to 50% from baseline. 10 & 15 patients showed good improvement in Serum Lactate 44.2% (mean 6.64 Vs 3.37) and serum creatinine 43.5% (2.80 Vs 1.58) respectively.
Conclusions: We conclude that substantial difference was seen in Serum lactate, Serum Creatinine and vasopressor requirement after cytosorb therapy, however multi organ failure had already set in all patients before initiating cytosorb therapy, hence the above mentioned outcomes were not demonstrated in all patients.
1. Kogelmann et al. Crit Care 21,74, 2017
P113 Early cytokine adsorption in septic shock (ACESS-trial): results of a proof concept, pilot study
N Öveges1, F Hawchar1, I László1, M Forgács1, T Kiss1, P Hankovszky1, P Palágyi1, A Bebes1, B Gubán1, I Földesi1, Á Araczki1, M Telkes1, Z Ondrik1, Z Helyes2, Á Kemény2, Z Molnár1
1University of Szeged, Szeged, Hungary,2University of Pécs, Pécs, Hungary
Introduction: Overwhelming cytokine release often referred to as “cytokine storm” is a common feature of septic shock, resulting in multiple organ dysfunction and early death. Attenuating this cytokine storm early by eliminating cytokines may have some pathophysiological rationale. Our aim was to investigate the effects of extracorporeal cytokine removal (CytoSorb) therapy on organ dysfunction and inflammatory response within the first 48 hours from the onset of septic shock.
Methods: Patients with: sepsis of medical origin, on mechanical ventilation, noradrenaline >10mg/min, procalcitonin >3ng/mL and no need for renal replacement therapy, were randomized into CytoSorb and Control groups. CytoSorb therapy lasted for 24 hours. In addition to detailed clinical data collection, blood samples were taken to determine IL-1, IL-1ra, IL-6, IL-8, IL-10, TNF-α, PCT, CRP levels. At this stage of the study, only PCT and CRP levels were analyzed. Data were recorded on enrollment (T0) then at T12, T24, and T48 hours. For statistical analysis, Mann-Whitney test was used.
Results: Twenty patients were randomized into CytoSorb (n=10), and Control-groups (n=10). Overall organ dysfunction as monitored by SOFA and MODS scores did not differ between the groups. In the CytoSorb-group noradrenaline requirement (T0=76±63, T24=48±43, T48=23±24 μg/min, p=0.016) showed a significant reduction in the CytoSorb-group but not in the Control-group. There was no difference in CRP, but PCT decreased significantly in the CytoSorb-group (T0=147.8±216.3, T48=78.9±140.1 mmol/L, p=0.004). Lactate decreased significantly in both groups.
Conclusions: These results suggest that a 24-hour long CytoSorb treatment at the early stages of septic shock has significant beneficial effects on noradrenaline requirement and PCT concentrations within the first 48 hours. Based on the results of this current pilot study we are planning to design a prospective randomized multicenter trial.
P114 Usage pattern of polymyxin-b in clinical practice for critical care management in Indian patients: a multicentric prospective observational study
Y Mehta1, K Zirpe2, R Pande3, S Katare4, A Khurana4, S Motlekar4, A Qamra4, A Shah4
1Medanta The Medicity, Gurgaon, India,2Ruby Hall Clinic, Pune, India,3BLK Super Speciality Hospital, New Delhi, India,4Wockhardt Limited, Mumbai, India
Introduction: Emergence of bacterial pathogens with acquired resistance to almost all available antimicrobial agents has severely jeopardized therapeutic choices in the last decade. Furthermore, treatment of MDR gram negative infections has been a major challenge in developing countries like India. Weak research pipeline has led to re-emergence of older antibiotics like Polymyxin B with limited clinical data . This study aims to evaluate the utilization profile of Polymyxin B in Intensive care practice in India.
Methods: This on-going prospective, observational multi-centric study has been approved by IRBs and is being conducted in 3 tertiary care centers in India. The interim data of 101 patients, who received polymyxin B as part of intensive care management, was analysed for utilization profile in terms of demographics, indication, dosage regimen, safety and clinical outcomes.
Results: Patients with mean age 53.1±19.3 years, (67.7% males) had baseline APACHE II, SOFA and GCS scores of 17.2±5.3, 13.7±4.9 and 9.8±5.2, respectively. Majority of patients had sepsis involving pulmonary (51.6%), neurological (25.3%) and cardiovascular (21.1%) systems (Fig. 1, Table 1). Commonest organisms isolated were K. pneumoniae and Acinetobacter spp. Major reasons for intensive care management were hemodynamic instability (52.5%), respiratory failure (42.6%), renal failure (14.9%) and trauma/surgery (37.6%). Mean daily Polymyxin B dose was 1.1±0.4 MIU administered for up to 14 days in 73.2% patients. Clinical response was observed in 67.2% patients. Clinical deterioration of serum Creatinine and all-cause mortality was seen in 28.8% and 32.7% patients, respectively.
Conclusions: In light of good clinical response, Polymyxin B can be considered as a feasible option in the intensive care management of gram negative infections.
1. Garg SK et al. Critical Care Research and Practice, 3635609:1-10, 2017
Distribution of body systems involved in patients receiving Polymyxin-B therapy
Percentage of cases
K Zirpe, A Deshmukh, S Patil
Ruby Hall Clinic, Pune, India
Introduction: Polymyxin B, though available since 1950s, was side-lined due to availability of safer antimicrobials. However, surge of multi-drug resistant gram negative infections has triggered resurgence of these older antimicrobials, despite paucity of available clinical data . This paper reports clinical experience of determinants and outcomes associated with Polymyxin B therapy at our institute
Methods: This study prospectively captures clinical and drug usage profile of patients receiving Polymyxin B, from their medical records, at our tertiary care hospital in Pune, India. The analysis of first 28 completed patients has been summarized here.
