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.     

Selenium in Intensive Care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock

OBJECTIVE: Sepsis is associated with an increase in reactive oxygen species and low endogenous antioxidative capacity. We postulated that high-dose supplementation of sodium-selenite would improve the outcome of patients with severe sepsis and septic shock. DESIGN: Prospective randomized, placebo-controlled, multiple-center trial. SETTING: Eleven intensive care units in Germany. PATIENTS: Patients were 249 patients with severe systemic inflammatory response syndrome, sepsis, and septic shock and an Acute Physiology and Chronic Health Evaluation (APACHE) III score >70. INTERVENTIONS: Patients received 1000 microg of sodium-selenite as a 30-min bolus injection, followed by 14 daily continuous infusions of 1000 microg intravenously, or placebo. MEASUREMENTS AND MAIN RESULTS: The primary end point was 28-day mortality; secondary end points were survival time and clinical course of APACHE III and logistic organ dysfunction system scores. In addition, selenium levels in serum, whole blood, and urine as well as serum glutathione-peroxidase-3 activity were measured. From 249 patients included, 11 patients had to be excluded. The intention-to-treat analysis of the remaining 238 patients revealed a mortality rate of 50.0% in the placebo group and 39.7% in the selenium-treated group (p = .109; odds ratio, 0.66; confidence interval, 0.39-1.1). A further 49 patients had to be excluded before the final analysis because of severe violations of the study protocol. In the remaining 92 patients of the study group, the 28-day mortality rate was significantly reduced to 42.4% compared with 56.7% in 97 patients of the placebo group (p = .049, odds ratio, 0.56; confidence interval, 0.32-1.00). In predefined subgroup analyses, the mortality rate was significantly reduced in patients with septic shock with disseminated intravascular coagulation (n = 82, p = .018) as well as in the most critically ill patients with an APACHE III score > or =102 (>75% quartile, n = 54, p = .040) or in patients with more than three organ dysfunctions (n = 83, p = .039). Whole blood selenium concentrations and glutathione peroxidase-3 activity were within the upper normal range during selenium treatment, whereas they remained significantly low in the placebo group. There were no side effects observed due to high-dose sodium-selenite treatment. CONCLUSIONS: The adjuvant treatment of patients with high-dose sodium-selenite reduces mortality rate in patients with severe sepsis or septic shock.     

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.     

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: .     

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.     

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.     

Can corticosteroids reduce the mortality of patients with severe sepsis? A systematic review and meta-analysis

BackgroundThe effects of corticosteroids on clinical outcomes of patients with sepsis remains controversial. We aimed to further determine the effectiveness of corticosteroids in reducing mortality in adult patients with severe sepsis by comparison with placebo.MethodsPubmed, Embase, Medline, Cochrane Central Register of Controlled Trials (CENTRAL) as well as the Information Sciences Institute (ISI) Web of Science were searched for all controlled studies that compared corticosteroids and placebo in adult patients with severe sepsis. The primary outcome was the mortality 28-day mortality and the secondary outcomes were mortality at longest follow up, occurrence, and reoccurrence of septic shock.ResultsA total of 19 trials involving 7035 patients were pooled in our final analyses. No significant heterogeneity was found in any of the outcome measures. Compared with placebo, corticosteroids were associated with a lower 28-day mortality (RR 0.91, 95% CI 0.85–0.98, Z = 2.57, P = 0.01) both in patients having sepsis and in those who developed septic shock (RR 0.92, 95% CI 0.85–0.99, Z = 2.19, P = 0.03), while no significant difference was found in mortality with the longest follow up in patients either having sepsis (RR 0.94, 95% CI 0.89–1.00, Z = 1.93, P = 0.05), or occurrence (RR 0.83, 95% CI 0.56–1.24, Z = 0.90, P = 0.37) or reoccurrence of septic shock (RR 1.08, 95% CI 1.00–1.16, Z = 1.89, P = 0.06).ConclusionsCorticosteroids were effective in reducing the 28-day mortality in patients with severe sepsis and in those with septic shock.     

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.     

