Bench-to-bedside review: The initial hemodynamic resuscitation of the septic patient according to Surviving Sepsis Campaign guidelines – does one size fit all?

The Surviving Sepsis Campaign guidelines for the management of severe sepsis and septic shock recommend that the initial hemodynamic resuscitation be done according to the protocol used by Rivers and colleagues in their well-known early goal-directed therapy (EGDT) study. However, it may well be that their patients were much sicker on admission than many other septic patients. Compared with other populations of septic patients, the patients of Rivers and colleagues had a higher incidence of severe comorbidities, a more severe hemodynamic status on admission (excessively low central venous oxygen saturation [ScvO2], low central venous pressure [CVP], and high lactate), and higher mortality rates. Therefore, it may well be that these patients arrived to the hospital in late untreated hypovolemic sepsis, which may have been due, in part at least, to low socioeconomic status and reduced access to health care. The EGDT protocol uses target values for CVP and ScvO2 to guide hemodynamic management. However, filling pressures do not reliably predict the response to fluid administration, while the ScvO2 of septic patients is characteristically high due to decreased oxygen extraction. For all these reasons, it seems that the hemodynamic component of the Surviving Sepsis Campaign guidelines cannot be applied to all septic patients, particularly those who develop sepsis during their hospital stay.     

Bench-to-bedside review: The initial hemodynamic resuscitation of the septic patient according to Surviving Sepsis Campaign guidelines – does one size fit all?

The Surviving Sepsis Campaign guidelines for the management of severe sepsis and septic shock recommend that the initial hemodynamic resuscitation be done according to the protocol used by Rivers and colleagues in their well-known early goal-directed therapy (EGDT) study. However, it may well be that their patients were much sicker on admission than many other septic patients. Compared with other populations of septic patients, the patients of Rivers and colleagues had a higher incidence of severe comorbidities, a more severe hemodynamic status on admission (excessively low central venous oxygen saturation [ScvO₂], low central venous pressure [CVP], and high lactate), and higher mortality rates. Therefore, it may well be that these patients arrived to the hospital in late untreated hypovolemic sepsis, which may have been due, in part at least, to low socioeconomic status and reduced access to health care. The EGDT protocol uses target values for CVP and ScvO₂ to guide hemodynamic management. However, filling pressures do not reliably predict the response to fluid administration, while the ScvO₂ of septic patients is characteristically high due to decreased oxygen extraction. For all these reasons, it seems that the hemodynamic component of the Surviving Sepsis Campaign guidelines cannot be applied to all septic patients, particularly those who develop sepsis during their hospital stay.     

The role of bundles in sepsis care

The understanding of the pathogenesis of sepsis has substantially changed in past years and continues to improve. New therapeutic options are being developed and incorporated into clinical practice. There are different specific interventions and therapies that benefit patients' outcome. As demonstrated by the early goal-directed therapy strategy, the success of the resuscitation treatment is strongly time dependent. The recognition of severe sepsis should be accompanied without delay by very well defined therapeutic measures. In 2002 the Surviving Sepsis Campaign was introduced with the overall goal of increasing clinicians' awareness and improving outcome in severe sepsis and septic shock.     

The incidence of low venous oxygen saturation on admission to the intensive care unit: a multi-center observational study in The Netherlands

Background  

Low mixed or central venous saturation (S(c)vO₂) can reveal global tissue hypoxia and therefore can predict poor prognosis in critically ill patients. Early goal directed therapy (EGDT), aiming at an ScvO₂ ≥ 70%, has been shown to be a valuable strategy in patients with sepsis or septic shock and is incorporated in the Surviving Sepsis Campaign guidelines.     

从“拯救Sepsis运动”指南变迁看血流动力学的巨变

血流动力学治疗是Sepsis救治必不可少的内容。从2004年开始, "拯救Sepsis运动(Surviving Sepsis Campaign, SSC)"指南先后经历了4次变迁, 每一次变迁均是前期基础上的进一步完善。在SSC指南的变迁过程中, 血流动力学治疗策略的制定和实施发生着重要改变。临床对于Sepsis血流动力学治疗认识的逐步深刻也是血流动力学巨变的过程, 有利于治疗调控更为精准。     

Early goal-directed therapy: what do we do now?

