Outcome Of Septic Patients Research Articles

Impact of obesity on outcomes in patients with sepsis

The purpose of this study was to evaluate the impact of obesity on outcomes in patients with severe sepsis. Since obesity is considered an inflammatory disease and is associated with elevations in several inflammatory mediators important in the outcome of sepsis, the relationship between obesity and outcome in septic patients was studied.

Vitamin D and ICU outcome in septic patients: a difficult connection?

Vitamin D, a secosteroid hormone, has roles in the optimal functioning of many organ systems and illnesses [1]. Recent reports show that most patients admitted to the ICU are vitamin D insufficient [2].

Soluble receptor for advanced glycation end products predicts 28-day mortality in critically ill patients with sepsis

Objective. Multiple biomarkers are used to assess sepsis severity and prognosis. Increased levels of the soluble receptor for advanced glycation end products (sRAGE) were previously observed in sepsis but also in end-organ injury without sepsis. We evaluated associations between sRAGE and (i) 28-day mortality, (ii) sepsis severity, and (iii) individual organ failure. Traditional biomarkers procalcitonin (PCT), C-reactive protein (CRP) and lactate served as controls. Methods. sRAGE, PCT, CRP, and lactate levels were observed on days 1 (D1) and 3 (D3) in 54 septic patients. We also assessed the correlation between the biomarkers and acute respiratory distress syndrome (ARDS), acute kidney injury (AKI) and acute heart failure. Results. There were 38 survivors and 16 non-survivors. On D1, non-survivors had higher sRAGE levels than survivors (p = 0.027). On D3, sRAGE further increased only in non-survivors (p < 0.0001) but remained unchanged in survivors. Unadjusted odds ratio (OR) for 28-day mortality was 8.2 (95% CI: 1.02–60.64) for sRAGE, p = 0.048. Receiver operating characteristic analysis determined strong correlation with outcome on D3 (AUC = 0.906, p < 0.001), superior to other studied biomarkers. sRAGE correlated with sepsis severity (p < 0.00001). sRAGE showed a significant positive correlation with PCT and CRP on D3. In patients without ARDS, sRAGE was significantly higher in non-survivors (p < 0.0001) on D3. Conclusion. Increased sRAGE was associated with 28-day mortality in patients with sepsis, and was superior compared to PCT, CRP and lactate. sRAGE correlated with sepsis severity. sRAGE was increased in patients with individual organ failure. sRAGE could be used as an early biomarker in prognostication of outcome in septic patients.

Farmaconutrición parenteral con selenio en la sepsis

Critical illness is characterized by oxidative stress which leads to multiple organ failure, and sepsis-related organ dysfunction remains the most common cause of death in the intensive care unit. Over the last 2 decades, different antioxidant therapies have been developed to improve outcomes in septic patients. According to recent evidence, selenium therapy should be considered the cornerstone of the antioxidant strategies. Selenium given as selenious acid or sodium selenite should be considered as a drug or pharmaconutrient with prooxidant and cytotoxic effects when a loading dose in intravenous bolus form is administered, particularly in the early stage of severe sepsis/septic shock. To date, several phase ii trials have demonstrated that selenium therapy may be able to decrease mortality, improve organ dysfunction and reduce infections in critically ill septic patients. The effect of selenium therapy in sepsis syndrome must be confirmed by large, well designed phase iii clinical trials. The purpose of this review is to discuss current evidence on selenium pharmaconutrition in sepsis syndrome.

Sepsis: Multiple Abnormalities, Heterogeneous Responses, and Evolving Understanding

Sepsis represents the host's systemic inflammatory response to a severe infection. It causes substantial human morbidity resulting in hundreds of thousands of deaths each year. Despite decades of intense research, the basic mechanisms still remain elusive. In either experimental animal models of sepsis or human patients, there are substantial physiological changes, many of which may result in subsequent organ injury. Variations in age, gender, and medical comorbidities including diabetes and renal failure create additional complexity that influence the outcomes in septic patients. Specific system-based alterations, such as the coagulopathy observed in sepsis, offer both potential insight and possible therapeutic targets. Intracellular stress induces changes in the endoplasmic reticulum yielding misfolded proteins that contribute to the underlying pathophysiological changes. With these multiple changes it is difficult to precisely classify an individual's response in sepsis as proinflammatory or immunosuppressed. This heterogeneity also may explain why most therapeutic interventions have not improved survival. Given the complexity of sepsis, biomarkers and mathematical models offer potential guidance once they have been carefully validated. This review discusses each of these important factors to provide a framework for understanding the complex and current challenges of managing the septic patient. Clinical trial failures and the therapeutic interventions that have proven successful are also discussed.

