Procalcitonin for early diagnosis and differentiation of SIRS,sepsis, severe sepsis,and septic shock

Objective To determine the value of procalcitonin (PCT) in the early diagnosis (and differentiation) of patients with SIRS, sepsis, severe sepsis, and septic shock in comparison to C-reactive protein (CRP), white blood cell and thrombocyte count, and APACHE-II score (AP-II). Design Prospective cohort study including all consecutive patients admitted to the ICU with the suspected diagnosis of infection over a 7-month period. Patients and methods A total of 185 patients were included: 17 patients with SIRS, 61 with sepsis, 68 with severe sepsis, and 39 patients with septic shock. CRP, cell counts, AP-II and PCT were evaluated on the first day after onset of inflammatory symptoms. Results PCT values were highest in patients with septic shock (12.89±4.39 ng/ml;P<0.05 vs patients with severe sepsis). Patients with severe sepsis had significantly higher PCT levels than patients with sepsis or SIRS (6.91±3.87 ng/ml vs 0.53±2.9 ng/ml;P<0.001, and 0.41±3.04 ng/ml;P<0.001, respectively). AP-II scores did not differ significantly between sepsis, severe sepsis and SIRS (19.26±1.62, 16.09±2.06, and 17.42±1.72 points, respectively), but was significantly higher in patients with septic shock (29.27±1.35,P<0.001 vs patients with severe sepsis). Neither CRP, cell counts, nor the degree of fever showed significant differences between sepsis and severe sepsis, whereas white blood cell count and platelet count differed significantly between severe sepsis and septic shock. Conclusions In contrast to AP-II, PCT appears to be a useful early marker to discriminate between sepsis and severe sepsis.     

早期诊断严重脓毒症脓毒性休克研究进展

脓毒症(sepsis)可发展成严重脓毒症(severe sepsis)甚至脓毒性休克(septic shock),其发展转归有众多复杂的机制参与,包括宿主对感染的反应以及氧的传输和利用障碍等。早期诊断和积极干预脓毒症,有利于改善脓毒症的预后。早期诊断的生物学指标包括降钙素原(procal-citonin,PCT)、前肾上腺髓质素(proadrenom edullin,proADM)及前心房尿钠肽(pro-atrial natriuretic peptide,proANP)等。     

Understanding sepsis: from SIRS to septic shock

Sepsis remains the leading cause of death in non-coronary ICU patients, despite improvements in supportive treatment modalities such as antimicrobial drugs and ventilation therapy. Further, the incidence of sepsis is projected to increase in years to come, related to factors including a rise in immunosuppressed patient populations and more widespread use of invasive lines and procedures. In this article, the authors seek to advance nurses' understanding of sepsis by reviewing the SIRS to septic shock paradigm and using a case study to illustrate how a patient progressed along the continuum. The role of the critical care nurse is an important aspect of the care of these patients. Early identification of patients at risk for, or who are developing, sepsis is crucial in order to improve patient outcomes.     

The Italian SEPSIS study: Preliminary results on the incidence and evolution of SIRS,sepsis, severe sepsis and septic shock

This prospective, multicenter, epidemiological study was carried out in 99 Italian ICUs, distributed throughout the country, from April 1993 to March 1994. In the study, we applied the new ACCP/SCCM classification system for sepsis (SIRS, sepsis, severe sepsis and septic shock) and determined the prevalence, incidence, evolution and outcome of these categories in critically ill patients. The preliminary analysis of 1101 patients showed that on admission SIRS accounted for about half of the diagnoses (52%) with sepsis, severe sepsis and septic shock accounting for 4.5%, 2.1% and 3% of patients, respectively. Patients with severe sepsis or septic shock more frequently had high SAPS scores than patients without sepsis. Mortality rates were similar in patients with SIRS (26.5%) and without SIRS or infection (24%), but rose to 36% in patients with sepsis, to 52% in those with severe sepsis and to 81.8% in those with septic shock. Sepsis, severe sepsis and septic shock were more common in patients with medical diagnoses, and neither severe sepsis nor septic shock was observed in trauma patients. With respect to evolution, the incidence of septic shock was progressively higher in patients admitted with more severe “sepsis-related” diagnoses, while only a trivial difference in rates of incidence was observed between SIRS patients and those admitted without SIRS or any septic disorder (nil). The breakdown of the various ACCP/SCCM “sepsis-related” diagnoses at any time during the study was: SIRS in 58% of the population, sepsis in 16.3%, severe sepsis in 5.5% and septic shock in 6.1%. It seems reasonable to expect from the final evaluation of our study answers to the questions raised by the ACCP/SCCM Consensus Conference about the correlations between “sepsis-related” diagnosis, severity score, organ dysfunction score and outcome.     

