Severe sepsis epidemiology: sampling,selection, and society

Three new articles in Critical Care add to an expanding body of information on the epidemiology of severe sepsis. Although there have been a range of approaches to estimate the incidence of severe sepsis, most studies report severe sepsis in about 10 ± 4% of ICU patients with a population incidence of 1 ± 0.5 cases per 1000. Importantly, the availability of ICU services may well determine the number of treated cases of severe sepsis, and it seems clear that these studies are reporting the treated incidence, not the incidence, of severe sepsis. In the future, we must focus on whether all severe sepsis should be treated, and, consequently, what level of ICU services is optimal.     

Epidemiology of Sepsis and Its Recognition by Emergency Medical Services Personnel in the Netherlands

Little is known about the epidemiology of sepsis in the Netherlands. In addition, information regarding the ability of emergency medical services (EMS) personnel to recognize sepsis is lacking. The aim of this study is to determine epidemiological characteristics of sepsis and the recognition of sepsis by EMS personnel in an urban area in the Netherlands. We conducted a retrospective cohort study using transport information from EMS Amsterdam and admission diagnoses at the emergency department gathered through discharge data from two academic hospitals in Amsterdam for the year 2012. A total of 253 patients with sepsis were evaluated, of which 131 were transported by ambulance. The in-hospital mortality rate of the total population was 21% and a mean length of hospital stay was of 13.5 days. Sixty-seven patients (26.5%) were admitted to the intensive care unit. Almost half of the patients were assigned to the internal medicine ward (117; 46.2%). The most common site of infection was the urinary tract (30%). E. coli was the most frequent cause of infections. EMS staff recognized 18/131 (13.7%) transported patients with (severe) sepsis or septic shock. In 52 cases (39.7%) sepsis went unrecognized, probably due to an incomplete primary survey. In 60 cases (45.8%) sepsis went unrecognized, although enough systemic inflammatory response syndrome criteria were present at initial presentation. Recognition of sepsis by EMS staff in the Netherlands is low, probably due to a lack of awareness of the syndrome and infrequent measurement of temperature and respiratory rate. As early initiation of treatment is crucial, the EMS staff, general practitioners, and other specialties could benefit from more education on this critical illness.     

Drotrecogin alfa: a new approach in the treatment of severe sepsis

Severe sepsis is a common and frequently fatal condition. Evidence showing a link between the coagulation system and the inflammatory response to sepsis led to the development of drotrecogin alfa (activated) as an agent in the treatment of sepsis. This recombinant form of the natural protein, activated protein C (Xigris^TM, Eli Lilly & Co.), has been shown to significantly reduce mortality in a large randomised, controlled Phase III study involving 1690 patients. The exact mode of action of drotrecogin alfa (activated) remains uncertain, although it clearly combines anticoagulant and anti-inflammatory properties. Although associated with an increased risk of bleeding, this is usually procedure-related rather than spontaneous. Although costly, this is a drug that effectively reduces mortality rates in patients with severe sepsis.     

应用序贯性器官衰竭评分预测急诊严重感染患者预后

目的：探讨序贯器官衰竭估计（SOFA）评分与急诊严重感染性患者预后的关系。方法：应用欧洲重症监护医学协会（ESICM）感染相关问题工作组制订的SOFA评分体系,对126名急诊严重感染性患者,进行回顾性统计分析,测量T0SOFA和T72SOFA,计算△SOFA,比较入院时T0SOFA评分与病死率的关系、T72小时的△SOFA评分与病死率的关系,评价SOFA评分在预后估计中的作用。结果：T0SOFA评分、T72小时△SOFA评分与病死率有明显显著性关系（均P     

