Two authors (MC and AR) independently searched MEDLINE, Embase, and Cochrane Database of Systematic Reviews using the keywords “sepsis” and “septic shock” and their related MeSH terms, with no language restrictions, for articles published up to April 2018. Review articles and guidelines, such as the Surviving Sepsis Campaign, were searched manually for additional references. The reference lists of the identified papers were also checked for additional articles.
SeminarSepsis and septic shock
Introduction
Sepsis is a complex disorder that develops as a dysregulated host response to an infection, and is associated with acute organ dysfunction and a high risk of death. This syndrome needs urgent treatment, and thus awareness of the presenting characteristics is of great importance. The incidence of sepsis is high, and the condition remains one of the leading causes of death globally. Thus, sepsis is an important public health issue1 with considerable economic consequences.2 Over the past 30 years, a substantial amount of research and improved clinical processes have increased the speed of recognition and treatment of sepsis. In 2016, a new definition was developed to further refine this process, with an increased focus on recognising organ dysfunction in the context of infection.3
The World Health Assembly and WHO made sepsis a global health priority in 2017, and have adopted a resolution to improve the prevention, diagnosis, and management of sepsis.4 In this Seminar, we summarise the most up-to-date evidence about sepsis. Although sepsis is a global priority, most of the available papers and evidence come disproportionately from high-income countries.
We acknowledge this limitation. More research and a greater understanding of sepsis is needed in every health-care system, particularly to better identify patient populations and personalise treatments. It is also important that the global research and quality-improvement agendas on sepsis do not neglect low-income and middle-income countries in the future. Three of the coauthors of this Seminar have been involved in the Surviving Sepsis Campaign (SSC), a global initiative aimed at improving survival in patients with sepsis and septic shock. Since its first publication in 2004, the SSC has established itself as the most important quality-improvement programme for sepsis globally, and the latest bundle was released in 2018. This Seminar presents up-to-date evidence and controversies about sepsis, and highlights the importance of driving quality improvement through initiatives such as the SSC.
Section snippets
Definition
In 2016, the Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction resulting from dysregulated host responses to infection,3 and defined septic shock as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are profound enough to substantially increase the risk of mortality. The Sequential Organ Failure Assessment (SOFA) score is used to codify the degree of organ dysfunction (table
Incidence
The true incidence of sepsis in any given country is unknown. The reported incidence is dependent on the specific definition used, the infecting organism, the reporting mechanism (such as the use of the International Classification of Diseases-9 coding systems) and the requirement for either organ support or intensive care. These factors result in marked differences between estimates and discrete geographical locations. Most data describing the incidence of sepsis are from high-income
Aetiology
Sepsis can originate from virtually any infecting organism. Therefore, the range of presentations of the syndrome is very wide and varies considerably between geographical regions.
Sepsis can originate from community locations or result from a stay in hospital or in another health-care facility. About 80% of hospital-treated sepsis cases arise in the community. The most common site of infection that leads to sepsis is the lung (64% of cases), followed by the abdomen (20%), bloodstream (15%), and
Pathophysiology
Sepsis is characterised by a systemic dysregulated host response to infection. One well-described pathway of immune activation in response to infection occurs when highly conserved microbial pathogen-associated molecular patterns are recognised by pattern-recognition receptors, including Toll-like receptors, on the cells of the innate immune system.26 This interaction triggers the release of both proinflammatory and anti-inflammatory mediators through activation of nuclear factor κB and
Risk factors
Most of the described risk factors for the development of sepsis focus on a patient's predisposition to infection (panel 1). Very old or very young age, immunosuppressive diseases (eg, AIDS), cancer, immunosuppressive medications, diabetes, alcohol abuse, indwelling catheters, or other conditions involving altered skin integrity all predispose patients to infection.21, 36, 38 There is also evidence that people who do not do adequate exercise have an increased risk of death if they develop
Clinical presentation
In sepsis, a host's response to an infection manifests as signs of infection together with acute organ dysfunction. This dysfunction can lead to multiple organ failure, acidosis, and death.36 Although traditionally the SIRS criteria have been used to describe the onset of sepsis, and they have been questioned for being too sensitive and not specific enough, Kaukonen and colleagues44 found that SIRS signs might not be sensitive enough. In their study, the authors found a subgroup of patients
Management
The management of sepsis and septic shock should be undertaken as a medical emergency. Screening patients for signs and symptoms of sepsis and septic shock facilitates earlier identification and intervention.36, 45 Effective treatment should focus on timely intervention, including removal of the source of infection. Aggressive assessment for an unrecognised source or undrained abscess through appropriate laboratory testing and diagnostic imaging is a critical aspect of the initial management of
Outcomes
Sepsis and septic shock are associated with high mortality and substantial morbidity. More than 25–30% of patients with sepsis die from the condition, with hospital mortality for septic shock approaching 40–60%.21, 23, 24 More recent data suggest that mortality due to sepsis has dropped substantially over the past two decades. In almost 30 000 patients in the SSC, the overall hospital mortality for patients with severe sepsis and septic shock was 32·8%.136 Mortality in clinical trials where
Quality-improvement initiatives and bundles
Multifaceted interventions have been shown to be more effective than single interventions for influencing behavioural change. Guidelines and education alone are unlikely to make substantial impacts, so the addition of audit and feedback systems is important. An important example of a multifaceted intervention in the ICU to improve care is the SSC performance-improvement initiative for sepsis management.45 This multifaceted intervention used local interdisciplinary teams, education materials,
Controversies
The main areas of controversy surrounding the early management of sepsis are the absence of a robust definition that facilitates early identification and definitive treatment strategies, the absence of a reliable diagnostic marker, the absence of clarity as to the most effective method for guiding resuscitation, and the absence of a definitive treatment to change the course of the disease.
Sepsis is a syndrome rather than a disease, and is therefore diagnosed according to a consensus definition.
Conclusions
Sepsis is a common condition that is still associated with an unacceptably high mortality and, for many patients who survive, long-term morbidity. With the increased awareness of the condition and with the ongoing quality-improvement campaigns, we now have better understanding of the evidence-based approaches to managing the problem, which have contributed to improved outcomes. With more precise definitions and patient-specific profiles that can delineate an individualised management strategy
Search strategy and selection criteria
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