The meta-analysis of early goal-directed therapy (EGDT) by Gu and colleagues in the previous issue of Critical Care adds to the ongoing controversy about the value of EGDT for resuscitating patients with severe sepsis and septic shock. The results of the ProCESS (protocolized care for early septic shock) and ARISE (Australasian resuscitation in sepsis evaluation) trials failed to demonstrate any benefit of EGDT or protocolized resuscitation when compared with ‘usual care’. The questions are the following: What is ‘usual’ care? What is ‘real world’ care? Do the results of a robust and well-conducted randomized controlled trial - in which many patients may be excluded for a variety of reasons - reflect the care given to patients on a daily basis in our emergency departments and intensive care units? Of course, there are no obvious answers to these questions, and many clinicians look forward to managing these patients without protocols. For now, the data do seem to support the management of patients with septic shock without mandated central lines or protocols. Does this mean we should go back to the era of ‘do whatever you want’? No consensus exists among clinicians regarding optimal hemodynamic monitoring, and to date no method has been proven to be superior. Given the amount of fluids given prior to randomization in the ProCESS and ARISE trials, ‘usual care’ appears to now include aggressive, early fluid resuscitation with at least 20 mL/kg of crystalloid and rapid administration of appropriate antibiotics. Certainly, this reflects the impact of the original trial by Rivers and colleagues and the broad-based implementation of the Surviving Sepsis Campaign Guidelines and bundles. If this continues to define ‘usual care’, then perhaps it is no longer necessary to mandate specific protocols for resuscitation, as it appears that standard sepsis management has evolved to be consistent with published protocols.     

Early goal-directed therapy: on terminal life support?

Early goal-directed therapy (EGDT) has become regarded as the standard of care for the management of patients with severe sepsis and septic shock. The elements of EGDT have been bundled together as the “Sepsis Bundle,” and compliance with the elements of the bundle is frequently used as an indicator of the quality of care delivered. The major elements of EGDT include fluid resuscitation to achieve a central venous pressure of 8 to 12 cm of water, followed by the transfusion of packed red cells or an inotropic agent to maintain the central venous oxygen saturation higher than 70%. Although the concept of early resuscitation is a scientifically sound concept, we believe that the major elements of the sepsis bundle are fatally flawed.     

Surviving the first hours in sepsis: getting the basics right (an intensivist's perspective)

Severe sepsis is a major cause of morbidity and mortality, claiming between 36?000 and 64?000 lives annually in the UK, with a mortality rate of 35%. International guidelines for the management of severe sepsis were published in 2004 by the Surviving Sepsis Campaign and condensed into two Care Bundles. In 2010, the Campaign published results from its improvement programme showing that, although an absolute mortality reduction of 5.4% was seen over a 2 year period in line with increasing compliance with the Bundles, reliability was not achieved and Bundle compliance reached only 31%. This article explores current challenges in sepsis care and opportunities for further improvements. Basic care tasks [microbiological sampling and antibiotic delivery within 1 h, fluid resuscitation, and risk stratification using serum lactate (or alternative)] are likely to benefit patients most, yet are unreliably performed. Barriers include lack of awareness and robust process, the lack of supporting controlled trials, and complex diagnostic criteria leading to recognition delays. Reliable, timely delivery of more complex life-saving tasks (such as early goal-directed therapy) demands greater awareness, faster recognition and initiation of basic care, and more effective collaboration between clinicians and nurses on the front line, in critical care and in specialist support services, such as microbiology and infectious diseases. Organizations such as Survive Sepsis, the Surviving Sepsis Campaign and the Global Sepsis Alliance are working to raise awareness and promote further improvement initiatives. Future developments will focus on sepsis biomarkers and microarray techniques to rapidly screen for pathogens, risk stratification using genetic profiling, and the development of novel therapeutic agents targeting immunomodulation.     

