Interventions for rapid recognition and treatment of sepsis in the emergency department: a narrative review

BackgroundSepsis is a major cause of morbidity and mortality worldwide. Early recognition and treatment of sepsis is associated with improved outcome. The emergency department (ED) is the department where patients with sepsis seek care. However, recognition of sepsis in the ED remains difficult. Different alert and triage systems, screening scores and intervention strategies have been developed to assist clinicians in early recognition of sepsis and to optimize management.ObjectivesThis narrative review describes currently applied interventions or interventions we can start using today, such as screening scores, (automated) triage systems, sepsis teams and clinical pathways in sepsis care; and it summarizes evidence for the effect of implementation of these interventions in the ED on patient management and outcomes.SourcesA systematic literature search was conducted in PubMed, resulting in 39 eligible studies.ContentThe main sepsis interventions in the ED are (automated) triage systems, sepsis teams and clinical pathways, the most integrative being a clinical pathway. Implementation of any of these interventions in sepsis care will generally lead to increased protocol adherence. Presumably increased adherence to sepsis guidelines and bundles will lead to better patient outcomes, but the level of evidence to support this improvement is low, whereas implementation of interventions is often complex and costly. No studies comparing different interventions were identified. Two essential factors for success of interventions in the ED are obtaining the support from all professionals and providing ongoing education. The vulnerability of these interventions lies in the lack of accurate tools to identify sepsis; diagnosing sepsis ultimately still relies on clinical assessments. A lack of specificity or sepsis alerts may lead to alert fatigue and/or overtreatment.ImplicationsThe severity and poor outcome of sepsis as well as the frequency of its presentation in EDs make a structured, protocol-based approach towards these patients essential, preferably as part of a clinical pathway.     

ESKAPE病原菌感染引起脓毒症的研究

感染一直是全球范围内重要的卫生问题,其中感染所导致的脓毒症发病率及死亡率极高,随着研究的深入,人们对脓毒症的认识也不断加深,2016年欧美危重病医学会制定了《脓毒症和感染性休克第三版国际共识定义》,重新定义了脓毒症。在脓毒症的众多病因中,具有突出的耐药性的ESKAPE（屎肠球菌、金黄色葡萄球菌、肺炎克雷伯杆菌、鲍曼不动杆菌、铜绿假单胞菌、肠道杆菌属）病原菌感染是其主要病因之一。ESKAPE感染的患者一般预后均较差,为了解ESKAPE所导致的脓毒症,降低其发病率和死亡率,本文主要从脓毒症、ESKAPE病原菌耐药机制,以及两者关系现状三个方面将国内外的研究进行综述。     

The new concept and diagnostic method of sepsis--not SARS, yes SIRS

Sepsis is one of the most complicated and common conditions clinicians encounter. The presence of causal bacteria has not been an essential element for sepsis, after the American College of Chest Physicians and the Society of Critical Care Medicine proposed SIRS as the new consensus and concept in 1991. The test kit "Hybrisep", detects pathogens in the blood directly. Effective use of it may be helpful in the further study of sepsis.     

脓毒症早期诊断和治疗进展

脓毒症是一项全球性公共卫生问题,具有发病率高、病情严重和病死率高的特点,是重症监护病房(ICU)患者病死的主要原因之一。脓毒症的早期诊断是降低病死率的关键,但是目前尚无诊断的金标准。近年来,液体复苏和抗生素的综合治疗一直是脓毒症治疗的主要方法,但是在许多方面还存在许多争议。此外,免疫治疗是脓毒症治疗的热点之一。本文就脓毒症的早期诊断和治疗进展进行总结和阐述。     