Treatment options for severe sepsis and septic shock

Despite significant advances in the understanding of the pathophysiology of sepsis, severe sepsis and septic shock continue to be associated with high morbidity and mortality. Eradication of infection, with appropriate antibiotics and source control, remains the cornerstone of sepsis management, but does not ensure survival. Aggressive supportive care, such as fluid resuscitation, vasoactive agents or mechanical ventilation, is often required. With the exception of drotrecogin alfa, attempts to modulate the inflammatory response in sepsis have generally been unsuccessful. Early goal-directed therapy targeting adequate central venous oxygen saturation appears to improve outcome. Recently, there has been renewed interest in the use of corticosteroids, not as anti-inflammatory agents, but as replacement therapy. There is also some evidence to suggest that tight glucose control may improve outcome in these patients.     

Management of severe sepsis and septic shock

PURPOSE OF REVIEW: Severe sepsis and septic shock are common and deadly conditions for which the epidemiology, pathogenesis, and management continue to evolve. Recent publications (2003 and early 2004) have been systematically reviewed for important new original research and scholarly reviews, with an emphasis on clinical advances in adults. RECENT FINDINGS: Important new epidemiologic studies establish the increasing frequency (nearly 9% per year) and falling mortality rates associated with sepsis. Sepsis definitions were reviewed by a group of experts, and the principal features of the 1991 consensus conference definitions were supported, with a new framework for evaluation of sepsis proposed. New research and thoughtful reviews continue to elucidate the pathogenesis of sepsis, with emphasis on innate immunity and time-based changes in immune status, varying from hyperreactive immunity and inflammation to immune depression with enhanced risk for nosocomial infections. A comprehensive evidence-based approach to the management of severe sepsis is presented in an important document developed by representatives from many critical care and infectious disease societies. Management includes early targeted resuscitation, broad empiric antibiotic coverage and source control, effective shock evaluation and treatment, adjuvant therapy with recombinant human activated protein C and moderate-dose hydrocortisone in selected patients, and comprehensive supportive care. Recently published multicenter clinical trials for novel agents have been disappointing, particularly for a nitric oxide synthase inhibitor that effectively supported blood pressure but increased mortality. SUMMARY: The works reviewed reflect the advances in the care of patients with sepsis.     

《2004严重感染和感染性休克治疗指南》系列讲座(3)严重感染和感染性休克的抗感染治疗

在积极液体复苏和器官功能支持的同时 ,有效清创引流和应用广谱抗生素是严重感染和感染性休克的根本性病因治疗措施。《2 0 0 4严重感染和感染性休克治疗指南》就病源学诊断、抗生素治疗和感染灶控制提出了推荐性意见 ,以指导严重感染和感染性休克的抗感染治疗。1　病源学诊断1 .1　抗生素治疗前应首先进行及时正确的微生物培养 (推荐级别 :D级 )。及时正确的培养是获得病源学证据的前提。怀疑血源性感染时 ,至少留取 2次血培养。当患者有血管内导管时 ,不但应从外周静脉抽血留取标本 ,还必须经留置导管留取血标本 ,导管血培养结果与外周血…     

Classification of sepsis,severe sepsis and septic shock: the impact of minor variations in data capture and definition of SIRS criteria

Purpose  

To quantify the effects of minor variations in the definition and measurement of systemic inflammatory response syndrome (SIRS) criteria and organ failure on the observed incidences of sepsis, severe sepsis and septic shock.     