Selenium supplementation for sepsis: a meta-analysis of randomized controlled trials

BackgroundRecently, several studies were conducted to investigate the effect of selenium supplementation in septic patients. However, no consistent conclusion was made. Thus, we aimed to systematically summarize the available randomized controlled trials (RCTs) to evaluate the effect of selenium supplementation on important clinical outcomes in septic patients. MethodsA systematic literature search of Pubmed, Embase, and the Cochrane Central Register of Controlled Trials was conducted (up to August 25, 2012). RCTs were included if they reported the effect of selenium supplementation on the treatment of septic patients. A fixed-effect model was used, and in the case of significant heterogeneity, a random-effects model was employed. ResultsFive studies with a total of 530 patients were included. Pooled analysis showed that selenium supplementation did not reduce all-cause mortality (relative risk [RR] = 0.89, 95% confidence interval [CI]: 0.73-1.07, P = .21), hospital-acquired pneumonia (RR = 1.15, 95% CI: 0.73-1.82, P = .55), or length of intensive care unit stay (weighted mean differences = 2.32 days, 95% CI: −0.05 to 4.69; P = .05). In addition, no significant difference was observed regarding adverse events between groups (RR = 0.97, 95% CI: 0.72-1.33, P = .87). ConclusionsThe present meta-analysis showed no benefit of selenium supplementation in patients with sepsis. Due to the limited number of RCTs included, more prospective multicenter clinical trials on selenium therapy in septic patients are warranted in the future.

Fighting hospital sepsis

Sepsis accounts for a very high mortality. The Surviving Sepsis Campaign recommends a first 6 hours resuscitative bundle to improve patient outcome. Despite this, the bundle is poorly performed because of several organizational and cultural barriers. In recognition of this, we guess that an Educational and Organizational Intervention out of the ICUs could impact on septic patient outcome. In order to test our hypothesis we carried out, in 12 hospitals, a pre-intervention survey of the human and organizational resources (HOR) available in the management of septic patients. The aim is to seek any barrier potentially affecting correct Guidelines implementation.

Interleukin-1 Receptor Antagonist Gene Polymorphism Increases Susceptibility to Septic Shock in Children With Acute Lymphoblastic Leukemia

Interleukin-1 receptor antagonist polymorphism (ILRN) 2 (ILRN*2) has been associated with a poor outcome in septic patients because of an elevated production of anti-inflammatory cytokines. In >70% of patients, morbidity and mortality in childhood acute lymphoblastic leukemia is caused by infections. The aim of this study was to determine the association between this polymorphism and the frequency of septic shock from the time of diagnosis until completion of treatment. This cohort study was conducted in 57 consecutive children with acute lymphoblastic leukemia. At the end of follow-up, children were stratified according to their IL1RN polymorphism (ILRN*1/ILRN*2), evaluating the impact of genotype on the severity of febrile neutropenic events during their treatment. Overall survival was 80% at 55 months after treatment. The average number of febrile neutropenic events in this cohort was 2.82 per patient. Genotype distribution was 50.9% for homozygote IL-1RN*1, 38.6% for heterozygote ILRN*1/ILRN*2 and 10.5% for homozygote IL-1RN*2. The risk of presenting septic shock for homozygote IL1RN*2/IL1RN*2 and heterozygote ILRN*1/ILRN*2 patients was significantly greater (odds ratio, 45; P = 0.001) adjusted for age, gender, risk of leukemia and presence of pathogenic bacteria. Genotype IL-1RN*2 is associated with the risk of development of septic shock in children with acute lymphoblastic leukemia. Further research in larger population-based studies is needed to replicate these findings. This information would allow us to identify more predictive factors in this group of acute lymphoblastic leukemia patients in whom this information is lacking to establish an earlier and more aggressive approach.

TIMP-1 gene polymorphism: are genetics able to predict outcome of septic patients?