Clinical spectrum, frequency, and significance of myocardial dysfunction in severe sepsis and septic shock

ObjectiveTo determine the frequency and spectrum of myocardial dysfunction in patients with severe sepsis and septic shock using transthoracic echocardiography and to evaluate the impact of the myocardial dysfunction types on mortality.Patients and MethodsA prospective study of 106 patients with severe sepsis or septic shock was conducted from August 1, 2007, to January 31, 2009. All patients underwent transthoracic echocardiography within 24 hours of admission to the intensive care unit. Myocardial dysfunction was classified as left ventricular (LV) diastolic, LV systolic, and right ventricular (RV) dysfunction. Frequency of myocardial dysfunction was calculated, and demographic, hemodynamic, and physiologic variables and mortality were compared between the myocardial dysfunction types and patients without cardiac dysfunction.ResultsThe frequency of myocardial dysfunction in patients with severe sepsis or septic shock was 64% (n=68). Left ventricular diastolic dysfunction was present in 39 patients (37%), LV systolic dysfunction in 29 (27%), and RV dysfunction in 33 (31%). There was significant overlap. The 30-day and 1-year mortality rates were 36% and 57%, respectively. There was no difference in mortality between patients with normal myocardial function and those with left, right, or any ventricular dysfunction.ConclusionMyocardial dysfunction is frequent in patients with severe sepsis or septic shock and has a wide spectrum including LV diastolic, LV systolic, and RV dysfunction types. Although evaluation for the presence and type of myocardial dysfunction is important for tailoring specific therapy, its presence in patients with severe sepsis and septic shock was not associated with increased 30-day or 1-year mortality.     

Red cell distribution width is a prognostic factor in severe sepsis and septic shock

ObjectiveThis study was performed to investigate the association of red cell distribution width (RDW) with 28-day mortality in patients with severe sepsis and septic shock.MethodsWe performed a retrospective analysis of patients with severe sepsis and septic shock. Patients' demographic data, comorbidities, the blood test results including RDW at admission to the emergency department, and Acute Physiologic and Chronic Health Evaluation II score were compared between 28-day survivors and nonsurvivors. Red cell distribution width was categorized into tertiles as 14% or less, 14.1% to 15.7%, and 15.8% or greater. Multivariate Cox proportional hazards regression analysis was performed to determine the risk factors for mortality.ResultsA total of 566 patients were included, and overall mortality was 29%. Red cell distribution width was significantly higher in nonsurvivors than in survivors, and the corresponding mortality of patients with an RDW of 14% or less, 14.1% to 15.7%, and 15.8% or greater was 13.1%, 30.1%, and 44.9%, respectively (P < .001). In Cox proportional hazards analysis, groups with higher RDW are independently associated with 28-day mortality compared with groups with an RDW of 14.0% or less: RDW 14.1% to 15.7% (hazard ratio, 1.66; 95% confidence interval [CI], 1.00-2.76) and RDW of 15.8% or greater (hazard ratio, 2.57; 95% CI, 1.53-4.34). The area under the receiver operating curve of RDW was 0.68 (95% CI, 0.63-0.72).ConclusionRed cell distribution width is associated with 28-day mortality in patients with severe sepsis and septic shock.     

Epidemiology of severe sepsis in Japanese intensive care units: A prospective multicenter study

Severe sepsis is a leading cause of morbidity and mortality in the intensive care unit (ICU). We conducted a prospective multicenter study to evaluate epidemiology and outcome of severe sepsis in Japanese ICUs. The patients were registered at 15 general critical care centers in Japanese tertiary care hospitals when diagnosed as having severe sepsis. Of 14,417 patients, 624 (4.3%) were diagnosed with severe sepsis. Demographic and clinical characteristics at enrollment (Day 1), physiologic and blood variables on Days 1 and 4, and mortality were evaluated. Mean age was 69.0 years, and initial mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were 23.4 and 8.6, respectively. The 28-day mortality was 23.1%, and overall hospital mortality was 29.5%. SOFA score and disseminated intravascular coagulation (DIC) score were consistently higher in nonsurvivors than survivors on Days 1 and 4. SOFA score, DIC score on Days 1 and 4, and hospital mortality were higher in patients with than without septic shock. SOFA score on Days 1 and 4 and hospital mortality were higher in patients with than without DIC. Logistic regression analyses showed age, presence of septic shock, DIC, and cardiovascular dysfunction at enrollment to be predictors of 28-day mortality and presence of comorbidity to be an additional predictor of hospital mortality. Presence of septic shock or DIC resulted in approximately twice the mortality of patients without each factor, whereas the presence of comorbidity may be a significant predictor of delayed mortality in severe sepsis.     