Results: The analysed patients (n=28) included 78.6% males, with mean age of 45.7 (±19.9) years. Polymyxin B was most commonly used in sepsis involving respiratory (63%) and abdominal (37%) systems. All the patients were treated in intensive care setup, among which 96.4% required mechanical ventilation (Fig. 1). Most of patients were initiated on Polymyxin B presumptively and Klebsiella pneumoniae and Acinetobacter spp were most common isolated organisms. Polymyxin B was initiated using bolus dose (equivalent to total daily dose) and administered at mean daily dose of 0.97±0.33 MIU in two divided doses. Majority (66.7%) of patients received Polymyxin B therapy for <7 days, (mean duration of therapy, 5.37±4.22 days) (Fig. 2). Meropenem (85.7%) was most commonly co-administered antimicrobial. No unlisted adverse drug reactions were reported. The all-cause mortality rate was 28.6%
Conclusions: Our experience suggests Polymyxin B to be favourable choice for management of MDR gram-negative infection. Further systematic evaluations are required for cementing therapeutic status of Polymyxin B in multi-drug resistant gram negative infections in ICU set-up.
1. Garg SK et al. Critical Care Research and Practice, 3635609:1-10, 2017
P116 Polymyxin b usage and outcomes: real world experience from an intensive care unit of tertiary care hospital in northern India
Y Mehta, C Mehta, S Nanda, J Chandel, J George
Medanta The Medicity, Gurgaon, India
Introduction: Limited antimicrobial agents and dry pipeline has compelled the intensivists to revisit older antibiotics such as Polymyxins, Fosfomycin, etc. for MDR/XDR gram negative infections. With limited clinical data available, especially from India, we planned to assess the drug utilization pattern of Polymyxin B in our ICU settings.
Methods: After Institutional Ethics Committee approval, this prospective observational study was initiated to collect the usage, demography, clinical presentations, indications, bacterial species isolated, treatment regimens, concomitant antimicrobials used and clinical outcomes of Polymyxin B based regimens. The data is collected using structured case record forms and summarized using descriptive statistics. This is the interim analysis of first 73 patients of the ongoing study.
Results: The mean age of patients (n=73, 62.5% males) was 56.0 (±18.26) years with mean baseline APACHE II score of 17.1 (±5.44). Polymyxin-B was most commonly prescribed for Sepsis (72.1%) and the most commonly system involved was Respiratory (47.1%). The most common bacterial species isolated was Klebsiella pneumoniae (23.1%) followed by Acinetobacter spp & Pseudomonas aeruginosa (5.5% each) (Table 1). The mean daily dose of Polymyxin-B was 1.19 (±0.39) MIU with mean duration of therapy of 15.36 (±14.2) days (Fig. 1). Clinical response was observed in 63.6% patients (bacteriological cure 60%) (Fig. 2). All-cause mortality was 34.2%. 71.2% of patients did not have clinically significant increase in serum creatinine levels, though 31.1 % of these had raised serum creatinine at baseline. No unexpected treatment emergent adverse events were reported.
Conclusions: This data suggests Polymyxin B to be an effective antimicrobial agent with good clinical response and acceptable all-cause mortality in an Indian intensive care setup.
Profile of bacterial species isolated in patients receiving Polymyxin-B based antimicrobial regimen
No. of cases (N = 73)
Percentage of cases
E.coli & Enterobactericae family
Miscellaneous or Pus cells (No isolation)
P117 Effect of selective plasma exchange for treatment of patients with severe sepsis due to multiorgan failure
R Iscimen, P Rahimi, HZ Dundar, N Kelebek Girgin, F Kahveci
Uludag University, Bursa, Turkey
Introduction: The mortality rate in severe sepsis ranges between 30-50% and independent liver and renal dysfunction significantly affect intensive care mortality, 4 or more organ failure causes mortality to exceed 90%. Selective plasma exchange is the most commonly used artificial liver support system and effectively removes albumin bound toxins. Selective plasma Exchange (SPE) eliminates low- and medium-molecular weight materials such as cytokines, albumin-bound toxins etc. Therefore, SPE is thought to decrease sepsis mortality by preventing multiple organ failure. In this study, we investigate the effect of selective plasma exchange on the treatment of patients with multiorgan failure and septic shock.
Methods: Selective plasma exchange was performed with Evaclio™(2c-20) in patients diagnosed with septic shock due to multiple organ failure. Pre-and post-treatment laboratory values, Sequential Organ Failure Assessment (SOFA) scores and 28days ICU mortality were calculated. Demographic data of patients are shown on the Table 1.
Results: After ethics committee approval 64 patients(29female/35male) diagnosed with septic shock were included in the study, 125 sessions of selective plasma exchange were performed totally. Value changes before and after the first SPE are shown on the Table 2. There was statistically significant decrease in respiratory, coagulation, renal and liver SOFA scores by SPE. ICU mortality rate was 65%.
Conclusions: Selective plasma exchange is a technique developed to eliminate toxins and cytokines and appear be useful in reducing severe sepsis mortality by decreasing SOFA score and preventing multiple organ failure.
APACHE II score
SOFA scores before and after SPE
A Chaari, W Assar, K Abdelhakim, K Bousselmi, M El Koumy, V Kumar, V Kauts, M Al Ansari
King Hamad University Hospital, Bussaiteen, Bahrain
Introduction: The aim of the current study is to assess the prognostic value of increased troponin on the outcome of patients with septic shock.
Methods: Retrospective study conducted between 01/01/217 and 30/07/217. All adult patients admitted with septic shock were screened for inclusion. Patients with known ischemic heart disease were excluded. Demographic data, baseline clinical and laboratory findings were recorded. Troponin I level on admission and the highest troponin level during intensive care unit (ICU) stay were collected. The echocardiographic findings on admission were reviewed. Two groups (survivors and non-survivors) were compared
Results: Thirty-one patients were included in the study. Median age was 71[62-78] years. Median APACHEII score was 19 [16-26]. Troponin I level on admission was 0.06 [0 - 0.43] ng/ml. The highest troponin level during ICU stay was 0.09 [0.36-1.11] ng/ml. Nine patients (29 %) had wall motion abnormalities. Median left ventriculqr ejection fraction (LVEF) was 55 [30 - 60] %. Median duration of ICU stay was 4 [2.8-12.8] days. ICU mortality was 22.6 %. Troponin level on admission was comparable between survivors and non-survivors (respectively 0.08 [0-0.6] and 0.01 [0-0.16]; p=0.242) whereas the highest troponin during ICU stay was significantly higher in non-survivors (1 [0.36-11.1] versus 0.31 [0.06 - 0.65]; p=0.036). LVEF was comparable between survivors and non-survivors (respectively 55 [29-60] versus 56 [55- 58] %; p = 0.547). The highest troponin was not identified by the multivariate analysis as independent factor predicting ICU mortality (OR=1.1, CI95% = 1.1 [0.92-1.16]; p=0.489). The only factor identified by the analysis was acute kidney injury requiring renal replacement therapy (OR=105, CI95% [5.5-198]; p=0.002).