The multicenter study conducted by Lorente and coworkers - published in the previous issue of Critical Care - suggests that levels of tissue inhibitor of metalloproteinase (TIMP)-1 in association with the 372 T/C genetic polymorphism of TIMP-1 are promising markers to predict the clinical outcome of septic patients. TIMPs bind to active matrix metalloproteinases and, amongst other effects, inhibit their proteolytic activity of the extracellular matrix. Previous clinical studies showed increased plasma levels of TIMP-1 in nonsurvivors of sepsis, and showed associations between the 372 T/C genetic polymorphism of TIMP-1 and increased risk of developing certain diseases. In recent years, there has been great interest in understanding whether genetic determinants of the host response to systemic infections are associated with poor outcome. Furthermore, the pharmacogenomics of sepsis may allow us to target immune-modulating therapies. Measurement of TIMP-1 protein levels and TIMP-1 polymorphism 372 T/C in the intensive care setting could therefore be an attractive noninvasive tool to determine the outcome of septic patients, and might help to select patients potentially benefitting from a target-specific immune-modulatory therapy directed to matrix metalloproteinase/TIMP homeostasis.

The angiogenic factors and their soluble receptors in sepsis: friend, foe, or both?

The endothelium represents an important source of, and a target for, inflammation in sepsis. Angiogenic factors and their receptors, including vascular endothelial growth factor (VEGF)/VEGF receptor and the angiopoietin/Tie2 signaling pathways, have recently received great attention in critically ill patients, including those with sepsis [1-3], because of their pivotal roles in both angiogenesis and microvascular permeability. VEGF, as the most potent proangiogenic factor, has already been identified as an important target for cancer therapy. Disassembly of an intact endothelial cell junction is necessary for the angiogenesis process. The endothelial barrier-breaking properties are indeed an important part of the VEGF role in the regulation of angiogenesis. However, a high dose or prolonged duration of VEGF may lead to excessive barrier-breaking effects. The favorable results observed with the only US Food and Drug Administration-approved anti-VEGF agent, bevacizumab, by Jeong and colleagues [4] are likely to provide potential advances for future therapeutic opportunities in sepsis. On the contrary, VEGF shows endothelial survival signals, and suppression of VEGF signaling inhibits endothelial survival and increases apoptosis, which in turn may contribute to the development of sepsis-induced organ dysfunction [5]. Furthermore, other than an independent function on endothelial cells, VEGF plays an important role in mobilizing endothelial progenitor cells under pathologic conditions such as cancer and sepsis. While the decrease of circulating endothelial progenitor cells (cEPCs) after anti-VEGF treatment is beneficial in cancer, this may not be so in sepsis. The endothelium is a chief target of sepsis-induced events, and clinical outcome in septic patients is largely dependent on the ability to reconstitute damaged endothelium. Indeed, several studies have observed an increase in cEPC numbers in septic patients and a correlation between cEPC concentration and survival. The increased number of cEPCs in sepsis might therefore be a consequence of the body’s attempt to limit vascular damage by inducing endogenous endothelial repair mechanisms. The dramatic decrease of cEPCs accompanied by anti-VEGF treatment may impair endothelial repair capacity and bring unfavorable effects in sepsis. The angiogenic factors and their soluble receptors therefore do have a complex role and seemingly play both good and bad roles during sepsis development and therapy. A certain level of VEGF is necessary for normalizing endothelial function, and abnormally high or low levels of VEGF might shift its role from endothelial protective to endothelial barrier disruptive. This view can also provide additional possible explanations for why Jeong and colleagues’ study suggests that a high dose of bevacizumab may have deleterious effects in an experimental sepsis model. Future studies on the dynamic change of the angiogenic factors, their soluble receptors and cEPC counts during and after each therapy, as well as the context-dependent role of them, may provide background data for using these angiogenic factors and their soluble receptors as therapeutic targets for sepsis treatment in clinical practice.

A Prospective Analysis of Disseminated Intravascular Coagulation in Patients with Infections

Disseminated intravascular coagulation (DIC) is often associated with infection and a poor outcome. In this study, useful markers for predicting poor outcomes were examined. The frequency of DIC and organ failure, outcomes and hemostatic markers were prospectively evaluated in 242 patients with infections. Seventy-seven patients were diagnosed with DIC, 36 of whom recovered from the condition. The rate of DIC or resolution of DIC was highest in the patients with sepsis and lowest in the patients with respiratory infections. Mortality tended to be high in the patients with respiratory infections. The DIC score, sepsis-related organ failure assessment (SOFA) score, prothrombin time (PT) ratio and thrombin-antithrombin complex level were significantly high in the patients who did not recover from DIC. The age, DIC score, SOFA score, PT ratio and levels of thrombomodulin and plasminogen activator inhibitor (PAI)-I were significantly high in the non-survivors. Factors related to a poor outcome included resolution of DIC, the SOFA score, age and the PT ratio. Factors related to resolution of DIC included the SOFA score and age, while factors related to the SOFA score included the levels of PAI-I, leukocytes, fibrinogen, D-dimer and platelets. The outcomes of septic patients primarily depend on the SOFA score and the resolution of DIC, which are related to organ failure.