脓毒症患者急性时相蛋白的动态联合检测

目的　研究血清急性时相蛋白水平在脓毒症和重度脓毒症患者炎症过程中的变化及其临床意义。方法　采用全自动特定蛋白定量分析方法,分组动态测定1、3、7、1 4和2 1 d 5个时间点2 9例脓毒症( SP)组和2 7例重度脓毒症( SSP)组患者的C反应蛋白( CRP)、a1酸性糖蛋白( AAG)、铜蓝蛋白( CER)以及结合珠蛋白( HP)的血清含量,并与3 0例健康体检者进行对照分析。结果　1 SP组:CRP和AAG在炎症早期1 d内就显著升高( P<0 .0 1和P<0 .0 5) ,其中CRP3 d达高峰,AAG3～7d达高峰,AAG持续高峰时间达1 4 d,CRP和AAG各时间点间差异显著( P均<0 .0 1 ) ;CER无显著升高( P>0 .0 5) ,各时间点差异不显著( P>0 .0 5) ;HP早期也显著升高( P<0 .0 5) ,但各时间点差异无显著性( P>0 .0 5)。2 SSP组:CRP和AAG均显著升高( P均<0 .0 1 ) ,高峰持续时间均长达1 4 d,各时间点间差异非常显著( P<0 .0 1 ) ;CER7d前呈下降趋势( P<0 .0 5) ,各时间点间差异有显著性( P<0 .0 5) ;HP在1 4 d才显著升高,2 1 d达峰值( P均<0 .0 5) ,各时间点间差异有显著性( P<0 .0 5)。组间趋势变化比较:CRP、AAG和HP差异均有显著性( P均<0 .0 5) ,CER差异无显著性( P>0 .0 5)。结论　CRP早期升高是感染的敏感指标,CRP和AAG高峰持续时间延长提示重度感染;HP不升     

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.     

外科重症监护室645例脓毒症患者临床流行病学调查

目的了解脓毒症在外科重症监护室（SICU）的发生情况。方法收集2003年1月～2004年12月上海市中西医结合医院SICU入住病例645例，统计全身炎症反应综合征（SIRS）、脓毒症、严重脓毒症和脓毒性休克的发生率、病死率及其与年龄、性别的关系，以及在住院时间上的差异。结果术后第1日SIRS的发生率为63．7％。术后第2日为49．8‰，在SICU期间SIRS发生率为74．3％；未发生SIRS组无死亡病例，发生SIRS组病死率为6．26％。脓毒症发生率为27．0％，严重脓毒症为10．9％，脓毒性休克为7．0％；其病死率分别为14．94％、34．29％和51．11％。脓毒症和非脓毒症患者在年龄上存在差异（P〈0．01），老年人更易发生；在性别上存在差异（P〈0．01）．男性比女性更易发生。在住院时间上脓毒症和非脓毒症患者间差异有显著性（P〈0．01）。结论脓毒症在SICU较为常见，有高龄、男性易发生的特点，严重影响患者预后；须重视明确定义，提高治疗效应。     

What is next in sepsis: current trials in sepsis

17th International Symposium on Infections in the Critically Ill Patient

Barcelona, Spain, 3–4 February 2012

International experts reviewed and updated the most recent and relevant scientific advances on severe sepsis during the 17th International Symposium on Infections in the Critically Ill Patients in Barcelona (Spain) in February 2012. All new pharmacological therapeutic strategies have failed to demonstrate a survival benefit. Despite the large variability among countries and hospitals, the improvement of standard care according to the Surviving Sepsis campaign recommendations reduced the 28-day mortality to 24%. These results may have implications for future clinical trials in which much larger samples sizes of patients at high risk of death will be necessary. The identification of novel proinflammatory endogeneous signals and pathways may lead to the discovery of new drugs to reduce inflammatory reactions and end-organ dysfunction in critically ill patients with sepsis. Extracorporeal blood purification stem or progenitor cells have received increasing interest for the treatment of inflammation and organ injury. A better understanding of how these therapies work is essential and its benefit should be confirmed in future prospective randomized studies.     

血presepsin对脓毒症诊断及病情判断的临床价值

目的探讨血可溶性白细胞分化抗原14亚型(sCD14-ST,presepsin)水平对脓毒症的诊断和病情判断的意义。方法对脓毒症患者72例、非感染全身炎症反应综合征(SIRS)患者23例、体检健康者20例,进行前瞻性研究。分别检测其入院时血presepsin、血清降钙素原(PCT)、C-反应蛋白(CRP)、乳酸(lactate)水平,WBC计数等,根据患者入院24 h内最差临床指标计算急性生理和慢性健康状况评分Ⅱ(APACHEⅡ),比较各组上述指标的差异。绘制ROC曲线并计算曲线下面积,比较各指标对脓毒症诊断的价值。根据患者病原体培养结果,对脓毒症患者分组,进行临床资料比较。根据疾病严重程度分组,比较各临床指标对脓毒症疾病严重程度的判断价值。结果脓毒症患者presepsin、PCT、CRP、WBC均明显高于健康人对照组及非感染SIRS组(P0.05)。presepsin的ROC曲线下面积(AUCROC)为0.975,以407 pg/mL为临界值,诊断脓毒症的敏感性为98.6%,特异性为90.7%。PCT、CRP、WBC的AUCROC分别为0.881、0.875和0.799。脓毒症革兰阳性菌感染组、革兰阴性菌感染组、细菌合并真菌感染组、真菌感染组的presepsin、PCT、CRP、WBC差异均无统计学意义(P0.05)。脓毒症组、严重脓毒症组和脓毒性休克组presepsin水平逐渐升高,各组间比较有统计学意义(P0.05)。结论 presepsin可作为脓毒症早期诊断的标志物之一,对脓毒症病情严重程度的判断有重要价值。     