Conclusions: Increased serum troponin I level is common in patients with septic shock. Our study suggests that the increase of troponin is higher in non-survivors.
O Adi, A Azma Haryaty
Hospital Raja Permaisuri Bainun, Perak, Malaysia
Introduction: Blind pericardiocentesis leading to low success rate and high complication rates such as ventricular wall or oesophageal perforations, pneumothorax or upper abdominal organ injury.Real time needle visualisation is allowing us to avoid this major complication .
Methods: We presented 2 cases of acute traumatic cardiac tamponade secondary to severe chest injury. Both patients presented with haemodynamic instability and echocardiographic features of pericardial tamponade. Pericardiocentesis under ultrasound guidance at left parasternal area with needle directed from medial to lateral technique were performed(Fig. 1). Real time needle tip visualisation done throughout the procedure(Fig. 2a). Needle placement in pericardial space was confirmed with agitated saline and guidewire visualisation(Fig. 2b). Pigtail catheter was inserted and blood was aspirated until the patient were haemodynamically improved. Repeated ultrasound was done to confirm the absence of ultrasonographic features of tamponade and complications.
Results: We demonstrated a successful real time needle visualisation ultrasound guided pericardiocentesis in 2 cases acute traumatic pericardial tamponade. Procedural time (time from needle piercing the skin to time needle entering the pericardium) in both cases were less than 1 minute. Post procedural ultrasound confirmed no major complications.
Conclusions: The real time needle visualisation using ultrasound was important to reduce major complications during pericardiocentesis. The safety of the highly invasive procedure can be improved with real time needle visualisation.
Osman A et al. Eur J Emerg Med (in press), 2017
P120 A novel method for early identification of cardiac tamponade in patients with continuous flow left ventricular assist devices by use of sublingual microcirculatory imaging
S Akin, C Ince, C Den Uil, A Struijs, R Muslem, I Ocak, G Guven, AA Constantinescu, OI Soliman, F Zijlstra, A J.J.C Bogers, K Caliskan
Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
Introduction: Diagnosis of cardiac tamponade post continuous-flow left ventricle assist devices (cf-LVADs) is challenging due to missing pulsatility. Recent case study of sublingually microcirculation with incident dark-field imaging (IDF) provide a new improved imaging for clinical assessment of cardiac tamponade in a patient with cf-LVAD. We sought to examine the changes in microvascular flow index (MFI) as a sign of cardiac tamponade following LVAD implantation.
Methods: Off-site quantitative analysis of sublingual microcirculation clips with Automated Vascular Analyses software (AVA; MicroVision Medical©), and the velocity distributions followed during admission till discharge in patients with end-stage heart failure treated with cf-LVAD complicated by cardiac tamponade.
Results: Eleven out of thirty LVAD implantations, 9 males, mean age 58 ± 10 years, April 2015 to January 2017, ((8 Heart Mate 3 (HM 3) and 3 HeartMate II (HM II) (Thoratec Corp., CA)), were complicated by rethoracotomy due to early postoperative cardiac tamponade within 1 week. There sublingual microcirculation was examined by a novel incident dark-field imaging (IDF) before and daily post-LVAD implantation. Pre-LVAD microcirculation was typical for heart failure, characterized by slowly, sludging movement of red blood cells (RBCs), (Fig. 1A arrows). Directly after implantation, a normal microcirculatory flow was seen with a high RBCs velocity (Fig. 1B). On the day of tamponade the patients were stable except for severe failure of microcirculation as reflected by drop in MFI (Fig. 1C) and congestion in venules (* in Fig. 1C). In 8 out of 11 patients there was a significant drop in MFI before tamponade was clinically recognized (p<0.05). Shortly after rethoracotomy a quick restoration of microcirculatory flow has been found.
Conclusions: Sublingual microcirculation imaging is a simple and sensitive non-invasive tool in early detection of cardiac tamponade.
T Kaufmann1, I Van der Horst1, JL Teboul2, T Scheeren1
1University Medical Centre Groningen, Groningen, Netherlands,2Hôpitaux Universitaires Paris-Sud, Paris, France
Introduction: Treatment decisions on patients with shock lack consensus. In an international survey we aimed to evaluate the indications, current practice, and therapeutic goals on the use of inotropes in the treatment of shock states.
Methods: From November 2016 to February 2017 an anonymous 27-question web-based survey was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 27 questions focused on the profile of respondents, and the triggering factors, first line choice, dosing, timing, targets, additional treatment strategy, and suggested effect of cardiovascular drugs.
Results: A total of 827 physicians responded. As detailed in Table 1, the respondents think that dobutamine is first-line inotrope to increase cardiac pump function (N=695, 84%) and should be started when signs of hypoperfusion or hyperlactatemia despite adequate use of fluids and vasopressors in the context of low left ventricular ejection fraction are present (N=359, 43%). The most accepted target was an adequate cardiac output (N=369, 45%). The combination of noradrenaline and dobutamine was preferred to single treatment with adrenaline mainly due to possibility to titrate individually (N=366, 44%). The main reason for adding another inotrope was to use synergistic effects of two different mechanisms of action (N=229, 27%). According to respondents, phosphodiesterase-inhibitors should be used in the treatment of predominant right heart failure because of prominent vasodilatory effect on the pulmonary circulation (N=360, 44%). They also believe levosimendan is the only inotrope that does not increase myocardial oxygen demand (N=350, 42%). Vasodilators are used in cardiogenic shock to decrease left ventricular afterload (N=244, 30%). There is no experience or no opinion about the use of ß-blockers in shock states (N=268, 32%).
Conclusions: This web-based survey provided latest trends on inotrope use in shock states which showed considerable diversity among respondents in opinions about its use.