The pursuit of a high central venous oxygen saturation in sepsis: growing concerns

In this issue of Critical Care, Dutch investigators report that, in a cohort of patients with sepsis/septic shock admitted to three different intensive care units (ICUs), low central venous oxygen saturation (ScvO₂) was uncommon at the time of ICU admission, and hospital mortality was <30%. Their findings, taken together with those of recent reports from Australia and New Zealand (ANZ), raise serious concerns about the utility of early goal directed therapy (EGDT) outside the context of the original trial. Despite inclusion of EGDT into the Surviving Sepsis Guidelines, in response to growing uncertainty, ANZ and US investigators will soon begin randomization of patients into two large multicentre trials comparing EGDT to standard therapy. Until such studies are completed, basing international treatment guidelines on a single centre study performed in what may turn out to be a highly atypical environment would seem premature.     

An audit of ward nurses' knowledge of sepsis

Many of the patients with sepsis admitted to intensive care and high dependency units develop severe sepsis/septic shock in general hospital wards. If the Surviving Sepsis Campaign's aim of a 25% reduction in mortality from sepsis is to be achieved by 2009, then it is essential that registered nurses are aware of the standard definitions of sepsis, and the recommendations for its initial management. The aim of this study was to audit ward nurses' knowledge of sepsis against standard definitions and evidence-based management guidelines. An audit was carried out in one acute hospital to assess ward nurses' knowledge of sepsis. Seventy-three registered nurses from medical, surgical and orthopaedic wards completed a questionnaire about the signs and symptoms of sepsis and its initial management. The results showed that some ward nurses appeared to have a poor knowledge of the signs and symptoms of sepsis, severe sepsis/septic shock and some aspects of its initial management. Following the results of the audit, a variety of educational initiatives were introduced to raise awareness of the standard definitions and the surviving sepsis management guidelines. In conclusion, targeted education must be provided for nurses working in general wards if the Surviving Sepsis Campaign is to achieve its aim of a 25% reduction in mortality by 2009.     

Implementation of sepsis management guideline in a community‐based teaching hospital – can education be potentially beneficial for septic patients?

Objective: To assess clinical outcomes associated with the implementation of the sepsis management guideline in a community‐based hospital. In addition, evaluate the utility and effectiveness of a Sepsis Education Program. Research Design and Methods: This is an observational cohort study of patients presenting to the Emergency Department at a community‐based teaching centre meeting severe sepsis or septic shock criteria. A quality improvement programme consisting of a comprehensive Sepsis Education Program based on recommendations from the Surviving Sepsis Campaign was implemented and evaluated. Patients were identify by the admission diagnosis and were evaluated over two time periods (7/2003–6/2004 and 7/2005–6/2006) and to show clinical outcomes before and after implementation of the sepsis guideline/quality improvement programme. Results: A total of 96 patients with severe sepsis (34 control group and 62 SSC group) were included. Both groups had similar intensive care unit (ICU)‐length of stay (3 vs. 3 days, p = 0.647). Patients who required mechanical ventilation (MV) had similar MV time (4 vs. 3.5 days p = 0.349). A greater percentage of survival was found in the SSC group [45% vs. 73% (p = 0.006)]. Patient received similar care with regards to appropriate early antibiotics (85% vs. 90%, p 0.459). The main difference between the two group was the early fluid resuscitation (2 l vs. 3 l, p = 0.006) over the first 3 h and a difference remained significant at 6 h (4.2 l vs. 6.3 l, p = 0.013). Conclusions: In a community based teaching hospital, implementing the surviving sepsis campaign guideline through an education programme was feasible and resulted in early therapy with aggressive fluid administration and appropriate antibiotics. The Sepsis Education Program resulted in early therapeutic interventions and contributed to the survival benefits.     

Emergency care staff can improve survival rates from sepsis

Patients die from sepsis. Reports of mortality as high as 50% are associated with patients who have severe sepsis. Often the signs and symptoms are unmanaged within the emergency care environment. This paper discusses the Surviving Sepsis Campaign and outlines a number of management steps that practitioners caring for patients within emergency care can use to reduce mortality. The sepsis resuscitation bundle is discussed in depth as its goals can be achieved within the emergency department. A number of relevant web sites are provided that guide interested readers to other information on the Surviving Sepsis Campaign.     

