IgMA-enriched immunoglobulin in neutropenic patients with sepsis syndrome and septic shock: a randomized, controlled, multiple-center trial

OBJECTIVE: To evaluate the effect of intravenous IgMA-enriched immunoglobulin (ivIGMA) therapy on mortality in neutropenic patients with hematologic malignancies and sepsis syndrome or septic shock. DESIGN: Multiple-center, prospective randomized, controlled study. SETTING: Six university hospitals in Germany. PATIENTS: Patients were 211 neutropenic patients with sepsis syndrome or septic shock after chemotherapy for severe hematologic disorders between 1992 and 1999. INTERVENTIONS: Patients received 1300 mL of ivIGMA (7.8 g IgM, 7.8 g IgA, and 49.4 g IgG) infused intravenously within a period of 72 hrs or human albumin according to the same schedule as ivIGMA. MEASUREMENTS AND MAIN RESULTS: All-cause mortality at 28 days, sepsis-related mortality at 28 days, all-cause mortality at 60 days, mortality from septic shock, and mortality from microbiologically proven Gram-negative sepsis and septic shock were recorded. Immunoglobulin had no benefit over human albumin. The 28-day mortality rate was 26.2% and 28.2% in the ivIGMA and control patients, respectively (difference, 2.0% [95% confidence interval, -10.2 to 14.2 percentage points]). Likewise, the 60-day mortality rate did not differ between both arms (29.6% vs. 34.7% in the ivIGMA and control patients, respectively). Mortality rates in patients with sepsis syndrome (17.1% vs. 16.7%) and septic shock (51.9% vs. 54.8%) were also found to be similar between both groups. CONCLUSIONS: Intravenous ivIGMA had no beneficial effects in neutropenic patients with hematologic malignancies and sepsis syndrome and septic shock.     

Use of polyclonal immunoglobulins as adjunctive therapy for sepsis or septic shock

OBJECTIVE: There is ongoing debate about the efficacy of polyvalent immunoglobulins as adjunctive therapy for sepsis or septic shock. Two meta-analyses by the Cochrane collaboration calculated a significant reduction in mortality. However, data of the largest study were missing in one, and a subset of four high-quality studies failed to show an effect in the other. To broaden the database, we performed a meta-analysis of all randomized controlled studies published so far. DATA SOURCE: MEDLINE, EMBASE, Cochrane Library of randomized trials, and personal files. STUDY SELECTION: Meta-analysis of all published randomized controlled studies published on polyvalent immunoglobulins (Ig) for treatment of sepsis or septic shock in adults, children, or neonates. DATA EXTRACTION: Twenty-seven trials with a total of 2,202 patients fulfilled the inclusion criteria. DATA SYNTHESIS: As the immunologic state of neonates is different than that of adults or older children, data were evaluated separately for each group. Fifteen trials on 1,492 adults could be included. The pooled effect on mortality was a relative risk of death (RR) of 0.79 (95% confidence interval [CI] 0.69-0.90, p 相似文献   

感染性休克集束治疗对病死率影响的前瞻性临床研究

目的 探讨集束治疗对感染性休克患者病死率的影响.方法 采用前瞻性研究方法,将2007年1月-2008年6月重症加强治疗病房(ICU)收治的成人感染性休克患者分为培训前(2007年1-9月)和培训后(2007年10月-2008年6月)两个阶段进行感染性休克集束治疗.分析6 h及24 h感染性休克集柬治疗各指标与预后的关系;采用多元回归分析方法,筛选出集束治疗对感染性休克预后影响的独立相关因素,并研究两个阶段感染性休克集束治疗的依从性、机械通气时间、ICU住院时间以及28 d病死率.结果 研究期间共收治符合条件的感染性休克患者100例,其中培训前51例,培训后49例;存活36例,死亡64例.多元回归分析显示,6 h早期目标导向治疗(EGDT)、24 h EGDT是与感染性休克28 d病死率相关的两个独立保护因素,优势比(OR)分别为0.046和0.120(P均<0.01).培训后集束治疗依从性均有明显提高,其中6 h EGDT和24 h EGDT分别从19.6%、35.3%提升至55.1%、65.3%(P均<0.01).培训后机械通气时间[(166.6±156.4)h比(113.6±73.6)h3、ICU住院时间[(9.4±7.6)d比(6.0±3.9)d]及28 d病死率(72.5%比55.1%)较培训前明显缩短(P<0.05或P<0.01).结论 继续教育培训可提高医务人员对感染性休克集束治疗的依从性,降低感染性休克患者的病死率.     