P122 Thermoshock: thermography assessment of thermal patterns in patients with shock: preliminary results
M Tosi1, A Andreotti1, M Girardis1, F Despini2, A Muscio2, P Tartarini2
1University Hospital of Modena, Modena, Italy,2University of Modena, Modena, Italy
Introduction: Recent literature data clearly indicated that in patients with shock the resuscitation of macro-circulation often does not match with microcirculation and tissue perfusion improvement.
Unfortunately, the bed-side assessment of regional perfusion remains difficult, particulary in critically ill patients. In the last years thermography has been used in different medical fields but no studies have been performed on the use of this technique in critically ill patients.
The aim of this study was to evaluate whether thermography is feasible and may provide useful data during resuscitation of patients with septic shock.
Methods: In 4 patients with septic shock we collected central systemic temperature and infrared images (FLIR-T640 digital camera) of limbs at 0, 3, 6 and 24 hours after shock occurrence. Thermal pattern distribution of the limbs was obtained by a specific analysis of the images (ThermaCAM™Researcher P). A systemic to peripheral temperature gradient called “∆ systemic-limb temperature” was calculated for each single temperature data collected.
Results: Macrocirculatory and perfusion parameters improved in all the patients throughout the study period: mean values of noradrenaline dose decreased from 0.21 to 0.13 γ/kg/min, mean MAP increased from 65 to 81 mmHg and mean blood lactate decreased from 6.6 to 4.2 mMol/L. The “∆ systemic-limb temperature” pattern showed an heterogenous time course in the 4 patients with a mean overall increase at 6 and 24 hours (Fig. 1).
Conclusions: As expected, the regional data obtained by thermography did not match with macrocirculatory and systemic perfusion parameters. The significance and the relationship between treatments and data observed will be investigated by appropriate studies.
P123 Regional differences in the treatment of refractory septic shock – an analysis of the ATHOS-3 data
M Abril1, A Khanna2, C McNamara2, D Handisides3, L Busse4
1Emory University, Atlanta, GA, USA,2Cleveland Clinic, Cleveland, OH, USA,3La Jolla Phapmaceutical Company, La Jolla, CA, USA,4Emory St. Joseph’s Hospital, Atlanta, GA, USA
Introduction: Vasodilatory shock is a common syndrome with high mortality. Despite established care protocols, regional differences in treatment remain. We sought to characterize these differences using data from the recently published ATHOS-3 study .
Methods: Individual patient data were analyzed at baseline and at 48h for regional differences in demographics, clinical characteristics, and treatment patterns, and grouped according to four geographical areas: the United States (US), Canada (CA), Europe (EU) and Australasia (AU). P-values were calculated by Kruskal-Wallis tests for continuous data and chi-square tests for categorical data. Subsequent temporal analysis compared changes in the treatment of shock, indexed by changes in patient acuity level.
Results: Regional differences existed with respect to BMI (p=0.0076), albumin (p<0.0001), CVP (p=0.0383), MELD score (p=0.0191), APACHE II score (p=0.0007) and SOFA score (p=0.0076). Baseline norepinephrine (NE) and NE equivalent doses were significantly higher in EU (p<0.0001 and p=0.0494, respectively), and utilization of vasopressin was correspondingly lower (p<0.0001). At baseline, stress dose steroids were utilized to a greater extent in the US and CA (p=0.0011). Temporal analysis revealed differences in the utilization of vasopressin and steroids with changes in patient acuity: in EU, increasing acuity was associated with a lower utilization of vasopressin, and in CA, increased acuity was associated with a lower utilization of steroids. Steroid utilization was higher with increased level of acuity in AU and the US.
Conclusions: Significant differences in the treatment of vasodilitory shock exist globally, with important implications: (a) there are widespread differences of best practices, (b) heterogeneity may render global studies of shock difficult to interpret, and (c) outcomes may be improved through appropriate use of adjunctive therapies like non-catecholamine vasopressors or corticosteroids.
 Khanna et al. N Engl J Med; 377(5):419-430, 2017
P124 Association of angiotensin II dose with all-cause mortality in patients with vasodilatory shock
M McCurdy1, LW Busse2, MN Gong3, DW Boldt4, SN Chock5, R Favory6, KR Ham7, K Krell8, XS Wang9, LS Chawla10, GF Tidmarsh10
1University of Maryland, School of Medicine, Baltimore, MD, USA,2Emory University, Atlanta, GA, USA,3Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA,4University of California, Los Angeles, Los Angeles, CA, USA,5Sunrise Hospital, Las Vegas, NV, USA,6CHU Lille, Critical Care Center and University of Lille School of Medicine, Lille, France,7Regions Hospital, University of Minnesota, St. Paul, MN, USA,8Eastern Idaho Regional Medical Center, Idaho Falls, ID, USA,9Duke University Medical Center, Durham, NC, USA,10La Jolla Pharmaceutical Company, San Diego, CA, USA
Introduction: Vasodilatory shock is associated with high risk of mortality. In the ATHOS-3 study, the addition of angiotensin II (Ang II) to standard vasopressors significantly increased mean arterial pressure (MAP) and decreased vasopressor utilization, with a trend towards improved survival to day 28. In this analysis of Ang II recipients in the ATHOS-3 study, we assess the relationship between different dose ranges of Ang II with MAP response and mortality.
Methods: Patients with persistent vasodilatory shock despite receiving >0.2 μg/kg/min of norepinephrine-equivalent dose vasopressors were randomized to receive IV Ang II, titrated per study protocol, or placebo with other vasopressors held constant for hours 0-3; for hours 3-48, all vasopressors could be titrated to maintain MAP. Ang II responsiveness was defined as the Ang II dose required to achieve a MAP of 75 mmHg. In this analysis, 28-day all-cause mortality was evaluated per prespecified categories based on the Ang II dose received 30 min after the start of dosing. These categories included “super-responders,” defined as patients who required physiological doses of Ang II (<=5 ng/kg/min), and patients who required higher doses.
Results: Among the 163 Ang II recipients, 79 (48.5%) were super-responders. Mortality at day 28 was 32.9% in super-responders vs 58.6% in patients requiring Ang II doses >5 ng/kg/min (n=84) and 53.9% in the placebo group (n=158). The hazard ratio for all-cause mortality in super-responders vs Ang II patients requiring higher doses was 0.45 (95% CI 0.28-0.72), p=0.0007; and 0.50 (95% CI 0.32-0.78), p=0.0018 for super-responders vs placebo.