Tropical fevers: Management guidelines

Tropical fevers were defined as infections that are prevalent in, or are unique to tropical and subtropical regions. Some of these occur throughout the year and some especially in rainy and post-rainy season. Concerned about high prevalence and morbidity and mortality caused by these infections, and overlapping clinical presentations, difficulties in arriving at specific diagnoses and need for early empiric treatment, Indian Society of Critical Care Medicine (ISCCM) constituted an expert committee to develop a consensus statement and guidelines for management of these diseases in the emergency and critical care. The committee decided to focus on most common infections on the basis of available epidemiologic data from India and overall experience of the group. These included dengue hemorrhagic fever, rickettsial infections/scrub typhus, malaria (usually falciparum), typhoid, and leptospira bacterial sepsis and common viral infections like influenza. The committee recommends a ‘syndromic approach’ to diagnosis and treatment of critical tropical infections and has identified five major clinical syndromes: undifferentiated fever, fever with rash / thrombocytopenia, fever with acute respiratory distress syndrome (ARDS), fever with encephalopathy and fever with multi organ dysfunction syndrome. Evidence based algorithms are presented to guide critical care specialists to choose reliable rapid diagnostic modalities and early empiric therapy based on clinical syndromes.     

Molecular and cellular aspects of sepsis-induced immunosuppression

Sepsis is a significant cause of death worldwide. Although the prevailing theory of the sepsis syndrome has been that of a condition of uncontrolled inflammation in response to infection, sepsis is increasingly being recognized as an immunosuppressive state. The immune modulations of sepsis result in altered innate and adaptive immune responses, thereby rendering the septic host susceptible to secondary infections. In this review, we present an overview of the clinical and experimental evidence for sepsis-induced immunosuppression and outline the mechanisms that underlie this phenotype. With an improved understanding of how host immune states may be altered during sepsis, better immunomodulatory therapies may be developed to address the immune derangements observed in patients with sepsis.     

The status of IT service management in health care - ITIL® in selected European countries

Background

Electronic documentation handling may facilitate information flows in health care settings to support better coordination of care among Health Care Providers (HCPs), but evidence is limited. Methods that accurately depict changes to the workflows of HCPs are needed to assess whether the introduction of a Critical Care clinical Information System (CCIS) to two Intensive Care Units (ICUs) represents a positive step for patient care. To evaluate a previously described method of quantifying amounts of time spent and interruptions encountered by HCPs working in two ICUs.

Methods

Observers used PDAs running the Work Observation Method By Activity Timing (WOMBAT) software to record the tasks performed by HCPs in advance of the introduction of a Critical Care clinical Information System (CCIS) to quantify amounts of time spent on tasks and interruptions encountered by HCPs in ICUs.

Results

We report the percentages of time spent on each task category, and the rates of interruptions observed for physicians, nurses, respiratory therapists, and unit clerks. Compared with previously published data from Australian hospital wards, interdisciplinary information sharing and communication in ICUs explain higher proportions of time spent on professional communication and documentation by nurses and physicians, as well as more frequent interruptions which are often followed by professional communication tasks.

Conclusions

Critical care workloads include requirements for timely information sharing and communication and explain the differences we observed between the two datasets. The data presented here further validate the WOMBAT method, and support plans to compare workflows before and after the introduction of electronic documentation methods in ICUs.     

Sepsis: from bench to bedside

Sepsis is a syndrome related to severe infections. It is defined as the systemic host response to microorganisms in previously sterile tissues and is characterized by end-organ dysfunction away from the primary site of infection. The normal host response to infection is complex and aims to identify and control pathogen invasion, as well as to start immediate tissue repair. Both the cellular and humoral immune systems are activated, giving rise to both anti-inflammatory and proinflammatory responses. The chain of events that leads to sepsis is derived from the exacerbation of these mechanisms, promoting massive liberation of mediators and the progression of multiple organ dysfunction. Despite increasing knowledge about the pathophysiological pathways and processes involved in sepsis, morbidity and mortality remain unacceptably high. A large number of immunomodulatory agents have been studied in experimental and clinical settings in an attempt to find an efficacious anti-inflammatory drug that reduces mortality. Even though preclinical results had been promising, the vast majority of these trials actually showed little success in reducing the overwhelmingly high mortality rate of septic shock patients as compared with that of other critically ill intensive care unit patients. Clinical management usually begins with prompt recognition, determination of the probable infection site, early administration of antibiotics, and resuscitation protocols based on "early-goal" directed therapy. In this review, we address the research efforts that have been targeting risk factor identification, including genetics, pathophysiological mechanisms and strategies to recognize and treat these patients as early as possible.     