严重脓毒症患者血管外肺水的监测价值与研究现状

脓毒症所致的多器官功能障碍中,肺脏是最易受损伤的靶器官。脓毒症相关性ARDS/ALI的发病机制复杂,迄今为止其发病机制尚未完全阐明〔1〕。其基本病理生理改变是肺泡-毛细血管屏障功能障碍所致通透性升高,表现为肺血管内液体渗出增加形成血管外肺水（extravascular lung water,EVLW）的聚集。EVLW增加引起的严重通     

急性胃肠损伤分级对严重脓毒症预后评估的价值

目的评估急性胃肠损伤（AGI）分级系统对严重脓毒症预后的评估价值。方法收集46例严重脓毒症患者进行 AGI诊断和分期,然后根据4周内存活或死亡情况分为存活组26例和死亡组20例,每日进行AGI的评估,同时进行序贯器官衰竭评分（SOFA）、急性生理及慢性健康状况评分（APACHEⅡ）,采用logistic多元回归分析方法评估它们对预后的预测,并采用ROC曲线评价各指标的诊断价值。结果所有严重脓毒症患者均出现AGI,发生率100%,AGI分级和第1天APACHEⅡ评分、最高SOFA评分、最高APACHEⅡ评分、入科时乳酸、6 h乳酸等5项指标之间有正相关性,和乳酸清除率、白蛋白等2项指标之间有负相关性,有统计学意义（P＜0.05）。 AGI分级、APACHEⅡ评分、SOFA评分判断严重脓毒症预后的曲线下面积分别为0.94、0.88、0.96。 logistic多元回归分析显示,AGI分级≥1.25、SOFA评分≥7.70、APACHEⅡ评分≥11.80是严重脓毒症死亡的预测指标。结论 AGI分级对严重脓毒症有较好的预后评估作用,AGI分级≥1.25是严重脓毒症死亡的预测指标。     

血栓前体蛋白测定在严重脓毒症中的临床意义

目的　评价血浆血栓前体蛋白( TPP)浓度变化在严重脓毒症中的意义。方法　应用酶联免疫技术测定2 2例严重脓毒症患者TPP浓度及凝血酶原时间( PT)、活化部分凝血激酶时间( APTT)、纤维蛋白原( Fib)、D- 二聚体含量,并与1 0例一般感染组、8例正常对照组进行比较。同时动态观察严重脓毒症患者收入重症监护治疗病房( ICU)后第1、3和5d各项凝血指标,及与感染相关器官衰竭评分系统( SOFA)、简化急性生理评分系统 ( SAPS )、Marshall多器官功能障碍综合征评分进行相关性分析。结果　1严重脓毒症组TPP浓度与D 二聚体含量阳性率显著高于一般感染组和正常对照组( P均<0 .0 5) ,而PT、APTT、Fib在3组间差异均无显著性( P均>0 .0 5)。2严重脓毒症死亡患者的TPP浓度持续升高,与SOFA、SAPS 、Marshall评分呈正相关。结论　TPP可作为严重脓毒症预后及早期高凝状态的诊断指标;与PT、APTT、Fib、D -二聚体相比具有更高的敏感性和特异性。     