心肌脂肪酸结合蛋白在脓毒症临床预后的预测价值研究

目的 探讨心肌脂肪酸结合蛋白(heart-type fatty acid-binding protein,H-FABP)在脓毒症患者临床预后的预测价值,提高脓毒症患者救治率.方法 采用前瞻性病例对照研究,纳入2014年10月至2015年10月就诊于新疆医科大学第一附属医院脓毒血症患者共50例,根据2012年脓毒症诊疗指南分为脓毒症组(16例)、严重脓毒症组(14例)、脓毒性休克组(20例);根据28 d后是否存活分为死亡组(22例)与存活组(28例).记录性别、年龄、族别等基本资料,入急诊6h内完善急性生理与慢性健康状况(APACHEⅡ)评分,H-FABP,B型脑钠利肽(B-typenatriuretic,BNP)、肌酸激酶(creatine kinase,CK)、肌酸激酶同工酶(creatine kinase isoenzymes,CK-MB)、肌钙蛋白(troponin-T,cTn-T)等指标.统计学采用SPSS 21.0软件,计量资料t检验或秩和检验、计数资料采用x2检验,非正态分布资料采用秩合检验,对生存状况进行ROC曲线分析.结果 脓毒性休克组的H-FABP明显高于严重脓毒症组和脓毒症组(P＜0.01).脓毒性休克组28天死亡率(80％)与严重脓毒症组28 d病死率高于脓毒症组28天死亡率(12.5％)(P＜0.01).死亡组H-FABP、BNP、cTn-T、CK、CK-MB均明显高于存活组,两组间差异具有统计学意义(P＜0.05);对H-FABP和BNP行ROC曲线结果提示H-FABP (AUC=0.748,P=0.003,95％CI:0.605 ～0.890)优于BNP (AUC =0.714,P=0.010,95％ CI:0.573 ～0.856),当H-FABP取 9.902 ng/mL,敏感度82.1％,特异度63.6％.H-FABP对28 d病死率的预测具有一定价值.结论 脓毒性休克组病死率明显高于严重脓毒血症及脓毒症组.H-FABP相比BNP、CK、CK-MB,对脓毒症患者预后具有较大的预测价值,随病情加重而增高.H-FABP可以预测28 d病死率.     

Initial fractal exponent of heart rate variability is associated with success of early resuscitation in patients with severe sepsis or septic shock: a prospective cohort study

Introduction

Heart rate variability (HRV) reflects autonomic nervous system tone as well as the overall health of the baroreflex system. We hypothesized that loss of complexity in HRV upon intensive care unit (ICU) admission would be associated with unsuccessful early resuscitation of sepsis.

Methods

We prospectively enrolled patients admitted to ICUs with severe sepsis or septic shock from 2009 to 2011. We studied 30 minutes of electrocardiogram, sampled at 500 Hz, at ICU admission and calculated heart rate complexity via detrended fluctuation analysis. Primary outcome was vasopressor independence at 24 hours after ICU admission. Secondary outcome was 28-day mortality.

Results

We studied 48 patients, of whom 60% were vasopressor independent at 24 hours. Five (10%) died within 28 days. The ratio of fractal alpha parameters was associated with both vasopressor independence and 28-day mortality (P = .04) after controlling for mean heart rate. In the optimal model, Sequential Organ Failure Assessment score and the long-term fractal α parameter were associated with vasopressor independence.

Conclusions

Loss of complexity in HRV is associated with worse outcome early in severe sepsis and septic shock. Further work should evaluate whether complexity of HRV could guide treatment in sepsis.     

Lenercept (p55 tumor necrosis factor receptor fusion protein) in severe sepsis and early septic shock: a randomized, double-blind, placebo-controlled, multicenter phase III trial with 1,342 patients