Clinical utility of B-type natriuretic peptide in early severe sepsis and septic shock

B-type natriuretic peptide (BNP) has diagnostic, therapeutic, and prognostic utility in critically ill patients. For severe sepsis and septic shock patients in particular, similar clinical utility from the most proximal aspects of hospital presentation to the intensive care unit has not been examined. BNP levels were measured at 0, 3, 6, 12, 24, 36, 48, 60, and 72 hours in 252 patients presenting to the emergency department with severe sepsis and septic shock. The clinicians were blinded to the BNP levels. Elevated BNP levels (>100 pg/mL) were seen in 42% and 69% of patients on presentation and at 24 hours, respectively. Elevated BNP ranges (>230 pg/mL) were significantly associated with myocardial dysfunction and severity of global tissue hypoxia. When adjusted for age, gender, history of heart failure, renal function, organ dysfunction, and mean arterial pressure, a BNP greater than 210 pg/mL at 24 hours was the most significant independent indicator of increased mortality: odds ratio 1.061 (1.026-1.097), P < .001, 95% confidence interval. Patients with severe sepsis and septic shock often have elevated BNP levels, which are significantly associated with organ and myocardial dysfunction, global tissue hypoxia, and mortality. Serial BNP levels may be a useful adjunct in the early detection, stratification, treatment, and prognostication of high-risk patients.     

对严重脓毒症患者应用早期目标导向性六部法护理的研究

目的研究脓毒症六部法护理对严重脓毒血症和脓毒性休克患者各功能脏器的影响及早期复苏的效果。方法采用历史对照,以2001．年6月至2004年12月共31例感染性休克患者按一般护理常规为对照,2005年6月至2009年7月对30例严重脓毒血症和脓毒性休克患者实施脓毒症六部法护理进行及时充分复苏治疗。比较两组患者对后续治疗的反应、脏器功能影响和死亡率。结果对照组需再次复苏治疗者占64．5％,实验组为16．1％（P〈0．01）;复苏7d后,实验组PaO2和PaO2／FiO2均高于对照组,转氨酶、肌酐低于对照组（P〈0．01）;院内死亡率,对照组为48．4％,实验组33．3％（P〈0．01）。结论脓毒症六部法护理护理可明显增强严重脓毒血症和脓毒性休克患者对后续治疗的敏感性,减轻对重要脏器功能的损害,降低其死亡率,脓毒症六部法在早期充分复苏治疗过程中简单、易行,是提高危重护理质量的好方法。     

Implementation of early goal-directed therapy for severe sepsis and septic shock: A decision analysis

OBJECTIVE: Early goal-directed therapy (EGDT) reduced mortality from septic shock in a single-center trial. However, implementation of EGDT faces several barriers, including perceived costs and logistic difficulties. We conducted a decision analysis to explore the potential costs and consequences of EGDT implementation. DESIGN: Estimates of effectiveness and resource use were based on data from the original trial and published sources. Implementation costs and lifetime projections were modeled from published sources and tested in sensitivity analyses. We generated incremental cost-effectiveness ratios from the hospital (short-term) and U.S. societal (lifetime) perspectives, excluding nonhealthcare costs, and applying a 3% annual discount. SETTING: Simulation of an average U.S. emergency department. PATIENTS: Total of 1,000 simulation cohorts (n = 263 for each cohort) of adult patients with severe sepsis/septic shock. INTERVENTIONS: EGDT under three alternative implementation strategies: emergency department-based, mobile intensive care unit team, and intensive care unit-based (after emergency department transfer). MEASUREMENTS AND MAIN RESULTS: For an average emergency department, we estimated 91 cases per yr, start-up costs from $12,973 (intensive care unit-based) to $26,952 (emergency department-based), and annual outlay of $100,113. EGDT reduced length of stay such that net hospital costs fell approximately 22.9% ($8,413-$8,978). EGDT implementation had a 99.4% to 99.8% probability of being dominant (saved lives and costs) from the hospital perspective, and cost from $2,749 (intensive care unit-based) to $7019 (emergency department-based) per quality-adjusted life-yr with 96.7% to 97.7% probability of being <$20,000 per quality-adjusted life-yr from the societal perspective. The intensive care unit-based strategy was the least expensive, because of lower start-up costs, but also least effective, because of implementation delay, and all three strategies had similar cost-effectiveness ratios. Sensitivity analyses showed these estimates to be particularly sensitive to EGDT's effect on mortality and intensive care unit length of stay, but insensitive to other variables. CONCLUSIONS: EGDT has important start-up costs, and modest delivery costs, but assuming LOS and mortality are reduced, EGDT can be cost-saving to the hospital and associated with favorable lifetime cost-effectiveness projections.     