Can Multidisciplinary Sepsis Teams Help Solve a Global Concern? A Review of the Literature

The aims of this reviews are to provide a background on sepsis and to discuss the role of multidisciplinary sepsis teams for those who may not provide direct patient care but play an important role in supporting those that manage patients with sepsis. Sepsis, a life-threatening organ dysfunction due to a dysregulated host response to infection, is one of the leading causes of death worldwide. Considered a medical emergency, prompt laboratory results and administration of appropriate antibiotics are critical. Numerous sepsis guidelines have been published, including the use of standardized bundles that can result in reduced mortality and better patient outcomes. Key to successful outcomes are early recognition and appropriate therapy, which is guided by multidisciplinary sepsis intervention teams; rapid laboratory testing, including Gram stains; molecular mass spectrometry; and clinical and electronic early warning surveillance systems that offer a systematic machine learning application to analyze patients’ medical data and send an alert to providers in real time to allow earlier intervention.     

Sepsis-associated encephalopathy: not just delirium

Sepsis is a major cause of mortality and morbidity in intensive care units. Organ dysfunction is triggered by inflammatory insults and tissue hypoperfusion. The brain plays a pivotal role in sepsis, acting as both a mediator of the immune response and a target for the pathologic process. The measurement of brain dysfunction is difficult because there are no specific biomarkers of neuronal injury, and bedside evaluation of cognitive performance is difficult in an intensive care unit. Although sepsis-associated encephalopathy was described decades ago, it has only recently been subjected to scientific scrutiny and is not yet completely understood. The pathophysiology of sepsis-associated encephalopathy involves direct cellular damage to the brain, mitochondrial and endothelial dysfunction and disturbances in neurotransmission. This review describes the most recent findings in the pathophysiology, diagnosis, and management of sepsis-associated encephalopathy and focuses on its many presentations.     

Modification of immunological features in human platelets during sepsis

Sepsis is an organic dysfunction that puts at risk the life of patients suffering this disorder due to an exacerbated immunological response to the infection mediated by the host. Platelets have been largely researched on sepsis owing to its role in Disseminated Intracellular Coagulation (DIC) and because thrombocytopenia is an important clinical feature of these patients. Nevertheless, a great number of evidence shows that platelets have also an important role in immunological response since they have pattern recognition receptors, chemokine receptors and granules with stored soluble mediators. In this work, the immunological features of platelets in individuals with sepsis are described. The results show that platelets of these individuals have high levels of surfaces expression of TLR4, CD62P, CD32 and thrombin receptor 1 (PAR-1), these platelets have also greater capability to join Escherichia coli, and show a different profile of soluble mediators (IL-1β, CD40L and TNF-α). Platelets from patients with sepsis form aggregates with neutrophils in circulation, but are unable to induce the production of reactive oxygen species. This research describes important features of platelets to help the understanding of the immunological role of these cells in sepsis.     

脓毒症继发急性肾损伤过程中的凝血变化

目的 脓毒症继发急性损伤是脓毒症患者死亡的重要原因之一,凝血变化是急性肾损伤重要因素.本研究旨在筛选脓毒症过程中同急性肾损伤相关的凝血指标.方法 本研究收集外科、急诊及呼吸重症监护室的脓毒症患者,纳入132例脓毒症患者,其中合并急性肾损伤64例,非急性肾损伤68例.收集各组患者一般资料及入ICU第1个24h内各项实验室...     