OBJECTIVE: Phase III study to confirm a trend observed in a previous phase II study showing that a single dose of lenercept, human recombinant p55 tumor necrosis factor receptor-immunoglobulin G1 (TNFR55-IgG1) fusion protein, decreased mortality in patients with severe sepsis or early septic shock. DESIGN: Multicenter, double-blind, phase III, placebo-controlled, randomized study. SETTING: A total of 108 community and university-affiliated hospitals in the United States (60), Canada (6) and Europe (42). PATIENTS: A total of 1,342 patients were recruited who fulfilled the entry criteria within the 12-hr period preceding the study drug administration. INTERVENTION: After randomization, an intravenous dose of 0.125 mg/kg lenercept or placebo was given. The patient was monitored for up to 28 days, during which standard diagnostic, supportive, and therapeutic care was provided. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was 28-day all-cause mortality. Baseline characteristics were as follows: a total of 1,342 patients were randomized; 662 received lenercept and 680 received placebo. The mean age was 60.5 yrs (range, 17-96 yrs); 39% were female; 65% had medical admissions, 8% had scheduled surgical admissions, and 27% had unscheduled surgical admissions; 73% had severe sepsis without shock, and 27% had severe sepsis with early septic shock. Lenercept and placebo groups were similar at baseline with respect to demographic characteristics, simplified acute physiology score II-predicted mortality, profiles of clinical site of infection and microbiological documentation, number of dysfunctioning organs, and interleukin-6 (IL-6) plasma concentration. Lenercept pharmacokinetics were similar in severe sepsis and early septic shock patients. Tumor necrosis factor was bound in a stable manner to lenercept as reflected by the accumulation of total serum tumor necrosis factor alpha concentrations. There were 369 deaths, 177 on lenercept (27% mortality) and 192 on placebo (28% mortality). A one-sided Cochran-Armitage test, stratified by geographic region and baseline, predicted 28-day all-cause mortality (simplified acute physiology score II), gave a p value of .141 (one-sided). Lenercept treatment had no effect on incidence or resolution of organ dysfunctions. There was no evidence that lenercept was detrimental in the overall population. CONCLUSION: Lenercept had no significant effect on mortality in the study population.     

One-year mortality of bloodstream infection-associated sepsis and septic shock among patients presenting to a regional critical care system

Objective The long-term mortality outcome associated with sepsis and septic shock has not been well defined in a nonselected critically ill population. This study investigated the occurrence and the role of bloodstream infection (BSI) associated sepsis and septic shock at time of intensive care unit (ICU) admission on the 1-year mortality of patients admitted to a regional critical care system.Design and setting Population-based inception cohort in all adult multidisciplinary and cardiovascular ICUs in the Calgary Health Region (population approx. 1 million) between 1 July 1999 and 31 March 2002.Patients and participants Adults (18 years; n=4,845) who had at least one ICU admission to CHR ICUs.Results In 251 (5%) patients there was BSI-associated sepsis at presentation to ICU, and 159 of these also had septic shock. The 28-day, 90-day, and 1-year mortality rates overall were 18%, 21%, and 24%: 23%, 30%, and 36% for BSI-associated sepsis without shock, and 51%, 57%, and 61% with shock, respectively. Surgical diagnosis, BSI-associated sepsis, and increasing age were independently associated with late (28-day to 1-year) mortality whereas higher APACHE II and TISS scores were associated with reduced odds in logistic regression analysis.Conclusions BSI-associated sepsis and septic shock are associated with increased risk of mortality persisting after 28-days up to 1 year or more. Follow-up duration beyond 28 days better defines the burden of illness associated with these syndromes.Electronic Supplementary Material Electronic supplementary material to this paper can be obtained by using the Springer Link server located at .     

Plasmapheresis in severe sepsis and septic shock: a prospective,randomised, controlled trial

OBJECTIVE: To determine the therapeutic efficacy and safety of plasmapheresis in the treatment of patients with severe sepsis and septic shock. DESIGN: Prospective, randomised, clinical trial with a planned, midstudy, interim analysis. SETTING: Intensive care unit in a university hospital in Archangels, Russia. PATIENTS: Consecutive patients with severe sepsis or septic shock. INTERVENTIONS: One hundred and six patients were randomised to receive either standard therapy or an add-on treatment with plasmapheresis. MEASUREMENTS AND RESULTS: The primary endpoint was 28-day survival. Septic shock was diagnosed in 57% of the plasmapheresis-treated patients and 54% of the control patients. Mean APACHE III score at entry was 56.4 in the plasmapheresis group and 53.5 in the control group. The 28-day, all-cause mortality rate was 33.3% (18/54) in the plasmapheresis group and 53.8% (28/52) in the control group. This represents a relative risk for fatal outcome in the plasmapheresis group of 0.61, an absolute risk reduction of 20.5% and a number of patients needed to treat of 4.9. Apart from six transient episodes of hypotension and one allergic reaction to fresh frozen plasma, no adverse reactions were attributable to the plasmapheresis treatment in this study. CONCLUSIONS: Plasmapheresis may be an important adjuvant to conventional treatment to reduce mortality in patients with severe sepsis or septic shock. Plasmapheresis is a safe procedure in the treatment of septic patients. A prospective randomised multicentre trial is warranted to confirm our results and to determine which subgroups of septic patients will benefit most from this treatment modality.     