Conclusions: Ang II super-responders, a large subgroup of Ang II recipients in ATHOS-3, had significantly reduced all-cause mortality at day 28 vs patients receiving placebo or higher doses of Ang II. Ang II doses <=5 ng/kg/min equates to a physiological level of Ang II, and may reflect a novel means of achieving normal homeostatic mechanisms to correct vasodilatory shock.
P125 Outcomes in patients with acute respiratory distress syndrome receiving angiotensin II for vasodilatory shock
L Busse1, T Albertson2, M Gong3, BT Thompson4, R Wunderink5, D Handisides6, G Tidmarsh6, L Chawla6
1Emory St. Joseph’s Hospital, Atlanta, GA, USA,2University of California, Davis, Davis, CA, USA,3Montefiore Medical Center, Bronx, NY, USA,4Harvard Medical School, Boston, MA, USA,5Northwestern University, Feinberg School of Medicine, Chicago, IL, USA,6La Jolla Pharmaceutical Company, San Diego, CA, USA
Introduction: ATHOS-3 was a randomized, placebo-controlled, double-blind study of patients with severe vasodilatory shock (VS), which demonstrated that the addition of angiotensin II (Ang II) to standard vasopressors significantly increased mean arterial pressure (MAP) and decreased vasopressor utilization, with a trend towards improved survival to day 28. Given the location of angiotensin-converting enzyme in the pulmonary endothelium, we analyzed the effect of Ang II treatment in the subset of ATHOS-3 patients with acute respiratory distress syndrome (ARDS), in whom the pulmonary endothelium may be damaged.
Methods: Patients with persistent VS despite >0.2 μg/kg/min norepinephrine equivalent dose vasopressors were randomized to receive either IV Ang II or placebo. Patients with ARDS were classified based on the PaO2/FIO2 ratio, per the Berlin definition, as mild, moderate, and severe. Clinical outcomes, including MAP response were compared between groups.
Results: In the Ang II cohort, 34%, 30%, and 11% of the 163 patients were classified with mild, moderate, and severe ARDS, respectively as compared to 32%, 32% and 12% of the 158 patients in the placebo cohort. MAP response, defined as an increase from baseline of at least 10 mm Hg or an increase to at least 75 mm Hg, was achieved by 24%, 25%, and 16% of patients in the placebo group, for mild, moderate and severe ARDS respectively. In the Ang II group, MAP responses were achieved by 67% (OR=6.7, p<0.001), 69% (OR=6.6, p<0.001), and 61% (OR=8.4, p=0.005). In the placebo group, the 28-day mortality for mild, moderate and severe ARDS increased with severity, while the trend for worse survival was reduced in the Ang II cohort when compared to placebo for mild and severe ARDS (Table 1).
Conclusions: In patients with ARDS, MAP response was significantly improved in each ARDS subgroup, and the trend for increased 28-day mortality with an increase in ARDS severity was reduced in the Ang II group compared to the placebo group.
28-day mortality % (95% Confidence Interval)
53 (40 - 67)
55 (42 - 69)
74 (53 - 90)
F Guarracino1, S Bouchet2, M Heringlake3, P Pollesello4
1Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy,2University Hospital, Ghent, Ghent, Belgium,3Universitätsklinikum Schleswig-Holstein, Lübeck, Germany,4Orion Pharma R&D, Espoo, Finland
Introduction: Levosimendan is a calcium sensitizer and KATP-channel opener exerting sustained hemodynamic and symptomatic effects. In the past fifteen years, levosimendan has been used in clinical practice also to stabilize at-risk patients undergoing cardiac surgery. Recently, the three randomized, placebo-controlled, multicenter studies LICORN , CHEETAH  and LEVO-CTS  have been testing the peri-operative use of levosimendan in patients with compromised cardiac ventricular function. Over 40 smaller trials conducted in the past  suggested beneficial outcomes with levosimendan in peri-operative settings. In contrast, the latest three studies were neutral or inconclusive. We aim to understand the reasons for such dissimilarity.
Methods: We re-analyzed the results of the latest trials in the light of the previous literature to find sub-settings in which levosimendan can be demonstrated harmful or beneficious.
Results: None of the three latest studies raised any safety concern, which is consistent with the findings of the previous smaller studies. In LEVO-CTS, mortality was significantly lower in the levosimendan arm than in the placebo arm in the subgroup of isolated CABG patients (Fig. 1) . The trend towards both hemodynamic and long term mortality benefits is maintained in recent meta-analyses [5,6] including the three larger recent studies.
Conclusions: Despite the fact that the null hypothesis could not be ruled out in the recent trials, we conclude that levosimendan can still be viewed as a safe and effective inodilator in cardiac surgery. Statistically significant mortality benefits seem to be limited to sub-groups, such as the isolated CABG procedures, and/or the low EF patients.
1. Cholley B et al. JAMA 318:548-556, 2017
2. Landoni G et al. N Engl J Med 376(21):2021-2031, 2017
3. Mehta RH et al. N Engl J Med 376(21):2032-2042, 2017
4. Harrison RH et al. J Cardiothorac Vasc Anesth 27:1224-1232, 2013
5. Sanfilippo F et al. Crit Care 21(1):252, 2017
6. Chen QH et al. Crit Care 21(1):253, 2017
P127 Effects of levosimendan on weaning from mechanical ventilation of patients with left ventricular dysfunction
I Kaltsi, C Gratsiou, S Nanas, C Routsi
National and Kapodistrian University of Athens, Athens, Greece
Introduction: This study aims to assess the effects of levosimendan, a calcium sensitizer, in the treatment of patients with impaired left ventricular function and difficult weaning from mechanical ventilation.
Methods: Difficult- to- wean from mechanical ventilation [failed >= 3 consecutive spontaneous breathing trials (SBTs)] patients, who had left ventricular dysfunction defined as left ventricular ejection fraction (LVEF) of less than 40%, were studied.For each patient, 2 SBTs were studied: the first one before and the second one after a continuous infusion of levosimendan over 24 h (Control day and Study day, respectively). On both days transthoracic echocardiography (TTE) was performed on mechanical ventilation and at the end of the SBT. Also, serum levels of troponin I were measured at the same time points.