Derivation of a screen to identify severe sepsis and septic shock in the ED-BOMBARD vs. SIRS and qSOFA

Study objectiveTo predict severe sepsis/septic shock in ED patients.MethodsWe conducted a retrospective case-control study of patients ≥18 admitted to two urban hospitals with a combined ED census of 162,000.Study cases included patients with severe sepsis/septic shock admitted via the ED. Controls comprised admissions without severe sepsis/septic shock. Using multivariate logistic regression, a prediction rule was constructed. The model's AUROC was internally validated using 1000 bootstrap samples.Results143 study and 286 control patients were evaluated. Features predictive of severe sepsis/septic shock included: SBP ≤ 110 mm Hg, shock index/SI ≥ 0.86, abnormal mental status or GCS < 15, respirations ≥ 22, temperature ≥ 38C, assisted living facility residency, disabled immunity.Two points were assigned to SI and temperature with other features assigned one point (mnemonic: BOMBARD). BOMBARD was superior to SIRS criteria (AUROC 0.860 vs. 0.798, 0.062 difference, 95% CI 0.022–0.102) and qSOFA scores (0.860 vs. 0.742, 0.118 difference, 95% CI 0.081–0.155) at predicting severe sepsis/septic shock. A BOMBARD score ≥ 3 was more sensitive than SIRS ≥ 2 (74.8% vs. 49%, 25.9% difference, 95% CI 18.7–33.1) and qSOFA ≥ 2 (74.8% vs. 33.6%, 41.2% difference, 95% CI 33.2–49.3) at predicting severe sepsis/septic shock. A BOMBARD score ≥ 3 was superior to SIRS ≥ 2 (76% vs. 45%, 32% difference, 95% CI 10–50) and qSOFA ≥ 2 (76% vs. 29%, 47% difference, 95% CI 25–63) at predicting sepsis mortality.ConclusionBOMBARD was more accurate than SIRS and qSOFA at predicting severe sepsis/septic shock and sepsis mortality.     

The influence of early hemodynamic optimization on biomarker patterns of severe sepsis and septic shock

BACKGROUND: Despite abundant experimental studies of biomarker patterns in early severe sepsis and septic shock, human data are few. Further, the impact of the severity of global tissue hypoxia resulting from resuscitative strategies on these early biomarker patterns remains unknown. METHODS: The temporal patterns of interleukin-1 receptor antagonist, intercellular adhesion molecule-1, tumor necrosis factor-alpha, caspase-3, and interleukin-8 were serially examined over the first 72 hrs of hospitalization after early hemodynamic optimization strategies of early goal-directed vs. standard therapy for severe sepsis and septic shock patients. The relationship of these biomarker patterns to each hemodynamic optimization strategy, severity of global tissue hypoxia (reflected by lactate and central venous oxygen saturation), organ dysfunction, and mortality were examined. RESULTS: Abnormal biomarker levels were present upon hospital presentation and modulated to distinct patterns within 3 hrs based on the hemodynamic optimization strategy. The temporal expression of these patterns over 72 hrs was significantly associated with the severity of global tissue hypoxia, organ dysfunction, and mortality. CONCLUSION: In early severe sepsis and septic shock, within the first 3 hrs of hospital presentation, distinct biomarker patterns emerge in response to hemodynamic optimization strategies. A significant association exists between temporal biomarker patterns in the first 72 hrs, severity of global tissue hypoxia, organ dysfunction, and mortality. These findings identify global tissue hypoxia as an important contributor to the early inflammatory response and support the role of hemodynamic optimization in supplementing other established therapies during this diagnostic and therapeutic "window of opportunity."     