Elevated plasma levels of heparin-binding protein in intensive care unit patients with severe sepsis and septic shock

ABSTRACT: INTRODUCTION: Rapid detection of, and optimized treatment for, severe sepsis and septic shock is crucial for successful outcome. Heparin-binding protein (HBP), a potent inducer of increased vascular permeability, is a potentially useful biomarker for predicting outcome in patients with severe infections. Our aim was to study the systemic release and dynamics of HBP in the plasma of patients with severe sepsis and septic shock in the ICU. METHODS: A prospective study was conducted of two patient cohorts treated in the ICU at Karolinska University Hospital Huddinge in Sweden. A total of 179 patients was included, of whom 151 had sepsis (126 with septic shock and 25 patients with severe sepsis) and 28 a non-septic critical condition. Blood samples were collected at five time points during six days after admission. RESULTS: HBP levels were significantly higher in the sepsis group as compared to the control group. At admission to the ICU, a plasma HBP concentration of ≥15 ng/mL and/or a HBP (ng/mL)/white blood cell count (109/L) ratio of >2 was found in 87.2% and 50.0% of critically ill patients with sepsis and non-septic illness, respectively. A lactate level of >2.5 mmol/L was detected in 64.9% and 56.0% of the same patient groups. Both in the sepsis group (n = 151) and in the whole group (n = 179), plasma HBP concentrations at admission and in the last measured sample within the 144 hour study period were significantly higher among 28-day non-survivors as compared to survivors and in the sepsis group, an elevated HBP-level at baseline was associated with an increased case-fatality rate at 28 days. CONCLUSIONS: Plasma HBP levels were significantly higher in patients with severe sepsis or septic shock compared to patients with a non-septic illness in the ICU. HBP was associated with severity of disease and an elevated HBP at admission was associated with an increased risk of death. HBP that rises over time may identify patients with a deteriorating prognosis. Thus, repeated HBP measurement in the ICU may help monitor treatment and predict outcome in patients with severe infections.     

Endotoxin concentration in neutropenic patients with suspected gram-negative sepsis: correlation with clinical outcome and determination of anti-endotoxin core antibodies during therapy with polyclonal immunoglobulin M-enriched immunoglobulins.

We carried out a study in patients with severe neutropenia from hematologic malignancy and suspected gram-negative sepsis to evaluate the clinical significance of endotoxin concentrations in plasma before and during a therapeutic intervention with a human polyclonal immunoglobulin M (IgM)-enriched immunoglobulin preparation (Pentaglobin; Biotest, Dreieich, Germany). Twenty-one patients with acute leukemia or non-Hodgkin's lymphoma entered the study upon the development of clinical signs of gram-negative sepsis and received the IgM-enriched immunoglobulin preparation every 6 h for 3 days (total dose, 1.3 liter with 7.8 g of IgM, 7.8 g of IgA, and 49.4 g of IgG), in addition to standardized antibiotic treatment. Concentrations of endotoxin and IgM and IgG antibodies against lipid A and Re lipopolysaccharide (LPS) in plasma were determined by a modified chromogenic Limulus amebocyte lysate test and semiquantitative enzyme linked immunosorbent assay, respectively, before each immunoglobulin infusion and during the following 25 days. Seventeen patients were endotoxin positive; in five of these patients, gram-negative infection was confirmed by microbiologic findings. Prior to therapy, endotoxemia correlated significantly with the occurrence of fever, and a quantitative correlation between the endotoxin concentration and body temperature was found during the individual course of infection in 8 of the 17 patients. Overall mortality from endotoxin-positive sepsis was 41% (7 of 17) and 64% (7 of 11) in patients with symptoms of septic shock. Nonsurvivors had significantly higher maximum concentration of endotoxin in plasma compared with those of survivors at the first study day (median of 126 versus 34 pg/ml; P < 0.05) and during the whole septic episode (median of 126 versus 61 pg/ml; P < 0.05). In survivors, immunoglobulin therapy resulted in a significant decrease in endotoxin levels in plasma within the initial 18-h treatment period, from a pretreatment median value of 28 pg/ml to a value of 8 pg/ml (P< 0.05). In the seven patients who died from uncontrollable infection, no effect of therapy on endotoxin levels in plasma was observed. IgM and IgG antibodies against lipid A and Re LPS increased significantly under immunoglobulin treatment, with significant correlations between antibodies against lipid A and Re LPS. These data strongly suggest a prognostic significance of the endotoxin levels in plasma and a potential effect of treatment with a polyclonal IgM-enriched immunoglobulin preparation. Further studies are needed to substantiate these findings and to assess the impact on the clinical course by way of a prospective placebo-controlled clinical trial.     