Results: Eleven patients (7 men; mean age of 72 ± 9 years) were studied. Whereas weaning failed in all patients on Control day, levosimendan administration enabled a successful spontaneous breathing trial in 8 out of 11 patients on Study day. Compared to the Control Day, left ventricular ejection fraction significantly increased on Study Day (from 27.5±9.6% to 36.9±2.8%, p< 0.05) whereas E/A significantly decreased both on mechanical ventilation and at the end of SBT: from 1.14±0.76 to 0.92±0.26, p<0.05 and from 1.29±0.73 to 0.88±0.12, respectively, p<0.05). Also, troponin I value decreased significantly on mechanical ventilation (from 217±268 to 163±194 mg/l) and at the end of SBT (from 196±228 to 146±180 mg/l). At the end of SBT, levosimendan treatment resulted in a lesser extent of arterial PO2 decrease: 96±35 vs. 66±27 mmHg, p<0.05) and similarly of ScvO2 decrease: 67±10 vs.60±8, p<0.05 (compared to the values on mechanical ventilation).
Conclusions: Levosimendan may provide significant benefit to difficult- to- wean patients with impaired left ventricular function.
G Haffner, G Ajob, M Cristinar, S Marguerite, W Oulehri, B Heger, M Kindo, PM Mertes, A Steib
Hôpitaux Universitaires, Strasbourg, France
Introduction: VA ECMO weaning is a challenging process. The aim of the study was to evaluate the putative benefit of levosimendan, for VA ECMO weaning.
Methods: This retrospective study, from 2014 to 2016, included patients referred to our ICU for primary cardiogenic shock or following cardiotomy, with VA ECMO in whom an attempt was made to wean mechanical support (death under VA ECMO or bridge to long-term device or transplantation were excluded). Incidence of weaning failure, VA ECMO support duration, length of stay in ICU and length of mechanical ventilation were compared in patients who received levosimendan or not in the whole population and in the post-cardiotomy sub-group. Levosimendan was used at doctor’s discretion. Independent factors associated with weaning failure were determined. Statistics were made throughout bayesian paradigm.
Results: 27 patients were included in levosimendan group and 36 in control group. In the whole population, weaning failure incidence and mortality was comparable between the 2 groups (respectively 24% vs 20%, Pr 0, 34 and 36% vs 38%, Pr=0,6). Higher assistance duration, longer stay under mechanical ventilation and longer duration of stay in critical care unit were observed in Levosimendan group. In the post-cardiotomy sub-group (Table 1), weaning failure was lower in levosimendan group (12% vs 29%, Pr 0,9) and levosimendan was an independent protective factor from weaning failure (OR 0,073, Pr 0,92). Positive impact of levosimendan may be explained in part by his calcium sensitizer effect and by facilitating recovery of myocardial calcium homeostasis in postcardiotomy cardiac stunning.
Conclusions: Levosimendan failed to reduce the incidence of ECMO weaning failure, except for post-cardiotomy population.
P129 Renal outcomes of vasopressin and its analogues in distributive shock: a systematic review and meta-analysis of randomized trials
T Rech, W Nedel, J Pellegrini, R Moraes
Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
Introduction: Previous trials have suggested a lower incidence of the need for renal replacement therapy (RRT) and acute kidney injury (AKI) in patients with shock treated with vasopressin or its analogues (VA) compared to other vasopressors [1, 2]. The aim of the present study was to systematically review the literature and synthesize evidence concerning the effects of VA compared to other vasopressors in distributive shock, focusing on renal outcomes.
Methods: MEDLINE, Embase, Cochrane CENTRAL and Clinicaltrials.gov databases were searched through June, 2017 without language restrictions. Randomized clinical trials that compared VA with other vasopressors and reported renal outcomes in adult patients with distributive shock were included. Paired reviewers independently screened citations, conducted data extraction and assessed risk of bias. Odds ratio (OR) and weighted mean differences (WMD) with 95% confidence intervals (CI) were used to pool effect estimates from trials. Four prespecified subgroup analysis was conducted. Sensitivity analysis was applied to explore heterogeneity. The quality of evidence for intervention effects was summarized using GRADE methodology.
Results: 3,026 potentially relevant studies were identified and 30 papers were reviewed in full. Sixteen studies met the inclusion criteria, including a total of 2,054 individuals. Of these, 10 studies (1,840 individuals) were suitable for quantitative meta-analysis. Overall, the evidence was of low to moderate quality. Patients who received VA had a reduced need for RRT (OR 0.5 [0.33 - 0.75]; I2 = 7%, P for heterogeneity = 0.37) and a lower AKI incidence (OR 0.58 [0.37 - 0.92]; I2 = 63%, P for heterogeneity = 0.004).
Conclusions: In patients with distributive shock, VA use is associated with a reduced need for RRT and lower AKI incidence, although these results are supported by low quality evidence.
1. Hajjar LA et al. Anesthesiology 126:85-93, 2017
2. Russell JA et al. N Engl J Med 358:877-87, 2008
A Hana1, PW Moller2, PP Heinisch1, J Takala1, D Berger1
1Inselspital, Bern University Hospital, Bern, Switzerland,2Institute of Clinical Sciences at the Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden
Introduction: Venous return (VR) is driven by the difference between mean systemic filling pressure (MSFP) and right atrial pressure (RAP) and determines the maximum ECMO flow. MSFP depends on stressed volume and vascular compliance. It can be modified by absolute blood volume changes and shifts between stressed and unstressed volume. Norepinephrine (NE) may increase stressed volume by constriction of venous capacitance and at the same time increase the resistance to systemic flow. We therefore studied the effects of NE on MSFP, maximum ECMO flow and the ECMO pressure head (MAP-RAP).
Methods: MSFP was measured with blood volume at Euvolemia and NE 1 to 3 (0.05, 0.125 and 0.2μg/kg/h) in a closed-chest porcine VA-ECMO model (n=9, central cannulation with left atrial vent and av-shunt) in ventricular fibrillation. The responses of RAP and VR (measured as ECMO flow, QECMO) were studied at variable pump speeds including maximum possible speed without clinically apparent vessel collapse at constant airway pressure.