降钙素原与血小板指标影响急诊脓毒症患者预后

目的：探讨脓毒症患者降钙素原及血小板指标变化与病死率等相关性,以期指导临床。方法：选择符合入选条件的脓毒症患者78例,入院即刻查血常规、降钙素原及行血培养,入院第4天复查血常规,血培养结果依据细菌染色分为革兰氏染色阴性（G-）和革兰氏染色阳性（G＋）。①依据降钙素原值分组,A组（〉100μg/L）、B组（10~100μg/L）、C组（1.5~10μg/L）、D组（〈1.5μg/L）,比较各组入院30d病死率、血培养细菌G-和G＋菌例数及病因差异;②依据入院时血小板数值将所有脓毒症患者分为血小板减少1组与血小板正常1组,后组依据入院第4天血小板数值分为血小板减少2组与血小板正常2组,比较组间病死率等。结果：所有脓毒症患者,随降钙素原增加,病死率增加,同时G-细菌所占比例增加,肺部感染增多。脓毒症患者入院3d后血小板减少,增加病死率。结论：脓毒症患者入院降钙素原数值在一定程度上可指导临床选择抗菌素及指导预后。脓毒症患者入院3d后血小板减少增加病死率。     

Insulin and metabolic substrates during human sepsis

Rusavy and colleagues recently endeavoured to dissect out the metabolic effects of insulin in patients with severe sepsis, in the setting of normoglycaemia. Twenty stable patients were studied 3–7 days after admission using a euglycaemic clamp at two supraphysiological insulin levels. Increased doses of exogenous insulin caused preferential use of glucose as a metabolic substrate, while total energy expenditure remained constant. Consequently, hyperinsulinaemia reduced tissue oxygen demand and catabolism of protein in patients with sepsis; the benefits of these effects are not proven. The effects of insulin at different time points in sepsis were not examined.     

Cardiac troponin I does not independently predict mortality in critically ill patients with severe sepsis

Objective: Patients with sepsis often have elevated cardiac troponin I even in the absence of coronary artery disease. The prognostic value of cardiac troponins in critically ill patients with sepsis remains debatable. Our objective was to evaluate the prognostic value of cardiac troponin I in critically ill patients with severe sepsis. Methods: In this retrospective study, we included patients with severe sepsis who had troponin assayed within 12 h of admission to intensive care over a 6 year period. Patients who had myocardial infarction at intensive care admission in the setting of sepsis were excluded. Included patients were classified into two groups based on their serum troponin I levels: low troponin group (troponin ≤ 0.1 µg/L) and elevated troponin group (troponin > 0.1 µg/L). The primary outcome of interest was hospital mortality. The secondary outcome measures included intensive care mortality, intensive care and hospital length of stay. Results: A total of 382 patients were admitted to intensive care with sepsis. Of these, 293 patients were included in analyses. There was a statistically significant difference in hospital (15% vs 36.1%; P < 0.01) and intensive care (11% vs 25%; P < 0.01) mortality, but not in intensive care and hospital duration of stay. Logistic regression analysis revealed temperature, simplified acute physiology score II and serum lactate to be independent predictors of hospital mortality. Cardiac troponin I was not an independent predictor of hospital mortality. Conclusion: Critically ill patients with severe sepsis who had elevated troponin had increased hospital and intensive care mortality. However, cardiac troponin I did not independently predict hospital mortality.     

Treatment effects of high-dose antithrombin without concomitant heparin in patients with severe sepsis with or without disseminated intravascular coagulation

BACKGROUND: Disseminated intravascular coagulation (DIC) is a serious complication of sepsis that is associated with a high mortality. OBJECTIVES: Using the adapted International Society on Thrombosis and Haemostasis (ISTH) diagnostic scoring algorithm for DIC, we evaluated the treatment effects of high-dose antithrombin (AT) in patients with severe sepsis with or without DIC. PATIENTS AND METHODS: From the phase III clinical trial in severe sepsis (KyberSept), 563 patients were identified (placebo, 277; AT, 286) who did not receive concomitant heparin and had sufficient data for DIC determination. RESULTS: At baseline, 40.7% of patients (229 of 563) had DIC. DIC in the placebo-treated patients was associated with an excess risk of mortality (28-day mortality: 40.0% vs. 22.2%, P < 0.01). AT-treated patients with DIC had an absolute reduction in 28-day mortality of 14.6% compared with placebo (P = 0.02) whereas in patients without DIC no effect on 28-day mortality was seen (0.1% reduction in mortality; P = 1.0). Bleeding complications in AT-treated patients with and without DIC were higher compared with placebo (major bleeding rates: 7.0% vs. 5.2% for patients with DIC, P = 0.6; 9.8% vs. 3.1% for patients without DIC, P = 0.02). CONCLUSIONS: High-dose AT without concomitant heparin in septic patients with DIC may result in a significant mortality reduction. The adapted ISTH DIC score may identify patients with severe sepsis who potentially benefit from high-dose AT treatment.     

