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: .     

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.     

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.     

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 .     

Safety and efficacy of affinity-purified, anti-tumor necrosis factor-alpha, ovine fab for injection (CytoFab) in severe sepsis

OBJECTIVE: Tumor necrosis factor (TNF) is a critical inflammatory mediator in sepsis. This trial was designed to evaluate the safety and effectiveness of polyclonal ovine anti-TNF fragment antigen binding (Fab) fragments (CytoFab) on plasma TNF-alpha, interleukin-6 (IL-6), and interleukin-8 (IL-8) concentrations and the number of shock-free and ventilator-free days in severely septic patients. DESIGN: Phase II, randomized, blinded, placebo-controlled trial conducted from September 1997 to July 1998. SETTING: Nineteen intensive care units in the United States and Canada. PATIENTS: Eighty-one septic patients with either shock or two organ dysfunctions. INTERVENTIONS: Patients were randomized to receive CytoFab, infused as a 250-units/kg loading dose, followed by nine doses of 50 units/kg every 12 hrs, or 5 mg/kg human albumin as placebo. MEASUREMENTS AND MAIN RESULTS: CytoFab promptly reduced plasma TNF-alpha (p = .001) and IL-6 concentrations (p = .002) compared with placebo. CytoFab also significantly decreased TNF-alpha in bronchoalveolar lavage (BAL) fluid (p < .001). The number of shock-free days did not differ between CytoFab and placebo (10.7 vs. 9.4, respectively) (p = .270). CytoFab increased mean ventilator-free days (15.0 vs. 9.8 for placebo; p = .040) and ICU-free days (12.6 vs. 7.6 for placebo; p = .030) at day 28. All-cause, 28-day mortality rates were 37% (14/38) for placebo recipients, compared with 26% (11/43) for CytoFab recipients (p = .274). No differences in incidences of adverse events, laboratory, or vital sign abnormalities were observed between groups. Although 41% of CytoFab-treated patients developed detectable plasma levels of human anti-sheep antibodies, none demonstrated clinical manifestations during the 28-day study. CONCLUSIONS: CytoFab is well tolerated in patients with severe sepsis, effectively reducing serum and BAL TNF-alpha and serum IL-6 concentrations and increasing the number of ventilator-free and ICU-free days at day 28.     

Early enteral immunonutrition vs. parenteral nutrition in critically ill patients without severe sepsis: a randomized clinical trial

Objectives We compared early parenteral nutrition (PN) and early enteral immunonutrition (iEN) in critically ill patients, distinguishing those with and without severe sepsis or septic shock (SS) on admission to intensive care units (ICUs).Design and setting Multicenter, randomized, unblinded clinical trial in 33 Italian general ICUs.Patients and participants The study included 326 patients, 287 of whom did not have SS on ICU admission. Eligibility criteria excluded the two tails in the spectrum of critical conditions, i.e., patients either too well or too ill. Of the patients recruited 160 were randomized to iEN (142 without SS) and 166 to PN (145 without SS).Interventions Patients were randomized to two arms: early iEN or early PN.Measurements and results Primary endpoint was 28-day mortality for all patients and the occurrence of SS during ICU stay for patients admitted without such condition. While 28-day mortality did not differ between iEN and PN (15.6% vs. 15.1%), patients without SS who received iEN had fewer episodes of severe sepsis or septic shock (4.9% vs. 13.1%). ICU length of stay was 4 days shorter in patients given iEN.Conclusions Compared to parenteral nutrition iEN appears to be beneficial in critical patients without severe sepsis or septic shock. Parenteral nutrition in these patients should be abandoned, at least when enteral nutrition can be administered, even at an initial low caloric content.Electronic supplementary material The electronic reference of this article is . The online full-text version of this article includes electronic supplementary material. This material is available to authorised users and can be accessed by means of the ESM button beneath the abstract or in the structured full-text article. To cite or link to this article you can use the above reference.The complete list of study participants is reported in the Electronic Supplementary Material, part AThe authors represent the Italian Group for the Evaluation of Interventions in Intensive Care Medicine.     

Before-after study of a standardized hospital order set for the management of septic shock

OBJECTIVE: To evaluate a standardized hospital order set for the management of septic shock in the emergency department. DESIGN: Before-after study design with prospective consecutive data collection. SETTING: Emergency department of a 1,200-bed academic medical center. PATIENTS: A total of 120 patients with septic shock. INTERVENTIONS: Implementation of a standardized hospital order set for the management of septic shock. MEASUREMENTS AND MAIN RESULTS: A total of 120 consecutive patients with septic shock were identified. Sixty patients (50.0%) were managed before the implementation of the standardized order set, constituting the before group, and 60 (50.0%) were evaluated after the implementation of the standardized order set, making up the after group. Demographic variables and severity of illness measured by the Acute Physiology and Chronic Health Evaluation II were similar for both groups. Patients in the after group received statistically more intravenous fluids while in the emergency department (2825 +/- 1624 mL vs. 3789 +/- 1730 mL, p = .002), were more likely to receive intravenous fluids of >20 mL/kg body weight before vasopressor administration (58.3% vs. 88.3%, p < .001), and were more likely to be treated with an appropriate initial antimicrobial regimen (71.7% vs. 86.7%, p = .043) compared with patients in the before group. Patients in the after group were less likely to require vasopressor administration at the time of transfer to the intensive care unit (100.0% vs. 71.7%, p < .001), had a shorter hospital length of stay (12.1 +/- 9.2 days vs. 8.9 +/- 7.2 days, p = .038), and a lower risk for 28-day mortality (48.3% vs. 30.0%, p = .040). CONCLUSIONS: Our study found that the implementation of a standardized order set for the management of septic shock in the emergency department was associated with statistically more rigorous fluid resuscitation of patients, greater administration of appropriate initial antibiotic treatment, and a lower 28-day mortality. These data suggest that the use of standardized order sets for the management of septic shock should be routinely employed.     