危重病严重脓毒症/脓毒性休克患者早期规范化液体复苏治疗——多中心、前瞻性、随机、对照研究

目的 探讨早期目标导向治疗(EGDT)对严重脓毒症/脓毒性休克患者的影响.方法 采用多中心、前瞻性、随机、对照研究方法,选择2005年1月至2008年1月浙江省8家三级甲等医院重症监护病房(ICU)住院的314例严重脓毒症/脓毒性休克患者,按随机数字表法分为常规组(151例)和EGDT组(163例).常规组以中心静脉压(CVP)、收缩压(SBP)和平均动脉压(MAP)、尿量变化指导液体复苏;EGDT组在此基础上增加中心静脉血氧饱和度(ScvO2)为观测指标进行复苏;对患者进行输液、输血和强等治疗,6 h内达标.比较两组患者28 d生存率、ICU住院病死率(主要终点)以及ICU住院时间、机械通气时间、抗生素使用时间、新发感染率和疾病严重程度评分(次要终点)的差异.结果 可供分析的有效病例中EGDT组为157例,常规组为146例.EGDT组28 d生存率较常规组增高约17.7%(75.2%比57.5%,P=0.001),EGDT组ICU住院病死率较常规组降低约15.7%(35.0%比50.7%,p=0.035).与常规组比较,EGDT能明显善患者的急性生理学与慢性健康状况评分系统Ⅱ(APACHEⅡ)评分(分:14.4±8.5比18.0±7.1,P=0.043)、多器官功能障碍综合征(MODS)评分(分:5.8±3.1比8.9±3.7,P=0.014)和感染相关器官功能衰竭评分系统(SOFA)评分(分:5.6±2.9比10.4±3.7,P=0.001),减少抗生素使用时间(d:13.4±10.0比19.7±13.5,P=0.004),降低新发感染的发生率(37.6%比53.4%,p=0.014);EGDT对ICU住院时间、机械通气间均无明显影响.结论 EGDT能显著改善ICU中严重脓毒症/脓毒性休克患者28 d生存率和临床疾病严重程度评分,减少抗生素使用时间及降低新发感染的发生率.     

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.     

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.     

Efficacy and safety of LY315920Na/S-5920, a selective inhibitor of 14-kDa group IIA secretory phospholipase A2, in patients with suspected sepsis and organ failure

OBJECTIVE: Concentrations of group IIA secretory phospholipase A, an inflammatory response mediator, are increased in the plasma of patients with sepsis and septic shock, and the extent of elevation is correlated with mortality. LY315920Na/S-5920 is a selective inhibitor of group IIA secretory phospholipase A that has been shown to inhibit serum group IIA secretory phospholipase A enzyme activity in patients with severe sepsis. The primary objectives of this study were to determine whether there was a dose-response relationship between two doses of LY315920Na/S-5920 compared with placebo in the reduction of 28-day all-cause mortality in patients with severe sepsis and to determine whether LY315920Na/S-5920 had an acceptable safety profile.(2) (2) (2) DESIGN: Multicenter, double-blind, placebo-controlled trial of two doses of LY315920Na/S-5920 in a parallel design. PATIENTS: A total of 586 patients with severe sepsis at 72 institutions in the United States.INTERVENTIONS Patients enrolled within 72 hrs from onset of first sepsis-induced organ failure were randomized (1:1:1) to low-dose LY315920Na/S-5920 (target plasma concentration of 200 ng/mL, n = 196), high-dose LY315920Na/S-5920 (800 ng/mL, n = 194), or placebo (n = 196). Study medication was administered as a constant-rate intravenous infusion for 168 hrs. MEASUREMENTS AND MAIN RESULTS: The study was stopped prematurely because it was unlikely that a statistically significant difference in mortality between LY315920Na/S-5920 and placebo would be found. There was no effect of LY315920Na/S-5920 on the primary end point of 28-day all-cause mortality across the entire study population. The 28-day all-cause mortality was distributed as follows: placebo group, 33.2% (65/196 patients); low-dose LY315920Na/S-5920, 37.2% (73/196); and high-dose LY315920Na/S-5920, 36.1% (70/194); p = .525. However, in a prospectively planned analysis, there was a favorable overall dose-response effect on 28-day all-cause mortality in patients administered LY315920Na/S-5920 within 18 hrs of onset of the first sepsis-induced organ failure. Among these patients, 28-day all-cause mortality was distributed as follows: placebo group, 43.5% (20/46 patients); low-dose LY315920Na/S-5920, 31.4% (16/51); and high-dose LY315920Na/S-5920, 20.8% (10/48); p = .018. CONCLUSIONS: Administration of LY315920Na/S-5920 had an acceptable safety profile in patients with severe sepsis. There was no overall survival benefit associated with the use of LY315920Na/S-5920 in this study. However, prospectively planned secondary analyses suggested that treatment with LY315920Na/S-5920 was associated with an improvement in survival in patients treated within 18 hrs of the first sepsis-induced organ failure.     