严重感染患者下丘脑-垂体-靶腺轴功能的早期改变

目的研究严重感染患者下丘脑-垂体-靶腺（HPTG）轴功能早期改变及其对病情危重程度和临床预后的影响。方法选择10例严重全身性感染患者（感染组）和12例感染性休克患者（休克组）在病程早期（确诊后1、3和5d）应用化学免疫发光法测定皮质醇（F）、三碘甲状腺原氨酸（T3）、甲状腺素（T4）、促甲状腺激素（TSH）、生长激素（GH）、催乳激素（PRL）、卵泡刺激素（FSH）和黄体生成素（LH）的血清含量以及促肾上腺皮质激素（ACTH）的血浆含量;同期选择12例非感染、非休克患者（对照组）进行对照分析。确诊后1d留取激素测定标本后,通过1μgACTH刺激试验评价严重感染患者下丘脑-垂体-肾上腺轴（HPAA）功能。结果感染组和休克组的ACTH、T3、T4、GH、FSH、LH和PRL均较对照组发生明显改变（P〈0.05或P〈0.01）,1μgACTH刺激试验结果显示,感染组无反应6例,有反应3例;休克组无反应9例,有反应2例,两组比较差异无显著性（P〉0.05）;以急性生理学与慢性健康状况评分系统（APACHE）和全身性感染相关器官功能衰竭评分系统（SOFA）为标准,ACTH、T3、T4、GH和PRL的变化与严重感染患者病情危重程度密切相关（P〈0.05或P〈0.01）;存活组与死亡组ACTH、T3、T4的差异非常显著（P〈0.05或P〈0.01）;ACTH、T4和SOFA评分与严重感染患者28d住院病死率独立相关（P〈0.05或P〈0.01）。结论严重感染发生早期出现的HPTG轴功能改变与患者病情危重程度及住院病死率密切相关。     

Brain natriuretic peptide: A marker of myocardial dysfunction and prognosis during severe sepsis

OBJECTIVE: To investigate the value of brain natriuretic peptide plasma levels as a marker of systolic myocardial dysfunction during severe sepsis and septic shock. DESIGN: Prospective observational study. SETTING: Intensive care unit. PATIENTS: A total of 34 consecutive patients with severe sepsis (nine patients) or septic shock (25 patients) without previous cardiac, respiratory, or chronic renal failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Myocardial systolic performance was assessed by fractional area contraction (FAC) using echocardiography performed on days 2 (FACD2) and 8. Plasma levels of brain natriuretic peptide were measured at days 1-4 and 8 after the beginning of severe sepsis. Among 34 patients (Simplified Acute Physiology Score II, 43 +/- 2.5), 15 (44%) presented with initial myocardial dysfunction (FACD2 < 50%). Lungs were the origin of sepsis in 65% of patients. The 28-day mortality was 29%. Comparisons were performed between patients with (FACD2 < 50%) and without (FACD2 > or = 50%) myocardial dysfunction. Plasma levels of brain natriuretic peptide were significantly higher in patients with FACD2 < 50% than in those with FACD2 > or = 50% (p <.05) from day 2 to day 4. Brain natriuretic peptide levels were also significantly higher on days 2 and 3 in patients who died during their intensive care unit stay (p <.05). CONCLUSIONS: Systolic myocardial dysfunction is present in 44% of patient with severe sepsis or septic shock. In this setting, brain natriuretic peptide seems useful to detect myocardial dysfunction, and high plasma levels appear to be associated with poor outcome of sepsis, but further studies are needed.     

Sepsis incidence and outcome: contrasting the intensive care unit with the hospital ward

OBJECTIVE: To describe the outcome of patients with sepsis according to location on a ward or in an intensive care unit. DESIGN: Prospective multicentered observational study. SETTING: Three academic hospitals in Madrid, Spain. PATIENTS: Consecutive patients with sepsis admitted to participating hospitals from March 1 to June 30, 2003. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During the study period, 15,852 patients >18 yrs of age were admitted. Sepsis was identified in 702 patients, giving an estimated cumulative incidence rate of 367 cases per 100,000 adult area residents per year and a cumulative incidence rate among patients admitted to the hospital of 4.4%. Most septic patients had a community-acquired infection (71%). Severe sepsis developed in 199 patients (incidence rate, 104 cases per 100,000 adult area residents per year), and 59 patients developed septic shock (incidence rate, 31 cases per 100,000 adult area residents per year). Most of the patients met the criteria for severe sepsis or septic shock on the same day that they would have qualified for the septic status one step down the scale. In the other patients, the median time between sepsis and severe sepsis was 2 days (interquartile range, 2-5) and between severe sepsis and septic shock was 3 days (interquartile range, 1-4). Only 32% of severe sepsis patients received intensive care. The hospital mortality for all septic patients was 12.8%; for severe sepsis, 20.7%; and for septic shock, 45.7%. CONCLUSIONS: This study shows the high incidence of sepsis in a general population of patients admitted to hospital. A significant proportion of patients with severe sepsis are not transferred to the intensive care unit.     