Results: The ECMO pump speed and QECMO showed a strictly linear relationship (r2 0.95 to 0.995, range over all conditions) despite increased pressure head, indicating that the maximum QECMO was determined by VR alone. NE led to both increases in MSFP and QECMO in a dose dependent way, indicating a rightward shift in the VR plot (Fig. 1) via recruitment of stressed from unstressed volume (Table 1, Fig. 2). This resulted in an increased MSFP during NE despite decreased absolute blood volume (3.9±0.4 L vs. 3.3±0.3L, p=0.009). The reduced blood volume was associated with hemoconcentration suggesting plasma leakage.
Conclusions: NE shifts the VR curve to the right, allowing a higher maximum ECMO flow. The NE induced increase in MSFP results from recruitment of unstressed volume to stressed volume, which may be modified by changes in vascular compliance. The effects on pump afterload were not limiting.
Effects of NE on MSFP, QECMO, pressure head and hemoglobin as compared to euvolemia
Max. QECMO; mL/min
Max. pressure head; mmHg
7.1 ± 1.1
4376 ± 887
93 ± 27
94 ± 6
6.7 ± 0.6
4369 ± 802
102 ± 21
100 ± 7
7.4 ± 1.0
4670 ± 746
114 ± 36
106 ± 7
7.9 ± 0.6
4967 ± 977
107 ± 37
108 ± 7
p value (RM ANOVA)
P131 Predictive value of right heart hemodynamics for acute kidney injury after heart transplantation
G Guven, M Brankovic, AA Constantinescu, JJ Brugts, DA Hesselink, S Akin, A Struijs, O Birim, C Ince, OC Manintveld, K Caliskan
Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
Introduction: Acute kidney injury (AKI) is a major complication after heart transplantation (HTx), but the relation with the preoperative right heart hemodynamics (RHH) remain largely unknown. The aim of this study was to determine whether the routine and novel RHH could predict the development of AKI and 1-year patient survival in patients with HTx.
Methods: Data of all consecutive HTx patients (n=595) in our tertiary referral center, between 1984 and 2016, were collected and analyzed for the occurrence of AKI and survival at 1 year.
Results: AKI was developed in 430 (72%) patients; 278 (47%) stage-1, 66 (11%) stage-2, and 86 (14%) stage-3. Renal replacement therapy (RRT) was needed in 41 (7%) patients, with subsequent increased risk for chronic RRT-dependency at 1-year (odds ratio: 3.3 [95% CI: 1.6–6.6], p=0.001). Patients with higher AKI stages had also higher baseline right atrial pressure (RAP) (median: 7, 7, 8, 11 mmHg, p-trend=0.021), RAP/PCWP ratio (0.37, 0.36, 0.40, 0.47, p-trend=0.009), and lower pulmonary artery pulsatility index (PAPi) values (2.83, 3.17, 2.54, 2.31, p-trend=0.012). Patients with higher AKI stages had significantly lower survival at 1-year (5, 7, 15, 14 %, log-rank, p-trend=0.021) with worst outcome for RRT patients (1-year mortality with RRT vs no RRT: 22% vs 8%, log-rank, p=0.001).
Conclusions: AKI is highly frequent early after HTx and is inversely associated with 1-year patient survival. The routinely collected preoperative PAPi and RAP predict the development and severity of AKI early after HTx and could be used to timely intervene and prevent the development of AKI.
A Taylor, S Stevenson, J Gardner, K Lake, K Litchfield
Princess Royal Maternity Unit, Glasgow Royal Infirmary, Glasgow, UK
Introduction: Haemorrhage and sepsis are the most common reasons for admission to our maternity HDU.
Methods: Data was gathered over a 26 month period from July 2015 to September 2017 looking at maternity HDU admissions with sepsis or haemorrhage. Using Excel length of stay, cardiovascular instability, monitoring, vasoactive drug use and baby with Mum was analysed. Local ethical approval granted.
Results: The total number of patients admitted was 514. 259 (50.4%) had a primary diagnosis of haemorrhage or sepsis. Haemorrhage was separated in to antepartum, 14 (9%) and postpartum 37 (90.7%). The most common reason for postpartum haemorrhage was uterine atony 62 (45.5%). 38 (35%) of sepsis admissions were antepartum and 70 (65%) postpartum. 1 (0.6%) was discharged to surgical HDU and 150 (99.3%) to ward. The most common source was gynaecological infection 29 (26%). 46 (42%) of admissions were from home; 26 (24%) antepartum and 20 (18%) postpartum. Most admissions 62 (57%) were via surgical or labour ward or post-theatre. 5 (3.9%) were discharged to medical or surgical HDU, 3 (2.7%) to ICU and 100 (92%) to ward. See Table 1.
Conclusions: Most admissions to HDU, 206 (79.5%) are in the postpartum period with haemorrhage accounting for the majority. These patients are more cardiovascularly unstable, require more invasive monitoring and blood pressure treatment but have a shorter overall stay. They are generally discharged straight to ward. This reflects the expected quicker improvement after haemostasis in well young women. The discrepancy between mum with baby (62% in sepsis cf 84% in bleeding) may reflect the higher likelihood of baby needing NICU in the sepsis group. Septic patients stay longer with higher risk of deterioration and escalation of care. This mirrors the recent MBRRACE  report stating sepsis as a major cause of morbidity.
1. Knight M et al. MBRRACE-UK Saving Lives, Improving Mothers’ Care 2016.
Cardiovascular instability and monitoring of maternity HDU patients with either sepsis or haemorrhage
Number of patients
Mean length of stay (unit days)
0.91 Median 0.6 SD 0.88
1.38 Median 0.9 SD 1.29
Single vasoactive drug
Baby with mum if postpartum
P133 Real-time guidance or prelocation using ultrasound for pediatric central venous catheterization; a systematic review and network meta-analysis
K Hosokawa, N Shime, M Kyo, Y Iwasaki, Y Kida
Hiroshima University Hospital, Hiroshima, Japan
Introduction: To locate vessels for percutaneous central venous catheterizations, it may be helpful to apply not only real-time ultrasound (US) guidance but also US-assistance vein prelocation. The aim of this study was to evaluate the superiority of two US methods compared to surface landmark methods by reviewing randomized control trials (RCTs).