B and T lymphocyte attenuator expression on CD4+ T-cells associates with sepsis and subsequent infections in ICU patients

IntroductionSepsis is a deadly inflammatory condition that often leads to an immune suppressed state; however, the events leading to this state remain poorly understood. B and T lymphocyte attenuator (BTLA) is an immune-regulatory receptor shown to effectively inhibit CD4+ T-cell function. Therefore, our objectives were to determine: 1) if lymphocyte BTLA expression was altered in critically ill patients and experimentally induced septic mice, 2) whether augmented CD4+ T-cell BTLA expression was associated with poor septic patient outcomes, and 3) if BTLA expression affected the CD4+ T-cell apoptotic cell loss observed in the lymphoid organs of septic mice.MethodsChanges in CD4+ lymphocyte BTLA expression were compared with morbid event development in critically ill ICU patients (11 septic and 28 systemic inflammatory response syndrome subjects). Wild type and BTLA gene deficient mice were utilized to evaluate the expression and role of BTLA in septic lymphocyte apoptotic cell loss.ResultsThe observed septic ICU patients had a significantly higher percentage of peripheral blood BTLA+ CD4+ lymphocytes compared with critically ill non-septic individuals. Moreover, the non-septic patients with CD4+ T-cells that were greater than 80% BTLA+ were more susceptible to developing nosocomial infections. Additionally, in general, critically ill patients with CD4+ T-cells that were greater than 80% BTLA+ had longer hospital stays. Comparatively, circulating CD4+ T-cell and B-cell BTLA expression increased in septic mice, which associated with the increased septic loss of these cells. Finally, the loss of these cells and cellular apoptosis induction in primary and secondary lymphoid organs were reversed in BTLA deficient mice.ConclusionsAn increased BTLA+ CD4+ lymphocyte frequency in the observed critically ill non-septic patients was associated with a subsequent infection; therefore, BTLA may act as a biomarker to help determine nosocomial infection development. Additionally, BTLA expression contributed to primary and secondary lymphoid organ apoptotic cell loss in experimentally septic mice; thus, BTLA-induced apoptotic lymphocyte loss may be a mechanism for increased nosocomial infection risk in critically ill patients. This study had a relatively small human subject cohort; therefore, we feel these findings warrant future studies evaluating the use of BTLA as a critically ill patient nosocomial infection biomarker.

Guidelines on the management of anaemia and red cell transfusion in adult critically ill patients.

Forward This document aims to summarize the current literature guiding the use of red cell transfusion in critically ill patients and provides recommendations to support clinicians in their day-to-day practice. Critically ill patients differ in their age, diagnosis, co-morbidities, and severity of illness. These factors influence their tolerance of anaemia and alter the risk to benefit ratio of transfusion. The optimal management for an individual may not fall clearly within our recommendations and each decision requires a synthesis of the available evidence and the clinical judgment of the treating physician. This guideline relates to the use of red cells to manage anaemia during critical illness when major haemorrhage is not present. A previous British Committee for Standards in Haematology (BCSH) guideline has been published on massive haemorrhage (Stainsby et al, 2006), but this is a rapidly changing field. We recommend readers consult recent guidelines specifically addressing the management of major haemorrhage for evidence-based guidance. A subsequent BCSH guideline will specifically cover the use of plasma components in critically ill patients.