Prevention of Healthcare-Associated Infections in Low- and Middle-Income Countries: The ‘Bundle Approach’

Background: Healthcare-associated infections (HCAI/HAIs) are one of the most common adverse events in patient care and account for substantial morbidity and mortality. The high rates of HCAIs in a facility are an indicator of poor quality of healthcare services. According to the World Health Organization, at any time, up to 7% of patients in developed and 10% in developing countries will acquire at least one HAI. These infections also present a significant economic burden at the societal level. However, a large percentage of HAIs are preventable through effective infection prevention and control measures. Objectives: Prevention of these infections also needs to be prioritised in view of the growing antimicrobial resistance in HAIs. The bundle approach to the prevention of HAIs is a relatively new concept that is revolutionising the care of high-risk patients in the Intensive Care Units. This report details the bundle approach for the prevention of HAIs, particularly the device-associated infections, for low- and middle-income countries. Conclusion: With the escalating armamentarium of antimicrobial resistance, healthcare sector has to go back to the very basics of hospital infection control; develop, assess and implement bundles of prevention. These are cost-effective and easily adaptable, to cater to the increasing HCAIs and MDR infections in the LMICs.     

Sepsis-induced acute kidney injury

Acute kidney injury (AKI) is a common sequel of sepsis in the intensive care unit. It is being suggested that sepsis-induced AKI may have a distinct pathophysiology and identity. Availability of biomarkers now enable us to detect AKI as early as four hours after it''s inception and may even help us to delineate sepsis-induced AKI. Protective strategies such as preferential use of vasopressin or prevention of intra-abdominal hypertension may help, in addition to the other global management strategies of sepsis. Pharmacologic interventions have had limited success, may be due to their delayed usage. Newer developments in extracorporeal blood purification techniques may proffer effects beyond simple replacement of renal function, such as metabolic functions of the kidney or modulation of the sepsis cascade.     

The immune system's role in sepsis progression,resolution, and long-term outcome

Sepsis occurs when an infection exceeds local tissue containment and induces a series of dysregulated physiologic responses that result in organ dysfunction. A subset of patients with sepsis progress to septic shock, defined by profound circulatory, cellular, and metabolic abnormalities, and associated with a greater mortality. Historically, sepsis-induced organ dysfunction and lethality were attributed to the complex interplay between the initial inflammatory and later anti-inflammatory responses. With advances in intensive care medicine and goal-directed interventions, early 30-day sepsis mortality has diminished, only to steadily escalate long after “recovery” from acute events. As so many sepsis survivors succumb later to persistent, recurrent, nosocomial, and secondary infections, many investigators have turned their attention to the long-term sepsis-induced alterations in cellular immune function. Sepsis clearly alters the innate and adaptive immune responses for sustained periods of time after clinical recovery, with immune suppression, chronic inflammation, and persistence of bacterial representing such alterations. Understanding that sepsis-associated immune cell defects correlate with long-term mortality, more investigations have centered on the potential for immune modulatory therapy to improve long-term patient outcomes. These efforts are focused on more clearly defining and effectively reversing the persistent immune cell dysfunction associated with long-term sepsis mortality.     

Culture-independent detection systems for bloodstream infection

BackgroundSepsis and bloodstream infection are associated with significant morbidity and mortality, and early effective antimicrobial therapy has been demonstrated to improve patient outcomes. Traditional culture-based methods, however, have several limitations that hamper a prompt diagnosis in bloodstream infection, including long turnaround times and limited sensitivity. In recent years, advances have been made in the development of several technologies that allow the identification of pathogens and their resistance markers directly from whole blood, possibly representing promising alternatives to conventional culture-based methods.ObjectivesTo review the currently commercially available emerging assays for the diagnosis of bloodstream infections directly from whole blood, including their performance and the available data about their impact on patient outcome.SourcesPeer-reviewed publications relevant to the topic have been searched through PubMed; manufacturers' websites have also been consulted as a data source.ContentWe have reviewed available data about the following technologies: multiplex real-time PCR working directly from whole blood (Magicplex Sepsis Real-Time test, Seegene), PCR combined with T2 Magnetic Resonance (T2Candida and T2Bacteria panel, T2Biosystem), and metagenomics-based assays (including SepsiTest, Molzym; iDTECT Dx Blood, PathoQuest; Karius NGS plasma Test, Karius). Performance characteristics, advantages and pitfalls of each method are described, and available data about their impact on patients' clinical outcomes are discussed.ImplicationsThe potential of rapid diagnostic tests applied on whole blood for improving the management of patients with bloodstream infection and sepsis is high, both in terms of reducing turnaround times and improving the sensitivity of pathogen and antimicrobial resistance detection. However, overall, there is still a scarcity of data about the real-life performance of such tests, and well-designed studies are awaited for assessing the impact of these emerging technologies on patient outcomes.     