B型利钠肽对严重感染及感染性休克患者预后的预测作用

目的 评价B型利钠肽(BNP)对严重感染及感染性休克预后的预测作用.方法 观察102例严重感染及感染性休克患者入重症监护病房(ICU)24 h血浆BNP水平、临床及预后相关资料.将患者分为28 d死亡组和存活组,比较其差异性,并用受试者工作特征曲线(ROC曲线)评价BNP水平对死亡的预测作用;进一步将存活患者分为BNP升高组和正常组,比较其差异性.结果 死亡组(39例)患者急性生理学与慢性健康状况评分系统Ⅱ(APACHEⅡ)评分显著高于存活组[63例,(28.9±5.9)分比(20.2±5.4)分,P<0.013,但两组白细胞计数、血乳酸值则差异无统计学意义.死亡组患者血浆BNP水平[(1 451.3±531.7)ng/L]明显高于存活组((394.55±81.7)ng/L,P<0.01);以血浆BNP水平>681.4 ng/L作为预测死亡的界点,敏感度为91.4%,特异性为80.3%.在存活组患者中,BNP升高组(48例)的ICU住院天数[(23.75±7.5)d]明显长于正常组(15例,(14.9±5.1)d,P<0.053;但两组APACHE 评分则差异无统计学意义.结论 血浆BNP水平可以预测严重感染及感染性休克的预后.     

5-氟尿嘧啶对重症感染大鼠细胞因子的双相调节作用

目的 观察5-氟尿嘧啶(5-FU)对重症感染大鼠致炎细胞因子和抗炎细胞因子的调节作用,探讨5-FU对重症感染大鼠保护作用的机制.方法 将30只健康雌性Wistar大鼠随机分成正常对照组、重症感染组和5-FU治疗组,每组10只.重症感染组以无菌操作技术将大肠杆菌悬液(1.8×10"cfu/L)注入大鼠腹腔(10 ml/kg),制成重症感染模型;5-FU治疗组在重症感染模型制作成功后40 min再经腹腔注射5-FU(50 mg/kg).观察各组大鼠6 h死亡率和腹水率,然后处死大鼠,抽取下腔静脉血测定血浆中自细胞介素-6(IL-6)和IL-10的含量,称取肺组织湿重.结果 5-FU治疗组大鼠6 h死亡率和腹水率均低于重症感染组(P＜0.05和P＜0.01);重症感染组大鼠肺湿重较正常对照组增加(P＜0.01),5-FU治疗组大鼠肺湿重较重症感染组降低(P＜0.05),并恢复到正常水平.重症感染组血浆IL-6和IL-10水平明显升高(P均＜0.01);5-FU治疗组IL-6水平较重症感染组降低(P＜0.01),并恢复到正常水平,IL-10水平较重症感染组降低,但仍高于正常对照组(P均＜0.01).结论 5-FU可减少大鼠血浆致炎细胞因子和抗炎细胞因子的释放,减轻肺水肿,对重症感染具有保护作用.     

连续性静脉血液滤过对脓毒症患者内皮功能的作用

目的观察连续性血液净化(CBP)对严重脓毒症患者的治疗作用,探讨CBP对严重脓毒症患者内皮细胞功能的影响。方法将严重脓毒症患者分为常规对照组22例,联合治疗CBP组20例。2组患者均行常规治疗,联合治疗组同时行连续性静脉血液滤过(CVVH),分别于治疗前及治疗1 d3、d行动脉血气分析,测定血管性血友病因子(vWF)含量,并观察患者重症监护病房(ICU)住院时间、机械通气时间及28 d生存率。结果联合治疗组患者ICU住院时间(d)及机械通气时间(d)均明显短于常规对照组,病死率明显低于常规对照组。治疗3 d后,2组急性生理学与慢性健康状况评分系统Ⅱ(APACHEⅡ)评分(分)均明显下降,且联合治疗组下降程度优于常规对照组。常规对照组治疗前后vWF均无明显变化。结论 CBP治疗能改善严重脓毒症患者受损的内皮细胞功能,减轻病情的严重程度,改善预后。