Procalcitonin Predicts Real-Time PCR Results in Blood Samples from Patients with Suspected Sepsis

BackgroundEarly diagnosis and rapid bacterial identification are of primary importance for outcome of septic patients. SeptiFast® (SF) real-time PCR assay is of potential utility in the etiological diagnosis of sepsis, but it cannot replace blood culture (BC) for routine use in clinical laboratory. Procalcitonin (PCT) is a marker of sepsis and can predict bacteremia in septic patients. The aim of the present study was to investigate whether PCT serum levels could predict SF results, and could help screening febrile patients in which a SF assay can improve the etiological diagnosis of sepsis.MethodsFrom 1009 febrile patients with suspected sepsis, 1009 samples for BC, SF real-time PCR, and PCT determination were obtained simultaneously, and results were compared and statistically analysed. Receiver operating characteristic (ROC) curves were generated to determine the area under the curve and to identify which cut-off of PCT value produced the best sensitivity to detect SF results.ResultsMean PCT values of sera drawn simultaneously with samples SF positive (35.42±61.03 ng/ml) or BC positive (23.14±51.56 ng/ml) for a pathogen were statistically higher than those drawn simultaneously with SF negative (0.84±1.67 ng/ml) or BC negative (2.79±16.64 ng/ml) samples (p<0.0001). For SF, ROC analysis showed an area under the curve of 0.927 (95% confidence interval: 0.899–0.955, p<0.0001). The PCT cut-off value of 0.37 ng/ml showed a negative predictive value of 99%, reducing the number of SF assays of 53.9%, still identifying the 96.4% of the pathogens.ConclusionPCT can be used in febrile patients with suspected sepsis to predict SF positive or negative results. A cut-off value of 0.37 ng/ml can be considered for optimal sensitivity, so that, in the routine laboratory activity, SF assay should not be used for diagnosis of sepsis in an unselected patient population with a PCT value <0.37 ng/ml.

Obesity and IL-6 interact in modulating the response to endotoxemia in mice

Obesity is associated with elevated levels of IL-6. High IL-6 is prognostic of mortality in sepsis, while controversial data link obesity to sepsis outcome. We used Lean and diet-induced obese (DIO) WT and IL-6 KO mice to investigate the interaction between obesity and IL-6 in endotoxemia. Circulating levels of IL-6 were significantly higher in WT DIO versus WT Lean mice receiving LPS (2.5μg/mouse, ip). Obesity lead to greater weight loss in response to LPS, with IL-6 deficiency being partially protective. Plasma TNFα, IFNγ, Galectin-3 and leptin were significantly elevated in response to LPS and were each differentially affected by obesity and/or IL-6 deficiency. Plasma Galectin-1 and adiponectin were significantly suppressed by LPS, with obesity and IL-6 deficiency modulating the response. However, LPS comparably increased IL-10 levels in each group. Leukopenia with relative neutrophilia and thrombocytopenia developed in each group after injection of LPS, with obesity and genotype affecting the kinetics, but not the magnitude, of the response. Hepatic induction of the acute-phase protein SAA by LPS was not affected by obesity or IL-6 deficiency, although baseline levels were highest in WT DIO mice. Injection of LPS significantly increased hepatic mRNA expression of PAI-1 in Lean WT and Lean KO mice, while it suppressed the high baseline levels observed in the liver of DIO WT and DIO KO mice. Thus, both IL-6 and obesity modulate the response to endotoxemia, suggesting a complex interaction that needs to be considered when evaluating the effect of obesity on the outcome of septic patients.

55 Change of Hemopexin Level Is Associated With the Severity of Sepsis in Endotoxemic Rat Model and the Outcome of Septic Patients