Effects of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in mechanically ventilated patients with severe sepsis and septic shock

OBJECTIVES: Enteral diets enriched with eicosapentaenoic acid (EPA), gamma-linolenic acid (GLA), and antioxidants have previously been shown to improve outcomes in patients with acute respiratory distress syndrome. Several studies using animal models of sepsis demonstrate that enteral nutrition enriched with omega-3 fatty acids reduces mortality rate. This study investigated whether an enteral diet enriched with EPA, GLA, and antioxidant vitamins can improve outcomes and reduce 28-day all-cause mortality in patients with severe sepsis or septic shock requiring mechanical ventilation. DESIGN: Prospective, double-blind, placebo-controlled, randomized trial. SETTING: Three different intensive care units of a tertiary hospital in Brazil. PATIENTS: The study enrolled 165 patients. INTERVENTIONS: Patients were randomized to be continuously tube-fed with either a diet enriched with EPA, GLA, and elevated antioxidants or an isonitrogenous and isocaloric control diet, delivered at a constant rate to achieve a minimum of 75% of basal energy expenditure x 1.3 during a minimum of 4 days. MEASUREMENTS AND MAIN RESULTS: Patients were monitored for 28 days. Patients who were fed with the study diet experienced a significant reduction in mortality rate compared with patients fed with the control diet, the absolute mortality reduction amounting to 19.4% (p = .037). The group who received the study diet also experienced significant improvements in oxygenation status, more ventilator-free days (13.4 +/- 1.2 vs. 5.8 +/- 1.0, p < .001), more intensive care unit (ICU)-free days (10.8 +/- 1.1 vs. 4.6 +/- 0.9, p < .001), and a lesser development of new organ dysfunctions (p < .001). CONCLUSIONS: In patients with severe sepsis or septic shock and requiring mechanical ventilation and tolerating enteral nutrition, a diet enriched with EPA, GLA, and elevated antioxidants contributed to better ICU and hospital outcomes and was associated with lower mortality rates.     

Treatment with IgM-enriched immunoglobulin in sepsis: a matched case-control analysis

The therapeutic potential of IgM-enriched immunoglobulin preparations (IgGAM) in sepsis remains a field of debate. The use of polyclonal immunoglobulins as adjuvant therapy (Esen & Tugrul, 2009; Kaukonen et al., 2014; Molnár et al., 2013; Taccone et al., 2009) has been shown to improve clinical outcomes in terms of mortality. This study analyze the impact of IgM-enriched IgG (IgGM) as additional immunomodulation. Patients and methods: This is a retrospective registry of 1196 patients with severe sepsis and septic shock from nine Intensive Care Units in Colombia, from routine clinical practice; 220 patients treated with IgGAM were registered. Fully matched comparators for severity and type of infection selected among patients non-treated with IgGAM. Mortality after 28 days was 30.5% among IgGAM-treated patients and 40.5% among matched comparators. Results: Multivariate Cox regression analysis showed IgGAM treatment to be the only variable protective from death after 28 days (hazard ratio 0.62; 0.45–0.86; p: 0.004). Results reinforce the importance of IgGAM treatment for favorable outcome after septic shock and are in line with recent published meta-analyses. This study showed that treatment with IgGM in patients with sepsis was an independent modulator of the 28-day associated with a lower mortality.     