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.     

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.     

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.     

ACCM/PALS haemodynamic support guidelines for paediatric septic shock: an outcomes comparison with and without monitoring central venous oxygen saturation

INTRODUCTION: The ACCM/PALS guidelines address early correction of paediatric septic shock using conventional measures. In the evolution of these recommendations, indirect measures of the balance between systemic oxygen delivery and demands using central venous or superior vena cava oxygen saturation (ScvO(2) > or = 70%) in a goal-directed approach have been added. However, while these additional goal-directed endpoints are based on evidence-based adult studies, the extrapolation to the paediatric patient remains unvalidated. OBJECTIVE: The purpose of this study was to compare treatment according to ACCM/PALS guidelines, performed with and without ScvO(2) goal-directed therapy, on the morbidity and mortality rate of children with severe sepsis and septic shock. DESIGN, PARTICIPANTS AND INTERVENTIONS: Children and adolescents with severe sepsis or fluid-refractory septic shock were randomly assigned to ACCM/PALS with or without ScvO(2) goal-directed resuscitation. MEASUREMENTS: Twenty-eight-day mortality was the primary endpoint. RESULTS: Of the 102 enrolled patients, 51 received ACCM/PALS with ScvO(2) goal-directed therapy and 51 received ACCM/PALS without ScvO(2) goal-directed therapy. ScvO(2) goal-directed therapy resulted in less mortality (28-day mortality 11.8% vs. 39.2%, p=0.002), and fewer new organ dysfunctions (p=0.03). ScvO(2) goal-directed therapy resulted in more crystalloid (28 (20-40) vs. 5 (0-20 ml/kg, p<0.0001), blood transfusion (45.1% vs. 15.7%, p=0.002) and inotropic (29.4% vs. 7.8%, p=0.01) support in the first 6 h. CONCLUSIONS: This study supports the current ACCM/PALS guidelines. Goal-directed therapy using the endpoint of a ScvO(2)> or =70% has a significant and additive impact on the outcome of children and adolescents with 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.     

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.     

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.     

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.     

Hypothermia in the sepsis syndrome and clinical outcome. The Methylprednisolone Severe Sepsis Study Group.

OBJECTIVE: To evaluate the consequences of clinical hypothermia associated with sepsis syndrome and septic shock. DESIGN: Analysis of data from a multi-institutional, randomized, placebo-controlled, prospective study with predetermined end-point analysis of development of shock, recovery from shock, hospital length of stay, and death. SETTING: Multi-institutional medical and surgical ICUs. PATIENTS: Patients meeting predetermined criteria for severe sepsis syndrome. INTERVENTIONS: Appropriate sepsis and shock care with 50% of patients receiving methylprednisolone and 50% receiving placebo. MEASUREMENTS AND MAIN RESULTS: The occurrence rate of hypothermia (< 35.5 degrees C) is 9% in this population. When compared with febrile patients, hypothermic patients had a higher frequency of central nervous system dysfunction (88% vs. 60%), increased serum bilirubin concentration (35% vs. 15%), prolonged prothrombin times (50% vs. 23%), shock (94% vs. 61%), failure to recover from shock (66% vs. 26%), and death (62% vs. 26%). The hypothermic patients were also more likely to be classified as having a rapidly or ultimately fatal disease upon study admission. CONCLUSIONS: This prospective study confirms that hypothermia associated with sepsis syndrome has a significant relationship to outcome manifest by increased frequency of shock and death from shock. This finding is in sharp contrast to the protective effects of induced hypothermia in septic animals and perhaps man.     