Sepsis与感染性休克的急诊救治及流程优化

Sepsis及感染性休克是临床常见的综合症,与患者预后密切相关。早期救治对Sepsis及感染性休克至关重要。急诊医师在早期诊断Sepsis、评价危险因素和早期复苏方面均起到至关重要的作用。目前证据表明,“Sepsis的集束化治疗”能够改善此类患者预后,2018年4月“拯救Sepsis运动”再次更新了相关推荐意见,提出了“1 h集束化治疗目标”,这对急诊医师提出了更高的要求。本文拟从救治流程、具体处理及可能的政策指导方面讨论Sepsis及感染性休克的急诊优化治疗,以期提高指南依从性和治疗质量,由此改善此类患者的预后。     

The Utility of a Quality Improvement Bundle in Bridging the Gap between Research and Standard Care in the Management of Severe Sepsis and Septic Shock in the Emergency Department

The research in the management of severe sepsis and septic shock has resulted in a number of therapeutic strategies with significant survival benefits. These results also emphasize the primary importance of early hemodynamic resuscitation, or early goal-directed therapy (EGDT), and place the emergency physician in the center of the multidisciplinary team caring for patients with this disease. However, in a busy emergency department, the translation of research into clinical practice is far from ideal. While the benefits are significant, the successful implementation of EGDT is filled with challenges and obstacles. In this article, we will discuss the steps taken at our institution to create, implement, measure, and improve on a six-hour severe sepsis and septic shock treatment bundle incorporating EGDT in the emergency department setting, resulting in significant mortality benefit.     

Diagnose und Therapie der Sepsis

A recent survey conducted by the publicly funded Competence Network Sepsis (Sep- Net) reveals that severe sepsis and/or septic shock occurs in 75,000 inhabitants (110 out of 100,000) and sepsis in 79,000 inhabitants (116 out of 100,000) in Germany annually. This illness is responsible for approx. 60,000 deaths and ranges as the third most frequent cause of death after acute myocardial infarction. Direct costs for the intensive care of patients with severe sepsis alone amount to approx. 1.77 billion euros, which means that about 30% of the budget in intensive care is used to treat severe sepsis. However, until now German guidelines for the diagnosis and therapy of severe sepsis did not exist. Therefore, the German Sepsis Society initiated the development of guidelines which are based on international recommendations by the International Sepsis Forum (ISF) and the Surviving Sepsis Campaign (SSC) and take into account the structure and organisation of the German health care system. Priority was given to the following guideline topics: a) diagnosis, b) prevention, c) causative therapy, d) supportive therapy, e) adjunctive therapy. The guidelines development process was carefully planned and strictly adhered to according to the requirements of the Working Group of Scientific Medical Societies (AWMF).     

Early goal-directed therapy for severe sepsis and septic shock: A living systematic review

Studies and meta-analyses conflict regarding the use of early goal-directed therapy (EGDT) for septic shock. We sought to clarify the conflict by performing a living systematic review and meta-regression.MethodsWe performed a meta-analysis and explored heterogeneity with meta-regression. We conformed with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist and qualified strength of evidence with a Grading of Recommendations Assessment, Development and Evaluation profile.ResultsOverall, EGDT did not significantly reduce mortality compared with usual care (relative risk, 0.85; 95% confidence interval, 0.67-1.08); however, heterogeneity was substantial (I² = 64%; 95% confidence interval, 12%-85%). Illness severity did not correlate with mortality reduction; however, there were significant correlations with control rate mortality and the strategy employed by the control group. Benefit was confined to trials with a control mortality greater than 35%. Compared with monitoring of lactate clearance and central venous pressure, EGDT mortality was higher.ConclusionThe benefit of EGDT is evident in populations with high mortality, in line with reported global mortality rates. In settings with low mortality the recent trials challenge the need for 6-hour goals; however, most patients in these trials met 3-hour resuscitation goals as defined by the Surviving Sepsis Campaign. In settings with higher mortality, EGDT or normalization of lactate/central venous pressure may be viable therapeutic options.     