重症肺炎及感染性休克的集束治疗

目的 探讨国内严重感染集束治疗的疗效.方法 在广州医学院附属第二医院呼吸重症监护病房中选用43例重症肺炎及感染性休克患者,进行14个月(2006年11月1日至2007年12月31日)前瞻性观察研究.患者入进标准参照2001年国际脓毒症会议.分教育、试验和运作3个连续阶段实施6 h严重感染集束治疗和24 h严重感染集束治疗.历史对照期内(2004年1月1日至2006年10月31日)合格患者门入对照组.计最资料以(x±s)表示,计数资料以率表爪.采用γ2检验、独立样本t榆验、配对t检验、单因素和多冈素Logistic回归分析,P＜0.05为差异具有统计学意义.结果 1)对照组和集束治疗组问的基础特征差异基本上无统计学意义.2)血清乳酸测定率、休克业组液体复苏率及6 h内所输入液体量、血糖榨制,与对照组相比较,其差异均有统计学意义(P值分别是0.024,0.009,0.045和0.000).3)72 h时,集束治疗组呼吸频率和氧合指数,与对照组相比较,其差异均有统计学意义(P值分别是0.033和0.041);集束治疗组中休克业绀急性生理和慢性疾病评分(A-PACHE)Ⅱ分值和预计死亡率的下降值,与对照组中休克业组比较,其差异均有统计学意义(P值分别是0.017和0.040).4)与对照组比较,集束治疗组病死率绝对值下降23.30%(P=0.019).结论 严重感染集束治疗能显著降低重症肺炎及感染性休克患者病死率.     

休克指数对急诊严重脓毒症和脓毒性休克预后评估的意义

目的 通过测定严重脓毒症和脓毒性休克患者休克指数(SI)水平,探讨其对严重脓毒症和脓毒性休克预后的影响.方法 本文采用回顾性研究的方法,选取2011年9月至2013年8月间入住首都医科大学附属北京友谊医院急诊监护室的严重脓毒症和脓毒症休克患者100例,根据28 d转归再分为生存组(n=48)和院内死亡组(n=52).分别测量并计算所有患者入院时的休克指数(SI1)和入院后就接受液体复苏后2h的休克指数(SI2).结果 (1)死亡组入院时和液体复苏后2h休克指数(1.5±0.05)、(1.2±0.04)高于生存组(1.3±0.08)、(0.9±0.05),二者的差异具有统计学意义(P＜0.01);(2)根据ROC曲线分析并计算AUC值,死亡组SI1、SI2曲线下面积(AUC)分别是0.707 5、0.889 4,SI2≥1为截断点评价严重脓毒症及脓毒性休克患者的预后评价的敏感性为80.3％,特异性为78.4％.结论 入院后复苏2h的休克指数(SI2)较入院时休克指数(SI1),能较好的预测严重脓毒症和脓毒性休克患者的预后.     

Glucocorticoids in the treatment of severe sepsis and septic shock

PURPOSE OF REVIEW: Septic shock remains one of the leading causes of death in intensive care units. In recent years, there is general use of low to moderate doses of corticosteroids in the treatment of septic shock. However, there are wide variations in the practical modality of this treatment, mainly with regard to patients' selection, treatment's dose, timing, route of administration, duration, and weaning. This review provides opinion-based guidelines for the use of corticosteroids in severe sepsis and septic shock. RECENT FINDINGS: A summary of the latest understanding of the mechanisms of action of corticosteroids and the most recent observations in the clinical and biologic responses to corticosteroids in severe sepsis and septic shock is presented. SUMMARY: In septic shock, intravenous hydrocortisone should be started immediately after a 250 microg corticotropin test, at a dose of 200-300 mg per day. When adrenal insufficiency is confirmed, treatment should be continued at full doses for 7 days. Otherwise, hydrocortisone should be stopped. It is worth considering adding enteral fludrocortisone at a dose of 50 microg per day for 7 days. In severe sepsis, despite growing evidence to support the use of a moderate dose of corticosteroids, the efficacy and safety of this treatment needs to be assessed in a large-scale study.