Methods: As updating an earlier systematic review , we searched PubMed and CENTRAL in November 2017. We included RCTs which compared the failure rates of internal jugular or femoral venous cannulations among 1) real-time US guidance, 2) US-assistance vein prelocation and 3) surface landmark methods. A frequentist network meta-analysis was conducted using the netmeta package on R.
Results: Out of 1395 citations, 11 RCTs (935 patients) were eligible. The number of studies comparing outcomes between real-time US guidance vs. surface landmark methods, US-assistance vein prelocation vs surface landmark methods and real-time US guidance vs US-assistance vein prelocation was 7, 3 and 1. Regarding cannulation failure rate, network meta-analysis in a fix-effect model showed that a p-score was lower in the real-time US guidance than US-assistance vein prelocation (0.61 vs. 0.88), by reference to surface landmark methods, and also regarding arterial punctures, a p-score was lower in the real-time US guidance than US-assistance vein prelocation (0.64 vs. 0.83).
Conclusions: Based on the present network meta-analysis of RCTs, p-scores of cannulation failure and arterial puncture were lower in the real-time US guidance, suggesting that the US-assistance vein prelocation is superior than the real-time US guidance, both of which achieve lower rates of failure and arterial puncture compared to the landmark methods. We speculates that the inferiority of real-time guidance is associated with difficulties in manipulating the needle together with an echo probe in targeting relatively smaller veins in children.
1. Shime N et al. Pediatr Crit Care Med 16(8):718-25, 2015.
M Charalambos, A Revill, D Howland
Torbay Hospital, Torquay, UK
Introduction: We present a case report of ‘Shoshin beriberi’ in a young female who was ‘fussy with food’ that developed an acutely progressive metabolic acidosis and multi-organ failure requiring intensive care support.
Methods: Our patient was a 36-year-old British woman who presented to the emergency department (ED) with a ten-day history of diarrhea, vomiting and increasing fatigue. She had a past medical history of gastroparesis, polycystic ovary syndrome (on metformin), laparoscopic cholecystectomy and hysteropexy. She lived with her husband and two children who had viral gastroenteritis two weeks previously.
Results: The patient had a metabolic acidosis (pH 6.9) with raised lactate (>16) on initial blood gas in the ED. A 1.26% sodium bicarbonate infusion and hemofiltration were commenced overnight. The patient’s pH and lactate remained static with an increasing work of breathing over this period. By morning she developed flash pulmonary oedema and hypotension, the first signs of acute cardiac failure. An echocardiogram displayed severely impaired left ventricular function with ejection fraction of 17%. The patient was intubated and inotropic support was commenced. It was thought that a micronutrient deficiency may have caused a rapid onset cardiac failure. Pabrinex (containing 250ml of Thiamine Hydrochloride) was commenced and within 9 hours the patient’s metabolic acidosis markedly improved (Fig. 1). Complete reversal of the cardiac failure occurred over 96 hours.
Conclusions: Shoshin is a rare clinical manifestation of thiamine deficiency . It is an important differential diagnosis to bear in mind after excluding more common aetiologies of heart failure. Especially in this case as our patient had no obvious risk factors at the time of presentation. We suggest empiric use of thiamine should be considered in treatment algorithms for young patients presenting with acute cardiac failure. The pateint had provided informed consent for publication.
1. Naidoo DP, et al. Clinical diagnosis of cardiac beriberi. S Afr Med J 77(3):125-7. 1990.
P135 Wells score is not a reliable predictor of the risk of pulmonary embolism in critically ill patients: a retrospective cohort study
T Rech, A Girardi, R Bertiol, M Gazzana
Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
Introduction: Pulmonary embolism (PE) is a commonly missed deadly diagnosis . At the emergency department, the pretest probability of PE can be assessed using clinical prediction tools. However, critically ill patients are at a high risk for PE and prediction rules have not been validated in this population. The aim of the present study was to assess the Wells scoring system as a predictor of PE in critically ill patients.
Methods: Computed tomographic (CT) pulmonary angiographies performed for suspected PE in adult critically ill patients during their intensive care unit stay were identified by the radiology information system. Wells score was retrospectively calculated based on medical records and its reliability as a predictor of PE was determined using a receiver operator characteristic (ROC) curve.
Results: From the 144 patients evaluated, 39 (27%) were positive for PE based on CT pulmonary angiography. Mean Wells score was 3.9 ± 2.7 in patients with PE versus 2.4 ± 1.5 in patients without PE (P <0.001). Sixty patients (41.6%) were considered as low probability for PE (Wells score <2). From them, 13 patients (22%) presented with filling defects on CT scan, including two patients with main stain pulmonary artery embolism and one patient with lobar artery embolism. The area under ROC curve was 0.656. When a Wells score >4 was used to predict risk of PE, the sensitivity was 43%, specificity was 88%, PPV was 59% and NPV was 88.6%.
Conclusions: In this population of critically ill patients, Wells score was not a reliable predictor of risk of PE.
Wiener RS et al. BMJ 347: F3368, 2015
C Facciorusso, M Bottiroli, A Calini, D De Caria, S Nonini, R Pinciroli, F Milazzo, M Gagliardone
ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
Introduction: Cardiogenic shock (CS) is a syndrome due to acute heart failure. Acute kidney injury (AKI) could be secondary to tissue congestion and hypoperfusion. While many studies have evaluated the incidence of AKI in post-ischemic CS there is a paucity of data on non-ischemic CS etiology. The aim of this study is to evaluate clinical and prognostic relevance of AKI in this setting.
Methods: Monocentric, retrospective observational study on patients with CS. Study period: 2010-2016. Exclusion criteria: ischemic and postcardiotomy etiology of CS. Demographic, clinical and biochemical variables were collected at baseline and during hospital stay. AKI was defined according to AKIN criteria. Continuous variables are presented as median (IQR). Data were analyzed using comparative statistics and multivariate analysis was performed with Cox regression. Survival analysis was performed with Kaplan-Meier.
Results: We recruited 71 patients. Etiologies of CS were: 44 acute decompensation of chronic cardiomyopathies (CCM), 14 acute myocarditis, and 13 other causes. AKI occurred in 47 (66%) pts; among these AK