纳美芬治疗感染性休克的临床疗效观察

目的 观察纳美芬治疗感染性休克患者的疗效.方法 选择2008年12月至2009年6月本院重症监护病房(ICU)收治的感染性休克早期患者20例,按随机数字表法均分成治疗组和对照组.两组均按照2008年国际严重感染和感染性休克治疗指南的要求进行常规抗休克治疗;治疗组早期静脉推注纳美芬,而对照组给予等量生理盐水.观察两组患者血流动力学、急性生理学与慢性健康状况评分系统Ⅱ(APACHE Ⅱ)评分及28 d病死率.结果 与对照组比较,治疗组治疗2、6、12、24 h时平均动脉压(MAP,mm Hg,1 mm Hg=0.133 kPa)明显升高(对照组:59.67±3.56、60.50±2.67、60.68±4.97、61.09±4.92,治疗组:65.83±5.76、70.83±5.76、83.63±5.87、82.85±8.36,均P＜0.05),心率(HR,次/min)明显下降(对照组:119.79±8.03、118.56±11.48、116.35±12.48、114.68±8.91,治疗组:103.33±10.87、92.29±12.55、90.49±17.29、86.66±11.53,均P＜0.05);治疗6、12、24 h时心排血指数(CI,L·min-1·m-2)明显升高(对照组:3.63±0.13、3.67±0.31、3.76±0.23,治疗组:4.01±0.45、4.22±0.39、4.45±0.32,均P＜0.05);治疗12 h、24 h时尿量(ml·kg-1·min-1)明显增多(对照组:0.53±0.39、0.51±0.40,治疗组:0.85±0.25、1.06±0.58,均P＜0.05),乳酸值(mmol/L)明显下降(对照组:5.54±3.98、4.91±2.98,治疗组:1.51±0.83、1.14±0.62,均P＜0.05).治疗组治疗24 h APACHE I评分(分)明显低于对照组(16.1±1.9比21.7±5.2,P＜0.05),但28 d病死率与对照组比较差异无统计学意义(20%比40%,P=0.629).结论 在常规抗休克治疗基础上早期应用纳美芬可以改善患者血流动力学,有利于抢救感染性休克,但对28 d病死率无明显影响.     

1小时集束治疗对感染性休克患者的预后影响

目的研究1 h集束治疗对感染性休克患者预后的影响。 方法采取前瞻性、多中心、队列临床研究的方法,纳入2018年1月至2019年12月间连续收治的扬州市江都人民医院及苏北人民医院重症医学科感染性休克患者,根据是否完成1 h集束治疗目标,分为1 h集束治疗组及对照组。比较2组患者的预后指标及28 d病死率、集束化治疗完成时间、机械通气时间、重症医学科住院时间等。 结果共纳入感染性休克患者332例,其中1 h集束治疗完成患者91例（27.4%,91/332）,1 h集束治疗未完成患者241例（72.6%,241/332）。1 h集束治疗完成患者28 d病死率（43.9%）明显低于1 h集束治疗未完成患者（58.9%）,差异有统计学意义（P＜0.05）。1 h集束治疗完成患者重症医学科住院天数［（7.2±2.9） d］低于1 h集束治疗未完成患者［（7.7±3.3） d］,但差异无统计学意义。 结论1 h集束治疗能降低感染性休克患者病死率,但医务人员对1 h集束治疗的依从性低,未来需要通过努力提高医务人员对感染性休克患者1 h集束治疗的依从性。     

Association of ischemia modified albumin with mortality in qSOFA positive sepsis patients by sepsis-3 in the emergency department

BackgroundThe early detection and treatment of sepsis and septic shock patients in emergency departments are critical. Ischemia modified albumin (IMA) is a biomarker produced by ischemia and oxygen free radicals which are related to the pathogenesis of sepsis-induced organ dysfunction. This study aimed to investigate whether IMA was associated with short-term mortality in quick sequential organ failure assessment (qSOFA)-positive sepsis or septic shock patients screened by the sepsis management program.MethodFrom September 2019 to April 2020, patients who arrived at the emergency departments with qSOFA-positive sepsis or septic shock were included in this retrospective observational study.ResultsAmong 124 patients analyzed, IMA was higher in the non-surviving group than in the surviving group (92.6 ± 8.1 vs. 86.8 ± 6.2 U/mL, p < 0.001). The area under the receiver operating characteristics curve was 0.703 (95% CI: 0.572–0.833, p < 0.001). The optimal IMA cutoff was 90.45 (sensitivity 60.9%, specificity 79.2%). IMA values were independently associated with 28-day mortality in the multivariate Cox proportional hazard model (adjusted hazard ratio (aHR) = 1.16, 95% CI: 1.06–1.27, p < 0.01).ConclusionsIn this study, we showed that IMA in the emergency departments was associated with 28-day mortality in qSOFA-positive sepsis and septic shock patients. Further studies are needed to evaluate the clinical value of IMA as a useful biomarker in large populations and multicenter institutions.