Surviving sepsis: a guide to the guidelines

The revised Surviving Sepsis Campaign (SSC) guidelines for the management of severe sepsis and septic shock have recently been published. These guidelines represent the end product of an intense process and provide a template approach to the early resuscitation and support of patients with sepsis, based on a synthesis of evidence that has been shown to improve the outcome of the septic patient. The SSC guidelines arose from a recognition that care of the septic patient was suboptimal for at least three reasons. First, the entity of sepsis was frequently not diagnosed in a timely fashion, allowing the process to evolve into a life-threatening syndrome of major physiologic organ system dysfunction. Secondly, even when sepsis was recognized, the urgency of treatment was underappreciated – and so haemodynamic resuscitation was tentative, and the administration of effective antibiotic therapy was often delayed. Finally, treatment was often suboptimal, and failed to take advantage of emerging insights into optimal approaches to patient management. The revised guidelines are far from perfect, but they represent the best available synthesis of contemporary knowledge in this area and as such should be promoted.     

Fitting a square peg into a round hole: are the current Surviving Sepsis Campaign guidelines feasible for Africa?

In their article, Baelani and colleagues surveyed anesthesia providers from African low- and middle-income countries (LMICs) to evaluate whether or not the current Surviving Sepsis Campaign (SSC) guidelines are feasible in such resource-constrained settings. The authors report that an alarmingly low percentage of hospitals have the capacity to implement the SSC guidelines in their entirety but a higher percentage are able to implement the majority of SSC guidelines and grade 1 recommendations. In reality, the probability of adherence to SSC guidelines for septic management is even lower than reported, given that the majority of sepsis management in African LMICs is likely performed by non-intensivists outside of intensive care units. Efforts to address the challenges of managing severely ill patients in LMICs have recently been taken on by the World Health Organization. After reviewing available evidence for sepsis management predominantly from high-income countries, a panel of experts developed a consensus-based strategy tailored for resource-limited settings. However, more research that can evaluate the challenges specific to sepsis management in LMICs and not currently addressed by the SSC guidelines is needed. Comprehensive, evidence-based guidelines combined with innovative approaches to sepsis management in LMICs are required to make a meaningful impact on worldwide sepsis survival.     

Early Goal-directed Therapy, Corticosteroid, and Recombinant Human Activated Protein C for the Treatment of Severe Sepsis and Septic Shock in the Emergency Department

Objectives: To describe our experience with early goal‐directed therapy (EGDT), corticosteroid administration, and recombinant human activated protein C (rhAPC) administration in patients with severe sepsis or septic shock and an Acute Physiology and Chronic Health Evaluation (APACHE) II score ≥25 in the emergency department (ED). Methods: This was a retrospective case series of a prospectively maintained ED sepsis registry. Data are presented as median (25th, 75th percentile). The setting was an academic tertiary ED with approximately 60,000 annual patient visits. Patients with severe sepsis or septic shock and an APACHE II score ≥25 entered in an ED sepsis registry over a four‐month period were included. Patients who received rhAPC in the intensive care unit were excluded. Central venous catheterization for central venous pressure and central venous oxygen saturation monitoring, antibiotics, fluid resuscitation, mechanical ventilation, vasopressors, inotropes, corticosteroids, and rhAPC were initiated by the emergency physicians and continued in the intensive care unit by intensivists. Results: Twenty‐four patients were enrolled. Patient characteristics were as follows: age, 79.5 (68.0, 83.5) years; APACHE II score, 31.5 (29.8, 36.0); ED length of stay, 6.5 (4.0, 10.5) hours; predicted mortality, 76.7% (71.9, 86.4); and in‐hospital mortality, 45.8%. All patients received broad‐spectrum antibiotics, 54.2% completed EGDT, 33.3% received corticosteroids, and 33.3% received rhAPC. Time of antibiotic administration was 1.5 (1.0, 2.0) hours, time of central venous pressure/central venous oxygen saturation monitoring was 1.0 (0.5, 2.5) hour, and time of rhAPC administration was 9.5 (6.8, 10.5) hours after patients met criteria for severe sepsis or septic shock. In‐hospital mortality of patients who received rhAPC in addition to other therapies was 25.0%. Conclusions: EGDT, corticosteroid administration, and rhAPC administration are feasible in the ED setting. While these evidence‐based therapies individually have been shown to improve outcomes for patients with severe sepsis or septic shock, further studies are needed to examine their combined effectiveness during the early stages of this disease.