Disease Progression in Hemodynamically Stable Patients Presenting to the Emergency Department With Sepsis

Background: Aggressive diagnosis and treatment of patients presenting to the emergency department (ED) with septic shock has been shown to reduce mortality. To enhance the ability to intervene in patients with lesser illness severity, a better understanding of the natural history of the early progression from simple infection to more severe illness is needed. Objectives: The objectives were to 1) describe the clinical presentation of ED sepsis, including types of infection and causative microorganisms, and 2) determine the incidence, patient characteristics, and mortality associated with early progression to septic shock among ED patients with infection. Methods: This was a multicenter study of adult ED patients with sepsis but no evidence of shock. Multivariable logistic regression was used to identify patient factors for early progression to shock and its association with 30‐day mortality. Results: Of 472 patients not in shock at ED presentation (systolic blood pressure > 90 mm Hg and lactate < 4 mmol/L), 84 (17.8%) progressed to shock within 72 hours. Independent factors associated with early progression to shock included older age, female sex, hyperthermia, anemia, comorbid lung disease, and vascular access device infection. Early progression to shock (vs. no progression) was associated with higher 30‐day mortality (13.1% vs. 3.1%, odds ratio [OR] = 4.72, 95% confidence interval [CI] = 2.01 to 11.1; p ≤ 0.001). Among 379 patients with uncomplicated sepsis (i.e., no evidence of shock or any end‐organ dysfunction), 86 (22.7%) progressed to severe sepsis or shock within 72 hours of hospital admission. Conclusions: A significant portion of ED patients with less severe sepsis progress to severe sepsis or shock within 72 hours. Additional diagnostic approaches are needed to risk stratify and more effectively treat ED patients with sepsis. ACADEMIC EMERGENCY MEDICINE 2010; 17:383–390 © 2010 by the Society for Academic Emergency Medicine     

强制性脓毒症治疗流程对严重脓毒症和脓毒性休克预后影响

目的 研究强制性脓毒症治疗流程对严重脓毒症和脓毒性休克患者预后的影响.方法 前瞻性研究2008年6月至2009年12月就诊于两个三级教学医院急诊科的严重脓毒症及脓毒性休克患者195例;应用拯救脓毒症运动标准数据库(SSC database)研究脓毒症患者临床的特点、治疗和预后.纳人标准:符合SSC database诊断标准.2008年6月至12月就诊患者进行现况调查,依据临床医师经验治疗,为对照组.2009年1月至12月间就诊患者采用强制性脓毒症治疗流程治疗,即治疗组.比较强制性脓毒症治疗流程实施前后两组住院病死率.采用SPSS 15.0软件进行数据分析.组间比较采用独立样本t检验.计数资料以率和构成比表示,采用χ2检验.用Kaplan-Meier进行生存曲线分析,以P＜0.05为差异具有统计学意义.结果 治疗组[98.3%(115/117)]与对照组[2.56%(2/78)]比较显著提高血乳酸的检测率(P＜0.01);治疗组69.2%(81/117)患者可以在来诊3 h内给予抗生素,对照组为35.8%(28/78)(P＜0.01);治疗组[47.9%(56/117)]与对照组[25.6%(20/78)]比较显著增加抗生素应用前血培养送检率(P=0.003);治疗组[80.3%(53/66)]与对照组[27%(10/37)]比较显著增加标准液体复苏率,P＜0.01;治疗组[8.1%(3/37)]与对照组[27.3%(18/66)]比较中心静脉压达标率增加(P=0.023);治疗组[29.1%(34/117)]与对照组[44.8%(35/78)]比较住院病死率显著下降(P=0.032).结论 强制性实施脓毒症治疗流程提高了严重脓毒症和脓毒性休克标准治疗依从性,住院病死率下降15.7%.