A Cost-effectiveness Analysis of Albumin in Septic Shock: A Patient-level Data Analysis

PurposeAlbumin-based fluid therapy in septic shock is a matter of debate and criticism. The aim of this study was to assess the cost-effectiveness of albumin therapy in patients with septic shock.MethodsA retrospective cohort study was conducted in Imam Khomeini, Sina, and Shariati hospitals on patients with septic shock admitted to intensive care units from March 31, 2016 to September 22, 2017. Data sources were the health information system database and patient medical records. The patients with potential septic shock were identified based on norepinephrine use. Septic shock was confirmed after medical record review based on systemic inflammatory response syndrome criteria, antibiotic use, and fluid therapy. Patients who received albumin in the fluid therapy were compared with patients treated without albumin. The 28-day mortality, life-year gain, and cost-effectiveness were evaluated.FindingsThe addition of albumin had no significant increase in life-year gain (mean difference = 0.67; 95% CI, −2.25 to 3.58). However, the addition of albumin increased the total cost of treatment by US $3846.07 (95% CI, US $2093.46–US $5598.98). The incremental cost-effectiveness ratio calculated based on the mean life-years gained was US$5740.40 per a life-year gained. The net monetary benefit was negative (−355.4; 95% CI, −15,387.61 to 14,676.81), and the probability that the addition of albumin will be cost-effective at a gross domestic product per capita was 40.0%.ImplicationsAlbumin-based fluid therapy does not improve the 28-day mortality of patients with septic shock. The addition of albumin in the fluid therapy of patients with septic shock was not cost-effective. Both the observational and retrospective nature of the study was expected to introduce bias. We recommend a cost-effectiveness analysis combined with clinical trials to settle the debate once and for all.     

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.     

Comparison of the effects of albumin and crystalloid on mortality in adult patients with severe sepsis and septic shock: a meta-analysis of randomized clinical trials

Introduction

The aim of this study was to examine whether albumin reduced mortality when employed for the resuscitation of adult patients with severe sepsis and septic shock compared with crystalloid by meta-analysis.

Methods

We searched for and gathered data from MEDLINE, Elsevier, Cochrane Central Register of Controlled Trials and Web of Science databases. Studies were eligible if they compared the effects of albumin versus crystalloid therapy on mortality in adult patients with severe sepsis and septic shock. Two reviewers extracted data independently. Disagreements were resolved by discussion with other two reviewers until a consensus was achieved. Data including mortality, sample size of the patients with severe sepsis, sample size of the patients with septic shock and resuscitation endpoints were extracted. Data were analyzed by the methods recommended by the Cochrane Collaboration Review Manager 4.2 software.

Results

A total of 5,534 records were identified through the initial search. Five studies compared albumin with crystalloid. In total, 3,658 severe sepsis and 2,180 septic shock patients were included in the meta-analysis. The heterogeneity was determined to be non-significant (P = 0.86, I² = 0%). Compared with crystalloid, a trend toward reduced 90-day mortality was observed in severe sepsis patients resuscitated with albumin (odds ratio (OR) 0.88; 95% CI, 0.76 to 1.01; P = 0.08). However, the use of albumin for resuscitation significantly decreased 90-day mortality in septic shock patients (OR 0.81; 95% CI, 0.67 to 0.97; P = 0.03). Compared with saline, the use of albumin for resuscitation slightly improved outcome in severe sepsis patients (OR 0.81; 95% CI, 0.64 to 1.08; P = 0.09).

Conclusions

In this meta-analysis, a trend toward reduced 90-day mortality was observed in severe sepsis patients resuscitated with albumin compared with crystalloid and saline. Moreover, the 90-day mortality of patients with septic shock decreased significantly.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0702-y) contains supplementary material, which is available to authorized users.     

A high angiopoietin-2/angiopoietin-1 ratio is associated with a high risk of septic shock in patients with febrile neutropenia

Introduction

Endothelial barrier breakdown is a hallmark of septic shock, and proteins that physiologically regulate endothelial barrier integrity are emerging as promising biomarkers of septic shock development. Patients with cancer and febrile neutropenia (FN) present a higher risk of sepsis complications, such as septic shock. Nonetheless, these patients are normally excluded or under-represented in sepsis biomarker studies. The aim of our study was to validate the measurement of a panel of microvascular permeability modulators as biomarkers of septic shock development in cancer patients with chemotherapy-associated FN.

Methods

This was a prospective study of diagnostic accuracy, performed in two distinct in-patient units of a university hospital. Levels of vascular endothelial growth factor A (VEGF-A), soluble fms-like tyrosine kinase-1 (sFlt-1) and angiopoietin (Ang) 1 and 2 were measured after the onset of neutropenic fever, in conditions designed to mimic the real-world use of a sepsis biomarker, based on our local practice. Patients were categorized based on the development of septic shock by 28 days as an outcome.

Results

A total of 99 consecutive patients were evaluated in the study, of which 20 developed septic shock and 79 were classified as non-complicated FN. VEGF-A and sFlt-1 levels were similar between both outcome groups. In contrast, Ang-2 concentrations were increased in patients with septic shock, whereas an inverse finding was observed for Ang-1, resulting in a higher Ang-2/Ang-1 ratio in patients with septic shock (5.29, range 0.58 to 57.14) compared to non-complicated FN (1.99, range 0.06 to 64.62; P = 0.01). After multivariate analysis, the Ang-2/Ang-1 ratio remained an independent factor for septic shock development and 28-day mortality.

Conclusions

A high Ang-2/Ang-1 ratio can predict the development of septic shock in cancer patients with febrile neutropenia.