脓毒症炎症反应与内皮细胞损伤研究进展

脓毒症被定义为机体对感染的异常反应最终引起危及生命的器官功障碍综合征.血管内皮细胞在多种炎症细胞和因子的作用下经历活化一损伤过程是脓毒症发展恶化的中心环节.了解炎症反应与血管内皮损伤关系对理解脓毒症发生发展及其治疗具有重要意义.     

The impact of mgrA on progression of Staphylococcus aureus sepsis

Sepsis induced by Staphylococcus aureus has worse outcome with the appearance of methicillin-resistant Staphylococcus aureus (MRSA) because of multi-resistance to a large group of antibiotics, which may lead to death from septic shock. Pathogenesis of S. aureus infections are involved in the production of a wide variety of virulence factors. MgrA, a noval global regulator, is a member of the MarR (multiple antibiotic resistance regulator)/SarA (staphylococcal accessory regulator A) family proteins, which plays a key role in regulating the expression of major virulence factors in S. aureus.In the present study, by using a murine model of sepsis, we investigated the role of mgrA in onset and progression of S. aureus induced sepsis. We found that mice inoculated with wild-type strain Newman had significantly higher mortality (p = 0.029), more weight lost, more bacterial load in blood, spleen and kidney, more intense inflammation response, and worse histopathology than mice inoculated with mgrA knockout strain. Our results has provided evidence that mgrA is a global regulator in S. aureus, and play an important role in S. aureus sepsis, could increase mortality and accelerate the onset and development of sepsis.     

拮抗内毒素的研究进展

由创伤及感染引起的脓毒症是导致临床病人死亡的主要原因.脓毒症的本质是机体对侵入机体的病原微生物所产生的过度炎症性反应,通常而言,内毒素与免疫炎症细胞,特别是巨噬细胞上相应的受体结合,是启动机体产生防御反应及由此而形成脓毒性反应或脓毒症的关键.研究内毒素介导脓毒症的分子病理学机制及近年有关拮抗内毒素措施的研究进展很重要.     

Sepsis-induced immunosuppression

The sepsis syndrome is characterized by the acute release of a variety of inflammatory mediators, which often result in detrimental effects to the host. The release of these mediators is regulated and counterbalanced by the coordinated expression of antiinflammatory molecules. It is the balance between the expression of pro- and anti-inflammatory mediators that often determines the magnitude of early tissue injury and subsequent risk of infectious complications. As our understanding of the pathophysiology of sepsis continues to evolve, we have gained a greater appreciation for the effects that sepsis and similar states of overwhelming stress have on host antimicrobial immunity. A number of functional defects in leukocytes isolated from sepsis patients have been characterized. These defects include diminished expression of important cell surface antigens, dysregulated cytokine production, alterations in antigen-presenting ability, and accelerated apoptosis. Impaired leukocyte function has important clinical ramifications, as high mortality rates have been observed in patients displaying evidence of sepsis-induced immune deactivation. In this article, we review the current literature supporting evidence of dysregulation of host immunity occurring during sepsis syndrome, characterize the underlying pathophysiology, and describe novel therapeutic interventions directed at augmenting host immunity during sepsis.