Abstract：

Objective To study the impact of therapy strategy on outcomes of patients suffering from severe sepsis and/or septic shock. Method A total of 195 patients diagnosed as severe sepsis or septic shock were enrolled for prospective study from June 2008 to December 2009. Patient's clinical manifestation,treatments and outcomes were studied by using SSC database. Patients were divided into control group and treatment group. In control group, patients enrolled from June 2008 to December 2008, were treated with conventional medical care In treatment group, patients enrolled from January 2009 to December 2009 were treated with a novel algorithm of mandatory treatment for sepsis In-hospital mortality of two groups was compared. SPSS15.0 software was used for analysis of data. Chi-square test and unpaired t-test were used for comparisons between groups. Results Compared to the control group The need for blood lactate test was significantly grown in treatment group [98.2% (115/117) versus 2.56% (2/78), P ＜ 0.001]. Antibiotics was administered to 69.2% (81/117) patients of treatment group within 3 hours after their arrival at the emergency department compared to 35.8% (28/78) in the control group (P ＜ 0. 001). Blood cultures made before antibiotics given were 47.9% (56/117) in the treatment group compared to the control group 25.6%(20/78), P = 0. 003. The rate of fluid resuscitation was 80.3% (53/66) in the treatment group and 27%(10/37) in the control group, P ＜0.001. The rate of CVP (8 mmHg was 27.3% (18/66) in the treatment group and 8.1% (3/37) in the control group, P = 0. 023. In-hospital mortality was 29.1% (34/117) in the treatment group and 44.8% (35/78) in the control group, P =0. 032. Conclusions The algorithm of mandatory treatment for sepsis improved the therapeutic efficacy of the treatment for severe sepsis and septic shock, decreasing in-hospital mortality.     

Prognostic performance of disease severity scores in patients with septic shock presenting to the emergency department

BackgroundAn accurate disease severity score that can quickly predict the prognosis of patients with sepsis in the emergency department (ED) can aid clinicians in distributing resources appropriately or making decisions for active resuscitation measures. This study aimed to compare the prognostic performance of quick sequential organ failure assessment (qSOFA) with that of other disease severity scores in patients with septic shock presenting to an ED.MethodsWe performed a prospective, observational, registry-based study. The discriminative ability of each disease severity score to predict 28-day mortality was evaluated in the overall cohort (which included patients who fulfilled previously defined criteria for septic shock), the newly defined sepsis subgroup, and the newly defined septic shock subgroup.ResultsA total of 991 patients were included. All disease severity scores had poor discriminative ability for 28-day mortality. The sequential organ failure assessment and acute physiology and chronic health evaluation II scores had the highest area under the receiver-operating characteristic curve (AUC) values, which were significantly higher than the AUC values of other disease severity scores in the overall cohort and the sepsis and septic shock subgroups. The discriminative ability of each disease severity score decreased as the mortality rate of each subgroup increased.ConclusionsAll disease severity scores, including qSOFA, did not display good discrimination for 28-day mortality in patients with serious infection and refractory hypotension or hypoperfusion; additionally, none of the included scoring tools in this study could consistently predict 28-day mortality in the newly defined sepsis and septic shock subgroups.     

Diagnostic value and prognostic evaluation of Presepsin for sepsis in an emergency department

Introduction

Presepsin levels are known to be increased in sepsis. The aim of this study was to evaluate the early diagnostic and prognostic value of Presepsin compared with procalcitonin (PCT), Mortality in Emergency Department Sepsis (MEDS) score and Acute Physiology and Chronic Health Evaluation II (APACHE II) score in septic patients in an emergency department (ED) and to investigate Presepsin as a new biomarker of sepsis.

Methods

This study enrolled 859 consecutive patients with at least two diagnostic criteria for systemic inflammatory response syndrome (SIRS) who were admitted to Beijing Chao-yang Hospital ED from December 2011 to October 2012, and 100 age-matched healthy controls. Patients were stratified into four groups: SIRS, sepsis, severe sepsis, and septic shock. Plasma Presepsin and serum PCT were measured, and MEDS score and APACHE II score were calculated at enrollment. Comparisons were analyzed using the Kruskal-Wallis and Mann–Whitney U tests.

Results

On admission, the median levels of plasma Presepsin increased with sepsis severity. The areas under the receiver operating characteristic (AUC) curves of Presepsin were greater than those of PCT in diagnosing sepsis, and predicting severe sepsis and septic shock. The AUC of Presepsin for predicting 28-day mortality in septic patients was slightly lower than that of PCT, MEDS score and APACHE II score. The AUC of a combination of Presepsin and MEDS score or APACHE II score was significantly higher than that of MEDS score or APACHE II score alone in predicting severe sepsis, and was markedly higher than that of Presepsin alone in predicting septic shock and 28-day mortality in septic patients, respectively. Plasma Presepsin levels in septic patients were significantly higher in non-survivors than in survivors at 28 days’ follow-up. Presepsin, MEDS score and APACHE II score were found to be independent predictors of severe sepsis, septic shock and 28-day mortality in septic patients. The levels of plasma Presepsin were positively correlated with PCT, MEDS score and APACHE II score in every septic group.