Study Objectives: In sepsis condition, serum hemopexin levels are correlated to patient's prognosis in some study, but there is little evidence about that. The purpose of this study is to identify the prognostic power of hemopexin from clinical study in septic shock patients and to identify differences in change of serum hemopexin level pursuant to the sepsis severity from pre-clinical study. Methods: 1.Clinical study: A prospective, cohort study conducted in an emergency intensive care unit of a tertiary referral hospital. We enrolled consecutive patients who were admitted to the emergency intensive care unit with septic shock from February 2006 to May 2010. After collecting data with respect to demographic findings, diagnosis, APACHE II scores, basal lactic acid and 28 days mortality, the enrolled patients were divided into 2 groups according to the mortality, 28 days survival groups (survivors) and 28 days death groups (non-survivors). We measured septic enrolled patients' serum hemopexin levels at the time of admission to the ICU 2. Pre-clinical study: Male Spraque-Dawley rats (300-400g) were used. Rats were categorized into 3 groups; 1) Control (n=6, normal saline), 2) low grade sepsis group (n=18, 5mg/kg LPS), 3) high grade sepsis group (n=20, 10mg/kg LPS). Rats of each group were infused saline, LPS and then we checked the serum hemopexin levels, TNF-α, IL-6 by time course (1, 3, 6 hours). Results: 1. Clinical study: Among 142 enrolled patients, 100 were survivors and 42 were non-survivors. The APACHE II score and initial lactic acid level of survivors were lower than non survivors. (respectively p<0.001, p<0.001). Initial serum hemopexin level of non-survivors was lower than that of non-survivors (p<0.001). The area under curve (AUC) of the hemopexin was 0.754 (95% confidence interval, 0.670 - 0.839). In multivariate logistic regression, hemopexin levels have inverse relationship with 28 days mortality (p=0.032). 2. Pre-clinical study: There are significant differences in change in serum hemopexin levels between high grade sepsis group and low grade sepsis group (p=0.013). Especially, serum hemopexin levels of high grade sepsis groups at 6 hours are significant lower than low grade sepsis group (p=0.002). Also, there are significant differences in change in serum TNF-α levels between 2 groups (p<0.001). Serum TNF-α levels of high grade sepsis groups at 3, 6 hours are significant higher than low grade sepsis group (p=0.002 3h, p=0.002 6h). Finally, there are significant differences in change in serum IL-6 levels between 2 groups (p<0.001). Serum IL-6 levels of high grade sepsis groups at 1, 3, 6 hours are significant higher than low grade sepsis group (p=0.026 1h, p=0.026 3h, p=0.002 6h). Conclusion: Initial low serum hemopexin concentration is significantly associated with higher 28 days mortality of patients with septic shock. In pre-clinical study, there are significant in change of serum hemopexin levels pursuant to the sepsis severity. Especially, serum hemopexin levels of high grade sepsis groups at 6 hours are significant lower than low grade sepsis group after LPS infusion.

A Collaborative Quality Improvement Model and Electronic Community of Practice to Support Sepsis Management in Emergency Departments: Investigating Care Harmonization for Provincial Knowledge Translation

Emergency medicine departments within several organizations are now advocating the adoption of early intervention guidelines for patients with the signs and symptoms of sepsis. This proposed research will lead to a comprehensive understanding of how diverse emergency department (ED) sites across British Columbia (BC), Canada, engage in a quality improvement collaborative to lead to improvements in time-based process measures and clinical outcomes for septic patients in EDs. To address the challenge of sepsis management, in 2007, the BC Ministry of Health began working with emergency health professionals, including health administrators, to establish a provincial ED collaborative: Evidence to Excellence (E2E). The E2E initiative employs the Institute for Healthcare Improvement (IHI) model and is supported by a Web-based community of practice (CoP) in emergency medicine. It aims to (1) support clinicians in accessing and applying evidence to clinical practice in emergency medicine, (2) support system change and clinical process improvement, and (3) develop resources and strategies to facilitate knowledge translation and process improvement. Improving sepsis management is one of the central foci of the E2E initiative. The primary purpose of our research is to investigate whether the application of sepsis management protocols leads to improved time-based process measures and clinical outcomes for patients presenting to EDs with sepsis. Also, we seek to investigate the implementation of sepsis protocols among different EDs. For example: (1) How can sepsis protocols be harmonized among different EDs? (2) What are health professionals’ perspectives on interprofessional collaboration with various EDs? and (3) What are the factors affecting the level of success among EDs? Lastly, working in collaboration with the BC Ministry of Health as our policy-maker partner, the research will investigate how the demonstrated efficacy of this research can be applied on a provincial and national level to establish a template for policy makers from other jurisdictions to translate knowledge into action for EDs. This research study will employ the IHI model for improvement, incorporate the principles of participatory action research, and use the E2E online CoP to engage ED practitioners (eg, physicians, nurses, and administrators, exchanging ideas, engaging in discussions, sharing resources, and amalgamating knowledge) from across BC to (1) share the evidence of early intervention in sepsis, (2) adapt the evidence to their patterns of practice, (3) develop a common set of orders for implementing the sepsis pathway, and (4) agree on common indicators to measure clinical outcomes. Our hypothesis is that combining the social networking ability of an electronic CoP and its inherent knowledge translation capacity with the structured project management of the IHI model will result in widespread and sustained improvement in the emergency and overall care of patients with severe sepsis presenting to EDs throughout BC.

Plasma nuclear and mitochondrial DNA levels as predictors of outcome in severe sepsis patients in the emergency room.