Conclusion

Presepsin is a valuable biomarker for early diagnosis of sepsis, risk stratification, and evaluation of prognosis in septic patients in the ED.     

Dopamine versus norepinephrine in the treatment of shock

CLINICAL QUESTION: Which vasopressor agent, norepinephrine or dopamine, is superior in the treatment of shock? ARTICLE CHOSEN: De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 2010;362:779-89. STUDY OBJECTIVE: The authors of this study set out to compare 28-day mortality in patients with shock who were treated with either dopamine or norepinephrine as initial vasopressor therapy. The authors' secondary outcome measures included mortality beyond 28 days and adverse events associated with each agent.     

Impact of recent intravenous chemotherapy on outcome in severe sepsis and septic shock patients with hematological malignancies

Objective To compare the characteristics and outcome of patients with hematological malignancies referred to the ICU with severe sepsis and septic shock who had or had not received recent intravenous chemotherapy, defined as within 3 weeks prior to ICU admission. Design and setting Retrospective observational cohort study on prospectively collected data in a medical ICU of a university hospital. Patients 186 ICU patients with hematological malignancies with severe sepsis or septic shock (2000–2006). Measurements and results There were 77 patients admitted with severe sepsis and 109 with septic shock; 91 (49%) had received recent intravenous chemotherapy. Patients with recent chemotherapy more often had a high-grade malignancy and were more often neutropenic, less often had pulmonary infiltrates, and less often required mechanical ventilation. ICU, 28-day, in-hospital, and 6-month mortality rates were 33% vs. 48.4%, 40.7% vs. 57.4%, 45.1% vs. 58.9%, and 50.5% vs. 63.2% in patients with and without recent chemotherapy, respectively. Logistic regression identified four variables independently associated with 28-day mortality: SOFA score at ICU admission, pulmonary site of infection, and fungal infection were associated with worse outcome whereas previous intravenous chemotherapy was protective at borderline significance. After adjustment with a propensity score for recent chemotherapy, chemotherapy was not associated with outcome. Conclusions Patients referred to the ICU with severe sepsis and septic shock complicating active chemotherapeutic treatment have better prognosis than commonly perceived. This article is discussed in the editorial available at: .     

Urinary liver-type fatty acid-binding protein in septic shock: effect of polymyxin B-immobilized fiber hemoperfusion

We aimed to determine retrospectively whether urinary liver-type fatty acid-binding protein (L-FABP) levels are altered in patients with septic shock or severe sepsis without shock and whether polymyxin B-immobilized fiber (PMX-F) hemoperfusion affects these levels. Forty patients with septic shock, 20 patients with severe sepsis without shock, 20 acute renal failure (ARF) patients without septic shock (mean serum creatinine, 2.8 mg/dL), and 30 healthy volunteers were included in this study. Polymyxin B-immobilized fiber hemoperfusion was performed twice in 40 patients. In addition, 10 patients with septic shock without PMX-F treatment (conventional treatment) were also enrolled in this study. Their families did not choose PMX-F treatment. Thus, their informed consents to perform PMX-F treatment were not obtained. Septic shock or severe sepsis was defined by the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee. Patients with septic shock were eligible for inclusion in the study if they had a definable source of infection and/or positive blood cultures. Patients with cardiogenic or hemorrhagic shock were excluded from the study. The patients were not randomly allocated to receive PMX-F treatment. Urinary and serum L-FABP levels were measured by enzyme-linked immunosorbent assay method. Plasma endotoxin levels in patients with septic shock were significantly higher than those in patients with severe sepsis (P < 0.05), patients with ARF (P < 0.001), and healthy subjects (P < 0.001). Urinary L-FABP levels in patients with septic shock were significantly higher than those in patients with severe sepsis without shock (P < 0.001), patients with ARF (P < 0.001), and healthy subjects (P < 0.001), whereas serum L-FABP levels showed no significant differences between patients with septic shock, patients with severe sepsis, patients with ARF, and healthy subjects. Urinary L-FABP was not correlated with serum L-FABP. Twenty-eight patients with septic shock survived, and 12 patients died. Polymyxin B-immobilized fiber treatment reduced plasma endotoxin levels (P < 0.01) and urinary L-FABP levels (P < 0.01). In 10 patients with septic shock without PMX-F treatment, L-FABP levels remained high 7 days after initiation of conventional treatment (P = 0.12). These results suggest that urinary L-FABP levels are significantly increased in patients with septic shock and that PMX-F treatment is effective in reducing these levels.