Background and aimThe sensitivity and specificity of biomarkers and scoring systems used for predicting fatality of severe sepsis patients remain unsatisfactory. This study aimed to determine the prognostic value of circulating plasma DNA levels in severe septic patients presenting at the Emergency Department (ED).MethodsSixty-seven consecutive patients with severe sepsis and 33 controls were evaluated. Plasma DNA levels were estimated by real-time quantitative polymerase chain reaction assay using primers for the human β-hemoglobin and ND2 gene. The patients’ clinical and laboratory data on admission were analyzed.ResultsThe median plasma nuclear and mitochondria DNA levels for severe septic patients on admission were significantly higher than those of the controls. The mean plasma nuclear DNA level on admission correlated with lactate concentration (γ = 0.36, p = 0.003) and plasma mitochondrial DNA on admission (γ = 0.708, p < 0.001). Significant prognostic factors for fatality included mechanical ventilation within the first 24 hours (p = 0.013), mean sequential organ failure assessment (SOFA) score on admission (p = 0.04), serum lactate (p < 0.001), and both plasma nuclear and mitochondrial DNA on admission (p < 0.001). Plasma mitochondrial DNA was an independent predictor of fatality by stepwise logistic regression such that an increase by one ng/mL in level would increase fatality rate by 0.7%.ConclusionPlasma DNA has potential use for predicting outcome in septic patients arriving at the emergency room. Plasma mitochondrial DNA level on admission is a more powerful predictor than lactate concentration or SOFA scores on admission.

The relationship between serum procalcitonin (PCT) level and acute physiology and chronic health evaluation II (APACHE II ) score in septic patients

Objective To investigate the relationships between serum procalcitonin (PCT) level and APACHE Ⅱ score as well the prognosis of septic patients.Methods Ninety patients with sepsis were collected from emergency and critical care department of Third Hospital,Peking University,Beijing.Within 24 hours after admission,the serum PCT,hypersensitive C-reactive protein (hs-CRP),leucocyte count (WBC) and lactic acid were examined,and APACHE Ⅱ score were calculated.According to APACHE Ⅱscore,the septic patients were divided into three groups of high,median and low scores.Based on the 28 -day outcomes of patients,the patients were divided into survival group and death group.The differences in PCT,APACHE score,WBC and lactic acid between the survival group and the death group were detected.Results The serum levels of PCT were significantly higher ( P ＜ 0.01 ) in patients with high APACHE Ⅱ score ( ＞ 20) than that in patients with median score (10-20) and low score ( ＜ 10 ).There was significant correlation between PCT level and APACHE Ⅱscore ( r =0.58,P ＜0.01 ).Conclusions There is a good correlation between serum PCT level and APACHE Ⅱ score.The serum PCT and APACHE Ⅱ can be used for predicting the outcomes of septic patients. Key words: Procalcitonin; Sepsis; Acute physiology and chronic health evaluation Ⅱ

Accuracy of plasma sTREM-1 for sepsis diagnosis in systemic inflammatory patients: a systematic review and meta-analysis

IntroductionEarly diagnosis of sepsis is vital to the clinical course and outcome of septic patients. Recently, soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) appears to be a potential marker of infection. The objective of this systematic review and meta-analysis was to evaluate the accuracy of plasma sTREM-1 for sepsis diagnosis in systemic inflammatory patients.MethodsA systematic literature search of PubMed, Embase and Cochrane Central Register of Controlled Trials was performed using specific search terms (up to 15 October 2012). Studies were included if they assessed the accuracy of plasma sTREM-1 for sepsis diagnosis in adult patients with systemic inflammatory response syndrome (SIRS) and provided sufficient information to construct a 2 X 2 contingency table.ResultsEleven studies with a total of 1,795 patients were included. The pooled sensitivity and specificity was 79% (95% confidence interval (CI), 65 to 89) and 80% (95% CI, 69 to 88), respectively. The positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 4.0 (95% CI, 2.4 to 6.9), 0.26 (95% CI, 0.14 to 0.48), and 16 (95% CI, 5 to 46), respectively. The area under the curve of the summary receiver operator characteristic was 0.87 (95% CI, 0.84 to 0.89). Meta-regression analysis suggested that patient sample size and assay method were the main sources of heterogeneity. Publication bias was suggested by an asymmetrical funnel plot (P = 0.02).ConclusionsThe present meta-analysis showed that plasma sTREM-1 had a moderate diagnostic performance in differentiating sepsis from SIRS. Accordingly, plasma sTREM-1 as a single marker was not sufficient for sepsis diagnosis in systemic inflammatory patients.